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IntroductionFamilial hypercholesterolemia, the highly prevalent form of dyslipidemia, is a well-known risk factor for premature heart disease and stroke worldwide. Statins, which inhibit 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the first-choice treatment for dyslipidemias, and have been effective in reducing the risk of stroke and myocardial infarction. However, emerging evidence indicates that statins may increase the incidence of new-onset type 2 diabetes by reducing β-cell mass and function. Notably, past in vitro reports studying the effects of statins on β-cells were performed without including free fatty acids in the model. This factor should have been addressed since these agents are used to treat individuals with hyperlipidemia.MethodsHere, we used a mouse insulinoma MIN6 β-cell culture model to assess the efficacy, cytotoxicity, and insulin-suppressive effects of simvastatin and pravastatin in the presence of palmitic, linoleic, and oleic acids cocktail to mimic mixed lipids challenge in a biologically relevant setting.Results and discussionOur findings indicate that simvastatin was more effective in lowering intracellular cholesterol but was more cytotoxic as compared to pravastatin. Similarly, simvastatin exhibited a higher suppression of total insulin content and insulin secretion. Both drugs suppressed insulin secretion in phases 1 and 2, dose-dependently. No significant effect was observed on mitochondrial respiration. More importantly, elution experiments showed that insulin content diminution by simvastatin treatment was reversible, while exogenous mevalonate did not improve total insulin content. This suggests that simvastatin's influence on insulin content is independent of its specific inhibitory action on HMG-CoA reductase. In conclusion, our study identified that simvastatin was more effective in lowering intracellular cholesterol, albeit it was more toxic and suppressive of β-cells function. Notably, this suppression was found to be reversible.

High-fat diets (HFDs) shape the gut microbiome and promote obesity, inflammation, and liver steatosis. Fish and soybean are part of a healthy diet; however, the impact of these fats, in the absence of sucrose, on gut microbial dysbiosis and its association with liver steatosis remains unclear. Here, we investigated the effect of sucrose-free soybean oil-and fish oil-based high fat diets (HFDs) (SF-Soy-HFD and SF-Fish-HFD, respectively) on gut dysbiosis, obesity, steatosis, hepatic inflammation, and insulin resistance. C57BL/6 mice were fed these HFDs for 24 weeks. Both diets had comparable effects on liver and total body weights. But 16S-rRNA sequencing of the gut content revealed induction of gut dysbiosis at different taxonomic levels. The microbial communities were clearly separated, showing differential dysbiosis between the two HFDs. Compared with the SF-Fish-HFD control group, the SF-Soy-HFD group had an increased abundance of Bacteroidetes, Firmicutes, and Deferribacteres, but a lower abundance of Verrucomicrobia. The Clostridia/Bacteroidia (C/B) ratio was higher in the SF-Soy-HFD group (3.11) than in the SF-Fish-HFD group (2.5). Conversely, the Verrucomicrobiacae/S24_7 (also known as Muribaculaceae family) ratio was lower in the SF-Soy-HFD group (0.02) than that in the SF-Fish-HFD group (0.75). The SF-Soy-HFD group had a positive association with S24_7, Clostridiales, Allobaculum, Coriobacteriaceae, Adlercreutzia, Christensenellaceae, Lactococcus, and Oscillospira, but was related to a lower abundance of Akkermansia, which maintains gut barrier integrity. The gut microbiota in the SF-Soy-HFD group had predicted associations with host genes related to fatty liver and inflammatory pathways. Mice fed the SF-Soy-HFD developed liver steatosis and showed increased transcript levels of genes associated with de novo lipogenesis (Acaca, Fasn, Scd1, Elovl6) and cholesterol synthesis (Hmgcr) pathways compared to those in the SF-Fish-HFD-group. No differences were observed in the expression of fat uptake genes (Cd36 and Fabp1). The expression of the fat efflux gene (Mttp) was reduced in the SF-Soy-HFD group. Moreover, hepatic inflammation markers (Tnfa and Il1b) were notably expressed in SF-Soy-HFD-fed mice. In conclusion, SF-Soy-HFD feeding induced gut dysbiosis in mice, leading to steatosis, hepatic inflammation, and impaired glucose homeostasis.

Abstract Background Women’s inability to recognize ovarian cancer (OC) causation myths to be incorrect may lead to behavioral changes that could distract them from actual risk factors and impact their treatment decision making. This study examined Palestinian women’s recognition of OC mythical causes, and explored factors associated with good recognition. Methods A national cross-sectional study was conducted. Adult Palestinian women were recruited from hospitals, primary healthcare facilities, and public areas in 11 governorates. The Cancer Awareness Measure-Mythical Causes Scale was modified and utilized for data collection. Awareness level was determined based on the number of myths around OC causation recognized to be incorrect: poor (0–4), fair (5–9), and good (10–13). Results A total of 5618 participants agreed and completed the questionnaire out of 6095 approached (response rate = 92.1%), and 5411 questionnaires were included in the final analysis. The most recognized food-related myth was ‘drinking from plastic bottles’ (n = 1370, 25.3%) followed by ‘eating burnt food’ (n = 1298, 24.0%). The least recognized food-related myth was ‘eating food containing additives’ (n = 611, 11.3%). The most recognized food-unrelated myth was ‘having a physical trauma’ (n = 2899, 53.6%), whereas the least recognized was ‘using mobile phones’ (n = 1347, 24.9%). Only 273 participants (5.1%) had good awareness of OC causation myths as incorrect. Earning higher monthly incomes as well as visiting governmental healthcare facilities were associated with a decrease in the likelihood of exhibiting good awareness. Conclusion The overall recognition of OC causation myths was low. Addressing mythical beliefs should be included in OC prevention strategies and public health interventions to improve women’s understanding of OC risk factors versus mythical causes.

Implant stability can be compromised by factors such as inadequate bone quality and infection, leading to potential implant failure. Ensuring implant stability and longevity is crucial for patient satisfaction and quality of life. In this multicenter, randomized, double-blind clinical trial, we assessed the impact of a bone bioactive liquid (BBL) on the Galaxy TS implant’s performance, stability, and osseointegration. We evaluated the impact stability, osseointegration, and pain levels using initial stability quotient (ISQ) measurements, CBCT scans, and pain assessment post-surgery. Surface analysis was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In vitro studies examined the BBL’s effects on dental pulp pluripotent stem cells’ (DPPSCs’) osteogenesis and inflammation modulation in human macrophages. All implants successfully osseointegrated, as demonstrated by the results of our clinical and histological studies. The BBL-treated implants showed significantly lower pain scores by day 7 (p < 0.00001) and improved stability by day 30 (ISQ > 62.00 ± 0.59, p < 8 × 10−7). By day 60, CBCT scans revealed an increased bone area ratio in BBL-treated implants. AFM images demonstrated the BBL’s softening and wettability effect on implant surfaces. Furthermore, the BBL promoted DPPSCs’ osteogenesis and modulated inflammatory markers in human primary macrophages. This study presents compelling clinical and biological evidence that BBL treatment improves Galaxy TS implant stability, reduces pain, and enhances bone formation, possibly through surface tension modulation and immunomodulatory effects. This advancement holds promise for enhancing patient outcomes and implant longevity.

