Accessing diverse bicyclic peptide conformations using 1,2,3-TBMB as a linker.

Bicyclic peptides are a powerful modality for engaging challenging drug targets such as protein-protein interactions. Here, we use 1,2,3-tris(bromomethyl)benzene (1,2,3-TBMB) to access bicyclic peptides with diverse conformations that differ from conventional bicyclisation products formed with 1,3,5-TBMB. Bicyclisation at cysteine residues under aqueous buffer conditions proceeds efficiently, with broad substrate scope, compatibility with high-throughput screening, and clean conversion (>90%) for 96 of the 115 peptides tested. We envisage that the 1,2,3-TBMB linker will be applicable to a variety of peptide screening techniques in drug discovery.

Oligo(styryl)benzenes liposomal AIE-dots for bioimaging and phototherapy in an in vitro model of prostate cancer.

Whilst the development of advanced organic dots with aggregation-induced emission characteristics (AIE-dots) is being intensively studied, their clinical translation in efficient biotherapeutic devices has yet to be tackled. This study explores the synergistic interplay of oligo(styryl)benzenes (OSBs), potent fluorogens with an increased emission in the aggregate state, and Indocyanine green (ICG) as dual Near Infrared (NIR)-visible fluorescent nanovesicles with efficient reactive oxygen species (ROS) generation capacity for cancer treatment using photodynamic therapy (PDT). The co-loading of OSBs and ICG in different nanovesicles has been thoroughly investigated. The nanovesicles' physicochemical properties were manipulated via molecular engineering by modifying the structural properties of the lipid bilayer and the number of oligo(ethyleneoxide) chains in the OSB structure. Diffusion Ordered Spectroscopy (DOSY) NMR and spectrofluorometric studies revealed key differences in the structure of the vesicles and the arrangement of the OSB and ICG in the bilayer. The in vitro assessment of these OSB-ICG nanovesicles revealed that the formulations can increase the temperature and generate ROS after photoirradiation, showing for the first time their potential as dual photothermal/photodynamic (PTT/PDT) agents in the treatment of prostate cancer. Our study provides an exciting opportunity to extend the range of applications of OSB derivates to potentiate the toxicity of phototherapy in prostate and other types of cancer.

Treatment of Helicobacter pylori with potassium competitive acid blockers: A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (H. pylori) infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating H. pylori is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there's growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for H. pylori eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for H. pylori eradication. AIM: To assess the efficacy of regimens containing P-CABs in eradicating H. pylori infection. METHODS: This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [("Helicobacter pylori" OR "H pylori") AND ("Treatment" OR "Therapy" OR "Eradication") AND ("Vonaprazan" OR "Potassium-Competitive Acid Blocker" OR "P-CAB" OR "PCAB" OR "Revaprazan" OR "Linaprazan" OR "Soraprazan" OR "Tegoprazan")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H. pylori were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and H. pylori eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated. RESULTS: A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in H. pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, P < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, P < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, P = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, P = 0.3), respectively. CONCLUSION: VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H. pylori, positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

Risk assessment of Benzene, Toluene, Ethyl benzene, and Xylene (BTEX) in the atmospheric air around the world: A review.

Volatile organic compounds, such as BTEX, have been the subject of numerous debates due to their detrimental effects on the environment and human health. Human beings have had a significant role in the emergence of this situation. Even though US EPA, WHO, and other health-related organizations have set standard limits as unhazardous levels, it has been observed that within or even below these limits, constant exposure to these toxic chemicals results in negative consequences as well. According to these facts, various studies have been carried out all over the world - 160 of which are collected within this review article, so that experts and governors may come up with effective solutions to manage and control these toxic chemicals. The outcome of this study will serve the society to evaluate and handle the risks of being exposed to BTEX. In this review article, the attempt was to collect the most accessible studies relevant to risk assessment of BTEX in the atmosphere, and for the article to contain least bias, it was reviewed and re-evaluated by all authors, who are from different institutions and backgrounds, so that the insights of the article remain unbiased. There may be some limitations to consistency or precision in some points due to the original sources, however the attempt was to minimize them as much as possible.

