Enhancing toxicity prediction for natural products in herbal medicine and dietary supplements: Integrating (Q)STR models and in vitro assays.

New approach methods (NAMs) are required to predict human toxicity effectively, particularly due to limitations in conducting in vivo studies. While NAMs have been established for various industries, such as cosmetics, pesticides, and drugs, their applications in natural products (NPs) are lacking. NPs' complexity (multiple ingredients and structural differences from synthetic compounds) complicates NAM development.

The antioxidant N-acetyl cysteine inhibits cytokine and prostaglandin release in human fetal membranes stimulated ex vivo with lipoteichoic acid or live group B streptococcus.

Backgrounds: Infection during pregnancy is a significant public health concern due to the increased risk of adverse birth outcomes. Group B Streptococcus or Streptococcus agalactiae (GBS) stands out as a major bacterial cause of neonatal morbidity and mortality. We aimed to explore the involvement of reactive oxygen species (ROS) and oxidative stress pathways in pro-inflammatory responses within human fetal membrane tissue, the target tissue of acute bacterial chorioamnionitis.

Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells.

Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood.

Group B streptococcus induces cellular senescence in human amnion epithelial cells through a partial interleukin-1-mediated mechanism.

Group B streptococcus (GBS) infection is a significant public health concern associated with adverse pregnancy complications and increased neonatal mortality and morbidity. However, the mechanisms underlying the impact of GBS on the fetal membrane, the first line of defense against pathogens, are not fully understood. Here, we propose that GBS induces senescence and inflammatory factors (IL-6 and IL-8) in the fetal membrane through interleukin-1 (IL-1).

Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity.

Exposure to environmental heavy metals such as cadmium (Cd) is often linked to neurotoxicity but the underlying mechanisms remain poorly understood. Here we show that Arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs)--an important class of extracellular vesicles (EVs) whose biogenesis occurs at the plasma membrane--protect against Cd-induced neurotoxicity. Cd increased the production of EVs, including ARMMs, in a human neural progenitor cell line, ReNcell CX (ReN) cells.

Electronic cigarette smoke reduces ribosomal protein gene expression to impair protein synthesis in primary human airway epithelial cells.

The widespread use of electronic cigarettes (e-cig) is a serious public health concern; however, mechanisms by which e-cig impair the function of airway epithelial cells-the direct target of e-cig smoke-are not fully understood. Here we report transcriptomic changes, including decreased expression of many ribosomal genes, in airway epithelial cells in response to e-cig exposure. Using RNA-seq we identify over 200 differentially expressed genes in air-liquid interface cultured primary normal human bronchial epithelial (NHBE) exposed to e-cig smoke solution from commercial e-cig cartridges.

Release of particulate matter from nano-enabled building materials (NEBMs) across their lifecycle: Potential occupational health and safety implications.

The present study investigates potential nanomaterial releases and occupational health risks across the lifecycle of nano-enabled building materials (NEBMs), namely, insulations and coatings. We utilized real-world degradation scenarios of a) sanding (mechanical), b) incineration (thermal), and c) accelerated UV-aging (environmental) followed by incineration. Extensive physicochemical characterization of the released lifecycle particulate matter (LCPM) was performed.

MicroRNA-124 Reduces Arsenic-induced Endoplasmic Reticulum Stress and Neurotoxicity and is Linked with Neurodevelopment in Children.

Arsenic (As) exposure adversely affects neurodevelopment in children. Accumulation of misfolded proteins in cells exposed to As leads to endoplasmic reticulum (ER) stress response, which, if not relieved, results in cell death. Despite the potential role of ER stress for As-induced neurotoxicity, the underlying mechanisms remain poorly understood.

Brominated diphenyl ether-47 differentially regulates cellular migration and invasion in a human first trimester trophoblast cell line.

Polybrominated diphenyl ethers (PBDEs) are flame retardant compounds detected in human placenta and linked to adverse pregnancy outcomes. Impaired trophoblast migration and invasion during early pregnancy have been implicated as potential mechanisms of pregnancy disorders. The present study investigated the effect of BDE-47, a prevalent PBDE congener, on cell migration, invasion, and matrix metalloproteinase (MMP) expression in a human first trimester extravillous trophoblast cell line, HTR-8/SVneo.

Genome-wide CRISPR screen identifies suppressors of endoplasmic reticulum stress-induced apoptosis.

Sensing misfolded proteins in the endoplasmic reticulum (ER), cells initiate the ER stress response and, when overwhelmed, undergo apoptosis. However, little is known about how cells prevent excessive ER stress response and cell death to restore homeostasis. Here, we report the identification and characterization of cellular suppressors of ER stress-induced apoptosis.

