Several meta-analyses of observational studies have been performed to examine the association between general obesity, as measured by body mass index (BMI), and lung cancer. These meta-analyses suggest an inverse relation between high BMI and this cancer. In contrast to general obesity, abdominal obesity appears to play a role in the development of lung cancer. However, the association between abdominal obesity (as measured by waist circumference (WC) (BMI adjusted) and waist to hip ratio (WHR)) and lung cancer is not fully understood due to sparse available evidence regarding this association. PubMed and Web of Science databases were searched for studies assessing the association between abdominal obesity and lung cancer up to October 2016. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. Six prospective cohort studies with 5827 lung cancer cases among 831,535 participants were included in our meta-analysis. Each 10 cm increase in WC and 0.1 unit increase in WHR were associated with 10% (RR 1.10; 95% CI 1.04, 1.17; I² = 27.7%, p-heterogeneity = 0.198) and 5% (RR 1.05; 95% CI 1.00, 1.11; I² = 25.2%, p-heterogeneity = 0.211) greater risks of lung cancer, respectively. According to smoking status, greater WHR was only positively associated with lung cancer among former smokers (RR 1.11; 95% CI 1.00, 1.23). In contrast, greater WC was associated with increased lung cancer risk among never smokers (RR 1.11; 95% CI 1.00, 1.23), former smokers (RR 1.12; 95% CI 1.03, 1.22) and current smokers (RR 1.16; 95% CI 1.08, 1.25). The summary RRs for highest versus lowest categories of WC and WHR were 1.32 (95% CI 1.13, 1.54; I² = 18.2%, p-heterogeneity = 0.281) and 1.10 (95% CI 1.00, 1.23; I² = 24.2%, p-heterogeneity = 0.211), respectively. In summary, abdominal obesity may play an important role in the development of lung cancer.

Background and Aims: The traditional treatment of diabetic wounds is unsatisfactory. Exosomes isolated from bone marrow mesenchymal stem cells (BMSCs) promote the healing of diabetic wounds. However, whether the exosomes secreted by interferon (IFN)‐γ‐pretreated BMSCs have an enhanced therapeutic effect on diabetic wound healing and the relevant mechanisms remain unclear.Methods: In this study, we isolated exosomes from the corresponding supernatants of BMSCs with (IExos) or without IFN‐γ treatment (NExos). Human umbilical vein endothelial cells (HUVECs) were used to investigate the proliferation, migration, and tube formation under different treatments in vitro. Diabetic mice were induced by intraperitoneal administration of streptozotocin, and a circular full‐thickness dermal defect was then made on the back of each mouse, followed by a multisite subcutaneous injection of phosphate buffered saline or exosomes. Hematoxylin–eosin (H&E) staining, Masson's trichrome staining, and histological analysis were performed to assess the speed and quality of wound healing.Results: NExos treatment accelerated the healing of diabetic wounds by promoting angiogenesis in vivo and in vitro, and IExos exhibited superior therapeutic efficiency. MicroRNA (miR)‐126‐3p was significantly increased in IExos, and exosomal miR‐126‐3p promoted angiogenesis and diabetic wound healing via its transfer to HUVECs. miR‐126‐3p regulates SPRED1 by directly targeting the 3′‐UTR. Mechanistically, IFN‐γ‐pretreated BMSCs secreted miR‐126‐3p‐enriched exosomes, which enhanced the function of HUVECs and promoted angiogenesis via the SPRED1/Ras/Erk pathway.Conclusion: Exosomal miR‐126‐3p secreted from IFN‐γ‐pretreated BMSCs exhibited higher therapeutic efficacy than NExos in diabetic wound healing by promoting angiogenesis via the SPRED1/Ras/Erk axis.