Exposure to volatile organic compounds and mortality in US adults: A population-based prospective cohort study.

Volatile organic compounds (VOCs) are ubiquitous in both indoor and outdoor environments. Evidence on the associations of individual and joint VOC exposure with all-cause and cause-specific mortality is limited. Measurements of 15 urinary VOC metabolites were available to estimate exposure to 12 VOCs in the National Health and Nutritional Examination Survey (NHANES) 2005-2006 and 2011-2018. The environment risk score (ERS) was calculated using LASSO regression to reflect joint exposure to VOCs. Follow-up data on death were obtained from the NHANES Public-Use Linked Mortality File through December 31, 2019. Cox proportional hazard models and restricted cubic spline models were applied to evaluate the associations of individual and joint VOC exposures with all-cause and cause-specific mortality. Population attributable fractions were calculated to assess the death burden attributable to VOC exposure. During a median follow-up of 6.17 years, 734 (8.34 %) deaths occurred among 8799 adults. Urinary metabolites of acrolein, acrylonitrile, 1,3-butadiene, and ethylbenzene/styrene were significantly associated with all-cause, cardiovascular disease (CVD), respiratory disease (RD), and cancer mortality in a linear dose-response manner. Linear and robust dose-response relationships were also observed between ERS and all-cause and cause-specific mortality. Each 1-unit increase in ERS was associated with a 33.6 %, 39.1 %, 109.8 %, and 67.8 % increase for all-cause, CVD, RD, and cancer mortality risk, respectively. Moreover, joint exposure to VOCs contributed to 17.95 % of all-cause deaths, 13.49 % of CVD deaths, 35.65 % of RD deaths, and 33.85 % of cancer deaths. Individual and joint exposure to VOCs may enhance the risk of all-cause and cause-specific mortality. Reducing exposure to VOCs may alleviate the all-cause and cause-specific death burden.

Exposure to benzene, toluene, ethylbenzene, and xylene (BTEX) at Nigeria's petrol stations: a review of current status, challenges and future directions.

Introduction: In Nigeria, because of increasing population, urbanization, industrialization, and auto-mobilization, petrol is the most everyday non-edible commodity, and it is the leading petroleum product traded at the proliferating Nigeria's petrol stations (NPSs). However, because of inadequate occupational health and safety (OHS) regulatory measures, working at NPSs exposes petrol station workers (PSWs) to a large amount of hazardous benzene, toluene, ethylbenzene, and xylene (BTEX) compounds. Methods: Studies on BTEX exposures among Nigerian PSWs are scarce. Thus, constraints in quantifying the health risks of BTEX limit stakeholders' ability to design practical risk assessment and risk control strategies. This paper reviews studies on the OHS of Nigerian PSWs at the NPSs. Results: Although knowledge, attitude, and practices on OHS in NPSs vary from one Nigeria's study setting to another, generally, safety practices, awareness about hazards and personal protective equipment (PPE), and the use of PPE among PSWs fell below expectations. Additionally, air quality at NPSs was poor, with a high content of BTEX and levels of carbon monoxide, hydrogen sulfide, particulate matter, and formaldehyde higher than the World Health Organization guideline limits. Discussion: Currently, regulatory bodies' effectiveness and accountability in safeguarding OHS at NPSs leave much to be desired. Understanding the OHS of NPSs would inform future initiatives, policies, and regulations that would promote the health and safety of workers at NPSs. However, further studies need to be conducted to describe the vulnerability of PSWs and other Nigerians who are occupationally exposed to BTEX pollution. More importantly, controlling air pollution from hazardous air pollutants like BTEX is an essential component of OHS and integral to attaining the Sustainable Development Goals (SDG) 3, 7, and 11.

