Inflammatory cytokines is a key point in the development of pathogenesis of SAP. Inflammatory mediators TNF-α and IL-6 are up-regulated in serum of patients with SAP and become good discriminators of SAP severity. In this study, we investigated the treatment effectiveness of Baicalein on SAP rat model. Baicalein was intravenously injected immediately after SAP induction in rats. The mortality, histopathology score, ascites fluid volume, and pro-inflammatory cytokine production were evaluated at 12 h after SAP induction. Baicalein decreased the pancreatic histopathology score, reduced ascites fluid production, protected against pancreatic injury, and improved survival in rats with SAP. The serum IL-6 and TNF-α concentrations were also down-regulated by Baicalein. Baicalein demonstrated a well curative capability on rats with SAP. The mechanism may be alleviateing pancreatic injury and inhibiting pro-inflammatory cytokines expression.

Drug induced liver injury (DILI) is a kind of liver dysfunction which caused by drugs, and gut microbiota could affect liver injury. However, the relationship between gut microbiota and its metabolites in DILI patients is not clear. The total gut microbiota DNA was extracted from 28 DILI patient and 28 healthy control volunteers (HC) and 16S rDNA gene were amplified. Next, differentially metabolites were screened. Finally, the correlations between the diagnostic strains and differentially metabolites were studied.The richness and uniformity of the bacterial communities decreased in DILI patients, and the structure of gut microbiota changed obviously. Enterococcus and Veillonella which belong to Firmicutes increased in DILI, and Blautia and Ralstonia which belong to Firmicutes, Dialister which belongs to Proteobacteria increased in HC. In addition, these diagnostic OTUs of DILI were associated with the DILI damage mechanism. On the other hands, there were 66 differentially metabolites between DILI and HC samples, and these metabolites were mainly enriched in pyrimidine metabolism and steroid hormone biosynthesis pathways. Furthermore, the collinear network map of the key microbiota-metabolites were constructed and the results indicated that Cortodoxone, Prostaglandin I1, Bioyclo Prostaglandin E2 and Anacardic acid were positively correlated with Blautia and Ralstonia, and negatively correlated with Veillonella.This study analyzed the changes of DILI from the perspective of gut microbiota and metabolites. Key strains and differentially metabolites of DILI were screened and the correlations between them were studied. This study further illustrated the mechanism of DILI.

The objective of this study was to analyse clinical and genetic features of patients with sporadic ALS in south-west China. All patients diagnosed with adult-onset sporadic ALS were consecutively followed up, and their clinical characteristics were collected. The frequencies of alleles of six SNPs in the FLJ10986 gene and the association between these SNPs and the clinical features of ALS were analysed. One hundred and sixty-one patients were included in the study. The mean age of onset was 50.9±11.4 years. The mean diagnostic delay was 16.5±14.3 months and the mean disease duration was 30.7±23.5 months. Forty patients (24.2%) died during the period of follow-up. Positive correlation between mean delay and disease duration was found, as was negative correlation between onset age, mean delay and disease duration. The frequency of the ‘G’ variant of the SNP (rs10493256) was significantly higher than that in a control population. There was no significant difference in the frequencies of variant alleles regarding clinical features. In conclusion, SNP (rs10493256) in the FLJ10986 gene appears to increase the risk of developing sporadic ALS in our Chinese population. Our Clinical findings are in line with other studies. No association between the polymorphisms and clinical features was found.

