Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats.

Gentamicin is an aminoglycoside antibiotic commonly used to treat Gram-negative bacterial infections that possesses considerable nephrotoxicity. Oxymatrine is a phytochemical with the ability to counter gentamicin toxicity. We investigated the effects and protective mechanism of oxymatrine in rats. The experimental groups were as follows: Control, Oxymatrine only group (100 mg/kg/d), Gentamicin only group (100 mg/kg/d), Gentamicin (100 mg/kg/d) plus Oxymatrine (100 mg/kg/d) group (n = 10). All rats were treated for seven continuous days. The results indicated that oxymatrine alleviated gentamicin-induced kidney injury, and decreased rats' kidney indices and NAG (N-acetyl-beta-d-glucosaminidase), BUN (blood urea nitrogen) and CRE (creatine) serum levels. The oxymatrine-treated group sustained less histological damage. Oxymatrine also relived gentamicin-induced oxidative and nitrative stress, indicated by the increased SOD (superoxidase dismutase), GSH (glutathione) and CAT (catalase) activities and decreased MDA (malondialdehyde), iNOS (inducible nitric oxide synthase) and NO (nitric oxide) levels. Caspase-9 and -3 activities were also decreased in the oxymatrine-treated group. Oxymatrine exhibited a potent anti-inflammatory effect on gentamicin-induced kidney injury, down-regulated the Bcl-2ax and NF-κB mRNAs, and upregulated Bcl-2, HO-1 and Nrf2 mRNAs in the kidney tissue. Our investigation revealed the renal protective effect of oxymatrine in gentamicin-induced kidney injury for the first time. The effect was achieved through activation of the Nrf2/HO-1 pathways. The study underlines the potential clinical application of oxymatrine as a renal protectant agent for gentamicin therapy.

Recent advances of artificial intelligence in melanoma clinical practice.

Skin melanoma is a lethal cancer. The incidence of melanoma is increasing rapidly in all regions of the world. Despite significant breakthroughs in melanoma treatment in recent years, precise diagnosis of melanoma is still a challenge in some cases. Even specialized physicians may need time and effort to make accurate judgments. As artificial intelligence (AI) technology advances into medical practice, it may bring new solutions to this problem based on its efficiency, accuracy, and speed. This paper summarizes the recent progress of AI in melanoma-related applications, including melanoma diagnosis and classification, the discovery of new medication, guiding treatment, and prognostic assessment. The paper also compares the effectiveness of various algorithms in melanoma application and suggests future research directions for AI in melanoma clinical practice.

Camostat mesilate inhibits pro-inflammatory cytokine secretion and improves cell viability by regulating MFGE8 and HMGN1 in lipopolysaccharide-stimulated DF-1 chicken embryo fibroblasts.

Camostat mesilate (CM) possesses potential anti-viral and anti-inflammatory activities. However, it remains unknown whether CM is involved in lipopolysaccharide (LPS)-mediated inflammatory responses and cell injury. In this project, differentially expressed proteins (DEPs, fold change ≥ 1.2 or ≤ 0.83 and Q value ≤ 0.05) in response to LPS stimulation alone or in combination with CM were identified through tandem mass tags (TMT)/mass spectrometry (MS)-based proteomics analysis in DF-1 chicken embryo fibroblasts. The mRNA expression levels of filtered genes were determined by RT-qPCR assay. The results showed that CM alleviated the detrimental effect of LPS on cell viability and inhibited LPS-induced TNF-α and IL-6 secretions in DF-1 chicken embryo fibroblasts. A total of 141 DEPs that might be involved in mediating functions of both LPS and CM were identified by proteomics analysis in DF-1 chicken embryo fibroblasts. LPS inhibited milk fat globule EGF and factor V/VIII domain containing (MFGE8) expression and induced high mobility group nucleosome binding domain 1 (HMGN1) expression, while these effects were abrogated by CM in DF-1 chicken embryo fibroblasts. MFGE8 knockdown facilitated TNF-α and IL-6 secretions , reduced cell viability, stimulated cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. HMGN1 loss did not influence TNF-α and IL-6 secretions, cell viability, and cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. In conclusion, CM exerted anti-inflammatory and pro-survival activities by regulating MFGE8 in LPS-stimulated DF-1 chicken embryo fibroblasts, deepening our understanding of the roles and molecular basis of CM in protecting against Gram-negative bacteria.

The Impact of Berberine on Intestinal Morphology, Microbes, and Immune Function of Broilers in Response to Necrotic Enteritis Challenge.

The objective of this study was to explore the therapeutic effects of berberine on necrotic enteritis (NE) in broilers caused by Clostridium perfringens. A total of 240 1-day-old Arbor Acres chicks were divided into four groups, as negative controls (NC), positive controls (PC), berberine- (BER-) treated, or lincomycin- (LMY-) treated groups. Broilers were challenged with C. perfringens at 15-21 days of age, followed by BER or LMY supplied in drinking water for 7 days. Experimental results showed that C. perfringens infection significantly decreased growth performance and increased intestinal necrosis index and the number of C. perfringens present to 6.45 Log10CFU/g (P < 0.001). Proinflammatory cytokines in the ileum were significantly increased, but the expression of ileal tight junction proteins occludin and claudin-1 was significantly reduced. Both BER and LMY ameliorated some of these observations. Compared with the PC group, the number of C. perfringens in the cecum was significantly decreased following treatment (P < 0.001), and growth performance and small intestine morphology were similar to those of the NC group (P > 0.05). IL-1ß, IL-6, and TNF-α levels as well as occludin and claudin-1 expression were also significantly improved (P < 0.05). BER has the potential to replace antibiotics for NE caused by C. perfringens.

