Unveiling population-specific outcomes: Examining life cycle traits of different strains of Chironomus riparius exposed to microplastics and cadmium questions generality of ecotoxicological results.

Ecotoxicological tests used for risk assessment of toxicants and its mixtures rely both on classical life-cycle endpoints and bioindicator organisms usually derived from long-term laboratory cultures. While these cultures are thought to be comparable among laboratories and more sensitive than field organisms, it is not well investigated whether this assumption is met. Therefore, we aimed to investigate differential life-cycle endpoints response of two different strains of C. riparius, one originally from Spain and the other from Germany, kept under the same laboratory conditions for more than five years. To highlight any possible differences, the two populations were challenged with exposure to cadmium (Cd), polyvinyl chloride (PVC) microplastics and a co-exposure with both. Our results showed that significant differences between the strains became evident with the co-exposure of Cd and PVC MPs. The German strain showed attenuation of the deleterious Cd effects with microplastic co-exposure in survival and developmental time. Contrary to that, the Spanish strain showed no interaction between the substances. In conclusion, the toxicity-effects of contaminants may vary strongly among laboratory populations, which makes a universal risk assessment evaluation challenging.

Microvesicles from quiescent and TGF-ß1 stimulated hepatic stellate cells: Divergent impact on hepatic vascular injury.

BACKGROUND: This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-ß1 stimulated hepatic stellate cells (HSC-MVs, TGF-ß1HSC-MVs) on H2O2-induced human umbilical vein endothelial cells (HUVECs) injury and CCl4-induced rat hepatic vascular injury. METHODS: HUVECs were exposed to hydrogen peroxide (H2O2) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-ß1HSC-MVs were co-cultured with H2O2-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-ß1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected. RESULTS: In H2O2-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-ß1HSC-MVs exhibited opposite effects. CCl4- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-ß1HSC-MVs demonstrated opposite effects. CONCLUSION: HSC-MVs demonstrated a protective effect on H2O2-treated HUVECs and CCl4-induced rat hepatic injury, while TGF-ß1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways.

Pulmonary osteoclast-like cells in silica induced pulmonary fibrosis.

The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.

The effects of iron oxide nanoparticles on antioxidant capacity and response to oxidative stress in Mozambique tilapia (Oreochromis mossambicus, Peters 1852).

Recent research has raised concern about the biocompatibility of iron oxide nanoparticles (IONPs), as they have been reported to induce oxidative stress and inflammatory responses, whilst prolonged exposure to high IONP concentrations may lead to cyto-/genotoxicity. Besides, there is concern about its environmental impact. The aim of our study was to investigate the effects of IONPs on the antioxidant defence system in freshwater fish Mozambique tilapia (Oreochromis mossambicus, Peters 1852). The fish were exposed to IONP concentration of 15 mg/L over 1, 3, 4, 15, 30, and 60 days and the findings compared to a control, unexposed group. In addition, we followed up the fish for 60 days after exposure had stopped to estimate the stability of oxidative stress induced by IONPs. Exposure affected the activity of antioxidant and marker enzymes and increased the levels of hydrogen peroxide and lipid peroxidation in the gill, liver, and brain tissues of the fish. Even after 60 days of depuration, adverse effects remained, indicating long-term nanotoxicity. Moreover, IONPs accumulated in the gill, liver, and brain tissues. Our findings underscore the potential health risks posed to non-target organisms in the environment, and it is imperative to establish appropriate guidelines for safe handling and disposal of IONPs to protect the aquatic environment.

In silico analysis of the impact of toxic metals on COVID-19 complications: molecular insights.

COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (IL1B, CXCL8, IL6, IL10, TNF) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.

Disruptive effects of plasticizers bisphenol A, F, and S on steroidogenesis of adrenocortical cells.

