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In this study, the anti-cancer and anti-inflammatory activities of PS14, a short peptide derived from the cellulase binding domain of pathogenic fungus, Aphanomyces invadans, have been evaluated, in vitro and in vivo. Bioinformatics analysis of PS14 revealed the physicochemical properties and the web-based predictions, which indicate that PS14 is non-toxic, and it has the potential to elicit anti-cancer and anti-inflammatory activities. These in silico results were experimentally validated through in vitro (L6 or Hep-2 cells) and in vivo (zebrafish embryo or larvae) models. Experimental results showed that PS14 is non-toxic in L6 cells and the zebrafish embryo, and it elicits an antitumor effect Hep-2 cells and zebrafish embryos. Anticancer activity assays, in terms of MTT, trypan blue and LDH assays, showed a dose-dependent inhibitory effect on cell proliferation. Moreover, in the epithelial cancer cells and zebrafish embryos, the peptide challenge (i) caused significant changes in the cytomorphology and induced apoptosis; (ii) triggered ROS generation; and (iii) showed a significant up-regulation of anti-cancer genes including BAX, Caspase 3, Caspase 9 and down-regulation of Bcl-2, in vitro. The anti-inflammatory activity of PS14 was observed in the cell-free in vitro assays for the inhibition of proteinase and lipoxygenase, and heat-induced hemolysis and hypotonicity-induced hemolysis. Together, this study has identified that PS14 has anti-cancer and anti-inflammatory activities, while being non-toxic, in vitro and in vivo. Future experiments can focus on the clinical or pharmacodynamics aspects of PS14.

Diabetes Mellitus is a metabolic disease that leads to microvascular complications like Diabetic retinopathy (DR), a major cause of blindness worldwide. Current medications for DR are expensive and report multiple side effects; therefore, an alternative medication that alleviates the disease condition is required. An interventional approach targeting the vascular endothelial growth factor (VEGF) remains a treatment strategy for DR. Anti-VEGF medicines are being investigated as the main therapy for managing vision-threatening complications of DR, such as diabetic macular oedema. Therefore, this study investigated the effect of flavonoid naringenin (NG) from citrus fruits on inhibiting early DR in zebrafish. When exposed to 130 mM glucose, the zebrafish larvae developed a hyperglycaemic condition accompanied by oxidative stress, cellular damage, and lipid peroxidation. Similarly, when adult zebrafish were exposed to 4% Glucose, high glucose levels were observed in the ocular region and massive destruction in the retinal membrane. High glucose upregulated the expression of VEGF. In comparison, the co-exposure to NG inhibited oxidative stress and cellular damage and restored the glutathione levels in the ocular region of the zebrafish larvae. NG regressed the glucose levels and cellular damage along with an inhibition of macular degeneration in the retina of adult zebrafish and normalized the overexpression of VEGF as a promising strategy for treating DR. Therefore, intervention of NG could alleviate the domestication of alternative medicine in ophthalmic research.

Obesity is linked to the development of major metabolic disorders such as type 2 diabetes, cardiovascular disease, and cancer. Recent research has focused on the molecular link between obesity and oxidative stress. Obesity impairs antioxidant function, resulting in dramatically increased reactive oxygen levels and apoptosis. In this study, we investigated the effect of IW13 peptide on inhibiting lipid accumulation and regulating the antioxidant mechanism to normalize the lipid metabolism in HFD induced zebrafish larvae. Our results showed that co-treatment with IW13 peptide showed a protective effect in HFD zebra fish larvae by increasing the survival and heart rate. However, IW13 peptide co-treatment reduced triglycerides and cholesterol levels while also restoring the SOD and CAT antioxidant enzymes. In addition, IW13 co-treatment inhibited the formation of lipid peroxidation and superoxide anion by regulating the glutathione level. Also, the results showed that IW13 specifically downregulated the expression of the lipogenic-specific genes (C/EBP-α, SREBP1, and FAS). The findings exhibited that the IW13 peptide with effective antioxidant and anti-obesity activity could act as a futuristic drug to treat obesity and oxidative stress-related diseases.

