Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae.

Glycosphingolipids (GSLs) are products of lipid glycosylation that have been implicated in the development of cardiovascular diseases. In diabetes, the adipocyte microenvironment is characterized by hyperglycemia and inflammation, resulting in high levels of GSLs. Therefore, we sought to assess the GSL content in extracellular vesicles derived from the adipose tissues (adiposomes) of obese-diabetic (OB-T2D) subjects and their impact on endothelial cell function. To this end, endothelial cells were exposed to adiposomes isolated from OB-T2D versus healthy subjects. Cells were assessed for caveolar integrity and related signaling, such as Src-kinase and caveolin-1 (cav-1) phosphorylation, and functional pathways, such as endothelial nitric oxide synthase (eNOS) activity. Compared with adiposomes from healthy subjects, OB-T2D adiposomes had higher levels of GSLs, especially LacCer and GM3; they promoted cav-1 phosphorylation coupled to an obvious loss of endothelial surface caveolae and induced eNOS-uncoupling, peroxynitrite generation, and cav-1 nitrosylation. These effects were abolished by Src kinase inhibition and were not observed in GSL-depleted adiposomes. At the functional levels, OB-T2D adiposomes reduced nitric oxide production, shear response, and albumin intake in endothelial cells and impaired flow-induced dilation in healthy arterioles. In conclusion, OB-T2D adiposomes carried a detrimental GSL cargo that disturbed endothelial caveolae and the associated signaling.

The risk of perinatal mortality following short inter-pregnancy intervals-insights from 692 402 pregnancies in 113 Demographic and Health Surveys from 46 countries: a population-based analysis.

BACKGROUND: Inter-pregnancy interval has been identified as a potentially modifiable risk factor to improve perinatal outcomes. We examined the WHO recommended interval of at least 24 months after a livebirth to next pregnancy, and its recommendation of waiting for at least 6 months after a pregnancy loss to improve subsequent pregnancy outcomes. We aimed to estimate the association between inter-pregnancy interval and perinatal mortality using the Demographic and Health Survey reproductive and contraceptive calendar. METHODS: For this population-based analysis, we extracted data for pregnancies with gestational age and pregnancy outcomes from 113 publicly available Demographic and Health Surveys conducted between 2000 and 2022 in 46 countries that included a reproductive or contraceptive calendar module. The primary outcome was perinatal mortality (stillbirth and early neonatal death) while the inter-pregnancy interval was the exposure of interest, grouped into categories of less than 6 months, 6-11 months, 12-17 months, 18-23 months, and 24-59 months. The analysis was stratified by preceding pregnancy outcome (livebirths, stillbirths, or abortions). The Kaplan-Meier method and Cox proportional hazard model were used to calculate the cumulative probability of perinatal mortality and the hazard ratios (HRs). FINDINGS: The analysis sample comprised of 692 402 pregnancies contributed by 570 145 women with a mean age of 28·4 years (SD 5·96). The overall HR of perinatal death was 2·72 (95% CI 2·52-2·93) times higher for an inter-pregnancy interval of less than 6 months compared with the WHO recommended optimal waiting time of 18-23 months following a livebirth. Overall HRs followed a context-related pattern, with the highest ratio of 2·95 (95% CI 2·67-3·25) in sub-Saharan Africa and the lowest of 1·98 (1·47-2·66) in north Africa, west Asia, and Europe. Inter-pregnancy intervals of less than 3 months, 6 months, and 12 months following stillbirth or abortion (spontaneous or induced) do not pose a higher risk for perinatal death in subsequent pregnancy. INTERPRETATION: Our study reaffirms the WHO recommendation on optimal interval between the last livebirth and the next pregnancy of at least 24 months and avoiding pregnancy before 18 months. However, our analysis does not support the WHO recommendation of delaying the next pregnancy for at least 6 months after a pregnancy loss for improved perinatal survival. FUNDING: None.

Racial Disparity in Anthracycline-induced Cardiotoxicity in Breast Cancer Patients.

