Mendelian randomization identifies causal effects of major depressive disorder on accelerated aging.

BACKGROUND: Evidence links major depressive disorder (MDD) with aging, but it's unclear if MDD accelerates aging and what factors mediate this transition. METHODS: Two-sample Mendelian randomization (MR) analyses were applied to estimate the causal association between MDD and frailty index (FI), telomere length (TL), and appendicular lean mass (ALM) from available genome-wide association studies in populations of European ancestry. Furthermore, we conducted mediation MR analyses to assess the mediating effects of 31 lifestyle factors or diseases on the causal relationship between MDD and aging. RESULTS: MDD was significantly causally associated with increased FI (ßIVW = 0.23, 95 % CI = 0.18 to 0.28, p = 1.20 × 10-17), shorter TL (ßIVW = -0.04, 95 % CI = -0.07 to -0.01, p = 0.01), and decreased ALM (ßIVW = -0.07, 95 % CI = -0.11 to -0.03, p = 3.54 × 10-4). The mediation analysis through two-step MR revealed smoking initiation (9.09 %), hypertension (6.67 %) and heart failure (5.36 %) mediated the causal effect of MDD on FI. Additionally, alcohol use disorders and alcohol dependence on the causal relationship between MDD and TL were found to be 17.52 % and 17.13 % respectively. LIMITATIONS: Confounding, statistical power, and Euro-centric focus limit generalization. CONCLUSION: Overall, individuals with MDD may be at a higher risk of experiencing premature aging, and this risk is partially influenced by the pathways involving smoking, alcohol use, and cardiovascular health. It underscores the importance of early intervention and comprehensive health management in individuals with MDD to promote healthy aging and overall well-being.

Brain-derived neurotrophic factor levels across psychiatric disorders: A systemic review and network meta-analysis.

As an important neurotrophic factor in the central nervous system, Brain-derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of psychiatric disorders in many studies. However, its value as a biomarker for the diagnosis and differential diagnosis of mental disorders is still controversial, and its change patterns among different mental disorders have not been compared. We conducted a network meta-analysis of BDNF levels in different psychiatric disorders including schizophrenia(SCZ), major depressive disorder(MDD), bipolar disorder(BD), panic disorder(PD), post-traumatic stress disorder(PTSD), obsessive-compulsive disorder(OCD), generalized anxiety disorder(GAD) and insomnia. Studies were identified by searching electronic databases through 31/05/2023. BDNF levels decreased in patients with BD, MDD, OCD, PD, SCZ compared with controls, while significantly increased in patients with PTSD. According to the network meta-analysis, BDNF levels were significantly decreased in MDD and SCZ compared with BD (-2.6, 95% CIs [-5.32 to -0.15] and - 2.68 95% CIs [-5.18 to -0.23] respectively). However, in the traditional meta-analysis, there was a trend towards lower BDNF levels in SCZ compared to BD, with no significant difference (SMD = -0.20, 95% CIs [-0.49 to 0.08]). In conclusion, abnormal BDNF levels have been found in psychiatric disorders, and the changes in peripheral BDNF levels in patients with psychiatric disorders were reconfirmed in this study, which suggests BDNF exhibits promising clinical utility and may hold diagnostic value in distinguishing between MDD and BD.

Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway.

Background: Chemotherapy resistance is a significant cause for poor prognosis of epithelial ovarian cancer (EOC). However, the molecular mechanism of chemo-resistance remains unclear, and developing available therapies and effective biomarkers for resistant EOC is in urgent demand. Stemness of cancer cells directly results in chemo-resistance. Exosomal miRNAs rebuild tumor microenvironment (TME) and act as widely used clinical liquid biopsy markers. Methods: In our study, high throughput screenings and comprehensive analysis were performed to screen for miRNAs, which were both up-regulated in resistant EOC tissues and related to stemness, and miR-6836 was identified accordingly. Results: Clinically, high miR-6836 expression was closely correlated with poor chemotherapy response and survival for EOC patients. Functionally, miR-6836 promoted EOC cell cisplatin resistance by increasing stemness and suppressing apoptosis. Mechanistically, miR-6836 directly targeted DLG2 to enhance Yap1 nuclear translocation, and was regulated by TEAD1 forming the positive feedback loop: miR-6836-DLG2-Yap1-TEAD1. Furthermore, miR-6836 could be packaged into secreted exosomes in cisplatin-resistant EOC cells and exosomal miR-6836 was able to be delivered into cisplatin-sensitive EOC cells and reverse their cisplatin response. Conclusion: Our study revealed the molecular mechanisms of chemotherapy resistance, and identified miR-6836 as the possible therapeutic target and effective biopsy marker for resistant EOC.

Peripheral cytokine levels across psychiatric disorders: A systematic review and network meta-analysis.