Transcriptomic response of primary human airway epithelial cells to flavoring chemicals in electronic cigarettes.

The widespread use of electronic cigarettes (e-cigarettes or e-cig) is a growing public health concern. Diacetyl and its chemical cousin 2,3-pentanedione are commonly used to add flavors to e-cig; however, little is known about how the flavoring chemicals may impair lung function. Here we report that the flavoring chemicals induce transcriptomic changes and perturb cilia function in the airway epithelium.

A functional splice variant associated with decreased asthma risk abolishes the ability of gasdermin B to induce epithelial cell pyroptosis.

Background: Genetic variants in the chromosomal region 17q21 are consistently associated with asthma. However, mechanistic studies have not yet linked any of the associated variants to a function that could influence asthma, and as a result, the identity of the asthma gene(s) remains elusive.

Objectives: We sought to identify and characterize functional variants in the 17q21 locus.

Group B streptococcus activates transcriptomic pathways related to premature birth in human extraplacental membranes in vitro.

Streptococcus agalactiae (group B streptococcus [GBS]) infection in pregnant women is the leading cause of infectious neonatal morbidity and mortality in the United States. Although inflammation during infection has been associated with preterm birth, the contribution of GBS to preterm birth is less certain. Moreover, the early mechanisms by which GBS interacts with the gestational tissue to affect adverse pregnancy outcomes are poorly understood.

Effects of Lead on Gene Expression in Neural Stem Cells and Associations between Up-regulated Genes and Cognitive Scores in Children.

Background: Lead (Pb) adversely affects neurodevelopment in children. Neural stem cells (NSCs) play an essential role in shaping the developing brain, yet little is known about how Pb perturbs NSC functions and whether such perturbation contributes to impaired neurodevelopment.

Objectives: We aimed to identify Pb-induced transcriptomic changes in NSCs and to link these changes to neurodevelopmental outcomes in children who were exposed to Pb.

Reactive Oxygen Stimulation of Interleukin-6 Release in the Human Trophoblast Cell Line HTR-8/SVneo by the Trichlorethylene Metabolite S-(1,2-Dichloro)-l-Cysteine.

Trichloroethylene (TCE) is a common environmental pollutant associated with adverse reproductive outcomes in humans. TCE intoxication occurs primarily through its biotransformation to bioactive metabolites, including S-(1,2-dichlorovinyl)-l-cysteine (DCVC). TCE induces oxidative stress and inflammation in the liver and kidney.

Protective effect of (±)α-tocopherol on brominated diphenyl ether-47-stimulated prostaglandin pathways in human extravillous trophoblasts in vitro.

Brominated diphenyl ether (BDE)-47 is a prevalent flame retardant chemical found in human tissues and is linked to adverse pregnancy outcomes in humans. Because dysregulation of the prostaglandin pathway is implicated in adverse pregnancy outcomes, the present study investigates BDE-47 induction of prostaglandin synthesis in a human extravillous trophoblast cell line, HTR-8/SVneo, examining the hypothesis that BDE-47 increases generation of reactive oxygen species (ROS) to stimulate the prostaglandin response. Treatment with 20 μM BDE-47 significantly increased mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2) at 4, 12 and 24 h, and 24-h treatment significantly increased cyclooxygenase (COX)-2 cellular protein expression and prostaglandin E2 (PGE2) concentration in culture medium.

Tetrabromobisphenol A activates inflammatory pathways in human first trimester extravillous trophoblasts in vitro.

Tetrabromobisphenol A (TBBPA) is a widely used flame retardant. Despite the presence of TBBPA in gestational tissues and the importance of proper regulation of inflammatory networks for successful pregnancy, there is no prior study on the effects of TBBPA on inflammatory responses in gestational tissues. The present study aimed to investigate TBBPA activation of inflammatory pathways, specifically cytokine and prostaglandin production, in the human first trimester placental cell line HTR-8/SVneo.

Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line.

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated.

Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro.

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood.

Effects of the beta-glycosidase reaction on bio-conversion of isoflavones and quality during tofu processing.

Background: Isoflavones are the most common group of phytoestrogens which are present in significantly large amounts in soybean and soy products such as tofu. Isoflavones occur naturally in glycoside forms having lower bioavailability than their aglycone forms. beta-Glycosidase acts as a bio-catalyst for the conversion of isoflavone glycosides to isoflavone aglycones, raising the bioavailability of isoflavones; therefore, it can be used to improve the quality of tofu.