Breast cancer has become the most common cancer in the US and worldwide. While advances in early detection and treatment have resulted in a 40% reduction in breast cancer mortality, this reduction has not been achieved uniformly among racial groups. A large percentage of non-metastatic breast cancer mortality is related to the cardiovascular effects of breast cancer therapies. These effects appear to be more prevalent among patients from historically marginalized racial/ethnic backgrounds, such as African American and Hispanic individuals. Anthracyclines, particularly doxorubicin and daunorubicin, are the first-line treatments for breast cancer patients. However, their use is limited by their dose-dependent and cumulative cardiotoxicity, manifested by cardiomyopathy, ischemic heart disease, arrhythmias, hypertension, thromboembolic disorders, and heart failure. Cardiotoxicity risk factors, such as genetic predisposition and preexisting obesity, diabetes, hypertension, and heart diseases, are more prevalent in racial/ethnic minorities and undoubtedly contribute to the risk. Yet, beyond these risk factors, racial/ethnic minorities also face unique challenges that contribute to disparities in the emerging field of cardio-oncology, including socioeconomic factors, food insecurity, and the inability to access healthcare providers, among others. The current review will address genetic, clinical, and social determinants that potentially contribute to this disparity.

Measuring stillbirth and perinatal mortality rates through household surveys: a population-based analysis using an integrated approach to data quality assessment and adjustment with 157 surveys from 53 countries.

BACKGROUND: In most low-income and middle-income countries (LMICs), national surveys are the main data source for stillbirths and perinatal mortality. Data quality issues such as under-reporting and misreporting have greatly limited the usefulness of such data. We aimed to enhance the use of mortality data in surveys by proposing data quality metrics and exploring adjustment procedures to obtain the best possible measure of perinatal mortality. METHODS: We performed a population-based analysis of data from 157 demographic and health surveys (DHSs) from 1990 to 2020, with reproductive calendar and birth history data from 53 LMICs. Pregnancies terminated before 7 months' gestation were excluded. We examined data quality and compared survey values with reference values obtained from a literature review to assess misreporting of the age at early neonatal death, omission and transference of stillbirths, and very early neonatal deaths. Real cohort life-table rates of stillbirth, early neonatal, and perinatal mortality per 1000 births were calculated. The underlying risks of stillbirth and daily deaths were modelled using modified Gompertz-Makeham models. FINDINGS: Data for 2 008 807 pregnancies of ≥7 months' gestational age were extracted from the reproductive calendar for the analysis period. Age heaping at day 7 occurred in most surveys. The median value for the heaping index of deaths at day 7 was 2·05 (IQR 1·36-2·87). The median ratio of stillbirths to deaths on days 0-1 was 1·15 (0·86-1·51). Of the 157 surveys, 23 (15%) were considered to have plausible ratios, 71 (45%) had probable ratios, and 63 (40%) had improbable ratios. The ratio of deaths on days 0-1 to deaths on days 2-6 varied considerably between surveys and 119 surveys (76%) had ratios of less than 2·4, indicative of under-reporting of very early neonatal deaths in most surveys. The fully adjusted model increased the median stillbirth rates from 12·2 (9·4-15·9) to 25·6 (18·0-33·4) per 1000 births, with a median relative increase of 95·0% (56·6-136·6). The median perinatal mortality rate also increased from 32·6 (23·6-38·3) to 44·8 (32·8-58·0) per 1000 births, with a median relative increase of 47·8% (6·9-61·0). INTERPRETATION: A simultaneous focus on stillbirths and early neonatal mortality facilitates a comprehensive assessment of inaccurate reporting in household surveys and allows for better use of surveys in planning and monitoring of efforts to reduce stillbirths and early neonatal mortality. FUNDING: None.

