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Cadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd‐induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd‐induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry‐based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd‐induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine‐specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd‐exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut‐derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro‐β‐muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd‐exposed mice. However, MT could not ameliorate Cd‐induced liver damage and fibrosis in Abx‐treated mice. Conversely, MT still exerted a protective effect on Cd‐induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd‐exposed intestinal epithelial cell‐specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd‐induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR‐mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice. [ABSTRACT FROM AUTHOR]

One of the major factors hindering efficient livestock production is the presence of high-impact infectious animal diseases, such as foot and mouth disease (FMD), lumpy skin disease (LSD), and bovine ephemeral fever (BEF), which are notable viral infections affecting cattle in Egypt, leading to significant economic losses. FMD is caused by the foot and mouth disease virus (FMDV) of the genus Aphthovirus in the Picornaviridae family. LSD is caused by lumpy skin disease virus (LSDV) of Capripox genus within the Poxviridae family, subfamily Chordopoxvirinae. BEF is caused by bovine ephemeral fever virus (BEFV) of genus Ephemerovirus in the Rhabdoviridae family. FMD is a highly contagious viral infection of domestic and wild cloven-hooved animals and can spread through the wind. On the other hand, LSD and BEF are arthropod-borne viral diseases that mainly affect domestic cattle and water buffalo. Despite government vaccination efforts, these three viral diseases have become widespread in Egypt, with several reported epidemics. Egypt's importation of large numbers of animals from different countries, combined with unregulated animal movements through trading and borders between African countries and Egypt, facilitates the introduction of new FMDV serotypes and lineages not covered by the current vaccination plans. To establish an effective control program, countries need to assess the real epizootic situation of various infectious animal diseases to develop an efficient early warning system. This review provides information about FMD, LSD, and BEF, including their economic impacts, causative viruses, global burden, the situation in Egypt, and the challenges in controlling these diseases. [ABSTRACT FROM AUTHOR]

Cholestatic liver disease is characterized by disturbances in the intestinal microbiota and excessive accumulation of toxic bile acids (BA) in the liver. Melatonin (MT) can improve liver diseases. However, the underlying mechanism remains unclear. This study aimed to explore the mechanism of MT on hepatic BA synthesis, liver injury, and fibrosis in 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC)‐fed and Mdr2–/– mice. MT significantly improved hepatic injury and fibrosis with a significant decrease in hepatic BA accumulation in DDC‐fed and Mdr2–/– mice. MT reprogramed gut microbiota and augmented fecal bile salt hydrolase activity, which was related to increasing intestinal BA deconjugation and fecal BA excretion in both DDC‐fed and Mdr2–/– mice. MT significantly activated the intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF‐15) axis and subsequently inhibited hepatic BA synthesis in DDC‐fed and Mdr2–/– mice. MT failed to improve DDC‐induced liver fibrosis and BA synthesis in antibiotic‐treated mice. Furthermore, MT provided protection against DDC‐induced liver injury and fibrosis in fecal microbiota transplantation mice. MT did not decrease liver injury and fibrosis in DDC‐fed intestinal epithelial cell‐specific FXR knockout mice, suggesting that the intestinal FXR mediated the anti‐fibrosis effect of MT. In conclusion, MT ameliorates cholestatic liver diseases by remodeling gut microbiota and activating intestinal FXR/FGF‐15 axis‐mediated inhibition of hepatic BA synthesis and promotion of BA excretion in mice. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa) exhibits tremendous aluminum (Al)-tolerance. The C2H2-transcription factor (TF) ART1 critically regulates rice Al tolerance via modulation of specific gene expression. However, little is known about the posttranscriptional ART1 regulation. Here, we identified an ART1-interacted gene OsNAC016 via a yeast two-hybrid (Y2H) assay. OsNAC016 was primarily expressed in roots and weakly induced by Al. Immunostaining showed that OsNAC016 was a nuclear protein and localized in all root cells. Knockout of OsNAC016 did not alter Al sensitivity. Overexpression of OsNAC016 resulted in less Al aggregation within roots and enhanced Al tolerance in rice. Based on transcriptomic and qRT-PCR evaluations, certain cell-wall-related or ART-regulated gene expressions such as OsMYB30 and OsFRDL4 were altered in OsNAC016-overexpressing plants. These results indicated that OsNAC016 interacts with ART1 to cooperatively regulate some Al-tolerance genes and is a critical regulatory factor in rice Al tolerance. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is one of the most harmful mycotoxins, which can cause multiple toxicological effects, especially nephrotoxicity in animals and humans. Taurine is an essential amino acid with various biological functions such as anti‐inflammatory and anti‐oxidation. However, the protective effect of taurine on OTA‐induced nephrotoxicity and pyroptosis had not been reported. Our results showed that OTA exposure induced cytotoxicity and oxidative stress in PK‐15 cells, including reactive oxygen species (ROS) accumulation, increased mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX‐2), and decreased mRNA levels of catalase (CAT), glutathione peroxidase 1 (GPx1), and glutathione peroxidase 4 (GPx4). In addition, OTA treatment induced pyroptosis by increasing the expressions of pyroptosis‐related proteins NLRP3, GSDMD, Caspase‐1 P20, ASC, Pro‐caspase‐1, and IL‐1β. Meanwhile, taurine could alleviate OTA‐induced pyroptosis and cytotoxicity, as well as reduce ROS level, COX‐2, and iNOS mRNA levels, and increase the mRNA levels of the antioxidant enzyme in PK‐15 cells. Taken together, taurine alleviated OTA‐induced pyroptosis in PK‐15 cells by inhibiting ROS generation and altering the activity of antioxidant enzymes, thereby attenuating its nephrotoxicity. [ABSTRACT FROM AUTHOR]