Introduction: Endocrine disrupting chemicals (EDCs) are known to interfere with endocrine homeostasis. Their impact on the adrenal cortex and steroidogenesis has not yet been sufficiently elucidated. This applies in particular to the ubiquitously available bisphenols A (BPA), F (BPF), and S (BPS). Methods: NCI-H295R adrenocortical cells were exposed to different concentrations (1nM-1mM) of BPA, BPF, BPS, and an equimolar mixture of them (BPmix). After 72 hours, 15 endogenous steroids were measured using LC-MS/MS. Ratios of substrate and product of CYP-regulated steps were calculated to identify most influenced steps of steroidogenesis. mRNA expression of steroidogenic enzymes was determined by real-time PCR. Results: Cell viability remained unaffected at bisphenol concentrations lower than 250 µM. All tested bisphenols and their combination led to extensive alterations in the quantified steroid levels. The most profound fold changes (FC) in steroid concentrations after exposure to BPA (>10µM) were seen for androstenedione, e.g. a 0.37±0.11-fold decrease at 25µM (p≤0.0001) compared to vehicle-treated controls. For BPF, levels of 17-hydroxyprogesterone were significantly increased by 25µM (FC 2.57±0.49, p≤0.001) and 50µM (FC 2.65±0.61, p≤0.0001). BPS treatment led to a dose-dependent decrease of 11-deoxycorticosterone at >1µM (e.g. FC 0.24±0.14, p≤0.0001 at 10µM). However, when combining all three bisphenols, additive effects were detected: e.g. 11-deoxycortisosterone was decreased at doses >10µM (FC 0.27±0.04, p≤0.0001, at 25µM), whereas 21-deoxycortisol was increased by 2.92±0.20 (p≤0.01) at 10µM, and by 3.21±0.45 (p≤0.001) at 50µM. While every measured androgen (DHEA, DHEAS, androstenedione, testosterone, DHT) was lowered in all experiments, estradiol levels were significantly increased by BPA, BPF, BPS, and BPmix (e.g. FC 3.60±0.54, p≤0.0001 at 100µM BPF). Calculated substrate-product ratios indicated an inhibition of CYP17A1-, and CYP21A2 mediated conversions, whereas CYP11B1 and CYP19A1 showed higher activity in the presence of bisphenols. Based on these findings, most relevant mRNA expression of CYP genes were analysed. mRNA levels of StAR, CYP11B1, and CYP17A1 were significantly increased by BPF, BPS, and BPmix. Discussion: In cell culture, bisphenols interfere with steroidogenesis at non-cytotoxic levels, leading to compound-specific patterns of significantly altered hormone levels. These results justify and call for additional in-vivo studies to evaluate effects of EDCs on adrenal gland functionality.

Ex Vivo Evaluation of the Function of Hematopoietic Stem Cells in Toxicology of Metals.

A variety of metals, e.g., lead (Pb), cadmium (Cd), and lithium (Li), are in the environment and are toxic to humans. Hematopoietic stem cells (HSCs) reside at the apex of hematopoiesis and are capable of generating all kinds of blood cells and self-renew to maintain the HSC pool. HSCs are sensitive to environmental stimuli. Metals may influence the function of HSCs by directly acting on HSCs or indirectly by affecting the surrounding microenvironment for HSCs in the bone marrow (BM) or niche, including cellular and extracellular components. Investigating the impact of direct and/or indirect actions of metals on HSCs contributes to the understanding of immunological and hematopoietic toxicology of metals. Treatment of HSCs with metals ex vivo, and the ensuing HSC transplantation assays, are useful for evaluating the impacts of the direct actions of metals on the function of HSCs. Investigating the mechanisms involved, given the rarity of HSCs, methods that require large numbers of cells are not suitable for signal screening; however, flow cytometry is a useful tool for signal screening HSCs. After targeting signaling pathways, interventions ex vivo and HSCs transplantation are required to confirm the roles of the signaling pathways in regulating the function of HSCs exposed to metals. Here, we describe protocols to evaluate the mechanisms of direct and indirect action of metals on HSCs. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Identify the impact of a metal on the competence of HSCs Basic Protocol 2: Identify the impact of a metal on the lineage bias of HSC differentiation Basic Protocol 3: Screen the potential signaling molecules in HSCs during metal exposure Alternate Protocol 1: Ex vivo treatment with a metal on purified HSCs Alternate Protocol 2: Ex vivo intervention of the signaling pathway regulating the function of HSCs during metal exposure.

Concomitant Effects of Metformin and Vitamin C on Indomethacin-Induced Gastric Ulcer in Rats: Biochemical and Histopathological Approach.