Increasing emissions from mobile sources have become a major focus in terms of health, environmental sustainability, and climate change. South Tangerang City is the Indonesian city with the highest yearly average pollution level. This study's objectives are to quantify the levels of pollutant concentrations that endanger human health and the environment and to devise a plan for reducing the pollution brought on by vehicle emissions. This study used an analytic observational research design. Data was taken from 32 points in 7 sub-districts in the city of South Tangerang with human and environmental samples. Human samples using the Hazard Quotient. Data is processed using Stella for the next 30 years. HQ value of PM2.5, NO2, SO2, and CO pollution has risen to greater than 1, endangering human health. CO and PM2.5, with HQ values of 3.315 and 1.644, both present serious health concerns. The accumulation of PM2.5, NO2, SO2, and CO pollutants over the next 30 years will have a substantial impact on South Tangerang's environmental conditions. South Tangerang could encourage the growth of a smart city by supporting the use of electric vehicles. Human health is at risk due to the increase in the HQ value of PM2.5, NO2, SO2, and CO pollution above 1. The environmental conditions in South Tangerang be significantly impacted by PM2.5, NO2, SO2, and CO pollutants over the ensuing 30 years. A mitigation strategy is needed in the form of smart transportation in the form of electric vehicles

BACKGROUND AND OBJECTIVES: The rising number of vehicles used for transportation, which is attributed to the steady increase in population, is known to be a major contributor of air pollution, which, in turn, can have adverse effects on the environment and human health. Therefore, in this study, we aimed to evaluate the concentration of carbon monoxide and fine particulate matter in the air and their potential health risks and further examine the use of probabilistic methods to simulate the sensitivity of people living in communities and school children to these pollutants.METHODS: This study collected carbon monoxide and fine particulate matter samples from 32 stations near community houses and 14 sites near schools located along roads. Hazard quotient and target hazard quotient calculations were used to estimate the non-carcinogenic health risks associated with exposure to these substances for both community adults and school children. Finally, Monte Carlo simulations were applied to analyze the sensitivity and uncertainty risks. FINDINGS: As per the results, the highest level of carbon monoxide was recorded in station 22, with 6729 microgram per cubic meter, while the lowest was in station 24, with 1037 microgram per cubic meter. Station 10 had the highest concentration of fine particulate matter at 116 microgram per cubic meter, as opposed to station 2 with the lowest level at 10 microgram per cubic meter. In children, the hazard quotient value for carbon monoxide was found to be highest at 3.013, with the lowest at 0.614. Similarly, the highest level of target hazard quotient for carbon monoxide in children was 7.370, whereas the lowest was 1.522. For fine particulate matter, the highest risk level was 0.180. Additionally, the highest, and lowest levels of target hazard quotient for fine particulate matter were 0.311 and 0.037, respectively. Deterministic and probabilistic approaches were used to assess the risks these pollutants impose on adults and school children based on their daily inhalation rate. The results revealed that the 5th and 95th percentiles of cancer risk for carbon monoxide in adults were 2.85 and 6.11, respectively, indicating medium risks. However, for fine particulate matter, the 5th, and 95th percentiles were 0.09 and 0.19, respectively, signifying lower risks. For school children, the percentiles for carbon monoxide and fine particulate matter were 1.20 and 2.50, respectively, demonstrating higher risks.CONCLUSION: As per the results, it was determined that the hazard quotient risk for carbon monoxide in adults exceeded the standard, >1, thus posing a risk. Only three stations had hazard quotient values lower than 1, which is deemed of safe level. Most of the fine particulate matter risk assessment results had hazard quotient values lower than 1, indicating a safe level. However, all other 30 stations had exceeded the World Health Organization standard (>1), thus demonstrating risks. The likelihood of the inhabitants being at risk increased as the frequency of discrete exposure occurrences increased; this is evidenced by target hazard quotient calculation results for both carbon monoxide and fine particulate matter at the 32 monitored station areas. These results warrant that future research should focus on reducing carbon monoxide and fine particulate matter in the environment by fostering awareness among local and national stakeholders as well as the academe; this may allow South Tangerang to become a center of excellence for green schools in the area.

Abstract Background Several factors contribute to delayed presentation with ovarian cancer (OC) symptoms including poor symptom awareness and barriers to seeking help. This study explored the anticipated time to seek medical advice for possible OC symptoms and its association with OC symptom awareness. In addition, it examined perceived barriers that may delay help-seeking among Palestinian women. Methods A cross-sectional study was conducted among adult women (≥ 18 years) recruited from hospitals, primary healthcare centers, and public spaces in 11 Palestinian governorates. A modified version of the OC awareness measure was used to collect data in face-to-face interviews. The questionnaire comprised three sections: sociodemographic details, awareness of 11 OC symptoms and time to seek medical advice, and barriers to early presentation. Results Of 6095 participants approached, 5618 completed the OCAM (response rate = 92.1%). The proportion of participants who would immediately seek medical advice for a possible OC symptom varied based on the symptom’s nature. For OC symptoms with pain, the proportion that reported immediate seeking of medical advice ranged from 7.9% for ‘persistent low back pain’ to 13.6% for ‘persistent pain in the pelvis’. For non-specific potential OC symptoms, the proportion that reported immediate seeking of medical advice ranged from 2.3% for ‘feeling full persistently’ to 15.8% for ‘increased abdominal size on most days’. Good OC symptom awareness was associated with higher likelihood of seeking medical advice within a week from recognizing 10 out of 11 OC symptoms. Emotional barriers were the most common barriers with ‘feeling scared’ as the most reported barrier (n = 1512, 52.4%). Displaying good OC symptom awareness was associated with a lower likelihood of reporting ≥ 4 emotional barriers (OR = 0.61, 95% CI: 0.38–0.98). Conclusion Participants with good OC symptom awareness were more likely to seek medical advice earlier and to display fewer emotional barriers. Establishing educational interventions to raise OC awareness may help in promoting earlier help-seeking and, thus, facilitate earlier diagnosis and improved prognosis.