EMP1 promotes the malignant progression of osteosarcoma through the IRX2/MMP9 axis.

BACKGROUND: Previous studies have demonstrated that EMP1 is an oncogene. In this paper, we aim to uncover the role of EMP1 in stimulating the malignant progression of osteosarcoma (OS) by the IRX2/MMP9 axis. METHODS: EMP1 levels in 49 OS tissues and adjacent ones were detected. Potential correlation between EMP1 level and clinical data of OS patients was determined. Migratory and invasive abilities in SaOS-2 and U2OS cells influenced by EMP1 were examined by Transwell and wound healing assay. The involvement of IRX2 in OS cell metastasis regulated by EMP1 was finally explored. RESULTS: EMP1 was upregulated in OS tissues than those of normal ones. Higher rates of lymphatic metastasis and distant metastasis were found in OS patients expressing higher level of EMP1, who suffered a worse prognosis. Knockdown of EMP1 inhibited migratory and invasive abilities in OS cells. Protein levels of IRX2 and MMP9 were upregulated after overexpression of EMP1. Rescue experiments verified that IRX2 was involved in EMP1-regulated malignant progression of OS. CONCLUSIONS: EMP1 is upregulated in OS tissues and closely linked to lymphatic metastasis and distant metastasis. It stimulates the malignant progression of OS through the IRX2/MMP9 axis.

Effects of xylo-oligosaccharide and flavomycin on the immune function of broiler chickens.

This study investigated the effects of xylo-oligosaccharide (XOS) and flavomycin (FLA) on the performance and immune function of broiler chickens. A total of 150 ArborAcres broilers were randomly divided into three groups and fed for six weeks from one day of age in cascade cages. The diets of each test group were (1) a basal diet, (2) the basal diet supplemented with 2 mg/kg FLA, and (3) the basal diet supplemented with 2 mg/kg XOS. At 21 and 42 days, the growth performance index values and short-chain fatty acid (SCFA) concentrations in the cecum were quantified. Furthermore, immunoglobulin G (IgG) and plasma interleukin 2 (IL-2) as well as mRNA expression of LPS-Induced TNF-alpha Factor (LITAF), Toll-like receptor-5 (TLR5) and interferon gamma (IFNγ ) in the jejunum were quantified. The results showed that administration of XOS or FLA to chickens significantly improved the average daily gain. Supplementation with XOS increased acetate and butyrate in the cecum, while FLA supplementation increased propionate in the cecum. An increase in plasma IgG was observed in XOS-fed 21-day-old broilers, but FLA supplementation decreased IgG in the plasma of 42-day-old broilers and increased plasma IL-2. Furthermore, FLA or XOS supplementation downregulated mRNA expression of IFNγ , LITAF and TLR5. The above data suggest that addition of XOS and FLA to the diet could improve the growth performance of broilers and reduce the expression of cytokine genes by stimulating SCFA.

Effects of protease and non-starch polysaccharide enzyme on performance, digestive function, activity and gene expression of endogenous enzyme of broilers.

Three hundred one-day-old male broiler chickens (Ross-308) were fed corn-soybean basal diets containing non-starch polysaccharide (NSP) enzyme and different levels of acid protease from 1 to 42 days of age to investigate the effects of exogenous enzymes on growth performance, digestive function, activity of endogenous digestive enzymes in the pancreas and mRNA expression of pancreatic digestive enzymes. For days 1-42, compared to the control chickens, average daily feed intake (ADFI) and average daily gain (ADG) were significantly enhanced by the addition of NSP enzyme in combination with protease supplementation at 40 or 80 mg/kg (p<0.05). Feed-to-gain ratio (FGR) was significantly improved by supplementation with NSP enzymes or NSP enzyme combined with 40 or 80 mg/kg protease compared to the control diet (p<0.05). Apparent digestibility of crude protein (ADCP) was significantly enhanced by the addition of NSP enzyme or NSP enzyme combined with 40 or 80 mg/kg protease (p<0.05). Cholecystokinin (CCK) level in serum was reduced by 31.39% with NSP enzyme combined with protease supplementation at 160 mg/kg (p<0.05), but the CCK level in serum was increased by 26.51% with NSP enzyme supplementation alone. After 21 days, supplementation with NSP enzyme and NSP enzyme combined with 40 or 80 mg/kg protease increased the activity of pancreatic trypsin by 74.13%, 70.66% and 42.59% (p<0.05), respectively. After 42 days, supplementation with NSP enzyme and NSP enzyme combined with 40 mg/kg protease increased the activity of pancreatic trypsin by 32.45% and 27.41%, respectively (p<0.05). However, supplementation with NSP enzyme and 80 or 160 mg/kg protease decreased the activity of pancreatic trypsin by 10.75% and 25.88%, respectively (p<0.05). The activities of pancreatic lipase and amylase were significantly higher in treated animals than they were in the control group (p<0.05). Supplementation with NSP enzyme, NSP enzyme combined with 40 or 80 mg/kg protease increased pancreatic trypsin mRNA levels by 40%, 44% and 28%, respectively. Supplementation with NSP enzyme and 160 mg/kg protease decreased pancreatic trypsin mRNA levels by 13%. Pancreatic lipase and amylase mRNA expression were significantly elevated in treated animals compared to the control group (p<0.05). These results suggest that the amount of NSP enzyme and acid protease in the diet significantly affects digestive function, endogenous digestive-enzyme activity and mRNA expression in broilers.