Recently, the non-high-density to high-density lipoprotein cholesterol ratio (NHHR) has gained growing attention as an indicator for predicting diseases associated with lipid metabolism. Hepatic steatosis and fibrosis are tightly associated lipid metabolism. Our study aims to analyze the correlations among NHHR, hepatic steatosis, and fibrosis. This study analysed data from 14,578 adults in the US National Health and Nutrition Examination Survey (2005–2018). The degree of hepatic steatosis was measured through the Fatty Liver Index (FLI), while liver fibrosis severity was evaluated with the Fibrosis-4 (FIB-4) index. Multivariate linear regression assessed the association between NHHR and the FLI and FIB-4 score. Smooth curve describing the relationship between NHHR and FLI or FIB-4. Additionally, a two-part linear regression model adopted in order to more accurately account for the nonlinear relationship, with threshold effects estimated through its two components. To confirm the robustness of the findings, interaction tests and subgroup analyses were conducted. The multivariate logistic regression analysis demonstrated a significantly positive correlation of lnNHHR with FLI across all three models. In Model 3, the association was (β = 11.14, 95%CI:10.38,11.90). Curve fitting indicated a nonlinear relationship. The positive correlation between lnNHHR and FLI persists across gender, BMI, and physical activity groups. Nevertheless, a notable negative correlation between lnNHHR and FIB-4 was observed in all three models. In Model 3, the relationship between lnNHHR and FIB-4 was as follows: (β = -0.20; 95% CI: -0.22, -0.17). Curve fitting revealed a V-shaped relationship, with threshold effect analysis identifying a breakpoint at 1.51. Above this threshold, the relationship was found to be statistically insignificant (p-value = 0.424). Receiver operating characteristic (ROC) curve analysis demonstrated that NHHR exhibited better predictive performance for MASLD compared to non-HDL-C, HDL-C, and LDL-C/HDL-C. The current study’s findings suggest that elevated levels of NHHR correlate with a greater risk of hepatic steatosis among adults in the U.S. Our findings imply that NHHR may be a valuable tool in improving MASLD prevention strategies in the general population.

Mitophagy is crucial for maintaining mitochondrial health, but how its levels adjust to different stress conditions remains unclear. In this study, we investigated the role of the DELE1-HRI axis of integrated stress response (ISR) in regulating mitophagy, a key mitochondrial stress pathway. Our findings show that the ISR suppresses mitophagy under non-depolarizing mitochondrial stress by positively regulating mitochondrial protein import, independent of ATF4 activation. Mitochondrial protein import is regulated by the rate of protein synthesis under both depolarizing and non-depolarizing stress. Without ISR, increased protein synthesis overwhelms the mitochondrial import machinery, reducing its efficiency. Under depolarizing stress, mitochondrial import is heavily impaired even with active ISR, leading to significant PINK1 accumulation. In contrast, non-depolarizing stress allows more efficient protein import in the presence of ISR, resulting in lower mitophagy. Without ISR, mitochondrial protein import becomes severely compromised, causing PINK1 accumulation to reach the threshold necessary to trigger mitophagy. These findings reveal a novel link between ISR-regulated protein synthesis, mitochondrial import, and mitophagy, offering potential therapeutic targets for diseases associated with mitochondrial dysfunction.

Mitophagy is crucial for maintaining mitochondrial health, but how its levels adjust to different stress conditions remains unclear. In this study, we investigated the role of the DELE1-HRI axis of the integrated stress response (ISR) in regulating mitophagy, a key mitochondrial quality control mechanism. Our findings show that the ISR suppresses PINK1-dependent mitophagy under many mitochondrial stress conditions by maintaining mitochondrial presequence protein import, independent of ATF4 activation. Mitochondrial presequence protein import efficiency is tightly linked to the rate of protein synthesis. Without the ISR, increased protein synthesis overwhelms the mitochondrial import machineries, reducing import efficiency. This impairment can be mitigated by pharmacological attenuation of protein synthesis, such as with mTOR or general translation inhibitors. Under severe depolarizing stress, mitochondrial import is heavily impaired even with an active ISR, leading to significant PINK1 accumulation. In contrast, mild mitochondrial stress allows more efficient protein import in the presence of the ISR, resulting in lower mitophagy. Without the ISR, mitochondrial protein import becomes significantly compromised, causing PINK1 accumulation to reach the threshold level necessary to trigger mitophagy. These findings reveal a link between ISR-regulated protein synthesis, mitochondrial protein import, and mitophagy, offering potential therapeutic targets for diseases associated with mitochondrial dysfunction.