NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic ß-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor ß1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1ß), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Hand-sewn gastrojejunal anastomosis reduces delayed gastric emptying after pancreaticoduodenectomy: A single-center retrospective clinical study of 1,077 consecutive patients.

BACKGROUND: Hand-sewn anastomosis and stapled anastomosis are the 2 main types of gastrojejunal anastomotic methods in pancreaticoduodenectomy. There is ongoing debate regarding the most effective anastomotic method for reducing delayed gastric emptying after pancreaticoduodenectomy. This study aims to identify factors that influence delayed gastric emptying after pancreaticoduodenectomy and assess the impact of different anastomotic methods on delayed gastric emptying. METHODS: The study included 1,077 patients who had undergone either hand-sewn anastomosis (n = 734) or stapled anastomosis (n = 343) during pancreaticoduodenectomy between December 2016 and November 2021 at our department. We retrospectively analyzed the clinical data, and a 1:1 propensity score matching was performed to balance confounding variables. RESULTS: After propensity score matching, 320 patients were included in each group. Compared with the stapled anastomosis group, the hand-sewn anastomosis group had a significantly lower incidence of delayed gastric emptying (28 [8.8%] vs 55 [17.2%], P = .001) and upper gastrointestinal tract bleeding (6 [1.9%] vs 17 [5.3%], P = .02). Additionally, the hand-sewn anastomosis group had a significantly reduced postoperative length of stay and lower hospitalization expenses. However, the hand-sewn anastomosis group had a significantly longer operative time, which was consistent with the analysis before propensity score matching. Logistic regression analysis showed that stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula were independent prognostic factors for delayed gastric emptying. CONCLUSION: Hand-sewn anastomosis was associated with a lower incidence rate of clinically relevant delayed gastric emptying after pancreaticoduodenectomy. Stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula could increase the incidence of postoperative clinically relevant delayed gastric emptying. Hand-sewn anastomosis should be considered by surgeons to reduce the occurrence of postoperative delayed gastric emptying and improve patient outcomes.

Is it necessary to stop glucagon-like peptide-1 receptor agonists prior to endoscopic procedure? A retrospective study.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective in diabetes and obesity, reducing hyperglycemia by increasing insulin release and delaying gastric emptying. However, they can cause gastroparesis, raising concerns about aspiration during procedures. Recent guidelines advise discontinuing GLP-1 RA before surgery to reduce the risk of pulmonary aspiration. AIM: To evaluate the effect of GLP-1 RAs on gastric residual contents during endoscopic procedures. METHODS: A retrospective chart review at BronxCare Health System, New York, from January 2019 to October 2023, assessed gastric residue and aspiration in GLP-1 RA patients undergoing endoscopic procedures. Two groups were compared based on dietary status before the procedure. Data included demographics, symptoms of gastroparesis, opiate use, hemoglobin A1c, GLP-1 agonist indication, endoscopic details, and aspiration occurrence. IBM SPSS was used for analysis, calculating means, standard deviations, and applying Pearson's chi-square and t-tests for associations, with P < 0.05 as being significant. RESULTS: During the study, 306 patients were included, with 41.2% on a clear liquid/low residue diet and 58.8% on a regular diet before endoscopy. Most patients (63.1%) were male, with a mean age of 60 ± 12 years. The majority (85.6%) were on GLP-1 RAs for diabetes, and 10.1% reported digestive symptoms before endoscopy. Among those on a clear liquid diet, 1.5% had residual food at endoscopy compared to 10% on a regular diet, which was statistically significant (P = 0.03). Out of 31 patients with digestive symptoms, 13% had residual food, all from the regular diet group (P = 0.130). No complications were reported during or after the procedures. CONCLUSION: The study reflects a significant rise in GLP-1 RA use for diabetes and obesity. A 24-hour liquid diet seems safe for endoscopic procedures without aspiration. Patients with upper gastrointestinal symptoms might have a higher residual food risk, though not statistically significant. Further research is needed to assess risks based on diabetes duration, gastroparesis, and GLP-1 RA dosing, aiming to minimize interruptions in therapy during procedures.