Lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with type 1 diabetes. A case-control study among UAE population.

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation and cause of endothelial dysfunction (ED). Heart rate variability (HRV) is a marker of sympathetic and parasympathetic autonomic nervous system dysfunction. We investigated the association of lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with T1DM among UAE population. Method: In this case-control study we recruited 126 adolescents (13-22 years) from Abu Dhabi, UAE (United Arab Emirates). Demographic, anthropometric, blood and urine samples were collected after an overnight fasting. HRV measurements were determined per Task Force recommendations. Independent t-test or Mann-Whitney U test and Pearson's Chi-squared test were used to compare groups. Adjusted conditional logistic regression model was used to identify the determinants independently associated with T1DM. Results: The mean ages in control (n = 47) and patient (n = 79) groups were 17.5 ± 4.6 and 18.6 ± 4.8 years, respectively. A family history of diabetes and waist and hip circumferences significantly differed between the groups (p = 0.030 and 0.010). The patients with T1DM exhibited significantly higher levels of atherogenic markers than control. Endothelial dysfunction biomarkers such as levels of sICAM-1 (p < 0.001), adiponectin (p < 0.001) and 25-hydroxyvitamin D (p < 0.001) were significantly different in the control group compared with those in the T1DM group. There was a significant difference in SDNN intervals, NN50, pNN50, and SD1/SD2 among the two groups. In adjusted analysis, total cholesterol (adjusted Odds Ratio (aOR): 2.78, 95 % CI:1.37-5.64; p = 0.005), LDL (2.66, 95%CI:1.19-5.92; p = 0.017), and triglycerides (5.51, 95%CI:1.57-19.41; p = 0.008) were significantly associated with developing T1DM. The HRV indicators were significantly associated with decrease odds of T1DM after controlling for SBP, BMI, and family history of DM. Conclusion: In this study, adolescents with T1DM showed a significant association with lipid profile, ED, and HRV compared with controls. Thus, an early attention to diabetes control is required to reduce the risk of cardiac autonomic neuropathy leading to various cardiovascular diseases.

Circulating ceramide levels and ratios in Emirati youth under 18 years: associations with cardiometabolic risk factors.

BACKGROUND: Circulating ceramide (Cer) drives various pathological processes associated with cardiovascular diseases, liver illness, and diabetes mellitus. Although recognized as predictors of cardiometabolic diseases (CMD) in research and clinical settings, their potential for predicting CMD risk in individuals under 18 remains unexplored. OBJECTIVES: This study was designed to utilize Liquid Chromatography-Mass Spectrometry (LC-MS/MS) methodology to determine the biological reference ranges for Cer in plasma samples of Emirati children and develop a risk assessment score (CERT-1) based on Cer concentrations. METHODS: Using LC-MS/MS, we developed a method to measure five Cer species in plasma samples of 582 Emirati participants aged 5-17. We used the circulating concentrations of these Cer to determine their reference intervals in this population. We employed traditional statistical analyses to develop a risk score (CERT-1) and assess the association between Cer levels and conventional biomarkers of CMD. RESULTS: We validated a high-throughput methodology using LC-MS/MS to quantify five Cer species in human plasma. Reference values for this population (n = 582) were quantified: CerC16:0 (0.12-0.29 µmol/L), CerC18:0 (0.019-0.067 µmol/L), CerC22:0 (0.102-0.525 µmol/L), CerC24:0 (0.65-1.54 µmol/L) and CerC24:1 (0.212-0.945 µmol/L). We devised a risk assessment score (CERT-1) based on plasma Cer content in the study participants, showing that 72.5% have low to moderate risk and 9.3% are at a higher risk of developing CMD. Our analyses also revealed a significant correlation (P < 0.05) between this score and the conventional risk factors linked to CMD, indicating its potential clinical implication. CONCLUSION: This study presents a clinical-scaled LC-MS/MS methodology for assessing clinically relevant Cer, setting reference ranges, and developing a risk score (CERT-1) for young Emirati individuals. Our findings can enhance primary risk prediction and inform the management and follow-up of CMD from an early age.

Galectin-3 and Autophagy in Renal Acute Tubular Necrosis.