Ultrasound-Guided Techniques for Postoperative Analgesia in Patients Undergoing Laparoscopic Sleeve Gastrectomy: Erector Spinae Plane Block vs. Quadratus Lumborum Block.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a common bariatric surgery. Regional anesthetic techniques decrease postoperative pain, narcotic analgesic requirements, and opioid-related adverse effects in patients scheduled for bariatric surgery. OBJECTIVES: The research team conducted this clinical trial to assess the effects of bilateral ultrasound (US)-guided erector spinae plane block (ESPB) on postoperative pain scores and postoperative analgesics consumption compared with bilateral US-guided quadratus lumborum block (QLB) in the first 24 hours following LSG. STUDY DESIGN: A randomized, double-blind, prospective, single-center study. SETTING: Ain-Shams University Hospitals. METHODS: Patients: One hundred twenty morbidly obese patients were scheduled for LSG. INTERVENTION: Were randomly assigned to 3 groups (40 each): bilateral US-guided ESPB, bilateral US-guided QLB, or control (C) group. MEASUREMENTS: The time to first rescue analgesia (ketorolac) was considered as a primary outcome. The time to perform the block, the duration of anesthesia, the time to first ambulation, the visual analog scale (VAS) at rest, VAS at movement, the total nalbuphine consumption (mg), the total requirements of rescue analgesia (ketorolac) over the first 24 hours after surgery and the study safety profile were considered as secondary outcomes. RESULTS: The time to perform the block and the duration of anesthesia were higher in the QLB group compared to other groups, with significant differences between ESPB and C groups (P < 0.001, P < 0.001, respectively). The ESPB and QLB groups were superior to the C group as regards the time to first rescue analgesia, the total dose of rescue analgesia, and the total nalbuphine consumption (P < 0.001, P < 0.001, P < 0.001, respectively). In the C group, VAS-R and VAS-M readings were higher in the first 18 hours after surgery (P < 0.001, P < 0.001, respectively). In the rest 6 hours of 24 hours after surgery, the QLB group had lower VAS-R and VAS-M readings than the C group (P < 0.001, P < 0.001, respectively). More patients in the C group had higher incidences of nausea and vomiting (P = 0.011, P = 0.002, respectively). In the C group, the time to first ambulation, the length of PACU stay, and the hospital stay were higher in comparison to the ESPB and QLB groups (P < 0.001, P < 0.001, P < 0.001, respectively). More patients in the ESPB and QLB groups were satisfied with postoperative pain management protocol (P < 0.001). LIMITATIONS: The lack of postoperative respiratory assessment (e.g., spirometry) precluded the identification of either ESPB or QLB effects on pulmonary functions in such patients. CONCLUSION: Bilateral ultrasound-guided erector spinae plane block and bilateral ultrasound-guided quadratus lumborum block provided adequate postoperative pain control and reduced postoperative analgesic requirements for morbidly obese patients scheduled for laparoscopic sleeve gastrectomy with priority to bilateral erector spinae plane block.

Obesity-Associated Vitamin D Deficiency Correlates with Adipose Tissue DNA Hypomethylation, Inflammation, and Vascular Dysfunction.

Vitamin D (VD) deficiency is a hallmark of obesity and vascular dysfunction. We sought to test the hypothesis that VD deficiency may contribute to obesity-related vascular dysfunction by inducing adipokine hypomethylation and augmented expression. To this end, we collected blood and adipose tissues (ATs) from a cohort of 77 obese participants who were classified as having mild, moderate, or severe VD deficiency. The body composition, vascular reactivity, cardiometabolic profiles, and DNA methylation of 94 inflammation-related adipokines were measured. Our results show that higher degrees of VD deficiency were associated with lower DNA methylation and induced the expression of inflammatory adipokines such as B-cell lymphoma 6 (BCL6), C-X-C Motif Chemokine Ligand 8 (CXCL8), histone deacetylase 5 (HDAC5), interleukin 12A (IL12A), and nuclear factor κB (NFκB) in the ATs. They were also associated with higher BMI and total and visceral fat mass, impaired insulin sensitivity and lipid profiles, AT hypoxia, and higher concentrations of circulating inflammatory markers. Moderate and severe VD deficiency correlated with impaired vasoreactivity of the brachial artery and AT-isolated arterioles, reduced nitric oxide generation, and increased arterial stiffness. In a multivariate regression analysis, the VD deficiency level strongly predicted the adipokine methylation score, systemic inflammation, and microvascular dysfunction. In conclusion, our findings suggest that VD deficiency is a possible contributor to obesity-related adipokine hypomethylation, inflammation, and vascular dysfunction.

Gene polymorphisms of cyclin-dependent kinase inhibitor and matrix metalloproteinase-9 in Sudanese patients with esophageal squamous cell carcinoma.

