Per- and poly-fluoroalkyl substances (PFAS) in circulation in a Canadian population: their association with serum-liver enzyme biomarkers and piloting a novel method to reduce serum-PFAS.

Extensive use of per- and polyfluoroalkyl substances (PFAS) has resulted in their ubiquitous presence in human blood. PFAS exposures have been associated with multiple adverse human health effects. Biomonitoring studies have focused on long-chain PFASs, but these are being replaced by short-chain PFASs or with alternate PFAS chemistries (or replacement chemistries such as GenX), resulting in changes in human exposures with time.

VIPER-TACs leverage viral E3 ligases for disease-specific targeted protein degradation.

In targeted protein degradation (TPD) a protein of interest is degraded by chemically induced proximity to an E3 ubiquitin ligase. One limitation of using TPD therapeutically is that most E3 ligases have broad tissue expression, which can contribute to toxicity via target degradation in healthy cells. Many pathogenic and oncogenic viruses encode E3 ligases (vE3s), which de facto have strictly limited expression to diseased cells.

A rifamycin SV in situ gelling formulation for the treatment of pouchitis.

Procto-colectomy with an ileal pouch anal anastomosis is performed in Ulcerative Colitis patients as a potential curative surgical option. However, in many patients a non-specific inflammation of the ileal reservoir can occur, named pouchitis. Some patients further develop a chronic antibiotic-resistant disease.

Association between urinary catecholamines and glucocorticoids and bone mineral density and osteoporosis in Puerto Rican adults.

Background: Chronic stress leads to elevated stress hormones, which may be linked to bone breakdown. Puerto Rican adults living on the US mainland have higher prevalence of stress than the general population, and higher and/or similar prevalence of osteoporosis compared with non-Hispanic Whites. The role of stress on bone remains unclear and may be modified by diet.

Comprehensive Analysis of TSPAN32 Regulatory Networks and Their Role in Immune Cell Biology.

Tetraspanin 32 (TSPAN32), a member of the tetraspanin superfamily, is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of chromosome 11p15.5, a critical tumor-suppressor gene region. Although the biology of TSPAN32 remains largely unexplored, accumulating evidence suggests its involvement in hematopoietic functions.

Tetraspanin32 (TSPAN32) is downregulated in rheumatoid arthritis: Evidence from animal models and patients.

This study aimed to investigate the role of TSPAN32, a member of the tetraspanin family, in rheumatoid arthritis (RA). The objective was to assess the expression levels of TSPAN32 in experimental RA models and in RA patient immune cells, exploring its potential as a regulatory factor in RA pathogenesis. The study employed adjuvant-induced arthritis in rats and collagen-induced arthritis (CIA) in mice as experimental models.

Serum and urinary levels of MIF, CD74, DDT and CXCR4 among patients with type 1 diabetes mellitus, type 2 diabetes and healthy individuals: Implications for further research.

Background: Macrophage migration inhibitory factor (MIF) is a highly conserved cytokine with pleiotropic properties, mainly pro-inflammatory. MIF seems to exert its pro-inflammatory features by binding to its transmembrane cellular receptor CD74. MIF also has CXCR4, which acts as a co-receptor in this inflammatory process.

Feel the breeze: Opening the therapeutic window with RIPTACs and induced proximity.

In this issue of Cell Chemical Biology, Raina et al. demonstrate proof of concept of a new chemical induced proximity strategy for targeted cancer therapeutics. Building on a recent surge in induced proximity modalities, RIPTACs represent a novel approach that offers promise in treating cancers with improved safety profiles.

Identification of Poliovirus Receptor-like 3 Protein as a Prognostic Factor in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, with a bad prognosis and lack of targeted therapeutic options. Characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, TNBC is often associated with a significantly lower survival rate compared to other breast cancer subtypes. Our study aimed to explore the prognostic significance of 83 immune-related genes, by using transcriptomic data from the TCGA database.

Evaluation of Toll-like Receptor 4 (TLR4) Involvement in Human Atrial Fibrillation: A Computational Study.

In the present study, we have explored the involvement of Toll-like Receptor 4 (TLR4) in atrial fibrillation (AF), by using a meta-analysis of publicly available human transcriptomic data. The meta-analysis revealed 565 upregulated and 267 downregulated differentially expressed genes associated with AF. Pathway enrichment analysis highlighted a significant overrepresentation in immune-related pathways for the upregulated genes.

Associations among diabetes medication use, serum magnesium, and insulin resistance in a cohort of older Puerto Rican adults.

Background: Hypomagnesemia is commonly observed in individuals with diabetes, but how diabetes medications alter magnesium (Mg) status remains unclear.

Objectives: We aimed to examine the association between diabetes medication and hypomagnesemia and evaluate whether serum Mg mediates the association between diabetes medication and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in a prospective cohort.

Methods: Adults from the Boston Puerto Rican Health Study were included (n = 1106).

Stool titanium dioxide is positively associated with stool alpha-1 antitrypsin and calprotectin in young healthy adults.