Background The development of diabetic nephropathy is aided by the presence of oxidative stress. Morin, a natural flavonoid molecule, has been shown to have antioxidant and anti-diabetic properties. However, little is known about the mechanism of its protective effect in diabetic nephropathy pathogenesis caused by oxidative stress. Methods Using Madin-Darby canine kidney (MDCK) cells as a working model, the current study investigates the detailed mechanism of morin's beneficial action. In hydrogen peroxide-induced oxidative stressed MDCK cells, there was a considerable rise in intracellular ROS and decreased antioxidant enzyme levels. Results Morin has a higher binding affinity for the antioxidant receptor; according to in silico study using molecular docking and ADMET, it is predicted to be an orally active molecule. While morin administration increased SOD and CAT activity in oxidative stress-induced MDCK cells, it also reduced mitochondrial oxidative stress and apoptosis. Furthermore, the present study discovered the molecular mechanism through which morin reduced oxidative stress in MDCK cells by upregulating antioxidant enzyme molecules including GST, GPx, and GCS. Conclusion These findings suggest that morin reduces H 2 O 2 -induced oxidative stress, reduces DNA oxidative damage, and prevents the depletion of antioxidant genes in MDCK cells.

Micro- and nano-plastics (MNPs) and per- and polyfluoroalkyl substances (PFAS) are prevalent in ecosystems due to their exceptional properties and widespread use, profoundly affecting both human health and ecosystem. Upon entering the environment, MNPs and PFAS undergo various transformations, such as weathering, transport, and accumulation, potentially altering their characteristics and structural dynamics. Their interactions, governed by factors like hydrogen bonding, hydrophobic interactions, Van der Waals forces, electrostatic attractions, and environmental conditions, can amplify or mitigate their toxicity toward human health within ecological conditions. Several studies demonstrate the in vivo effects of PFAS and MNPs, encompassing growth and reproductive impairments, oxidative stress, neurotoxicity, apoptosis, DNA damage, genotoxicity, immunological responses, behavioral changes, modifications in gut microbiota, and histopathological alterations. Moreover, in vitro investigations highlight impacts on cellular uptake, affecting survival, proliferation, membrane integrity, reactive oxygen species (ROS) generation, and antioxidant responses. This review combines knowledge on the co-existence and adsorption of PFAS and MNPs in the environment, defining their combined in vivo and in vitro impacts. It provides evidence of potential human health implications. While significant research originates from China, Europe, and the USA, studies from other regions are limited. Only freshwater and marine organisms and their impacts are extensively studied in comparison to terrestrial organisms and humans. Nonetheless, detailed investigations are lacking regarding their fate, combined environmental exposure, mode of action, and implications in human health studies. Ongoing research is imperative to comprehensively understand environmental exposures and interaction mechanisms, addressing the need to elucidate these aspects thoroughly.

Alcoholic liver disease is one of the most prominent liver diseases in the world. Lipid accumulation accompanied by oxidative stress and inflammation in the liver is the most important pathogenesis of ALD. This study was designed to investigate the anti-oxidative, fat metabolism-regulating, and anti-inflammatory potential of N2, a seminatural analog of Nimbin. The ethanol exposure was found to induce liver injury on zebrafish larvae, such as liver inflammation, lipid accumulation, oxidative stress, and hepatocytes apoptosis. N2 was subjected to ADMET screening in-silico, and it was observed N2’s co-exposure decreased the ROS, apoptosis, lipid peroxidation, and macrophage accumulation in the liver of larval zebrafish. To further study the mechanism behind ethanol hepatotoxicity and the hepatoprotective behavior of N2, gene expression changes were determined in zebrafish. The results of this study revealed that ethanol exposure upregulated mRNA expressions of SREBP1, C/EBP-α, FAS and provoked more severe oxidative stress and hepatitis via upregulation of inflammatory cytokines TNF-α, IL-10, IL-1β, iNOS, COX-2. However, the N2 co-exposure protected the hepatocyte damage and almost reversed the condition by downregulating the mRNA levels. The study suggested that N2 could be an effective therapeutic agent for the treatment of ALD and other inflammatory conditions.

