Safety of Prolonged Exposure of Human Skin to Aqueous Ozone in a Test Hand Hygiene Model.

AIMS: This research assessed the safety of aqueous ozone (AO) on human skin after multiple exposures for up to 40 hours. METHODS AND RESULTS: Full thickness recombinant human skin (EpiDerm FT, EFT-400) was exposed to AO for 7 seconds per minute for the first 6 minutes of each hour, repeated hourly over four time periods (4, 10, 20 and 40 hours). An MTT assay assessed viability of skin cells after exposure, compared to incubator control, negative control and vehicle control (distilled water). No significant difference in tissue viability was found between the AO condition and any of the control conditions through 20 hours of exposures. At 40 hours of exposure, tissue viability was lower in the AO group when compared with negative control (p = 0.030) but not the other controls. CONCLUSIONS: The current study supports further consideration of repeated application of AO on human skin, such as for hand hygiene. IMPACT STATEMENT: The present research is the first well-controlled in vitro study assessing the cytotoxicity of repeated exposures of AO on a full-thickness human skin model. This information helps to inform the evaluation of AO as a potential alternative for hand and wound antisepsis.

Endoscopic Dilatation with Ultrathin Endoscope Assisted Method for Esophageal and Pyloric Stricture related Corrosive Injury: 4 Years Case Series Study.

Corrosive injuries (CI) become medical problems related complications include esophageal, pyloric stricture and squamous cell carcinoma, physical and quality of life. Endoscopic (ED) dilatation is primary therapy. The ultrathin endoscope-assisted method is potentially safe and useful in avoiding technical failure. Describe clinical outcomes of ED ED-related CI including successful, refractory, recurrent, and complications-related procedures. Case series study of esophageal and/or pyloric stricture patients after CI who underwent dilatation at Soetomo General Hospital (July 2018 - July 2022). One - biweekly ED using Through The Scope (TTS) balloon or Savary Bougie dilator. The target diameter is 14mm. Fifteen patients with stricture-related CI. Eleven patients underwent ED with a total of 73 procedures. Mean age 31,45 years, predominantly male patients (6), suicide attempt (7), acid agent (9), located at esophagus (3), pylorus (3), or both (5). Number of esophageal dilatation to achieve the target of 14 mm was 1-2 and 2-15 procedures for simple and complex stricture. Five esophageal strictures were successfully dilated but 2 patients were recurrent and 3 cases were refractory to ED. Pyloric dilatation resulted in a lower success rate. Recurrent and refractory cases were 5 and 3 patients respectively. ED with ultrathin endoscope method is useful for traversing guidewire during ED. Ongoing inflammation and fibrosis were linked to recurrent and refractory stricture.

Sex-dependent alterations of inflammatory factors, oxidative stress, and histopathology of the brain-gut axis in a VPA-induced autistic-like model of rats.

INTRODUCTION: In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain-gut axis in male and female rats prenatally exposed to VPA. METHODS: Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600 mg/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress. RESULTS: An increase of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and a decrease of interleukin-10 (IL-10) were observed in the two sexes and two tissues of the autistic rats. In the VPA-exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals. CONCLUSION: The inflammatory and antioxidant factors were in line in the brain-gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA-exposed male animals.

Synergistic interplay between melatonin and hydrogen sulfide enhances cadmium-induced oxidative stress resistance in stock (Matthiola incana L.).

Ornamental crops particularly cut flowers are considered sensitive to heavy metals (HMs) induced oxidative stress condition. Melatonin (MLT) is a versatile phytohormone with the ability to mitigate abiotic stresses induced oxidative stress in plants. Similarly, signaling molecules such as hydrogen sulfide (H2S) have emerged as potential options for resolving HMs related problems in plants. The mechanisms underlying the combined application of MLT and H2S are not yet explored. Therefore, we evaluated the ability of individual and combined applications of MLT (100 µM) and H2S in the form of sodium hydrosulfide (NaHS), a donor of H2S, (1.5 mM) to alleviate cadmium (Cd) stress (50 mg L-1) in stock (Matthiola incana L.) plants by measuring various morpho-physiological and biochemical characteristics. The results depicted that Cd-stress inhibited growth, photosynthesis and induced Cd-associated oxidative stress as depicted by excessive ROS accumulation. Combined application of MLT and H2S efficiently recovered all these attributes. Furthermore, Cd stress-induced oxidative stress markers including electrolyte leakage, malondialdehyde, and hydrogen peroxide are partially reversed in Cd-stressed plants by MLT and H2S application. This might be attributed to MLT or H2S induced antioxidant plant defense activities, which effectively reduce the severity of oxidative stress indicators. Overall, MLT and H2S supplementation, favorably regulated Cd tolerance in stock; yet, the combined use had a greater effect on Cd tolerance than the independent application.