Acute kidney injury (AKI) is a public health burden with increasing morbidity and mortality rates and health care costs. Acute tubular necrosis (ATN) is the most common cause of AKI. Cisplatin (CIS) is a platinum-based chemotherapeutic agent used in the treatment of a wide variety of malignancies such as lung, breast, ovary, testis, bladder, cervix, and head and neck cancers. Autophagy plays an important role in AKI. Galectin-3 (Gal-3) is significantly increased in renal tubules in AKI; however, its role in autophagy is not well understood. Male C57B6/J and B6.Cg-Lgals3 /J Gal-3 knockout (KO) mice were used to induce AKI using a CIS mouse model of ATN. Renal Gal-3 and autophagy proteins' expression were measured using standard histologic, immunofluorescent, and enzyme-linked immunosorbent assay techniques. The data were presented as the mean ± S.E. Statistically significant differences (p < 0.05) were calculated between experimental groups and corresponding control groups by one-way analysis of variance. There was a significant increase in renal concentrations of Gal-3 in the Gal-3 wild-type CIS-treated mice when compared with sham control mice. There were significantly higher concentrations of renal LC3B, ATG13, Ulk-1, Beclin, ATG5, ATG12, ATG9A, and p-AMPK in the CIS-treated Gal-3 KO mice than in the Gal-3 wild-type CIS-treated mice. Further, there were significantly higher concentrations of mTOR, p- NF-κB, beta-catenin, and p62 in the kidneys of the Gal-3 wild-type CIS-treated mice than in the Gal-3 KO CIS-treated mice. Our findings affirm the connection between Gal-3 and autophagy, revealing its central role as a connector with prosurvival signaling proteins. Gal-3 plays a pivotal role in orchestrating cellular responses by interacting with prosurvival signal pathways and engaging with autophagy proteins. Notably, our observations highlight that the absence of Gal-3 can enhance autophagy in CIS-induced ATN.

Unraveling the complex interplay between obesity and vitamin D metabolism.

Vitamin D deficiency and obesity are a worldwide health issue. Obesity refers to the accumulation of excessive fats in the body which could lead to the development of diseases. Obese people have low vitamin D levels for several reasons including larger volume of distribution, vitamin D tightly bound in fatty tissues, reduced absorption, and diets with low vitamin D. Accurately measuring vitamin D metabolites is challenging. The Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the analysis of vitamin D metabolites in the serum. Blood samples were collected from 452 subjects which consisted of baseline (vitamin D deficient obese subjects), follow-up (supplemented obese subjects), and healthy volunteers. The vitamin D metabolites were separated adequately by the developed UHPLC-MS/MS method. Moreover, the validation criteria for the method were within an acceptable range. The baseline, follow-up and even healthy volunteers were deficient in 25OHD3 and 25OHD2. The baseline and healthy subjects had comparable concentration of vitamin D2 and D3. However, healthy subjects had a higher concentration of 25OHD and its epimer compared to the baseline subjects. The vitamin D3 was increased significantly in the follow- up subjects; therefore, the 25OHD3 was increased significantly compared to the baseline as well; however, the increase was insufficient to achieve the optimal range. The UHPLC-MS/MS method test was applied successfully on estimation of vitamin D metabolites in subjects. This study indicates the significance of taking into account the metabolic and storage effects when evaluating the vitamin D status in obese subjects.

Does Hypertension Affect the Recovery of Renal Functions after Reversal of Unilateral Ureteric Obstruction?

Research has demonstrated that hypertension can lead to an exaggeration in the renal functional and histological changes caused by ureteral obstruction. These changes were particularly observed shortly after the release of a relatively brief period of unilateral ureteral obstruction (UUO). However, the long-term impact of hypertension on the recovery of renal functions has not been investigated beyond the immediate period after UUO reversal. In order to investigate this effect, a group of spontaneously hypertensive rats (G-SHR, n = 11) and a group of normotensive Wistar Kyoto rats (G-NTR, n = 11) were subjected to a 48 h reversible left UUO. The impact of UUO was then examined 45 days after the reversal of obstruction. The glomerular filtration rate, renal blood flow, and the fractional excretion of sodium in the post-obstructed left kidney (POK) showed similarities to the non-obstructed right kidney (NOK) in both groups. However, the changes in the albumin creatinine ratio, renal injury markers, pro-apoptotic markers, and histological changes in the G-SHR were much more pronounced compared to the G-NTR. We conclude that hypertension continues to have a significant impact on various aspects of renal injury and function, even several weeks after UUO reversal.

Pathophysiologic effects of waterpipe (shisha) smoke inhalation on liver morphology and function in mice.