The Impact of Environmental Benzene, Toluene, Ethylbenzene, and Xylene Exposure on Blood-Based DNA Methylation Profiles in Pregnant African American Women from Detroit.

African American women in the United States have a high risk of adverse pregnancy outcomes. DNA methylation is a potential mechanism by which exposure to BTEX (benzene, toluene, ethylbenzene, and xylenes) may cause adverse pregnancy outcomes. Data are from the Maternal Stress Study, which recruited African American women in the second trimester of pregnancy from February 2009 to June 2010. DNA methylation was measured in archived DNA from venous blood collected in the second trimester. Trimester-specific exposure to airshed BTEX was estimated using maternal self-reported addresses and geospatial models of ambient air pollution developed as part of the Geospatial Determinants of Health Outcomes Consortium. Among the 64 women with exposure and outcome data available, 46 differentially methylated regions (DMRs) were associated with BTEX exposure (FDR adjusted p-value < 0.05) using a DMR-based epigenome-wide association study approach. Overall, 89% of DMRs consistently exhibited hypomethylation with increasing BTEX exposure. Biological pathway analysis identified 11 enriched pathways, with the top 3 involving gamma-aminobutyric acid receptor signaling, oxytocin in brain signaling, and the gustation pathway. These findings highlight the potential impact of BTEX on DNA methylation in pregnant women.

Ambient air pollutants and breast cancer stage in Tehran, Iran.

This study aimed to examine the impacts of single and multiple air pollutants (AP) on the severity of breast cancer (BC). Data of 1148 diagnosed BC cases (2008-2016) were obtained from the Cancer Research Center and private oncologist offices in Tehran, Iran. Ambient PM10, SO2, NO, NO2, NOX, benzene, toluene, ethylbenzene, m-xylene, p-xylene, o-xylene, and BTEX data were obtained from previously developed land use regression models. Associations between pollutants and stage of BC were assessed by multinomial logistic regression models. An increase of 10 µg/m3 in ethylbenzene, o-xylene, m-xylene, and 10 ppb of NO corresponded to 10.41 (95% CI 1.32-82.41), 4.07 (1.46-11.33), 2.89 (1.08-7.73) and 1.08 (1.00-1.15) increase in the odds of stage I versus non-invasive BC, respectively. Benzene (OR, odds ratio = 1.16, 95% CI 1.01-1.33) and o-xylene (OR = 1.18, 1.02-1.38) were associated with increased odds of incidence of BC stages III & IV versus non-invasive stages. BC stage I and stage III&IV in women living in low SES areas was associated with significantly higher levels of benzene, ethylbenzene, o-xylene, and m-xylene. The highest multiple-air-pollutants quartile was associated with a higher odds of stage I BC (OR = 3.16) in patients under 50 years old. This study provides evidence that exposure to AP is associated with increased BC stage at diagnosis, especially under premenopause age.

Co-exposure of petrochemical workers to noise and mixture of benzene, toluene, ethylbenzene, xylene, and styrene: Impact on mild renal impairment and interaction.

Epidemiological evidence concerning effects of simultaneous exposure to noise and benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) on renal function remains uncertain. In 2020, a cross-sectional study was conducted among 1160 petrochemical workers in southern China to investigate effects of their co-exposure on estimated glomerular filtration rate (eGFR) and mild renal impairment (MRI). Noise levels were assessed using cumulative noise exposure (CNE). Urinary biomarkers for BTEXS were quantified. We found the majority of workers had exposure levels to noise and BTEXS below China's occupational exposure limits. CNE, trans, trans-muconic acid (tt-MA), and the sum of mandelic acid and phenylglyoxylic acid (PGMA) were linearly associated with decreased eGFR and increased MRI risk. We observed U-shaped associations for both N-acetyl-S-phenyl-L-cysteine (SPMA) and o-methylhippuric acid (2-MHA) with MRI. In further assessing the joint effect of BTEXS (ß, -0.164 [95% CI, -0.296 to -0.033]) per quartile increase in all BTEXS metabolites on eGFR using quantile g-computation models, we found SPMA, tt-MA, 2-MHA, and PGMA played pivotal roles. Additionally, the risk of MRI associated with tt-MA was more pronounced in workers with lower CNE levels (P = 0.004). Multiplicative interaction analysis revealed antagonisms of CNE and PGMA on MRI risk (P = 0.034). Thus, our findings reveal negative dose-effect associations between noise and BTEXS mixture exposure and renal function in petrochemical workers. With the exception of toluene, benzene, xylene, ethylbenzene, and styrene are all concerning pollutants for renal dysfunction. Effects of benzene, ethylbenzene, and styrene exposure on renal dysfunction were more pronounced in workers with lower CNE.

