This study aimed to identify chemical compounds derived from Vassobia breviflora methanolic extract using ESI-ToF-MS and their antioxidant potential activity utilizing the following methods: total phenols, DPPH, and ABTS. The MTT assay measured cytotoxic activity, while DCFH-DA and nitric oxide assays were employed to determine reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels using African green monkey kidney (VERO) and human keratinocyte (HaCat) cell lines. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were assessed in seven clinical isolates and nine ATCC strains. Biofilm inhibition was tested against four biofilm-forming strains. The antioxidant properties of the methanolic extract were identified as follows: 35.74 mg GAE/g (gallic acid equivalents)/g for total phenols, 10.5 µg/ml for DPPH, and 50.68 µmol trolox/µg for ABTS. The mean inhibitory concentration (IC) values were 622.86 µg/ml (VERO) and 784.33 µg/ml (HaCat). These concentrations did not markedly alter levels of ROS and RNS. Conversely, β-hemolytic displayed higher sensitivity to the extract, with MIC of 64 µg/ml and MBC of 128 µg/ml. exhibited the lowest biofilm formation among the tested bacteria. The studied plant exhibited activity against all bacterial strains at concentrations lower than the IC50 VERO and HaCat cells, suggesting potential for future studies. Data present a comprehensive molecular docking analysis against the HlyIIR protein (PDB ID: 2FX0) and determined antimicrobial and endocrine-modulating potentials. Notably, lancifodilactone I and nicandrin B demonstrated the strongest binding affinities, with binding energies of -9.8 kcal/mol and -8.3 kcal/mol, respectively, and demonstrated significant antimicrobial effects against B. cereus. In addition, several compounds showed potential interactions with nuclear receptors, indicating potential endocrine-modulating effects. These findings provide insights into developing target-specific antimicrobial therapies and endocrine-modulating agents.

Designing ideal human biomonitoring studies involves the selection of reliable markers of exposure in adequate biological matrix. Besides conventional matrices such as blood or urine, hair has been increasingly investigated as a promising noninvasive alternative. However, understanding the pollutant distribution between differing biological compartments is essential for reliable interpretation of data collected. Therefore, the contamination levels and the distribution of some persistent (8 perfluoroalkyl substances - PFAS - and 6 polychlorobiphenyls - PCBs) and non-persistent pollutants (2 bisphenols and 3 parabens) were investigated in paired serum and hair samples, or paired spot urine and hair samples obtained from 30 Belgian non-occupationally exposed individuals. The levels measured were close to those reported in recent larger-scale studies. PFAS, PCB and bisphenol distributions largely differed depending upon the matrix and within the same chemical family depending upon the congener. The correlation and agreement between pollutant levels in differing matrices demonstrated that the information provided is comparable only for highly chlorinated PCBs and parabens, while the classification of exposure for bisphenols was substantially different according to the matrix. The selection of the human matrix thus remains complex and might markedly bias the results obtained, especially when assessing the health risk related to chemical exposure.

The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4-10 (murine endothelial) cell lines. Cell viability, migration, and clonogenicity were assessed using the following assays MTT, scratch, and colony formation. Antioxidant levels of GSH, as well as activities catalase (CAT), and superoxide dismutase (SOD) were measured. BSO alone exhibited minimal cytotoxic effects, while DOX alone reduced cell viability significantly. The combination of BSO+DOX decreased IC values for most cell lines, demonstrating a synergistic effect, especially in B16/F10, S180, and SVEC4-10 cells. BSO+DOX combination significantly inhibited cell migration and clonogenicity compared to DOX alone. While GSH levels were decreased with BSO+DOX treatment activities of CAT and SOD increased following DOX administration but remained unchanged by BSO. These results suggest that BSO may be considered a valuable tool to improve DOX therapeutic efficacy, particularly in cases of chemotherapy-resistant tumors, as BSO enhances DOX activity while potentially reducing systemic chemotherapeutic drug toxicity.