IntroductionA high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or increase this adverse effect. Fish oil and cocoa butter are a significant part of our diets. Yet comparisons of these commonly used fat sources with high sucrose on pancreas morphology and function are not made. This study investigated the comparative effects of a fish oil-based high-fat/high-sucrose diet (Fish-HFDS) versus a cocoa butter-based high-fat/high-sucrose diet (Cocoa-HFDS) on endocrine pancreas morphology and function in mice.MethodsC57BL/6 male mice (n=12) were randomly assigned to dietary intervention either Fish-HFDS (n=6) or Cocoa-HFDS (n=6) for 22 weeks. Intraperitoneal glucose and insulin tolerance tests (IP-GTT and IP-ITT) were performed after 20-21 weeks of dietary intervention. Plasma concentrations of c-peptide, insulin, glucagon, GLP-1, and leptin were measured by Milliplex kit. Pancreatic tissues were collected for immunohistochemistry to measure islet number and composition. Tissues were multi-labelled with antibodies against insulin and glucagon, also including expression on Pdx1-positive cells.Results and discussionFish-HFDS-fed mice showed significantly reduced food intake and body weight gain compared to Cocoa-HFDS-fed mice. Fish-HFDS group had lower fasting blood glucose concentration and area under the curve (AUC) for both GTT and ITT. Plasma c-peptide, insulin, glucagon, and GLP-1 concentrations were increased in the Fish-HFDS group. Interestingly, mice fed the Fish-HFDS diet displayed higher plasma leptin concentration. Histochemical analysis revealed a significant increase in endocrine pancreas β-cells and islet numbers in mice fed Fish-HFDS compared to the Cocoa-HFDS group. Taken together, these findings suggest that in a high-fat/high-sucrose dietary setting, the source of the fat, especially fish oil, can ameliorate the effect of sucrose on glucose homeostasis and endocrine pancreas morphology and function.

This study unveils verapamil’s compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil’s capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resilience. A pivotal revelation of our research is verapamil’s induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil’s efficacy in fostering β-cell recovery post-metronidazole infliction. Collectively, our findings advocate for verapamil’s reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell regeneration, thereby offering fresh avenues for diabetes management strategies aimed at preserving and augmenting β-cell functionality.

Verapamil is a well-known drug used for treating angina and hypertension. Emerging data from current clinical trials suggest that this calcium channel blocker has a potential benefit for pancreatic β-cells through the elevation and sustenance of C-peptide levels in patients with diabetes mellitus (DM). This is intriguing, given the fact that the current therapeutic options for DM are still limited to using insulin and incretins which, in fact, fail to address the underlying pathology of β-cell destruction and loss. Moreover, verapamil is widely available as an FDA-approved, cost-effective drug, supported also by its substantial efficacy and safety. However, the molecular mechanisms underlying the β-cell protective potentials of verapamil are yet to be fully elucidated. Although, verapamil reduces the expression of thioredoxin-interacting protein (TXNIP), a molecule which is involved in β-cell apoptosis and glucotoxicity-induced β-cell death, other signaling pathways are also modulated by verapamil. In this review, we revisit the historical avenues that lead to verapamil as a potential therapeutic agent for DM. Importantly, this review provides an update on the current known mechanisms of action of verapamil and also allude to the plausible mechanisms that could be implicated in its β-cell protective effects, based on our own research findings.

This study investigated potentially toxic elements (PTEs) pollution in groundwater across the Maros karst area. The groundwater quality was evaluated using three indexing methods, the heavy metal pollution index (HPI), the heavy metal evaluation index (HMEI) and the contamination index ( The levels of PTEs were calculated to determine the noncancer and cancer risks to the residents through ingestion and dermal adsorption. To obtain high-level accuracy in cancer risk estimation, a Monte Carlo simulation model and sensitivity analysis were performed. The mean values of PTEs in rainy and summer season were followed the order of Cr > Pb > Zn > Cu and Cr > Zn > Pb > Cu, respectively. The high level of Pb and Cr were exceeded the permissible limit of the World Health Organization (WHO) and Indonesian Standards. However, TDS, pH, EC and temperature were still in accordance with WHO guidelines. The geostatistical interpolation of HPI, HMEI and revealed that the groundwater quality around Maros karst is low, particularly in Tukamasea and Leang-Leang village. Hazard index values were lower than one, implying no possibility of noncancer risk. The Monte Carlo simulation results with 95% confidence demonstrated children and adults are at risk for developing cancer due to PTE exposure.

Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here, we report studies that address this question. After 14 weeks on a high-fat diet (HFD) with high sucrose, C57BL/6 mice revealed a phenotype of liver steatosis. Transcriptional profiling analysis of the liver tissues was performed using RNA sequencing (RNA-seq). Our RNA-seq data revealed 692 differentially expressed genes involved in processes of lipid metabolism, oxidative stress, immune responses, and cell proliferation. Notably, the gene encoding neutral sphingomyelinase, SMPD3, was predominantly upregulated in the liver tissues of the mice displaying a phenotype of steatosis. Moreover, nSMase2 activity was elevated in these tissues of the liver. Pharmacological and genetic inhibition of nSMase2 prevented intracellular lipid accumulation and TNFα-induced inflammation in in-vitro HepG2-steatosis cellular model. Furthermore, nSMase2 inhibition ameliorates oxidative damage by rescuing PPARα and preventing cell death associated with high glucose/oleic acid-induced fat accumulation in HepG2 cells. Collectively, our findings highlight the prominent role of nSMase2 in hepatic steatosis, which could serve as a potential therapeutic target for NAFLD and other hepatic steatosis-linked disorders.

Implant stability can be compromised by factors such as inadequate bone quality and infection, leading to potential implant failure. Ensuring implant stability and longevity is crucial for patient satisfaction and quality of life. In this multicenter, randomized, double-blind clinical trial, we assessed the impact of a bone bioactive liquid (BBL) on the Galaxy TS implant's performance, stability, and osseointegration. We evaluated the impact stability, osseointegration, and pain levels using initial stability quotient (ISQ) measurements, CBCT scans, and pain assessment post-surgery. Surface analysis was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In vitro studies examined the BBL's effects on dental pulp pluripotent stem cells' (DPPSCs') osteogenesis and inflammation modulation in human macrophages. All implants successfully osseointegrated, as demonstrated by the results of our clinical and histological studies. The BBL-treated implants showed significantly lower pain scores by day 7 (p < 0.00001) and improved stability by day 30 (ISQ > 62.00 ± 0.59, p < 8 × 10−7). By day 60, CBCT scans revealed an increased bone area ratio in BBL-treated implants. AFM images demonstrated the BBL's softening and wettability effect on implant surfaces. Furthermore, the BBL promoted DPPSCs' osteogenesis and modulated inflammatory markers in human primary macrophages. This study presents compelling clinical and biological evidence that BBL treatment improves Galaxy TS implant stability, reduces pain, and enhances bone formation, possibly through surface tension modulation and immunomodulatory effects. This advancement holds promise for enhancing patient outcomes and implant longevity. [ABSTRACT FROM AUTHOR]

