Neonatal incubators are critical to the care for newborns in hospital settings, such as neonatal intensive care units (NICU). In 2023, the US Food and Drug Administration (FDA) reported that some neonatal incubators could potentially expose patients to various volatile organic compounds (VOCs). Exposure to elevated concentrations of VOCs may lead to adverse health responses. The goal of this study was to develop a simple, cost-effective method for evaluating VOCs from incubators without the need for specialized equipment and expertise. VOC monitoring badges were placed inside and outside of two new commercial incubators from different manufacturers and removed every 24 h over a 7-day test duration. For Incubator 1, formaldehyde levels were detected at each 24-hour interval, which slowly decreased throughout the test duration, and very low levels of other VOCs were detected with no consistent trends. For Incubator 2, low levels of formaldehyde were found on Day 1 only. This method can be used to screen for suspected release of VOCs from NICU incubators, and to determine if exposures would fall below health-based tolerable thresholds for VOCs. In 2025, FDA determined that new neonatal incubators currently supplied in the United States do not demonstrate concerning levels of airborne chemicals.

The first-line anti-tuberculosis regimen HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) frequently causes drug-induced liver injury (DILI). However, the mechanisms underlying this combination hepatotoxicity remain unclear. Therefore, this study used a hierarchical network toxicology and molecular docking approach to systematically investigate the hepatotoxic mechanisms of the HRZE regimen, aiming to identify core and non-core hepatotoxic drugs and elucidate their synergistic effects. We identified 315 DILI-related targets associated with the HRZE regimen. Protein-protein interaction network analysis revealed seven hub genes, and enrichment analysis identified the biological processes involved and signaling pathways. Isoniazid, rifampicin, and pyrazinamide were classified as core hepatotoxic drugs due to the significant enrichment of their targets in DILI pathways and their high clinical risk. In contrast, ethambutol was identified as a non-core hepatotoxic drug, with lower target enrichment and a lower risk of liver injury. The targets of the core hepatotoxic drugs were widely distributed across major DILI pathways, while ethambutol may synergistically modulate pathway activity through a limited set of targets, including Carbonic Anhydrase II (CA2). Molecular docking confirmed that all four drugs bind stably to Cytochrome P450 family 2 subfamily E member 1 (CYP2E1); the high affinity of ethambutol for CA2 suggests its involvement in cholestatic injury. In conclusion, HRZE-induced hepatotoxicity is a multi-pathway process driven predominantly by isoniazid, rifampicin, and pyrazinamide, with ethambutol playing a synergistic role and potentially contributing to cholestatic injury. By establishing a multi-level toxicological framework, this study provides a theoretical basis for understanding combination hepatotoxicity and offers potential targets for DILI intervention.

Kidney damage, often caused by oxidative stress and inflammation, can lead to renal failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including Ertugliflozin (Ertu), demonstrate renoprotective effects that may extend beyond glucose control. Our research studied the therapeutic potential and underlying mechanisms of Ertu against subchronic kidney injury in rats induced by TAA, focusing on the integrative crosstalk between oxidative stress, TLR4/STAT3 inflammation, and the YAP/TAZ fibrotic pathway, a previously unexplored axis for SGLT2 inhibitors in nephroprotection. Rats were divided into four groups: control, TAA-induced renal damage, and TAA-induced damage treated with Ertu (5 or 10 mg/kg). We assessed renal function (creatinine, urea), oxidative stress (GSH, MDA, Nrf2), inflammation (IL-1β, TNF-α, TLR4, STAT3/p-STAT3), and fibrosis (YAP1, TAZ, TGF-β1) in serum and renal tissue. Immunohistochemistry was performed to quantify TLR4 and Caspase-1 expression. TAA administration significantly induced renal dysfunction, oxidative stress, and inflammation, evidenced by elevated creatinine, urea, MDA, IL-1β, TNF-α, TLR4, and p-STAT3/STAT3 ratio, alongside depleted GSH and Nrf2. Fibrotic markers (YAP1, TAZ, TGF-β1) were also markedly upregulated. Ertu treatment, particularly at the 10 mg/kg dose, effectively reversed these alterations. It restored antioxidant defenses (GSH, Nrf2), suppressed inflammatory signaling (TLR4/IL-1β/TNF-α), normalized STAT3 activation, and downregulated profibrotic pathways. Histological improvements corroborated these biochemical findings. Ertugliflozin confers significant protection against renal damage caused by TAA by concurrently modulating oxidative stress, inflammation, and fibrotic signaling. These mechanistic findings underscore its potential as a repurposed therapeutic agent for subchronic kidney injury.