Chum. Schl. (Rosaceae) is used in traditional medicine as a remedy to treat diabetes and other diseases. However, there are reports that the extract of this plant and others of the genus may produce cellular and/or genetic toxicity. Niga-ichigoside F1 (NIF1) and 2β,3β-19α-trihydroxyursolic acid (2B) are major compounds found in extract known to exert pharmacological effects which may be responsible for the observed toxicity. Thus, this study was aimed to examine the cytogenotoxic potential of NIF1 and 2B in human peripheral blood mononuclear cells (PBMC) following acute exposure. Cytotoxicity was determined by trypan blue staining and genotoxicity by micronucleus and comet assays. Data obtained showed that both compounds, at concentrations ranging from 0.1 and 20 µg/ml, did not markedly affect cell viability. In addition, genetic toxicity testing (comet assay) detected no evidence of DNA damage or chromosomal mutations by the micronucleus test. Under these experimental conditions and considering that both compounds exhibit biological effects at low concentrations, it may be concluded that NIF1 and 2B did not induce cytogenotoxic effects in primary human PBMC.

Microcystin-LR (MC-LR), produced by cyanobacterial harmful algal blooms, poses a serious threat to aquatic ecosystems and human health. Biodegradation is an important method for MC-LR elimination. Aerobic biodegradation has been extensively studied and many bacteria were identified. However, few MC-degrading bacteria have been isolated from anaerobic environments, and these degradation mechanisms are poorly understood. The aim of this study was to collect anaerobic MC-degrading bacteria from lake sediments in Lake Taihu using acclimation culture to assess biodegradation. Five strains with MC-LR degradation ability were isolated, with strain A4 belonging to (). exhibiting the highest efficiency at 0.486 μg/ml/d. High-performance liquid chromatography (HPLC) identified two novel MC-LR degradation products. Further polymerase chain reaction (PCR) analysis suggested that A4 did not possess the known MC-degrading gene , suggesting the involvement of an -independent anaerobic degradation pathway. Data demonstrated that the bacterial strain A4 found in Lake Taihu exhibited high anaerobic MC-LR degradation properties, which indicated that anaerobic biodegradation may constitute an important biological method for MC-LR removal in natural environment.

Myocardial ischemia reperfusion injury (MIRI) remains a major clinical challenge. Polyphenols derived from L (PPA) were found to possess anti-hypoxic-ischemic . The aim of this study was to examine (1) whether this plant exerts a protective effect and (2) whether the underlying mechanisms involving inflammatory responses and the Wnt/β-catenin signaling pathway were involved in rats. Rats were randomly divided as follows (1): Sham operation (2); ischemia-reperfusion (MIRI) (3); polyphenols (PPA) (4); Wnt inhibitor group (XAV939). In cardiomyocytes (1), HE staining was used to examine morphology (2), enzyme-linked immunosorbent assay to determine interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels and (3) Western blot to measure protein expression of Wnt and β-catenin. HE staining showed in MIRI edema of cardiomyocytes, localized inflammatory cell infiltration, unclear outline of cells and cell fragmentation, and some cardiomyocytes were seen to have disordered arrangement of tissues. PPA markedly lowered the morphological alterations in MIRI. The levels of levels of IL-1β and TNF-α in MIRI were significantly elevated; however, PPA reduced these cytokine concentrations compared to MIRI. Western blot analysis demonstrated that MIRI increased the relative protein expression levels of Wnt and β-catenin. Treatment of MIRI with PPA resulted in a significant decrease in protein expression levels of Wnt and β-catenin. The involvement of the Wnt/β-catenin pathway in MIRI was further affirmed with the use Wnt inhibitor group (XAV939) that also diminished protein expression levels of Wnt and β-catenin.

The larvicidal effect of dillapiole and its semi-synthetic derivatives on (), the main transmitter of arboviruses such as dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV), is well - established. Among dillapiole derivatives, the -butyl ether dillapiole stands out attributed to significant larvicidal potential against . However, studies are needed to assess the adverse risk following exposure to this chemical on non-target organisms. The aim of this study was to examine the risk of toxic consequences attributed to exposure to dillapiole -butyl ether (DBE) by determining pharmacokinetic, biochemical and histopathological parameters. Dillapiole -butyl ether was tested utilizing male Balb/C mice at concentrations of 10, 20 or 40 mg/kg. Subsequently, peripheral blood was obtained for biochemical analyses, kidney and livers for histopathological examination. DBE decreased serum creatinine levels et 10 or 40 mg/kg. Urea levels were reduced at 10 mg/kg but elevated at 20 mg/kg. Serum gamma-GT was significantly lowered at 40 mg/kg. Alkaline phosphatase activity was significantly decreased at 20 and 40 mg/kg/. In contrast, alanine aminotransferase activity was significantly elevated. At concentrations of 10 and 20 mg/kg DBE, dose-dependent elevation in number of binucleated hepatocytes, steatosis (micro- and macrovacuolar) and necrotic foci were observed. In kidney, progressive impairment of glomerular and tubular structure was detected accompanied by inflammation, degeneration, and cellular necrosis more pronounced at higher doses, resulting in significant loss of renal parenchyma at 40 mg/kg. Data demonstrate that DBE initiated dose-dependent hepatic and renal structural changes.