Summary: Foamy and inflammatory macrophages play pathogenic roles in metabolic disorders. However, the mechanisms that promote foamy and inflammatory macrophage phenotypes under acute-high-fat feeding (AHFF) remain elusive. Herein, we investigated the role of acyl-CoA synthetase-1 (ACSL1) in favoring the foamy/inflammatory phenotype of monocytes/macrophages upon short-term exposure to palmitate or AHFF. Palmitate exposure induced a foamy/inflammatory phenotype in macrophages which was associated with increased ACSL1 expression. Inhibition/knockdown of ACSL1 in macrophages suppressed the foamy/inflammatory phenotype through the inhibition of the CD36-FABP4-p38-PPARδ signaling axis. ACSL1 inhibition/knockdown suppressed macrophage foaming/inflammation after palmitate stimulation by downregulating the FABP4 expression. Similar results were obtained using primary human monocytes. As expected, oral administration of ACSL1 inhibitor triacsin-C in mice before AHFF normalized the inflammatory/foamy phenotype of the circulatory monocytes by suppressing FABP4 expression. Our results reveal that targeting ACSL1 leads to the attenuation of the CD36-FABP4-p38-PPARδ signaling axis, providing a therapeutic strategy to prevent the AHFF-induced macrophage foaming and inflammation.

Accumulating evidence indicates that most primary Wharton’s jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., their ability to modulate their microenvironment by releasing bioactive molecules and factors collectively known as secretome. These bioactive molecules and factors can either be released directly into the surrounding microenvironment or can be embedded within the membrane-bound extracellular bioactive nano-sized (usually 30–150 nm) messenger particles or vesicles of endosomal origin with specific route of biogenesis, known as exosomes or carried by relatively larger particles (100 nm–1 μm) formed by outward blebbing of plasma membrane called microvesicles (MVs); exosomes and MVs are collectively known as extracellular vesicles (EVs). The bioactive molecules and factors found in secretome are of various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, and regulatory nucleic acid molecules. As expected, the secretome performs different biological functions, such as immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory and anti-fibrotic effects. This review highlights the current advances in research on the WJ-MSCs’ secretome and its prospective clinical applications.

Nadeem Akhter,1 Shihab Kochumon,1 Amal Hasan,1 Ajit Wilson,1 Rasheeba Nizam,2 Ashraf Al Madhoun,2,3 Fatema Al-Rashed,1 Hossein Arefanian,1 Fawaz Alzaid,2,4 Sardar Sindhu,1,3 Fahd Al-Mulla,1 Rasheed Ahmad1 1Immunology & Microbiology Department, Dasman Diabetes Institute, Kuwait City, Kuwait; 2Genetics & Bioinformatics, Dasman Diabetes Institute, Kuwait City, Kuwait; 3Animal and Imaging Core Facility, Dasman Diabetes Institute, Kuwait City, Kuwait; 4Institut Necker Enfants Malades (INEM), French Institute of Health and Medical Research (INSERM), Immunity & Metabolism of Diabetes (IMMEDIAB), Université de Paris Cité, Paris, FranceCorrespondence: Rasheed Ahmad, Immunology & Microbiology Department, Dasman Diabetes Institute, Kuwait City, Kuwait, Tel +965 2224 2999 Ext. 4311, Email rasheed.ahmad@dasmaninstitute.orgBackground: Overexpression of CCL2 (MCP-1) has been implicated in pathogenesis of metabolic conditions, such as obesity and T2D. However, the mechanisms leading to increased CCL2 expression in obesity are not fully understood. Since both IFN-γ and LPS levels are found to be elevated in obesity and shown to be involved in the regulation of metabolic inflammation and insulin resistance, we investigated whether these two agents could synergistically trigger the expression of CCL2 in obesity.Methods: Monocytes (Human monocytic THP-1 cells) were stimulated with IFN-γ and LPS. CCL2 gene expression was determined by real-time RT-PCR. CCL2 protein was determined by ELISA. Signaling pathways were identified by using epigenetic inhibitors and STAT1 siRNA. Acetylation of H3K27 was analyzed by Western blotting. The acetylation level of histone H3K27 in the transcriptional initiation region of CCL2 gene was determined by ChIP-qPCR.Results: Our results show that the co-incubation of THP-1 monocytes with IFN-γ and LPS significantly enhanced the expression of CCL2, compared to treatment with IFN-γ or LPS alone. Similar results were obtained using primary monocytes and macrophages. Interestingly, IFN-γ priming was found to be more effective than LPS priming in inducing synergistic expression of CCL2. Moreover, STAT1 deficiency significantly suppressed this synergy for CCL2 expression. Mechanistically, we showed that IFN-γ priming induced acetylation of lysine 27 on histone 3 (H3K27ac) in THP-1 cells. Chromatin immunoprecipitation (ChIP) assay followed by qRT-PCR revealed increased H3K27ac at the CCL2 promoter proximal region, resulting in stabilized gene expression. Furthermore, inhibition of histone acetylation with anacardic acid suppressed this synergistic response, whereas trichostatin A (TSA) could substitute IFN-γ in this synergy.Conclusion: Our findings suggest that IFN-γ, in combination with LPS, has the potential to augment inflammation via the H3K27ac-mediated induction of CCL2 in monocytic cells in the setting of obesity.Keywords: CCL2, monocytes/macrophages, LPS, IFN-γ, H3K27 ac, inflammation

Introduction: Familial hypercholesterolemia, the highly prevalent form of dyslipidemia, is a well-known risk factor for premature heart disease and stroke worldwide. Statins, which inhibit 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the first-choice treatment for dyslipidemias, and have been effective in reducing the risk of stroke and myocardial infarction. However, emerging evidence indicates that statins may increase the incidence of new-onset type 2 diabetes by reducing β-cell mass and function. Notably, past in vitro reports studying the effects of statins on β-cells were performed without including free fatty acids in the model. This factor should have been addressed since these agents are used to treat individuals with hyperlipidemia. Methods: Here, we used a mouse insulinoma MIN6 β-cell culture model to assess the efficacy, cytotoxicity, and insulin-suppressive effects of simvastatin and pravastatin in the presence of palmitic, linoleic, and oleic acids cocktail to mimic mixed lipids challenge in a biologically relevant setting. Results and discussion: Our findings indicate that simvastatin was more effective in lowering intracellular cholesterol but was more cytotoxic as compared to pravastatin. Similarly, simvastatin exhibited a higher suppression of total insulin content and insulin secretion. Both drugs suppressed insulin secretion in phases 1 and 2, dose-dependently. No significant effect was observed on mitochondrial respiration. More importantly, elution experiments showed that insulin content diminution by simvastatin treatment was reversible, while exogenous mevalonate did not improve total insulin content. This suggests that simvastatin's influence on insulin content is independent of its specific inhibitory action on HMG-CoA reductase. In conclusion, our study identified that simvastatin was more effective in lowering intracellular cholesterol, albeit it was more toxic and suppressive of β-cells function. Notably, this suppression was found to be reversible. [ABSTRACT FROM AUTHOR]

Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the contrasting roles of oxidative phosphorylation (OXPHOS) and glycolysis as primary energy-generating pathways within cells. Building on earlier research, we explore how a shift towards one pathway over the other serves as a foundational aspect in the development of cancer and T2D. Unlike previous reviews, we posit that this shift may occur in seemingly opposing yet complementary directions, akin to the Yin and Yang concept. These metabolic fluctuations reveal an intricate network of underlying defective signaling pathways, orchestrating the pathogenesis and progression of each disease. The Warburg phenomenon, characterized by the prevalence of aerobic glycolysis over minimal to no OXPHOS, emerges as the predominant metabolic phenotype in cancer. Conversely, in T2D, the prevailing metabolic paradigm has traditionally been perceived in terms of discrete irregularities rather than an OXPHOS-to-glycolysis shift. Throughout T2D pathogenesis, OXPHOS remains consistently heightened due to chronic hyperglycemia or hyperinsulinemia. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, featuring differential tissue-specific alterations that affect OXPHOS. Recent findings suggest that addressing the metabolic imbalance in both cancer and diabetes could offer an effective treatment strategy. Numerous pharmaceutical and nutritional modalities exhibiting therapeutic effects in both conditions ultimately modulate the OXPHOS–glycolysis axis. Noteworthy nutritional adjuncts, such as alpha-lipoic acid, flavonoids, and glutamine, demonstrate the ability to reprogram metabolism, exerting anti-tumor and anti-diabetic effects. Similarly, pharmacological agents like metformin exhibit therapeutic efficacy in both T2D and cancer. This review discusses the molecular mechanisms underlying these metabolic shifts and explores promising therapeutic strategies aimed at reversing the metabolic imbalance in both disease scenarios.

This article addresses the causes of instability and non-sustainability of municipal water and wastewater by the 25 Service Providers (SPs) in the Gaza Strip (GS), Palestine. The analysis of Key Performance Indicators (KPIs) of municipal water and wastewater SPs in the GS shows a serious deficiency in the administrative, financial, and operational dimensions; such deficiency affects efforts to achieve the UN Sustainable Development Goal 6 (SDG 6). The deficiencies include inappropriate planning, lack of comprehensive capacity-building programmes, very high levels of Non-Revenue Water, and distortions in the tariff structures of almost all service providers, where the average selling price per m3 of water was less than the average unit cost of m3 of water sold. Moreover, levels of collection efficiency were very low, which resulted in a serious cash flow problem for the SPs'. The study has found a lack or absence of accurate or completed customer complaint, satisfaction, and inquiry logs; this is clearly reflected in customer behaviour related to reluctance to pay bills and high levels of illegal connections.

IntroductionBoth obesity and a poor diet are considered major risk factors for triggering insulin resistance syndrome (IRS) and the development of type 2 diabetes mellitus (T2DM). Owing to the impact of low-carbohydrate diets, such as the keto diet and the Atkins diet, on weight loss in individuals with obesity, these diets have become an effective strategy for a healthy lifestyle. However, the impact of the ketogenic diet on IRS in healthy individuals of a normal weight has been less well researched. This study presents a cross-sectional observational study that aimed to investigate the effect of low carbohydrate intake in healthy individuals of a normal weight with regard to glucose homeostasis, inflammatory, and metabolic parameters.MethodsThe study included 120 participants who were healthy, had a normal weight (BMI 25 kg/m2), and had no history of a major medical condition. Self-reported dietary intake and objective physical activity measured by accelerometry were tracked for 7 days. The participants were divided into three groups according to their dietary intake of carbohydrates: the low-carbohydrate (LC) group (those consuming

Abstract Background Healthcare workers (HCWs) have been impacted psychologically due to their professional responsibilities over the prolonged era of the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to identify the predictors of psychological distress, fear, and coping during the COVID-19 pandemic among HCWs. Methods A cross-sectional online survey was conducted among self-identified HCWs across 14 countries (12 from Asia and two from Africa). The Kessler Psychological Distress Scale, the Fear of COVID-19 Scale, and the Brief Resilient Coping Scale were used to assess the psychological distress, fear, and coping of HCWs, respectively. Results A total of 2447 HCWs participated; 36% were doctors, and 42% were nurses, with a mean age of 36 (±12) years, and 70% were females. Moderate to very-high psychological distress was prevalent in 67% of the HCWs; the lowest rate was reported in the United Arab Emirates (1%) and the highest in Indonesia (16%). The prevalence of high levels of fear was 20%; the lowest rate was reported in Libya (9%) and the highest in Egypt (32%). The prevalence of medium-to-high resilient coping was 63%; the lowest rate was reported in Libya (28%) and the highest in Syria (76%). Conclusion COVID-19 has augmented the psychological distress among HCWs. Factors identified in this study should be considered in managing the wellbeing of HCWs, who had been serving as the frontline drivers in managing the crisis successfully across all participating countries. Furthermore, interventions to address their psychological distress should be considered.

Abstract Introduction Ovarian cancer (OC) is often diagnosed at advanced stages. This study aimed to assess the Palestinian women’s knowledge about OC symptoms and determine the factors associated with having good knowledge. Methods A cross-sectional study was conducted from July 2019 to March 2020 in the two main areas of Palestine: the West Bank and Jerusalem as well as the Gaza Strip. A translated-into-Arabic version of the validated OC awareness measure (OCAM) was utilized for data collection. Stratified convenience sampling was used to recruit adult women attending hospitals, primary healthcare centers, and public spaces at 11 governorates. The knowledge level was categorized into three categories based on the number of symptoms recognized: poor (0 to 4), fair (5 to 8), and good (9 to 11). Results Of 6095 approached, 5618 participants completed the Arabic OCAM (response rate = 92.1%).A total of 5411 questionnaires were included in the analysis: 2278 from the Gaza Strip and 3133 from the West Bank and Jerusalem. Participants living in the West Bank and Jerusalem were older, of higher monthly income, and with more chronic diseases than those living in the Gaza Strip. The most frequently identified symptoms were ‘extreme generalized fatigue’ (n = 3821, 70.6%), ‘unexplained weight loss’ (n = 3607, 66.7%), and ‘increased abdominal size on most days’ (n = 3252, 60.1%). On the other hand, the least recognized symptoms were ‘feeling full persistently’ (n = 1553, 28.7%) and ‘difficulty eating on most days’ (n = 1971, 36.4%). Only 943 participants (17.4%) displayed good knowledge of OC symptoms. Participants from the Gaza Strip had a higher likelihood than participants from the West Bank and Jerusalem to have a good level of knowledge (21.0% vs. 14.8%). Being married, knowing someone with cancer, and visiting hospitals were all associated with a higher likelihood of having good knowledge level. However, living in the West Bank and Jerusalem was associated with a lower likelihood of having good knowledge. Conclusion The overall knowledge of OC symptoms in this study was low. Educational interventions are needed to improve Palestinian women’s knowledge about OC symptoms.

