Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota

BackgroundWith the development of healthcare services, drug efficacy, and safety have become the focus of drug use, and processing alters drug toxicity and efficacy, exploring the effects of processing on Evodiae fructus (EF) can guide the clinical use of drugs.MethodsFifty male Kunming mice were randomly divided into the control group (CCN), raw small-flowered EF group (CRSEF), raw medium-flowered EF group (CRMEF), processing small-flowered EF group (CPSEF), and processing medium-flowered EF group (CPMEF). The CRSEF, CRMEF, CPSEF, and CPMEF groups were gavaged with aqueous extracts of raw small-flowered EF dry paste (RSEF), medium-flowered EF dry paste (RMEF), processing small-flowered EF dry paste (PSEF) and processing medium-flowered EF dry paste (PMEF), respectively, for 21 days at 5 times the pharmacopeial dosage. Upon concluding the experiment, histopathological sections of liver and kidney tissues were examined. Additionally, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) were determined. DNA from the intestinal contents of the mice was extracted, and 16S rRNA full-length high-throughput sequencing was performed.ResultsAfter fed EF 21 days, mice exhibited a decreasing trend in body weight. Comparative analysis with the CCN group revealed an upward trend in SCr, BUN, AST, and ALT levels in both CRSEF and CRMEF groups. The CRMEF group displayed notably elevated BUN and AST levels, with an observed increasing trend in Scr and ALT. Kidney sections unveiled cellular edema and considerable inflammatory cell infiltrates, whereas significant liver damage was not evident. Compared with CRSEF, Bun levels were significantly lower while AST levels were significantly higher in the CPMEF group. Additionally, the intestinal microbiota diversity and the relative abundance of Psychrobacter decreased significantly, and the relative abundance of Staphylococcus, Jeotgalicoccus, and Salinicoccus increased significantly in the CPMEF group. AST, ALT, and SCr were positively correlated with Staphylococcus, Jeotgalicoccus, and Salinicoccus.ConclusionIn conclusion, PMEF significantly increased harmful bacteria (Staphylococcus, Jeotgalicoccus, and Salinicoccu) and decreased beneficial bacteria. SEF with 5 times the clinical dose showed nephrotoxicity and SEF nephrotoxicity decreased after processing, but EF hepatotoxicity was not significant, which may be due to insufficient dose concentration and time

Identification and profiling of growth-related microRNAs in Chinese perch (Siniperca chuatsi)

Abstract Background MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play important roles in the regulation of diverse biological processes in eukaryotes. Chinese perch (Siniperca chuatsi) is one of the most economically important fish species widely cultured in China. Growth is an extremely important characteristic in fish. Individual differences in body size are common in Siniperca chuatsi, which significantly influence the aquaculture production of Siniperca chuatsi. However, the underline growth-related regulatory factors, such as miRNAs, are still unknown. Results To investigate the growth-related miRNAs in Siniperca chuatsi, two RNA libraries from four growth-related tissues (brain, pituitary, liver, and muscle) of Siniperca chuatsi at 6-month stage with relatively high or low growth rates (big-size group or small-size group) were obtained and sequenced using Solexa sequencing. A total of 252 known miRNAs and 12 novel miRNAs were identified. The expression patterns of these miRNAs in big-size group and small-size group were compared, and the results showed that 31 known and 5 novel miRNAs were differently expressed (DE). Furthermore, to verify the Solexa sequencing, five DE miRNAs were randomly selected and quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results showed that their expression patterns were consistent with those of Solexa sequencing. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of target genes of DE miRNAs was performed. It showed that the target genes were involved in multiple biological processes including metabolic process, suggesting that metabolic process played an important role in growth of fish. Conclusions Siniperca chuatsi is a popular and economically important species in aquaculture. In this study, miRNAs in Siniperca chuatsi with different growth rates were identified, and their expression profiles were compared. The data provides the first large-scale miRNA profiles related to growth of Siniperca chuatsi, which is expected to contribute to a better understanding of the role of miRNAs in regulating the biological processes of growth and possibly useful for Siniperca chuatsi breeding

Additional file 1: of Identification and profiling of growth-related microRNAs in Chinese perch (Siniperca chuatsi)

Target gene prediction and analysis of miRNAs. (XLS 1498 kb

12/15-Lipoxygenase Regulation of Diabetic Cognitive Dysfunction Is Determined by Interfering with Inflammation and Cell Apoptosis

This study aimed to discuss the role of 12/15-lipoxygenase (12/15-LOX) regulation involved in diabetes cognitive dysfunction. First, Mini Mental State Examination (MMSE) test was used to evaluate cognitive ability in diabetic patients and normal controls. The plasma test showed that the plasma level of 12/15-LOX in patients with MMSE scores below 27 was significantly increased compared with that of the normal group. Second, 12/15-LOX inhibitor was administered to diabetic rats. Behavioral tests, biochemistry, enzyme-linked immunosorbent assays, and Western blotting were used in this study. We found that the levels of fasting and random blood glucose increased rapidly in diabetic rats, the levels of triglycerides and total cholesterol in the diabetic group increased, and insulin levels decreased significantly. In the Morris water maze test, the escape latency was prolonged, and the crossing times decreased in the diabetic group. Under the microscope, the apoptosis of hippocampal neurons in diabetic rats increased significantly. The levels of TNF-α, IL-6 and 12-hydroxyindoleic acid (12(S)-HETE) significantly increased, and the protein expression of 12/15-LOX, p38 MAPK, Aβ1-42, caspase-3, caspase-9 and cPLA2 increased, while that of Bcl-2 decreased. However, the use of 12/15-LOX inhibitor reversed these results. Third, 12/15-LOX shRNA and p38MAPK inhibitor were administered to HT22 cells in high-glucose medium. The results of the cell experiment were consistent with those of the animal experiment. Our results indicated that the 12/15-LOX pathway participates in diabetic brain damage by activating p38MAPK to promote inflammation and neuronal apoptosis, and intervention 12/15-LOX can improve diabetic cognitive dysfunction