Autotaxin signaling facilitates β cell dedifferentiation and dysfunction induced by Sirtuin 3 deficiency.

Objective: β cell dedifferentiation may underlie the reversible reduction in pancreatic β cell mass and function in type 2 diabetes (T2D). We previously reported that β cell-specific Sirt3 knockout (Sirt3) mice developed impaired glucose tolerance and glucose-stimulated insulin secretion after feeding with high fat diet (HFD). RNA sequencing showed that Sirt3-deficient islets had enhanced expression of Enpp2 (Autotaxin, or ATX), a secreted lysophospholipase which produces lysophosphatidic acid (LPA).

Legacy effect of high glucose on promoting survival of HCT116 colorectal cancer cells by reducing endoplasmic reticulum stress response.

Patients with diabetes have increased risk of cancer and poor response to anti-cancer treatment. Increased protein synthesis is associated with endoplasmic reticulum (ER) stress which can trigger the unfolded protein response (UPR) to restore homeostasis, failure of which can lead to dysregulated cellular growth. We hypothesize that hyperglycemia may have legacy effect in promoting survival of cancer cells through dysregulation of UPR.

A novel binary matrix consisting of graphene oxide and caffeic acid for the analysis of scutellarin and its metabolites in mouse kidney by MALDI imaging.

Although the in vivo metabolic pathways of scutellarin, a traditional Chinese medicine, have been investigated via different liquid chromatography techniques, studies on the distribution and location of scutellarin within organ tissue sections have not been reported. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can generate in situ spatial distribution profiles for scutellarin and its metabolites in a kidney section. However, the direct detection of a small molecule (m/z < 600) using conventional matrices often results in ion suppression and matrix interferences.

Mass spectrometry imaging and monitoring of glutathione-triggered cisplatin release from nanoparticles in the kidneys.

An increasing number of studies have reported the use of various nanoparticles to encapsulate cisplatin, a frontline chemotherapeutic drug against a broad-spectrum of cancers, for overcoming its inherent drawbacks in clinical applications. Nevertheless, few analytical methods or instruments could provide the precise distribution information on this platinum drug in biological tissues. Herein, we provide the first evidence of applying matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to assess the spatial distribution of cisplatin released from the cell-penetrating poly(disulfide) (CPD)-modified hollow iron oxide nanoparticles (hFeO-MPS-CPD) at the kidneys an glutathione (GSH) responsive mode.

Pancreatic Sirtuin 3 Deficiency Promotes Hepatic Steatosis by Enhancing 5-Hydroxytryptamine Synthesis in Mice With Diet-Induced Obesity.

Sirtuin 3 (SIRT3) is a protein deacetylase regulating β-cell function through inhibiting oxidative stress in obese and diabetic mice, but the detailed mechanism and potential effect of β-cell-specific SIRT3 on metabolic homeostasis, and its potential effect on other metabolic organs, are unknown. We found that glucose tolerance and glucose-stimulated insulin secretion were impaired in high-fat diet (HFD)-fed β-cell-selective knockout ( ) mice. In addition, mice had more severe hepatic steatosis than mice upon HFD feeding.

Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization.

Background & Aims: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus.

Methods: We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020.

Derivatization strategy combined with parallel reaction monitoring for the characterization of short-chain fatty acids and their hydroxylated derivatives in mouse.

Short-chain fatty acids (SCFAs) and hydroxylated short-chain fatty acids (OH-SCFAs) are crucial intermediates related to a variety of diseases, such as bowel disease, cardiovascular disease, renal disease and cancer. A global profiling method to screen SCFAs and OH-SCFAs was developed by tagging these analytes with d/d-N, N-dimethyl-6,7-dihydro-5H-pyrrolo [3,4-d] pyrimidine-2-amine (d/d-DHPP) and using ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-MS/MS) in parallel reaction monitoring (PRM) mode. The derivatization procedure was simple and rapid.

Immunotoxic Potential of Bisphenol F Mediated through Lipid Signaling Pathways on Macrophages.

As a bisphenol A (BPA) alternative, bisphenol F (BPF) has been detected in various products, such as paper products, personal care products, and food. More importantly, the toxicity of BPF remains underexplored. We reported an integrated method to study the immunotoxic potentials and the underlying mechanisms of BPF on cell apoptosis, macrophage polarization, reactive oxygen species generation, expression and secretion of immune-related cytokines, and reprogramming of lipid signaling.

