Fatty acid metabolism is closely linked to the progression of gastric cancer (GC), a very aggressive and life-threatening tumor. This study examines linked molecules, such as Sterol Regulatory Element-Binding Protein 1 (SREBP1), ATP Citrate Lyase (ACLY), Acetyl-CoA Synthases (ACSs), Acetyl-CoA Carboxylase (ACC), Fatty Acid Synthase (FASN), Stearoyl-CoA Desaturase 1 (SCD1), CD36, Fatty Acid Binding Proteins (FABPs), and Carnitine palmitoyltransferase 1 (CPT1), as well as their latest studies and findings in gastric cancer to unveil its core mechanism. The major enzymes of fatty acid de novo synthesis are ACLY, ACSs, ACC, FASN, and SCD1, while SREBP1 is the upstream molecule of fatty acid anabolism. Fatty acid absorption is mediated by CD36 and FABPs, and fatty acid catabolism is mediated by CPT1. If at all possible, we will discover novel links between fatty acid metabolism and a prospective gastric cancer target.

Background Severe acute pancreatitis (SAP) manifests as a critical state marked by acute abdominal symptoms, often associated with intestinal barrier dysfunction, exacerbating SAP retroactively. Ganoderic acid A (GAA) demonstrates anti-inflammatory properties in various inflammatory disorders. Nonetheless, its potential therapeutic impact on SAP and the underlying mechanisms remain unexplored. Methods In both wild-type and TLR4^-/- mice, experimental SAP was induced using caerulein plus lipopolysaccharide. Caerulein injections were administered intraperitoneally following 7 days of intragastric GAA administration. Additionally, the potential mechanisms by which GAA ameliorates SAP were further investigated using fecal microbiota transplantation and TLR4-overexpressing IEC-6 cells. Results We observed that GAA treatment significantly ameliorated serum levels of amylase, lipase, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in SAP mice. Pretreatment with GAA mitigated pathological injuries and reduced M1 macrophage and neutrophil infiltration in pancreatic or ileal tissues. Additionally, GAA treatment down-regulated TLR4-MAPK/NF-κB signaling and NLRP3 inflammasome activation in the pancreatic and ileal tissues of SAP mice. The results further revealed that the gavage of GAA decreased bacterial translocation (Escherichia coli and EUB338), repaired intestinal barrier dysfunction (ZO-1, occludin, DAO, and FITC), increased lysozyme and MUC2 expression, and raised the levels of short-chain fatty acids. Analysis of the gut microbiome showed that the beneficial effects of GAA treatment were associated with improvements in pancreatitis-associated gut microbiota dysbiosis, characterized by notable increases in α-diversity and the abundance of probiotics such as Akkermansia, GCA-900066575, and Parvibacter. Fecal transplantation experiments further confirmed that GAA exerts protective effects by modulating intestinal flora. The protective role of GAA in intestinal and pancreatic injuries is mediated by the inhibition of TLR4 signaling, as further evidenced in TLR4-deficient mice and TLR4-overexpressed IEC-6 cells. The results of docking indicated that GAA interacts with TLR4 via a hydrophobic interaction. Conclusions The study demonstrates that GAA significantly alleviates SAP through its anti-inflammatory and antioxidant capacities, as well as by restoring intestinal homeostasis, thereby providing insights into novel treatments for SAP.

Background: An increasing number of studies have focused on the association between leptin, adiponectin levels and the risk as well as the prognosis of hepatocellular carcinoma. However, the reported results are conflicting.Methods: A meta-analysis was performed to assess the correlation between leptin, adiponectin levels and risk and prognosis of hepatocellular carcinoma (CRD42020195882). Through June 14, 2020, PubMed, Cochrane Library and EMBASE databases were searched, including references of qualifying articles. Titles, abstracts, and main texts were reviewed by at least 2 independent readers. Stata 16.0 was used to calculate statistical data.Results: Thirty studies were included in this meta-analysis and results showed that hepatocellular carcinoma group had significantly higher leptin levels than the cancer-free control group (SMD = 1.83, 95% CI (1.09, 2.58),P = 0.000), the healthy control group (SMD = 4.32, 95% CI (2.41, 6.24),P = 0.000) and the cirrhosis group (SMD = 1.85, 95% CI (0.70, 3.01),P = 0.002). Hepatocellular carcinoma group had significantly higher adiponectin levels than the healthy control group (SMD = 1.57, 95% CI (0.37, 2.76),P = 0.010), but no statistical difference compared with the cancer-free control group (SMD = 0.24, 95% CI (− 0.35, 0.82),P = 0.430) and the cirrhosis group (SMD = − 0.51, 95% CI (− 1.30, 0.29),P = 0.213). The leptin rs7799039 polymorphism was associated with increased risk of hepatocellular carcinoma (G vs A: OR = 1.28, 95% CI (1.10, 1.48),P = 0.002). There were linear relationships between adiponectin levels and the risk of hepatocellular carcinoma (OR = 1.066, 95% CI (1.03, 1.11),P = 0.001). In addition, the results showed that high/positive expression of adiponectin was significantly related to lower overall survival in hepatocellular carcinoma patients (HR = 1.70, 95% CI (1.22, 2.37),P = 0.002); however, there was no significantly association between the leptin levels and overall survival (HR = 0.92, 95% CI (0.53, 1.59),P = 0.766).Conclusion: The study shows that high leptin levels were associated with a higher risk of hepatocellular carcinoma. Adiponectin levels were proportional to hepatocellular carcinoma risk, and were related to the poor prognosis.