Vitamin B12 (VB12) plays vital roles as a cofactor in reactions related to biosynthesis and metabolic regulation. Animals with diarrhoea from intestinal inflammation are susceptible to VB12 deficiency due to dysfunctional absorption. No current medications for canine intestinal inflammation can simultaneously act as VB12 supplements. Here we have tested a strain of VB12‐producing Lactobacillus, to investigate its safety in healthy dogs and test for hypothesized therapeutic and preventive effects on murine colitis. Results from enzyme‐linked immunosorbent assay, histopathological analysis, and quantitative polymerase chain reaction showed normal physical conditions of healthy dogs given Lactobacillus, and blood biochemical indices showed no significant differences in markers, indicating safety of Lactobacillus to healthy dogs. The microbiota in animals receiving VB12‐producing Lactobacillus probiotic exhibited decreased abundance of Escherichia coli and concomitant increase in Lactobacillus. The probiotic supplement also resulted in downregulation of proinflammatory cytokines in murine colon tissues, reduced myeloperoxidase activity and malondialdehyde level, and significantly increased serum VB12 level and decreased homocysteine in therapeutic and preventive experiments. Moreover, Lactobacillus supplement decreased colonic inflammation and injury, improved gut microbiota, and ameliorated VB12 deficiency as an adjunctive therapy. We conclude this product is potentially beneficial for efficient therapy and prevention of VB12 deficiency form intestinal inflammation in canine clinical practice. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is universally known to induce nephrotoxicity via inducing oxidative stress and apoptosis, inhibiting protein synthesis and activating autophagy. Our previous studies have proved that OTA induces nephrotoxicity in vitro and in vivo by adjusting the NOD‐like receptor protein 3 (NLRP3) inflammasome activation and caspase‐1‐dependent pyroptosis. Based on these findings, we further investigated the protective role of selenomethionine (SeMet) on OTA‐caused nephrotoxicity using the Madin‐Darby canine kidney (MDCK) epithelial cells as an in vitro model, proposing to offer a new way for remedying OTA‐induced nephrotoxicity by nutritional manipulation. We measured the cell vitality, lactate dehydrogenase (LDH) activity and the expression of renal fibrotic genes, NLRP3 inflammasome and pyroptosis related genes. MTT and LDH results indicated that SeMet supplementation significantly mitigated 2.0 μg/ml OTA‐induced cytotoxicity in MDCK cells (p < 0.05). Meanwhile, SeMet alleviated OTA induced increase of reactive oxygen species in MDCK cells. Then, the expressions of α‐SMA, Vimentin, and TGF‐β were detected both in mRNA and protein levels. The results indicated 8 μM SeMet supplementation could significantly downregulate the expression of OTA‐induced renal fibrosis‐related genes (p < 0.05). In addition, the upregulation of OTA‐induced NLRP3 inflammasome and pyroptosis downstream genes was also significantly inhibited by 8 μM of SeMet (p < 0.05). In summary, SeMet could alleviate OTA‐induced renal fibrotic genes expression and reduce NLRP3‐caspase‐1‐dependent pyroptosis. Therefore, SeMet supplementation may become an effective approach for preserving animals from renal injury exposed to OTA. [ABSTRACT FROM AUTHOR]