Progress toward the Total Synthesis of Nogalamycin Using a Benzyne Cycloaddition Strategy.

Nogalamycin (NOG) is a member of the anthracycline glycoside natural products; no total syntheses have yet been reported, and there is minimal understanding of how the aglycone substitution pattern and identities of the A- and D-ring sugars impact the anticancer activity and toxicity. This paper reports progress toward a modular approach to NOG that could enable systematic structure-activity relationship studies. Key steps include a regioselective benzyne cycloaddition and reductive ring-opening to assemble a versatile AB core for analogue synthesis.

Exposure to BTEX is associated with cardiovascular disease, dyslipidemia and leukocytosis in national US population.

BACKGROUND: Comprehensive research on the effects of individual benzene, toluene, ethylbenzene, and xylenes (BTEX) and their mixture measured in blood samples, on cardiovascular diseases (CVD) and related risk factors among the general population is limited. OBJECTIVES: To investigate the effects of blood individual and mixed BTEX on total CVD and its subtypes, lipid profiles, and white blood cell (WBC) count. METHODS: Survey-weighted multivariate logistic regression was used to examine the associations between blood individual and mixed BTEX with CVD and its subtypes in 17,007 participants from NHANES 1999-2018. The combined effect of BTEX mixture on CVD was estimated using weighted quantile sum modeling and quantile g-computation. Weighted multivariate linear regression assessed the effects of BTEX on lipid profiles and WBC, including its five-part differential count. RESULTS: In comparison to the reference quartile of BTEX mixture, individuals in the highest quartile had a significantly increased adjusted odds ratio of CVD risk (1.64, 95 % CI: 1.23 to 2.19, P for trend = 0.008). Positive associations were observed for benzene, toluene, ethylbenzene, and m-/p-xylene, demonstrating a monotonically increasing exposure-response relationship. Mixed BTEX was associated with congestive heart failure (CHF), angina pectoris, and heart attack. Individual benzene, toluene, and ethylbenzene were associated with CHF, while toluene, ethylbenzene, and all xylene isomers were linked to angina pectoris. Benzene, toluene, and o-xylene were associated with heart attack. Both mixed and individual BTEX showed positive associations with triglycerides, cholesterol, low-density lipoprotein, and WBC, including its five-part differential count, but a negative relationship with high-density lipoprotein. Subgroup analyses identified modifying effects of smoking, drinking, exercise, BMI, hypertension, and diabetes on the associations between specific toxicants and CVD risk. CONCLUSIONS: Exposure to BTEX was associated with cardiovascular diseases and cardiovascular risk factors. These findings emphasize the importance of considering blood BTEX levels when assessing cardiovascular health risks.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Selectivity and Activity of Benzene-1,2,4-triol and its Dimers as Antimicrobial Compounds Against Xanthomonas citri subsp. citri.