INTRODUCTION: Gastric ulcer is one of the most common and serious conditions in the gastrointestinal tract. One of the main causes of gastric ulcers is using of non-steroidal anti-inflammatory drugs (NSAIDs) which have limited their use in clinical practice. Several studies have revealed that metformin and Vitamin C (Vit C) exhibit protective effects against gastric mucosal damage in different animal models. However, no studies indicate their combination's effect on gastric ulcer models. Therefore, this study aims to investigate the protective effects of metformin and Vit C combination on indomethacin-induced gastric ulcers. MATERIAL AND METHODS: In total, thirty rats were divided into six groups, including the control group, rats received indomethacin (50 mg/kg, i.p.), rats received indomethacin and pretreated with ranitidine (100 mg/kg), metformin (100 mg/kg, i.p.), Vit C (100 mg/kg), or metformin combined with Vit C. Four hours after indomethacin administration, rats were euthanized, and gastric tissues were removed for macroscopic, histopathologic, and biochemical examinations. RESULTS: All therapeutics used in this study were found to alleviate gastric mucosal injury caused by indomethacin, as observed in histopathologic and macroscopic evaluations. Both Vit C and metformin were observed to significantly decrease lipid peroxidation and enhance the activity of anti-oxidative enzymes, SOD, GPx, and catalase. However, a more significant effectiveness was observed in catalase and GPx activities when Vit C was co-administered with metformin. CONCLUSIONS: In conclusion, the present study revealed that metformin and Vit C combination therapy could potentially treat gastric ulcers associated with indomethacin.

Effects of triclosan adsorption on intestinal toxicity and resistance gene expression in Xenopus tropicalis with different particle sizes of polystyrene.

Microplastics (MPs) are commonly found with hydrophobic contaminants in the water column and pose a serious threat to aquatic organisms. The effects of polystyrene microplastics of different particle sizes on the accumulation of triclosan in the gut of Xenopus tropicalis, its toxic effects, and the transmission of resistance genes were evaluated. The results showed that co-exposure to polystyrene (PS-MPs) adsorbed with triclosan (TCS) caused the accumulation of triclosan in the intestine with the following accumulation capacity: TCS + 5 µm PS group > TCS group > TCS + 20 µm PS group > TCS + 0.1 µm PS group. All experimental groups showed increased intestinal inflammation and antioxidant enzyme activity after 28 days of exposure to PS-MPs and TCS of different particle sizes. The TCS + 20 µm PS group exhibited the highest upregulated expression of pro-inflammatory factors (IL-10, IL-1ß). The TCS + 20 µm group showed the highest increase in enzyme activity compared to the control group. PS-MPs and TCS, either alone or together, altered the composition of the intestinal microbial community. In addition, the presence of more antibiotic resistance genes than triclosan resistance genes significantly increased the expression of tetracycline resistance and sulfonamide resistance genes, which may be associated with the development of intestinal inflammation and oxidative stress. This study refines the aquatic ecotoxicity assessment of TCS adsorbed by MPs and provides informative information for the management and control of microplastics and non-antibiotic bacterial inhibitors.

Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165.

BACKGROUND: Aberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored. OBJECTIVES: We aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation. METHODS: We constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge. RESULTS: HDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10fl/fl-LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI. CONCLUSION: These results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI.

Transglutaminase 2 knockout mice are protected from bleomycin-induced lung fibrosis with preserved lung function and reduced metabolic derangements.

Pulmonary fibrosis is an interstitial scarring disease of the lung characterized by poor prognosis and limited treatment options. Tissue transglutaminase 2 (TG2) is believed to promote lung fibrosis by crosslinking extracellular matrix components and activating latent TGFß. This study assessed physiologic pulmonary function and metabolic alterations in the mouse bleomycin model with TG2 genetic deletion. TG2-deficient mice demonstrated attenuated the fibrosis and preservation of lung function, with significant reduction in elastance and increases in compliance and inspiratory capacity compared to control mice treated with bleomycin. Bleomycin induced metabolic changes in the mouse lung that were consistent with increased aerobic glycolysis, including increased expression of lactate dehydrogenase A and increased production of lactate, as well as increased glutamine, glutamate, and aspartate. TG2-deficient mice treated with bleomycin exhibited similar metabolic changes but with reduced magnitude. Our results demonstrate that TG2 is required for a typical fibrosis response to injury. In the absence of TG2, the fibrotic response is biochemically similar to wild-type, but lesions are smaller and lung function is preserved. We also show for the first time that profibrotic pathways of tissue stiffening and metabolic reprogramming are interconnected, and that metabolic disruptions in fibrosis go beyond glycolysis.

Equations for estimating binary mixture toxicity: 3-methyl-2-butanone with a series of electrophiles.

