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.

Disease-modifying potential of diphenyl diselenide in an experimental osteoarthritis model.

Oxidative stress is a key factor in the disruption of cartilage homeostasis during the development of osteoarthritis (OA). Organic selenium (Se)-containing compounds such as diselenides have excellent antioxidant activity and may prevent related diseases. We aimed to examine the benefits of the synthetic small molecule diphenyl diselenide (DPDSe) in OA models in vitro and in vivo. Our findings showed that DPDSe could maintain extracellular matrix (ECM) homeostasis and inhibit reactive oxygen species (ROS) production in IL-1ß-treated chondrocytes. In a destabilization of the medial meniscus (DMM)-induced OA mouse model, intra-articular administration of DPDSe alleviated joint degeneration, as evidenced by a decrease in the OARSI score and the restoration of collagen II (COL2) and MMP-13 expression in cartilage tissues. We confirmed that DDS activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in IL-1ß-treated chondrocytes, and its chondroprotective effects were significantly counteracted when Nrf2 signaling was blocked by the inhibitor ML385 or by siRNA-mediated Nrf2 knockdown. The relatively strong performance of DPDSe makes it an ideal candidate for further trials as a disease-modifying OA drug (DMOAD).

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.

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.

Synthesis and Mesomorphic Properties of Liquid Crystals with 5-(4-Alkoxyphenylethynyl)tropolone.

New troponoid liquid crystals with 5-(4-alkoxyphenylethynyl)tropolone cores were synthesized. The 5-(4-alkoxyphenylethynyl)tropolones were obtained by the palladium-catalyzed cross-coupling of 5-iodotropolone with 4-alkoxyphenylacetylenes. The 2-alkoxy-5-(4-alkoxyphenylethynyl)tropones (1A) showed enantiotropic smectic phases, such as smectic A, C, and B. The 2-(4-alkoxy)benzoyloxy-5-(4-alkoxyphenylethynyl)tropones (1B) had enantiotropic nematic and smectic C phases. The 2-alkoxytropone derivatives (1A) had higher clearing temperatures and lower melting points than the corresponding benzene derivatives (2A). However, the 2-(4-alkoxybenzoyl)tropone derivatives (1B) had lower clearing temperatures and higher melting points than the corresponding benzene derivatives (2B).

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.

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.

Association between blood volatile organic aromatic compound concentrations and hearing loss in US adults.

OBJECTIVE: Benzene, ethylbenzene, meta/para-xylene, and ortho-xylene, collectively referred to as benzene, ethylbenzene, and xylene (BEX), constitute the main components of volatile organic aromatic compounds (VOACs) and can have adverse effects on human health. The relationship between exposure to BEX and hearing loss (HL) in the adult U.S. population was aimed to be assessed. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) for the years 2003-2004, 2011-2012, and 2015-2016 were analyzed. This dataset included complete demographic characteristics, pure-tone audiometry measurements, and volatile organic compound detection data from the NHANES database. A weighted multivariate logistic regression model was employed to investigate the associations between blood BEX concentrations HL, low-frequency hearing loss (SFHL), and high-frequency hearing loss (HFHL). RESULTS: 2174 participants were included, with weighted prevalence rates of HL, SFHL, and HFHL being 46.81%, 25.23%, and 45.86%, respectively. Exposure to benzene, ethylbenzene, meta/para-xylene, and ortho-xylene, and cumulative BEX concentrations increased the risk of hearing loss (odds ratios [ORs] were 1.36, 1.22, 1.42, 1.23, and 1.31, respectively; all P < 0.05). In the analysis with SFHL as the outcome, ethylbenzene, m-/p-xylene, o-xylene, benzene, and overall BEX increased the risk (OR 1.26, 1.21, 1.28, 1.20, and 1.25, respectively; all P < 0.05). For HFHL, exposure to ethylbenzene, m-/p-xylene, o-xylene, benzene, and overall BEX increased the risk (OR 1.36, 1.22, 1.42, 1.22, and 1.31, respectively; all P < 0.05). CONCLUSION: Our study indicated that a positive correlation between individual or cumulative exposure to benzene, ethylbenzene, meta/para-xylene, and ortho-xylene and the risk of HL, SFHL, and HFHL. Further research is imperative to acquire a more comprehensive understanding of the mechanisms by which organic compounds, notably BEX, in causing hearing loss and to validate these findings in longitudinal environmental studies.

