Intestinal ischemia-reperfusion (I/R) injury is a life-threatening vascular emergency and has long been a disturbing problem for surgeons. Oxidative stress is considered a vital factor in I/R injury. Metformin has anti-oxidative properties and protects against I/R injury. The present study aimed to investigate whether Metformin protects against intestinal I/R injury and reveal the protective mechanism of Metformin. I/R injury was induced in mice by temporary superior mesenteric artery occlusion, and Caco-2 cells were subjected to OGD/R to establish an in vitro model. Different doses of Metformin were administered in vivo and in vitro. We found that I/R injury led to intestinal barrier disruption and cell death by examining histopathological results and the intestinal barrier index, including TER, tight junction proteins and serum biomarkers. We confirmed the existence of pyroptosis in intestinal I/R injury. Moreover, we confirmed the role of pyroptosis in intestinal I/R injury by silencing the gasdermin D (GSDMD). Then, we confirmed that Metformin treatment protected barrier function against intestinal I/R injury and reduced oxidative stress and the inflammatory response. Importantly, Metformin reduced pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and the N-terminus of GSDMD. Knocking down the GSDMD could reversed the protective effects of Metformin, which showed pyroptosis was one of the major cell death pathways controlled by Metformin treatment in setting of intestinal I/R injury. We also discovered that Metformin suppressed the expression of TXNIP and the interaction between TXNIP and NLRP3. We performed siRNA knockdown and found that the protective effects were abolished, which further confirmed our findings. In conclusion, we believe that Metformin protects against intestinal I/R injury in a TXNIP-NLRP3-GSDMD-dependent manner.

AIM: To investigate whether central obesity is associated with nonalcoholic fatty liver disease (NAFLD) formation after adjusting for general obesity. METHODS: The online databases PubMed, EMBASE, and ISI Web of Science were searched for studies estimating the influence of central obesity on NAFLD occurrence published through April 2014. Studies that did not adjust for body mass index (BMI) were excluded. In addition, the independent effect of BMI was also assessed with the included studies. The pooled effect sizes and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on the degree of heterogeneity. Furthermore, subgroup analyses, meta-regression, sensitivity analyses, and publication bias were performed. RESULTS: Twenty eligible studies were identified. The summary odds ratio (OR) values per-unit increase in waist circumference (WC) and BMI for NAFLD formation were 1.07 (95%CI: 1.03-1.10, I² = 73.9%, n = 11 studies) and 1.25 (95%CI: 1.13-1.38, I² = 88.7%, n = 11 studies), respectively. When the indices were expressed as binary variables (with the non-obesity group as reference), the pooled OR in WC, waist-to-hip ratio, and BMI were 2.34 (95%CI: 1.83-3.00, I² = 41.8%, n = 7 studies), 4.06 (95%CI: 1.53-10.79, I² = 65.7%, n = 3 studies), and 2.85 (95%CI: 1.60-5.08, I² = 57.8%, n = 5 studies), respectively. Using the same studies as the latter (n = 5), pooled OR in WC was 3.14 (95%CI: 2.07-4.77), which is greater than that in BMI. CONCLUSION: Central obesity may pose a greater threat to national health than general obesity, although both are independently associated with increased risk of NAFLD.

Lactate is a glycolytic product and a significant energy source. Moreover, it regulates gene transcription via lactylation of histones and non-histone proteins, i.e., a novel posttranslational modification. This review summarizes recent advances related to lactylation in lactate metabolism and diseases. Notably, lactylation plays a vital role in cancer, inflammation, and regeneration; however, the specific mechanism remains unclear. Histone lactylation regulates oncogenic processes by targeting gene transcription and inflammation via macrophage activation. Eventually, we identified research gaps and recommended several primary directions for further studies.

Thioredoxin‐interacting protein (TXNIP) was originally named vitamin D₃ upregulated protein‐1 (VDUP1) because of its ability to bind to thioredoxin (TRX) and inhibit TRX function and expression. TXNIP is an alpha‐arrestin protein that is essential for redox homeostasis in the human body. TXNIP may act as a double‐edged sword in the cell. The balance of TXNIP is crucial. A study has shown that TXNIP can travel between diverse intracellular locations and bind to different proteins to play different roles under oxidative stress. The primary function of TXNIP is to induce apoptosis or pyroptosis under oxidative stress. TXNIP also inhibits proliferation and migration in cancer cells, although TXNIP levels decrease, and function diminishes in various cancers. In this review, we summarized the main structure, binding proteins, pathways, and the role of TXNIP in diseases, aiming to explore the double‐edged sword role of TXNIP, and expect it to be helpful for future treatment using TXNIP as a therapeutic target.

DNA replication is a central procedure of cell proliferation, whereas aberrant DNA replication is indicated to be a driving force of oncogenesis. Minichromosome maintenance complex component 7 (MCM7) plays an essential role in initiating DNA replication. To investigate the potential oncogenic properties and prognostic value of MCM7 in hepatocellular carcinoma (HCC), we conducted immunohistochemistry staining of MCM7 in 153 HCC samples and found that MCM7 high expression level was associated with worse overall survival (OS) of HCC patients. Mechanistically, knockdown of MCM7 significantly inhibited cellular proliferation in vitro and HCC tumorigenicity in vivo. Cyclin D1 was proved to be regulated by MCM7–MAPK signaling pathway. Clinically, high expression of both MCM7 and cyclin D1 exhibited a relatively high sensitivity and specificity to predict worse outcome of HCC patients. Taken together, our results suggest that MCM7–cyclin D1 pathway may participate in cancer progression and serve as a biomarker for prognosis in HCC.

Rationale: Recently, long non-coding RNAs (lncRNAs), known to be involved in human cancer progression, have been shown to encode peptides with biological functions, but the role of lncRNA-encoded peptides in cellular senescence is largely unexplored. We previously reported the tumor-suppressive role of PINT87aa, a peptide encoded by the long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT). Here, we investigated PINT87aa's role in hepatocellular carcinoma (HCC) cellular senescence.