Citrus canker, caused by the bacterium Xanthomonas citri subsp. citri, is one of the main threats to citrus fruit production. Several phenolic compounds active against X. citri have been described in recent years. Benzene-1,2,4-triol is a bio-based phenolic compound that has shown high potential as a scaffold for the synthesis of new anti-X. citri compounds. However, benzene-1,2,4-triol is prone to oxidative dimerization. We evaluated the antibacterial activity of benzene-1,2,4-triol, its oxidized dimers, and analogous compounds. Benzene-1,2,4-triol has a low inhibitory concentration against X. citri (0.05 mM) and is also active against other bacterial species. Spontaneous formation of benzenetriol dimers (e. g. by contact with oxygen in aqueous solution) reduced the antimicrobial activity of benzenetriol solutions. Dimers themselves displayed lower antibacterial activity and where shown to be more stable in solution. Unlike many other phenolic compounds with anti-X. citri activity, benzene-1,2,4-triol does not act by membrane permeabilization, but seems to limit the availability of iron to cells. Benzene-1,2,4-triol is widely recognized as toxic - our results indicate that the toxicity of benzene-1,2,4-triol is largely due to spontaneously formed dimers. Stabilization of benzene-1,2,4-triol will be required to allow the safe use of this compound.

Exploring stingless bee honey from selected regions of Peninsular Malaysia through gas chromatography-mass spectrometry-based untargeted metabolomics.

Volatile organic compounds in honey are known for their considerable impact on the organoleptic properties of honey, such as aroma, flavor, taste, and texture. The type and composition of volatile organic compounds are influenced by entomological, geographical, and botanical origins; thus, these compounds have the potential to be chemical markers. Sixty-two volatile compounds were identified using gas chromatography-mass spectrometry from 30 Heterotrigona itama (H. itama) honey samples from 3 different geographical origins. Hydrocarbons and benzene derivatives were the dominant classes of volatile organic compounds in the samples. Both clustering and discriminant analyses demonstrated a clear separation between samples from distant origins (Kedah and Perak), and the volcano plot supported it. The reliability and predictability of the partial least squares-discriminant analysis model from the discriminant analysis were validated using cross-validation (R2 : 0.93; Q2 : 0.83; accuracy: 0.97) and the permutation test (p < 0.001), and the output depicted that the model is legitimate. In combination with the variable importance of projection (VIP > 1.0) and the Kruskal-Wallis test (p < 0.01), 19 volatile organic compounds (encompassed aldehydes, benzene derivatives, esters, hydrocarbons, and terpenoids) were sorted and named potent chemical markers in classifying honey samples from three geographical origins. In brief, this study illustrated that volatile organic compounds of stingless honey originated from the same bee species, but different geographical origins could be applied as chemical markers.

Epac2 activation mediates glucagon-induced glucogenesis in primary rat hepatocytes.

AIMS/INTRODUCTION: Glucagon plays an essential role in hepatic glucogenesis by enhancing glycogen breakdown, inducing gluconeogenesis, and suppressing glycogenesis. Moreover, glucagon increases cyclic adenosine monophosphate (cAMP) levels, thereby activating protein kinase A (PKA) and cAMP guanine nucleotide exchange factor (also known as Epac). Although the function of PKA in the liver has been studied extensively, the function of hepatic Epac is poorly understood. The aim of this study was to elucidate the role of Epac in mediating the action of glucagon on the hepatocytes. MATERIALS AND METHODS: Epac mRNA and protein expression, localization, and activity in the hepatocytes were analyzed by reverse transcription polymerase chain reaction, western blotting, immunofluorescence staining, and Rap1 activity assay, respectively. Additionally, we investigated the effects of an Epac-specific activator, 8-CPT, and an Epac-specific inhibitor, ESI-05, on glycogen metabolism in isolated rat hepatocytes. Further mechanisms of glycogen metabolism were evaluated by examining glucokinase (GK) translocation and mRNA expression of gluconeogenic enzymes. RESULTS: Epac2, but not Epac1, was predominantly expressed in the liver. Moreover, 8-CPT inhibited glycogen accumulation and GK translocation and enhanced the mRNA expression of gluconeogenic enzymes. ESI-05 failed to reverse glucagon-induced suppression of glycogen storage and partially inhibited glucagon-induced GK translocation and the mRNA expression of gluconeogenic enzymes. CONCLUSIONS: Epac signaling plays a role in mediating the glucogenic action of glucagon in the hepatocytes.