Modulation efficiency of clove oil nano-emulsion against genotoxic, oxidative stress, and histological injuries induced via titanium dioxide nanoparticles in mice.

Titanium dioxide nanoparticles (TiO2-NPs) have found wide applications in medical and industrial fields. However, the toxic effect of various tissues is still under study. In this study, we evaluated the toxic effect of TiO2-NP on stomach, liver, and kidney tissues and the amelioration effect of clove oil nanoemulsion (CLV-NE) against DNA damage, oxidative stress, pathological changes, and the apoptotic effect of TiO2-NPs. Four groups of male mice were subjected to oral treatment for five consecutive days including, the control group, the group treated with TiO2-NPs (50 mg/kg), the group treated with (CLV-NE) (5% of the MTD), and the group treated with TiO2-NPs plus CLV-NE. The results revealed that the treatment with TiO2-NPs significantly caused DNA damage in the liver, stomach, and kidney tissues due to increased ROS as indicated by the reduction of the antioxidant activity of SOD and Gpx and increased MDA level. Further, abnormal histological signs and apoptotic effect confirmed by the significant elevation of p53 expression were reported after TiO2-NPs administration. The present data reported a significant improvement in the previous parameters after treatment with CLV-NE. These results showed the collaborative effect of the oils and the extra role of nanoemulsion in enhancing antioxidant effectiveness that enhances its disperse-ability and further promotes its controlled release. One could conclude that CLV-NE is safe and can be used as a powerful antioxidative agent to assess the toxic effects of the acute use of TiO2-NPs.

Estrogenic endocrine disruptor exposure directly impacts erectile function.

Erectile dysfunction (ED) is an extremely prevalent condition which significantly impacts quality of life. The rapid increase of ED in recent decades suggests the existence of unidentified environmental risk factors contributing to this condition. Endocrine Disrupting Chemicals (EDCs) are one likely candidate, given that development and function of the erectile tissues are hormonally dependent. We use the estrogenic-EDC diethylstilbestrol (DES) to model how widespread estrogenic-EDC exposure may impact erectile function in humans. Here we show that male mice chronically exposed to DES exhibit abnormal contractility of the erectile tissue, indicative of ED. The treatment did not affect systemic testosterone production yet significantly increased estrogen receptor α (Esr1) expression in the primary erectile tissue, suggesting EDCs directly impact erectile function. In response, we isolated the erectile tissue from mice and briefly incubated them with the estrogenic-EDCs DES or genistein (a phytoestrogen). These acute-direct exposures similarly caused a significant reduction in erectile tissue contractility, again indicative of ED. Overall, these findings demonstrate a direct link between estrogenic EDCs and erectile dysfunction and show that both chronic and acute estrogenic exposures are likely risk factors for this condition.

Kaempferol attenuates inflammation in lipopolysaccharide-induced gallbladder epithelial cells by inhibiting the MAPK/NF-κB signaling pathway.

Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti-inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)-induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10-200 µM) were tested. LPS-induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL-1ß, IL-6, and TNF-α) levels were quantified using ELISA, The modulation of the MAPK/NF-κB signaling pathway was measured by western blot using specific antibodies against pathway components (p-IκBα, IκBα, p-p65, p65, p-JNK, JNK, p-ERK, ERK, p-p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 µM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS-induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL-1ß, IL-6, and TNF-α) and protein expression (iNOS and COX-2) in LPS-induced HGBECs. Furthermore, KPR reversed LPS-induced elevation of p-IκBα/IκBα, p-p65/p65, p-JNK/JNK, p-ERK/ERK, and p-p38/p38 ratios. KPR attenuates the LPS-induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF-κB signaling.

Analysis of human health effects under ozone exposure in the oasis area of Hetao Plain.

