<![CDATA[Glioma]]> https://www.eurekaselect.com RSS Feed for Disease Wise Article | BenthamScience EurekaSelect (+http://eurekaselect.com) Thu, 28 Mar 2024 17:45:37 +0000 <![CDATA[Glioma]]> https://www.eurekaselect.com https://www.eurekaselect.com <![CDATA[Bioactives in Disease Prevention and Health Promotion: Exploiting Combinatorial Effects]]>https://www.eurekaselect.comarticle/107297Background: Many bioactive molecules, such as lycopene, resveratrol, lignan, tannins, indoles, fatty acids, etc., found in small amounts in plants, animals, and micro-organisms have been extensively investigated for their diverse preventive, therapeutic, immune-modulating and toxicological effects. Currently, the growing interest of the consumers is shifted towards a novel bioinspired strategy of cocktailing two or more bioactives at a lower concentration to reduce both side and cost effects, and to enhance positive effects for the development of novel compounds by the food, pharmaceutical, and chemical industries.

Methods: Even though there are several regularly updated and published reports showing the importance of beneficial effects of bioactives individually, no systematic reviews are outlining how the bioactives have combinatorially acted together to provide such health benefits and disease preventive effects. Hence, various electronic scientific databases, such as Pub Med, Science Direct, Google scholar, Sci-Finder were searched to collect the data of the present review.

Results: One hundred and sixty-two research and review papers collected from peer-reviewed journals are cited in the present review covering the broad spectrum of many bioactives and their importance in the field of food, feed, and drug industries.

Conclusion: The present systematic review discusses and highlights the current knowledge on the concept of synergistic and combinatorial effects of various bioactives from the plant, animal, micro- organism sources, and synthetic drugs in disease prevention and health promotion. These findings may pave a way for the discovery of new bioactive products and process development, which could add to economic importance.

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<![CDATA[Advancing the Therapeutic Efficacy of Bioactive Molecules by Delivery Vehicle Platforms]]>https://www.eurekaselect.comarticle/1071321R), as well as quercetin and silibinin. The encapsulation of these drugs in supramolecules or other systems refines their solubility and metabolic stability, increases their selectivity and therefore decreases their effective dose and improves their therapeutic index. In this mini review we report on the formulations of silibinin and AT1R antagonist candesartan in a 2-HP-β-cyclodextrin host molecule, which displayed enhanced cytotoxicity and increased silibinin’s and candesartan’s stability, respectively. Moreover, we describe the encapsulation of quercetin in gold nanoparticles bearing a calixarene supramolecular host. Also, the encapsulation of temozolomide in a calixarene nanocapsule has been described. Finally, we report on the activity enhancement that has been achieved upon using these formulations as well as the analytical and computational methods we used to characterize these formulations and explore the molecular interactions between the host and quest molecules.]]> <![CDATA[Comprehensive Analysis Reveals GPRIN1 is a Potential Biomarker for Non-sm all Cell Lung Cancer]]>https://www.eurekaselect.comarticle/106983Background: Non-small cell lung cancer (NSCLC) is one of the most leading cause of tumor related mortality worldwide. However, the prognosis of NSCLC remained to be poor and the mechanisms remained to be further investigated.

Objective: This study aimed to evaluate whether GPRIN1 could be a potential biomarker for NSCLC.

Methods: The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov/) and GEO database(http://www.ncbi.nlm.nih.gov/geo) were used to analyze the GPRIN1 expression between normal and human cancers. The protein-protein interaction among centromere proteins was determined using STRING database (http://www.bork.emblheidelberg.de/STRING/). GraphPad Prism 5.0 software was utilized for the independent and paired samples’ t-test or ANOVA to analyze the difference of GPRIN1 expression between two groups.

Results: This study showed GPRIN1 was overexpressed and correlated to shorter OS time in human cancers. In NSCLC, we found that GPRIN1 was up-regulated in NSCLC samples compared to normal lung tissues by analyzing TCGA and GEO datasets. Bioinformatics analysis indicated that this gene was involved in regulating cancer proliferation and metabolism. Finally, we identified key targets of GPRIN1 in NSCLC by constructing PPl networks, including MCM3, KIF20A, UHRF1, BRCA1, KIF4A, HMMR, KIF18B, KIFC1, ASPM, and NCAPG2.

Conclusion: These analyses showed GPRIN1 could act as a prognosis biomarker in patients with NSCLC.

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<![CDATA[Comprehensive Analysis of Key Proteins Involved in Radioresistance of Prostate Cancer by Integrating Protein-protein Interaction Networks]]>https://www.eurekaselect.comarticle/107125Background: Radioresistance remains a significant obstacle in the treatment of prostate cancer (PCa). The mechanisms underlying the radioresistance in PCa remained to be further investigated.

Methods: GSE53902 dataset was used in this study to identify radioresistance-related mRNAs. Protein-protein interaction (PPI) network was constructed based on STRING analysis. DAVID system was used to predict the potential roles of radioresistance-related mRNAs.

Results: We screened and re-annotated the GSE53902 dataset to identify radioresistance-related mRNAs. A total of 445 up-regulated and 1036 down-regulated mRNAs were identified in radioresistance PCa cells. Three key PPI networks consisting of 81 proteins were further constructed in PCa. Bioinformatics analysis revealed that these genes were involved in regulating MAP kinase activity, response to hypoxia, regulation of the apoptotic process, mitotic nuclear division, and regulation of mRNA stability. Moreover, we observed that radioresistance-related mRNAs, such as PRC1, RAD54L, PIK3R3, ASB2, FBXO32, LPAR1, RNF14, and UBA7, were dysregulated and correlated to the survival time in PCa.

Conclusion: We thought this study would be useful to understand the mechanisms underlying radioresistance of PCa and identify novel prognostic markers for PCa.

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<![CDATA[Identification of Glioma Specific Genes as Diagnostic and Prognostic Markers for Glioma]]>https://www.eurekaselect.comarticle/106076Background: Malignant gliomas are the most prevalent malignancy of the brain. However, there was still lack of sensitive and accurate biomarkers for gliomas.

Objective: To explore the mechanisms underlying glioma progression and identify novel diagnostic and prognostic markers for glioma.

Methods: By analyzing TCGA dataset, whole-genome genes expression levels were evaluated in 19 different types of human cancers. A protein-protein interacting network was constructed to reveal the potential roles of these glioma special genes. KEGG and GO analysis revealed the potential effect of these genes.

Results: We identified 698 gliomas specially expressed genes by analyzing TCGA dataset. A protein-protein interacting network was constructed to reveal the potential roles of these glioma special genes. KEGG and GO analysis showed gliomas specially expressed genes were involved in regulating neuroactive ligand-receptor interaction, retrograde endocannabinoid signaling, Glutamatergic synapse, chemical synaptic transmission, nervous system development, central nervous system development, and learning. Of note, GRIA1, GNAO1, GRIN1, CACNA1A, CAMK2A, and SYP were identified to be down-regulated and associated with poor prognosis in gliomas.

Conclusion: GRIA1, GNAO1, GRIN1, CACNA1A, CAMK2A, and SYP were identified to be down-regulated and associated with poor prognosis in gliomas. We thought this study will provide novel biomarkers for gliomas.

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<![CDATA[Dual-target Inhibitors Based on BRD4: Novel Therapeutic Approaches for Cancer]]>https://www.eurekaselect.comarticle/107247Background: Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new strategies for cancer treatment. Multi-target therapies aim to have additive or synergistic effects and reduce the potential for the development of resistance by integrating different pharmacophores into a single drug molecule. Given the fact that majority of diseases are multifactorial in nature, multi-target therapies are being exploited with increasing intensity, which has brought improved outcomes in disease models and obtained several compounds that have entered clinical trials. Thus, it is potential to utilize this strategy for the treatment of BRD4 related cancers. This review focuses on the recent research advances of dual-target inhibitors based on BRD4 in the aspect of anti-tumor.

Methods: We have searched the recent literatures about BRD4 inhibitors from the online resources and databases, such as pubmed, elsevier and google scholar.

Results: In the recent years, many efforts have been taken to develop dual-target inhibitors based on BRD4 as anti-cancer agents, such as HDAC/BRD4 dual inhibitors, PLK1/BRD4 dual inhibitors and PI3K/BRD4 dual inhibitors and so on. Most compounds display good anti-tumor activities.

Conclusion: Developing new anti-cancer agents with new scaffolds and high efficiency is a big challenge for researchers. Dual-target inhibitors based on BRD4 are a class of important bioactive compounds. Making structural modifications on the active dual-target inhibitors according to the corresponding structure-activity relationships is of benefit to obtain more potent anti-cancer leads or clinical drugs. This review will be useful for further development of new dual-target inhibitors based on BRD4 as anti-cancer agents.

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<![CDATA[Recent Progress in the Development of Quinoline Derivatives for the Exploitation of Anti-Cancer Agents]]>https://www.eurekaselect.comarticle/106665Background: Along with the progress in medicine and therapies, the exploitation of anti-cancer agents focused more on the vital signaling pathways and key biological macromolecules. With rational design and advanced synthesis, quinoline derivatives have been utilized frequently in medicinal chemistry, especially in developing anti-cancer drugs or candidates.

Methods: Using DOI searching, articles published before 2020 all over the world have been reviewed as comprehensively as possible.

Results: In this review, we selected the representative quinoline derivate drugs in market or clinical trials, classified them into five major categories with detailed targets according to their main mechanisms, discussed the relationship within the same mechanism, and generated a summative discussion with prospective expectations. For each mechanism, the introduction of the target was presented, with the typical examples of quinoline derivate drugs.

Conclusion: This review has highlighted the quinoline drugs or candidates, suited them into corresponding targets in their pathways, summarized and discussed. We hope that this review may help the researchers who are interested in discovering quinoline derivate anti-cancer agents obtain considerable understanding of this specific topic. Through the flourishing period and the vigorous strategies in clinical trials, quinoline drugs would be potential but facing new challenges in the future.

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<![CDATA[Circular RNAs and Glioma: Small Molecule with Big Actions]]>https://www.eurekaselect.comarticle/107243 <![CDATA[Antioxidant, Anti-Inflammatory and Cytotoxic Properties of <i>Centaurea africana</i> Lamk var. [Bonnet] M]]>https://www.eurekaselect.comarticle/107214Background: In Algerian traditional medicine, Centaurea species are well known in traditherapy. Centaurea africana has been used in folk medicine for the treatment of several inflammatory disorders.

Objective: This study aims to examine the antioxidant, anti-inflammatory and anti-proliferative potential of both n-Butanol (BECA) and ethyl acetate (EAECA) extracts of Centaurea africana.

Methods: The phytochemical analysis of both BECA and EAECA were explored and the antioxidant activities were investigated by measuring the DPPH° scavenging effect, the reducing power and the inhibition of lipid peroxidation (LPO) induced by by Fe2+/ ascorbic acid system. The antiinflammatory properties were determined by measuring the NO° scavenging effect and by using carrageenan-induced rat paw oedema. The antiproliferative activity was studied on HT29 (human colorectal adenocarcinoma), OV2008 (human ovarian cancer) and C6 (Rattus norvegicus brain glioma) cell lines using the Sulforhodamine B assay.