AIMS: The global prevalence of waterpipe tobacco smoking is increasing. Although the cardiorespiratory, renal, and reproductive effects of waterpipe smoking (WPS) are well-documented, there is limited knowledge regarding its adverse impact on the liver. Therefore, our study aimed to assess the effects and potential mechanisms of WPS inhalation for one or four weeks on the liver. MAIN METHODS: Mice were exposed to WPS for 30 min per day, five days per week, while control mice were exposed to clean air. KEY FINDINGS: Analysis using light microscopy revealed the infiltration of immune cells (neutrophils and lymphocytes) accompanied by vacuolar hepatic degeneration upon WPS inhalation. At the four-week timepoint, electron microscopy analysis demonstrated an increased number of mitochondria with a concomitant pinching-off of hepatocyte plasma membranes. WPS exposure led to a significant rise in the activities of liver enzymes alanine aminotransferase and aspartate aminotransferase in the bloodstream. Additionally, WPS inhalation elevated lipid peroxidation and reactive oxygen species levels and disrupted the levels of the antioxidant glutathione in liver tissue homogenates. The concentration of proinflammatory cytokines, including tumor necrosis factor α, interleukin (IL)-6, and IL-1ß, was significantly increased in the WPS-exposed group. Furthermore, WPS inhalation induced DNA damage and a significant increase in the levels of cleaved caspase-3, cytochrome C and hypoxia-inducible factor 1α along with alterations in the activity of mitochondrial complexes I, II, III and IV. SIGNIFICANCE: Our findings provide evidence that WPS inhalation triggers changes in liver morphology, oxidative stress, inflammation, DNA damage, apoptosis, and alterations in mitochondrial activity.

Distribution and Association of Cardiometabolic Risk Factors Among Youth From Al Ain City, United Arab Emirates.

AIM: The purpose of this study was to examine the distribution of cardiometabolic risk factors (CMRF) among UAE University students. METHODS: The present study employed a cross-sectional design to investigate the characteristics of a sample of young individuals aged 17-26 years. The participants were exclusively drawn from the student population of UAE University. Anthropometric measurements, including weight, height, blood pressure, and random blood collection, were conducted. The statistical methods employed for comparison included the Chi-square test, Fisher's exact test, and either the two-sample t-test or the Wilcoxon rank sum test. Logistic models, both adjusted and unadjusted, were utilized to evaluate the correlation between excessive body weight and various cardiovascular and metabolic risk factors (CMRFs). All P-values were calculated using a two-sided test, and a significance level of P < 0.05 was used to determine statistical significance. The statistical computing and graphics software R (version 4.2.2) was utilized to perform all data analyses. RESULTS: Among the 269 individuals who took part in the study, a significant proportion of 55% (n=148) were identified as males. Additionally, 36% (n=97) of the participants reported having a family history of hypertension. It is worth noting that the total sample consisted of younger individuals, with a mean age of 19 years (standard deviation ±1.8). There was a significant association between overweight/obesity and male gender (p=0.003), as well as having a family history of heart attack (p=0.038), high lipid profile, and high-sensitivity C-reactive protein (hs-CRP). There was no observed correlation between a family history of hypertension and HbA1C levels in individuals with a non-normal weight. substantially elevated cardiometabolic risk variables, including systolic blood pressure (SBP) equal to or greater than 130 mmHg, diastolic blood pressure (DBP) equal to or greater than 80 mmHg, triglyceride (TG) levels equal to or greater than 150 mg/dL, high-density lipoprotein cholesterol (HDL-C) levels equal to or less than 35 mg/dL, apolipoprotein B (Apo B) levels equal to or greater than 1.3 g/L, and high-sensitivity C-reactive protein (hs-CRP) levels equal to or more than 1 mg/L, were observed to be substantially more prevalent in individuals with excess body weight compared to those with normal weight. Furthermore, the likelihood of having low HDL levels is observed to increase by 14% (Adjusted Odds Ratio = 1.14, 95% Confidence Interval [1.07 to 1.23]) among students who have extra body weight, while accounting for age and gender as controlling factors. CONCLUSIONS: Excess body weight, already in youth, was associated with increased CMRF, particularly high SBP and TG plus low HDL-C.

Incidence of malignant pericardial effusion in pericardiocentesis patients and post-procedure care: an oncology center pilot study.

The etiology of pericardial effusion can affect many important factors during and after pericardiocentesis. The frequency of etiologies varies among different patient populations. Pericardiocentesis is an important diagnostic and therapeutic intervention; however, data on the characteristics of malignant pericardial effusion are lacking in the United Arab Emirates (UAE). Thus, we conducted a pilot study on the incidence and post-procedure care of patients who underwent pericardiocentesis in our facility to enhance their management and treatment. This retrospective study included all cases of pericardiocentesis between 2011-2019. Epidemiological, clinical, and biochemical data were collected and analyzed. Pericardial fluid analysis, malignancy type, recurrence rate, need for a repeat procedure, and echocardiography findings were reviewed. Thirty-three patients (mean: 47.2 years) underwent pericardiocentesis, and 22 of these patients (66.7%) had malignancy. The predominant cancers were breast cancer (27.3%), lung cancer (27.3%), exudative pericardial effusion and malignant effusion (68%), and bloody fluid (73%). An average of 350 ml was drained from the patients, and the drain was retained for 4 days. Six patients (18.2%) had re-accumulation of pericardial effusion, and 4 patients required repeat procedures. All patients underwent post-procedure echocardiography, and 82% underwent follow-up echo within one week. More than two-thirds of our cancer patients had malignant pericardial effusion. The early diagnosis of the etiology of pericardial effusion may alter its management and prognosis. We would like to conduct further research to determine its influence on the prognosis of cancer patients in the UAE.