Design, Synthesis, and Biological Evaluation of Water-Soluble Prodrugs of C5-Curcuminoid GO-Y030 Based on Reversible Thia-Michael Reaction.

Although curcumin and its analogs exhibit anticancer activity, they are still not used as anticancer drugs because of their water insolubility and extremely poor bioavailability. This study describes the development of water-soluble prodrugs of GO-Y030, a potent antitumor C5-curcuminoid, in an attempt to enhance its bioavailability. These prodrugs release the parent compound via a retro-thia-Michael reaction. To endow sufficient hydrophilicity onto GO-Y030 via a single thia-Michael reaction of an aqueous entity, we used a modified glycoconjugate with a thiol group. The water-solubilizing motif was installed on GO-Y030 by the thia-Michael reaction of propargyl-polyethylene glycol (PEG)-thiol and subsequent click chemistry (CuAAC) reaction with 1-glycosyl azide. Turbidity measurements revealed a significantly improved water solubility of the prodrugs, demonstrating that disaccharide conjugates were completely dissolved in water at 100 µM. Their cytotoxicity was comparable to that of the parent compound GO-Y030, indicating the gradual in situ release of GO-Y030. The release of GO-Y030 from GO-Y199 via the retro-thia-Michael reaction was demonstrated through a degradation study in water. Our retro-thia-Michael reaction-based prodrug system can be used for targeting cancer cells.

Diphenyl Diselenide Through Reduction of Inflammation, Oxidative Injury and Caspase-3 Activation Abates Doxorubicin-Induced Neurotoxicity in Rats.

Neurotoxicity associated with chemotherapy is a debilitating side effect of cancer management in humans which reportedly involves inflammatory and oxidative stress responses. Diphenyl diselenide (DPDS) is an organoselenium compound which exhibits its anti-tumoral, anti-oxidant, anti-inflammatory and anti-mutagenic effects. Nevertheless, its possible effect on chemotherapy-induced neurotoxicity is not known. Using rat model, we probed the behavioral and biochemical effects accompanying administration of antineoplastic agent doxorubicin (7.5 mg/kg) and DPDS (5 and 10 mg/kg). Anxiogenic-like behavior, motor and locomotor insufficiencies associated with doxorubicin were considerably abated by both DPDS doses with concomitant enhancement in exploratory behavior as demonstrated by reduced heat maps intensity and enhanced track plot densities. Moreover, with exception of cerebral glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, biochemical data demonstrated reversal of doxorubicin-mediated decline in cerebral and cerebellar antioxidant status indices and the increase in acetylcholinesterase (AChE) activity by both doses of DPDS. Also, cerebellar and cerebral lipid peroxidation, hydrogen peroxide as well as reactive oxygen and nitrogen species levels were considerably diminished in rats administered doxorubicin and DPDS. In addition, DPDS administration abated myeloperoxidase activity, tumour necrosis factor alpha and nitric oxide levels along with caspase-3 activity in doxorubicin-administered rats. Chemoprotection of doxorubicin-associated neurotoxicity by DPDS was further validated by histomorphometry and histochemical staining. Taken together, DPDS through offsetting of oxido-inflammatory stress and caspase-3 activation elicited neuroprotection in doxorubicin-treated rats.

Negative Association of Serum ß-Cryptoxanthin With Benzene and Its Derivatives.