Mixture toxicity was determined for 32 binary combinations. One chemical was the non-reactive, non-polar narcotic 3-methyl-2-butanone (always chemical A) and the other was a potentially reactive electrophile (chemical B). Bioluminescence inhibition in Allovibrio fischeri was measured at 15-, 30-, and 45-minutes of exposure for A, B, and the mixture (MX). Concentration-response curves (CRCs) were developed for each chemical and used to develop predicted CRCs for the concentration addition (CA) and independent action (IA) mixture toxicity models. Also, MX CRCs were generated and compared with model predictions using the 45-minute data. Classification of observed mixture toxicity used three specific criteria: 1) predicted IA EC50 vs. CA EC50 values at 45-minutes, 2) consistency of 45-minute MX CRC fit to IA, CA, or otherwise at three effect levels (EC25, EC50 and EC75), and 3) the known/suspected mechanism of toxicity for chemical B. Mixture toxicity was then classified into one of seven groupings. As a result of the predicted IA EC50 being more toxic than the predicted CA EC50, IA represented the greater toxic hazard. For this reason, non-sham MXs having toxicity consistent with CA were classified as being "coincident" with CA rather than mechanistically-consistent with CA. Multiple linear regression analyses were performed to develop equations that can be used to estimate the toxicity of other 3M2B-containing binary mixtures. These equations were developed from the data for both IA and CA, at each exposure duration and effect level. Each equation had a coefficient of determination (r2) above 0.950 and a variance inflation factor <1.2. This approach can potentially reduce the need for mixture testing and is amenable to other model systems and to assays that evaluate toxicity at low effect levels.

The cytotoxic, genotoxic and mitotoxic effects of Atractylis gummifera extract in vitro.

Background: The Mediterranean thistle Atractylis gummifera L. (Asteraceae; AG) has diterpenoid glucosides; atractyloside and carboxyatractyloside that interact with mitochondrial protein adenine nucleotide translocator (ANT) and resulted in ATP inhibition. Despite its well-known toxicity, acute poisonings still occur with this plant. Although most symptoms are attributed to ANT and diterpenoids interaction, in-depth investigation of the effects of AG extract on various cellular processes has not been performed. Objective/method: We tested in vitro induction of mitochondrial permeability transition pore (MPTP) opening in bovine liver mitochondria and evaluated its cytotoxicity and genotoxicity using Allium cepa test. Cell division, mitotic index (MI) and total chromosomal and mitotic aberrations (TAs), that all seem potentially affected by ATP shortage, were studied in root cells of Allium cepa exposed to Atractylis gummifera extract. Results: With the two different doses of two purified AG fractions, stronger induction of MPTP was observed compared to the induction with the standard pure atracyloside. Aqueous AG extract exerted inhibition root growth in A. cepa at 6 different doses. The TAs was increased in a dose-dependent manner too, while mitotic index was decreased at the same doses. Evaluation of mitotic phases revealed mitodepressive effect of AG on A. cepa roots. Conclusion: this work highlights cellular and mitochondrial adverse effects of Atractylis gummifera extracts. A purified fraction that likely corresponds to ATR derivatives induces MPTP opening leading to swelling of mitochondria and its dysfunction. Allium cepa test provides the evidence for A. gummifera genotoxicity and cytotoxicity.

The impact of environmental factors and contaminants on thyroid function and disease from fetal to adult life: current evidence and future directions.

The thyroid gland regulates most of the physiological processes. Environmental factors, including climate change, pollution, nutritional changes, and exposure to chemicals, have been recognized to impact thyroid function and health. Thyroid disorders and cancer have increased in the last decade, the latter increasing by 1.1% annually, suggesting that environmental contaminants must play a role. This narrative review explores current knowledge on the relationships among environmental factors and thyroid gland anatomy and function, reporting recent data, mechanisms, and gaps through which environmental factors act. Global warming changes thyroid function, and living in both iodine-poor areas and volcanic regions can represent a threat to thyroid function and can favor cancers because of low iodine intake and exposure to heavy metals and radon. Areas with high nitrate and nitrite concentrations in water and soil also negatively affect thyroid function. Air pollution, particularly particulate matter in outdoor air, can worsen thyroid function and can be carcinogenic. Environmental exposure to endocrine-disrupting chemicals can alter thyroid function in many ways, as some chemicals can mimic and/or disrupt thyroid hormone synthesis, release, and action on target tissues, such as bisphenols, phthalates, perchlorate, and per- and poly-fluoroalkyl substances. When discussing diet and nutrition, there is recent evidence of microbiome-associated changes, and an elevated consumption of animal fat would be associated with an increased production of thyroid autoantibodies. There is some evidence of negative effects of microplastics. Finally, infectious diseases can significantly affect thyroid function; recently, lessons have been learned from the SARS-CoV-2 pandemic. Understanding how environmental factors and contaminants influence thyroid function is crucial for developing preventive strategies and policies to guarantee appropriate development and healthy metabolism in the new generations and for preventing thyroid disease and cancer in adults and the elderly. However, there are many gaps in understanding that warrant further research.