Frequency of Vitamin D Receptor Gene Polymorphisms in a Population with a very High Prevalence of Vitamin D Deficiency, Obesity, Diabetes and Hypertension.

BACKGROUND: Although vitamin D levels and underlying vitamin D receptor (VDR) genetic polymorphisms have been linked to many common diseases including obesity, the association remains unclear. There is also co-existence of pathologically high proportions of obesity and vitamin D deficiency conditions in our UAE society. We therefore aimed to determine the genotypes and allele percentage frequency distribution of four polymorphisms-FokI, BsmI, ApaI and TaqI-in the VDR gene in healthy Emirati individuals and their association with vitamin D levels and chronic conditions including diabetes mellitus, hypertension and obesity. METHODS: 277 participants who were part of a randomized controlled trial had their assessment that included clinical and anthropometric data. Whole blood samples were taken for measurements of vitamin D [25(OH) D], four vitamin D receptor gene polymorphism SNPs, including BsmI, FokI, TaqI and ApaI, metabolic and inflammatory markers and related biochemical variables. Multiple logistic regression analysis was used to assess the influence of vitamin D receptor gene SNPs on vitamin D status after adjusting for clinical parameters known to influence vitamin D status in the study population. RESULTS: Overall, 277 participants with a mean (±SD) age of 41 ± 12, 204 (74%) of them being female, were included in the study. There were statistically significant differences in vitamin D concentrations between different genotypes of the four VDR gene polymorphisms (p < 0.05). There were, however, no statistically significant differences in vitamin D concentrations between subjects with and those without the four VDR gene polymorphisms genotype and alleles except for AA and AG and allele G in Apal SNP (p < 0.05). Multivariate analysis revealed no significant independent associations between vitamin D status and the four VDR gene polymorphisms after adjusting for dietary intake, physical activity, sun exposure, smoking and body mass index. In addition, no significant differences were found in the frequency of the genotypes and alleles of the four VDR genes among patients with obesity, diabetes and hypertension compared to those without these medical conditions. CONCLUSIONS: Although we found statistically significant differences in vitamin concentrations between different genotypes of the four VDR gene polymorphisms, multivariate analysis revealed no association after adjusting for clinical parameters known to influence vitamin D status. Furthermore, no association was found between obesity and related pathologies and the four VDR gene polymorphisms.

Increased Fruit and Vegetable Consumption Mitigates Oxidative Damage and Associated Inflammatory Response in Obese Subjects Independent of Body Weight Change.

INTRODUCTION: The growing prevalence of obesity and related type 2 diabetes is reaching epidemic proportions in the Gulf countries. Oxidative damage and inflammation are possible mechanisms linking obesity to diabetes and other related complications, including cardiovascular disease (CVD). AIMS: To measure the effects of increased fruit and vegetable consumption on body weight, waist circumference, oxidative damage, and inflammatory markers. MATERIALS AND METHODS: We recruited and followed up with 965 community free-living subjects. All recruited subjects had fruit and vegetable intakes, physical activity, antioxidants, and markers of oxidative damage and inflammation measured at baseline and follow up. A validated, semi-quantitative food-frequency questionnaire was used to assess subjects' fruit and vegetable consumption. We stratified subjects based on their daily fruit and vegetable consumption and compared metabolic risk factors between those with high fruit and vegetable consumption and those with low consumption. A multiple logistic regression analysis was performed to determine the independent effects of fruit and vegetable intake on changes in body weight and waist circumference (WC). RESULTS: A total of 965 community free-living subjects (801 (83%) females, mean (SD) age 39 ± 12 years) were recruited and followed up with for a mean (SD) period of 427 ± 223 days. Using WHO cut-off points for body mass index (BMI), 284 (30%) subjects were overweight and 584 (62%) obese, compared to 69 (8%) at normal body weight. An increased fruit and vegetable consumption was associated with a significant decrease in inflammatory markers (hs CRP, TNF-α) and oxidative damage markers (TBARs) and with increased antioxidant enzymes (catalase, glutathione peroxidase) compared to a low consumption (p < 0.05). The benefits of an increased fruit and vegetable consumption in obese subjects was independent of changes in body weight and WC and was maintained at follow up. CONCLUSION: Our results support the beneficial role of a higher fruit and vegetable intake in obese subjects independent of changes in body weight and WC.