In Situ Detection and Imaging of PFOS in Mouse Kidney by Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry.

Perfluorooctanesulfonic acid (PFOS) is an emerging environmental organic pollutant that has been widely used in daily life products in the last century. Numerous studies showed that the accumulation of PFOS in human through food chain would lead to various disease. However, there is currently no report about its in situ localization in the tissue.

Chronic exposure to tetrabromodiphenyl ether (BDE-47) aggravates hepatic steatosis and liver fibrosis in diet-induced obese mice.

Exposure to polybrominated diphenyl ethers (PBDEs), is closely associated with the occurrence of obesity and non-alcoholic fatty liver disease (NAFLD), yet their pathological effects and underlying mechanisms remain unclear. To examine the role of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) in the progression of NAFLD under obese condition, male C57BL/6 J mice were fed with diet interaction for 15 weeks and subcutaneously injected with BDE-47 (7 mg/kg or 70 mg/kg) or the vehicle weekly. BDE-47 exposure (70 mg/kg) significantly elevated the body weight and worsened hepatic steatosis along with increased inflammation in high fat diet (HFD) fed mice.

PFOA and PFOS promote diabetic renal injury in vitro by impairing the metabolisms of amino acids and purines.

Background: Environmental pollutants, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are common surfactants in various consumer products. Epidemiological studies have demonstrated the association of diabetic kidney diseases with PFOA and PFOS. However, mechanisms of metabolic alterations involved are still unclear.

The brominated flame retardant BDE 47 upregulates purine metabolism and mitochondrial respiration to promote adipocyte differentiation.

Adipocyte differentiation is closely associated with obesity and obesity-induced metabolic disorders. Epidemiological studies have demonstrated the association of obesity with environmental pollutants, such as polybrominated diphenyl ethers (PBDEs), common flame retardants in various consumer products. However, their obesogenic effects and mechanism are underexplored.

Prenatal exposure to ambient fine particulate matter induces dysregulations of lipid metabolism in adipose tissue in male offspring.

Prenatal exposure to ambient fine particles (diameter < 0.25 μm, PM) has been found to be associated with abnormal growth and development in offspring. However, the effects of PM on the lipid metabolism of adipose tissue in offspring are unclear.

Early-life exposure to endocrine disrupting chemicals associates with childhood obesity.

Increasing prevalence of childhood obesity poses threats to the global health burden. Because this rising prevalence cannot be fully explained by traditional risk factors such as unhealthy diet and physical inactivity, early-life exposure to endocrine disrupting chemicals (EDCs) is recognized as emerging novel risk factors for childhood obesity. EDCs can disrupt the hormone-mediated metabolic pathways, affect children's growth and mediate the development of childhood obesity.

Metabolic perturbation, proliferation and reactive oxygen species jointly contribute to cytotoxicity of human breast cancer cell induced by tetrabromo and tetrachloro bisphenol A.

Halogenated bisphenol A analogues (X-BPA) have been widely used in industrial production, such as flame retardant. Although BPA exposure was found to result in cytotoxicity, toxicity of X-BPA and molecular mechanism remain under-explored. In this study, we employed human breast cancer cell as a model to investigate the concentration-dependent toxicity and underlying mechanisms of tetrabromo bisphenol A (TBBPA) and tetrachloro bisphenol A (TCBPA).

Large-Scale Longitudinal Metabolomics Study Reveals Different Trimester-Specific Alterations of Metabolites in Relation to Gestational Diabetes Mellitus.

Despite the increasing research attention paid to gestational diabetes mellitus (GDM) due to its high prevalence, limited knowledge is available about its pathogenesis. In this study, 428 serum samples were collected from 107 pregnant women suffering from GDM and 107 matched healthy controls. The nontargeted metabolomics data of maternal serum samples from the first (T1, n = 214) and second trimesters (T2, n = 214) were acquired by using ultrahigh performance liquid chromatography coupled with Orbitrap mass spectrometry (MS).

Profiles, variability, and predictors of urinary benzotriazoles and benzothiazoles in pregnant women from Wuhan, China.

Background: Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging contaminants with high production volume worldwide, which exhibit potential health risk to human. To date, little is known about the exposure of BTRs and BTHs (BTs) on human, especially in the context of pregnancy.

Objectives: We aimed to characterize the exposure profiles, temporal variability, and potential predictors of urinary BTs during pregnancy.

Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise.

Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia, hyperglycemia and insulin resistance, which correlated with high mortality worldwide. Exercise is one of the effective lifestyle interventions in maintaining blood glucose level in the normal range and lowering risk factors. Metabolomics approaches are powerful tools in systematic study of overall metabolic changes in response to disease or interventions.

Integrative Chemical Proteomics-Metabolomics Approach Reveals Acaca/Acacb as Direct Molecular Targets of PFOA.

Identification of the direct molecular targets of environmental pollutants is of great importance for toxicity mechanism studies. Despite numerous studies have been conducted to investigate the toxicity mechanism of perfluorinated compounds (PFCs), their direct-binding protein targets which trigger downstream toxicity effects remain largely unknown. Herein, we present a systematic chemical proteomic study to profile the target proteins of PFCs by taking PFOA as a representative.

MALDI-MS Imaging Reveals Asymmetric Spatial Distribution of Lipid Metabolites from Bisphenol S-Induced Nephrotoxicity.

With the continuous exposure of environmental pollutants in organisms, determination of abundance variation and spatial distribution of lipids might expand our understanding of toxicological mechanisms occurring in the kidney. Herein, an integrated method involving mass spectrometry (MS)-based lipidomics and matrix-assisted laser desorption/ionization-MS imaging (MALDI-MSI) was developed for the study of nephrotoxicity in mice exposed to 10 and 100 μg bisphenol S (BPS)/kg body weight/day. The BPS exposure remarkable perturbed abundances of 91 potential markers that mainly involved in five metabolic pathways.

LC-MS-based metabolomics revealed SLC25A22 as an essential regulator of aspartate-derived amino acids and polyamines in -mutant colorectal cancer.

SLC25A22, which encodes the mitochondrial glutamate transporter, is overexpressed in colorectal cancer (CRC) and is essential for the proliferation of CRC cells harboring mutations. However, the role of SLC25A22 on metabolic regulation in -mutant CRC cells has not been comprehensively characterized. We performed non-targeted metabolomics, targeted metabolomics and isotope kinetic analysis of -mutant DLD1 cells with or without SLC25A22 knockdown using ultra-high-performance liquid chromatography (UHPLC) coupled to Orbitrap mass spectrometry (MS) or tandem MS (MS/MS).

Persistent Organic Pollutants as Risk Factors for Obesity and Diabetes.

Purpose Of Review: The rising prevalence of obesity and diabetes cannot be fully explained by known risk factors, such as unhealthy diet, a sedentary lifestyle, and family history. This review summarizes the available studies linking persistent organic pollutants (POPs) to obesity and diabetes and discusses plausible underlying mechanisms.

Recent Findings: Increasing evidence suggest that POPs may act as obesogens and diabetogens to promote the development of obesity and diabetes and induce metabolic dysfunction.

Sirt3 Deficiency Increased the Vulnerability of Pancreatic Beta Cells to Oxidative Stress-Induced Dysfunction.

Aims: Hyperlipidemia-induced oxidative stress is considered to be one of the main pathogenic factors that contribute to pancreatic beta cell dysfunction in the development of type 2 diabetes (T2D). Sirtuin 3 (Sirt3) is abundantly expressed in the mitochondria as an NAD-dependent deacetylase and regulates mitochondrial adaptive responses to oxidative stress. We examined the antioxidant defense mechanism of Sirt3 in pancreatic beta cells in the context of hyperlipidemia.

TGF-β/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis.

Myofibroblasts are a main cell-type of collagen-producing cells during tissue fibrosis, but their origins remains controversial. While bone marrow-derived myofibroblasts in renal fibrosis has been reported, the cell origin and mechanisms regulating their transition into myofibroblasts remain undefined. In the present study, cell lineage tracing studies by adoptive transfer of GFP+ or dye-labelled macrophages identified that monocyte/macrophages from bone marrow can give rise to myofibroblasts via the process of macrophage-myofibroblast transition (MMT) in a mouse model of unilateral ureteric obstruction.

microRNAs in Diabetic Kidney Disease.

Diabetes and diabetic kidney diseases have continually exerted a great burden on our society. Although the recent advances in medical research have led to a much better understanding of diabetic kidney diseases, there is still no successful strategy for effective treatments for diabetic kidney diseases. Recently, treatment of diabetic kidney diseases relies either on drugs that reduce the progression of renal injury or on renal replacement therapies, such as dialysis and kidney transplantation.