Bendixforeman5657

Paclitaxel (PTX) is a widely used chemotherapeutic drug particularly effective against lung, breast, and ovarian cancer, though its usefulness is limited due to its multi-organ toxicity. The mechanisms underlying PTX toxicity are currently not yet known and there are no approved treatments for its control or prevention. This study aimed to investigate whether hesperidin (HSP) had a protective effect on paclitaxel-induced hepatotoxicity and nephrotoxicity from biochemical, and molecular perspectives. The rats were administered PTX 2 mg/kg, b.w. intraperitoneally for the first 5 consecutive days, then 100 or 200 mg/kg b.w. HSP orally for 10 consecutive days. Our results demonstrated that HSP decreased the PTX induced lipid peroxidation, improved the serum hepatic and renal functions (by decreasing the levels of AST, ALT, ALP, urea, and creatinine), and restored the liver and kidney antioxidant armory (SOD, CAT, GPx, and GSH). HSP also significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-1β, IL-6, MAPK 14, Caspase-3, Bax, LC3A, LC3B, MMP2, and MMP9 whereas caused an increase in levels of Nrf2, HO-1, and Bcl-2 in the kidney and liver of PTX-induced rats. In addition, caspase-3, Bax, and Bcl-2 protein levels were examined by Western blot analysis, and it was determined that HSP decreased caspase-3 and Bax protein levels, but increased Bcl-2 protein levels. The findings of the study suggest that HSP has chemopreventive potential against PTX-induced hepatorenal toxicity plausibly through the attenuation of oxidative stress, inflammation, apoptosis, and autophagy.A series of seleno-biotin analogs were synthesized and their anticancer activity and mode of action were assessed using ovarian cancer cells. Compound 2, out of the other analogs, in direct comparison to biotin alone, more effectively reduced the cell viability and induced apoptosis in ovarian cancer cell lines in a dose dependent manner as demonstrated by the cell viability assay, trypan blue dye exclusion assay, Annexin V/7-AAD, and Caspase 3/7 apoptosis assays. Furthermore, compound 2 showed efficacy better than 5-fluorouracil (5-FU) and similar to cisplatin, in vitro; notably it was more cytotoxic to drug-resistant Hey A8 cells than cisplatin. The cytotoxicity of compound 2 was primarily mediated by reactive oxygen species (ROS) as demonstrated by DCFDA based ROS estimation. Biotin receptors (BR) saturation and the use of a BR negative cell line showed a significant decline in the cytotoxic ativity of the compound 2, confirming that its activity is BR-mediated. These experiments demonstrated that selenium modified biotin which contains an ester linked redox cycling selenocyanate group has the potential for human therapeutic applications against ovarian and other cancers over-expressing BR.The chemotherapeutic drug Doxorubicin is the most commonly prescribed in the world. However, its clinical wide application is limited due to harmful side effects like cardiotoxicity. The cardiotoxic mechanism of DOX is not fully clear, however, it is considered as a potential etiological factor to the generation of ROS and Iron complexes, impairment, Ca2⁺homeostasis, mitochondrial dysfunction, and cell membrane damage. Moreover, it is generally believed that mitochondrial dysfunction plays a central role in the cardiotoxic effect of DOX. Additionally, SIRTs are considered to play an important role, which is activated by small energy molecules to generate energy by stimulation of transcription factors and enzymatic regulation of cardiac energy metabolism. In the heart tissue, SIRT1 and SIRT3 are present in large amounts. This review paper focuses on "DOX mediated cardiomyopathy & cardiomyocytes death" and "The modulation of mitochondrial processes by SIRT1, SIRT3, and DOX". This paper expounds from the following aspects, respectively. 1. A target to mitochondria; (1) ROS overproduction under mitochondrial dysfunction; (2) Lipid peroxidation by oxidative stress after ROS overproduction; (3) Disturbance of calcium homeostasis and mitochondrial permeability transition; 2. SIRTs participate in the process of cardiotoxicity; (1) SIRT1 and toxic myocardial injury; ①Over-expression of SIRT1 in toxic myocardial injury; ②SIRT1 mediated DOX-induced cardiotoxicity; (2) SIRT3 and mitochondrial damage; ①A central role of SIRT3 in cardiac metabolism; ② Role of SIRT3 in DOX-induced cardiotoxicity; This review is based on SIRTs mediated role in the regulation of mitochondrial function, and evaluates their role on DOX induced cardiotoxicity.Metabolic engineering seeks to rewire the metabolic network of cells for the efficient production of value-added compounds from renewable substrates. However, it remains challenging to evaluate and identify strains with the desired phenotype from the vast rational or random mutagenesis library. One effective approach to resolve this bottleneck is to design an efficient high-throughput screening (HTS) method to rapidly detect and analyze target candidates. L-cysteine is an important sulfur-containing amino acid and has been widely used in agriculture, pharmaceuticals, cosmetics, and food additive industries. However, HTS methods that enable monitoring of L-cysteine levels and screening of the enzyme variants and strains to confer superior L-cysteine biosynthesis remain unavailable, greatly limiting the development of efficient microbial cell factories for L-cysteine production at the industrial scale. Here, we took advantage of the L-cysteine-responsive transcriptional regulator CcdR to develop a genetically eormance and to screen the high L-cysteine-producing strains from the random mutagenesis library. These results presented a paradigm of design and optimization of biosensors to dynamically detect metabolite concentrations and provided a promising tool enabling HTS and metabolic regulation to construct L-cysteine hyperproducing strains to satisfy industrial demand.Cancer cells adapt their intracellular energy metabolism to the oxygen-deprived tumor microenvironment (TME) to ensure tumor progression. This adaptive mechanism has focused attention on the metabolic phenotypes of tumor cells under hypoxic TME for developing novel cancer therapies. Although widely used monolayer (2D) culture does not fully reflect in vivo hypoxic TME, spheroid (3D) culture can produce a milieu similar to the TME in vivo. However, how different metabolic phenotypes are expressed in 3D cultures mimicking tumor hypoxia compared with 2D cultures under hypoxia remains unclear. To address this issue, we investigated the metabolic phenotypes of 2D- and 3D-cultured cancer cells by 13C-metabolic flux analysis (13C-MFA). Principal component analysis of 13C mass isotopomer distributions clearly demonstrated distinct metabolic phenotypes of 3D-cultured cells. 