The Effect of Hypertension on the Recovery of Renal Dysfunction following Reversal of Unilateral Ureteral Obstruction in the Rat.

Both ureteral obstruction (UO) and hypertension are common conditions that affect kidney functions. Hypertension and chronic kidney disease are closely associated with an overlapping and intermingled cause-and-effect relationship. The effect of hypertension on the renal dysfunction following reversible UO has not been studied previously. To study this effect, spontaneously hypertensive (G-HT, n = 10) and normotensive Wistar (G-NT, n = 10) rats underwent 48-h reversible left unilateral UO (UUO), and the effect of UUO was studied 96 h following UUO reversal. The glomerular filtration rate, renal blood flow, and renal tubular functions such as the fractional excretion of sodium in the post-obstructed left kidney (POK) in both groups were significantly altered compared with the non-obstructed right kidney (NOK). However, the alterations in the G-HT were significantly more exaggerated when compared with the G-NT. Similar findings were observed with the histological features, gene expression of kidney injury markers, pro-inflammatory, pro-fibrotic and pro-apoptotic cytokines, and pro-collagen, as well as tissue levels of apoptotic markers. We conclude that hypertension has significantly exaggerated the alterations in renal functions and other parameters of renal injury associated with UUO.

Mechanisms and Effect of Increased Physical Activity on General and Abdominal Obesity and Associated Metabolic Risk Factors in a Community with Very High Rates of General and Abdominal Obesity.

BACKGROUND: The growing prevalence of obesity and related type 2 diabetes is reaching epidemic proportions in the UAE. Physical inactivity is one of the possible factors linking obesity to diabetes and other related complications. However, the molecular mechanisms through which physical inactivity is contributing to increased obesity-related pathologies are not clear. AIMS: to measure the effects of increased physical activity on obesity and related metabolic risk factors. MATERIALS AND METHODS: We investigated the effects of physical activity on body weight, waist circumference (WC) and metabolic risk factors in 965 community free-living Emirati subjects. Physical activity, dietary intake, antioxidant enzymes and markers of oxidative damage and inflammation were measured both at baseline and follow up. A validated questionnaire was used to assess occupation and leisure-related physical activity. We compared metabolic risk factors between subjects stratified by physical activity levels. The Cox proportional hazards analysis was used to determine the independent effects of increased physical activity on presence and absence of obesity, body weight and waist circumference (WC) change at follow up. RESULTS: A total of 965 community free-living subjects [801 (83%) females, mean (SD) age 39 ± 12 years] were recruited and followed up with for a period of 427 ± 223 days. Using WHO cut-of-points for body mass index (BMI), 284 (30%) subjects were overweight and 584 (62%) subjects were obese, compared to 69 (8%) at normal body weight. We found men to be more physically active than women at both leisure and work times. BMI, hip circumference, total body fat, HDL and inflammatory markers (us CRP, TNF) were significantly higher in female subjects, whilst fat free-mass, WC, blood pressure and HbA1c were higher in male subjects (p < 0.05). Hypertension and diabetes were more common in male subjects compared to female subjects (p < 0.05). Increased physical activity both at baseline and follow up were associated with decreased BMI, WC and inflammatory markers, including us-CRP and TNF. Increased physical activity was associated with significant decrease in abdominal obesity in female subjects and general obesity in both male and females after adjusting for important prognostic indicators [hazard ratio (95% CI): 0.531 (0.399, 0.707); p < 0.001; 0.475 (0.341, 0.662); p < 0.001 respectively]. CONCLUSION: Our findings suggest that increased physical activity may decrease the risk of obesity and also mitigate the associated oxidative damage and inflammatory responses.

Re-catheterization in a young patient with acute myocardial infarction: is it preventable?

