Ethnic-Based Assessment of Vitamin D and Magnesium Status in the Kingdom of Bahrain.

BACKGROUND: Vitamin D deficiency is a major global health problem. Most previous studies focused attention on the significant role of sunlight exposure in the homeostasis of vitamin D and calcium blood levels. Magnesium is pivotal in the proper functioning of vitamin D, and the physiologic functions of different organs require a balanced vitamin D and magnesium status. The relationship between sunlight exposure and blood levels of vitamin D and magnesium has often been overlooked. The aim of this study was to evaluate vitamin D and magnesium status based on sunlight exposure and ethnicity in Bahraini and expatriate workers. METHODS: A cross-sectional study was conducted between October 2018 and September 2019. One hundred and seventy-four subjects participated in this study were subdivided based on their ethnicity and work environment-dependent exposure to sunlight into four groups: (1) Bahraini exposed (n=94), (2) Bahraini non-exposed (n=25), (3) expatriate exposed (n=31), and (4) expatriate non-exposed (n=24). Blood levels of vitamin D and magnesium were evaluated for all the participants. RESULTS:  Independent of ethnicity, vitamin D levels were insignificantly different among the studied groups and were all below the normal reference range. Yet, there was still a sunlight-dependent increase in vitamin D level that could be seen only in Bahraini workers. Magnesium levels were significantly higher in expatriates when compared to Bahraini workers. Sunlight-exposed expatriates had significantly higher magnesium levels than their Bahraini counterparts, while there was no significant difference between both ethnicities in the non-exposed groups. CONCLUSION: Country- and ethnic-specific definitions for vitamin D status and sunlight exposure are recommended. The assessment of magnesium status is pivotal in the overall assessment of vitamin D status.

Anticancer Properties of Selenium-Enriched Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes), in Colon Cancer In Vitro.

Mushrooms have become an important way to safely supply the body with the daily needs of organic selenium and they also possess remarkable medicinal properties. In this study, we examined the ability of the Pleurotus ostreatus mushroom to grow in selenium (Se) and its ability to accumulate and convert Se from inorganic form to organic form during growth. Additionally, we achieved the potential anticancer properties of mushroom extract in colon cancer cells using the CaCo-2 cell and the normal human colon mucosal epithelial cell line, NCM-460 cell line. Interestingly, Se-enriched mushroom extract (SME) showed a competitive regulation in colon cancer cell line; CaCo-2 cell line indicated by cell morphology, the number of survived cells, lactate dehydrogenase (LDH) production, and cell viability rate. Moreover, SME treatment regulates the expression profile of the cancer cell proliferation factor Raf-1 and pro-apoptotic related factors P53 and Caspase-3 Furthermore, the production of inflammatory-regulated cytokines, including interleukin 6 (IL-6) and IL-10, increased. At the same time, the level of produced tumor necrosis factor-alpha (TNF-α) markedly decreased in a dose and time-dependent of colon cancer-treated cells. Notably, the purified selenomethionine (SeMe) showed sufficient inhibition of colon cancer proliferation compared with the inorganic form of selenium (sodium selenite) via blocking the Raf/MEK/ERK signaling pathway. In addition, SeMe treatment also stimulated the production of IL-6 and IL-10 while decreasing the production of TNF-α, which plays a crucial role in the necrotic event. Meanwhile, the SeMe treatment showed a neglected cytotoxic effect in the normal colon epithelial cells. Collectively, these findings indicate that the fruiting bodies of Se-enriched mushrooms revealed anti-colon cancer activity via targeting Raf-1 signaling pathway and increasing the production of IL-6 and IL-10.

Prevalence and associated risk factors of cannabinoid abuse among Egyptian university students: a cross-sectional study.