Parkinson's Disease (PD) a progressive neurodegenerative disorder is attributed to dopaminergic neuronal cell loss in the mid-brain substantia nigra pars compacta. A major risk factors associated with PD development is presence of excess oxidative stress. Previously, glycosides derived from were reported to play a key role in counteracting PD; however, the underlying mechanisms remain to be determined. This study aimed to examine the neuroprotective effect attributed to glycosides derived from in PD model in mice. The model of PD was established by injecting intraperitoneally 1-methyl-4-penyl-1,2,3,6-tetrahydropyridine (MPTP). Rotarod and pole tests determined neurological behavior. The following immunohistochemistry, and metabolic biomarkers were measured mid-brain substantia nigra: (1) number of dopaminergic neuronal cell using immunohistochemistry (2) oxidative stress as evidenced by activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well levels of malondialdehyde (MDA), (3) inflammatory infiltration as measured by levels of IL-1β and TNF-α (4) by Western blot involvement of protein expression levels of Nrf2 signaling pathway. Data demonstrated that glycosides treatment improved behavioral performance, increased number of dopaminergic neurons, reduced cytokine levels of IL-1β and TNF-α accompanied by enhanced antioxidant activity in PD mice. These observations were associated with activation of Nrf2 signaling pathway. Data suggest that glycosides may thus be considered as an alternative compound for PD treatment.

(Vochysiaceae), present in the flooded fields of Pantanal in the state of Mato Grosso, Brazil, is traditionally used to treat infections. However, studies on the toxicological safety of using the stem bark of this vegetable are lacking. This study aimed to investigate acute oral toxicity using rats, genotoxicity utilizing mice, and toxicity to non-vertebrate animals, the insect and the nematode following exposure to stem bark ethanolic extract (VDSE). In addition, phytochemical analyses were performed using HPLC-PDA, and the total triterpene content in VDSE was determined. At 2000 mg/kg, VDSE did not induce acute toxicity. In mice treated with different VDSE doses (500, 1000, or 2000 mg/kg), no chromosomal damages or altered ratios of polychromatic erythrocytes to total erythrocytes were noted. VDSE also did not induce toxicity to as evidenced by 100% survival. The extract contained a total triterpene content of 780 mg g (39%). Since VDSE exerts a beneficial role in treating infections, it is essential to determine the risks associated with consuming these plant species to establish safety. Consequently, the present results expand knowledge regarding VDSE chemical quality control and safety.

The covalent binding of sensitizer to skin proteins is referred to as key event 1 of the adverse outcome pathway in skin sensitization. Recently, -acetyl-L-cysteine methyl ester (NACME) was demonstrated to react selectively with skin sensitizers , such that NACME might be applied as an electron donor in developing a spectrophotometric test for determining skin sensitization potential of chemicals. To avoid possible color interference by certain test chemicals, a fluorometric test method was developed using monobromobimane (mBBr), a thiol-reactive fluorescent probe. Similar to previous methods utilizing the reaction of NACME with sensitizers, unreacted NACME occurred which was then measured fluorometrically using mBBr, rather than 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Following the optimization of test conditions, the same 64 test chemicals used in the previous study were tested to determine the predictive capacity of the current method. Results showed a predictive capacity of 81.1% sensitivity, 81.5% specificity, and 81.3% accuracy with a cutoff NACME depletion of 11.3%. Although these values were relatively lower than the previous test using DTNB, the results were still comparable to OECD-approved test methods and that color interference issues might be ruled out. Data demonstrated that NACME might be viewed as a candidate for identifying reactive skin sensitizers. Further, this method might be considered as a complementary or supportive method to the former DTNB assay as a screening tool for assessing the tendency of a chemical to initiate skin sensitization in case of test chemicals showing color interference.

