Antioxidant, anti-inflammatory, and anti-DNA damage effects of carnosic acid against aflatoxin B1-induced hepatic, renal, and cardiac toxicities in rats.

Background: Aflatoxin B1 (AFB1) food contamination is a global health hazard that has detrimental effects on both human and animal health. The objective of the current study is to assess the protective impact of carnosic acid against AFB1-induced toxicities in the liver, kidneys, and heart. Methods: Forty male Wistar Albino rats (weighting 180 ~ 200 g) were allocated into 5 groups (8 rats each); the 1st group received saline as served as a control, the 2nd group received carnosic acid (CA100) at a dose of 100 mg/kg bw/day by gavage for 14 days, the 3rd group received AFB1 at a dose of 2.5 mg/kg bw, orally twice on days 12 and 14, the 4th group (AFB1-CA50) received AFB1 as in the 3rd group and CA at a dose of 50 mg/kg bw/day, and the 5th group (AFB1-CA100) received AFB1 as in the 3rd group and CA as in the 2nd group. Results: CA significantly decreased the liver enzymes (ALT, AST. ALP), renal function products (LDH, BUN, creatinine), and cardiac enzymes (CK and CK-MB) to control levels after the high increment by AFB1 exposure. Moreover, CA significantly decreased the oxidative stress (MDA, NO, 8-OHdG) and increased the antioxidant enzyme activities (CAT, GSH, GSH-Px, and SOD) after severe disruption of oxidant/antioxidant balance by AFB1 exposure. Interestingly, CA significantly decreased the proinflammatory mediators (IL-6, IL-1ß, and TNF-α) to the control levels after severe inflammation induced by AFB1 exposure. Conclusions: Conclusively, CA had antioxidant, anti-inflammatory, and anti-DNA damage effects against hepatic, renal, and cardiac AFB1-induced toxicities.

Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study.

BACKGROUND AND AIMS: Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast. MATERIALS AND METHODS: Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software. RESULTS: A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV. CONCLUSION: In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.

Spirulina platensis ameliorates hepatic oxidative stress and DNA damage induced by aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is a widely distributed mycotoxin, causing hepatotoxicity and oxidative stress. One of the most famous unicellular cyanobacteria is Spirulina platensis (SP) which is well known for its antioxidant characteristics against many toxicants. Therefore, this study aimed to investigate the antioxidant potential and hepatoprotective ability of SP against oxidative stress and cytotoxicity in male Wistar albino rats intraperitoneally injected with AFB1. Rats were separated into five groups as follows: negative control administered with saline; SP (1000 mg/kg BW) for two weeks; AFB1 (2.5 mg/kg BW) twice on days 12 and 14; AFB1 (twice) + 500 mg SP/kg BW (for two weeks) and AFB1 (twice) + 1000 mg SP/kg BW (for two weeks). Liver and blood samples were assembled for histological and biochemical analyses. AFB1 intoxicated rats showed a marked elevation in serum biochemical parameters (ALP, ALT, and AST), hepatic lipid peroxidation (MDA and NO), and proliferating cell nuclear antigen (PCNA) indicating DNA damage. Moreover, AFB1 caused suppression of antioxidant biomarkers (SOD, GHS, GSH-Px, and CAT). However, the elevated serum levels of biochemical parameters and PCNA expression were reduced by SP. Moreover, SP lowered oxidative stress and lipid peroxidation markers in a dose-dependent manner. To sum up, SP supplementation is capable of decreasing AFB1 toxicity through its powerful antioxidant activity.

Acute aflatoxin B1-induced hepatic and cardiac oxidative damage in rats: Ameliorative effects of morin.