Results: The total polyphenol contents (TPC) of EAECA and BECA are recorded at 125.24±10.14 and 53.03±2.50 mgGAE/g extract, respectively. Both extracts revealed the antioxidant activity in a concentration-dependent manner; this effect is more pronounced with EAECA. The BECA exhibited a higher anti-inflammatory activity. This anti-inflammatory activity was reflected in a reduction of swelling of carrageenan-evoked edemas (48.45 %), inhibition of nitric oxide (84.7 %), effective decrease in myeloperoxidase activity (58.82 %) and malondialdehyde level (65.58 %). The cytotoxic effect of BECA was found to be more pronounced against C6 cell lines (IC50 value: 131.93 μg/mL) while the cytotoxic activity of EAECA was more effective against HT29 and OV2008 cell lines.

Conclusion: The obtained results indicated that EAECA exhibited a high antioxidant activity, while BECA has significant anti-inflammatory activity. Both extracts showed cytotoxic effects against cancer cell lines at certain concentrations in a cell-specific manner.

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<![CDATA[Brain MR Image Classification for Glioma Tumor detection using Deep Convolutional Neural Network Features]]>https://www.eurekaselect.comarticle/105148 Objective: Classification of the brain MR images into tumorous and non-tumorous using deep features and different classifiers to get higher accuracy.

Methods: In this study, a novel four-step process is proposed; pre-processing for image enhancement and compression, feature extraction using convolutional neural networks (CNN), classification using the multilayer perceptron and finally, tumor segmentation using enhanced fuzzy cmeans method.

Results: The system is tested on 65 cases in four modalities consisting of 40,300 MR Images obtained from the BRATS-2015 dataset. These include images of 26 Low-Grade Glioma (LGG) tumor cases and 39 High-Grade Glioma (HGG) tumor cases. The proposed CNN feature-based classification technique outperforms the existing methods by achieving an average accuracy of 98.77% and a noticeable improvement in the segmentation results are measured.

Conclusion: The proposed method for brain MR image classification to detect Glioma Tumor detection can be adopted as it gives better results with high accuracies.]]> <![CDATA[Multifunctional Hydroxyapatite-based Nanoparticles for Biomedicine: Recent Progress in Drug Delivery and Local Controlled Release]]>https://www.eurekaselect.comarticle/105899 <![CDATA[Integrative Analysis of miRNA-mediated Competing Endogenous RNA Network Reveals the lncRNAs-mRNAs Interaction in Glioblastoma Stem Cell Differentiation]]>https://www.eurekaselect.comarticle/106515Background: Competing endogenous RNA (ceRNA) networks play a pivotal role in tumor diagnosis and progression. Numerous studies have explored the functional landscape and prognostic significance of ceRNA interaction within differentiated tumor cells.

Objective: We propose a new perspective by exploring ceRNA networks in the process of glioblastoma stem cell (GSC) differentiation.

Methods: In this study, expression profiles of lncRNAs and mRNAs were compared between GSCs and differentiated glioblastoma cells. Using a comprehensive computational method, miRNAmediated and GSC differentiation-associated ceRNA crosstalk between lncRNAs and mRNAs was identified. A ceRNA network was then established to select potential candidates that regulate GSC differentiation.

Results: Based on the specific ceRNA network related to GSC differentiation, we identified lnc MYOSLID: 11 as a ceRNA that regulated the expression of the downstream gene PXN by competitively binding with hsa-miR-149-3p. After Kaplan-Meier (KM) survival analysis, the expression of PXN gene (PPXN = 0.0015) and lnc MYOSLID: 11 (PMYOSLID: 11=0.041) showed significant correlation with glioblastoma in 160 patients from TCGA.

Conclusion: This result sheds light on a potential way of studying the ceRNA network, which can provide clues for developing new diagnostic methods and finding therapeutic targets for clinical treatment of glioblastoma.

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<![CDATA[Use of Bimetallic Nanoparticles in the Synthesis of Heterocyclic Molecules]]>https://www.eurekaselect.comarticle/105743 <![CDATA[Nifurtimox Hampered the Progression of Astroglioma <i>In vivo Via</i> Manipulating the AKT-GSK3β axis]]>https://www.eurekaselect.comarticle/105745Background: Astroglioma, one major form of brain tumors, has remained principally tough to handle for decades, due to the complexity of tumor pathology and the poor response to chemo- and radio-therapies.

Methods: Our previous study demonstrated that nifurtimox could regulate the signaling axis of AKT-GSK3β in various tumor types including the astroglioma U251 cells. Intriguingly, earlier case studies suggested that nifurtimox could possibly permeate the blood brain barrier and arrest neuroblastoma in the brain. These observations jointly encouraged us to explore whether nifurtimox would hinder the growth of astroglioma in vivo.

Results: Our results exhibited that nifurtimox could competently hinder the development of astroglioma in the mouse brain as compared to temozolomide, the first line of drug for brain tumors. Meanwhile the surviving rate, as well as the body-weight was dramatically upregulated upon nifurtimox treatment, as compared to that of temozolomide. These findings offered nifurtimox as a better alternative drug in treating astroglioma in vivo.

Conclusion: Persistently, the manipulation of the signaling axis of AKT-GSK3β in astroglioma was found in line with earlier findings in neuroblastoma when treated with nifurtimox.

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<![CDATA[Chemical Variability and Antioxidant Activities of the Essential Oils of the Aerial Parts of Ammoides verticillata and the Roots of Carthamus caeruleus and their Synergistic Effect in Combination]]>https://www.eurekaselect.comarticle/107143Aim and Objective: Oxidative stress is implicated in the development and progression of many diseases. Some of the appropriate actions that could taken to resolve the problem of these diseases are search for new antioxidant substances isolated from plants. The aims of this study were to research the intraspecies variations of A. verticillata and C. caeruleus essential oils from 8 locations using statistical analysis, the in vitro antioxidant properties of collective essential oils and in combinations.

Materials and Methods: The essential oils were analyzed by GC and GC-MS. The intraspecies variations of the essential oil compositions were discussed using principal component analysis (PCA) and cluster analysis (CA). The antioxidant properties were evaluated DPPH-radical scavenging activity and β-carotene bleaching test.

Results: The main components of Ammoides verticillata collective essential oil (Coll EO) were thymol (30.5%), carvacrol (23.2%), p-cymene (13.1%), limonene (12.5%) and terpinene-4-ol (12.3%). While roots of Carthamus caeruleus essential oil were dominated by carline oxide (86.2%). The chemical variability allowed the discrimination of two main Groups for both Coll EOs. A direct correlation between the altitudes, climate and the chemical compositions was evidenced. Ammoides verticulata and Carthamus caeruleus Coll Eos showed good antioxidant activity. In binary mixture, the interaction between both Coll Eos and between oils rich of thymol and/or carvacrol with carlina oxide produced the best synergistic effects compared to individual essential oils and the synthetic antioxidant (BHT).

Conclusion: Ammoides verticillata and Carthamus caeruleus essential oil blends can be used as a natural food preservative and alternative to chemical antioxidants.

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<![CDATA[Flavonoids and other Non-alkaloidal Constituents of Genus Erythrina: Phytochemical Review]]>https://www.eurekaselect.comarticle/107215Background: Genus Erythrina belongs to family Fabaceae, which is widely distributed in tropical and subtropical areas. It has been used in both traditional herbal medicines and pharmacological applications. Original research articles and publications on the overview of alkaloids related to this genus are available, but a supportive systematic review account which highlighted phytochemical aspects of other types of secondary metabolites is currently insufficient.

Objective: With the utilization of data and information from SCI-Finder, Google Scholar, the Web of Science, Scopus, Science Direct, PubMed, Chemical Abstracts, ACS journals, Springer, Taylor Francis, Bentham Science and IOP Science, the reliable material sources of this systematic review paper were obtained from the literature published from the 1980s to now.

Conclusion: A vast amount of data showed that the non-alkaloidal secondary metabolites were obtained from genus Erythrina with various classes of chemical structures. Herein, approximately five hundred constituents were isolated, comprising flavonoids, terpenoids, saponins, phytosterols, phenols, arylbenzofurans, coumarins, alcohols, ceramides, mono-sugars and fatty acid derivatives. In agreement with the previous phytochemical reports on the plants of the family Fabaceae, flavonoids reached a high amount in the plants of genus Erythrina. Numerous biological activity investigations such as anti-bacteria, anti-cancer, anti-virus using isolated compounds from Erythrina species suggested that secondary metabolites of Erythrina plants are now becoming the promising agents for drug developments.

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<![CDATA[Melatonin Receptor as a Drug Target for Neuroprotection]]>https://www.eurekaselect.comarticle/105974Background: Melatonin, a neurohormone secreted from the pineal gland, circulates throughout the body and then mediates several physiological functions. The pharmacological effects of melatonin can be mediated through its direct antioxidant activity and receptor-dependent signaling.

Objective: This article will mainly review receptor-dependent signaling. Human melatonin receptors include melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2), which are widely distributed throughout the brain.

Result: Several lines of evidence have revealed the involvement of the melatonergic system in different neurodegenerative diseases. Alzheimer’s disease pathology negatively affects the melatonergic system. Melatonin effectively inhibits β-amyloid (Aβ) synthesis and fibril formation. These effects are reversed by pharmacological melatonin receptor blockade. Reductions in MT1 and MT2 expression in the amygdala and substantia nigra pars compacta have been reported in Parkinson’s disease patients. The protective roles of melatonin against ischemic insults via its receptors have also been demonstrated. Melatonin has been reported to enhance neurogenesis through MT2 activation in cerebral ischemic/reperfusion mice. The neurogenic effects of melatonin on mesenchymal stem cells are particularly mediated through MT2.

Conclusion: Understanding the roles of melatonin receptors in neuroprotection against diseases may lead to the development of specific analogs with specificity and potency greater than those of the original compound. These successfully developed compounds may serve as candidate preventive and disease-modifying agents in the future.

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<![CDATA[MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma]]>https://www.eurekaselect.comarticle/106664

Objective: This study aims to investigate the potential role of miR-372-3p in enhancing Dox effects on HCC cell line (HepG2). Additionally, the correlation between miR-372-3p and HCC patients who received Transarterial Chemoembolization (TACE) with Dox treatment has been analyzed.

Methods: Different cell processes were elucidated by cell viability, colony formation, apoptosis and wound healing assays after miR-372-3p transfection in HepG2 cells Furthermore, the miR-372-3p level has been estimated in the blood of primary HCC patients treated with TACE/Dox by quantitative real-time PCR assay. Receiver Operating Curve (ROC) analysis for serum miR-372-3p was constructed for its prognostic significance. Finally, the protein level of Mcl-1, the anti-apoptotic player, has been evaluated using western blot.

Results: We found a significantly higher level of miR-372-3p in the blood of the responder group of HCC patients who received TACE with Dox than of non-responders. Ectopic expression of miR-372-3p reduced cell proliferation, migration and significantly induced apoptosis in HepG2 cells which was coupled with a decrease of anti-apoptotic protein Mcl-1.