Abstract Background The current pandemic of COVID-19 impacted the psychological wellbeing of populations globally. Objectives We aimed to examine the extent and identify factors associated with psychological distress, fear of COVID-19 and coping. Methods We conducted a cross-sectional study across 17 countries during Jun-2020 to Jan-2021. Levels of psychological distress (Kessler Psychological Distress Scale), fear of COVID-19 (Fear of COVID-19 Scale), and coping (Brief Resilient Coping Scale) were assessed. Results A total of 8,559 people participated; mean age (±SD) was 33(±13) years, 64% were females and 40% self-identified as frontline workers. More than two-thirds (69%) experienced moderate-to-very high levels of psychological distress, which was 46% in Thailand and 91% in Egypt. A quarter (24%) had high levels of fear of COVID-19, which was as low as 9% in Libya and as high as 38% in Bangladesh. More than half (57%) exhibited medium to high resilient coping; the lowest prevalence (3%) was reported in Australia and the highest (72%) in Syria. Being female (AOR 1.31 [95% CIs 1.09-1.57]), perceived distress due to change of employment status (1.56 [1.29-1.90]), comorbidity with mental health conditions (3.02 [1.20-7.60]) were associated with higher levels of psychological distress and fear. Doctors had higher psychological distress (1.43 [1.04-1.97]), but low levels of fear of COVID-19 (0.55 [0.41-0.76]); nurses had medium to high resilient coping (1.30 [1.03-1.65]). Conclusions The extent of psychological distress, fear of COVID-19 and coping varied by country; however, we identified few higher risk groups who were more vulnerable than others. There is an urgent need to prioritise health and well-being of those people through well-designed intervention that may need to be tailored to meet country specific requirements.

Background: Animal and cell model studies have implicated CAV1 in the pathophysiology of metabolic disorders. Our previous studies demonstrated a potential association of CAV1 rs1997623 C/A variant with pediatric metabolic syndrome (MetS) in Arab children. In the present study, we evaluate whether the CAV1 variant associates with MetS Arab adults as well. The association signal is further examined for ancestry-specific variation by considering cohorts of other ethnicities.Method: The CAV1 rs1997623 was genotyped in three cohorts of Arab (n = 479), South Asian (n = 660), and South East Asian (n = 362) ethnic adults from Kuwait. MetS status of the individuals was diagnosed using the IDF criteria (presence of central obesity and at least two abnormalities out of: elevated TG, low HDL, hypertension, or T2D). The quantitative measure of MetS was calculated as siMS = 2 × WC/Height + FBG/5.6 + TG/1.7 + SBP/130–HDL/1.02 for males or HDL/1.28 for females. Allelic associations with quantitative and dichotomous MetS traits were assessed using linear and logistic regression models adjusted for age and sex. In addition, empirical p-values (Pemp) were generated using max(T) permutation procedure based on 10,000 permutations.Results: The CAV1 variant was significantly associated with MetS status (OR = 1.811 [1.25–2.61]; p-value = 0.0015; Pemp = 0.0013) and with siMS (Effect size = 0.206; p-value = 0.0035; Pemp = 0.0028) in the cohort of Arab individuals. The association was weak and insignificant in the South Asian and South East Asian cohorts (OR = 1.19 and 1.11; p-values = 0.25 and 0.67, respectively).Conclusion: The reported association of CAV1 rs1997623 C/A with MetS in Arab pediatric population is now demonstrated in an adult Arab cohort as well. The weak association signal seen in the Asian cohorts lead us to propose a certain extent of ethnic-specificity in CAV1 rs1997623 association with MetS.

Abstract The role of leukocyte inflammatory markers and toll like receptors (TLRs)2/4 in pathologies associated with elevated resting heart rate (RHR) levels in healthy obese (HO) individuals is not well elucidated. Herein, we investigated the relationship of RHR with expression of leukocyte-inflammatory markers and TLRs in HO individuals. 58-obese and 57-lean participants with no history of a major medical condition, were recruited in this study. In HO individuals, the elevated-RHR correlated positively with diastolic blood pressure, cholesterol, pro-inflammatory monocytes CD11b+CD11c+CD206− phenotype (r = 0.52, P = 0.0003) as well as with activated T cells CD8+HLA-DR+ phenotype (r = 0.27, P = 0.039). No association was found between RHR and the percentage of CD16+CD11b+ neutrophils. Interestingly, elevated RHR positively correlated with cells expressing TLR4 and TLR2 (CD14+TLR4+, r = 0.51, P ≤ 0.0001; and CD14+TLR2+, r = 0.42, P = 0.001). TLR4+ expressing cells also associated positively with the plasma concentrations of proinflammatory or vascular permeability/matrix modulatory markers including TNF-α (r = 0.36, P = 0.005), VEGF (r = 0.47, P = 0.0002), and MMP-9 (r = 0.53, P ≤ 0.0001). Multiple regression revealed that RHR is independently associated with CD14+TLR4+ monocytes and VEGF. We conclude that in HO individuals, increased CD14+TLR4+ monocytes and circulatory VEGF levels associated independently with RHR, implying that RHR monitoring could be used as a non-invasive clinical indicator to identify healthy obese individuals at an increased risk of developing inflammation and cardiovascular disease.