Neuropathic pain (NP) consists of a range of unpleasant sensations attributed to a lesion or a disease of the somatosensory nervous system. It is important to note that the sensations initiated by NP are debilitating and adversely affect quality of life; however, the underlying mechanisms involved in the occurrence and development of this type of pain remain to be determined. Previously data demonstrated that inhibition of TLR4/NF-κB signaling pathway diminished the adverse consequences attributed to NP. Thus, the purpose of this study was to examine whether saponins derived from might exert an analgesic effect on NP in rats using a chronic constriction injury (CCI) involving sciatic nerve. Male rats were randomly divided into Sham, CCI, low 100 mg/kg , high 200 mg/kg , and compared to pregabalin 10 mg/kg, the recognized first line of defense in NP. Three days after surgery, rats were treated with sham control (water) or drugs. The paw mechanical withdrawal threshold (PMWT) and thermal latency (TL) of rats were measured 1 day before operation and 3, 7, and 10 days after. Nissl staining was used to observe the morphology and Western Blot to detect protein expression of NF-κB and TLR4 on the 10th day after operation. ELISA was employed to detect levels of IL-1β, IL-6, and TNF-ɑ in spinal cord. CCI significantly decreased PMWT and TL. In CCI neurons and glial cells in the spinal dorsal horn were deeply stained with swelling and atrophy observed. The protein expression levels of NF-κB and TLR4 in the spinal dorsal horn of the injured side were significantly increased accompanied by elevated levels of inflammatory mediators IL-1β, IL-6, and TNF-ɑ. Treatment with low 100 mg/kg or high 200 mg/kg or pregabalin reduced effects of CCI on PMW, TL, histopathological changes as well as levels of inflammatory cytokines IL-1β and IL-6 associated with inhibition of TLR4/NF-κB pathway. Data suggest that exerts an analgesic effect on peripheral NP which involves TLR4/NF-κB pathway inhibition.

Alzheimer 's disease, a neurodegenerative disease, is considered a serious global type of dementia affecting predominantly elderly associated with progressive memory loss. Alzheimer 's disease exhibits typical pathological manifestations including neuronal loss, β-amyloid deposition, and tau protein neurofibrillary tangles. Significantly increased expression of long-non -coding transcript RNA, LncRNA SNHG1, was detected in the brain of AD patients. However, it is not clear whether knockdown of LncRNA SNHG1 might improve autophagy function in SH-SY5Y cells and reduce the number of apoptotic cells. The aim of this study was to (1) examine the role of LncRNA SNHG1 on autophagic function of SH-SY5Y cells following induction by Aβ1-42 and (2) elucidate the underlying mechanisms. SH-SY5Y cells were transfected with lentiviral vectors to construct a cell line with stable genetic ability to knock down LncRNA SNHG1 and compared to control empty vector cell line. Following induction with Aβ1-42 for 24 hr, an AD cell model was constructed. Downregulation with LncRNA SNHG1 significantly increased cell viability and lowered the number of apoptotic cells. Concomitantly downregulation of the expression of LncRNA SNHG1 in SH-SY5Y cells induced significant decrease in expression of p-tau and caspase3 associated with elevated expression of Beclin1 and AMBRA1. Our results showed that knockdown of LncRNA SNHG1 in SH-SY5Y cells reduced the number of apoptotic cells by enhancing expression of Beclin1 and AMBRA1. Data suggest that by knocking down the expression of LncRNA SNHG1 may be considered a potential target for compounds to treat AD.