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. The goal of our study was to determine the causes of re-catheterization in a young population who were admitted with myocardial infarction and previously underwent cardiac catheterization, and determine what measures can be applied to prevent their re-catheterization. A retrospective study was conducted at Tawam hospital for 6 years (2009-2014). 50 patients between 18 and 50 years of age admitted with acute coronary syndrome who had re-catheterization within a year from their first cardiac catheterization were included. Medical records were reviewed to gather demographic data, cardiac risk factors, laboratory data, hospital course, and angiographic findings. All data was analyzed using descriptive analysis. One third of study participants had been re-admitted electively for a staged PCI, while another third had been admitted and were found to have angina as they did not have significant lesions during re-catheterization; 12 of them had ballooning done while the remaining participants had no intervention. The final third of the participants had re-catheterization due to the development of a new infarction (STEMI/NSTEMI). Of those who had a new infarction, 14% had stent thromboses while 12% had stent restenosis. Stent thrombosis and stent restenosis were found to present as STEMI regardless of the diagnosis at first catheterization. Those with a bare metal stent were found to have a higher risk of ST/ISRS compared to those with a drug-eluting stent (DES). Among the cardiovascular risk factors, we determined that patients who had dyslipidemia (80%) presented the highest risk of having a re-catheterization, followed by those with hypertension or smoking (each 70%). No mortality was documented in the study population. Further research is warranted using accurate statistical analysis and a larger study population to determine the etiology and means of prevention of re-catheterization in the younger population.

Cross-Sectional Association Between Body Fat Composition and Biomarkers of Inflammation and Endothelial Dysfunction in Children with Overweight/Obesity.

Background: Childhood obesity is most prevalent nutritional disorder worldwide. Studies on clinical correlations between body fat (BF) composition, lipid profile, inflammatory biomarkers, and endothelial dysfunction (ED) parameters in children from United Arab Emirates (UAE) are limited. Therefore, we aimed to study obesity pattern in children and determine clinical correlations with biomarkers. Methods: Children (6-13 years) from different schools were divided into obese, overweight, and normal groups based upon Centers for Disease Control and Prevention weight-for-age centiles study (n=166). Anthropometric, BF composition, lipid profile, inflammatory, and ED biomarkers were determined and analyzed using SPSS software. Results: The mean age and weight ± SD of participants were 10.6 ± 2.6 years and 48.2 ± 19.5 kg with 65% as overweight or obese. In normal, overweight, and obese group male were 40 (70.2%), 35 (67.3%), and 40 (70.2%) and female were 17 (29.8%), 17 (32.7%) and 17 (29.8%). There was significant difference in age (p<0.01), height (p< 0.01), weight (p< 0.01) among groups. Obesity markers (MCP-1, leptin, adiponectin) showed positive correlation with age, height, weight, WC, BF%, body fat mass (BFM), body muscle mass (BMM). A significant correlation (all p<0.01) of BMM with SBP (r=0.412), DBP (r=0.255), MCP-1 (r=0.558), adiponectin (r=0.635), hs-CRP (r=0.263), IL-6 (r=0.348), TNF-alpha (r=0.370), ICAM-1 (r=0.237), and VCAM-1 (r=0.343). The inflammatory markers (ICAM-1, VCAM-1) showed significant correlations with age, height, weight, WC, BF%, BFM, BMM. Leptin significantly (all p<0.01) correlated with age (r=0.470), height (r=0.423), weight (r=0.677), WC (r=0.606), BF (r=0.700), BFM (r=0.752), and BMM (r=0.524) and negatively correlated with TBW (r=-0.701). Adiponectin also showed a significant (all p<0.01) positive correlation with age, height, weight, WC, BF, BFM, and BMM. Conclusion: A strong association between BF composition, lipid profile, and inflammatory and ED biomarkers was observed in the study. Thus, immediate measures should be implemented to reduce risk of obesity and associated diseases.

Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease.

Chronic kidney disease (CKD) is a stealthy disease, and its development is linked to mechanisms including inflammation and oxidative stress. Catalpol (CAT), an iridoid glucoside from the root of Rehmannia glutinosa, is reported to manifest anti-inflammatory, antioxidant, antiapoptotic and antifibrotic properties. Hence, we studied the possible nephroprotective effects of CAT and its mechanisms in an adenine-induced (0.2% w/w in feed for 4 weeks) murine model of CKD by administering 5 mg/kg CAT to BALB/c mice for the duration of 4 weeks except during weekends. Upon sacrifice, the kidney, plasma and urine were collected and various physiological, biochemical and histological endpoints were assessed. CAT significantly ameliorated the adenine-induced altered body and kidney weight, water intake, urine volume, and concentrations of urea and creatinine in plasma, as well as the creatinine clearance and the albumin and creatinine ratio. Moreover, CAT significantly ameliorated the effect of adenine-induced kidney injury by reducing the kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, cystatin C and adiponectin. Similarly, the augmented concentrations of markers of inflammation and oxidative stress in the adenine-treated group were markedly reduced with CAT pretreatment. Furthermore, CAT prevented adenine-induced deoxyribonucleic acid damage and apoptotic activity in the kidneys. Histologically, CAT significantly reduced the formation of tubular necrosis and dilation, as well as interstitial fibrosis in the kidney. In addition to that, CAT significantly decreased the adenine-induced increase in the phosphorylated NF-κB and reversed the reduced expression of sirtuin-1 in the kidney. In conclusion, CAT exhibits salutary effects against adenine-induced CKD in mice by mitigating inflammation, oxidative stress and fibrosis via mechanisms involving sirtuin-1 activation and NF-κB inhibition. Confirmatory studies are warranted in order to consider CAT as a potent nephroprotective agent against CKD.