Fatema Al-Rashed,1 Sardar Sindhu,2 Ashraf Al Madhoun,2,3 Abdulwahab Alghaith,4 Rafaat Azim,1 Fahd Al-Mulla,3 Rasheed Ahmad1 1Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman, Kuwait; 2Animal and Imaging Core Facility, Dasman Diabetes Institute, Dasman, Kuwait; 3Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman, Kuwait; 4Royal College of Surgeons in Ireland, Dublin, IrelandCorrespondence: Fatema Al-Rashed; Rasheed AhmadMicrobiology & Immunology Department, Dasman Diabetes Institute, Al-Soor Street, Kuwait, P.O. Box 1180, Dasman, 15462, KuwaitTel +965 2224 2999 Ext. 4335; 4311Fax +965 2249 2406Email fatema.alrashed@dasmaninstitute.org; rasheed.ahmad@dasmaninstitute.orgBackground: Efficient sleep duration and its quality are increasingly recognized as important contributors for maintaining normal body weight. However, lifestyle and social structure within the Arab-gulf region differ compared to those in the western world. This study was specifically conducted in Kuwait’s population to investigate the link between sleep quality (SQ) and obesity in the absence of sleep apnea (SA) onset.Methods: SQ was measured by the Pittsburgh Sleep Quality Index (PQSI) in 984 participants, then verified in 60 individuals including 20 lean (Body mass index/BMI: 18.5– 24.9 kg/m2), 20 overweight (BMI: 25– 29.9 kg/m2) and 20 obese (BMI: ≥ 30 kg/m2) through actigraph worn over the right-hip for 7 consecutive days to characterize their sleep–wake cycle, rest-activity, and physical activity. Blood samples were collected for metabolic markers.Results: 59.6% of participants reported a PSQI score higher than 5, with 57.6% of the participants reporting less than 6 hours of sleep per day. The data show that both SQ and sleep duration are considered inadequate in comparison to the international SQ standards. We found a significant association between SQ and obesity independent of age and sex. Actigraph data further supported the independent association of sleep duration on BMI within the population (p < 0.001). Additionally, total sleep time (TST) was found to significantly correlate with several other metabolic factors including diastolic blood pressure, elevated resting heart rate (RHR), triglycerides, total cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), C-peptide, and C-Reactive Protein (CRP) secretion. Further multiple-regression analysis showed a significant independent association between blood pressure (p < 0.03), HOMA-IR (p < 0.04), and C-peptide (p < 0.3) and sleep duration.Conclusion: These findings suggest that sleep deprivation and disturbance could be indirect factors involved in the development of not only obesity in Kuwait but also other metabolic syndromes such as type 2 diabetes.Keywords: sleep, Kuwait, obesity, PSQI

Abstract The imipramine ONC201 has antiproliferative effects in several cancer cell types and activates integrated stress response pathway associated with the induction of Damage Inducible Transcript 3 (DDIT3, also known as C/EBP homologous protein or CHOP). We investigated the signaling pathways through which ONC201/CHOP crosstalk is regulated in ONC201-treated nonmetastatic and metastatic cancer cell lines (Dukes' type B colorectal adenocarcinoma nonmetastatic SW480 and metastatic LS-174T cells, respectively). Cell proliferation and apoptosis were evaluated by MTT assays and flow cytometry, gene expression was assessed by Affymetrix microarray, signaling pathway perturbations were assessed in silico, and key regulatory proteins were validated by Western blotting. Unlike LS-174T cells, SW480 cells were resistant to ONC201 treatment; Gene Ontology analysis of differentially expressed genes showed that cellular responsiveness to ONC201 treatment also differed substantially. In both ONC201-treated cell lines, CHOP expression was upregulated; however, its upstream regulatory mechanisms were perturbed. Although, PERK, ATF6 and IRE1 ER-stress pathways upregulated CHOP in both cell types, the Bak/Bax pathway regulated CHOP only LS-174T cells. Additionally, CHOP RNA splicing profiles varied between cell lines; these were further modified by ONC201 treatment. In conclusion, we delineated the signaling mechanisms by which CHOP expression is regulated in ONC201-treated non-metastatic and metastatic colorectal cell lines. The observed differences could be related to cellular plasticity and metabolic reprogramming, nevertheless, detailed mechanistic studies are required for further validations.

Background. Cement plants generate particulate matter (PM) across processes from raw material preparation to packaging. The presence of total suspended particulates (TSP) coming out of the stack causes a high accumulation of dust in residential areas. Human exposure to TSP could affect human health and wellbeing. Objectives. The present study aims to evaluate concentrations of TSP and to estimate the health risks of TSP exposure through the inhalation pathway in communities surrounding a private cement industry in Maros regency, Indonesia. Methods. Total suspended particulates were collected using a high-volume air sampler (HVAS) at five locations. Samples were taken by grab sampling for 24 hours. The SCREEN3 program was used to view the maximum range and distribution of pollutants based on the geographical, stack profiles and meteorological factors in the study area. Hazard quotient (HQ) was used to estimate non-carcinogenic risks of TSP in surrounding communities. Results. Total suspended particulate concentrations were measured with a maximum value of 133.24 μg/m3 and a minimum value of 18.48 μg/m3. This maximum value exceeds the minimum acceptable level from Canadian National Ambient Air Quality Objectives (C-NAAQOs). The non-carcinogenic risks from the inhalation pathway were low except for location 3 (HQ>1) across all locations. Conclusions. The cement plant may significantly contribute to total TSP concentrations in air and may potentially have adverse effects on human health. Communities near the cement plant are vulnerable to TSP exposure and measures are needed to reduce TSP in Maros regency, Indonesia. Participant Consent. Obtained Ethics Approval. This study was approved by the Health Research Ethics Committee of Hasanuddin University with protocol number 28920093022. Competing Interests. The authors declare no competing financial interests.

Objectives: Bariatric surgery is a well-established treatment for obesity and type 2 diabetes. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has emerged as a promising therapy for type 2 diabetes. This study aimed to compare the effects of bariatric surgery, semaglutide (a GLP-1 receptor agonist), and tirzepatide in Sprague-Dawley rats fed a high-fat diet. Methods: Rats were divided into surgery, semaglutide, and tirzepatide treatment groups, along with a control group (sham). Weight, oral glucose tolerance, and levels of metabolic markers were assessed, along with adipose and liver tissue analysis. Results: Surgery led to a 15.5% weight reduction, while rats treated with semaglutide exhibited a 10.7% reduction. Tirzepatide treatment at various concentrations (10, 50, and 100 nmol/kg) resulted in weight reductions of 5.0%, 14.9%, and 17.7%, respectively, compared to the sham group. Metabolic analyte levels decreased in intervention groups compared to the sham group, indicating improved metabolic health and glucose tolerance. Adipose tissue weight and hepatic liver fat droplets decreased in the intervention groups. Conclusion: Bariatric surgery and tirzepatide treatment significantly improved metabolic parameters in obese rats. Tirzepatide, particularly at higher concentrations, showed pronounced improvements compared to surgery and semaglutide. These findings suggest that high doses of tirzepatide could be explored as an alternative to bariatric surgery for the treatment of obesity. [ABSTRACT FROM AUTHOR]

