Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis.

Introduction: A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy. Methods: We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study. Results: Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38). Discussion: In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.

Graphene oxide leads to mitochondrial-dependent apoptosis by activating ROS-p53-mPTP pathway in intestinal cells.

Owing to its unique physical and chemical properties, graphene oxide (GO) has a wide range of applications in biomedical field. However, with the gradual improvement of biosafety investigations on nanomaterials, growing literatures have pointed out that GO could lead to oxidative stress, aggravation of inflammatory responses, and even irreversible lesions in human multi-tissues, while its damage to small intestinal remained unclear. In this study, we conducted an in-depth study on the toxicological effect of GO on intestinal tissues, and further clarified its toxic effect and molecular mechanism on inducing intestinal cell death. Firstly, we characterized the shape size, potential value, Fourier Transform infrared spectroscopy (FT-IR) characterization and pro-oxidant properties of GO nanosheets. The cytotoxicity of different concentrations of GO to Caco-2 and IEC-6 cell lines was thereafter observed, which was specifically manifested as invoking NADPH Oxidase 1 (NOX1) proteins, accompanied generation of reactive oxygen species (ROS). Since that, more p53 flowed into mitochondria to combine with cyclophilin D (CYPD), thus induced mitochondrial permeability transition pore (mPTP) opening. Through ROS-CyPD-mPTP signaling pathway, GO exerted imbalance of mitochondrial homeostasis, while released cytochrome c (CytC) would ultimate caspase-dependent cell apoptosis. In vivo experiment also confirmed that the microstructure of small intestine was damaged, and the apoptosis rate and oxidative markers were significantly increased in GO-treated Sprague- Dawley (SD) rats (40 mg/kg once every other day from day 1 to day 9 by oral gavage). Based on these findings, we conclude that the adverse effects of oral exposure of GO on the biological system mainly concentrate in the digestive tract, and clarify the key role of ROS-mitochondrial homeostasis-apoptosis axis in GO-derived intestinal toxicity. Considering all these results and the fact that GO exhibited intestinal toxicity, we believe that this research providing a safety reference for its biomedical applications.

Long Non-coding RNA LINC00115 Contributes to the Progression of Colorectal Cancer by Targeting miR-489-3p via the PI3K/AKT/mTOR Pathway.

Long non-coding RNAs (lncRNAs) are tumor-related regulators and have been found to be involved in the underlying molecular mechanisms of colorectal cancer (CRC). However, the role of lncRNA LINC00115 during CRC progression is not entirely elucidated. In this study, we discovered that LINC00115 was significantly overexpressed in CRC, and its overexpression predicted poor patient outcomes. Downregulation of LINC00115 markedly inhibited CRC cell proliferation, increased cell apoptosis, and suppressed cell migration and invasion. Moreover, downregulation of LINC00115 led to the inactivation of PI3K/AKT/mTOR signaling. Bioinformatics analysis identified miR-489-3p as a candidate target of LINC00115. Furthermore, we revealed an inverse correlation between LINC00115 and miR-489-3p in CRC tissues. Importantly, by luciferase reporter assay, we found that miR-489-3p might directly target LINC00115, and downregulation of miR-489-3p could rescue the biological effects induced by the absence of LINC0015. In conclusion, our findings demonstrated that LINC00115 serves as an oncogene in CRC metastasis. Deeper understanding of the LINC00115/miR-489-3p axis might provide potential therapeutic targets against CRC metastasis.

Clinical curative effect of oxaliplatin combined with flurouracil in the treatment of gastrointestinal tumor.

Aiming at exploring clinical curative effect of oxaliplatin combined with flurouracil in the treatment of gastrointestinal tumor, this study divided 60 patients with gastrointestinal tumor into control and observation groups, each containing 30 patients. The observation group was treated with oxaliplatin combined with flurouracil, while the control was treated with FOLFOX4, i.e., intravenously dropping 85mg/m(2)Oxaliplatin (L-OHP), 200mg/m(2) calcium folinate (CF) and intravenously injecting 400mg/m(2) 5-fluorouracil (5-Fu), and 600mg/m(2) 5-Fu; then continuously performing intravenous drop infusion for 22h, every two weeks for a cycle. Hypodermic injection of granulocyte colony-stimulating factor (G-CSF) was conducted immediately when leukocytes occurred the III, IV degree of inhibition. The observation results of curative effect and negative reaction indicated higher effective rate with 83.33% in the observation and 50.00% in the control. Besides, in the observation, negative reactions possessed 10.00% that was much lower than 33.33% in the control. Thereby, the conclusion reached that the treatment of gastrointestinal tumor with oxaliplatin combined with flurouracil was worth promoting.

Activable enriched stable isotope iron-58 for monitoring absorption rate of juvenile athletes for iron: a case study.

Activable enriched stable isotopes can play a unique role in studies of nutritional status, metabolism, absorption rates, and bioavailability of minerals. As a practical example, eight juvenile athletes were selected to test the absorption rates of iron during training and non-training periods by enriched stable isotope of Fe-58 (enriched degree: 51.1%) via activation analysis Fe-58 (n, gamma) Fe-59 of the collected feces samples. The results indicated that the average iron absorption rates of the juvenile athletes with and without training are 9.1 +/- 2.8 and 11.9 +/- 4.7%, respectively, which implies that the long-term endurance training with high intensity makes the iron absorption rate of athletes lower. In the meantime, the comparison of the activable enriched isotope technique with atomic absorption spectrometry was performed, which showed that the former was better than the latter in reliability and sensitivity. It is because this nuclear method can distinguish the exogenous and endogenous iron in the samples, but not for non-nuclear methods.

Overview of the methodology of nuclear analytical techniques for speciation studies of trace elements in the biological and environmental sciences.

Recent achievements in speciation studies of trace elements in the biological and environmental sciences by nuclear analytical techniques, mainly molecular activation analysis, position-sensitive spectrometry with a variety of exciting sources, and synchronous radiation-based analytical techniques (although radioisotope or enriched stable isotope-based speciation techniques are also used), particularly in our laboratory, are outlined. In this paper the merits and drawbacks of the nuclear analytical techniques are discussed, as are reagent blanks, contamination, and artifacts.