This article, based on OMI data products, utilizes spatial distribution, ozone-sensitive control areas, Pearson correlation methods, and the Ben-MAP model to study the changes in ozone column concentration from 2018 to 2022, along with the influencing factors and the health of populations exposed to ozone. The findings suggest a spatial variation in the ozone column concentration within the study area, with an increasing trend observed from west to east and from south to north. Over time, the ozone column concentration exhibits an initial increase followed by a subsequent decrease, with the peak concentration observed in 2019 at 37.45 DU and the nadir recorded in 2022 at 33.10 DU. The monthly mean distribution exhibits an inverted V-shaped pattern during the warm season from April to September, with a peak in July (46.71 DU) and a trough in April (35.29 DU). The Hetao Plain Oasis area is primarily a NOx control area in sensitive control areas. The concentrations of O3 and precursor HCHO exhibited significant positive correlations with vegetation index and air temperature, while showing significant negative correlations with wind speed and air pressure. The precursor NO2, in contrast, exhibited a significant negative correlation with both the vegetation index and relative humidity. Based on the ground-based monitoring sites and analysis of human health benefits, the study area witnessed 1944.45 deaths attributed to warm season O3 exposure in 2018, with a subsequent reduction in premature deaths by 149.7, 588.2, and 231.75 for the years 2019 to 2021 respectively when compared to the baseline year. In 2021, the observed decrease in warm-season O3 concentration within that region compared to 2018 resulted in a significant reduction, leading to the prevention of 126 premature deaths.

A poisonous cocktail: interplay of cereulide toxin and its structural isomers in emetic Bacillus cereus.

Food intoxications evoked by emetic Bacillus cereus strains constitute a serious threat to public health, leading to emesis and severe organ failure. The emetic peptide toxin cereulide, assembled by the non-ribosomal peptide synthetase CesNRPS, cannot be eradicated from contaminated food by usual hygienic measures due to its molecular size and structural stability. Next to cereulide, diverse chemical variants have been described recently that are produced concurrently with cereulide by CesNRPS. However, the contribution of these isocereulides to the actual toxicity of emetic B. cereus, which produces a cocktail of these toxins in a certain ratio, is still elusive. Since cereulide isoforms have already been detected in food remnants from foodborne outbreaks, we aimed to gain insights into the composition of isocereulides and their impact on the overall toxicity of emetic B. cereus. The amounts and ratios of cereulide and isocereulides were determined in B. cereus grown under standard laboratory conditions and in a contaminated sample of fried rice balls responsible for one of the most severe food outbreaks caused by emetic B. cereus in recent years. The ratios of variants were determined as robust, produced either under laboratory or natural, food-poisoning conditions. Examination of their actual toxicity in human epithelial HEp2-cells revealed that isocereulides A-N, although accounting for only 10% of the total cereulide toxins, were responsible for about 40% of the total cytotoxicity. An this despite the fact that some of the isocereulides were less cytotoxic than cereulide when tested individually for cytotoxicity. To estimate the additive, synergistic or antagonistic effects of the single variants, each cereulide variant was mixed with cereulide in a 1:9 and 1:1 binary blend, respectively, and tested on human cells. The results showed additive and synergistic impacts of single variants, highlighting the importance of including not only cereulide but also the isocereulides in routine food and clinical diagnostics to achieve a realistic toxicity evaluation of emetic B. cereus in contaminated food as well as in patient samples linked to foodborne outbreaks. Since the individual isoforms confer different cell toxicity both alone and in association with cereulide, further investigations are needed to fully understand their cocktail effect.

Acute toxicity of total ammonia to Macrobrachium rosenbergii postlarvae at different salinity levels.

Nitrogen compounds, particularly ammonium, nitrite and nitrate, are a major problem in shrimp production systems. These compounds can accumulate in the aquatic environment and reach harmful or even lethal levels. Thus, monitoring the levels of nitrogenous compounds such as ammonia and studying their effects on the animals are essential. One tool used for this purpose is acute toxicity testing based on the evaluation of LC50 values. Furthermore, tools that can help improve the performance of aquatic organisms in culture are needed. The present study aimed to evaluate the effect of salinity on the toxicity of total ammonia to postlarvae of the freshwater prawn Macrobrachium rosenbergii. For this purpose, acute toxicity testing (LC50-96h) was performed using 540 postlarvae with a mean weight of 0.13 g and a mean total length of 2.47 cm, divided into 54 experimental units of two liters each. A completely randomized design in a 3×6 factorial scheme was used, combining three salinities (0, 5, and 10 g.L-1) and six total ammonia concentrations (0, 8, 16, 32, 64, and 128 mg.L-1), with three replicates per combination. The LC50 values for M. rosenbergii postlarvae at 24, 48, 72, and 96 h and their respective confidence intervals (95%) were estimated using the trimmed Spearman-Karber method. The results showed that salinities of 5 or 10 g.L-1 did not reduce the acute toxicity of total ammonia.