The current study aims to explore the role of endoplasmic reticulum stress (ER stress) in acrylamide (ACR)-induced nephrotoxicity. In addition, the role of ER stress is pharmacologically validated by a chemical chaperone, 4-phenylbutyric acid (4-PBA). In the present study, 24 male Albino Wistar rats (n = 6) were randomly divided into four groups. The control group received normal saline orally (p.o.) for 4 weeks. The acrylamide toxic group received ACR (10 mg/kg, p.o. in normal saline) for 4 weeks. The 4-PBA treatment groups received ACR for 28 days and 4-PBA (500 mg/kg and 1000 mg/kg, p.o. in saline) for the last 14 days. On the 29th day, rats were euthanized, and blood as well as kidney samples were collected. Renal function parameters along with oxido-nitrosative stress biomarkers in kidney were analyzed. Western blotting was used to quantify the protein expression of key ER stress indicators, and finally, histopathological examination was conducted. Findings from the study indicated that ACR markedly increased the levels of kidney function markers, renal oxido-nitrosative stress, upregulated protein expression of ER stress-related proteins and disrupted normal morphology as compared to the control group. However, 4-PBA treatment reduced oxido-nitrosative stress, improved renal functioning, downregulated ER stress-related proteins and recovered the distorted morphology of the rat’s kidney. These findings suggest the significant role of ER stress in the progression of ACR-induced nephrotoxicity as well as the ameliorative effect of 4-PBA against ACR-induced nephrotoxicity. Moreover, our findings provide the first evidence that activation of the ER stress pathway plays a critical role in acrylamide-induced nephrotoxicity.

Alpha-hexylcinnamaldehyde (HCA) and 3-(4-tert-butylphenyl)-2-methylpropanal (Lilial) are widely used synthetic fragrance aldehydes found in personal care and household products. Individually, HCA is primarily recognized as a weak skin sensitizer with mild cytotoxic potential, whereas Lilial has been classified as a Category 1B reproductive toxicant under the European Union Classification, Labeling and Packaging (CLP) Regulation due to evidence of reproductive and developmental toxicity. Despite regulatory restrictions in parts of Europe, both compounds continue to be detected globally in consumer products, and co-occurrence within fragrance formulations has been documented. Although their individual toxicological profiles have been investigated, limited information exists regarding their potential combined effects. Mechanistically, HCA is an α,β-unsaturated aldehyde capable of Michael addition with nucleophilic residues, while Lilial is a saturated aromatic aldehyde that may form reversible Schiff base adducts. Both compounds have been associated with oxidative stress, mitochondrial damage, and modulation of endocrine-related pathways. Emerging mixture data suggests that co-exposure may influence steroidogenesis and cellular stress responses beyond what is observed for individual compounds, although experimental evidence remains limited. This review synthesizes available in vitro, in vivo, mechanistic, and regulatory data on HCA and Lilial, examines plausible interaction pathways including electrophile-mediated protein modification and metabolic competition, and identifies key gaps requiring mixture-oriented investigation. Greater integration of mechanistic toxicology with cumulative risk assessment frameworks is needed to better reflect real-world co-exposure scenarios involving fragrance aldehydes.

2-Hydroxyethyl methacrylate (HEMA) is the most abundantly released monomer from dental restorative materials, and it has been suggested that it may also affect periodontal tissue cells. This study aimed to clarify the influence of HEMA on gingival inflammation, focusing particularly on its effects on chemokine production involved in leukocyte migration and on the signaling pathways regulating their expression in human gingival fibroblasts (HGFs). Chemokine production from interleukin (IL)-1β-stimulated HGFs was evaluated using an enzyme-linked immunosorbent assay (ELISA), and the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB, the nuclear translocation of NF-κB p65, and the expression of heme oxygenase-1 (HO-1) were examined by Western blot analysis. HEMA inhibited IL-1β–induced production of chemokines (CCL2, CCL20, CXCL10, and IL-8) in a concentration-dependent manner. Although HEMA did not affect the activation of MAPKs, it suppressed the activation of the NF-κB pathway and reduced the nuclear translocation of NF-κB p65 in IL-1β–stimulated HGFs. Furthermore, HEMA treatment increased HO-1 expression in HGFs. These findings suggest that HEMA may influence the immune response in periodontal lesions by suppressing chemokine production in HGFs.

Human blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are useful markers to assess the effects of pesticides exposure and the potential of compounds involved in the treatment of Alzheimer disease. Therefore, there is crucial importance to establish protocols for blood cholinesterase analysis comparing different methods that can adapt to the needs of each laboratory. Thus, the objective of this study was to compare two widely used methods for analysis of blood cholinesterase activity. To achieve this objective, multiple conditions of substrate concentration, time of reaction and sample dilution were tested. Multivariate analysis involving age of the men and women volunteers, systolic and diastolic pressure, human plasma protein, AChE and BChE activity were also performed. In addition, the concentrations of four compounds able to inhibit 50% of enzymes activity (IC50 value) were determined to demonstrate the differences between the two methods. Multiple conditions tested could help researchers to choose the best condition according to their purpose. Our results demonstrate the relevance of jointly evaluating AChE and BChE and suggest that the colorimetric method yields more sensitive results, while the electrometric method contributes to a faster and cheaper analysis of enzymatic activity. Ellman’s method stood out for the BChE, showing lower IC50 values, while Mohammad’s method was more effective for the AChE. These results indicate that method selection can be guided by the target enzyme and the type of inhibitor, and that the combined use of the two techniques tends to offer a more comprehensive and reliable approach for toxicological evaluation.

