Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers.

Drug resistance in cancer remains a major challenge in oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as a critical player in the development of drug resistance in cancer cells. This comprehensive review explores the intricate relationship between NF-κB and drug resistance in cancer. We delve into the molecular mechanisms through which NF-κB activation contributes to resistance against chemotherapeutic agents, targeted therapies, and immunotherapies. Additionally, we discuss potential strategies to overcome this resistance by targeting NF-κB signaling, such as small molecule inhibitors and combination therapies. Understanding the multifaceted interactions between NF-κB and drug resistance is crucial for the development of more effective cancer treatment strategies. By dissecting the complex signaling network of NF-κB, we hope to shed light on novel therapeutic approaches that can enhance treatment outcomes, ultimately improving the prognosis for cancer patients. This review aims to provide a comprehensive overview of the current state of knowledge on NF-κB and its role in drug resistance, offering insights that may guide future research and therapeutic interventions in the fight against cancer.

Comprehensive analysis to construct a novel immune-related prognostic panel in aging-related gastric cancer based on the lncRNA‒miRNA-mRNA ceRNA network.

Introduction: Gastric cancer (GC) is the fifth frequent malignancy and is responsible for the third leading cause of cancer-related deaths. Gastric cancer is an aging-related disease, with incidence and mortality rates increasing with aging. The development of GC is affected by lncRNAs, miRNAs, and mRNAs at the transcriptional and posttranscriptional levels. This study aimed to establish a prognostic panel for GC based on competing endogenous RNA (ceRNA) networks. Methods: RNA sequences were obtained from the TCGA database. Different expressions of RNAs were scrutinized with the EdgeR package. The ceRNA network was built using the starBase database and the Cytoscape. The prognostic panel was constituted with the LASSO algorithm. We developed a nomogram comprising clinical characteristic and risk score. The receiver operating characteristic (ROC) was used to evaluate the accuracy of the nomogram prediction. Hub RNAs expressions were detected by qPCR, immunohistochemistry and western blot respectively. Clinical relevance and survival analyses were analyzed. The relationship between RNAs and immune infiltrations, as well as immune checkpoints, was analyzed and evaluated using the CIBERSORT, TIMER and TISIDB databases. Results: Four DElncRNAs, 21 DEmiRNAs and 45 DEmRNAs were included in the ceRNA network. A 3-element panel (comprising lncRNA PVT1, hsa-miR-130a-3p and RECK) with poor overall survival (OS) was established and qPCR was applied to validate the expressions of hub RNAs. Hub RNAs were firmly associated with T, M, and N stage. The CIBERSORT database showed that the high lassoScore group exhibited a significantly high ratio of resting memory CD4+ T cells, M2 macrophages and a significantly low ratio of activated memory CD4+ T cells and M1 macrophages. According to the TIMER database, this panel was linked to immune infiltrations and immune cell gene markers. TISIDB database indicated that RECK was positively correlated with immune checkpoints (including CD160, CD244, PDCD1, and TGFBR1). Discussion: A novel triple prognostic panel of GC constructed based on the ceRNA network was associated with clinical prognostic, clinicopathological features, immune infiltrations, immune checkpoints and immune gene markers. This panel might provide potential therapeutic targets for GC and more experimental verification research is needed.

Prevalence and characteristics of gastric remnant cancer: A systematic review and meta-analysis.

The incidence and outcomes of GRC remain variable. Minority published researches have paid attention to the characteristics of GRC. This study aimed to make a systematic review and meta-analysis of the prevalence of GRC, with a focus on characteristics and survival rates of GRC. PubMed, EMBASE, and CENTRAL were searched for related clinical studies. Data were pooled using Stata 11.0, and subgroup and sensitivity analyses were performed if necessary and feasible. Moreover, SPSS (version 19.0) was used for comparing the clinical characteristics of GRC. Twenty studies were selected in this meta-analysis. The results indicated that the pooled prevalence of GRC was 2.6% (95% confidence interval (CI), 2.2-3.0%, p = 0.000). European population and American populations have a higher rate of prevalence of GRC than Chinese populations and Japan. There is no significant difference in histology and the TNM stage between the benign group and the malignant group. The five-year survival rate for GRC cases with benign primary gastric diseases is poorer than the primary gastric diseases malignant. Gastric remnant cancer is not a very rare clinical problem, especially for European and American patients. Active treatment and regular follow-up are conductive to increase 5-years survival rate.

Bile acid, glucose, lipid profile, and liver enzyme changes in prediabetic patients 1 year after sleeve gastrectomy.

BACKGROUND: Few articles have studied individuals with prediabetes after sleeve gastrectomy. Bile acid and lipid levels remain inconsistent in postbariatric patients. The purpose of this study was to explore bile acid, glucose, lipid, and liver enzyme changes in patients with different diabetes statuses who underwent sleeve gastrectomy. The impact of bariatric surgery and its potential benefits for prediabetic patients was also discussed. METHODS: A total of 202 overweight and obese patients who underwent bariatric surgery in our hospital between January 2016 and October 2018 were retrospectively reviewed. Patients were divided into prediabetes (n = 32), nondiabetes (n = 144), and diabetes (n = 26) groups and analysed. Glucose and lipid data were collected from medical records at baseline and at each follow-up visit. RESULT: Significant improvements in body weight, glucose and lipid levels, and liver enzymes (P ≤ 0.05) in prediabetic patients were found throughout the first year postoperatively. Improvement in glycaemic control was first seen one month postoperatively, followed by persistent improvement in the next 12 months. Total bile acid (TBA) decreased, which was associated with ALT improvement in prediabetic patients 1-year post-surgery. There were no significant differences in HbA1c, glucose, or triglycerides (TGs) between prediabetic and T2DM patients or between prediabetic and nondiabetic patients at 12 months post-surgery. CONCLUSION: LSG is highly effective at interfering with glucose and lipid levels as well as total bile acid levels in prediabetic patients in the first year postoperatively. Thus, LSG is indeed an alternative for overweight and obese prediabetic patients.