Conclusion: Our study demonstrated that miR-372-3p acts as a tumor suppressor in HCC and can act as a predictor biomarker for drug response. Furthermore, the data referred for the first time its potential role in drug sensitivity that might be a therapeutic target for HCC.]]> <![CDATA[Determining the Relative Gene Expression Level of Hypoxia Related Genes in Different Cancer Cell Lines]]>https://www.eurekaselect.comarticle/106814Objective: This study aims to identify the changes in the expression of hypoxia-inducible genes in seven different cancer cell lines that vary in their oxygen levels in an attempt to identify hypoxia biomarkers that can be targeted in therapy. Profiling of hypoxia inducible-gene expression of these different cancer cell lines can be used as baseline data for further studies.

Methods: Human cancer cell lines obtained from the American Type Culture Collection were used; MCF7 breast cancer cells, PANC-1 pancreatic cancer cells, PC-3 prostate cancer cells, SHSY5Y neuroblastoma brain cancer cells, A549 lung cancer cells, and HEPG2 hepatocellular carcinoma. In addition, we used the MCF10A non-tumorigenic human breast epithelial cell line as a normal cell line. The differences in gene expression were examined using real-time PCR array (PAHS- 032Z, Human Hypoxia Signaling Pathway PCR Array) and analyzed using the ΔΔCt method.

Results: Almost all hypoxia-inducible genes showed a PO2-dependent up- and down-regulated expression. Noticeable gene expression differences were identified. The most important changes occurred in the HIF1α and NF-KB signaling pathways targeted genes and in central carbon metabolism pathway genes such as HKs, PFKL, and solute transporters.

Conclusion: This study identified possible hypoxia biomarkers genes such as NF-KB, HIF1α, HK, PFKL, and PIM1 that were expressed in all hypoxic cells. Pleiotropic pathways that play a role in inducing hypoxia directly, such as HIF1 α and NF-kB pathways, were upregulated. In addition, genes expressed only in the severe hypoxic liver and pancreatic cells indicate that severe and intermediate hypoxic cancer cells vary in their gene expression. Gene expression differences between cancer and normal cells showed the shift in gene expression profile to survive and proliferate under hypoxia.

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<![CDATA[Effects of Galbanic Acid on Proliferation, Migration, and Apoptosis of Glioblastoma Cells Through the PI3K/Akt/MTOR Signaling Pathway]]>https://www.eurekaselect.comarticle/106549Background: Glioblastoma is one of the most aggressive tumors of the central nervous system. Galbanic acid, a natural sesquiterpene coumarin, has shown favorable effects on cancerous cells in previous studies.

Objective: The aim of the present work was to evaluate the effects of galbanic acid on proliferation, migration, and apoptosis of the human malignant glioblastoma (U87) cells.

Methods: The anti-proliferative activity of the compound was determined by the MTT assay. Cell cycle alterations and apoptosis were analyzed via flow cytometry. Action on cell migration was evaluated by scratch assay and gelatin zymography. Quantitative Real-Time PCR was used to determine the expression of genes involved in cell migration (matrix metalloproteinases, MMPs) and survival (the pathways of PI3K/Akt/mTOR and WNT/β-catenin). Alteration in the level of protein Akt was determined by Western blotting.

Results: Galbanic acid significantly decreased cell proliferation, inhibited cell cycle, and stimulated apoptosis of the glioblastoma cells. Moreover, it could decrease the migration capability of glioblastoma cells, which was accompanied by inhibition in the activity and expression of MMP2 and MMP9. While galbanic acid reduced the gene expression of Akt, mTOR, and PI3K and increased the PTEN expression, it had no significant effect on WNT, β-catenin, and APC genes. In addition, the protein level of p-Akt decreased after treatment with galbanic acid. The effects of galbanic acid were observed at concentrations lower than those of temozolomide.

Conclusion: Galbanic acid decreased proliferation, cell cycle progression, and survival of glioblastoma cells through inhibiting the PI3K/Akt/mTOR pathway. This compound also reduced the migration capability of the cells by suppressing the activity and expression of MMPs.

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<![CDATA[The Radio-Sensitizing Effect of Pharmacological Concentration of Ascorbic Acid on Human Pancreatic Cancer Cells]]>https://www.eurekaselect.comarticle/107304Background: Previous studies reported the inevitable destructive effects of radiotherapy on normal adjacent cells. Ascorbic Acid (AA) has been proposed as an effective anti-cancer agent with no obvious effects on normal cells.

Objective: The effects of Ascorbic acid in combination with radiotherapy on human pancreatic carcinoma cell line were studied.

Methods: The human pancreatic cancer cells were cultured and divided into four groups: control group (A) without any treatment, group B that received 2Gy radiotherapy alone, group C that was treated with 4mM AA alone, and group D that was co-treated with AA and radiotherapy. Cell viability, DNA fragmentation, expression of apoptotic genes, and Reactive Oxygen Species (ROS) production were determined in treated cells.

Results: There was a noticeable decrease in cell viability after treatment with AA (and/or) radiotherapy. All treated groups showed elevated ROS production, Bax/Bcl2 expression, DNA fragmentation, and cytotoxycity compared with the control group. Cells under combination therapy showed the most cytotoxicity.

Conclusion: The results suggest that AA at a dose of 4mmol/l may be used as an effective radio-sensitizing agent in pancreatic cancer cell line.

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<![CDATA[Schiff Bases and Complexes: A Review on Anti-Cancer Activity]]>https://www.eurekaselect.comarticle/106427 <![CDATA[Role of ATP-Binding Cassette Transporter Proteins in CNS Tumors: Resistance- Based Perspectives and Clinical Updates]]>https://www.eurekaselect.comarticle/104772 <![CDATA[Isolation, Characterization and Preliminary Cytotoxic and Antifungal Evaluations of Novel Lancifoliate Isolated from Methanol Extract of <i>Conocarpus lancifolius</i>]]>https://www.eurekaselect.comarticle/106080Background: Combretaceae is a large family comprising of 500 species and 20 genera distributed in subtropical and tropical regions of the world. Conocarpus genus is an ornamental tree native to coastal and riverine areas of East Africa and is also planted as an ornamental plant in different areas of Pakistan. This genus has proved medicinal value as a cytotoxic, antibacterial, antiprotozoal, anti-leishmanial, antifungal and antidiabetic agent.

Objective: The current study was designed to screen the selected pharmacological attributes of sulphur containing novel compound isolated from Conocarpus lancifolius using a series of in vitro and molecular docking models.

Materials and Methods: After collection and authentication of plant material, methanolic extract was prepared from which various secondary metabolites were qualitatively examined. The compound was isolated using open column chromatography and the structure was established with spectroscopic techniques such as UV-visible, infrared spectroscopy, proton nuclear magnetic resonance (1H-NMR), 13C NMR (BB, DEPT-135, 90), twodimensional correlation techniques (HMBC, HSQC) and mass spectrometry (HRMS) respectively. C. lancifolius extract and isolated compound were studied for cytotoxic and antifungal potentials using in vitro Sulforhodamine B (SRB) and disc diffusion methods, respectively. Molecular docking studies were conducted to check the interaction of the isolated compound with major oncogenic proteins.

Results: Qualitative phytochemical screening revealed the presence of saponins, steroids, flavonoids, anthraquinones, and cardiac glycosides while alkaloids were absent in C. lancifolius extract. Isolated compound was characterized as lancifoliate, which showed cytotoxic activity towards a variety of cancer cell lines including murine lymphocytic leukemia (P-388, IC50 = 2.65μg/ml), human colon cancer (Col-2, IC50 = 0.84μg/ml), human breast cancer (MCF-7, IC50 = 0.72μg/ml) while no cytotoxic activity was observed towards human lung cancer (Lu-1), rat normal glioma cells (ASK, IC50 = 11.6μg/ml) and human embryonic kidney cells (Kek293, IC50 = 6.74μg/ml) respectively. Minimum Inhibitory Concentration (MIC) of Lancifoliate towards Aspergillus fumigatus, Aspergillus nigar (skin sample), Aspergillus flavus (pleural fluid) and Candida albicans (urine and blood samples) was found to be 54.5, 44.8, 43.5, 22.4 and 20.2μg/ml respectively. Moreover, docking results are in strong agreement with our experimental finding, which has identified lancifoliate to be a more potent antiproliferative agent than previously known compound ellipticine.

Conclusion: C. lancifolius extract and lancifoliate possess potent cytotoxic and antifungal properties and thus has potential to be further studied. To the best of our knowledge, this is the first study that highlights isolation, identification and pharmacological activities of lancifoliate from Conocarpus lancifolius.

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<![CDATA[Targeting MUC15 Protein in Cancer: Molecular Mechanisms and Therapeutic Perspectives]]>https://www.eurekaselect.comarticle/107017 <![CDATA[Folate-modified Graphene Oxide as the Drug Delivery System to Load Temozolomide]]>https://www.eurekaselect.comarticle/104868Objective: The folate-modified graphene oxide (GO-FA), which had good stability and biocompatibility on rat glioma cells was successfully prepared.

Methods: The formation and composition of GO-FA were confirmed by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier Transform Infrared Spectrum (FT-IR), Raman spectra and X-ray Photoelectron Spectroscopy (XPS spectra). The cell experiment suggested good biocompatibility of GO-FA on rat glioma cells.

Results: The experiment of GO-FA loading with Temozolomide (TMZ) showed that the maximum drug loading of GO-FA was 8.05 ± 0.20 mg/mg, with the drug loading rate of 89.52 ± 0.19 %. When TMZ was released from the folate-modified graphene oxide loading with temozolomide (GO-FATMZ), its release behavior in vitro showed strong pH dependence and sustained release property. The growth of rat glioma cells can be effectively inhibited by GO-FA-TMZ, with the cell inhibition rate as high as 91.72 ± 0.13 % at the concentration of 600 μg/mL and time of 72 h.

Conclusion: According to the above experimental results, this composite carrier has potential applications in drug delivery and cancer therapy.

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<![CDATA[Nano-Carriers of Combination Tumor Physical Stimuli-Responsive Therapies]]>https://www.eurekaselect.comarticle/106882via the platform of nanocarriers into combination TPSRTs, which include Photothermal Therapy (PTT) with Magnetic Hyperthermia Therapy (MHT), PTT with Sonodynamic Therapy (SDT), MHT with Photodynamic Therapy (PDT), and PDT with PTT. To achieve such therapies, it requires to fully utilize the versatile functions of a specific nanocarrier, which depend on a pellucid understanding of the traits of those nanocarriers. This review covers the principles of different TPSRTs and their combinations, summarizes various types of combination TPSRTs nanocarriers and their therapeutic effects on tumors, and discusses the current disadvantages and future developments of these nanocarriers in the application of combination TPSRTs.]]> <![CDATA[Modern Treatments for Gliomas Improve Outcome]]>https://www.eurekaselect.comarticle/101584 <![CDATA[Radiotherapy for Brain Tumors: Current Practice and Future Directions]]>https://www.eurekaselect.comarticle/94882 <![CDATA[Central Nervous System Neoplasms in Hong Kong: An Inscription of Local Studies]]>https://www.eurekaselect.comarticle/96156A registry of brain and central nervous system (CNS) tumor patients in Hong Kong comprising of data from both public and private neurosurgical practices (with approximately 98% patients of Chinese origin), suggested geographical or racial variations in disease incidence. The data confers the finding of a comparatively lower incidence rate of meningioma and malignant gliomas as in other parts of Southeast Asia.