Titanium dioxide (TiO2/E171) is used widely in foods, primarily as a food additive. Animal models have shown that chronic TiO exposure may disturb homeostasis of the gastrointestinal tract by increasing gut permeability, inducing gut inflammation, and increasing the likelihood of microbial infection. Adults have a wide range of ingested TiO,which span two to three orders of magnitude, with a small portion of individuals consuming near gram quantities of TiO2/day.

Emerging Therapeutic Potential of Polyphenols from L. in Viral Infections, Including SARS-CoV-2.

The existing literature supports the anti-inflammatory, antioxidant, and antiviral capacities of the polyphenol extracts derived from L. These extracts exhibit potential in hindering viral replication by inhibiting enzymes like DNA polymerase and reverse transcriptase. The antiviral properties of L.

Daily yogurt consumption does not affect bone turnover markers in men and postmenopausal women of Caribbean Latino descent: a randomized controlled trial.

Background: Caribbean Latino adults are at high risk for osteoporosis yet remain underrepresented in bone research. This increased risk is attributed to genetics, diet, and lifestyle known to drive inflammation and microbial dysbiosis.

Objective: The primary objective of this study was to determine whether consuming 5 oz of yogurt daily for 8wks improves bone turnover markers (BTMs) among Caribbean Latino adults > 50 years; and secondarily to determine the impact on the gut microbiota and markers of intestinal integrity and inflammation.

Evaluation of Cell-Specific Alterations in Alzheimer's Disease and Relevance of In Vitro Models.

Alzheimer's disease (AD) is a neurodegenerative disorder classically characterized by two neuropathological hallmarks: β-amyloid plaques and tau tangles in the brain. However, the cellular and molecular mechanisms involved in AD are still elusive, which dampens the possibility of finding new and more effective therapeutic interventions. Current in vitro models are limited in modelling the complexity of AD pathogenesis.

TAC-tics for Leveraging Proximity Biology in Drug Discovery.

Chemically induced proximity (CIP) refers to co-opting naturally occurring biological pathways using synthetic molecules to recruit neosubstrates that are not normally encountered or to enhance the affinity of naturally occurring interactions. Leveraging proximity biology through CIPs has become a rapidly evolving field and has garnered considerable interest in basic research and drug discovery. PROteolysis TArgeting Chimera (PROTAC) is a well-established CIP modality that induces the proximity between a target protein and an E3 ubiquitin ligase, causing target protein degradation via the ubiquitin-proteasome system.

Racial and Ethnic Differences in Studies of the Gut Microbiome and Osteoporosis.

Purpose Of Review: The purpose of this review is to summarize the scientific evidence published in the past 5 years examining the epidemiology of bone health as it relates to the gut microbiome, across race and ethnicity groups.

Recent Findings: The link between the gut microbiome and bone health is well established and is supported by numerous biological mechanisms. However, human study research in this field is dominated by studies of older adults residing in Asian countries.

The newly engineered monoclonal antibody ON104, targeting the oxidized Macrophage Migration Inhibitory Factor (oxMIF), ameliorates clinical and histopathological signs of collagen-induced arthritis.

Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic inflammatory cytokine that emerged as a pivotal regulator in the pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA). MIF occurs in two immunologically distinct conformational isoforms, indicated as reduced (redMIF) and oxidized MIF (oxMIF) where the latter exerts disease-related activities. In this study we demonstrate the presence of circulating oxMIF in RA patients and investigate the in vivo effects of an oxMIF-neutralizing antibody in a murine model of RA.

Evaluation of the Involvement of Heme Oxygenase-1 Expression in Discoid Lupus Erythematosus Lesions.

Discoid lupus erythematosus (DLE) is a chronic autoimmune disease that primarily affects the skin, causing red, scaly patches that may be disfiguring and can cause permanent scarring. This study aimed to investigate the potential clinical and therapeutic applications of heme oxygenase-1 (HMOX1) in the context of DLE. Immunohistochemical staining and bioinformatics analysis were performed on skin biopsy samples from DLE patients to examine the levels of HMOX1 and to correlate with markers of inflammation.

Transcriptional upregulation of galectin-3 in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune, demyelinating disorder of the central nervous system (CNS) affecting approximately 2.5 million people worldwide. The mechanisms underlying the pathogenesis of MS are still only partially elucidated.

The longitudinal impact of the SARS-CoV-2 pandemic on participants from the Boston Puerto Rican Health Study.

Objective: to investigate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on older Hispanic adults.

Methods: A total of 522 participants (or their family member, if deceased) from the Boston Puerto Rican Health Study were asked whether they had been diagnosed with SARS-CoV-2, across 2 survey phases. In phase 1 (May - Aug 2020, n=497), participants answered survey questions related to SARS-CoV-2 exposure, diagnosis, and transmission and 5 family members reported deaths.

Anti-COVID-19 Potential of Ellagic Acid and Polyphenols of L.

Pomegranate ( L.) is a rich source of polyphenols, including ellagitannins and ellagic acid. The plant is used in traditional medicine, and its purified components can provide anti-inflammatory and antioxidant activity and support of host defenses during viral infection and recovery from disease.