Hippocampal acetylcholinesterase activation induced by streptozotocin in mice is protected by an organotellurium compound without evidence of toxicity.

The cognitive deficit, which is like Alzheimer's disease and is associated with oxidative damage, may be induced by exposure to streptozotocin. This study aimed to evaluate if the tellurium-containing organocompound, 3j, 5'-arylchalcogeno-3-aminothymidine derivative, interferes with the effects of streptozotocin, as well as to investigate its toxicity in adult mice. Cognitive deficit was induced by two doses of streptozotocin (2.25 mg/kg/day, 48 h interval) intracerebroventricularly. After, the mice were subcutaneously treated with 3j (8.62 mg/kg/day) for 25 days. The effects were assessed by evaluating hippocampal and cortical acetylcholinesterase and behavioral tasks. 3j toxicity was investigated for 10 (0, 21.55, or 43.10 mg/kg/day) and 37 (0, 4.31, or 8.62 mg/kg/day) days by assessing biometric parameters and glucose and urea levels, and alanine aminotransferase activity in blood plasma. 3j exposure did not alter the behavioral alterations induced by streptozotocin exposure. On the other hand, 3j exposure normalized hippocampus acetylcholinesterase activity, which is enhanced by streptozotocin exposure. Toxicity evaluation showed that the administration of 3j for either 10 or 37 days did not cause harmful effects on the biometric and biochemical parameters analyzed. Therefore, 3j does not present any apparent toxicity and reverts acetylcholinesterase activity increase induced by streptozotocin in young adult mice.

Pollution levels and probability risk assessment of potential toxic elements in soil of Pb-Zn smelting areas.

Soil pollution around Pb-Zn smelters has attracted widespread attention around the world. In this study, we compiled a database of eight potentially toxic elements (PTEs) Pb, Zn, Cd, As, Cr, Ni, Cu, and Mn in the soil of Pb-Zn smelting areas by screening the published research papers from 2000 to 2023. The pollution assessment and risk screening of eight PTEs were carried out by geo-accumulation index (Igeo), potential ecological risk index (PERI) and health risk assessment model, and Monte Carlo simulation employed to further evaluate the probabilistic health risks. The results suggested that the mean values of the eight PTEs all exceeded the corresponding values in the upper crust, and more than 60% of the study sites had serious Pb and Cd pollution (Igeo > 4), with Brazil, Belgium, China, France and Slovenia having higher levels of pollution than other regions. Besides, PTEs in smelting area caused serious ecological risk (PERI = 10912.12), in which Cd was the main contributor to PREI (86.02%). The average hazard index (HI) of the eight PTEs for adults and children was 7.19 and 9.73, respectively, and the average value of total carcinogenic risk (TCR) was 4.20 × 10-3 and 8.05 × 10-4, respectively. Pb and As are the main contributors to non-carcinogenic risk, while Cu and As are the main contributors to carcinogenic risk. The probability of non-carcinogenic risk in adults and children was 84.05% and 97.57%, while carcinogenic risk was 92.56% and 79.73%, respectively. In summary, there are high ecological and health risks of PTEs in the soil of Pb-Zn smelting areas, and Pb, Cd, As and Cu are the key elements that cause contamination and risk, which need to be paid attention to and controlled. This study is expected to provide guidance for soil remediation in Pb-Zn smelting areas.

Joint toxicity of cadmium (II) and microplastic leachates on wheat seed germination and seedling growth.

