Neurometabolomic impacts of wood smoke and protective benefits of anti-aging therapeutics in aged female C57BL/6J mice.

Background: Wildland fires in the United States have increased in frequency and scale over the past 30 years exposing millions of people to hazardous air pollutants. Among others, aging individuals are particularly vulnerable to the effects of wildfire smoke. In this study, we assessed the neurobiological impacts of wood smoke (WS) on aged mice and the potential of anti-aging therapeutics to mitigate these impacts.

Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy.

Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer's Disease and related dementias (ADRD).

Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans.

Cadmium-induced gut dysbiosis precedes the onset of hippocampus-dependent learning and memory deficits in mice.

Cadmium (Cd) is a heavy metal recognized as a neurotoxicant, but the detailed mechanisms contributing to its neurotoxicity remain to be fully elucidated. The gut-brain axis-a bidirectional communication pathway between the gut microbiome and the central nervous system-has been implicated in various neurological disorders. Since Cd targets the gut microbiome, it is important to investigate whether this axis contributes to Cd-induced neurotoxicity.

exposure of mixed microplastic particles in mice and its impacts on the murine gut microbiome and metabolome.

Microplastics (MPs) are emerging environmental contaminants due to increasing global plastic production and waste. Microplastics, defined as plastic particles less than 5 mm in diameter, are formed through degradation of larger plastics via sunlight, weathering, and microbes. These plastic compounds are widely detected in water, soil, food, as well as human stool and blood.

Anti-Obesity and Metabolic Effects of Forskolin in Obese C57BL/6J Mice.

Forskolin (FSK) induces the browning of white adipose tissue (WAT) through the activation of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) generation. When administered intravenously or orally, FSK undergoes significant metabolism and accumulation in the liver and other tissues, resulting in high side effects and low anti-obesity effects due to trivial amounts reaching WAT. This study examines the potential anti-obesity and metabolic effects of the inguinal WAT (IWAT) delivery of FSK in high-fat diet-induced C57BL/6J obese mice.

Exploratory Metabolomic and Lipidomic Profiling in a Manganese-Exposed Parkinsonism-Affected Population in Northern Italy.

Background/objectives: Chronic manganese (Mn) exposure is a recognized environmental contributor to Parkinsonian syndromes, including Mn-induced Parkinsonism (MnIP). This study aimed to evaluate whole-blood Mn levels and investigate disease/exposure-status-related alterations in metabolomic and lipidomic profiles.

Methods: A case-control study (N = 97) was conducted in Brescia, Italy, stratifying participants by Parkinsonism diagnosis and residential Mn exposure.

Metabolomic profiles impacted by brief mindfulness intervention with contributions to improved health.

Mounting evidence indicates that mindfulness-based interventions improve physical and mental health. However, whether brief mindfulness intervention supports health benefits by regulating metabolic profiles is poorly understood. To address this gap, this randomized controlled trial compared ten 1-hour sessions of integrative body-mind training (IBMT) with relaxation training (RT) in 42 participants.

Longitudinal assessment of food insecurity status on the gut microbiome and metabolome of first-year college students.

Food insecurity affects the health of college-aged individuals, but its impact on the gut microbiome (GM) over time is poorly understood. This study explored the association between food insecurity and the GM in eighty-five college students, identifying microbial taxa, metabolites and pathways linked to food security status and examining GM stability and microbe–metabolite interactions. Longitudinal GM and metabolomic data were collected from first-year students over an academic year, encompassing periods of variable food security status.

Multiomics-Based Profiling of the Fecal Microbiome Reveals Potential Disease-Specific Signatures in Pediatric IBD (PIBD).

Inflammatory bowel disease (IBD), which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), is a chronic gastrointestinal (GI) disorder affecting 1 in 100 people in the United States. Pediatric IBD (PIBD) is estimated to impact 15 per 100,000 children in North America. Factors such as the gut microbiome (GM), genetic predisposition to the disease, and certain environmental factors are thought to be involved in pathogenesis.

Single-Cell and Spatial Transcriptomics Identified Fatty Acid-Binding Proteins Controlling Endothelial Glycolytic and Arterial Programming in Pulmonary Hypertension.