With data suggesting epidemiological difference, the treatment response, particularly in highgrade glioma, was studied. Patients suffering from glioblastoma (GBM) in Hong Kong received the standard of care, which involves safe, maximal resection followed by the Stupp regime. 5-aminolevulinic acid (5-ALA)-based fluorescence-guided surgery was found to be feasible and safe to adopt in the treatment of local WHO Grade III & IV gliomas patients. Survival benefit was seen in a group of patients using extended adjuvant temozolomide (TMZ) treatment for newly diagnosed GBM as compared to those treated with the standard 6 cycles. Salvage therapies with either single agent bevacizumab or bevacizumab plus irinotecan appeared to be effective treatment options in Hong Kong patients with recurrent malignant glioma, with a good associated 6- month progression-free survival (PFS) rate which was comparable to previously published overseas data in this disease type in the same overall population.

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<![CDATA[Overview of Modern Surgical Management of Central Nervous System Tumors: North American Experience]]>https://www.eurekaselect.comarticle/96577 <![CDATA[<i>In Vitro</i> Characteristics of Glioma Cells Targeting by OX26-modified Liposomal Cisplatin]]>https://www.eurekaselect.comarticle/105539

Objective: This study aimed to evaluate the therapeutic effects of cisplatin-loaded PEGylated liposomes, targeted with the OX26 antibody (targeted liposomal cisplatin) against transferrin receptor expressing rat glioma C6 cells in vitro.

Methods: The liposomes were synthesized using reverse phase evaporation method and were conjugated to the OX26 monoclonal antibody. They were characterized in terms of size, drug encapsulation efficiency, morphology and drug release experiments using dynamic light scattering, atomic absorption spectrometry, scanning electron microscopy, and dialysis membrane methods. Then, their biological activities were evaluated on targeting the BBB.

Results and Discussion: The characterization results showed that spherical nanodrug with a size of 157 nm and drug loading efficiency of 24% was synthesized, which released 64% of the loaded cisplatin after 72 h in a controlled release manner. The nanoparticles caused an increase in the cisplatin cytotoxicity effects by 1.7-, 1.8- and 1.8-fold, compared to cisplatin-loaded PEGylated liposomes (liposomal cisplatin) after 24, 48 and 72h incubation, respectively against C6 cells. Moreover, targeted liposomal cisplatin showed promising results in the transport of cisplatin across the BBB, in which it caused an increase in the cisplatin cytotoxicity on C6 cells by 2.7- and 2.4-fold, compared to cisplatin and liposomal cisplatin, respectively.

Conclusion: Regarding the properties of the targeted liposomal cisplatin, it suggests that the potency of the formulation, to be evaluated, for the transport of cisplatin across the BBB, delivers it to the brain tumor in vivo.]]>
<![CDATA[Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier]]>https://www.eurekaselect.comarticle/105883 <![CDATA[Role of Nanomedicine in Treatment of Brain Cancer]]>https://www.eurekaselect.comarticle/94612Background: Drug delivery to cancerous brain is a challenging task as it is surrounded by an efficient protective barrier. The main hurdles for delivery of bioactive molecules to cancerous brain are blood brain barrier (BBB), the invasive nature of gliomas, drug resistance, and difficult brain interstitium transportation. Therefore, treatment of brain cancer with the available drug regimen is difficult and has shown little improvement in recent years.

Methods: We searched about recent advancements in the use of nanomedicine for effective treatment of the brain cancer. We focused on the use of liposomes, nanoparticles, polymeric micelles, and dendrimers to improve brain cancer therapy.

Results: Nanomedicines are well suited for the treatment of brain cancer owing to their highly acceptable biological, chemical, and physical properties. Smaller size of nanomedicines also enhances their anticancer potential and penetration into blood brain barrier (BBB).

Conclusion: Recently, nanomedicine based approaches have been developed and investigated for effective treatment of brain cancer. Some of these have been translated into clinical practice, in order to attain therapeutic needs of gliomas. Future advancements in nanomedicines will likely produce significant changes in methods and practice of brain cancer therapy.

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<![CDATA[Brain Tumor Detection from MR Images Employing Fuzzy Graph Cut Technique]]>https://www.eurekaselect.comarticle/95101Background: This research aims at the accurate selection of the seed points from the brain MRI image for the detection of the tumor region. Since, the conventional way of manual seed selection leads to inappropriate tumor extraction therefore, fuzzy clustering technique is employed for the accurate seed selection for performing the segmentation through graph cut method.

Methods: In the proposed method Fuzzy Kernel Seed Selection technique is used to define the complete brain MRI image into different groups of similar intensity. Among these groups the most accurate kernels are selected empirically that show highest resemblance with the tumor. The concept of fuzziness helps making the selection even at the boundary regions.

Results: The proposed Fuzzy kernel selection technique is applied on the BraTS dataset. Among the four modalities, the proposed technique is applied on Flair images. This dataset consists of Low Grade Glioma (LGG) and High Grade Glioma (HGG) tumor images. The experiment is conducted on more than 40 images and validated by evaluating the following performance metrics: 1. Disc Similarity Coefficient (DSC), 2. Jaccard Index (JI) and 3. Positive Predictive Value (PPV). The mean DSC and PPV values obtained for LGG images are 0.89 and 0.87 respectively; and for HGG images it is 0.92 and 0.90 respectively.

Conclusion: On comparing the proposed Fuzzy kernel selection graph cut technique approach with the existing techniques it is observed that the former provides an automatic accurate tumor detection. It is highly efficient and can provide a better performance for HGG and LGG tumor segmentation in clinical application.

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<![CDATA[Potential of Radiolabeled PSMA PET/CT or PET/MRI Diagnostic Procedures in Gliomas/Glioblastomas]]>https://www.eurekaselect.comarticle/101555Background: Radiolabeled prostate-specific membrane antigen PSMA-based PET/CT or PET/MRI is a whole-body imaging technique currently performed for the detection of prostate cancer lesions. PSMA has been also demonstrated to be expressed by the neovasculature of many other solid tumors.

Objective: The aim of this review is to evaluate the possible diagnostic role of radiolabeled PSMA PET/CT or PET/MRI in patients with gliomas and glioblastomas, by summarizing the available literature data.

Methods: A comprehensive literature search of the PubMed/MEDLINE, Scopus, Embase and Cochrane library databases was conducted to find relevant published articles about the diagnostic performance of radiolabeled PSMA binding agents in PET/CT or PET/MRI imaging of patients with suspected gliomas or glioblastomas.

Results: Seven case reports or case series and 3 studies enrolling more than 10 patients showed that gliomas and glioblastoma are PSMA-avid tumors.

Conclusion: Radiolabeled PSMA imaging seems to be useful in analyzing glioma/glioblastoma. Further studies enrolling a wider population are needed to clarify the real clinical and diagnostic role of radiolabeled PSMA in this setting and its possible position in the diagnostic flow-chart.

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<![CDATA[Curcumin Sensitizes Cancers Towards TRAIL-induced Apoptosis via Extrinsic and Intrinsic Apoptotic Pathways]]>https://www.eurekaselect.comarticle/104949 <![CDATA[SDResU-Net: Separable and Dilated Residual U-Net for MRI Brain Tumor Segmentation]]>https://www.eurekaselect.comarticle/100209Background: Glioma is one of the most common and aggressive primary brain tumors that endanger human health. Tumors segmentation is a key step in assisting the diagnosis and treatment of cancer disease. However, it is a relatively challenging task to precisely segment tumors considering characteristics of brain tumors and the device noise. Recently, with the breakthrough development of deep learning, brain tumor segmentation methods based on fully convolutional neural network (FCN) have illuminated brilliant performance and attracted more and more attention.

Methods: In this work, we propose a novel FCN based network called SDResU-Net for brain tumor segmentation, which simultaneously embeds dilated convolution and separable convolution into residual U-Net architecture. SDResU-Net introduces dilated block into a residual U-Net architecture, which largely expends the receptive field and gains better local and global feature descriptions capacity. Meanwhile, to fully utilize the channel and region information of MRI brain images, we separate the internal and inter-slice structures of the improved residual U-Net by employing separable convolution operator. The proposed SDResU-Net captures more pixel-level details and spatial information, which provides a considerable alternative for the automatic and accurate segmentation of brain tumors.

Results and Conclusion: The proposed SDResU-Net is extensively evaluated on two public MRI brain image datasets, i.e., BraTS 2017 and BraTS 2018. Compared with its counterparts and stateof- the-arts, SDResU-Net gains superior performance on both datasets, showing its effectiveness. In addition, cross-validation results on two datasets illuminate its satisfying generalization ability.

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<![CDATA[Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms]]>https://www.eurekaselect.comarticle/104902 <![CDATA[Artemia species: An Important Tool to Screen General Toxicity Samples]]>https://www.eurekaselect.comarticle/105658 <![CDATA[Spontaneous Chest Abscess Caused by Salmonella Enterica subsp. Arizonae in the Desert Southwest; A Case Report and Review of the Current Literature]]>https://www.eurekaselect.comarticle/94269Salmonella enterica subspecies arizonae is a rare pathogen but has been reported in the literature in immunosuppressed and rarely immunocompetent patients. Most disease states have been reported in animals and reptiles. Human exposure has resulted in a range of complications from skin and soft tissue infections to bacteremia and periprosthetic joint infections. Predisposing factors such as age, comorbidities, and use of Mexican folk healing practices increase the risk of developing an infection. S. arizonae has been associated with gastrointestinal infections in several parts of the country and on rare occasions have been isolated from skin and soft tissues, prosthetic joints, and empyema.

Case: This is a unique case of a large de novo chest abscess that developed in a 59-year-old diabetic male from the Southwest region with cultures growing Salmonella enterica subspecies arizonae. This patient presented without predisposing factors and did not appear to be ill at the time of admission. He was treated successfully by aspirating the abscess along with a 2-week course of ceftriaxone intravenously.

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<![CDATA[FAT10: Function and Relationship with Cancer]]>https://www.eurekaselect.comarticle/102314 <![CDATA[B7-H3-targeted Radioimmunotherapy of Human Cancer]]>https://www.eurekaselect.comarticle/96941Background: Targeted Radioimmunotherapy (RIT) is an attractive approach to selectively localize therapeutic radionuclides to malignant cells within primary and metastatic tumors while sparing normal tissues from the effects of radiation. Many human malignancies express B7-H3 on the tumor cell surface, while expression on the majority of normal tissues is limited, presenting B7-H3 as a candidate target for RIT. This review provides an overview of the general principles of targeted RIT and discusses publications that have used radiolabeled B7-H3-targeted antibodies for RIT of cancer in preclinical or clinical studies.