[The mechanism of SSO regulating SiO(2)-induced lipid metabolism disorders in macrophages was explored based on lipid metabolomics].

Objective: To investigate the mechanism of Sulfo-N-succinimidyloleate (SSO) regulating lipid metabolism disorder induced by silicon dioxide (SiO(2)) . Methods: In March 2023, Rat alveolar macrophages NR8383 were cultured in vitro and randomly divided into control group (C), SSO exposure group (SSO), SiO(2) exposure group (SiO(2)) and SiO(2)+SSO exposure group (SiO(2)+SSO). NR8383 cells were exposure separately or jointly by SSO and SiO(2) for 36 h to construct cell models. Immunofluorescence and BODIPY 493/ 503 staining were used to detect cluster of differentiation (CD36) and intracellular lipid levels, the protein expression levels of CD36, liver X receptors (LXR), P-mammalian target of rapamycin (P-mTOR) and cholinephosphotransferase 1 (CHPT1) were detected by Western blot, respectively, and lipid metabolomics was used to screen for different lipid metabolites and enrichment pathways. Single-factor ANOVA was used for multi-group comparison, and LSD test was used for pair-to-group comparison. Results: SiO(2) caused the expression of CD36 and P-mTOR to increase (P=0.012, 0.020), the expression of LXR to decrease (P=0.005), and the intracellular lipid level to increase. After SSO treatment, CD36 expression decreased (P=0.023) and LXR expression increased (P=0.000) in SiO(2)+SSO exposure group compared with SiO(2) exposure group. Metabolomics identified 87 different metabolites in the C group and SiO(2) exposure group, 19 different metabolites in the SiO(2) exposure group and SiO(2)+SSO group, and 5 overlaps of different metabolites in the two comparison groups, they are PS (22∶1/14∶0), DG (O-16∶0/18∶0/0∶0), PGP (i-13∶0/i-20∶0), PC (18∶3/16∶0), and Sphinganine. In addition, the differential metabolites of the two comparison groups were mainly concentrated in the glycerophospholipid metabolism and sphingolipid metabolism pathways. The differential gene CHPT1 in glycerophospholipid metabolic pathway was verified, and the expression of CHPT1 decreased after SiO(2) exposure. Conclusion: SSO may improve SiO(2)-induced lipid metabolism disorders by regulating PS (22∶1/14∶0), DG (O-16∶0/18∶0/0∶0), PGP (i-13∶0/i-20∶0), PC (18∶3/16∶0), SPA, glycerophospholipid metabolism and sphingolipid metabolism pathways.

[Role of CTGF and PI3K/Akt signaling pathway in paraquat-induced mesenchymal changes in alveolar epithelial cells].

Objective: To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) . Methods: In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 µmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 µmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 µmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 µmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 µmol/L PQ), and inhibitor group (200 µmol/L PQ+20 µmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted. Results: The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance (P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group (P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group (P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group (P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group (P<0.05/3) . Conclusion: CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.

[Research progress on the developmental toxicity and mechanism of brominated flame retardants during pregnancy exposure on offspring].

Brominated flame retardants (BFRs) are a kind of brominated compounds widely used in electronic and electrical appliances, textiles, construction materials and other industrial products to improve the flame retardant property. Because of its strong chemical stability, environmental persistence, long-distance transmission, biological accumulation, the exposure of humans and organisms in the ecosystem is increasing, and its potential biological effects are of great concern. Now BFRs can be detected in breast milk, serum, placenta and cord blood. Studies have shown that exposure to BFRs during pregnancy can lead to adverse birth outcomes such as low birth weight, malformation, gestational age changes and impairment of neurobehavioral development. This article summarizes the pollution and population exposure of three traditional BFRs, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), as well as the impact and mechanism of prenatal exposure on offspring birth outcomes and growth and development. It explores the harm of prenatal exposure to BFRs to offspring and proposes preventive measures for occupational populations for reference.