BACKGROUND: The polymorphisms of the cyclin-dependent kinase inhibitor (CDKN1A) gene and matrix metalloproteinase-9 (MMP9) gene may increase one's susceptibility to malignancies. In this study, the association of the single nucleotide polymorphisms (SNPs) CDKN1A rs1059234 c.70C>T at the 3' untranslated region and MMP9 rs17576 (c.836A>G, p.Gln279Arg) with esophageal squamous cell carcinoma (ESCC) in Sudanese individuals were investigated. MATERIALS AND METHODS: A case-control study involving age- and gender-matched groups were conducted in a cancer center in eastern Sudan (Gadarif) between April and October 2020. The case group consisted of ESCC patients, whereas the control group comprised healthy subjects. Polymerase chain reaction-restriction fragment length polymorphism was performed for the genotyping of the CDKN1A rs1059234 and MMP9 rs17576 SNPs. The genotyping results were confirmed by Sanger sequencing. RESULTS: The genotype distributions for CDKN1A rs1059234 and MMP9 rs17576 were in agreement with the Hardy-Weinberg equilibrium. The variant allele T in CDKN1 rs1059234 c.70C>T was significantly more prevalent in the ESCC patients than in the healthy controls [51.3% vs. 19.2%; OR = 4.4; 95% CI (2.6-7.4); p < 0.001]. Moreover, in CDKN1A rs1059234, the genotype TC + TT [76.9% vs. 38.4%; OR = 5.3; 95% CI (2.6-10.7); p < 0.001] was more frequent in the cases than in the controls, and it was significantly associated with ESCC risk. In MMP9 rs17576, the variant allele G was also significantly prevalent in the cases relative to the controls, and it was significantly associated with increased ESCC risk in the cases compared with the controls [27.5% vs. 1.9%; OR = 19.4; 95%CI (5.8-64.1); p < 0.001]. Both genotypes containing the allele G (AG + GG) were the most common genotypes in the cases [48.7% vs. 3.8%; OR = 23.7; 95%CI (6.8-81.7); p < 0.001], and they significantly increased the risk of ESCC. CONCLUSION: A significant increase in ESCC risk is associated with the SNPs CDKN1A rs1059234 and MMP9 rs17576.

DNA Hypomethylation as a Potential Link between Excessive Alcohol Intake and Cardiometabolic Dysfunction in Morbidly Obese Adults.

A large percentage of obese patients in the United States suffer a comorbid substance use disorder, mainly alcohol use. Alcohol consumption interferes with the absorption of dietary methyl donors such as folate required for the one-carbon metabolism pathway and subsequently for DNA methylation. In this study, we assessed the association between alcohol consumption and DNA methylation in obese subjects. We obtained visceral adipose tissue (VAT) biopsies from bariatric patients. DNA methylation of 94 genes implicated in inflammation and immunity were analyzed in VAT in relation to alcohol consumption data obtained via questionnaires. Vasoreactivity was measured in the brachial artery and the VAT-isolated arterioles. Pro-inflammatory genes were significantly hypomethylated in the heavy drinking category correlating with higher levels of circulating inflammatory cytokines. Alcohol consumption correlated positively with body mass index (BMI), fat percentage, insulin resistance, impaired lipid profile, and systemic inflammation and negatively with plasma folate and vitamin B12, inflammatory gene DNA methylation, and vasoreactivity. In conclusion, these data suggest that alcohol intake is associated with lower DNA methylation and higher inflammation and cardiometabolic risk in obese individuals.

Taurine-Derived Compounds Produce Anxiolytic Effects in Rats Following Developmental Lead Exposure.