Methods: Databases including PubMed, Scopus, and Google Scholar were searched for publications through June 2018 using a combination of terms including “B7-H3”, “radioimmunotherapy”, “targeted”, “radiotherapy”, and “cancer”. After screening search results for relevancy, ten publications were included for discussion.

Results: B7-H3-targeted RIT studies to date range from antibody development and assessment of novel Radioimmunoconjugates (RICs) in animal models of human cancer to phase II/III trials in humans. The majority of clinical studies have used B7-H3-targeted RICs for intra- compartment RIT of central nervous system malignancies. The results of these studies have indicated high tolerability and favorable efficacy outcomes, supporting further assessment of B7-H3-targeted RIT in larger trials. Preclinical B7-H3-targeted RIT studies have also shown encouraging therapeutic outcomes in a variety of solid malignancies.

Conclusion: B7-H3-targeted RIT studies over the last 15 years have demonstrated feasibility for clinical development and support future assessment in a broader array of human malignancies. Future directions worthy of exploration include strategies that combine B7-H3- targeted RIT with chemotherapy or immunotherapy.

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<![CDATA[Modulation of Immuno-biome during Radio-sensitization of Tumors by Glycolytic Inhibitors]]>https://www.eurekaselect.comarticle/90858 <![CDATA[Brain Cancer-Activated Microglia: A Potential Role for Sphingolipids]]>https://www.eurekaselect.comarticle/98373Almost no neurological disease exists without microglial activation. Microglia has exert a pivotal role in the maintenance of the central nervous system and its response to external and internal insults. Microglia have traditionally been classified as, in the healthy central nervous system, “resting”, with branched morphology system and, as a response to disease, “activated”, with amoeboid morphology; as a response to diseases but this distinction is now outmoded. The most devastating disease that hits the brain is cancer, in particular glioblastoma. Glioblastoma multiforme is the most aggressive glioma with high invasiveness and little chance of being surgically removed. During tumor onset, many brain alterations are present and microglia have a major role because the tumor itself changes microglia from the pro-inflammatory state to the anti-inflammatory and protects the tumor from an immune intervention.

What are the determinants of these changes in the behavior of the microglia? In this review, we survey and discuss the role of sphingolipids in microglia activation in the progression of brain tumors, with a particular focus on glioblastoma.

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<![CDATA[Plasminogen Receptors in Human Malignancies: Effects on Prognosis and Feasibility as Targets for Drug Development]]>https://www.eurekaselect.comarticle/102536 <![CDATA[Ligand Conjugated Targeted Nanotherapeutics for Treatment of Neurological Disorders]]>https://www.eurekaselect.comarticle/105881Background: Human brain is amongst the most complex organs in human body, and delivery of therapeutic agents across the brain is a tedious task. Existence of blood brain barrier (BBB) protects the brain from invasion of undesirable substances; therefore it hinders the transport of various drugs used for the treatment of different neurological diseases including glioma, Parkinson's disease, Alzheimer's disease, etc. To surmount this barrier, various approaches have been used such as the use of carrier mediated drug delivery; use of intranasal route, to avoid first pass metabolism; and use of ligands (lactoferrin, apolipoprotein) to transport the drug across the BBB. Ligands bind with proteins present on the cell and facilitate the transport of drug across the cell membrane via. receptor mediated, transporter mediated or adsorptive mediated transcytosis.

Objective: The main focus of this review article is to illustrate various studies performed using ligands for delivering drug across BBB; it also describes the procedure used by various researchers for conjugating the ligands to the formulation to achieve targeted action.

Methods: Research articles that focused on the used of ligand conjugation for brain delivery and compared the outcome with unconjugated formulation were collected from various search engines like PubMed, Science Direct and Google Scholar, using keywords like ligands, neurological disorders, conjugation, etc.

Results and Conclusion: Ligands have shown great potential in delivering drug across BBB for treatment of various diseases, yet extensive research is required so that the ligands can be used clinically for treating neurological diseases.

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<![CDATA[Spectroscopic and Chromatographic Characterization of Crude Natural Shilajit from Himachal Pradesh, India]]>https://www.eurekaselect.comarticle/95732Background: Shilajit is a natural herbomineral ethnomedicinal substance used in Indian traditional systems of medicine since centuries as a rejuvenator, anti-aging and for several health conditions/ailments. Shilajit composition has exhibited considerable variability from different geographical sites and hence there is a need to determine its composition and concentration of bioactive compounds to correlate it with pharmacological activities.

Objective: To determine the chemical and mineral constitution of Shilajit obtained from Himachal Pradesh, India.

Method: In the present study, Shilajit was chemically characterized by Fourier Transform Infrared (FTIR) spectroscopy, Gas Chromatography-Mass Spectrometry (GC-MS), Inductively-Coupled Plasma Mass Spectrometry (ICP-MS), UV-Vis spectroscopy and High-Performance Liquid Chromatography (HPLC) analysis.

Results: Chemical elucidation of crude Shilajit from three geographical sites revealed the presence of humic acid, fulvic acid, dibenzo-α-pyrones and several other organic constituents in crude Shilajit. The presence of metals/trace elements was evident in Shilajit samples with potassium being predominant followed by magnesium, calcium, sodium, iron and aluminium.

Conclusion: Characterization of Shilajit from Himachal Pradesh supported the structural details of Shilajit already known and also revealed variations in key chemical parameters which might be due to geographical variations and ecological conditions which determine its natural synthesis.

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<![CDATA[Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells]]>https://www.eurekaselect.comarticle/104190Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown.

Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines.

Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR).

Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53.

Conclusion: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

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<![CDATA[Focus on the Use of Resveratrol as an Adjuvant in Glioblastoma Therapy]]>https://www.eurekaselect.comarticle/105571 <![CDATA[The Potential Targets and Mechanisms of a Carbazole and Pyrazole Containing Anticancer Compound]]>https://www.eurekaselect.comarticle/103669Aims: Characterization of a small anticancer compound.

Background: The development of small molecules as new anti-cancer therapeutics is necessary to improve anti-tumor efficacy and reduce toxicities, especially for the treatment of brain tumors, where only small molecules can effectively cross the brain-blood barrier. Several novel hits were previously selected by concurrently screening colon and glioma cancer cell lines with a sensorconjugated reporter system. Here, we focused on one of them.

Objective: Elucidating the potential target(s) of a novel anticancer compound.

Methods: Computer-assisted structural and motif analysis (least absolute shrinkage and selection operator or LASSO score) was used to assess compound’s targets, then direct kinase activity assays were used for the confirmation; Western blot of phosphorylated kinases, as well as FACS and caspase 3/7 activity assays, were used to decipher the action mechanisms. Finally, the expression profiling of proteins involved in various G-protein pathways by real-time PCR was performed.

Results: The small chemical, (4E)-4-[2-(9-ethyl-9H-carbazol-3-yl)hydrazin-1-ylidene]-3-methyl- 4,5-dihydro-1H-pyrazol-5-one, with a formula C18H17N5O and MW of 319.36, designated as VUGX01, was predicted to be a ligand/inhibitor to receptor tyrosine kinases (RTKs) by computer analysis (least absolute shrinkage and selection operator or LASSO score). However, direct analysis with recombinant kinases showed that it is not an effective inhibitor to the popular receptor kinases at 1μM concentration. This compound can activate caspases in some tumor cell lines but has minimal effects on the cell cycle. Drug treatments lead to the changes in phosphorylation of AKT and c- RAF, as well as the expression level of MAP2K, suggesting this compound may interact with Gprotein coupled receptors (GPCRs). The expression profiling of 82 proteins involved in various Gprotein pathways by real-time PCR showed that the treatment up-regulates the expression of several proteins, including angiotensinogen, angiotensin II receptor, and IP3-kinase catalytic subunit gamma.

Conclusion: VUGX01 can effectively block proliferation and induce apoptosis of certain types of cancer cells, even it is predicted by high LASSO score, but it is not an effective RTKs inhibitor, it may inhibit cell growth through acting as a novel ligand to one or several GPCRs.

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<![CDATA[Novel Homeodomain Transcription Factor Nkx2.2 in the Brain Tumor Development]]>https://www.eurekaselect.comarticle/87675Background: Complex central nervous system (CNS) is made up of neuronal cells and glial cells. Cells of central nervous system are able to regenerate after injury and during repairing. Sonic hedgehog pathway initiated by Shh-N a glycoprotein plays vital role in CNS patterning growth, development and now tumorigenesis. Nkx2.2 homeodomain transcription factor is an effecter molecule, which is positively regulated by Shh during normal growth. Nkx2.2 is essential for V3 domain specification during neural tube patterning at embryonic stage. MBP + oligodendrocytes are differentiated from progenitor cells which express Olig2. Nx2.2 is co-expressed with Olig2 in oligodendrocytes and is essential for later stage of oligodendrocyte maturation.

Objective: This review paper explores the potential role of Nkx2.2 transcription factor in glioblastoma development.

Conclusion: Shh pathway plays a vital role in oligodendrocytes differentiation and Nkx2.2 transcription factor is essential for oligodendrocytes differentiation and maturation. Intriguingly, down regulation of Nkx2.2 transcription factor with aberrant Shh signaling pathway is reported in glioma samples. So here it is suggested that Nkx2.2 expression pattern could be used as a potential biomarker for the early diagnosis of glioma.

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<![CDATA[Glioblastoma: Prognostic Factors and Predictive Response to Radio and Chemotherapy]]>https://www.eurekaselect.comarticle/104111Glioblastoma multiforme (GBM) is characterized by poor prognosis despite an aggressive therapeutic strategy. In recent years, many advances have been achieved in the field of glioblastoma biology.

Here we try to summarize the main clinical and biological factors impacting clinical prognostication and therapy of GBM patients. From that standpoint, hopefully, in the near future, personalized therapies will be available.

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<![CDATA[Idronoxil as an Anticancer Agent: Activity and Mechanisms]]>https://www.eurekaselect.comarticle/103419 <![CDATA[Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules]]>https://www.eurekaselect.comarticle/94306 <![CDATA[Epidermal Growth Factor Receptor and its Trafficking Regulation by Acetylation: Implication in Resistance and Exploring the Newer Therapeutic Avenues in Cancer]]>https://www.eurekaselect.comarticle/104286Background: The EGFR is overexpressed in numerous cancers. So, it becomes one of the most favorable drug targets. Single-acting EGFR inhibitors on prolong use induce resistance and side effects. Inhibition of EGFR and/or its interacting proteins by dual/combined/multitargeted therapies can deliver more efficacious drugs with less or no resistance.

Objective: The review delves deeper to cover the aspects of EGFR mediated endocytosis, leading to its trafficking, internalization, and crosstalk(s) with HDACs.

Methods and Results: This review is put forth to congregate relevant literature evidenced on EGFR, its impact on cancer prognosis, inhibitors, and its trafficking regulation by acetylation along with the current strategies involved in targeting these proteins (EGFR and HDACs) successfully by involving dual/hybrid/combination chemotherapy.

