Multi-omics investigation of metabolic dysregulation in depression: integrating metabolomics, weighted gene co-expression network analysis, and mendelian randomization.

Background: The etiology of depressive disorder, the leading cause of global mental disability, is characterized by systemic metabolic dysregulation. However, the causal metabolites and their mechanistic networks remain elusive.

Methods: We combined untargeted LC/GC-MS metabolomics (N=98 Chinese elderly), weighted gene co-expression network analysis (WGCNA), and two-sample Mendelian randomization (MR) using GWAS data (59,333 depression cases with 434,831 controls) to identify depression-associated metabolites and pathways.

α-Lipoic Acid Ameliorates Arsenic-Induced Lipid Disorders by Promoting Peroxisomal β-Oxidation and Reducing Lipophagy in Chicken Hepatocyte.

Liver disease poses a significant threat to global public health, with arsenic (As) recognized as a major environmental toxin contributing to liver injury. However, the specific mechanisms and the protective effects of α-lipoic acid (LA) remain unclear. Therefore, this study employs network toxicology and network pharmacology to comprehensively analyze the hepatotoxic mechanism of As and the hepatoprotective mechanism of LA, and further verifies the mechanisms of peroxisomal β-oxidation and lipophagy in the process.

Fluoride induces hepatointestinal damage and vitamin B mitigation by regulating IL-17A and Bifidobacterium in ileum.

Introduction: Fluorosis is a global public health disease affecting more than 50 countries and 500 million people. Excessive fluoride damages the liver and intestines, yet the mechanisms and therapeutic approaches remain unclear.

Objectives: To explore the mechanisms by which fluoride-induced intestinal-hepatic damage and vitamin B alleviation.

MiRNA-seq and mRNA-seq revealed the mechanism of fluoride-induced cauda epididymal injury.

The widespread presence of fluoride in water, food, and the environment continues to exacerbate the impact of fluoride on the male reproductive health. However, as a critical component of the male reproductive system, the intrinsic mechanism of fluoride-induced cauda epididymis damage and the role of miRNAs in this process are still unclear. This study established a mouse fluorosis model and employed miRNA and mRNA sequencing; Evans blue staining, Oil Red O staining, TEM, immunofluorescence, western blotting, and other technologies to investigate the mechanism of miRNA in fluoride-induced cauda epididymal damage.

Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice.

Excessive consumption of fluoride can cause skeletal fluorosis. Mitophagy has been identified as a novel target for bone disorders. Meanwhile, calcium supplementation has shown great potential for mitigating fluoride-related bone damage.

α-Lipoic acid improves mitochondrial biogenesis and dynamics by enhancing antioxidant and inhibiting Wnt/Ca pathway to relieve fluoride-induced hepatotoxic injury.

Fluoride (F), widely present in water and food, poses a serious threat to liver health, and oxidative damage and mitochondrial damage are its main causes. As a natural mitochondrial protector and antioxidant, α-lipoic acid (ALA)'s alleviating effect on fluorosis liver injury and its underlying mechanism are still unclear. Therefore, this study established a fluorosis ALA intervention mice model to explore the mechanism of mitochondrial biogenesis, mitochondrial dynamics, and Wnt/Ca pathway in ALA attenuating fluorosis liver injury.

Interleukin-17A knockout or self-recovery alleviated autoimmune reaction induced by fluoride in mouse testis.

Fluoride (F) is usually treated as a hazardous material, and F-caused public health problem has attracted global attention. Previous studies demonstrate that interleukin-17A (IL-17A) plays a crucial role in F-elicited autoimmune orchitis and self-recovery reverses F-induced testicular toxicity to some extent, but these basic mechanisms remain unclear. Thus, we established a 180 d F exposure model of wild type (WT) mice and IL-17A knockout mice (C57BL/6 J background), and 60 d & 120 d self-recovery model based on F exposure model of WT mice, and used various techniques like qRT-PCR, western blot, immunohistochemistry and ELISA to further explore the mechanism of F-induced autoimmune reaction, the role of IL-17A in it and the reversibility of F-caused toxicity in testis.

Ameliorative effects of different doses of selenium against fluoride-triggered apoptosis and oxidative stress-mediated renal injury in rats through the activation of Nrf2/HO-1/NQO1 signaling pathway.

Excess fluoride (F) exposure can cause oxidative stress in the kidney. As an antioxidant, selenium (Se) can potentially protect the kidney from F-induced injury in rats. Hence, the histopathological, renal biochemical, oxidative stress, and apoptotic-related indices upon exposure to 100 mg/L sodium fluoride (NaF) and various doses of sodium selenite (NaSeO; 0.

α-Lipoic Acid Alleviated Fluoride-Induced Hepatocyte Injury via Inhibiting Ferroptosis.

Fluoride is widely used in agricultural production and food packaging. Excessive fluoride in water and food is a serious threat to liver health. α-Lipoic acid, a natural free radical scavenger, has hepatoprotective properties.

Alleviating effects of selenium on fluoride-induced testosterone synthesis disorder and reproduction toxicity in rats.

Fluoride (F) exists widely in food, water and other natural resources, and can cause damage to the reproductive system of human and animals. Studies have shown that selenium (Se) is a necessary trace element to maintain the normal male reproductive system. However, it is not clear whether it can alleviate the damage of reproductive system induced by F.

