The decoction of the whole plant of Enhydra fluctuans is used ethno medicinally by various tribes for the treatment of kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on urinary stone formation and crystallisation. Hence, the present study is proposed to investigate the effect of the aqueous extract of Enhydra fluctuans extract on in vitro crystallisation of calcium oxalate. The present study also evaluated. in silico studies of the metabolites with the target proteins present in the renal calcium oxalate stone matrix. The plant material was subjected to decoction to obtain an aqueous extract. The effect of the extract on calcium oxalate crystallization was evaluated by in vitro nucleation and aggregation assays. Further, the metabolites present in E. fluctuans were mined from the existing literature and their number was found to be 35. The selected 35 metabolites of E. fluctuans were subjected to molecular docking with the 5 proteins which are known to be responsible for calcium oxalate crystal growth. Results of in vitro studies indicated that the extract (50, 100, and 200 μg/mL) and standard drug cystone (1,000 μg/mL) exhibited an inhibitory role in the nucleation process where the percentage inhibitions were 52.69, 43.47, 21.98, and 31.67 μg/mL respectively. The results of molecular docking studies revealed that 2 out of 35 metabolites i.e. Baicalein-7-O-diglucoside and 4′,5,6,7-Tetrahydroxy-8-methoxy isoflavone-7-O-beta-D- galactopyranosyl-(1→3)-O-beta-D-xylopyranosyl-(1→4)- O-alpha-L-rhamnopyranoside showed modulatory effects on the four renal stone matrix-associated protein (Human CTP: Phosphoethanolamine Cytidylyltransferase (Protein Data Bank ID: 3ELB), UDP glucose: glycoprotein glucosyltransferase 2 (Gene: UGGT2) (AlphaFold) and RIMS-binding protein 3A (Gene: RIMBP3) (AlphaFold), and Ras GTPase activating-like protein (PDB: 3FAY) based on their docking scores which indicates that they may inhibit the crystallization process. Findings from this study show that Enhydra fluctuans may be effective in the prevention of the crystallization of calcium oxalate. However, further, in vivo studies as well as molecular studies are needed to be conducted to confirm and strengthen its anti-urolithiatic activity and to elucidate the possible mechanism of action involved therein.
Chimeric antigen receptor T-cells or CAR T-cell therapy is a newly discovered method that has shown great promise for the global patient population to cure cancer. Chimeric antigen receptor T-cells are generally prepared by removing T-cells from the patients’ blood and modifying them using genetic engineering, to express a Chimeric Antigen Receptor on their surface. The studies done so far have shown its major effectiveness against Beta-cell malignancy, ovarian carcinoma, and lymphoblastic leukemia. The therapy can cause Cytokine Release Syndrome, neurotoxicity syndrome, tumor lysis, etc. as its major adverse event. But recent improvements in the therapy has proved that these adverse events can be effectively minimized to a great extent. The future of CAR T-cell therapy is very promising and is expected to fulfil all global regulatory requirements as well as overcome any manufacturing and toxicological obstacles and become available for a large number of populations. This review is based on the overall prospects of CAR T-cell therapy, the major toxicity related problems, and the prospect of this therapy.
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