Conclusion: The current information on cross-talk of EGFR and HDACs would likely assist researchers in designing and developing dual or multitargeted inhibitors through combining the required pharmacophores.

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<![CDATA[Isoform-Selective PI3K Inhibitors for Various Diseases]]>https://www.eurekaselect.comarticle/103500 <![CDATA[Knockdown of Enhancer of Zeste Homolog 2 Affects mRNA Expression of Genes Involved in the Induction of Resistance to Apoptosis in MOLT-4 Cells]]>https://www.eurekaselect.comarticle/104079Background: The Enhancer of Zeste Homolog 2 (EZH2) is a subunit of the polycomb repressive complex 2 that silences the gene transcription via H3K27me3. Previous studies have shown that EZH2 has an important role in the induction of the resistance against the Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis (TIA) in some leukemia cells.

Objective: The aim of this study was to determine the effect of silencing EZH2 gene expression using RNA interference on the expression of death receptors 4 and 5 (DR4/5), Preferentially expressed Antigen in Melanoma (PRAME), and TRAIL human lymphoid leukemia MOLT-4 cells.

Methods: Quantitative RT-PCR was used to detect the EZH2 expression and other candidate genes following the siRNA knockdown in MOLT-4 cells. The toxicity of the EZH2 siRNA was evaluated using Annexin V/PI assay following the transfection of the cells by 80 pM EZH2 siRNA at 48 hours.

Results: Based on the flow-cytometry results, the EZH2 siRNA had no toxic effects on MOLT-4 cells. Also, the EZH2 inhibition increased the expression of DR4/5 but reduced the PRAME gene expression at the mRNA levels. Moreover, the EZH2 silencing could not change the TRAIL mRNA in the transfected cells.

Conclusion: Our results revealed that the down-regulation of EZH2 in MOLT-4 cells was able to affect the expression of important genes involved in the induction of resistance against TIA. Hence, we suggest that the silencing of EZH2 using RNA interference can be an effective and safe approach to help defeat the MOLT-4 cell resistance against TIA.

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<![CDATA[Determination of Dysregulated miRNA Expression Levels by qRT-PCR after the Application of Usnic Acid to Breast Cancer]]>https://www.eurekaselect.comarticle/100969Background and Purpose: Breast cancer still remains to be one of the most threatening cancer types in women. Recent studies have allowed scientists to better investigate the potential use of natural compounds in the treatment of breast cancers. Usnic acid is a secondary metabolite extracted from lichen species and has many biological activities. The response of microRNAs regulated by drug molecules may provide useful diagnostic and prognostic biomarkers, as well as potential therapeutics for breast cancers. Although the aberrant expression of microRNAs was observed after drug treatment, the regulatory mechanisms remain partially known. Micro RNAs (miRNAs) play an important role in gene regulation at the post-transcriptional level.

Methods: In this study, we used quantitative Real-Time PCR (qRT-PCR) technology to demonstrate that usnic acid significantly changes the expression profile of miRNAs.

Results: Eleven miRNAs were significantly and differentially expressed in breast cancer cells after treatment with usnic acid. Three miRNAs were up-regulated, while eight were down-regulated in usnic acid treated cells. Target prediction and GO analysis revealed many target genes and their related pathways that are potentially regulated by usnic acid regulated differentially expressed miRNAs. We found that usnic acid treatment caused significant changes in the expression of hsa-miR-5006-5p, hsa-miR-892c-3p, hsa-miR-4430, hsa-miR-5194, hsa-miR-3198, hsa-miR-3171, hsa-miR-933 and hsa-miR-185-3p in breast cancer cells.

Conclusion: Usnic acid response miRNAs might play important regulatory roles in the tumorigenesis and development of breast cancer, and they could serve as prognostic predictors for breast cancer patients.

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<![CDATA[Akt Pathway Inhibitors]]>https://www.eurekaselect.comarticle/104753 <![CDATA[Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review]]>https://www.eurekaselect.comarticle/104114 <![CDATA[DLEU1: A Functional Long Noncoding RNA in Tumorigenesis]]>https://www.eurekaselect.comarticle/103829

Methods: In this review, current studies concerning the biological functions and mechanisms of DLEU1 in tumor development are summarized and analyzed; the related researches are collected through a systematic retrieval of PubMed.

Results: DLEU1 is a novel cancer-associated lncRNA that has been proved to be abnormally elevated in various malignancies, containing osteosarcoma, glioma, glioblastoma multiforme, hepatocellular carcinoma, bladder cancer, cervical cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, colorectal cancer, oral squamous cell carcinoma, endometrial cancer, gastric cancer, Burkitt lymphoma and ovarian carcinoma. Besides, lncRNA LDEU1 has been demonstrated involving in the procession of proliferation, migration, invasion and inhibition of apoptosis of cancer cells.

Conclusion: Long non-coding RNA DLEU1 is likely to represent an available biomarker or a potential therapeutic target in multiple tumors.]]>
<![CDATA[Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers]]>https://www.eurekaselect.comarticle/103820 <![CDATA[Aquaporins and Roles in Brain Health and Brain Injury]]>https://www.eurekaselect.comarticle/101616 <![CDATA[Expression of P-gp in Glioblastoma: What we can Learn from Brain Development]]>https://www.eurekaselect.comarticle/105348 <![CDATA[Lipid-based Nanoplatforms in Cancer Therapy: Recent Advances and Applications]]>https://www.eurekaselect.comarticle/103666 <![CDATA[Active Targeting Towards and Inside the Brain based on Nanoparticles: A Review]]>https://www.eurekaselect.comarticle/102718

Methods: The coherence structure of the brain is due to the presence of the blood-brain barrier (BBB), which consists of a continuous layer of capillary endothelial cells. The BBB prevents most drugs from entering the brain tissue and is highly selective, permitting only metabolic substances and nutrients to pass through.

Results: Although this challenge has caused difficulties for the treatment of neurological diseases, it has opened up a broad research area in the field of drug delivery. Through the utilization of nanoparticles (NPs), nanotechnology can provide the ideal condition for passing through the BBB.

Conclusion: NPs with suitable dimensions and optimum hydrophobicity and charge, as well as appropriate functionalization, can accumulate in the brain. Furthermore, NPs can facilitate the targeted delivery of therapeutics into the brain areas involved in Alzheimer’s disease, Parkinson’s disease, stroke, glioma, migraine, and other neurological disorders. This review describes these methods of actively targeting specific areas of the brain.]]>
<![CDATA[Circulating Biomarkers for Tumor Angiogenesis: Where Are We?]]>https://www.eurekaselect.comarticle/92573

Objectives: The purpose of this review is to describe current reports on circulating diagnostic and prognostic biomarkers related to angiogenesis. We further discuss how this non-invasive strategy could improve the monitoring of tumor treatment and help clinical strategy.

Results: We discuss the latest evidence in the literature regarding circulating anti-angiogenic markers. Besides growth factor proteins, different circulating miRNAs could exert a pro- or anti-angiogenic activity so as to represent suitable candidates for a non-invasive strategy. Recent reports indicate that tumor-derived exosomes, which are small membrane vesicles abundant in biological fluids, also have an impact on vascular remodeling.

Conclusion: Numerous circulating biomarkers related to angiogenesis have been recently identified. Their use will allow identifying patients who are more likely to benefit from a specific anti-angiogenic treatment, as well as detecting those who will develop resistance and/or adverse effects. Nonetheless, further studies are required to elucidate the role of these biomarkers in clinical settings.]]>
<![CDATA[Pharmacokinetics and Acute Toxicity of a Histone Deacetylase Inhibitor, Scriptaid, and its Neuroprotective Effects in Mice After Intracranial Hemorrhage]]>https://www.eurekaselect.comarticle/103108

Methods: The pharmacokinetics, acute toxicity, and tissue distribution were determined in C57BL/6 male and female mice after the intraperitoneal administration of a single dose. Behavioral tests, as well as investigations of brain atrophy and white matter injury, were used to evaluate the neuroprotective effect of Scriptaid after ICH. Western blotting was used to investigate if Scriptaid could offer antiinflammatory benefits after ICH.

Results: No significant differences were observed in body weight or brain histopathology between the group that received Scriptaid at 50 mg/kg and the group that received dimethyl sulfoxide (control). The pharmacokinetics of Scriptaid in mice was nonlinear, and it was cleared rapidly at low doses and slowly at higher doses. Consistent with the pharmacokinetic data, Scriptaid was found to distribute in several tissues, including the spleen and kidneys. In the ICH model, we found that Scriptaid could reduce neurological deficits, brain atrophy, and white matter injury in a dose-dependent manner. Western blotting results demonstrated that Scriptaid could decrease the expression of pro-inflammatory cytokines IL1β and TNFα, as well as iNOS, after ICH.

Conclusion: These findings indicate that Scriptaid is safe and can alleviate brain injury after ICH, thereby providing a foundation for the pharmacological action of Scriptaid in the treatment of brain injury after ICH.]]>
<![CDATA[Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency]]>https://www.eurekaselect.comarticle/104346Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment.

Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor.

Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs).

Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells.

Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

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<![CDATA[Understanding the Pharmaceutical Aspects of Dendrimers for the Delivery of Anticancer Drugs]]>https://www.eurekaselect.comarticle/102011 <![CDATA[Anticancer Potential of Dietary Natural Products: A Comprehensive Review]]>https://www.eurekaselect.comarticle/101453 <![CDATA[Factors Affecting the Metabolite Productions in Endophytes: Biotechnological Approaches for Production of Metabolites]]>https://www.eurekaselect.comarticle/99238 <![CDATA[Therapy Based on the Regulation of Thiol-dependent Redox Systems]]>https://www.eurekaselect.comarticle/106065 <![CDATA[Redox Regulation in the Base Excision Repair Pathway: Old and New Players as Cancer Therapeutic Targets]]>https://www.eurekaselect.comarticle/98296Background: Reactive Oxygen Species (ROS) are by-products of normal cellular metabolic processes, such as mitochondrial oxidative phosphorylation. While low levels of ROS are important signalling molecules, high levels of ROS can damage proteins, lipids and DNA. Indeed, oxidative DNA damage is the most frequent type of damage in the mammalian genome and is linked to human pathologies such as cancer and neurodegenerative disorders. Although oxidative DNA damage is cleared predominantly through the Base Excision Repair (BER) pathway, recent evidence suggests that additional pathways such as Nucleotide Excision Repair (NER) and Mismatch Repair (MMR) can also participate in clearance of these lesions. One of the most common forms of oxidative DNA damage is the base damage 8-oxoguanine (8-oxoG), which if left unrepaired may result in G:C to A:T transversions during replication, a common mutagenic feature that can lead to cellular transformation.

Objective: Repair of oxidative DNA damage, including 8-oxoG base damage, involves the functional interplay between a number of proteins in a series of enzymatic reactions. This review describes the role and the redox regulation of key proteins involved in the initial stages of BER of 8-oxoG damage, namely Apurinic/Apyrimidinic Endonuclease 1 (APE1), human 8-oxoguanine DNA glycosylase-1 (hOGG1) and human single-stranded DNA binding protein 1 (hSSB1). Moreover, the therapeutic potential and modalities of targeting these key proteins in cancer are discussed.