13C-MFA clarified that 3D culture significantly upregulated pyruvate carboxylase flux in line with the pyruvate carboxylase protein expression level. On the other hand, 3D culture downregulated glutaminolytic flux. Consistent with our findings, 3D-cultured cells are more resistant to a glutaminase inhibitor than 2D-cultured cells. This study suggests the importance of considering the metabolic characteristics of the particular in vitro model used for research on cancer metabolism.Irrational use of antibiotics produces a large number of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Wastewater treatment plants (WWTPs) act as important sources and sinks of ARGs, and play an important role in their generation, treatment, and dissemination. This study summarizes the types, concentrations, and factors of ARGs in WWTPs, investigates the sources of ARGs in wastewater, compares the removal efficiencies of different treatment processes on ARGs, and analyzes the potential risks of ARGs accumulation in effluent, sludge and their emission into the air. The results show that the main ARGs detected in the influent of WWTPs are the genes resistant to macrolides (ermB, ermF), tetracyclines (tetW, tetA, tetC), sulfonamides (sul1, sul2), and β-lactams (blaOXA, blaTEM). The concentrations of ARGs in the influent of the WWTPs are 2.23 × 102-3.90 × 109 copies/mL. Wastewater quality and microbial community are the dominant factors that affect the distribution characteristics of ARGs. The accumulation of ARGs in effluent, sludge, and aerosols pose potential risks to the regional ecological environment and human health. Based on these results, research trends with respect to ARGs in WWTPs are also prospected.We compared the clinical course of pregnant women with coronavirus disease 2019 (COVID-19) before and after the emergence of the omicron variant and based on vaccination status. We retrospectively reviewed the electronic medical charts of 224 patients and 82 deliveries from November 1, 2020, to March 7, 2022; of these, 42% were diagnosed during the omicron dominance period. Disease severity and morbidity of COVID-19 were significantly decreased during the omicron era. The vaccination rates among the patients were higher after omicron emergence (31.9%) than before (6.9%). Overall, 4.1% and 25% of patients had severe symptoms, and 2.6% and 16.2% required oxygen therapy in the vaccination and non-vaccination groups, respectively. Overall, patients had a more favorable clinical course in the omicron era; moreover, vaccinated patients were better protected than non-vaccinated patients, indicating the importance of vaccination against COVID-19.Glaucoma is a leading cause of irreversible blindness. The use of topical eye drops to reduce intraocular pressure remains the mainstay treatment. These eye drops frequently contain preservatives designed to ensure sterility of the compound. A growing number of clinical and experimental studies report the detrimental effects of not only these preservatives but also the active pharmaceutical compounds on the ocular surface, with resultant tear film instability and dry eye disease. Herein, we critically appraise the published literature exploring the effects of preservatives and pharmaceutical compounds on the ocular surface.Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) are important pathogens that cause high mortality and heavy economic losses in grouper aquaculture. Interestingly, SGIV infection in grouper cells induces paraptosis-like cell death, while RGNNV infection induces autophagy and necrosis characterized morphologically by vacuolation of lysosome. Here, a comparative transcriptomic analysis was carried out to identify the different molecular events during SGIV and RGNNV infection in grouper spleen (EAGS) cells. The functional enrichment analysis of DEGs suggested that several signaling pathways were involved in CPE progression and host immune response against SGIV or RGNNV. Most of DEGs featured in the KEGG "lysosome pathway" were up-regulated in RGNNV-infected cells, indicating that RGNNV induced lysosomal vacuolization and autophagy might be due to the disturbance of lysosomal function. More than 100 DEGs in cytoskeleton pathway and mitogen-activated protein kinase (MAPK) rlying different host cell responses against fish DNA and RNA virus.Autophagy impacts the replication cycle of many viruses. Grass Carp Reovirus (GCRV) is an agent that seriously affects the development of the grass carp aquaculture industry. The role of autophagy in GCRV infection is not clearly understood. In this study, we identified that GCRV infection triggered autophagy in CIK cells, which was demonstrated by transmission electron microscopy, the conversion of LC3B I to LC3B II and the level of autophagy substrate p62. Furthermore, we found that GCRV infection activated Akt-mTOR signaling pathway, and the conversion of LC3B I to LC3B II was increased by inhibiting mTOR with rapamycin (Rap) but decreased by activating Akt with insulin. We then assessed the effects of autophagy on GCRV replication. selleck compound We found that inducing autophagy with Rap promoted GCRV proliferation but inhibiting autophagy with 3 MA or CQ inhibited GCRV replication in CIK cells. Moreover, it was found that enhancing Akt-mTOR activity by insulin, GCRV VP7 protein and viral titers of GCRV were decreased. Collectively, these results indicated that GCRV infection induced autophagy involved in GCRV replication via the Akt-mTOR signal pathway.