Malnutrition often induces an adverse prognosis in cancer surgery patients. The elderly nutrition risk index (GNRI) is an example of the objective indicators of nutrition-related risks. We performed a meta-analysis to thoroughly examine the evidence for the GNRI in predicting the outcomes of patients undergoing stomach cancer surgery. Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by 24 October 2022. The clinical outcomes were overall survival (OS), cancer-specific survival (CSS), and post-operative complications. A total of 11 articles with 5593 patients were included in this meta-analysis. The combined forest plot showed that for every unit increase in the preoperative GNRI score in patients with stomach cancer, their postoperative mortality was reduced by 5.6% (HR: 0.944; 95% CI: 0.933–0.956, p < 0.001). The pooled results also demonstrated that a low GNRI was correlated with poor OS (HR: 2.052; 95% CI: 1.726–2.440, p < 0.001) and CSS (HR: 1.684; 95% CI: 1.249–2.270, p = 0.001) in patients who underwent stomach cancer surgery. Postoperative complications were more likely to occur in patients with a low GNRI, as opposed to those with a high GNRI (OR: 1.768; 95% CI: 1.445–2.163, p < 0.001). There was no evidence of significant heterogeneity, and the sensitivity analysis supported the stability and dependability of the above results. the GNRI is a valuable predictor of long-term outcomes and complications in stomach cancer patients undergoing surgery.

Uridine is a key metabolite used as a substrate for the production of DNA, RNA, and glucose, and it is mainly synthesized in the liver. Currently, it is not known whether uridine levels are altered in the tumor microenvironment of patients with hepatocellular carcinoma (HCC) and whether uridine can be a target for tumor therapy. In this study, the detection of genes associated with de novo uridine synthesis, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) (n = 115), and dihydroorotate dehydrogenase (DHODH) (n = 115) in HCC tissues through tissue microarrays revealed that the expression of CAD and DHODH was higher in tumor compared with paraneoplastic tissues. Next, we collected tumor tissues from surgically resected HCC patients and the corresponding adjacent non-tumor tissues (n = 46) for LC–MS/MS assays. The results showed that the median and interquartile ranges of uridine content in non-tumor and tumor tissues were 640.36 (504.45–807.43) and 484.22 (311.91–626.73) nmol/g, respectively. These results suggest that uridine metabolism is disturbed in HCC patients. To further investigate whether uridine can be used as a tumor-therapeutic target, a series of high concentrations of uridine were incubated with HCC cells in vitro and in vivo. It was observed that uridine dose-dependently inhibited the proliferation, invasion, and migration of HCC cells by activating the ferroptosis pathway. Overall, these results reveal for the first time the range of uridine content in human HCC tissues and suggest that uridine may be a new target for HCC therapy.

Cancer is a leading cause of death globally. Immunotherapy has shown promise in treating various types of cancer, but its effectiveness varies among patients. The Controlling Nutritional Status (CONUT) score has been linked to the prognosis of different cancers. However, its predictive value for immunotherapy outcomes is not well understood. Our research represents the pioneering meta-study to examine the prognostic value of the CONUT score on cancer patients treated with an immune checkpoint inhibitor (ICI). A comprehensive literature search was conducted using various databases including PubMed, the Cochrane Library, EMBASE, and Google Scholar. The study was conducted until July 28, 2023. This analysis encompassed a comprehensive evaluation of various clinical outcomes, namely overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). 663 patients from 8 studies were included in this study. It showed that cancer patients with high CONUT score had poorer OS (HR: 1.94, 95% CI, 1.52–2.47, p < 0.001) and PFS (HR: 2.22, 95% CI, 1.48–3.31, p < 0.001), as well as worse ORR (OR: 0.46, 95% CI, 0.25–0.85, p = 0.013) and DCR (HR: 0.29, 95% CI, 0.14–0.59, p = 0.001). The CONUT score can predict the prognosis of tumor patients treated with ICIs.