Lead (Pb2+) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain's excitation-to-inhibition (E/I) balance. Taurine is a well-established neuroprotective and inhibitory compound for regulating brain excitability. Since mechanistically taurine can facilitate neuronal inhibition through the GABA-AR, the present study examined the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1,000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random drug assignments to either saline, taurine, or taurine-derived compound (TD-101, TD-102, or TD-103) to assess the rats' responsivity to each drug in mitigating the developmental Pb2+-exposure and anxiety-like behaviors through the GABAergic system. Long-Evans hooded rats were assessed using an open field (OF) test for preliminary locomotor assessment. Twenty-four hours later, the same rats were exposed to the elevated plus maze (EPM) and were given an i.p. injection of 43 mg/Kg of the saline, taurine, or TD drugs 15 min prior to testing. Each rat was tested using the triple-blind random assignment method for each drug condition. The OF data revealed that Control female rats had increased locomotor activity over Control male rats, and the Pb2+-exposed males and females had increased locomotor activity when compared to the Control male and female rats. However, in the EPM, the Control female rats exhibited more anxiety-like behaviors over Control male rats, and the Pb2+-exposed male and female rats showed selective responsivity to TD drugs when compared to taurine. For Pb2+-exposed males, TD-101 showed consistent recovery of anxiety-like behaviors similar to that of taurine regardless of Pb2+ dose, whereas in Pb2+-exposed females TD-101 and TD-103 showed greater anxiolytic responses in the EPM. The results from the present psychopharmacological study suggests that taurine and its derivatives are interesting drug candidates to explore sex-specific mechanisms and actions of taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for neurodevelopmental Pb2+ exposure.

Multivariate Analysis of Agronomic Traits in Newly Developed Maize Hybrids Grown under Different Agro-Environments.

Developing high-yielding maize hybrids is essential under the fast-growing global population and abrupt global climate change. Planting density is one of the imperative components for enhancing maize productivity. This study assessed newly developed maize hybrids under three planting densities on two sowing dates. The evaluated hybrids were 40 maize genotypes comprised of 36 F1-developed hybrids and 4 commercial high-yielding check hybrids. The developed hybrids were generated from selected maize inbred lines according to their adaptive traits to high planting density, such as prolificacy, erect leaves, short plants, early silking, anthesis-silking interval, and small tassel size. The applied planting densities were high, intermediate, and low, with 95,000, 75,000, and 55,000 plants/ha, respectively, under timely and late sowing. The high planting density displayed the uppermost grain yield compared with the intermediate and low densities at both sowing dates. The developed hybrid G36 exhibited the highest agronomic performance under high planting density at timely and late sowing. Additionally, G38, G16, G37, G23, G5, G31, G18, G7, G2, G20, G29, and G17 displayed high agronomic traits at both sowing dates. Joint regression and AMMI analyses revealed significant genotype, agro-environment, and genotype × agro-environment interaction effects for grain yield. The AMMI biplot displayed that G39 was closest to the ideal stable hybrid, and the hybrids G36, G18, G38, G17, G2, and G37 were considered desirable stable hybrids. Moreover, the GGE biplot indicated that a high planting density at an optimal sowing date could be considered a representative environment for discriminating high-yielding maize hybrids. The designated promising hybrids are recommended for further inclusion in maize breeding due to their stability and high yields.

Genetic Potential and Inheritance Patterns of Physiological, Agronomic and Quality Traits in Bread Wheat under Normal and Water Deficit Conditions.

Water scarcity is a major environmental stress that adversatively impacts wheat growth, production, and quality. Furthermore, drought is predicted to be more frequent and severe as a result of climate change, particularly in arid regions. Hence, breeding for drought-tolerant and high-yielding wheat genotypes has become more decisive to sustain its production and ensure global food security with continuing population growth. The present study aimed at evaluating different parental bread wheat genotypes (exotic and local) and their hybrids under normal and drought stress conditions. Gene action controlling physiological, agronomic, and quality traits through half-diallel analysis was applied. The results showed that water-deficit stress substantially decreased chlorophyll content, photosynthetic efficiency (FV/Fm), relative water content, grain yield, and yield attributes. On the other hand, proline content, antioxidant enzyme activities (CAT, POD, and SOD), grain protein content, wet gluten content, and dry gluten content were significantly increased compared to well-watered conditions. The 36 evaluated genotypes were classified based on drought tolerance indices into 5 groups varying from highly drought-tolerant (group A) to highly drought-sensitive genotypes (group E). The parental genotypes P3 and P8 were identified as good combiners to increase chlorophyll b, total chlorophyll content, relative water content, grain yield, and yield components under water deficit conditions. Additionally, the cross combinations P2 × P4, P3 × P5, P3 × P8, and P6 × P7 were the most promising combinations to increase yield traits and multiple physiological parameters under water deficit conditions. Furthermore, P1, P2, and P5 were recognized as promising parents to improve grain protein content and wet and dry gluten contents under drought stress. In addition, the crosses P1 × P4, P2 × P3, P2 × P5, P2 × P6, P4 × P7, P5 × P7, P5 × P8, P6 × P8, and P7 × P8 were the best combinations to improve grain protein content under water-stressed and non-stressed conditions. Certain physiological traits displayed highly positive associations with grain yield and its contributing traits under drought stress such as chlorophyll a, chlorophyll b, total chlorophyll content, photosynthetic efficiency (Fv/Fm), proline content, and relative water content, which suggest their importance for indirect selection under water deficit conditions. Otherwise, grain protein content was negatively correlated with grain yield, indicating that selection for higher grain yield could reduce grain protein content under drought stress conditions.

DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults.

Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are CXCL1, CXCL12, CXCL6, IGF2BP2, HDAC4, IL12A, and IL17RA. Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are CXCL6, TLR5, IL6ST, EGR1, IL15RA, and HDAC4. Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.

Adipose Tissue Hypoxia Correlates with Adipokine Hypomethylation and Vascular Dysfunction.

Obesity is characterized by the accumulation of dysfunctional adipose tissues, which predisposes to cardiometabolic diseases. Our previous in vitro studies demonstrated a role of hypoxia in inducing adipokine hypomethylation in adipocytes. We sought to examine this mechanism in visceral adipose tissues (VATs) from obese individuals and its correlation with cardiometabolic risk factors. We propose an involvement of the hypoxia-inducible factor, HIF1α, and the DNA hydroxymethylase, TET1. Blood samples and VAT biopsies were obtained from obese and non-obese subjects (n = 60 each) having bariatric and elective surgeries, respectively. The analyses of VAT showed lower vascularity, and higher levels of HIF1α and TET1 proteins in the obese subjects than controls. Global hypomethylation and hydroxymethylation were observed in VAT from obese subjects along with promoter hypomethylation of several pro-inflammatory adipokines. TET1 protein was enriched near the promotor of the hypomethylated adipokines. The average levels of adipokine methylation correlated positively with vascularity and arteriolar vasoreactivity and negatively with protein levels of HIF1α and TET1 in corresponding VAT samples, serum and tissue inflammatory markers, and other cardiometabolic risk factors. These findings suggest a role for adipose tissue hypoxia in causing epigenetic alterations, which could explain the increased production of adipocytokines and ultimately, vascular dysfunction in obesity.

High Glucose and Advanced Glycation End Products Induce CD147-Mediated MMP Activity in Human Adipocytes.

Basigin (CD147) is a transmembrane glycoprotein that regulates several physiological processes, including the production and activity of matrix metalloproteinases (MMPs). The activity of CD147 depends mainly on its glycosylation, which varies among pathophysiological conditions. However, it is unknown whether CD147 activity or its function in MMP regulation are affected by the diabetic environment, which is characterized by high glucose (HG) levels and an excess of glycation end products (AGEs). In this study, we investigated the effect of HG and AGEs on CD147 expression in human adipocytes. We also examined the mediating role of nuclear factor kappa B (NFκB) and receptor of AGE (RAGE) to this effect. Our findings show that carboxymethyl lysine and HG increased CD147 expression and glycosylation, which was accompanied by increases in MMP2 and MMP9 expression and activity, as well as upregulations of the N-acetylglucosaminyltransferase, MGAT5. These effects were abolished by NFκB and RAGE inhibition, CD147 gene silencing, and by the glycosylation inhibitor, tunicamycin. In conclusion, the current findings indicate that AGEs and HG induce CD147 expression and glycosylation in adipocytes, with possible mediation by NFκB and RAGE. One of the critical outcomes of this pathway is augmented MMP activity known to contribute to cardiovascular complications in diabetes.

Wuxal amino (Bio stimulant) improved growth and physiological performance of tomato plants under salinity stress through adaptive mechanisms and antioxidant potential.