Effect of Bariatric Surgery on Serum Enzyme Status in Obese Patients.

BACKGROUND: Scarce data exists about serum enzyme in bariatric patients. We attempted to evaluate serum enzyme status in patients receiving Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) and to identify related predictors. METHODS: We retrospectively reviewed the patients receiving RYGB and SG in our center from January 2013 to January 2018. Anthropometric data and serum enzyme data were collected preoperatively and 6 and 12 months postoperatively. RESULTS: Five hundred patients (201 RYGB, 299 SG) were included. Serum enzyme abnormalities were common preoperatively, with 50.8% for elevated alanine aminotransferase (ALT), 33.0% for elevated aspartate aminotransferase (AST), 36.6% for elevated γ-glutamyltranspeptidase (γ-GT), 17.6% for elevated creatine kinase (CK), 15.2% for elevated lactic dehydrogenase (LDH), 9.0% for elevated adenosine deaminase (ADA), 6.2% for elevated hydroxybutyrate dehydrogenase (HBDH), and 8.4% for decreased superoxide dismutase (SOD). After RYGB and SG, the prevalence of serum ALT, AST, γ-GT, LDH, and HBDH abnormalities reduced. The levels of ALT, AST, γ-GT, ADA, cholinesterase (CHE), LDH, CK, and HBDH reduced significantly, while amylase and SOD levels increased. Age and preoperative γ-GT level were independent predictors of ALT, AST, γ-GT, and LDH change 1 year postoperatively. Preoperative ALT, AST, ALP, LDH, and HBDH levels could predict postoperative change, respectively. Gender and surgical procedure could predict postoperative ALP change. CONCLUSION: Serum enzyme abnormalities are common in bariatric surgery candidates, with reduced prevalence of abnormalities postoperatively. RYGB and SG are related with reduced ALT, AST, γ-GT, ADA, CHE, LDH, CK, and HBDH levels, as well as increased amylase and SOD levels.

Different surgical techniques that influenced internal hernia prevalence rate after laparoscopic roux-en-Y gastric bypass: a retrospective analysis of 331 cases.

BACKGROUND: Internal hernia (IH) is a serious complication following laparoscopic Roux-en-Y gastric bypass (LRYGB), and closure of mesenteric defect has been recommended to reduce this complication. But what kind of material about suture and how to close the mesenteric defects were still controversial. The main aim of this study was to compare the incidence rate of internal hernia after LRYGB between patients with different surgical techniques. METHOD: Three hundred and thirty-one patients underwent LRYGB between June 2004 and December 2017 in one single institute were retrospective analysed. The IH rate was evaluated according to different surgical methods and surgical materials before and 12 months after LRYGB. RESULTS: All the cases were subdivided into three groups based on the suturing method, Roux limb position, and Suture material. The mean follow up time was 36 ± 12 months, and the total incident rate of IH was 1.8% (n = 6). In the six IH cases, the duration of IH occurred time ranged from 1 month to 36 months postoperatively, and for the IH sites, one for intestinal defect, three for transverse mesocolon defect and two Peterson defect respectively. There was a significant difference about IH rate between interrupted suture and running suture groups (p = 0.011), and there were no significant differences between the other two groups. CONCLUSION: Compare with interrupted suture, running suture may prevent IH after LRYGB. Patient's gender, age, body mass index(BMI), glycometabolism condition, and Roux limb position and suture material had no effects on the IH prevalence after LRYGB.

A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis.

Circular RNAs (circRNAs) play an important regulatory role in a variety of human cancers, including gastric cancer. The mechanisms for the circRNAs in gastric cancers are not fully understood. This study aims to uncover the mechanism by which circRNAs regulate gastric cancer tumorigenesis. Among the microarray data, we screened dysregulated circRNAs and identified an up-regulated circRNA, hsa_circ_0008035. Functionally, the hsa_circ_0008035 silencing by the siRNA transfection inhibited the proliferation and invasion of gastric cancer cells. Mechanically, hsa_circ_0008035 acted as a sponge for the miR-375 and absorbed its expression, and miR-375 was found to target YBX1 3'-UTR, constructing a hsa_circ_0008035/miR-375/YBX1 axis. Taken together, these findings are evidence that circRNA hsa_circ_0008035 promotes gastric cancer cell proliferation and invasion by regulating miR-375/YBX1.

Mid-long-term Revisional Surgery After Sleeve Gastrectomy: a Systematic Review and Meta-analysis.

This study aimed to make a meta-analysis regarding mid-long-term outcomes (≥ 3-year follow-up) after sleeve gastrectomy (SG), focusing on incidence, reasons, and results of revisional surgery. PubMed, EMBASE, and CENTRAL were searched and 32 studies were included. The overall revision rate was 10.4%, but for patients with ≥ 10-year follow-up, the rate was 22.6%. European studies had a higher revision rate (14.4%) than other studies. The most common reason for revision was failure in weight loss, and the most frequent revisional procedure was gastric bypass. Revisional surgery was favorable for weight reduction and comorbidity resolution. In conclusion, revision rate is not rare after SG, especially when looking at long-term follow-up. Bariatric surgeons and patients need to fully understand and deal with the need for revision after SG.