The Effect of Nerolidol Renal Dysfunction following Ischemia-Reperfusion Injury in the Rat.

Efforts to decrease the deleterious effects of renal ischemia-reperfusion injury (IRI) are ongoing. Recently, there has been increasing interest in using natural phytochemical compounds as alternative remedies in several diseases. Nerolidol is a natural product extracted from plants with floral odors and has been proven to be effective for the treatment of some conditions. We investigated the effect of nerolidol in a rat model of renal IRI. Nerolidol was dissolved in a vehicle and administered orally as single daily dose of 200 mg/kg for 5 days prior to IRI and continued for 3 days post IRI. G-Sham (n = 10) underwent sham surgery, whereas G-IRI (n = 10) and G-IRI/NR (n = 10) underwent bilateral warm renal ischemia for 30 min and received the vehicle/nerolidol, respectively. Renal functions and histological changes were assessed before starting the medication, just prior to IRI and 3 days after IRI. Nerolidol significantly attenuated the alterations in serum creatinine and urea, creatinine clearance, urinary albumin and the urinary albumin-creatinine ratio. Nerolidol also significantly attenuated the alterations in markers of kidney injury; proinflammatory, profibrotic and apoptotic cytokines; oxidative stress markers; and histological changes. We conclude that nerolidol has a renoprotective effect on IRI-induced renal dysfunction. These findings might have clinical implications.

Combined Treatment with KV Channel Inhibitor 4-Aminopyridine and either γ-Cystathionine Lyase Inhibitor ß-Cyanoalanine or Epinephrine Restores Blood Pressure, and Improves Survival in the Wistar Rat Model of Anaphylactic Shock.

The mechanism of anaphylactic shock (AS) remains incompletely understood. The potassium channel blocker 4-aminopyridine (4-AP), the inhibitors of cystathionine γ-lyase (ICSE), dl-propargylglycine (DPG) or ß-cyanoalanine (BCA), and the nitric oxide (NO) synthase produce vasoconstriction and could be an alternative for the treatment of AS. The aim of this study was to demonstrate the ability of L-NAME, ICSE alone or in combination with 4-AP to restore blood pressure (BP) and improve survival in ovalbumin (OVA) rats AS. Experimental groups included non-sensitized Wistar rats (n = 6); AS (n = 6); AS (n = 10 per group) treated i.v. with 4-AP (AS+4-AP), epinephrine (AS+EPI), AS+DPG, AS+BCA, or with L-NAME (AS+L-NAME); or AS treated with drug combinations 4-AP+DPG, 4-AP+BCA, 4-AP+L-NAME, or 4-AP+EPI. AS was induced by i.v. OVA (1 mg). Treatments were administered i.v. one minute after AS induction. Mean arterial BP (MAP), heart rate (HR), and survival were monitored for 60 min. Plasma levels of histamine, prostaglandin E2 (PGE2) and F2 (PGF2α), leukotriene B4 and C4, angiotensin II, vasopressin, oxidative stress markers, pH, HCO3, PaO2, PaCO2, and K+ were measured. OVA induced severe hypotension and all AS rats died. Moreover, 4-AP, 4-AP+EPI, or 4-AP+BCA normalized both MAP and HR and increased survival. All sensitized rats treated with 4-AP alone or with 4-AP+BCA survived. The time-integrated MAP "area under the curve" was significantly higher after combined 4-AP treatment with ICSE. Metabolic acidosis was not rescued and NO, ICSE, and Kv inhibitors differentially alter oxidative stress and plasma levels of anaphylactic mediators. The AS-induced reduction of serum angiotensin II levels was prevented by 4-AP treatment alone or in combination with other drugs. Further, 4-AP treatment combined with EPI or with BCA also increased serum PGF2α, whereas only the 4-AP+EPI combination increased serum LTB4. Serum vasopressin and angiotensin II levels were increased by 4-AP treatment alone or in combination with other drugs. Moreover, 4-AP alone and in combination with inhibition of cystathionine γ-lyase or EPI normalizes BP, increases serum vasoconstrictor levels, and improves survival in the Wistar rat model of AS. These findings suggest possible investigative treatment pathways for research into epinephrine-refractory anaphylactic shock in patients.

Early Doxorubicin Myocardial Injury: Inflammatory, Oxidative Stress, and Apoptotic Role of Galectin-3.

