Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial barrier. However, whether necroptosis occurs in IECs during liver cirrhosis and whether sodium butyrate (NaB) can regulate necroptosis have not yet been reported. In this study, we aimed to investigate whether IECs undergo necroptosis in cirrhosis and whether NaB can regulate necroptosis and the related regulatory mechanisms.

Serum levels of RIPK3, MLKL, and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL, and tight junction proteins were measured. We conducted an in vitro investigation of the effect of NaB on necroptosis in the HT29 cell line.

Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but had no effect on RIPK1 and RIPK3 in vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL.

NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.

Cholesterol synthesis and gallstone formation are promoted by trimethylamine-N-oxide (TMAO), a derivative of trimethylamine, which is a metabolite of gut microbiota. However, the underlying mechanisms of TMAO-induced lithogenesis remain incompletely understood. This study aimed to explore the specific molecular mechanisms through which TMAO promotes gallstone formation.

Enzyme-linked immunosorbent assays were used to compare serum concentrations of TMAO, apolipoprotein A4 (APOA4), and proprotein convertase subtilisin/kexin type 9 (PCSK9) between patients with cholelithiasis and normal controls. A murine model of TMAO-induced cholelithiasis was employed, incorporating assays of gallstone weight and bile cholesterol content, along with RNA sequencing of murine hepatic tissue. A TMAO-induced AML12 hepatocyte line was constructed and transfected with targeted small interfering RNAs and overexpression plasmids. In vivo and in vitro experiments were performed to determine the expression and regulation of genes related to cholesterol metabolism.

Serum TMAO and PCSK9 levels were elevated, whereas APOA4 levels were reduced in patients with cholelithiasis. Furthermore, our murine model demonstrated that TMAO upregulated hepatic expression of PCSK9, 3-hydroxy-3-methylglutaryl-CoA reductase, and ATP-binding cassette sub-family G member 5/8, while reducing APOA4 expression, thereby modulating cholesterol metabolism and promoting lithogenesis. PCSK9 and APOA4 were identified as key regulatory genes in the cholesterol metabolic pathway. PCSK9 knockdown increased APOA4 expression, while APOA4 overexpression led to reduced PCSK9 expression.

TMAO upregulated hepatic PCSK9 expression and reduced APOA4 expression, initiating a feedback loop that dysregulated cholesterol metabolism and promoted lithogenesis.

Severe COVID-19 pneumonia often requires high concentrations of oxygen, which can potentially lead to oxidative stress and lung injury. This study aimed to investigate the impact of different oxygen therapy modalities on oxidative stress by comparing malondialdehyde (MDA) levels, an oxidative stress marker, and glutathione (GSH), an antioxidant marker, in patients with severe COVID-19 pneumonia.

This study included 50 patients with COVID-19 pneumonia who received oxygen therapy using a reservoir mask at ≥15 L/m, high-flow oxygen therapy at 60 L/m, or oxygen therapy with noninvasive mechanical ventilation at fraction of inspired O2 (FiO2) levels of ≥60%. GSH and MDA levels were measured 48 h after starting oxygen therapy at FiO2 ≥ 60% and 48 h after switching to nasal cannula oxygen therapy at 2–4 L/m.

Overall, 60% (n = 30) of the patients were men, and 40% (n = 20) were women. In patients with accompanying hypertension, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.046). A significant difference in MDA was not found after switching to lower oxygen flow (p = 0.064) in patients with underlying diabetes mellitus. GSH levels in patients with underlying diabetes mellitus were higher during oxygen therapy at FiO2 ≥ 60% and decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.021).

This study compared MDA and GSH levels among patients receiving oxygen therapy at high and low concentrations for severe COVID-19 pneumonia. The results revealed that patients who died of COVID-19 pneumonia had significantly higher mean MDA levels than those who survived. In patients with underlying HT, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased during nasal oxygen therapy at 2–4 L/m; this difference was significant. The increase in serum MDA levels during high-flow oxygen therapy and the decrease during low-flow therapy in patients with COVID-19 pneumonia accompanied by hypertension suggest that oxidative stress due to hyperoxia should be taken into consideration.

The effect of tenofovir amibufenamide (TMF) on blood lipid profiles in patients with chronic hepatitis B (CHB) remains unclear. This study aimed to explore whether TMF affects blood lipids during 48 weeks in patients with CHB.

A total of 91 patients with CHB undergoing TMF treatment for 48 weeks were divided into two groups: Lipid Normal (n = 42) and Lipid Abnormal (n = 49), based on baseline blood lipid levels. Lipid indices, virological responses, and biochemical indicators were compared between the two groups. Clinical observations were further verified through in vitro experiments.

