ABSTRACT
Objective: Selenium is an essential micronutrient and a type of dietary antioxidant. This study aimed to investigate the associations of dietary selenium intake with the risk of human chronic disease [cardiovascular disease (CVD), diabetes mellitus (DM), and cancer] and mortality among US general adults. Methods: The dietary and demographic data in this study were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Death outcomes were determined by associating with the National Death Index (NDI) records as of December 31, 2019. Logistic regression analyses were used to investigate the relationship of selenium intake with the risk of CVD, DM, and cancer. The effect of dietary selenium on all-cause and disease-specific mortality was estimated with restricted cubic spline (RCS) curves based on the univariate and multivariate Cox proportional hazard models. Results: Among the 25,801 participants, dietary selenium intake was divided into quintiles (Q1-Q5). After covariate adjustment, the results showed that the participants with higher quintiles (Q4 and Q5) of selenium intake tended to have a low risk of CVD (OR = 0.97, 95% CI: 0.96, 0.99; OR = 0.98, 95% CI: 0.97, 1.00, respectively). Moreover, the RCS curves showed a significant nonlinear association between selenium intake and the risk of all-cause (with a HR of 0.82, 95% CI: 0.68, 0.99) and DM-specific mortality (with the lowest HR of 0.30; 95% CI, 0.12-0.75). Furthermore, we conducted a subgroup analysis and found a negative correlation between the highest quartile of selenium intake and all-cause mortality among participants aged 50 and above (HR = 0.75, 95% CI: 0.60-0.93, p = 0.009). Conclusion: Our results indicated that a moderate dietary selenium supplement decreased the risk of CVD and displayed a nonlinear trend in association with the risk of all-cause and DM-specific mortality among US adults. In addition, we found that participants aged 50 and older may benefit from higher selenium intake. However, these findings still need to be confirmed through further mechanism exploration.
ABSTRACT
FAM135B (family with sequence similarity 135, member B) is related to the progression of esophageal squamous cell carcinoma (ESCC). However, the role played by the gene in radiosensitivity remains unknown. Herein, we examined the relationship between FAM135B and radiosensitivity. According to the results, FAM135B is highly expressed in ESCC cells, and ESCC cells with high levels of FAM135B are resistant to irradiation. Silencing FAM135B inhibits colony formation capability and cell cycle protein expression (pP53, CDK1), promotes cell cycle arrest at the G2/M phase following irradiation. Moreover, transcriptome sequencing analysis demonstrates that FAM135B regulates downstream PI3K/Akt/mTOR signaling pathway, and western blot verifies the result. One of the mechanisms of increasing radiosensitivity by silencing FAM135B expression in ESCC cells may be achieved by regulating the PI3K/Akt/mTOR signaling pathway. Silencing FAM135B shows synergy with PI3K/Akt/mTOR pathway inhibitor (rapamycin) in increasing radiosensitivity, regulating the expression of cell cycle protein and inducing apoptosis of ESCC cells. The results indicate that FAM135B could be a potential treatment target for ESCC in management of radiosensitivity.
Subject(s)
Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Intracellular Signaling Peptides and Proteins/genetics , RNA, Small Interfering/pharmacology , Up-Regulation/drug effects , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/therapy , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Gene Silencing , Humans , Radiation Tolerance/drug effects , Signal Transduction/drug effects , Signal Transduction/radiation effects , Sirolimus/pharmacologyABSTRACT
BACKGROUND: Increasing evidence has indicated that gut microbiota is closely associated with radiation-induced bowel injury. We aimed to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in patients with chronic radiation enteritis (CRE). METHODS: A pilot study of FMT for CRE was performed. The primary outcomes were safety and response to FMT which was defined as a ≥1-grade reduction in Radiation Therapy Oncology Group (RTOG/EORTC) late toxicity grade from baseline, by 8 weeks post-FMT. The secondary outcomes included a decrease in the severity of four common symptoms (diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence) in CRE and changes in Karnofsky Performance Status (KPS) score. Microbial analyses were performed by 16S rRNA sequencing. RESULTS: Five female patients underwent FMT from January to November 2018 with a median age of 58 (range 45-81) years. The median baseline RTOG/EORTC grade was 2 (range 2-4). Three patients responded to FMT and experienced improvement in diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence as well as a decrease in KPS score. No FMT-related death and infectious complications occurred. One mild FMT-related AE was observed during a follow-up ranged from 8 to 18 months. 16S rRNA sequencing indicated that FMT altered the composition of gut microbiota of patients. CONCLUSION: The present case series first demonstrated that FMT might be safe and effective to improve intestinal symptoms and mucosal injury in patients with CRE for a period of time. Trial registration ID: NCT03516461.