Choline alleviated perinatal fluoride exposure-induced learning and memory impairment through α4β2 nAChRs and α7 nAChRs in offspring mice.

Fluoride pollution is widely present in the living environment. As a critical period of brain development, the perinatal period is extremely vulnerable to fluoride. Studies have found that choline can protect the brain's memory and enhance the ability to focus.

Multiomics Analysis Revealed the Molecular Mechanism of miRNAs in Fluoride-Induced Hepatic Glucose and Lipid Metabolism Disorders.

Fluoride-induced liver injury seriously endangers human and animal health and animal food safety, but the underlying mechanism remains unclear. This study aims to explore the mechanism of miRNAs in fluoride-induced hepatic glycolipid metabolism disorders. C57 male mice were used to establish the fluorosis model (22.

Moderate exercise relieves fluoride-induced liver and kidney inflammatory responses through the IKKβ/NFκB pathway.

With the intensification of environmental pollution, the content of fluoride is increasing in human and animal living environments. Long-term fluoride exposure can cause damage to the liver and kidney, which are the main sites for fluoride metabolism, storage and removal. Moreover, exercise often accompanies the entire process of fluoride exposure in humans and animals.

Exposure to Fluoride From in Utero to Puberty Alters Gonadal Structure and Steroid Hormone Expression in Offspring Rats.

The reproductive toxicity of fluoride has been proven by a large number of studies. While the underlying mechanism of reproductive toxicity during pregnancy is still unclear. Hence, in this study, we investigated the effects of fluoride exposure on ovarian and testicular steroid hormone synthesis in young and adult rat offspring.

Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway.

Depression is a mental health problem with typically high levels of distress and dysfunction, and 150 mg/L fluoride (F) can induce depression-like behavior. The development of depression is correlated with neuronal atrophy, insufficient secretion of monoamine neurotransmitters, extreme deviations from the normal microglial activation status, and immune-inflammatory response. Studies found that Se supplementation was related to the improvement of depression.

Calcium alleviates fluoride-induced kidney damage via FAS/FASL, TNFR/TNF, DR5/TRAIL pathways in rats.

Long-term excessive intake of fluoride (F) can cause osseous and non-osseous damage. The kidney is the main fluoride excretion organ of the body. This study aimed to explore whether dietary calcium (Ca) supplementation can alleviate kidney damage caused by fluorosis and to further investigate the effects of Ca on the mitigation mechanism of renal cell apoptosis triggered by F.

Fluoride exposure induces mitochondrial damage and mitophagy via activation of the IL-17A pathway in hepatocytes.

As an environmental toxicant, the damage of fluoride to the body has attracted global attention. Because liver is an essential organ for fluoride accumulation and damage. Our previous studies revealed fluoride-induced hepatic injury through interleukin 17A (IL-17A) pathway, but the underlying cellular mechanism remains unclear.

The inhibition of NFкB signaling and inflammatory response as a strategy for blunting bile acid-induced hepatic and renal toxicity.

The cholestatic liver injury could occur in response to a variety of diseases or xenobiotics. Although cholestasis primarily affects liver function, it has been well-known that other organs such as the kidney could be influenced in cholestatic patients. Severe cholestasis could lead to tissue fibrosis and organ failure.

Dietary Calcium Alleviates Fluorine-Induced Liver Injury in Rats by Mitochondrial Apoptosis Pathway.

Excessive fluoride (F) exposure can lead to liver damage; moreover, recent studies found that the addition of appropriate calcium (Ca) can alleviate the symptom of skeletal fluorosis. However, whether Ca can relieve F-induced liver damage through the mitochondrial apoptosis pathway has not been reported yet. Therefore, we assessed the liver morphology, serum transaminase content, liver oxidative stress-related enzymes, and apoptosis-related gene and protein expression in Sprague Dawley (SD) rats treated with 150 mg/L sodium fluoride (NaF) and different concentrations of calcium carbonate (CaCO) for 120 days.

Arsenic-induced autophagy regulates apoptosis in AML-12 cells.

Arsenic (As), a potent toxicant, is known to be a hepatotoxicant. Although As induced liver apoptosis and autophagy, the relationship between apoptosis and autophagy of hepatocytes caused by As remains largely unknown. 3-methyladenine (3-MA) and rapamycin can inhibit and promote autophagy of AML-12 cells, respectively.

Interleukin 17A deficiency alleviates fluoride-induced testicular injury by inhibiting the immune response and apoptosis.

The reproductive toxicity of fluoride (F) has been verified by various epidemiological and experimental studies. Our previous work suggested that the interleukin 17A (IL-17A) is involved in the testicular damage induced by excessive F exposure. In this study, we further investigated the role of IL-17A in F-induced testicular injury.

Effects of fluoride on PIWI-interacting RNA expression profiling in testis of mice.

Excessive fluoride intake can damage testis by breaking the integrity of sperm DNA and changing the expression profiles of testicular mRNAs and microRNAs. However, the effects of fluoride on the expression of PIWI-interacting RNAs (piRNAs) in mouse testes have not been reported. In this study, we determined the effect of fluoride on PIWI-interacting RNA expression profiling in testis of mice, using deep-sequencing technology.