OBJECTIVE: Benzene is widely recognized as a potential carcinogen. Furthermore, the deficiency of specific nutrients may render individuals more vulnerable to cancer. For instance, ß-cryptoxanthin, which possesses anti-inflammatory, antioxidant, and anticancer properties, has been identified as one such nutrient. Elevated benzene levels and reduced ß-cryptoxanthin levels are reportedly correlated with an augmented susceptibility to cancer. To date, whether these 2 substances are linked with one another in the above correlation is yet to be determined. METHOD: This study included 1358 participants with data on the serum concentration of ß-cryptoxanthin as well as benzene and its derivatives. The data were sourced from the 2003-2004 National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. Headspace solid-phase microextraction with gas chromatography and mass spectrometry was used to measure serum benzene and its derivatives, while high-performance liquid chromatography using multiwavelength photodiode-array absorbance detection was employed to quantify serum ß-cryptoxanthin. RESULTS: In this study, male and female participants showed average ß-cryptoxanthin levels of 9.10 ± 6.35 and 9.92 ± 8.95 ug/dL, respectively (p = 0.049). Styrene exhibited the strongest correlation with the change in ß-cryptoxanthin concentration (ß = -3.30, p for trend <0.001) upon comparing highest-quartile participants with those in the lowest quartile, followed by benzene (ß = -2.95, p for trend <0.001), toluene (ß = -2.90, p for trend <0.001), and ethylbenzene (ß = -1.43, p for trend = 0.09). Subgroup analysis by sex displayed a statistically significant negative correlation of ß-cryptoxanthin with benzene, styrene, and toluene in both the unadjusted and multivariate-adjusted models. CONCLUSIONS: The sera of noninstitutionalized US individuals exhibit a negative association of ß-cryptoxanthin levels with benzene and its derivatives. Styrene demonstrates the strongest link with a substantial decline in serum ß-cryptoxanthin levels, followed by benzene, toluene, and ethylbenzene.

Low-level occupational exposure to BTEX and dyschromatopsia: a systematic review and meta-analysis.

Objectives. The present study aimed to assess whether occupational exposure to low concentrations of benzene, toluene, ethylbenzene and xylene (BTEX) is associated with color vision impairment. Methods. We queried PubMed, Scopus, Embase, Web of Science and ProQuest as the main databases, as well as gray literature such as Google Scholar. A random-effects model was used to assess relative risk. A funnel plot was created to assess publication bias. Meta-regression analysis was applied to identify variables that explain the between-study variation in the reported risk estimate. Results. An overall standardized mean difference of 0.529 (95% confidence interval [0.269, 0.788]; p < 0.0001) was obtained in the random-effects model, which corresponded to a medium-size effect. Duration and the levels of exposure to benzene, toluene and xylene were the significant predictors of the magnitude of the combined risk estimate. Chronic exposure to low levels of BTEX was associated with dyschromatopsia determined by the color confusion index. Conclusions. The impairments can occur even at exposures lower than the occupational exposure limits of BTEX. However, there are several flaws in the determination of workers' exposure, which did not allow to establish how low a level of these chemicals can cause color vision impairment.

Health risk assessment of exposure to benzene, toluene, ethyl benzene, and xylene in shoe industry-related workplaces.

Benzene, toluene, ethyl benzene, and xylene (BTEX) are prevalent pollutants in shoe industry-related workplaces. The aim of this study was to assess exposure to BTEX and their carcinogenic and non-carcinogenic risks in shoe-industry-related workplaces. This study was carried out at different shoe manufactures, small shoe workshop units, shoe markets, and shoe stores in Tabriz, Iran in 2021. Personal inhalation exposure to BTEX was measured using the National Institute for Occupational Safety and Health (NIOSH) 1501 method. Carcinogenic and non-carcinogenic risks due to inhalation exposure to BTEX were estimated by United States Environmental Protection Agency (U.S. EPA) method based on Mont Carlo simulation. Results showed that the concentrations of benzene and toluene were higher than the threshold limit value (TLV) in both gluing and non-gluing units of shoe manufactures. The total carcinogenic risk (TCR) due to exposure to benzene and ethyl benzene was considerable in all shoe industry-related workplaces. Also, the hazard index (HI) as a non-carcinogenic index was higher than standard levels in all shoe industry-related workplaces. Therefore, shoe industry-related workers are at cancer and non-cancer risks due to exposure to BTEX. Prevention measures need to be implemented to reduce the concentration of BTEX in shoe industry-related workplaces.