This study investigated the potential pulmonary toxicity of polycarbonate (PC) emissions from fused filament fabrication (FFF) three-dimensional printing (3DP) via inhalation in Sprague Dawley rats. Previously, our results demonstrated no significant pulmonary effects following exposure to a 0.5 mg/m PC. A new exposure apparatus was developed that exposed animals at a concentration of 2.5 mg/m. Sixty rats were randomized into control (filtered air) and exposure groups ( = 30/group). Each group was further divided into five subgroups ( = 6/subgroup) with exposure durations of 1, 4, 8, 15, or 30 days (4 hr/day, 4 days/week). Following a 24-hr post-exposure period, body weight was measured, and blood samples were collected for hematological and biochemical analysis. Bronchoalveolar lavage fluid (BALF) was obtained from the right lung for cytology. The left lung and head/nasal tissues were preserved for histopathological evaluation. Lung deposition was estimated using the Multiple-Path Particle Dosimetry model, electron microscopy, and enhanced darkfield microscopy. In addition, filter samples were collected to measure bisphenol A. Exposure resulted in an estimated deposition of 0.28 µg/day within the alveoli and small airways. Microscopy indicated limited evidence of macrophage uptake. No significant changes were observed in BALF cell counts, lactate dehydrogenase activity, or hematological parameters. BALF levels of tissue inhibitor of metalloproteinases-1 and protein were elevated in the 30-day exposure group, although histopathology revealed no exposure-related changes in the lungs. In conclusion, this study found no marked pulmonary inflammation or toxicity in rats exposed to 2.5 mg/m of PC 3D printing emissions for up to 30 days (4 hr/day).

Acteoside, a naturally occurring compound found in various plants, was found to exert antihyperlipidemic effects; however, the underlying mechanisms in nonalcoholic fatty liver disease associated with type 2 diabetes remain to be elucidated. This study aimed to examine (1) acteoside initiated hepatoprotection in diabetic mice and (2) whether the beneficial actions involved activation of Nrf2/HO-1 signaling pathway. Male mice given a high fat diet were injected with streptozotocin (STZ 50 mg/kg) to initiate type 2 diabetes mellitus (T2DM). Animals were randomly assigned to four groups (10 animals per group): (1) control, (2) diabetes, (3) acteoside (70 mg/kg) and (4) metformin (250 mg/kg). In diabetic mice, a significant increase in plasma levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) was accompanied by a fall in high-density lipoprotein (HDL). In diabetes, malondialdehyde (MDA) content was elevated in serum, accompanied by a decrease in superoxide dismutase (SOD) activity. Treatment with acteoside was found to significantly reduce plasma levels TC, TG, LDL, and VLDL accompanied by elevation in HDL, lowered MDA content accompanied by a rise in SOD activity. The metabolic alterations induced by metformin, the drug of choice in T2DM were similar to those noted for acteoside. Results showed that beneficial effects of acteoside involved activation of the Nrf2/HO-1 pathway. The potent antioxidant properties and lipid-lowering effects attributed to acteoside in T2DM may be considered as a promising therapeutic candidate for diabetic liver disease.

bark traditionally used in folk medicine attributed to its anti-inflammatory properties is due to the presence of bergenin. This study aimed to determine the toxicological parameters associated with exposure to a phenolic-enriched extract of bark and bergenin a bioactive byproduct of this compound. The total phenolic and flavonoid contents were determined through spectrometric analyses, while phenolic compounds were identified using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-MS). Antioxidant activity was assessed in vitro using the DPPH assay. Cytotoxicity and genotoxicity were assessed via the MTT assay and comet assay, respectively, whereas mutagenic activity was examined using Salmonella/microsome assay and micronucleus (MN) test. A high content of phenolic (732.22 ± 9.48 mg/g) GAE (gallic acid equivalence) and flavonoid 252.47 ± 5.7 mg/g QE (quercetin) compounds was found in bergenin the phenolic-enriched extract byproduct as well as isomers of gallic acid, epicatechin, isoquercitrin, castalagin, punicalin, and punicalagin. The DPPH value was 23.74 ± 0.45 μg/ml. In MTT assay, the extract exhibited an IC50 of 72.5 ± 2.6 µg/ml. Both extract and bergenin displayed genotoxic activity in L929 fibroblast cells at 50 µg/ml but not mutagenic effects in the Salmonella/microsome assay or MN test. Despite the genotoxic actions, bark and bergenin extract did not induce gene or chromosomal mutations, suggesting a low risk of compromising genomic stability. The presence of bioactive compounds such as bergenin and punicalagin in bark demonstrates a therapeutic potential of this native tree for treating inflammatory diseases.