Aflatoxins (AFs) are secondary metabolites produced by the fungus Aspergillus flavus, of which Aflatoxin-B1 (AFB1) appears to be the most cancerogenic and of the highest toxicity. AFB1 causes serious effects on several organs including the liver. Morin is a flavonol that exists in many fruits and plants and has diverse biological properties including anticancer, anti-atherosclerotic, antioxidant, anti-inflammatory, immunomodulatory, and multi-organ protective activities. The present study aims to evaluate the potential protective effects of morin against acute AFB1-induced hepatic and cardiac toxicity in rats. Forty rats were divided into five groups (n = 8) as follows: control received the vehicle, morin was orally administered 30/mg/kg body weight (MRN30), the AFB1 was administered orally at a dose of 2.5 mg/kg, twice on days 12 and 14 of the experiment for the 3rd, 4th, and 5th groups., AFB1-MRN15 was orally given morin at a dose of 15 mg/kg body weight, and AFB1-MRN30 orally received morin at 30 mg/kg body weight. The results indicated a significant decrease in serum AST, ALP, LDH, GGT, CK, CK-MB, 8-OHdG, IL-1ß, IL-6, TNF-a levels in MRN30 compared to AFB1, and AFB1-MRN15 groups. However, the results indicated non-significant differences in the serum levels between MRN30, control, and AFB1-MRN30 groups. Meanwhile, regarding the hepatic and cardiac parameters, there were significant differences in the levels of MDA, NO, GSH, GSH-Px, SOD, and CAT in MRN30 compared to AFB1, and AFB1-MRN15 groups, overall implying the protective effects of morin. To conclude, morin at a dose of 30 mg/kg b. wt. showed significant enhancements in acute AFB1-induced hepatic and cardiac toxicity in rats, which could play a role in limiting the public health hazards of AFs.

Harnessing role of sesamol and its nanoformulations against neurodegenerative diseases.

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.

Dietary Thymoquinone Alone or Combined with Swimming Exercise Protect against Microcystin-LR-Induced Oxidative Injury in Mice.

Microcystin-leucine-arginine (MCLR) is the most abundant cyanotoxin produced by cyanobacteria. It induces potent cytotoxicity through oxidative stress and DNA damage. Thymoquinone (TQ) is a natural nutraceutical antioxidant derived from black cumin (Nigella sativa). Physical exercise (EX) improves whole-body metabolic homeostasis. Therefore, this study examined the protective role of swimming exercise and TQ against MC-induced toxicity in mice. Fifty-six healthy adult male albino mice (25-30 g) were randomized into seven groups; group (I) was the negative control and received oral physiological saline for 21 days; group (II) received water EX for 30 min daily; group (III) was intraperitoneally injected with TQ (5 mg/kg daily, for 21 days); group (IV) was intraperitoneally administered MC (10 µg/kg daily, for 14 days) and acted as the positive toxic control; group (V) was treated with MC and water EX; group (VI) was injected with MC and TQ; finally, group (VII) was treated with MC with TQ and water EX. In comparison with the control group, the results showed hepatic, renal, and cardiac toxicity in the MCLR-treated group, indicated by a significant increase (p < 0.05) in serum levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transferase (ALT), cholesterol, lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-myocardial band (CK-MB), urea, creatinine, interleukin-6, interleukin -1ß, and tumor necrosis factor-α levels. In addition, there were significant elevations (p < 0.05) in malondialdehyde (MDA) and nitric oxide (NO) levels and a significant decrease in reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in hepatic, cardiac, and renal tissues. Treatment with either TQ or water EX significantly improved (p < 0.05) the MC-induced toxicity with superiority of the TQ group in the restoration of normal ranges; however, cotreatment with both TQ and swimming EX showed the most improvement and restoration to normal ranges as a result of increasing EX clinical efficacy by TQ.

Hospital and laboratory outcomes of patients with COVID-19 who received vitamin D supplementation: a systematic review and meta-analysis of randomized controlled trials.