Backgrounds: the relations of waist circumference (WC) and waist to hip ratio (WHR) to total gastroesophageal cancer, gastric cancer and esophageal cancer are remains largely unexplored. Methods: PubMed and Web of Science databases were searched for studies assessing the association between abdominal obesity and gastroesophageal cancer (gastric cancer and/or esophageal cancer) up to August 2016. A random-effect model was used to calculate the summary risk estimates. Results: Seven prospective cohort studies—one publication included two separate cohort—from six publications were included in the final analysis. A total of 2,130 gastroesophageal cancer cases diagnosed among 913,182 participants. Greater WC and WHR were significantly associated with increased risk of total gastroesophageal cancer (WC: RR 1.68, 95% CI 1.38, 2.04; WHR: RR 1.49, 95% CI 1.19, 1.88), gastric cancer (WC: RR 1.48, 95% CI 1.24, 1.78; WHR: 1.36, 95% CI 1.07, 1.73), and esophageal cancer (WC: RR 2.06, 95% CI 1.30, 3.24; WHR: RR 1.99, 95% CI 1.05, 3.75). Findings from our subgroup analyses showed non-significant positive associations between gastric non-cardia adenocarcinoma and both measures of abdominal adiposity, while gastric non-cardia adenocarcinoma was positively associated with WC but not with WHR. On analysis restricted to studies that adjusted for BMI, WC was positively associated with gastric cancer and esophageal cancer, whereas WHR was positively associated with risk of gastric cancer only. Conclusions: Although limited, the findings from our meta-analysis suggest the potential role of abdominal obesity in the etiology of gastric and esophageal cancers.

Advanced glycation end products (AGEs) play a causative role in the complications involved with diabetes mellitus (DM). Nowadays, DM with hypothyroidism (DM‐hypothyroidism) is indicative of an ascended tendency in the combined morbidity. In this study, we examine the role of the receptor (RAGE) played for AGEs in thyroid hormone (TH) secretion via the silent information regulator 1 (SIRT1)/nuclear factor erythroid‐derived factor 2‐related factor 2 (Nrf2) pathway. Blood samples were collected from patients with type 2 DM (T2DM)‐hypothyroidism and from patients with T2DM, followed by detection of serum AGEs level. The underlying regulatory mechanisms of RAGE were analyzed in association with the treatment of high glucose, siRNA against RAGE, AGE, SIRT1, or Nrf2 vector in normal immortalized thyroid Nthy‐ori 3‐1 cells. Serum of patients with T2DM‐hypothyroidism indicated promoted levels of AGEs vs those with just T2DM. Both AGEs and high glucose triggered cellular damage, increased oxidative stress, as well as displayed a decreased survival rate along with TH secretion in the Nthy‐ori 3‐1 cells. Moreover, AGEs and high glucose also led to RAGE upregulation, both SIRT1 and NRF2 downregulation, and the decreased expression of TH secretion–related proteins in Nthy‐ori 3‐1 cells. Notably, these alternations induced by the AGEs can be reserved by silencing RAGE or upregulating either SIRT1 or Nrf2, indicating a mechanism of regulating TH secretion through the SIRT1/Nrf2 pathway. Collectively, our data proposed that AGEs and high glucose exerted a potent effect on cellular damage and TH deficiency in Nthy‐ori 3‐1 cells through the RAGE upregulation as well as SIRT1/Nrf2 pathway inactivation. This mechanism may underlie the occurrence of DM‐hypothyroidism.

Objective/Main Outcome To study the expression of OX40 on T follicular helper (Tfh) cells and the ligand OX40L on antigen-presenting cells (APCs) in peripheral blood of patients with type 1 diabetes mellitus (T1DM) and the role of OX40 signaling in promoting Tfh cells to assist B-cell differentiation. Design Cross-sectional study. Setting Endocrinology department of a university hospital. Participants Twenty-five patients with T1DM and 35 with newly diagnosed type 2 diabetes mellitus (T2DM) from January 2021 to December 2021 (39 males, 21 females; mean age: 31.0 ± 4.5, range: 19-46 years). Interventions None. Methods The peripheral blood proportion of CD4⁺CD25⁻CD127⁺CXCR5⁺PD1⁺ Tfh cells in patients with T1DM or T2DM and the OX40L expression in CD14⁺ monocytes and CD19⁺ B cells were analyzed by flow cytometry. The OX40 signal effect on Tfh-cell function was analyzed by coincubating B cells with Tfh cells under different conditions. Flow cytometry detected the ratio of CD19⁻CD138⁺ plasmacytes. Results The Tfh cells ratio and intracellular IL-21 expression in peripheral blood was significantly higher in patients with T1DM than with T2DM, and the OX40 expression in peripheral Tfh cells and OX40L expression in APC were significantly higher in T1DM. After adding OX40L protein, the CD19⁻CD138⁺-plasmacytes percentage was significantly increased and higher in T1DM. Blocking of anti-OX40L monoclonal antibodies significantly reduced the plasmacytes ratio. Conclusion The peripheral Tfh cells proportion increased and the OX40 expression in peripheral Tfh cells was upregulated in patients with T1DM vs patients with T2DM. OX40/OX40L signaling enhanced the Tfh-cell function to assist B-cell differentiation, which may contribute to the pathogenesis of T1DM.