Cadmium (Cd) pollution ranks first in soils (7.0%) and microplastics usually have a significant adsorption capacity for it, which could pose potential threats to agricultural production and human health. However, the joint toxicity of Cd and microplastics on crop growth remains largely unknown. In this study, the toxic effects of Cd2+ and two kinds of microplastic leachates, polyvinyl chloride (PVC) and low-density polyethylene (LDPE), on wheat seed germination and seedlings' growth were explored under single and combined conditions. The results showed that Cd2+ solution and two kinds of microplastic leachates stimulated the wheat seed germination process but inhibited the germination rate by 0-8.6%. The combined treatments promoted wheat seed germination but inhibited the seedlings' growth to different degrees. Specifically, the combination of 2.0 mg L-1 Cd2+ and 1.0 mgC L-1 PVC promoted both seed germination and seedlings' growth, but they synergistically increased the antioxidant enzyme activity of seedlings. The toxicity of the PVC leachate to wheat seedlings was stronger than LDPE leachate. The addition of Cd2+ could alleviate the toxicity of PVC leachate on seedlings, and reduce the toxicity of LDPE leachate on seedlings under the same concentration class combinations but aggravated stress under different concentration classes, consistent with the effect on seedlings' growth. Overall, Cd2+, PVC, and LDPE leachates have toxic effects on wheat growth, whether treated under single or combined treatments. This study has important implications for the joint toxicity of Cd2+ solution and microplastic leachates in agriculture.

Long-term exposure to fine particulate matter constituents in relation to chronic kidney disease: evidence from a large population-based study in China.

The effects of long-term exposure to fine particulate matter (PM2.5) constituents on chronic kidney disease (CKD) are not fully known. This study sought to examine the association between long-term exposure to major PM2.5 constituents and CKD and look for potential constituents contributing substantially to CKD. This study included 81,137 adults from the 2018 to 2019 baseline survey of China Multi-Ethnic Cohort. CKD was defined by the estimated glomerular filtration rate. Exposure concentration data of 7 major PM2.5 constituents were assessed by satellite remote sensing. Logistic regression models were used to estimate the effect of each PM2.5 constituent exposure on CKD. The weighted quantile sum regression was used to estimate the effect of mixed exposure to all constituents. PM2.5 constituents had positive correlations with CKD (per standard deviation increase), with ORs (95% CIs) of 1.20 (1.02-1.41) for black carbon, 1.27 (1.07-1.51) for ammonium, 1.29 (1.08-1.55) for nitrate, 1.20 (1.01-1.43) for organic matter, 1.25 (1.06-1.46) for sulfate, 1.30 (1.11-1.54) for soil particles, and 1.63 (1.39-1.91) for sea salt. Mixed exposure to all constituents was positively associated with CKD (1.68, 1.32-2.11). Sea salt was the constituent with the largest weight (0.36), which suggested its importance in the PM2.5-CKD association, followed by nitrate (0.32), organic matter (0.18), soil particles (0.10), ammonium (0.03), BC (0.01). Sulfate had the least weight (< 0.01). Long-term exposure to PM2.5 sea salt and nitrate may contribute more than other constituents in increasing CKD risk, providing new evidence and insights for PM2.5-CKD mechanism research and air pollution control strategy.

Association and mediation analyses among multiple metal exposure, mineralocorticoid levels, and serum ion balance in residents of northwest China.

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou-Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose-response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.

Neurotoxic non-protein amino acids in commercially harvested Lobsters (Homarus americanus H. Milne-Edwards).

Cyanobacteria produce neurotoxic non-protein amino acids (NPAAs) that accumulate in ecosystems and food webs. American lobsters (Homarus americanus H. Milne-Edwards) are one of the most valuable seafood industries in Canada with exports valued at > $2 billion. Two previous studies have assessed the occurrence of ß-N-methylamino-L-alanine (BMAA) in a small number of lobster tissues but a complete study has not previously been undertaken. We measured NPAAs in eyeballs, brain, legs, claws, tails, and eggs of 4 lobsters per year for the 2021 and 2022 harvests. Our study included 4 male and 4 female lobsters. We detected BMAA and its isomers, N-(2-aminoethyl)glycine (AEG), 2,4-diaminobutyric acid (DAB) and ß-aminomethyl-L-alanine (BAMA) by a fully validated reverse phase chromatography-tandem mass spectrometry method. We quantified BMAA, DAB, AEG and BAMA in all of the lobster tissues. Our quantification data varied by individual lobster, sex and collection year. Significantly more BMAA was quantified in lobsters harvested in 2021 than 2022. Interestingly, more BAMA was quantified in lobsters harvested in 2022 than 2021. Monitoring of lobster harvests for cyanobacterial neurotoxins when harmful algal bloom events occur could mitigate risks to human health.

PI3K/Akt/FoxO Pathway Mediates Antagonistic Toxicity in HepG2 Cells Coexposed to Deoxynivalenol and Enniatins.