Coronavirus disease 2019 (COVID-19) has a wide-ranging spectrum of clinical symptoms, from asymptomatic/mild to severe. Recent research indicates that, among several factors, a low vitamin D level is a modifiable risk factor for COVID-19 patients. This study aims to evaluate the effect of vitamin D on hospital and laboratory outcomes of patients with COVID-19.Five databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) and clinicaltrials.gov were searched until July 2022, using relevant keywords/Mesh terms. Only randomized clinical trials (RCTs) that addressed the topic were included. The Cochrane tool was used to assess the studies' risk of bias, and the data were analyzed using the review manager (RevMan 5.4).We included nine RCTs with 1586 confirmed COVID-19 patients. Vitamin D group showed a significant reduction of intensive care unit (ICU) admission (risk ratio = 0.59, 95% confidence interval (CI) [0.41, 0.84], P = 0.003), and higher change in vitamin D level (standardized mean difference = 2.27, 95% CI [2.08, 2.47], P < 0.00001) compared to the control group. Other studied hospital and laboratory outcomes showed non-significant difference between vitamin D and the control group (P ≥ 0.05).In conclusion, vitamin D reduced the risk of ICU admission and showed superiority in changing vitamin D level compared to the control group. However, other outcomes showed no difference between the two groups. More RCTs are needed to confirm these results.

Factors associated with the prevalence of malnutrition among adult hemodialytic patients: A two-center study in the Jeddah region, Saudi Arabia.

Chronic kidney disease, one of the most common diseases in the world, is characterized by irreversible impairment of the kidney's metabolic, excretory, and endocrine functions. During end-stage renal disease, patients require renal replacement therapy, such as hemodialysis (HD). Protein-energy wasting is a common health problem among HD patients. This study aims to assess the nutritional status of HD patients at two HD centers in Jeddah, Saudi Arabia, and to determine its associated factors. A cross-sectional study was conducted at two different dialysis centers in Jeddah, Saudi Arabia; 211 female and male HD patients. Malnutrition was recognized using the modified-subjective global assessment (M-SGA) comprising two parts: medical history and physical examination. Sociodemographic and health status for all patients were also determined. Patients were classified based on their M-SGA score into two groups: normal and malnourished. Overall, 54.5% of the participants showed malnutrition. Unemployment, low muscle strength and mass, high level of medication use, and high dialysis vintage were positively (P < .05) associated with malnutrition. In conclusion, the M-SGA score indicates a high prevalence of malnutrition among HD patients. These results show the importance of regular assessment and follow-ups for HD patients ensuring better health and nutritional status.

Genetic etiology and clinical challenges of phenylketonuria.

This review discusses the epidemiology, pathophysiology, genetic etiology, and management of phenylketonuria (PKU). PKU, an autosomal recessive disease, is an inborn error of phenylalanine (Phe) metabolism caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene. The prevalence of PKU varies widely among ethnicities and geographic regions, affecting approximately 1 in 24,000 individuals worldwide. Deficiency in the PAH enzyme or, in rare cases, the cofactor tetrahydrobiopterin results in high blood Phe concentrations, causing brain dysfunction. Untreated PKU, also known as PAH deficiency, results in severe and irreversible intellectual disability, epilepsy, behavioral disorders, and clinical features such as acquired microcephaly, seizures, psychological signs, and generalized hypopigmentation of skin (including hair and eyes). Severe phenotypes are classic PKU, and less severe forms of PAH deficiency are moderate PKU, mild PKU, mild hyperphenylalaninaemia (HPA), or benign HPA. Early diagnosis and intervention must start shortly after birth to prevent major cognitive and neurological effects. Dietary treatment, including natural protein restriction and Phe-free supplements, must be used to maintain blood Phe concentrations of 120-360 µmol/L throughout the life span. Additional treatments include the casein glycomacropeptide (GMP), which contains very limited aromatic amino acids and may improve immunological function, and large neutral amino acid (LNAA) supplementation to prevent plasma Phe transport into the brain. The synthetic BH4 analog, sapropterin hydrochloride (i.e., Kuvan®, BioMarin), is another potential treatment that activates residual PAH, thus decreasing Phe concentrations in the blood of PKU patients. Moreover, daily subcutaneous injection of pegylated Phe ammonia-lyase (i.e., pegvaliase; PALYNZIQ®, BioMarin) has promised gene therapy in recent clinical trials, and mRNA approaches are also being studied.

Natural therapeutics and nutraceuticals for lung diseases: Traditional significance, phytochemistry, and pharmacology.