After an average follow-up of 373 ± 121 days, lipid indices in all 91 patients had not significantly changed compared with baseline (total cholesterol: 4.67 vs. 4.69 mmol/L, P = 0.2499; triglycerides: 1.08 vs. 1.04 mmol/L, P = 0.4457; high-density lipoprotein cholesterol: 1.25 vs. 1.25 mmol/L, P = 0.3063; low-density lipoprotein cholesterol: 3.03 vs. 3.02 mmol/L, P = 0.5765). Subgroup comparisons showed lipid indices remained stable. Among treatment-naïve patients (n = 82), complete viral suppression rates were 23.2%, 59.8%, 70.7%, and 86.6% at four, 12, 24, and 48 weeks, respectively. Cellular experiments revealed that TMF did not promote lipid metabolism in primary hepatocytes and AML12 cells.

Regardless of baseline blood lipid characteristics, 48 weeks of antiviral treatment with TMF in patients with CHB had no significant lipid-raising effect.

Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed to investigate the role of clinical and histologic risk factors on long-term outcomes in patients with MASLD.

A retrospective cohort study of 451 adults with biopsy-proven MASLD was conducted at a U.S. academic hospital from 2012 to 2020. An experienced pathologist evaluated the index liver biopsy. Patients with a prior liver transplant or alternative etiologies of chronic liver disease were excluded. The duration of the risk exposure was determined from the date of the index liver biopsy to an outcome event or the last follow-up examination. Outcome events of interest included incident liver-related events, liver decompensation, and all-cause mortality.

In the final cohort of 406 patients followed for a median of 3.7 years (interquartile range: 4.8 years), 35 patients died, 41 developed hepatic decompensation, and 70 experienced a liver-related event. Among histologic risk factors, stage 3 (adjusted Hazard ratio (aHR) 2.68, 95% confidence interval (CI) 1.18–6.11) and stage 4 (aHR 6.96, 95% CI 3.55–13.64) fibrosis were associated with incident liver-related events compared to stage 0–1 fibrosis. Stage 4 (aHR 8.46, 95% CI 3.26–21.99) fibrosis alone was associated with incident liver decompensation events compared to stage 0–1 fibrosis. Among clinical risk factors, hypertension (aHR 2.58, 95% CI 1.05–6.34) was associated with incident liver decompensation.

In a U.S. single-center cohort of patients with biopsy-proven MASLD, advanced fibrosis was the primary risk factor for incident liver decompensation and liver-related events.

Pyrrolizidine alkaloids (PAs), widely distributed in plants, are known to induce liver failure. Hepatic platelet accumulation has been reported during the progression of PA-induced liver injury (PA-ILI). This study aimed to investigate the mechanisms underlying platelet accumulation in PA-ILI.

Cases of PA-ILI, non-PA-ILI, and control subjects were collected from patients hospitalized at Zhongshan Hospital, Fudan University (Shanghai, China) between 2012 and 2019. A mouse model of PA-ILI was established using monocrotaline administration. Liver RNA sequencing was performed, and gene interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database. Low-molecular-weight heparin and recombinant a disintegrin and metalloproteinase with a thrombospondin type I motif member 13 (ADAMTS13) were applied. The necrotic liver area, hepatic platelet accumulation, and von Willebrand factor (VWF) deposition were examined using hematoxylin and eosin staining and immunofluorescence assay.

Hepatic platelet accumulation, necrotic area expansion, and increased VWF expression were observed in both PA-ILI patients and mice. The Search Tool for the Retrieval of Interacting Genes/Proteins database indicated that ADAMTS13 regulates VWF expression and was differentially expressed in the livers of PA-ILI mice. Plasma and hepatic ADAMTS13 levels were significantly downregulated in both PA-ILI patients and mice. Systemic administration of recombinant ADAMTS13 decreased hepatic platelet accumulation, downregulated VWF expression, and mitigated mouse hepatic necrosis.

Hepatic platelet accumulation in PA-ILI was confirmed in both patients and mice. Deficiency of ADAMTS13 plays a critical role in platelet accumulation in PA-ILI, suggesting that ADAMTS13 could be a potential therapeutic target for this condition.