Effect of combined red and infrared wavelengths on inflammation, hemorrhage, and muscle damage caused by Bothrops leucurus snake venom.

To evaluate the effects of red and infrared wavelengths, separately and combined, on the inflammatory process and collagen deposition in muscle damage caused by B. leucurus venom. 112 mice were inoculated with diluted venom (0.6mg/kg) in the gastrocnemius muscle. The animals were divided into four groups: one control (CG) and three treatments, namely: 1) red laser (λ=660 nm) (RG), 2) infrared laser (λ=808 nm) (IG) and 3) red laser (λ=660 nm) + infrared (λ=808 nm) (RIG). Each group was subdivided into four subgroups, according to the duration of treatment application (applications every 24 hours over evaluation times of up to 144 hours). A diode laser was used (0.1 W, CW, 1J/point, ED: 10 J/cm2). Both wavelengths reduced the intensity of inflammation and the combination between them significantly intensified the anti-inflammatory response. Photobiomodulation also changed the type of inflammatory infiltrate observed and RIG had the highest percentage of mononuclear cells in relation to the other groups. Hemorrhage intensity was significantly lower in treated animals and RIG had the highest number of individuals in which this variable was classified as mild. As for collagen deposition, there was a significant increase in RG in relation to CG, in RIG in relation to CG and in RIG in relation to IG. Photobiomodulation proved to be effective in the treatment of inflammation and hemorrhage caused by B. leucurus venom and stimulated collagen deposition. Better results were obtained with the combined wavelengths.

Vitamin D alleviation of oxidative stress in human retinal pigment epithelial cells.

BACKGROUND: Oxidative stress-induced retinal pigment epithelium (RPE) cell damage is a major factor in age-related macular degeneration (AMD). Vitamin D3 (VD3) is a powerful antioxidant and it has been suggested to have anti-aging properties and potential for treating AMD. This study aimed to investigate the effect of VD3 on RPE cell oxidative apoptosis of RPE cells in order to provide experimental evidence for the treatment of AMD. METHODS: Human retinal pigment epithelial cell 19 (ARPE-19) cells were divided into four groups: blank group (untreated), model group (incubated in medium with 400 µmol/L H2O2 for 1 h), VD3 group (incubated in medium with 100 µmol/L VD3 for 24 h), and treatment group (incubated in medium with 400 µmol/L H2O2 for 1 h and 100 µmol/L VD3 for 24 h). Cell viability, cell senescence, ROS content, expression levels of vitamin D specific receptors, Akt, Sirt1, NAMPT, and JNK mRNA expression levels, SOD activity, and MDA, GSH, and GPX levels were measured. RESULTS: We first established an ARPE-19 cell stress model with H2O2. Our control experiment showed that VD3 treatment had no significant effect on ARPE-19 cell viability within 6-48 h. Treating the stressed ARPE-19 cells with VD3 showed mixed results; caspase-3 expression was decreased, Bcl-2 expression was increased, MDA level of ARPE-19 cells was decreased, GSH-PX, GPX and SOD levels were increased, the relative mRNA expression levels of Akt, Sirt1, NAMPT were increased (P < 0.05), and the relative mRNA expression level of JNK was decreased (P < 0.05). CONCLUSION: VD3 can potentially slow the development of AMD.

HISTOLOGICAL EFFECTS OF CO ENZYME Q10 ON DOXORUBICIN-INDUCED DEFICITS OF CARDIOPULMONARY AXIS IN WHITE ALBINO RATS.

Doxorubicin is the common chemotherapeutic agent that has been harnessed for the treatment of various types of malignancy including the treatment of soft tissue and osteosarcoma and cancers of the vital organs like breast, ovary, bladder, and thyroid. It is also used to treat leukaemia and lymphoma, however, this is an obstacle because of their prominent side effects including cardiotoxicity and lung fibrosis, we do aim to determine the role of CoQ10 as an antioxidant on the impeding the deleterious impacts of doxorubicin on tissue degenerative effects. To do so, 27 rats were subdivided into 3 groups of 9 each; CoQ10 exposed group, Doxorubicin exposed group, and CoQ10 plus Doxorubicin group. At the end of the study, the animals were sacrificed and lungs with hearts were harvested, and slides were prepared for examination under a microscope. The results indicated that doxorubicin induced abnormal cellular structure resulting in damaging cellular structures of the lung and heart while CoQ10 impeded these damaging effects and nearly restoring normal tissue structure. As a result, CoQ10 will maintain normal tissue of the lung and heart.