Conclusion: It is becoming increasingly apparent that some DNA repair proteins function in multiple repair pathways. Inhibiting these factors would provide attractive strategies for the development of more effective cancer therapies.

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<![CDATA[Thioredoxin, Glutathione and Related Molecules in Tumors of the Nervous System]]>https://www.eurekaselect.comarticle/96286Background: Central Nervous System (CNS) tumors have a poor survival prognosis due to their invasive and heterogeneous nature, in addition to the resistance to multiple treatments.

Objective: In this paper, the main aspects of brain tumor biology and pathogenesis are reviewed both for primary tumors of the brain, (i.e., gliomas) and for metastasis from other malignant tumors, namely lung cancer, breast cancer and malignant melanoma which account for a high percentage of overall malignant brain tumors. We review the role of antioxidant systems, namely the thioredoxin and glutathione systems, in the genesis and/or progression of brain tumors.

Methods: Although overexpression of Thioredoxin Reductase (TrxR) and Thioredoxin (Trx) is often linked to increased malignancy rate of brain tumors, and higher expression of Glutathione (GSH) and Glutathione S-Transferases (GST) are associated to resistance to therapy, several knowledge gaps still exist regarding for example, the role of Peroxiredoxins (Prx), and Glutaredoxins (Grx).

Conclusion: Due to their central role in redox homeostasis and ROS scavenging, redox systems are potential targets for new antitumorals and examples of innovative therapeutics aiming at improving success rates in brain tumor treatment are discussed.

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<![CDATA[The Disposal of Reactive Carbonyl Species through Carnosine Conjugation: What We Know Now]]>https://www.eurekaselect.comarticle/99168Reactive Carbonyl Species are electrophiles generated by the oxidative cleavage of lipids and sugars. Such compounds have been described as important molecules for cellular signaling, whilst their accumulation has been found to be cytotoxic as they may trigger aberrant modifications of proteins (a process often referred to as carbonylation).

A correlation between carbonylation of proteins and human disease progression has been shown in ageing, diabetes, obesity, chronic renal failure, neurodegeneration and cardiovascular disease. However, the fate of reactive carbonyl species is still far from being understood, especially concerning the mechanisms responsible for their disposal as well as the importance of this in disease progression.

In this context, some data have been published on phase I and phase II deactivation of reactive carbonyl species. In the case of phase II mechanisms, the route involving glutathione conjugation and subsequent disposal of the adducts has been extensively studied both in vitro and in vivo for some of the more representative compounds, e.g. 4-hydroxynonenal.

There is also emerging evidence of an involvement of carnosine as an endogenous alternative to glutathione for phase II conjugation. However, the fate of carnosine conjugates is still poorly investigated and, unlike glutathione, there is little evidence of the formation of carnosine adducts in vivo. The acquisition of such data could be of importance for the development of new drugs, since carnosine and its derivatives have been proposed as potential therapeutic agents for the mitigation of carbonylation associated with disease progression.

Herein, we wish to review our current knowledge of the binding of reactive carbonyl species with carnosine together with the disposal of carnosine conjugates, emphasizing those aspects still requiring investigation such as conjugation reversibility and enzyme assisted catalysis of the reactions.

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<![CDATA[Do We have a Satisfactory Cell Viability Assay? Review of the Currently Commercially-Available Assays]]>https://www.eurekaselect.comarticle/93199Cell-based assays are an important part of the drug discovery process and clinical research. One of the main hurdles is to design sufficiently robust assays with adequate signal to noise parameters while maintaining the inherent physiology of the cells and not interfering with the pharmacology of target being investigated.

A plethora of assays that assess cell viability (or cell heath in general) are commercially available and can be classified under different categories according to their concepts and principle of reactions. The assays are valuable tools, however, suffer from a large number of limitations. Some of these limitations can be procedural or operational, but others can be critical as those related to a poor concept or the lack of proof of concept of an assay, e.g. those relying on differential permeability of dyes in-and-out of viable versus compromised cell membranes. While the assays can differentiate between dead and live cells, most, if not all, of them can just assess the relative performance of cells rather than providing a clear distinction between healthy and dying cells. The possible impact of relatively high molecular weight dyes, used in most of the assay, on cell viability has not been addressed. More innovative assays are needed, and until better alternatives are developed, setup of current cell-based studies and data interpretation should be made with the limitations in mind. Negative and positive control should be considered whenever feasible. Also, researchers should use more than one orthogonal method for better assessment of cell health.

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<![CDATA[Deglucohellebrin: A Potent Agent for Glioblastoma Treatment]]>https://www.eurekaselect.comarticle/102511Background: Glioblastoma is the most common primary brain tumor in adults with a dismal prognosis. To date, several anticancer agents have been isolated from plants. Helleborus odorus subsp. Cyclophyllus is an endemic plant of the Balcan flora. Herewith, we investigated for the first time, the anti-glioma effect of deglucohellebrin (DGH) extracted from the roots of Helleborus.

Methods: We investigated the effect of DGH in U251MG, T98G and U87G glioblastoma cell lines. We selected the T98G cells because of their inherent temozolomide resistance.

Results: The IC50 value of reduced viability for DGH was 7x10-5M in U251MG cells, 5x10-5M for the T98G cells and 4x10-5M in U87G cells during 72h treatment. DGH induced G2/M cell cycle arrest, caspace-8 activation and significant mitochondrial membrane depolarization, suggesting the activation of the intrinsic, mitochondrial- dependent apoptotic pathway. DGH and temozolomide induced changes in CDs’ expression in U251MG and T98G cells. In zebrafish, DGH did not induce toxicity or behavioral alterations.

Conclusion: The present study is the first to determine the anti-glioma activity of DGH. DGH may be a potent agent for glioblastoma treatment and further studies are needed.

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<![CDATA[Oxidative Stress Modulation and Radiosensitizing Effect of Quinoxaline-1,4-Dioxides Derivatives]]>https://www.eurekaselect.comarticle/101937Background: Quinoxaline-1,4-dioxide (QNX) derivatives are synthetic heterocyclic compounds with multiple biological and pharmacological effects.

Objective: In this study, we investigated the oxidative status of quinoxaline-1,4-dioxides derivatives in modulating melanoma and glioma cell lines, based on previous results from the research group and their capability to promote cell damage by the production of Reactive Oxygen Species (ROS).

Methods: Using in vitro cell cultures, the influence of 2-amino-3-cyanoquinoxaline-1,4-dioxide (2A3CQNX), 3- methyl-2-quinoxalinecarboxamide-1,4-dioxide (3M2QNXC) and 2-hydroxyphenazine-1,4-dioxide (2HF) was evaluated in metabolic activity, catalase activity, glutathione and 3-nitrotyrosine (3-NT) quantitation by HPLC in malignant melanocytes (B16-F10, MeWo) and brain tumor cells (GL-261 and BC3H1) submitted to radiotherapy treatments (total dose of 6 Gy).

Results: 2HF increased the levels of 3-NT in non-irradiated MeWo and glioma cell lines and decreased cell viability in these cell lines with and without irradiation.

Conclusion: Quinoxaline-1,4-dioxides derivatives modulate the oxidative status in malignant melanocytes and brain tumor cell lines and exhibited a potential radiosensitizer in vitro action on the tested radioresistant cell lines.

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<![CDATA[Will Arsenic Trioxide Benefit Treatment of Solid Tumor by Nano- Encapsulation?]]>https://www.eurekaselect.comarticle/101625 <![CDATA[Omega-3 Polyunsaturated Fatty Acid Derived Lipid Mediators and their Application in Drug Discovery]]>https://www.eurekaselect.comarticle/93273 <![CDATA[A Walk in Nature: Sesquiterpene Lactones as Multi-Target Agents Involved in Inflammatory Pathways]]>https://www.eurekaselect.comarticle/91816 <![CDATA[Marine Natural Products with High Anticancer Activities]]>https://www.eurekaselect.comarticle/103621 <![CDATA[Carbohydrates: Potential Sweet Tools Against Cancer]]>https://www.eurekaselect.comarticle/91819Cancer, one of the most devastating degenerative diseases nowadays, is one of the main targets in Medicinal Chemistry and Pharmaceutical industry. Due to the significant increase in the incidence of cancer within world population, together with the complexity of such disease, featured with a multifactorial nature, access to new drugs targeting different biological targets connected to cancer is highly necessary.

Among the vast arsenal of compounds exhibiting antitumor activities, this review will cover the use of carbohydrate derivatives as privileged scaffolds. Their hydrophilic nature, together with their capacity of establishing selective interactions with biological receptors located on cell surface, involved in cell-to-cell communication processes, has allowed the development of an ample number of new templates useful in cancer treatment.

Their intrinsic water solubility has allowed their use as of pro-drug carriers for accessing more efficiently the pharmaceutical targets. The preparation of glycoconjugates in which the carbohydrate is tethered to a pharmacophore has also allowed a better permeation of the drug through cellular membranes, in which selective interactions with the carbohydrate motifs are involved. In this context, the design of multivalent structures (e.g. gold nanoparticles) has been demonstrated to enhance crucial interactions with biological receptors like lectins, glycoproteins that can be involved in cancer progression.

Moreover, the modification of the carbohydrate structural motif, by incorporation of metal complexes, or by replacing their endocyclic oxygen, or carbon atoms with heteroatoms has led to new antitumor agents.

Such diversity of sugar-based templates with relevant antitumor activity will be covered in this review.

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<![CDATA[Cordycepin in Anticancer Research: Molecular Mechanism of Therapeutic Effects]]>https://www.eurekaselect.comarticle/93307Background: Cordycepin is a nucleotide analogue from Cordyceps mushrooms, which occupies a notable place in traditional medicine.

Objective: In this review article, we have discussed the recent findings on the molecular aspects of cordycepin interactions with its recognized cellular targets, and possible mechanisms of its anticancer activity.

Methods: We have explored databases like pubmed, google scholar, scopus and web of science for the update information on cordycepin and mechanisms of its anticancer activity, and reviewed in this study.

Results: Cordycepin has been widely recognized for its therapeutic potential against many types of cancers by various mechanisms. More specifically, cordycepin can induce apoptosis, resist cell cycle and cause DNA damage in cancer cells, and thus kill or control cancer cell growth. Also cordycepin can induce autophagy and modulate immune system. Furthermore, cordycepin also inhibits tumor metastasis. Although many success stories of cordycepin in anticancer research in vitro and in animal model, and there is no successful clinical trial yet.

Conclusion: Ongoing research studies have reported highly potential anticancer activities of cordycepin with numerous molecular mechanisms. The in vitro and in vivo success of cordycepin in anticancer research might influence the clinical trials of cordycepin, and this molecule might be used for development of future cancer drug.