Mercury (Hg) remains a prominent global contaminant despite regulatory interventions such as the Minamata Convention. Inorganic mercury (Hg2+), particularly mercuric chloride (HgCl2), persists in aquatic ecosystems and poses significant risks to both environmental and human health. While its neurotoxicity is well recognized, the systemic interplay between brain and liver responses under sub-lethal exposure remains poorly understood. Here, we exposed zebrafish (Danio rerio) to an environmentally relevant concentration of HgCl2 (0.04 ppm) for 15 days to examine behavioral, neurochemical, molecular, and hepatic alterations. Mercury exposure induced pronounced anxiety-like behavior and delayed social recognition, accompanied by decreased locomotor activity. These behavioral deficits are supported with depletion of dopamine, serotonin, and acetylcholinesterase activity, implicating disrupted monoaminergic and cholinergic signaling. Molecular profiling revealed downregulation of aldh1l1 and ugt8, indicating glial dysfunction, and upregulation of il6, consistent with neuroinflammation. In the liver, mercury triggered a shift toward apoptosis (bax/bcl2 ratio increase), inflammation (il6 elevation), and loss of junctional integrity (cldn7a downregulation). Biochemically, exposure to HgCl2 elevated serum SGPT levels, enhanced lipid peroxidation, and caused dyslipidaemia characterized by reduced HDL, triglyceride, and cholesterol levels. Immunohistochemistry confirmed strong hepatic Hsp90 overexpression, marking oxidative and proteotoxic stress, while histological analysis revealed steatosis, parenchymal disorganization, and nuclear pyknosis. Together, these findings establish that even low-level inorganic mercury exposure perturbs both central and peripheral systems through convergent oxidative and inflammatory mechanisms. Our study highlights mercury as a systemic toxicant disrupting the liver–brain axis and underscores the importance of integrating multi-organ endpoints in environmental risk assessment of heavy metals.

Constipation and gastrointestinal (GI) dysmotility are prevalent disorders often associated with impaired gut–brain axis regulation and limited therapeutic options. This study investigated the safety and gastrokinetic efficacy of CL18100F4 (Digexin®), a standardized polyherbal formulation comprising extracts of Withania somnifera (Ashwagandha) root and Abelmoschus esculentus (Okra) pods. Ex vivo assays using isolated rat ileum demonstrated that CL18100F4 significantly enhanced intestinal contractility in a dose-dependent manner, with muscarinic receptor involvement confirmed by atropine inhibition. In vivo administration of CL18100F4 (200- and 300 mg/kg body weight for eight days) to Wistar rats showed significant improvements in gastric emptying (73.97 ± 15.12%, p = 0.0410), intestinal transit (80.43 ± 4.76%, p = 0.0184), and fecal moisture content (57.42 ± 5.05%, p = 0.0101), without affecting fecal pellet count. Serum corticosterone levels were significantly reduced, while serotonin levels increased, suggesting modulation of the gut–brain axis. No adverse alterations were observed in liver, kidney, or metabolic biochemical parameters, indicating systemic safety. Collectively, these findings demonstrate that CL18100F4 exerts synergistic gastrokinetic and neuroendocrine regulatory effects while maintaining a good safety profile. The formulation shows promise as a functional food or nutraceutical for managing GI motility disorders by modulating the gut–brain axis–associated biomarkers.

Methotrexate (METX) is a widely used chemotherapeutic and immunosuppressive agent, frequently employed as a first-line treatment for various malignancies and autoimmune disorders. Despite its clinical efficacy, METX is known to induce cardiotoxicity primarily through mechanisms involving oxidative stress, inflammation, and apoptosis. Apigenin (API), a natural dietary flavonoid, exhibits potent antioxidant and anti-inflammatory properties. The current study evaluated the protective effects of API against METX-induced cardiotoxicity in mice, focusing on the modulation of transforming growth factor-β (TGF-β)/(SMAD2) signaling. Molecular docking was done to investigate the possible inhibition of TGF-β by API and bioinformatic tools were utilized to investigate the correlation between the target proteins. Male Swiss albino mice were randomly distributed to four groups: Group I: a saline group, Group II: a METX control group (20 mg/kg, per week), Group III: METX + API (40 mg/kg, per day) and Group IV: METX + API (80 mg/kg, per day, via oral gavage); the study continued for three weeks. Our findings suggest that API administration significantly mitigated METX cardiotoxicity and serum CK-MB, likely through attenuation of the inflammatory cytokines (NF-κB, IL-1β, TNF-α, and IL-6) and suppression of cardiac TGF-β/SMAD2 signaling. The congruence between bioinformatics and experimental validation findings strongly highlighted API as a promising therapeutic candidate for alleviating METX cardiotoxicity. While the current data reveals key underlying molecular mechanisms for API′s cardioprotective effect, further comprehensive studies across diverse cardiotoxicity models are essential to fully elucidate cardioprotective effect of API.