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.

Natural attenuation of BTEX and chlorobenzenes in a formerly contaminated pesticide site in China: Examining kinetics, mechanisms, and isotopes analysis.

Groundwater contamination from abandoned pesticide sites is a prevalent issue in China. To address this problem, natural attenuation (NA) of pollutants has been increasingly employed as a management strategy for abandoned pesticide sites. However, limited studies have focused on the long-term NA process of co-existing organic pollutants in abandoned pesticide sites by an integrated approach. In this study, the NA of benzene, toluene, ethylbenzene, and xylene (BTEX), and chlorobenzenes (CBs) in groundwater of a retired industry in China was systematically investigated during the monitoring period from June 2016 to December 2021. The findings revealed that concentrations of BTEX and CBs were effectively reduced, and their NA followed first-order kinetics with different rate constants. The sulfate-reducing bacteria, nitrate-reducing bacteria, fermenting bacteria, aromatic hydrocarbon metabolizing bacteria, and reductive dechlorinating bacteria were detected in groundwater. It was observed that distinct environmental parameters played a role in shaping both overall and key bacterial communities. ORP (14.72%) and BTEX (12.89%) were the main drivers for variations of the whole and key functional microbial community, respectively. Moreover, BTEX accelerated reductive dechlorination. Furthermore, BTEX and CBs exhibited significant enrichment of 13C, ranging from +2.9 to +27.3‰, demonstrating their significance in situ biodegradation. This study provides a scientific basis for site management.

Effects of sodium dodecylbenzene sulfonate (SDBS) on zebrafish (Danio rerio) gills and blood.

Sodium dodecylbenzene sulfonate (SDBS) is an important surfactant used as a cleaning agent and industrial additive to remove unwanted chemicals which have been detected in the aquatic environment. The aim of this study was to examine the toxicological potential of SDBS on the gills of adult male zebrafish (Danio rerio) exposed to this chemical. For the 96 hr acute exposure, fish were divided into three groups: control, 0.25 mg/L, and 0.5 mg/L of SDBS. After the experiment, morphophysiological analyses (gill histopathology and histochemistry), oxidative stress (determination of gill activities of superoxide dismutase (SOD) and catalase (CAT)), and hematological analyses (leukocyte differentiation) were conducted. Data demonstrated that SDBS at both tested concentrations altered the histopathological index and initiated circulatory disturbances, as well as adverse, progressive, and immunological changes in the gills. In the 0.5 mg/L group, SOD activity decreased significantly, but CAT activity was not altered. Prominent blood changes observed in this group were neutrophilia and lymphocytosis. The number of mucous and chloride cells increased significantly in both groups. Taken together, our findings demonstrated that exposure of D. rerio to SDBS, even for 96 hr, produced adverse morphological and hematological effects associated with a reduction in SOD activity. Our findings indicate that exposure of aquatic species to the anionic surfactant SDBS may lead to adverse consequences associated with oxidative stress. Therefore, this study highlights the risks that this substance may pose to aquatic ecosystems and emphasizes the need for further investigations and strict regulations on its disposal.

Association of the blood levels of specific volatile organic compounds with nonfatal cardio-cerebrovascular events in US adults.