Global surveys have highlighted rise in consumption of cannabinoids among residents of both developed and developing countries. Cannabinoids cause severe damage to the cardiovascular, nervous, respiratory, and renal systems, and have been linked with several deaths. Despite these adverse health effects, the use of cannabinoids has rapidly increased. This work seeks to estimate the prevalence of cannabinoid abuse among Egyptian university students and explore the associated risk factors. A cross-sectional study was carried out over 3 months (1st of July-1st of October 2020) and included 2380 students. Participants were subjected to a pre-designed self-administered questionnaire that included demographic data, Addiction Severity Index, and Depression Anxiety Stress Scale. Among the participating students, 4.9% of them reported cannabinoid abuse and 41% reported smoking cigarettes. The most used substances were hashish (96.5%), Strox (41.3%), Bhang (34.4%), voodoo (34.4%), and Tramadol (31.1%). Gender and social status were also significantly related to rates of substances abuse; most illicit drug users were males (93.1%), and the majority was of low (41.3%) or moderate (50.8%) socioeconomic status. The most significant risk factors associated with substance use were positive history of family conflict (OR=6.48; CI95%: 5.08-8.64, p<0.001), encouragement by peers (OR=2.95; CI95%: 1.73-5.05, p<0.001), male gender (OR=5.46; CI95%: 2.40-12.44, p=0.001), positive history of child abuse (OR=2.85; CI95%: 1.96-3.04, p=0.001), having a stay-at-home mother (OR= 1.56, CI95%: 1.19-2.04, p=0.001), living in an urban area (OR=2.22; CI95%: 1.53-5.0, p=0.002), and positive family history of substance use (OR=1.98; CI95%: 1.48-2.08, p=0.045). This study emphasizes the possible significant rise in substance use among university students. Awareness campaigns should target both students and student families.

Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension.

BACKGROUND: The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model. METHODS: Thirty male Wistar rats weighing 150-200 g were equally divided into: 1-Control group (fed normal laboratory diet for 24 weeks), 2-Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3-Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies. RESULTS: High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions. CONCLUSION: Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.

Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis.

BACKGROUND: Age-dependent male osteoporosis remains a poorly studied medical problem despite its significance. It is estimated that at least 1 of 5 men will suffer from osteoporotic consequences. Given that multiple mechanisms are involved in the process of senescence, much attention has been given to compounds with polymodal actions. To challenge such a health problem, we tested here the therapeutic potential of resveratrol in male osteoporosis. We also studied the possible molecular mechanisms that may underlie resveratrol effects. METHODS: Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control (3-4 months old weighing 150-200 g receiving vehicle), aged (18-20 months old, weighing 350-400 g and receiving vehicle), and resveratrol treated aged (18-20 months old, weighing 350-400 g and receiving resveratrol 20 mg/kg/day for 6 weeks) groups. Assessment of serum calcium, phosphate, bone specific alkaline phosphatase, inflammatory cytokines, oxidative stress markers, and rat femur gene expression of FoxO1, SIRT1, RANKL and OPG proteins was carried out. Histopathological assessment of different levels of rat femur was also performed. RESULTS: Age-dependent osteoporosis resulted in significant increase in serum levels of phosphate, bone specific alkaline phosphatase, hsCRP, IL-1ß, IL-6, TNF-α, MDA, NO, and RANKL gene expression. However, there was significant decrease in serum level of GSH, and gene expression of FoxO1, SIRT1 and OPG. Osteoporotic changes were seen in femur epiphysis, metaphysis and diaphysis. Resveratrol restored significantly age-dependent osteoporotic changes. CONCLUSION: We concluded that resveratrol can play an important role in the prevention of male osteoporosis. Resveratrol can counter the molecular changes in male osteoporosis via anti-inflammatory, anti-oxidant and gene modifying effects.

Potential therapeutic effects of endothelial cells trans-differentiated from Wharton's Jelly-derived mesenchymal stem cells on altered vascular functions in aged diabetic rat model.

BACKGROUND: Diabetes mellitus in elderly represents an exceptional subset in the population vulnerable to cardiovascular events. As aging, diabetes mellitus and hypertension share common pathways, an ideal treatment should possess the ability to counter more than one of, if not all, the underlying mechanisms. Stem cells emerged as a potential approach for complicated medical problems. We tested here the possible role of trans-differentiated endothelial cells (ECs) in the treatment of diabetes mellitus in old rats. METHODS: Mesenchymal stem cells where isolated from umbilical cord Wharton's Jelly and induced to differentiate into endothelial like-cells using vascular endothelial growth factor-enriched media. Thirty aged male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control group (18-20 months old, weighing 350-400 g, received single intraperitoneal injection as well as single intravenous injection via tail vein of the vehicles), aged diabetic group (18-20 months old, weighing 350-400 g, received single intraperitoneal injection of 50 mg/kg streptozotocin, and also received single intravenous injection of saline via tail vein), and aged diabetic + ECs group (18-20 months old, weighing 350-400 g, received single intraperitoneal injection of 50 mg/kg streptozotocin, and also received single intravenous injection of 2*106 MSC-derived ECs in 0.5 ml saline via tail vein) groups. Assessment of SBP, aortic PWV, and renal artery resistance was performed. Serum levels of ET1, ANG II, IL-6, TNF-α, MDA, ROS, and VEGF were evaluated, as well as the aortic NO tissue level and eNOS gene expression. Histopathological and immunostaining assessments of small and large vessels were also performed. RESULTS: Induction of diabetes in old rats resulted in significant increase in SBP, aortic PWV, renal artery resistance, and serum levels of ET1, ANG II, IL-6, TNF-α, MDA, ROS, and VEGF. While there was significant decrease in aortic NO tissue level and eNOS gene expression in the aged diabetic group when compared to aged control group. ECs treatment resulted in significant improvement of endothelial dysfunction, inflammation and oxidative stress. CONCLUSION: We report here the potential therapeutic role of trans-differentiated ECs in aged diabetics. ECs demonstrated anti-inflammatory, antioxidant, gene modifying properties, significantly countered endothelial dysfunction, and improved vascular insult.