The emerging mycotoxins enniatins (ENNs) and the traditional mycotoxin deoxynivalenol (DON) often co-contaminate various grain raw materials and foods. While the liver is their common target organ, the mechanism of their combined effect remains unclear. In this study, the combined cytotoxic effects of four ENNs (ENA, ENA1, ENB, and ENB1) with DON and their mechanisms were investigated using the HepG2 cell line. Additionally, a population exposure risk assessment of these mycotoxins was performed by using in vitro experiments and computer simulations. The results showed that only ENA at 1/4 IC50 and ENB1 at 1/8 IC50 coexposed with DON showed an additive effect, while ENB showed the strongest antagonism at IC50 (CI = 3.890). Co-incubation of ENNs regulated the signaling molecule levels which were disrupted by DON. Transcriptome analysis showed that ENB (IC50) up-regulated the PI3K/Akt/FoxO signaling pathway and inhibited the expression of apoptotic genes (Bax, P53, Caspase 3, etc.) via phosphorylation of FoxO, thereby reducing the cytotoxic effects caused by DON. Both types of mycotoxins posed serious health risks, and the cumulative risk of coexposure was particularly important for emerging mycotoxins.

Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice.

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

Effect of total flavonoids of Dracocephalum moldavica L. On neuroinflammation in Alzheimer's disease model amyloid-ß (Aß1-42)-peptide-induced astrocyte activation.

One of the main pathological features noted in Alzheimer's disease (AD) is the presence of plagues of aggregated ß-amyloid (Aß1-42)-peptides. Excess deposition of amyloid-ß oligomers (AßO) are known to promote neuroinflammation. Sequentially, following neuroinflammation astrocytes become activated with cellular characteristics to initiate activated astrocytes. The purpose of this study was to determine whether total flavonoids derived from Dracocephalum moldavica L. (TFDM) inhibited Aß1-42-induced damage attributed to activated C8-D1A astrocytes. Western blotting and ELISA were used to determine the expression of glial fibrillary acidic protein (GFAP), and complement C3 to establish the activation status of astrocytes following induction from exposure to Aß1-42. Data demonstrated that stimulation of C8-D1A astrocytes by treatment with 40 µM Aß1-42 for 24 hr produced significant elevation in protein expression and protein levels of acidic protein (GFAP) and complement C3 accompanied by increased expression and levels of inflammatory cytokines. Treatment with TFDM or the clinically employed drug donepezil in AD therapy reduced production of inflammatory cytokines, and toxicity initiated following activation of C8-D1A astrocytes following exposure to Aß1-42. Therefore, TFDM similar to donepezil inhibited inflammatory secretion in reactive astrocytes, suggesting that TFDM may be considered as a potential compound to be utilized in AD therapy.

The transcriptomic signature of respiratory sensitizers using an alveolar model.

Environmental contaminants are ubiquitous in the air we breathe and can potentially cause adverse immunological outcomes such as respiratory sensitization, a type of immune-driven allergic response in the lungs. Wood dust, latex, pet dander, oils, fragrances, paints, and glues have all been implicated as possible respiratory sensitizers. With the increased incidence of exposure to chemical mixtures and the rapid production of novel materials, it is paramount that testing regimes accounting for sensitization are incorporated into development cycles. However, no validated assay exists that is universally accepted to measure a substance's respiratory sensitizing potential. The lungs comprise various cell types and regions where sensitization can occur, with the gas-exchange interface being especially important due to implications for overall lung function. As such, an assay that can mimic the alveolar compartment and assess sensitization would be an important advance for inhalation toxicology. Some such models are under development, but in-depth transcriptomic analyses have yet to be reported. Understanding the transcriptome after sensitizer exposure would greatly advance hazard assessment and sustainability. We tested two known sensitizers (i.e., isophorone diisocyanate and ethylenediamine) and two known non-sensitizers (i.e., chlorobenzene and dimethylformamide). RNA sequencing was performed in our in vitro alveolar model, consisting of a 3D co-culture of epithelial, macrophage, and dendritic cells. Sensitizers were readily distinguishable from non-sensitizers by principal component analysis. However, few differentially regulated genes were common across all pair-wise comparisons (i.e., upregulation of genes SOX9, UACA, CCDC88A, FOSL1, KIF20B). While the model utilized in this study can differentiate the sensitizers from the non-sensitizers tested, further studies will be required to robustly identify critical pathways inducing respiratory sensitization.