Background Pancreatic β-cells are susceptible to oxidative stress, leading to β-cell death and dysfunction due to enhanced ROS levels and type 2 diabetes. To inhibit the β-cells damages induced by the oxidative stress, the present study investigates the beneficial effect of various peptides (WL15, RF13, RW20, IW13 and MF18) of immune related proteins (cysteine and glycine-rich protein 2, histone acetyltransferase, vacuolar protein sorting associated protein 26B, serine threonine-protein kinase and CxxC zinc finger protein, respectively). Also, the molecular mechanism of WL15 from cysteine and glycine-rich protein 2 on β-cell regeneration was identified through PEPCK and insulin pathway. Materials and methods In this study, a total of five peptides including WL15, RF13, RW20, IW13, and MF18 were derived from immune-related proteins such as cysteine and glycine-rich protein 2, histone acetyltransferase, vacuolar protein sorting associated protein 26B, serine threonine-protein kinase and CxxC zinc finger protein, respectively. These protein sequences were obtained from an earlier constructed transcriptome database of a teleost Channa striatus. The identified peptides were evaluated for their antioxidant as well as antidiabetic activity. Based on the in silico analysis and in-vitro screening experiments, WL15 was predicted to have better antioxidant and antidiabetic activity among the five different peptides. Therefore, WL15 alone was further analyzed for apoptosis, antioxidant capacity, glucose metabolism, and gene expression performance, which was investigated on the alloxan (500 µM) induced zebrafish in vivo larval model. Results The results showed alloxan exposure to zebrafish larvae for a day, the ROS was generated in the β-cells. Interestingly, WL15 treatment showed a protective effect by reducing the toxicity of alloxan exposed zebrafish larvae by increasing their survival and heart rate. Moreover, WL15 reduced the intracellular ROS level and apoptosis in alloxan-induced larvae. The superoxide anion and lipid peroxidation levels are also reduced by improving the glutathione content after the WL15 treatment. Besides, WL15 treatment increased the proliferation rate of β-cells and decreased the glucose level. Further, the gene expression studies revealed that WL15 treatment normalized the PEPCK expression while upregulating the insulin expression in alloxan exposed larvae. Conclusion Overall, the findings indicate that WL15 of cysteine and glycine-rich protein 2 can act as a potential antioxidant for type 2 diabetes patients in respect of improving β-cell regeneration.

In this study, the anti-cancer and anti-inflammatory activities of PS14, a short peptide derived from the cellulase binding domain of pathogenic fungus, Aphanomyces invadans, have been evaluated, in vitro and in vivo. Bioinformatics analysis of PS14 revealed the physicochemical properties and the web-based predictions, which indicate that PS14 is non-toxic, and it has the potential to elicit anti-cancer and anti-inflammatory activities. These in silico results were experimentally validated through in vitro (L6 or Hep-2 cells) and in vivo (zebrafish embryo or larvae) models. Experimental results showed that PS14 is non-toxic in L6 cells and the zebrafish embryo, and it elicits an antitumor effect Hep-2 cells and zebrafish embryos. Anticancer activity assays, in terms of MTT, trypan blue and LDH assays, showed a dose-dependent inhibitory effect on cell proliferation. Moreover, in the epithelial cancer cells and zebrafish embryos, the peptide challenge (i) caused significant changes in the cytomorphology and induced apoptosis; (ii) triggered ROS generation; and (iii) showed a significant up-regulation of anti-cancer genes including BAX, Caspase 3, Caspase 9 and down-regulation of Bcl-2, in vitro. The anti-inflammatory activity of PS14 was observed in the cell-free in vitro assays for the inhibition of proteinase and lipoxygenase, and heat-induced hemolysis and hypotonicity-induced hemolysis. Together, this study has identified that PS14 has anti-cancer and anti-inflammatory activities, while being non-toxic, in vitro and in vivo. Future experiments can focus on the clinical or pharmacodynamics aspects of PS14.