Natural products, although frequently associated with beneficial effects and considered harmless, still require thorough analysis; therefore, their bioactive compounds need to be used with caution. Biological assays using plant models represent an appropriate alternative for evaluating the cytogenotoxicity associated with these products. In this study, the phyto- cytotoxic potential of extracts from the bark of DC. a species widely used for treatment of constipation was investigated due to its anthraquinone content. To this end, seeds of L. were employed in phyto-cytogenotoxic assays under chronic exposure to lyophilized and spray-dried extracts. The results showed that extraction methods directly influence the phytochemical composition and biological effects of the extracts. Both extracts exhibited high anthraquinone content, expressed as cascaroside A, with concentrations ranging from 45.65 to 72.17 μg/ml. The spray-dried extract demonstrated a more potent inhibitory effect on morphological parameters, such as root elongation, while lyophilized extract exhibited higher cytotoxicity. Both extracts induced mitodepressive effects and aneugenic damage. Notably, the lyophilized extract induced a 300% increase in mitotic abnormalities compared to control, with a higher frequency of C-metaphases and stickiness. Although is widely used in traditional medicine, the scarcity of studies on cascaroside A raises concerns regarding socio-environmental safety and continued use of this species in dietary supplements.

Infants' and children's health is particularly susceptible to exposure to various environmental contaminant insults as their immune systems are immature and daily activities may present differing patterns of exposure. Although some studies noted an association between long-term exposure to ambient fine particulate matter (PM) and increased infant mortality frequency, few investigations examined the relationship between reduced exposure to PM and changes in infant mortality rates. Therefore, this study was conducted to determine whether diminished levels of PM in Taiwan improved post-neonatal infant health. Avoidable premature post-neonatal infant mortality was employed as an indicator of health impact. A mean value was calculated for annual PM levels across Taiwan for the years 2006, 2015, and 2023. Using these averages and following WHO methodology, differences in the number of post-neonatal infant deaths attributed to ambient PM exposure were determined. PM concentrations fell markedly throughout Taiwan over the 20-year study period. In conjunction with this decline, a lowered health burden was noted, which was represented as a fall in post-neonatal infant deaths (14.8% in 2006 to 10.3% in 2023). Reduction in annual levels of PM to 10 µg/m was associated with a decrease in the total burden of post-neonatal infant mortality occurrence, with a 5.58-9.31% decline in PM-related deaths during that period. Evidence indicates that exposure to PM air pollution poses a significant burden to Taiwan children's health. Our findings indicate that the potential benefits to children's health need to be given importance when considering improving air quality policies.

Cerebral ischemia-reperfusion injury (CIRI) is a prevalent clinical complication associated with reperfusion following ischemic stroke resulting in neuronal damage and cognitive impairment. Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist with sedative, and analgesic properties, is frequently utilized as a sedative anesthetic in clinical surgeries, and believed to play a crucial role in the prognosis of patients suffering from CIRI. However, the mechanism underlying DEX in CIRI remains to be determined. This study aimed to investigate the neuroprotective effects of Dex in rats suffering from CIRI. In the treatment group, DEX (50 µg/kg) was administered intraperitoneally 30 min prior to surgery. Middle cerebral artery occlusion (MCAO) used as a model of CIRI occurred with cerebral artery occlusion for 2 h was followed by reperfusion with blood for 24, 72, 120 or 168 h. Neurological function as assessed by the Longa neurological function score test demonstrated significantly reduced neurological scores and increased % infarct size in MCAO group which was blocked by DEX suggesting that DEX might be effective in treating ischemic stroke. In the MCAO animals, 2,3,5-triphenyltetrazolium chloride (TTC) showed large marked areas of cerebral infarction which were diminished in size by DEX. Using Western blot analysis, results showed that in MCAO rats protein expression levels of TNF-α and IL-6 were increased accompanied by reduced protein expression levels of PI3K/AKT signaling pathway. DEX pretreatment reversed the effects of MCAO as evidenced by decrease in protein expression levels of TNF-α and IL-6 associated with elevated protein expression levels of PI3K/AKT/NF-κB signaling pathway. Data demonstrated that DEX pretreatment improved the neuromotor performance and cognitive functions in animals suffering from consequences of MCAO by diminishing inflammation and activation of the PI3K/AKT/NF-κB signaling pathway.

