Epigallocatechin 3-gallate: From green tea to cancer therapeutics.

Natural products can be used in therapeutic management of COVID-19: Probable mechanistic insights

Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat multiple diseases, including cancer, diabetic neuropathy, and inflammatory diseases. UA inhibits cancer proliferation, metastasis, angiogenesis, and induced cell death, scavenging free radicals and triggering numerous anti- and pro-apoptotic proteins. The biochemistry of UA has been examined broadly based on the literature, with alterations frequently having been prepared on positions C-3 (hydroxyl), C12-C13 (double bonds), and C-28 (carboxylic acid), leading to several UA derivatives with increased potency, bioavailability and water solubility. UA could be used as a protective agent to counter neural dysfunction via anti-oxidant and anti-inflammatory effects. It is a potential therapeutic drug implicated in the treatment of cancer and diabetic complications diseases provide novel machinery to the anti-inflammatory properties of UA. The pharmacological efficiency of UA is exhibited by the therapeutic theory of one-drug → several targets → one/multiple diseases. Hence, UA shows promising therapeutic potential for cancer and diabetic neuropathy diseases. This review aims to discuss mechanistic insights into promising beneficial effects of UA. We further explained the pharmacological aspects, clinical trials, and potential limitations of UA for the management of cancer and diabetic neuropathy diseases.

Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases

Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.

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Computational Modeling on Aquaporin-3 as Skin Cancer Target: A Virtual Screening Study.

An overview of peroxidation reactions using liposomes as model systems and analytical methods as monitoring tools.

Biomembranes and lipid systems are rich in unsaturated lipid components and are subject to photo-induced lipid peroxidation. The peroxidized lipid products in cellular systems are known to affect t...

Atomic-scale modeling of the effect of lipid peroxidation on the permeability of reactive species.

Glioma predominantly targets glial cells in the brain and spinal cord. There are grade I, II, III, and IV gliomas with anaplastic astrocytoma and glioblastoma multiforme as the most severe forms of the disease. Current diagnostic methods are limited in their data acquisition and interpretation, markedly affecting treatment modalities and patient outcomes. Circulating extracellular vesicles (EVs) or "magic bullets" contain bioactive signature molecules such as DNA, RNA, proteins, lipids, and metabolites. These secretory "smart probes" participate in myriad cellular activities, including glioma progression. EVs are released by all cell populations and may serve as novel diagnostic biomarkers and efficient nanovehicles in the targeted delivery of encapsulated therapeutics. The present review describes the potential of EVbased biomarkers for glioma management.

Role of Extracellular Vesicles in Glioma Progression: Deciphering Cellular Biological Processes to Clinical Applications.

Meningioma is the second most common type of intracranial brain tumor. Immunohistochemical techniques have shown prodigious results in the role of epidermal growth factor receptor variant III (EGFR vIII) in glioma and other cancers. However, the role of EGFR vIII in meningioma is still in question. This study attempt the confer searches for the position attained by EGFR vIII in progression and expression of meningioma. Immunohistochemistry technique showed that EGFR vIII is highly expressed in benign tumors as compared to the atypical meningioma with a highly significant p-value (p<0.05). Further analysis by flow cytometry results supported these findings thus presented high intensity of EGFR vIII in low grades of meningioma. The study revealed that the significant Ki 67 values, to predictor marker for survival and prognosis of the patients. Higher expression of EGFR vIII in low grades meningiomas as compared to high-grade tumors indicate towards its oncogenic properties. To our knowledge, limited studies reported in literature expressing the EGFR vIII in meningioma tumors. Hence, Opinions regarding the role that EGFR vIII in tumorigenesis and tumor progression are clearly conflicting and, therefore, it is crucial not only to find out its mechanism of action, but also to definitely identify its role in meningioma.

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Exploring the role of epidermal growth factor receptor variant III in meningeal tumors.

Gliomas are the most common type of the malignant brain tumor, which arise from glial cells. They make up about 40% of all primary brain tumors and around 70% of all primary malignant brain tumors. They can occur anywhere in the central nervous system (CNS), and have a poor prognosis. The average survival of glioma patients is approximately 6-15 months with poor aspects of life. In this edge, identification of proteins secreted by cancer cells is of special interest because it may provide a better understanding of tumor progression and provide early diagnosis of the diseases. Extracellular vesicles (EVs) were isolated from pooled plasma of healthy controls (n=03) and patients with different grades of glioma (Grade I or II or III, n=03 each). Nanoparticle tracking analysis, western blot and flow cytometery were performed to determine the size, morphology, the concentration of glioma-derived vesicles and EV marker, CD63. Further, iTRAQ based LC-MS/MS analysis of EV protein was performed to determine the differential protein abundance in extracellular vesicles across different glioma grades. We further verified galactin-3-binding protein (LGALS3BP) by ELISA in individual blood plasma and plasma-derived vesicles from control and glioma patients (n=40 each). Analysis by Max Quant identified 123 proteins from the pooled patient exosomes, out of which 34, 21 and 14 proteins were found to be differentially abundant by more than 1.3-fold in the different grades of glioma grade I-pilocytic astrocytoma, grade II- diffuse astrocytoma, grade III- anaplastic astrocytoma respectively in comparison with the control samples. A total of 7 proteins namely CRP, SAA2, SERPINA3, SAA1, C4A, LV211 and KV112, showed differential abundance in all the three grades. LGALS3BP was seen to be up-regulated across the different grades and ELISA analysis from individual blood plasma and plasma derived extracellular vesicles confirmed the increased expression of LGALS3BP in glioma patients (p<0.001). The present study provides LGALS3BP as a potential biomarker for early detection of glioma and improve survival outcome of the patient. The present study further provides the information of progression and monitoring the tumor grades (grade 1, grade II, grade III).

Rashmi Rana

Papers

Atomic-scale modeling of the effect of lipid peroxidation on the permeability of reactive species.

Role of Extracellular Vesicles in Glioma Progression: Deciphering Cellular Biological Processes to Clinical Applications.

Exploring the role of epidermal growth factor receptor variant III in meningeal tumors.

Plasma-Derived Extracellular Vesicles Reveal Galectin-3 Binding Protein as Potential Biomarker for Early Detection of Glioma