Lung cancer (LC) remains the leading cause of cancer-related deaths worldwide, characterized by high mortality rates and limited treatment options. MicroRNAs (miRNAs) are critical regulators of gene expression and play significant roles in the development of LC. This review aimed to provide a comprehensive analysis of oncogenic miRNAs involved in LC, focusing on their dysregulation, functional roles, and potential implications for diagnosis and therapy. In this review, we collected data from published literature, specifically selecting English articles closely related to the topic. We conducted a thorough review of studies published between 2013 and 2023, utilizing prominent academic databases such as PubMed, Scopus, and Google Scholar to gather relevant data. Our investigation highlights several oncogenic miRNAs that have been shown to play critical roles in lung cancer biology, including miR-9-5p, miR-21, and miR-31. These miRNAs are known to facilitate various key processes, such as tumor cell proliferation, enhanced migratory capabilities, and the development of resistance to chemotherapeutic agents. Additionally, miRNAs present significant diagnostic and therapeutic potential. In conclusion, the unique roles and regulatory networks of miRNAs in LC warrant extensive further research. Further research is essential to uncover the complex networks of miRNAs and to develop innovative miRNA-based therapies for lung cancer.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Epigenetic mechanisms have revealed that noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in HCC progression. This study aimed to construct a circRNA-miRNA-mRNA network in HCC and validate one axis within the network.

HCC-related transcriptome data were obtained from the Gene Expression Omnibus, and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs. The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted. The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.

We identified six differentially expressed circRNAs in HCC, which were linked to 13 miRNAs and 88 mRNAs. A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed. Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression, possibly through the miR-140-3p/KRAS axis. Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.

The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus (PLHIV), especially in low-and middle-income countries. This study was designed to investigate the sociodemographic factors associated with depression among PLHIV on antiretroviral therapy in a Nigerian cosmopolitan city.

A hospital-based, cross-sectional study was conducted among 592 consenting, randomly selected adult PLHIV receiving treatment at a university teaching hospital in Jos, Nigeria, in 2022, using the PHQ-9 questionnaire and an interviewer-administered sociodemographic questionnaire. Associated variables in univariate analysis were used in multivariable binary logistic regression to obtain adjusted odds ratios (AOR) with a significance level set at α = 0.05.

Depression was found to be highly prevalent among study participants, with 44.9% of them affected. Findings revealed that being male [AOR = 0.62; 95% confidence interval (CI): 0.42–0.92], being employed (AOR = 0.55; 95%CI: 0.31–0.97), and earning a monthly income of ₦50,000–100,000 ($65–130) (AOR = 0.49; 95% CI: 0.27–0.91) and >₦100,000–200,000(>$130–260) (AOR = 0.33; 95% CI: 0.13–0.77) were significantly associated with reduced odds of depression.

The significant association of being male, having formal employment, and earning a moderate monthly income with reduced odds of depression may have implications for policy and strategies for managing mental health issues among PLHIV in cosmopolitan areas like Jos, which face peculiar challenges such as cultural tensions, traffic congestion, and gentrification. PLHIV categories with a relatively higher likelihood of depression may benefit from targeted mental health support systems, in addition to other mental health management strategies generally available to PLHIV.

Waist circumference (WC) is closely associated with metabolic diseases, including diabetes mellitus (DM), metabolic syndrome, and mortality. However, the correlation between WC and mortality varies across populations and has rarely been examined specifically in patients with DM. In this study, we explored the relationships between WC and both all-cause and cardiovascular mortalities among individuals with DM.

Participants from the National Health and Nutrition Examination Survey 2003–2018 included 3,151 women and 3,473 men with DM who had baseline WC measurements. Survival data were collected from enrollment until December 31, 2019. Cox proportional hazard models were adjusted for demographic features and other confounders. Restricted cubic spline curves and threshold effect analyses were performed separately for men and women. Sensitivity analyses were conducted to minimize reverse causality.

Among 6,624 participants with DM, 621 women and 871 men died during median follow-ups of 6.8 and 6.3 years, respectively. WC demonstrated a U-shaped association with all-cause and cardiovascular mortalities in women, and a J-shaped trend in men. The optimal WC thresholds for minimizing mortality risk were 107.0 cm for women and 89.0 cm for men. For women, adjusted hazard ratios for all-cause mortality were 0.97 (95% confidence interval (CI): 0.96–0.98, P < 0.001) for WC below 107.0 cm and 1.04 (95% CI: 1.02–1.05, P < 0.001) for WC above 107.0 cm. In men, the corresponding ratios were 0.94 (95% CI: 0.90–0.97, P < 0.001) for WC below 89.0 cm and 1.03 (95% CI: 1.02–1.05, P < 0.001) for WC above 89.0 cm.

WC showed a U-shaped association with all-cause and cardiovascular mortalities in women and a J-shaped association in men among U.S. adults with DM from the National Health and Nutrition Examination Survey. Further research is needed to explore the underlying mechanisms rather than promoting preconceived notions about an optimal WC.