Doxorubicin (DOXO) is an effective drug that is used in the treatment of a large number of cancers. Regardless of its important chemotherapeutic characteristics, its usage is restricted because of its serious side effects; the most obvious is cardiotoxicity, which can manifest acutely or years after completion of treatment, leading to left ventricular dysfunction, dilated cardiomyopathy, and heart failure. Galectin 3 (Gal-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. Gal-3 was found to be upregulated in animal models, correlating with heart failure, atherosclerosis, and myocardial infarction. Male C57B6/J and B6.Cg-Lgals3 /J Gal-3 knockout (KO) mice were used for a mouse model of acute DOXO-induced cardiotoxicity. Mice were given DOXO or vehicle (normal saline), after which the mice again had free access to food and water. Heart and plasma samples were collected 5 days after DOXO administration and were used for tissue processing, staining, electron microscopy, and enzyme-linked immunosorbent assay (ELISA). There was a significant increase in the heart concentration of Gal-3 in Gal-3 wild type DOXO-treated mice when compared with the sham control. There were significantly higher concentrations of heart cleaved caspase-3, plasma troponin I, plasma lactate dehydrogenase, and plasma creatine kinase in Gal-3 KO DOXO-treated mice than in Gal-3 wild type DOXO-treated mice. Moreover, there were significantly higher heart antioxidant proteins and lower oxidative stress in Gal-3 wild type DOXO-treated mice than in Gal-3 KO DOXO-treated mice. In conclusion, Gal-3 can affect the redox pathways and regulate cell survival and death of the myocardium following acute DOXO injury.

Origanum majorana essential oil decreases lung tumor growth and metastasis in vitro and in vivo.

Current targeted- and immuno-therapies have prolonged the overall survival of non-small cell lung cancer (NSCLC) patients by few months in a small percentage of patients responding to these treatments. This situation has prompted us to investigate the anticancer potential of the Origanum majorana Essential Oil (OMEO). In this pre-clinical study and using two major human NSCLC, namely A549 and LNM35, we demonstrated that OMEO significantly decreases the viability of these cells and the growth of their pre-formed colonies in vitro in a concentration-dependent manner and partly via the induction of caspase 3/7-dependent cell death and downregulation of survivin. Moreover, OMEO significantly slow down the growth of A549 and LNM35 tumor xenografts in the CAM and in nude mice models in vivo. Furthermore, OMEO significantly reduces in vitro A549 and LNM35 cancer cell migration and invasion, and the incidence and growth of lymph nodes metastasis in vivo in nude mice xenografted subcutaneously with the highly metastatic LNM35 cells. Three months of treatment of mice with OMEO did not affect blood, kidney, and liver functions. Our study demonstrates that OMEO is a safe and robust anticancer option.

Relationship between lipid profile, inflammatory and endothelial dysfunction biomarkers, and type 1 diabetes mellitus: a case-control study.

OBJECTIVE: Inflammation is a major factor in endothelial dysfunction (ED) which is the earliest predictor of cardiovascular disease and premature mortality in type 1 diabetes mellitus (T1DM) patients. This study aimed to describe the possible relationship between plasma lipids and inflammatory and ED biomarkers in young Emirati patients with and without T1DM. METHODS: This case-control study included 158 patients with T1DM and 157 healthy controls from the local population of the United Arab Emirates (UAE). Anthropometric data, clinical variables, lipid profiles, liver enzymes, HbA1c, inflammatory, and ED biomarkers were measured for all participants using sophisticated techniques and assays. RESULTS: The mean ages ± SD of patients with T1DM and healthy controls was 19.3 ± 6.4 years (59.5% females) and 9.2 ± 6.8 years (61.5% females), respectively. The mean duration of T1DM was 9.3 ± 5.7 years, with HbA1c of 8.9 ± 2.1%. BMI, WC, SBP, and DBP significantly differed between the two groups. The mean lipid profiles (HDL, TG, TC, ApoA, and ApoB), liver enzymes (GGT, ALT), inflammatory (IL-6, adiponectin, TNF-α, hs-CRP), and ED biomarker levels (ICAM-1, VCAM-1, selectin, and ET-1) were also significantly different between patients and controls. Based on Spearman's rank and logistic regression analysis, there was a significant association between elevated lipid profile, liver enzymes, inflammatory markers, and ED markers in T1DM patients compared to controls. Among the biomarkers studied, ApoA, ApoB, and TC were significantly increased in T1DM patients compared to controls. CONCLUSION: This study revealed a strong association between an elevated lipid profile and inflammatory and ED markers with T1DM, which could lead to cardiovascular events in the UAE population.