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Furthermore, exposure of HeLa cells to hypochlorite resulted in a considerable increase in cytoplasmic calcium concentrations and a decrease in mitochondrial ones. Applying specific inhibitors of calcium transfer systems, we demonstrated that mitochondria play a key role in the redistribution of cytoplasmic Ca2+ ions under hypochlorite action and act as mediators of calcium release from the endoplasmic reticulum into the cytoplasm.l-Valine, l-isoleucine, and l-leucine are three key proteinogenic amino acids, and they are also the essential amino acids required for mammalian growth, possessing important and to some extent, special physiological and biological functions. Because of the branched structures in their carbon chains, they are also named as branched-chain amino acids (BCAAs). This review will highlight the advance in studies of the enzymes involved in the biosynthetic pathway of BCAAs, concentrating on their chemical mechanisms and applications in screening herbicides and antibacterial agents. The uses of some of these enzymes in lab scale organic synthesis are also discussed.In contrast to the conventional ocular formulations, contact lenses are well known for their diverse applications ranging from bio-sensing, prevention of myopia, cosmetics, and drug delivery. With a tremendous change in the lifestyle, contact lenses for therapeutic purposes have increased several fold. Contact lenses as medicated lenses suffer from several disadvantages, and to overcome the same numerous approaches have been explored. Researches worldwide have come a long way from cyclodextrin-based and vitamin E-based modified contact lenses to bioinspired approaches to enhance the effectiveness of the drug-eluting contact lenses. The bioinspired approach exploits bioinspired polymeric systems to enhance biocompatibility, specific molecule recognition technique by molecular imprinting, or stimuli-responsive system to improve the biocompatibility, drug loading, and drug delivery efficacy of the drug-eluting contact lenses. Moreover, recent innovations in ocular therapeutics such as nanowafers and microneedle contact lenses, and ocular patches have gained tremendous attention in ocular therapeutics. Another potential application of the contact lenses are smart lenses applied in the biosensing and diagnosis of various ocular disorders. The review summarizes and discusses the widespread therapeutic applications of next-generation contact lenses and various fabrication approaches, including its clinical implications, efforts taken by researchers in exploring the novel materials and diverse forms of the lenses, mechanisms of drug release, clinical trials, and their toxicity and safety concerns.Depression is a common mental disorder, and its main environmental risk factor is chronic stress. The activation of mammalian STE20-like kinase 1 (MST1), a key factor involved in the underlying pathophysiology of stress, can trigger synaptic plasticity impairment, neuronal dysfunction and neuroinflammation. However, it is unclear whether down-regulation of MST1 in the hippocampus protects against stress-induced behavioural dysfunctions. In this study, three mouse models were used to assess the role of MST1 in stress. Various behavioural tests, in vivo electrophysiological recordings, Western blotting, Golgi staining and immunofluorescence assay were used. The data showed that the level of phospho-MST1 (T183) was significantly increased in the hippocampus of mice subjected to chronic unpredictable mild stress (CUMS) and that mice with MST1 overexpression showed depression-like behaviours. Importantly, the impairment of cognitive functions and the hippocampal synaptic plasticity induced by CUMS were significantly improved by MST1 knockdown, suggesting that MST1 down-regulation effectively protected against stress-induced behavioural dysfunctions. Moreover, MST1 knockdown suppressed CUMS-induced microglial activation, reduced the abnormal expression of inflammatory cytokines and impeded the activation of p38, implying that the antidepressant-like effects of MST1 knockdown were associated with inhibiting the p38 pathway. These findings suggest that hippocampal MST1 is an essential regulator of stress, which can be an ideal target for the development of antidepressants in the future.Depression is a serious disease that has considerable impact on lipid metabolism and inflammatory responses. Recent studies have shown that leptin, which is well known as a mediator of energy homeostasis and is a cytokine in inflammatory response, plays an important role in depression. Acupuncture is widely used to treat depression; however, the underlying mechanisms and the effect of acupuncture on depression remain poorly understood. In this study, we utilized the chronic restraint stress (CRS) induced depression model and acupuncture treatment was performed at KI10, LR8, LU8, LR4 (AP) or non-acupoint (NP). Then, lipidomics was applied to investigate the effects of acupuncture on lipid metabolism and analyze leptin signals in the brain and changes of immune markers. Acupuncture treatment at AP improved depression-like behavior in an open-field test, forced swimming test, and marble burying test. Concurrently, CRS mice treated with AP acupuncture (CRS + AP) had significantly lower levels of aspartate aminotrectively alleviated the depression-like behavior, affected immune responses, and altered hepatic lipid metabolism through the attenuation of leptin insensitivity.A growing body of studies indicated that exosomes are one of vital players in pathological process of neuropsychiatric diseases, but their role in major depressive disorder (MDD) remains poorly understood. SNX-5422 molecular weight Here we purified plasma exosomes from depression including lipopolysaccharide (LPS)-challenged depression, chronic restraint stress (CRS)-induced depression, MDD subjects, and from control mice or volunteers. The therapeutic effect of these exogenous exosomes was assessed utilizing behavioral tests and biochemical approaches in the LPS-caused depression or microglial BV2 cells. The expression of exosomal sigma-1 receptor (Sig-1R) was evaluated by western blotting. The role of Sig-1R in the biological function of exosomes was determined using Sig-1R knockout mice and HEK 293 cells. Our results revealed that injection of exosomes from depression models or patients rather than normal controls significantly ameliorated depressive-like behaviors, deficiency of BDNF expression and neuro-inflammation in LPS-challenged mice.