In the present study, ameliorative capabilities of wuxal amino (bio stimulant) under salt stress has been investigated through adaptive mechanisms and antioxidant potential in tomato plants. In the experiment, two different concentrations (2 cm L-1 and 3 cm L-1) of wuxal amino through foliar application and soil irrigation were applied to the salt (150 mM) treated tomato plants and then morphological traits, photosynthetic pigments, osmolytes, secondary metabolites, oxidative stress and antioxidant enzymes activity were assessed at 60 days after planting. The results revealed that salt stress decreased the growth parameters, photosynthetic pigments, soluble sugars and soluble protein whereas, content of proline, ascorbic acid, total phenols, malondialdehyde, hydrogen peroxide and the activity of antioxidant enzymes activity increased under salt stress. Moreover, Wuxal amino application through foliar or soil to salt stressed plants improved morphological traits, photosynthetic pigments, osmolytes, total phenol and antioxidant enzymes activity. Interestingly, the deleterious impact of salinity on tomato plants were significantly reduced and it can be evident from reduced MDA and H2O2 levels. These responses varied with the mode (foliar or soil) of application of Wuxal amino under different concentrations (2 cm L-1 and 3 cm L-1). It was concluded that application of Wuxal amino (2 cm L-1, foliar) and (3 cm L-1; soil) proved best and could be commercially used as eco-friendly tool for the protection of tomato plants grown under salinity stress.

Exogenously Used 24-Epibrassinolide Promotes Drought Tolerance in Maize Hybrids by Improving Plant and Water Productivity in an Arid Environment.

The influence of 24-epibrassinolide (EBR24), applied to leaves at a concentration of 5 µM, on plant physio-biochemistry and its reflection on crop water productivity (CWP) and other agronomic traits of six maize hybrids was field-evaluated under semi-arid conditions. Two levels of irrigation water deficiency (IWD) (moderate and severe droughts; 6000 and 3000 m3 water ha-1, respectively) were applied versus a control (well-watering; 9000 m3 water ha-1). IWD reduced the relative water content, membrane stability index, photosynthetic efficiency, stomatal conductance, and rates of transpiration and net photosynthesis. Conversely, antioxidant enzyme activities and osmolyte contents were significantly increased as a result of the increased malondialdehyde content and electrolyte leakage compared to the control. These negative influences of IWD led to a reduction in CWP and grain yield-related traits. However, EBR24 detoxified the IWD stress effects and enhanced all the above-mentioned parameters. The evaluated hybrids varied in drought tolerance; Giza-168 was the best under moderate drought, while Fine-276 was the best under severe drought. Under IWD, certain physiological traits exhibited a highly positive association with yield and yield-contributing traits or CWP. Thus, exogenously using EBR24 for these hybrids could be an effective approach to improve plant and water productivity under reduced available water in semi-arid environments.

Socioeconomic variations in risky sexual behavior among adolescents in 14 sub-Saharan Africa countries who report ever having had sex.

BACKGROUND: Equity is a guiding principle of the Global Strategy for Women, Children and Adolescents' Health (2016-2030) aimed at improving adolescent health and responding more effectively to adolescents' needs. We investigated the socioeconomic differentials in having multiple sexual partners and condom use among unmarried adolescents who reported ever having had sex aged 15-19 years in 14 sub-Saharan countries. METHODS: Using the most recent publicly available Demographic and Health Surveys conducted between 2011 and 2018, we calculated survey- and sex-specific proportions of two or more partners and condomless sex, both overall and by selected socioeconomic characteristics and we fitted logistic regression models to estimate the survey- and sex-specific adjusted odds ratios. The pooled adjusted odds ratios were estimated using multilevel logistic regression. RESULTS: In most countries, higher percentages of male adolescents than female adolescents reported having more than one partner in the last 12 months. Conversely, a lower percentage of young male reported having condomless sex when compared to young female: from 19.8% in Gabon to 84.5% in Sierra Leone among male adolescents and from 32.6% in Gabon to 93.2% in Sierra Leone among female adolescents. In the multilevel analyses, condomless sex was associated with place of residence, wealth and schooling for both female and male adolescents, while among male adolescents multiple partnerships was significantly associated with place of residence. CONCLUSION: Our findings on disparities in condomless sex associated with socioeconomic characteristics might reflect constraint choice and decision making. Results also suggest the need for educational programming and services and better access to barrier methods.