Targeting programmed cell death in inflammatory bowel disease through natural products: New insights from molecular mechanisms to targeted therapies.

Inflammatory bowel disease (IBD) is an autoimmune disorder primarily characterized by intestinal inflammation and recurrent ulceration, leading to a compromised intestinal barrier and inflammatory infiltration. This disorder's pathogenesis is mainly attributed to extensive damage or death of intestinal epithelial cells, along with abnormal activation or impaired death regulation of immune cells and the release of various inflammatory factors, which contribute to the inflammatory environment in the intestines. Thus, maintaining intestinal homeostasis hinges on balancing the survival and functionality of various cell types. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and neutrophil extracellular traps, are integral in the pathogenesis of IBD by mediating the death of intestinal epithelial and immune cells. Natural products derived from plants, fruits, and vegetables have shown potential in regulating PCD, offering preventive and therapeutic avenues for IBD. This article reviews the role of natural products in IBD treatment by focusing on targeting PCD pathways, opening new avenues for clinical IBD management.

A novel prognostic signature for lung adenocarcinoma based on cuproptosis-related lncRNAs: A Review.

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease with complex pathogenesis, high mortality, and poor prognosis. Cuproptosis is a new type of programmed cell death triggered by copper accumulation that may play an important role in cancer. LncRNAs are becoming valuable prognostic factors in cancer patients. The effect of cuproptosis-related lncRNAs (CRlncRNAs) on LUAD has not been clarified. Based on the Cancer Genome Atlas database, CRlncRNAs were screened by co-expression analysis of cuproptosis- related genes and lncRNAs. Using CRlncRNAs, Cox and LASSO regression analyses constructed a risk prognostic model. The predictive efficacy of the model was assessed and validated using survival analysis, receiver operating characteristic curve, univariate and multifactor Cox regression analysis, and principal component analysis. A nomogram was constructed and calibration curves were applied to enhance the predictive efficacy of the model. Tumor Mutational Burden analysis and chemotherapeutic drug sensitivity prediction were performed to assess the clinical feasibility of the risk model. The novel prognostic signature consisted of 5 potentially high-risk CRlncRNAs, MAP3K20-AS1, CRIM1-DT, AC006213.3, AC008035.1, and NR2F2-AS1, and 5 potentially protective CRlncRNAs, AC090948.1, AL356481.1, AC011477.2, AL031600.2, and AC026355.2, which had accurate and robust predictive power for LUAD patients. Collectively, the novel prognostic signature constructed based on CRlncRNAs can effectively assess and predict the prognosis of patients and provide a new perspective for the diagnosis and treatment of LUAD.

Endoscopic Submucosal Dissection for Early Gastric Cancer in Elderly vs. Non-Elderly Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to review the applicability and complications rate associated with endoscopic submucosal dissection (ESD) for early gastric cancer in elderly patients. METHODS: Databases of PubMed, Embase, CENTRAL, and ScienceDirect were searched till 15th April 2021. All types of studies comparing ESD in the elderly vs non-elderly were included. Subgroup analysis was conducted for the following groups: ≥80 years vs <80 years, ≥75 years vs < 75 years, and ≥65 years vs <65 years. RESULTS: 17 studies were included. Meta-analysis indicated no statistically significant difference in the en-bloc resection rates (OR: 0.92 95% CI: 0.68, 1.26 I2 = 8% p=0.62) and histological complete resection rates (OR: 0.93 95% CI: 0.75, 1.15 I2 = 26% p=0.50) between elderly and non-elderly patients. The results were non-significant even on subgroup analysis. Overall, we found a non-significant but a tendency of increased perforation rates in the elderly as compared to non-elderly patients (OR: 1.22 95% CI: 0.99, 1.52 I2 = 0% p=0.06). However, there was a significantly increased risk of perforation in elderly patients aged ≥80 years as compared to patients <80 years (OR: 1.50 95% CI: 1.00, 2.24 I2 = 3% p=0.05). Bleeding rates were not different in the two groups (OR: 1.07 95% CI: 0.87, 1.32 I2 = 19% p=0.52). Pooled analysis indicated a statistically significantly increased risk of pneumonia in elderly patients (OR: 2.52 95% CI: 1.72, 3.70 I2 = 7% p<0.00001). Length of hospital stay was reported only by five studies. Meta-analysis indicated no significant difference between the two study groups (MD: 0.67 95% CI: -0.14, 1.48 I2 = 83% p=0.10). CONCLUSION: En-bloc and histological complete resection rates do not differ between elderly and non-elderly patients undergoing ESD for early gastric cancer. Elderly patients have a small tendency of increased risk of perforation with significantly increased rates in the super-elderly (≥80 years of age). The risk of pneumonia is significantly higher in elderly patients but the rates of bleeding do not differ. The certainty of evidence is "very low" and there is a need for high-quality studies taking into account confounding factors to enhance the quality of evidence.