Background: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for patients with PAH. Recent studies showed that FABP (fatty acid-binding protein) 4 and FABP5 are expressed in endothelial cells (ECs) across multiple tissues, and circulating FABP4 level is elevated in patients with PAH.

Impact of Manganese on Neuronal Function: An Exploratory MultiOmic Study on Ferroalloy Workers in Brescia, Italy.

Interest is growing in the potential role of manganese (Mn) in Alzheimer's Disease (ADRD). This nested pilot study of a ferroalloy workers cohort was aimed to investigate the effects of long-term occupational Mn exposure on cognitive function through β-amyloid (Aβ) modification and brain deposition, as well as metabolomic, lipidomic and proteomic profiling. We examined 6 male exposed workers (median age 63, exposure duration 31 yrs), and 5 historical controls (median age 60) who had undergone brain PET scan imaging showing higher Aβ deposition among the exposed compared to the controls (p < 0.

ALDH4A1 functions as an active component of the MPC complex maintaining mitochondrial pyruvate import for TCA cycle entry and tumour suppression.

MPC1 and MPC2 are two well-known components of the mitochondrial pyruvate carrier (MPC) complex maintaining MPC activity to transport pyruvate into mitochondria for tricarboxylic acid (TCA) cycle entry in mammalian cells. It is currently unknown whether there is an additional MPC component crucially maintaining MPC complex activity for pyruvate mitochondrial import. Here we show that ALDH4A1, a proline-metabolizing enzyme localized in mitochondria, serves as a previously unrecognized MPC component maintaining pyruvate mitochondrial import and the TCA cycle independently of its enzymatic activity.

Neurometabolomic impacts of wood smoke and protective benefits of anti-aging therapeutics in aged female C57BL/6J mice.

Background: Wildland fires have become progressively more extensive over the past 30 years in the United States, routinely generating smoke that deteriorates air quality for most of the country. We explored the neurometabolomic impact of biomass-derived smoke on older (18 months) female C57BL/6J mice, both acutely and after 10 weeks of recovery from exposures.

Methods: Mice were exposed to wood smoke (WS) 4 hours/day, every other day, for 2 weeks (7 exposures total) to an average concentration of 448 μg particulate matter (PM)/m per exposure.

Baseline gut microbiome and metabolites are correlated with changes in alcohol consumption in participants in a randomized Zonisamide clinical trial.

Development and severity of alcohol use disorder (AUD) has been linked to variations in gut microbiota and their associated metabolites in both animal and human studies. However, the involvement of the gut microbiome in alcohol consumption of individuals with AUD undergoing treatment remains unclear. To address this, stool samples (n = 32) were collected at screening (baseline) and trial completion from a double-blind, placebo-controlled trial of zonisamide in individuals with AUD.

Unlocking the potential: FKK6 as a microbial mimicry-based therapy for chronic inflammation-associated colorectal cancer in a murine model.

Chronic intestinal inflammation significantly contributes to the development of colorectal cancer and remains a pertinent clinical challenge, necessitating novel therapeutic approaches. Indole-based microbial metabolite mimics Felix Kopp Kortagere 6 (FKK6), which is a ligand and agonist of the pregnane X receptor (PXR), was recently demonstrated to have PXR-dependent anti-inflammatory and protective effects in a mouse model of dextran sodium sulfate (DSS)-induced acute colitis. Here, we examined the therapeutic potential of FKK6 in a mouse model (C57BL/6 FVB humanized PXR mice) of colitis-associated colon cancer (CAC) induced by azoxymethane and DSS.

Metabolic Reprogramming in Gut Microbiota Exposed to Polystyrene Microplastics.

: Microplastics (MPs) are small plastic fragments with diameters less than 5 mm in size and are prevalent in everyday essentials and consumables. Large global plastic production has now led to a flooding of MPs in our natural environment. Due to their detrimental impacts on the planet's ecosystems and potentially our health, MPs have emerged as a significant public health concern.