Immune dysregulated cytokine production is involved in mental diseases. However, the results are inconsistent and the pattern of cytokine alterations has not been compared across disorders. We performed a network impact analysis of cytokine levels for different psychiatric disorders including schizophrenia, major depressive disorder, bipolar disorder, panic disorder, post-traumatic stress disorder and obsessive compressive disorder to evaluate their clinical impact across conditions. Studies were identified by searching the electronic databases up to 31/05/2022. A total of eight cytokines, together with (high-sensitivity) C-reactive proteins (hsCRP/CRP) were included in the network meta-analysis. The levels of proinflammatory cytokines, hsCRP/CRP and interleukin 6 (IL-6) were significantly increased in patients with psychiatric disorders when compared to controls. IL-6 showed no significant difference among comparisons between disorders according to the network meta-analysis. Interleukin 10 (IL-10) is significantly increased in patients with bipolar disorder compared to major depressive disorder. Further, the level of interleukin-1 beta (IL-1ß) was significantly increased in major depressive disorder as compared to bipolar disorder. The level of interleukin 8 (IL-8) varied among these psychiatric disorders based on the network meta-analysis result. Overall, abnormal cytokine levels were found in psychiatric disorders, and some of the cytokines displayed differential characteristics in these disorders, especially IL-8, pointing to a role as potential biomarkers for general and differential diagnosis.

Heart rate variability in generalized anxiety disorder, major depressive disorder and panic disorder: A network meta-analysis and systematic review.

BACKGROUND: Heart rate variability (HRV) in patients with emotional disorders and healthy controls (HCs) has been investigated in many studies but the difference between these emotional disorders was unclear. METHODS: The PubMed, Embase, Medline and Web of Science databases were systematically searched for studies published in English that compared HCs with generalized anxiety disorder (GAD), major depressive disorder (MDD), panic disorder (PD) patients in HRV. We conducted a network meta-analysis to compare HRV in patients with GAD, MDD, PD and HCs. HRV outcomes, including time domain indices (the standard deviation of NN intervals (SDNN) and the root mean square of the successive differences between normal heartbeats (RMSSD)), and frequency domain indices (High-frequency (HF), Low-frequency (LF) and the ratio of LF to HF (LF/HF)) were obtained. A total of 4008 participants from 42 studies were included. RESULTS: The results of pairwise meta-analysis showed that compared with controls, GAD, PD and MDD patients exhibited significantly reduced HRV. Similar findings were also confirmed in network meta-analysis. The most important finding from network meta-analysis was that GAD patients had significantly lower SDNN than PD patients (SMD = -0.60, 95 % CI [-1.09, -0.11]). CONCLUSION: Our findings provided a potential objective biological marker to distinguish between GAD and PD. In the future, a large sample of research is needed to directly compare HRV of various mental disorders, which is crucial for finding biomarkers to distinguish them.

Association between gastroesophageal reflux disease and vocal fold polyps.

ABSTRACT: The aim of this study is to explore the relationship between gastroesophageal reflux disease (GERD) and vocal fold polyps (VFPs).This is a Case-Control study and was performed with the help of The Second Affiliated Hospital of Chongqing Medical University.Twenty-seven patients with VFP and 20 controls without VFP were recruited between May and October 2018. All the subjects underwent a saliva pepsin test, completed the GerdQ questionnaire and 24-hour multichannel intraluminal impedance with pH (24-h MII-pH) monitoring. Twenty-five resected VFP specimens were examined with immunohistochemical (IHC) and double immunofluorescence (IF) staining.The incidence of GERD in the VFP group was significantly higher than that in the control group (P = .003). Patients with VFP had significantly higher GerdQ scores, pepsin concentrations, and pepsin-positive rates (P < .05). Moreover, the number of proximal and upright reflux events was significantly higher in the VFP group (P < .05). The pepsin concentration in saliva showed a significant positive correlation with the pepsin levels in tissues (r2 = 0.50, P = .011). Pepsin and TGF-ß1-positive cells were colocalized with CD45RO-positive cells. IHC staining showed that the majority of VFP patients had a positive expression of pepsin (20/25, 80%) and pepsin-positive cells were found in both the squamous epithelium and mesenchymal tissues. IHC staining of TGF-ß1 in VFP revealed findings similar to those of pepsin staining.GERD is an important risk factor for VFP. Pepsin may promote the aggregation of immune cells, increase the local cytokines, and promote inflammatory reaction, suggesting a potential new pathogenesis for VFP. The saliva pepsin test is a reliable method for GERD diagnosis.

Comparative of Quercus spp. and Salix spp. for phytoremediation of Pb/Zn mine tailings.

A pot experiment was conducted to evaluate the feasibility of using tree seedlings for the phytoremediation of lead/zinc (Pb/Zn) mine tailings. Seedlings of three Quercus spp. (Q. shumardii, Q. phellos, and Q. virginiana) and rooted cuttings of two Salix spp. (S. matsudana and S. integra) were transplanted into pots containing 50 and 100 % Pb/Zn mine tailings to evaluate their tolerance of heavy metals. The five species showed different tolerance levels to the Pb/Zn tailings treatments. Q. virginiana was highly tolerant to heavy metals and grew normally in the Pb/Zn tailings. The root systems showed marked differences between the Quercus spp. and Salix spp., indicating that different mechanisms operated to confer tolerance of heavy metals. The maximum efficiency of photosystem II photochemistry value of the five species showed no differences among the treatments, except for Q. shumardii. All species showed low metal translocation factors (TFs). However, S. integra had significantly higher TF values for Zn (1.42-2.18) and cadmium (1.03-1.45) than did the other species. In this respect, Q. virginiana showed the highest tolerance and a low TF, implying that it is a candidate for phytostabilization of mine tailings in southern China. S. integra may be useful for phytoextraction of tailings in temperate regions.