High-fat diets (HFDs) shape the gut microbiome and promote obesity, inflammation, and liver steatosis. Fish and soybean are part of a healthy diet; however, the impact of these fats, in the absence of sucrose, on gut microbial dysbiosis and its association with liver steatosis remains unclear. Here, we investigated the effect of sucrose-free soybean oil-and fish oilbased high fat diets (HFDs) (SF-Soy-HFD and SF-Fish-HFD, respectively) on gut dysbiosis, obesity, steatosis, hepatic inflammation, and insulin resistance. C57BL/6 mice were fed these HFDs for 24 weeks. Both diets had comparable effects on liver and total body weights. But 16S-rRNA sequencing of the gut content revealed induction of gut dysbiosis at different taxonomic levels. The microbial communities were clearly separated, showing differential dysbiosis between the two HFDs. Compared with the SF-Fish-HFD control group, the SF-Soy-HFD group had an increased abundance of Bacteroidetes, Firmicutes, and Deferribacteres, but a lower abundance of Verrucomicrobia. The Clostridia/Bacteroidia (C/B) ratio was higher in the SF-Soy-HFD group (3.11) than in the SF-Fish-HFD group (2.5). Conversely, the Verrucomicrobiacae/S24_7 (also known as Muribaculaceae family) ratio was lower in the SF-Soy-HFD group (0.02) than that in the SF-Fish-HFD group (0.75). The SF-Soy-HFD group had a positive association with S24_7, Clostridiales, Allobaculum, Coriobacteriaceae, Adlercreutzia, Christensenellaceae, Lactococcus, and Oscillospira, but was related to a lower abundance of Akkermansia, which maintains gut barrier integrity. The gut microbiota in the SF-Soy-HFD group had predicted associations with host genes related to fatty liver and inflammatory pathways. Mice fed the SF-Soy-HFD developed liver steatosis and showed increased transcript levels of genes associated with de novo lipogenesis (Acaca, Fasn, Scd1, Elovl6) and cholesterol synthesis (Hmgcr) pathways compared to those in the SF-Fish-HFDgroup. No differences were observed in the expression of fat uptake genes (Cd36 and Fabp1). The expression of the fat efflux gene (Mttp) was reduced in the SFSoy-HFD group. Moreover, hepatic inflammation markers (Tnfa and Il1b) were notably expressed in SF-Soy-HFD-fed mice. In conclusion, SF-Soy-HFD feeding induced gut dysbiosis in mice, leading to steatosis, hepatic inflammation, and impaired glucose homeostasis. [ABSTRACT FROM AUTHOR]

The automated classification of ambient air pollutants is an important task in air pollution hazard assessment and life quality research. In the current study, machine learning (ML) algorithms are used to identify the inter-correlation between dominant air pollution index (API) for PM10 percentile values and other major air pollutants in order to detect the vital pollutants’ clusters in ambient monitoring data around the study area. Two air quality stations, CA0016 and CA0054, were selected for this research due to their strategic locations. Non-linear RPart and Tree model of Decision Tree (DT) algorithm within the R programming environment were adopted for classification analysis. The pollutants’ respective significance to PM10 occurrence was evaluated using Random forest (RF) of DT algorithms and K means polar cluster function identified and grouped similar features, and also detected vital clusters in ambient monitoring data around the industrial areas. Results show increase in the number of clusters did not significantly alter results. PM10 generally shows a reduction in trend, especially in SW direction and an overall minimal reduction in the pollutants’ concentration in all directions is observed (less than 1). Fluctuations were observed in the behaviors of CO and NOx during the day while NOx displayed relative stability. Results also show that a direct and positive linear relationship exists between the PM10 (target pollutant) and CO, SO2, which suggests that these pollutants originate from the same sources. A semi-linear relationship is observed between the PM10 and others (O3 and NOx) while humidity shows a negative linearity with PM10. We conclude that most of the major pollutants show a positive trend toward the industrial areas in both stations while traffic emissions dominate this site (CA0016) for CO and NOx. Potential applications of nuggets of information derived from these results in reducing air pollution and ensuring sustainability within the city are also discussed. Results from this study are expected to provide valuable information to decision makers to implement viable strategies capable of mitigating air pollution effects.

Obesity is characterized by chronic low-grade inflammation. Obese people have higher levels of caveolin-1 (CAV1), a structural and functional protein present in adipose tissues (ATs). We aimed to define the inflammatory mediators that influence CAV1 gene regulation and the associated mechanisms in obesity. Using subcutaneous AT from 27 (7 lean and 20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor-alpha (TNF-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). CAV1 gene expression was associated with proinflammatory cytokines and chemokines and their cognate receptors (r ≥ 0.447, p ≤ 0.030), but not with anti-inflammatory markers. CAV1 expression was correlated with CD163, indicating a prospective role for CAV1 in the adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces CAV1 gene transcription by mediating NF-κB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and the TNF-α signaling pathway is intriguing and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.

Introduction Having a good awareness of ovarian cancer (OC) risk and protective factors could facilitate early diagnosis. This study aimed to assess Palestinian women’s awareness about OC risk and protective factors and to identify the factors associated with having good awareness. Methods A cross-sectional study was conducted from July 2019 to March 2020 in the two main areas of Palestine: the West Bank and Jerusalem (WBJ) and the Gaza Strip. A translated-into-Arabic version of the validated OC awareness measure was utilized. Adult women attending hospitals, primary healthcare centers, and public spaces at 11 governorates were invited to participate. The awareness level was categorized based on the number of factors recognized: poor (0 to 5), fair (6 to 10) and good (11 to 15). Results Of the 6095 women approached, 5618 agreed and completed the questionnaire (response rate = 92.1%). The final analysis included 5411 questionnaires. The most identified modifiable OC risk factor was ‘being a smoker’ (n = 4024, 74.4%), whereas the least identified was ‘having in vitro fertilization treatment’ (n = 1652, 30.5%). The most identified non-modifiable OC risk factor was ‘having ovarian cysts’ (n = 3136, 58.0%), whereas the least identified was ‘having endometriosis’ (n = 1880, 34.7%). The most identified OC protective factor was ‘breastfeeding’ (n = 4770, 88.2%), whereas the least identified was ‘using the pill for a long time’ (n = 930, 17.2%). Only 820 women (15.2%) displayed good awareness of OC risk and protective factors. Women from the Gaza Strip were slightly more likely than women from the WBJ to have good awareness (16.4% vs. 14.2%). In contrast, post-secondary education, higher monthly income, being married, and knowing someone with cancer were associated with an increase in the likelihood of displaying good awareness. Conclusion The overall awareness of OC risk and protective factors in this study was low. Educational interventions are needed to improve Palestinian women’s awareness.