Attenuation of sleep deprivation dependent deterioration in male fertility parameters by vitamin C.

PURPOSE: Male fertility is multifaceted and its integrity is as well multifactorial. Normal spermatogenesis is dependent on competent testicular function; namely normal anatomy, histology, physiology and hormonal regulation. Lifestyle stressors, including sleep interruption and even deprivation, have been shown to seriously impact male fertility. We studied here both the effects and the possible underlying mechanisms of vitamin C on male fertility in sleep deprived rats. METHODS: Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control (remained in their cages with free access to food and water), sleep deprivation (SD) group (subjected to paradoxical sleep deprivation for 5 consequent days, rats received intra-peritoneal injections of vehicle daily throughout the sleep deprivation), and sleep deprivation vitamin C-treated (SDC) group (subjected to sleep deprivation for 5 consequent days with concomitant intra-peritoneal injections of 100 mg/kg/day vitamin C). Sperm analysis, hormonal assay, and measurement of serum oxidative stress and inflammatory markers were performed. Testicular gene expression of Nrf2 and NF-κß was assessed. Structural changes were evaluated by testicular histopathology, while PCNA immunostaining was conducted to assess spermatogenesis. RESULTS: Sleep deprivation had significantly altered sperm motility, viability, morphology and count. Serum levels of cortisol, corticosterone, IL-6, IL-17, MDA were increased, while testosterone and TAC levels were decreased. Testicular gene expression of Nrf2 was decreased, while NF-κß was increased. Sleep deprivation caused structural changes in the testes, and PCNA immunostaining showed defective spermatogenesis. Administration of vitamin C significantly countered sleep deprivation induced deterioration in male fertility parameters. CONCLUSION: Treatment with vitamin C enhanced booth testicular structure and function in sleep deprived rats. Vitamin C could be a potential fertility enhancer against lifestyle stressors.

CoQ10 ameliorates monosodium glutamate-induced alteration in detrusor activity and responsiveness in rats via anti-inflammatory, anti-oxidant and channel inhibiting mechanisms.

BACKGROUND: Competent detrusor muscles with coordinated contraction and relaxation are crucial for normal urinary bladder storage and emptying functions. Hence, detrusor instability, and subsequently bladder overactivity, may lead to undesirable outcomes including incontinence. Multiple mechanisms may underlie the pathogenesis of detrusor overactivity including inflammation and oxidative stress. Herein, we tested the possibility that CoQ10 may have a potential therapeutic role in detrusor overactivity. METHODS: Forty adult male Wistar albino rats weighing 100-150 g were used in the present study. Rats were divided (10/group) into control (receiving vehicles), monosodium glutamate (MSG)-treated (receiving 5 mg/kg MSG daily for 15 consecutive days), MSG + OO-treated (receiving concomitantly 5 mg/kg MSG and olive oil for 15 consecutive days), MSG + CoQ10-treated (receiving concomitantly 5 mg/kg MSG and 100 mg/kg CoQ10 daily for 15 consecutive days) groups. RESULTS: MSG resulted in significant increase in bladder weight and sensitised the bladder smooth muscles to acetylcholine. MSG has also resulted in significant increase in bladder TNF-α, IL-6, malondialdehyde, nerve growth factor and connexion 43, with significant decrease in the antioxidant enzymes superoxide dismutase and catalase. Olive oil had no effect on MSG induced alterations of different parameters. Treatment with CoQ10 has resulted in a significant restoration of all the altered parameters. CONCLUSION: Taken together, our results suggest that CoQ10 antagonizes the deleterious effects of MSG on detrusor activity. We propose that CoQ10 could be a therapeutic strategy targeting urinary bladder dysfunction.