Metabolome Alterations Associated with Three-Month Sitting-Time Reduction Among Sedentary Postmenopausal Latinas with Cardiometabolic Disease Risk.

Incidence of cardiometabolic disease among U.S. Hispanics/Latinos is higher than in non-Hispanic Whites.

The combined treatment with ketogenic diet and metformin slows tumor growth in two mouse models of triple negative breast cancer.

Background: Many tumors contain hypoxic microenvironments caused by inefficient tumor vascularization. Hypoxic tumors have been shown to resist conventional cancer therapies. Hypoxic cancer cells rely on glucose to meet their energetic and anabolic needs to fuel uncontrolled proliferation and metastasis.

IMPA1-derived inositol maintains stemness in castration-resistant prostate cancer via IMPDH2 activation.

Acquisition of prostate cancer stem cells (PCSCs) manifested during androgen ablation therapy (ABT) contributes to castration-resistant prostate cancer (CRPC). However, little is known about the specific metabolites critically orchestrating this process. Here, we show that IMPA1-derived inositol enriched in PCSCs is a key metabolite crucially maintaining PCSCs for CRPC progression and ABT resistance.

Maternal Dietary Deficiencies in Folic Acid and Choline Change Metabolites Levels in Offspring after Ischemic Stroke.

: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring after ischemic stroke. : A total of 32 mice (17 males and 15 females) were used to analyze sex-specific differences in response to these deficiencies.

Sitting Interruption Modalities during Prolonged Sitting Acutely Improve Postprandial Metabolome in a Crossover Pilot Trial among Postmenopausal Women.

Older adults sit during most hours of the day; more than 30% are considered physically inactive. The accumulation of prolonged sitting time is an exercise-independent risk factor for aging-related conditions such as cardiometabolic disease and cancer. Archival plasma samples from a randomized controlled, four-condition crossover study conducted in 10 postmenopausal women with overweight or obesity were analyzed.

Metabolomic and Lipidomic Analysis of Manganese-Associated Parkinsonism: a Case-Control Study in Brescia, Italy.

Background And Objectives: Excessive Manganese (Mn) exposure is neurotoxic and can cause Mn-Induced Parkinsonism (MnIP), marked by cognitive and motor dysfunction. Although metabolomic and lipidomic research in Parkinsonism (PD) patients exists, it remains limited. This study hypothesizes distinct metabolomic and lipidomic profiles based on exposure status, disease diagnosis, and their interaction.

Microbial Ecology and Metabolism of Emerging Adulthood: Gut Microbiome Insights from a College Freshman Cohort.

The human gut microbiome (GM) undergoes dynamic changes throughout life, transitioning from infancy to adulthood. Despite improved understanding over the past years about how genetics, lifestyle, and the external environment impact the GM, limited research has explored the GM's evolution during late-stage adolescence, especially among college students. This study addresses this gap by investigating the longitudinal dynamics of fecal microbial, functional, and metabolomic signatures in a diverse group of first-year, dormitory-housed college students.

Unlocking the Potential: FKK6 as a Microbial Mimicry-Based Therapy for Chronic Inflammation-Associated Colorectal Cancer in a Murine Model.

Chronic intestinal inflammation significantly contributes to the development of colorectal cancer (CRC) and remains a pertinent clinical challenge, necessitating novel therapeutic approaches. Indole-based microbial metabolite mimics FKK6, which is a ligand and agonist of the pregnane X receptor (PXR), was recently demonstrated to have PXR-dependent anti-inflammatory and protective effects in a mouse model of dextran sodium sulfate (DSS)-induced acute colitis. Here, we examined the therapeutic potential of FKK6 in a mouse model (C57BL/6 FVB humanized PXR mice) of colitis-associated colon cancer (CAC) induced by azoxymethane (AOM) and dextran sodium sulfate (DSS).

Metabolite Predictors of Breast and Colorectal Cancer Risk in the Women's Health Initiative.

Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [ = 577 breast (BC) and = 181 colorectal (CRC)] and = 758 controls with available specimens (collected mean 7.2 years prior to diagnosis) in the Women's Health Initiative Bone Mineral Density subcohort.