Hazardous noise is a pervasive environmental pollutant with significant adverse health impacts on auditory and non-auditory organs. It is noteworthy that even acute noise exposure might pose immediate detrimental effects to various organs. However, the long-term effects of acute noise exposure remain largely unknown. This study aimed to explore this gap by randomizing 12 Long-Evans rats into acute noise and control groups. The acute noise regimen was a single three-hr wideband noise (12.5 hz-20 kHz) at 105 dB SPL. Four weeks following exposure cessation, animals from both groups were sacrificed. Genomic DNA and RNA were extracted from the cochlea, brain, heart, and liver. Long-target polymerase assays and real-time quantitative polymerase chain reactions were performed to assess DNA integrity and p53-targeted gene expression, respectively, with results being compared between the two groups. Data demonstrated that noise-induced changes in DNA integrity depended upon organ type, with significant interaction effects between treatment conditions (noise or control) and organ type for nuclear and mitochondrial DNA integrity. In addition, there were significant changes in p53-targeted gene expression between noise-exposed and control in all tested organs. In conclusion, the long-term impact of acute hazardous noise exposure on DNA integrity was complex, highlighting organ-specificity in response to noise. However, such noise significantly altered p53-targeted genes systemically, indicating ongoing cellular stress. Overall, these results suggest that acute exposure to hazardous noise may have potential long-term adverse consequences. Immediate care following exposure might mitigate possible impacts on long-term health.

Inflammatory bowel disease (IBD) is a complex gastrointestinal disorder attributed to genetic and environmental factors. Microcystin-leucine-arginine (MC-LR) is an environmental toxin that accumulates in the gut and produces intestinal damage. The aim of this study was to investigate the effects of exposure to MC-LR on development and progression of IBD as well examine the underlying mechanisms of microcystin-initiated tissue damage. Male C57BL/6 mice were treated with either MC-LR alone or concurrently with dextran-sulfate sodium (DSS). Mice were divided into 4 groups (1): PBS gavage (control, CT) (2); 200 μg/kg MC-LR gavage (MC-LR) (3); 3% DSS Drinking Water (DSS); and (4) 3% DSS Drinking Water + 200 μg/kg MC-LR gavage (DSS + MC-LR). The mice in each experimental group exhibited reduced body weight, shortened colon length, increased disease activity index (DAI) score, a disrupted intestinal barrier, and elevated levels of proinflammatory cytokines compared to control. Compared to the group treated with MC-LR alone, colitis symptoms were exacerbated following combined exposure to both DSS and MC-LR. Subsequent experiments confirmed that MC-LR or DSS increased protein phosphorylation levels of Janus Kinase1 (JAK1) and Signal Transducer and Activator of Transcription3 (STAT3). Compared to group treated with MC-LR alone, the combined treatment of DSS and MC-LR also significantly upregulated the expression of related proteins. In conclusion, our study indicates that MC-LR-induced colitis involves activation of JAK1/STAT3 signaling pathway and that MC-LR exacerbates DSS-induced colitis through the same pathway.

This study aimed to examine the dose-response effects of polyphenon-60 derived from green tea (P60-GT) on hexavalent chromium [Cr(VI)]-induced genotoxic damage and apoptosis. Male Hsd:ICR mice were divided into 4 groups: (1) Control (vehicle only), (2) P60-GT (15, 30, or 45 mg/kg gavage), (3) Cr(VI) (20 mg/kg of CrO intraperitoneally), and (4) P60-GT+CrO (P60-GT administered 4 hr before CrO). Peripheral blood samples were collected at 24, 48, and 72 hr to assess the number of micronuclei (MN), apoptosis, and cell viability, while plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured at 0 and 48 hr. Cr(VI) significantly increased MN frequency, suppressed 8-OHdG repair, and reduced cell viability. Pre-treatment with P60-GT reduced MN frequency by up to 74%, with the 30 mg/kg dose demonstrating the highest efficacy. This dose restored cell viability, enhanced 8-OHdG repair, and enhanced apoptosis, suggesting activation of DNA repair and apoptotic pathways as potential antigenotoxic mechanisms. The 15 mg/kg dose exhibited anti-apoptotic effects, while the 30 and 45 mg/kg doses promoted apoptosis. However, the 45 mg/kg dose resulted in 100% lethality by 72 hr, likely due to synergistic toxicity with Cr(VI). These findings demonstrate the dose-dependent protective effects of P60-GT and emphasize the need for dosage optimization to maximize therapeutic benefits while minimizing toxicity.