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<![CDATA[Hydrogel-clay Nanocomposites as Carriers for Controlled Release]]>https://www.eurekaselect.comarticle/92742 <![CDATA[Phytochemical-Mediated Glioma Targeted Treatment: Drug Resistance and Novel Delivery Systems]]>https://www.eurekaselect.comarticle/100269 <![CDATA[Anti-inflammatory Property of AMP-activated Protein Kinase]]>https://www.eurekaselect.comarticle/100533Background: One of the many debated topics in inflammation research is whether this scenario is really an accelerated form of human wound healing and immunityboosting or a push towards autoimmune diseases. The answer requires a better understanding of the normal inflammatory process, including the molecular pathology underlying the possible outcomes. Exciting recent investigations regarding severe human inflammatory disorders and autoimmune conditions have implicated molecular changes that are also linked to normal immunity, such as triggering factors, switching on and off, the influence of other diseases and faulty stem cell homeostasis, in disease progression and development.

Methods: We gathered around and collected recent online researches on immunity, inflammation, inflammatory disorders and AMPK. We basically searched PubMed, Scopus and Google Scholar to assemble the studies which were published since 2010.

Results: Our findings suggested that inflammation and related disorders are on the verge and interfere in the treatment of other diseases. AMPK serves as a key component that prevents various kinds of inflammatory signaling. In addition, our table and hypothetical figures may open a new door in inflammation research, which could be a greater therapeutic target for controlling diabetes, obesity, insulin resistance and preventing autoimmune diseases.

Conclusion: The relationship between immunity and inflammation becomes easily apparent. Yet, the essence of inflammation turns out to be so startling that the theory may not be instantly established and many possible arguments are raised for its clearance. However, this study might be able to reveal some possible approaches where AMPK can reduce or prevent inflammatory disorders.

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<![CDATA[Bicycloheptylamine-Doxorubicin Conjugate: Synthesis and Anticancer Activities in σ2 Receptor-Expressing Cell Lines]]>https://www.eurekaselect.comarticle/96997Background: Novel bicycloheptylamines were designed and synthesized. These compounds were found to be selective for sigma-2 receptors. These receptors have been found to be up to 10 fold over-expressed in certain cancer cell lines, leading to investigation of possible uses as a biomarker in diagnosis and/or treatment especially in cancers with poor prognosis.

Objectives: The aim was to conjugate a novel sigma-2 receptor ligand to doxorubicin to examine anticancer activities, with and without conjugation, and therefore possibilities in drug delivery.

Methods: Conjugation was conducted using N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide HCl as a coupling agent. Affinity towards the sigma-2 receptor was tested using ligand-receptor binding studies. Anticancer activities against cancer cell lines were carried out using cell viability assays. Caspase dependency was tested using Z-VAD-FMK, a pan-caspase inhibitor, to begin to investigate mechanisms of action.

Results: The target compound retained affinity towards the sigma-2 receptor and exhibited potent anticancer activities on cancer cell lines expressing the sigma-2 receptor. The potencies exceeded those of doxorubicin, the lead sigma-2 receptor ligand, as well as non-covalent combination of both drugs. The activity was also found to be caspase-dependent.

Conclusion: The conjugation of target bicycloheptylamines with cytotoxic moieties may yield potent and selective molecules for detection and/or treatment of certain cancers.

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<![CDATA[Current Development of Metal Complexes with Diamine Ligands as Potential Anticancer Agents]]>https://www.eurekaselect.comarticle/94136Background: The discovery of cisplatin and the subsequent research revealed the importance of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover, certain diamine ligands alone display cytotoxicity that contributes to the overall activity of corresponding complexes.

Objective: To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms of action of metal complexes with various types of diamine ligands.

Methods: The contribution of aliphatic acyclic, aliphatic cyclic, and aromatic diamine ligands to the anticancer activity and selectivity/toxicity of metal complexes with different metal ions were analyzed by comparison with organic ligand alone and/or conventional platinum-based chemotherapeutics.

Results: The aliphatic acyclic diamine ligands are present mostly in complexes with platinum. Aliphatic cyclic diamines are part of Pt(II), Ru(II) and Au(III) complexes, while aromatic diamine ligands are found in Pt(II), Ru(II), Pd(II) and Ir(III) complexes. The type and oxidation state of metal ions greatly influences the cytotoxicity of metal complexes with aliphatic acyclic diamine ligands. Lipophilicity of organic ligands, dependent on alkyl-side chain length and structure, determines their cellular uptake, with edda and eddp/eddip ligands being most useful in this regard. Aliphatic cyclic diamine ligands improved the activity/toxicity ratio of oxaliplatin-type complexes. The complexes with aromatic diamine ligands remain unexplored regarding their anticancer mechanism. The investigated complexes mainly caused apoptotic or necrotic cell death.

Conclusion: Metal complexes with diamine ligands are promising candidates for efficient and more selective alternatives to conventional platinum-based chemotherapeutics. Further research is required to reveal the chemico-physical properties and molecular mechanisms underlying their biological activity.

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<![CDATA[Role of microRNAs in Chronic Lymphocytic Leukemia Pathogenesis]]>https://www.eurekaselect.comarticle/100724 <![CDATA[Natural Compounds Therapeutic Features in Brain Disorders by Experimental, Bioinformatics and Cheminformatics Methods]]>https://www.eurekaselect.comarticle/94145Background: Synthetic compounds with pharmaceutical applications in brain disorders are daily designed and synthesized, with well first effects but also seldom severe side effects. This imposes the search for alternative therapies based on the pharmaceutical potentials of natural compounds. The natural compounds isolated from various plants and arthropods venom are well known for their antimicrobial (antibacterial, antiviral) and antiinflammatory activities, but more studies are needed for a better understanding of their structural and pharmacological features with new therapeutic applications.

Objectives: Here we present some structural and pharmaceutical features of natural compounds isolated from plants and arthropods venom relevant for their efficiency and potency in brain disorders. We present the polytherapeutic effects of natural compounds belonging to terpenes (limonene), monoterpenoids (1,8-cineole) and stilbenes (resveratrol), as well as natural peptides (apamin, mastoparan and melittin).

Methods: Various experimental and in silico methods are presented with special attention on bioinformatics (natural compounds database, artificial neural network) and cheminformatics (QSAR, drug design, computational mutagenesis, molecular docking).

Results: In the present paper we reviewed: (i) recent studies regarding the pharmacological potential of natural compounds in the brain; (ii) the most useful databases containing molecular and functional features of natural compounds; and (iii) the most important molecular descriptors of natural compounds in comparison with a few synthetic compounds.

Conclusion: Our paper indicates that natural compounds are a real alternative for nervous system therapy and represents a helpful tool for the future papers focused on the study of the natural compounds.

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<![CDATA[Meet Our Editorial Board Member]]>https://www.eurekaselect.comarticle/103278 <![CDATA[Uptake of [¹⁸F]tetrafluoroborate in MCF-7 Breast Cancer Cells is Induced after Stimulation of the Sodium Iodide Symporter]]>https://www.eurekaselect.comarticle/101539Background: The human sodium iodide symporter (hNIS) has been the most important target in nuclear medicine regarding thyroid-related diseases. Although hNIS-expression can also be determined in extra-thyroidal tumors, imaging hNIS with positron emission tomography has not been exploited clinically.

Objective: Here, we evaluated the accumulation of the novel hNIS-substrate [18F]tetrafluoroborate ([18F]TFB) in the endogenously hNIS-expressing breast cancer cell line MCF-7 after an improved radiosynthesis and pharmacological stimulation.

Methods: [18F]TFB was prepared under mild reaction conditions (40°C, 25 min) and its uptake properties were investigated in MCF-7 cells pretreated with a combination of all-trans retinoic acid plus methasone-derivatives and compared to the clinically established tracers [131I]iodide and [99mTc]pertechnetate. Specificity of the tracer accumulation was assessed by inhibition experiments using NaBF4, KSO3F, KI and KIO3.

Results:[18F]TFB was obtained with a radiochemical yield of 24.0 ± 6.6 % (n = 17) within 40 min after high pressure liquid chromatography-separation and with 26.8 ± 6.2 % (n = 13) within 45 min after adapting the procedure on a synthesis module using higher starting activities (> 10 GBq). After pharmacological treatment, a 4-fold increase in hNIS-expression on the MCF-7 cell surface was achieved, resulting in a significantly higher [18F]TFB uptake into the cells (up to 58-fold) as compared to control experiments. Inhibition studies using various NIS-substrates confirmed the specificity of [18F]TFB for hNIS.

Conclusion: [18F]TFB was shown to be a promising hNIS-substrate in our model using the human MCF-7 breast cancer cell line mandating in vivo evaluations in xenografted studies and in patients.

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<![CDATA[New Entrants into Clinical Trials for Targeted Therapy of Breast Cancer: An Insight]]>https://www.eurekaselect.comarticle/101637 <![CDATA[Recent Advances in Characterizing Natural Products that Regulate Autophagy]]>https://www.eurekaselect.comarticle/101454 <![CDATA[Synergistic Effect of α-Solanine and Cisplatin Induces Apoptosis and Enhances Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells]]>https://www.eurekaselect.comarticle/101087Aim: The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid α-solanine on human hepatocellular carcinoma cells was evaluated.

Methods: HepG2 cells were exposed to low doses of α-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement.

Results: α-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G2/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression.

Conclusion: Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.

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<![CDATA[Optimal Saturated Neuropilin-1 Expression in Normal Tissue Maximizes Tumor Exposure to Anti-Neuropilin-1 Monoclonal Antibody]]>https://www.eurekaselect.comarticle/102111Background: As involved in tumor angiogenesis, Neuropilin Receptor type-1 (NRP-1) serves as an attractive target for cancer molecular imaging and therapy. Widespread expression of NRP-1 in normal tissues may affect anti-NRP-1 antibody tumor uptake.

Objective: To assess a novel anti-NRP-1 monoclonal antibody A6-11-26 biodistribution in NRP-1 positive tumor xenograft models to understand the relationships between dose, normal tissue uptake and tumor uptake.

Methods: The A6-11-26 was radiolabeled with 131I and the mice bearing U87MG xenografts were then administered with 131I-labelled A6-11-26 along with 0, 2.5, 5, and 10mg·kg-1 unlabelled antibody A6-11-26. Biodistribution and SPECT/CT imaging were evaluated.

Results: 131I-A6-11-26 was synthesized successfully by hybridoma within 60min. It showed that most of 131IA6- 11-26 were in the plasma and serum (98.5 ± 0.16 and 88.9 ± 5.84, respectively), whereas, less in blood cells. For in vivo biodistribution studies, after only injection of 131I-A6-11-26, high levels of radioactivity were observed in the liver, moderate level in lungs. However, liver and lungs radioactivity uptakes could be competitively blocked by an increasing amount of unlabeled antibody A6-11-26, which can increase tumor radioactivity levels, but not in a dose-dependent manner. A dose between 10 and 20mg·kg-1 of unlabeled antibody A6-11-26 may be the optimal dose that maximized tumor exposure.

Conclusion: Widespread expression of NRP-1 in normal tissue may affect the distribution of A6-11-26 to tumor tissue. An appropriate antibody A6-11-26 dose would be required to saturate normal tissue antigenic sinks to achieve acceptable tumor exposure.

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<![CDATA[Meet Our Editorial Board Member]]>https://www.eurekaselect.comarticle/104270