Sociodemographic, Electrophysiological, and Biochemical Profiles in Children with Attention Deficit Hyperactivity Disorder and/or Epilepsy.

Attention deficit hyperactivity disorder (ADHD) is among the most prevalent neurobehavioral disorders affecting children worldwide. The prevalence of ADHD is higher in children with epilepsy. Despite the plethora of conducted work, the precise cause of ADHD is not identified yet. We studied here the sociodemographic, clinical, electrophysiological, and biochemical profiles of children with ADHD, epilepsy, and ADHD with epilepsy. Subjects were divided into 4 groups (25 child/group): I-control, II-ADHD, III-epilepsy, and IV-ADHD with epilepsy. Male to female ratio was significantly (p < 0.05) higher in the ADHD (3.1) and ADHD with epilepsy (2.1) groups when compared to the control (1.08) or epilepsy (1.08) groups. Positive family history was significantly evident in patients with epilepsy and ADHD with epilepsy, but not in the control or ADHD groups. Speech development was significantly delayed in the ADHD and ADHD with epilepsy groups. EEG abnormalities were detected in patients with ADHD (12%) and ADHD with epilepsy (68%). Focal frontal activities were significantly detectable in the ADHD (100%) and ADHD with epilepsy (77.8%) groups, whereas focal temporal activity was significantly present in the epilepsy (83.3%) group. Serum ferritin was significantly lower in the ADHD group (110.27 ± 6.64 ηg/ml) when compared to the control (134.23 ± 14.82 ηg/ml), epilepsy (159.66 ± 33.17 ηg/ml), and ADHD with epilepsy (203.04 ± 50.64 ηg/ml) groups. Serum zinc was significantly higher in the ADHD, epilepsy, and ADHD with epilepsy groups (236.63 ± 20.89, 286.74 ± 43.84, and 229.95 ± 67.34 µg/dl, respectively), when compared to the control group (144.21 ± 17.40 µg/dl). Serum adenosine deaminase was insignificantly different among the groups. Our results indicate that gender and family history are significant moderators in the aetiology of ADHD and epilepsy or their comorbidity. We also demonstrated that EEG could be central in the assessment of ADHD with epilepsy cases. Serum ferritin and zinc alteration may contribute significantly in ADHD and epilepsy pathophysiology.

Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress in acetaminophen-induced hepato-renal injury.

BACKGROUND: Acetaminophen (APAP)-induced toxicity is a predominant cause of acute hepatic and renal failure. In both humans and rodents toxicity begins with a reactive metabolite that binds to proteins. This leads to mitochondrial dysfunction and nuclear DNA fragmentation resulting in necrotic cell death. Pleurotus ostreatus (an edible oyster mushroom) is well recognized as a flavourful food, as well as a medicinal supplement. In the present study, we evaluated the role of Pleurotus ostreatus in the protection against APAP-induced hepato-renal toxicity. We also explored the mechanism by which Pleurotus ostreatus exerts its effects. METHODS: Ninety adult male Swiss albino mice were divided into three groups (30 mice/group). Mice were offered normal diet (control and APAP groups), or diet supplemented with 10% Pleurotus ostreatus (APAP + Pleurotus ostreatus) for 10 days. Mice were either treated with vehicle (control group, single intra-peritoneal injection.), or APAP (APAP and APAP + Pleurotus ostreatus groups, single intra-peritoneal injection, 500 mg/kg), 24 hours after the last meal. RESULTS: APAP increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) glutamate dehydrogenase (GDH), creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), and hepatic and renal malondialdehyde (MDA) content. APAP decreased hepatic and renal glutathione (GSH) content, as well as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Supplementation with Pleurotus ostreatus significantly reduced APAP-induced elevated levels of ALT, AST, GDH, creatinine, BUN, KIM-1and MDA, while GSH level, and GSH-Px and SOD activities were significantly increased. Our findings were further validated by histopathology; treatment with Pleurotus ostreatus significantly decreased APAP-induced cell necrosis in liver and kidney tissues. CONCLUSIONS: We report here that the antioxidant effect of Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress accompanying APAP over-dose, with subsequent clinically beneficial effects on liver and kidney tissues.