BACKGROUND: Cardio-cerebrovascular diseases constitute a major global public health burden. Volatile organic compounds (VOCs) exposure has become progressively severe, endangering human health and becoming one of the main concerns in environmental pollution. The associations of VOCs exposure with nonfatal cardio-cerebrovascular events have not been identified in observational study with a large sample size, so we aim to examine the association in US adult population. METHODS: Adults aged > 18 years with complete data regarding selected blood levels of VOCs (including benzene, ethylbenzene, o-xylene, and m-/p-xylene) and nonfatal cardio-cerebrovascular events were included in the analysis (n = 3,968, National Health and Nutrition Examination Survey, NHANES, 2013-2018 survey cycle). Participants were classified into low- and high-exposure based on whether above selected VOCs low limit detect concentration or median value. Weighted multivariate logistic analyses and subgroup analyses were used to detect the association between selected VOCs exposure and nonfatal cardio-cerebrovascular events in US adults. RESULTS: Weighted multivariate logistic analyses showed that the high-VOCs exposure group had an increased risk of nonfatal cardio-cerebrovascular events compared with the low-VOCs exposure group; the adjusted odds ratios (OR) and 95% confidence intervals (CI) of nonfatal cardio-cerebrovascular events for the high-VOCs exposure group were 1.41 (0.91, 2.19), 1.37 (0.96, 1.95), 1.32 (0.96, 1.82), and 1.17 (0.82, 1.67) for benzene, ethylbenzene, o-xylene, and m-/p-xylene, respectively, which was not significant assuming statistical significance at a 0.05 significance level (95% CI) for a two-tailed test. Lastly, we found high-VOCs exposure was associated with increased incidence of nonfatal cardio-cerebrovascular events in both daily smokers an non-daily smokers (p-interaction > 0.01), but the association was not statistically significant in non-daily smokers. CONCLUSIONS: This study found that VOCs (benzene, ethylbenzene, o-xylene, and m-/p-xylene) exposure was associated with increased incidence of nonfatal cardio-cerebrovascular events in US adults, and the results need to be confirmed by larger cohort studies.

Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent Hypoxia.

Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)2] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe)2 was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe)2 content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe)2 effectively crossed the blood-brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe)2 on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe)2 should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases.

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.

Sodium dodecylbenzene sulphonate (SDBS) present in detergents: action on the gills, skin, and blood of D. rerio fish.

1. Sodium dodecylbenzene sulphonate (SDBS) is one of the surfactants used worldwide in detergents which, due to high residual discharges, has great potential to cause ecotoxicological impacts. Therefore, the sublethal effects of SDBS on the gills and skin of male Danio rerio fish were investigated.2. The fish were distributed into three groups: GC (control), GT1 (0.25 mg/L of SDBS), and GT2 (0.5 mg/L of SDBS) and exposed for 21 days. After the experiment, histopathological analyses of the gills, histochemical analyses (counting of mucous cells), and biochemical analyses (antioxidant defense enzyme analysis, SOD, and CAT) were conducted.3. A significant increase (p < 0.05) in the incidence of circulatory disorders, progressive, and regressive alterations occurred in the GT1 and GT2 groups. Due to these changes, the total histopathological index of the gills was higher in these groups. Mucous cells in the gills and skin increased. There was an increase in SOD activity and a reduction in CAT activity in these groups. Haematology revealed neutrophilia and lymphocytosis in the blood of GT1 and GT2.4. The results clearly demonstrate that a 21-day exposure to SDBS causes severe morphophysiological damage to the gills, skin, and blood of D. rerio fish.

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.

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.

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.

Discovery of LH10, a novel fexaramine-based FXR agonist for the treatment of liver disease.

Farnesoid X receptor (FXR) was considered as a promising drug target in the treatment of cholestasis, drug-induced liver injury, and non-alcoholic steatohepatitis (NASH). However, the existing FXR agonists have shown different degrees of side effects in clinical trials without clear interpretation. MET-409 in clinical phase Ⅲ, has been proven significantly fewer side effects than that of other FXR agonists. This may be due to the completely different structure of FEX and other non-steroidal FXR agonists. Herein, the structure-based drug design was carried out based on FEX, and the more active FXR agonist LH10 (FEX EC50 = 0,3 µM; LH10 EC50 = 0.14 µM)) was screened out by the comprehensive SAR studies. Furthermore, LH10 exhibited robust hepatoprotective activity on the ANIT-induced cholestatic model and APAP-induced acute liver injury model, which was even better than positive control OCA. In the nonalcoholic steatohepatitis (NASH) model, LH10 significantly improved the pathological characteristics of NASH by regulating several major pathways including lipid metabolism, inflammation, oxidative stress, and fibrosis. With the above attractive results, LH10 is worthy of further evaluation as a novel agent for the treatment of liver disorders.

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.