BACKGROUND: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities. PURPOSE: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease. METHODS: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases. RESULTS: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases. CONCLUSION: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2.

Malva parviflora Leaves and Fruits Mucilage as Natural Sources of Anti-Inflammatory, Antitussive and Gastro-Protective Agents: A Comparative Study Using Rat Models and Gas Chromatography.

Malva parviflora L., Little mallow, has been traditionally used as an alternative food source. It acts as a medicinal herb containing a potential source of mucilage thus herein; we aimed to assess the toxicity, anti-inflammatory, antitussive and gastro-protective actions of M. parviflora mucilage extracted from its leaves (MLM) and fruit (MFM). Toxicity studies were investigated by in vitro hemolytic assay whereas acute anti-inflammatory and antitussive activities were assessed by carrageenan-induced paw edema and sulphur dioxide induced cough model in rats, respectively. Gastro-protective effects were studied using ethanol induced acute and chronic gastric ulcer rat models. Their metabolic profiles were determined using gas chromatography. The results revealed that MLM and MFM were non-toxic towards human erythrocytes and their lethal doses were found to be greater than 5 g/kg. Pretreatment with MLM (500 mg/kg) and MFM (500 mg/kg) significantly reduced the carrageenan-induced paw thickness (p < 0.001). Maximum edema inhibition (%) was observed at 4 h in diclofenac sodium (39.31%) followed by MLM (27.35%) and MFM (15.68%). Animals pretreated with MLM (500 mg/kg) significantly lower the cough frequency in SO2 gas induced cough models in contrast to control. Moreover, MLM at doses of 250 and 500 mg/kg reduced the ethanol induced gastric mucosal injuries in acute gastric ulcer models presenting ulcer inhibition of 23.04 and 38.74%, respectively. The chronic gastric ulcer model MFM (500 mg/kg) demonstrated a remarkable gastro-protective effect showing 63.52% ulcer inhibition and results were closely related to standard drug sucralfate. In both models, MLM and MFM decreased gastric juice volume and total acidity in addition to an increased gastric juice pH and gastric mucous content justifying an anti-secretary role of this mucilage that was further confirmed by histopathological examination. Meanwhile, GC analyses of the mucilage revealed their richness with natural as well as acidic monosaccharides. It is concluded that MLM and MFM can be used therapeutically for the management of inflammation, cough and gastric ulcer.

Jojoba Oil: An Updated Comprehensive Review on Chemistry, Pharmaceutical Uses, and Toxicity.

Jojoba is a widely used medicinal plant that is cultivated worldwide. Its seeds and oil have a long history of use in folklore to treat various ailments, such as skin and scalp disorders, superficial wounds, sore throat, obesity, and cancer; for improvement of liver functions, enhancement of immunity, and promotion of hair growth. Extensive studies on Jojoba oil showed a wide range of pharmacological applications, including antioxidant, anti-acne and antipsoriasis, anti-inflammatory, antifungal, antipyretic, analgesic, antimicrobial, and anti-hyperglycemia activities. In addition, Jojoba oil is widely used in the pharmaceutical industry, especially in cosmetics for topical, transdermal, and parenteral preparations. Jojoba oil also holds value in the industry as an anti-rodent, insecticides, lubricant, surfactant, and a source for the production of bioenergy. Jojoba oil is considered among the top-ranked oils due to its wax, which constitutes about 98% (mainly wax esters, few free fatty acids, alcohols, and hydrocarbons). In addition, sterols and vitamins with few triglyceride esters, flavonoids, phenolic and cyanogenic compounds are also present. The present review represents an updated literature survey about the chemical composition of jojoba oil, its physical properties, pharmacological activities, pharmaceutical and industrial applications, and toxicity.

The Combined Effect of Vitamin D Deficiency and Hyperparathyroidism on Postural Stability among Healthy Adult Males.

BACKGROUND AND OBJECTIVE: Vitamin D has been shown to improve muscle strength and bone health; consequently, be important for maintaining good balance. Possible risk factors related to postural stability in young adults still underdetermined. However, this study was designed to determine the effect of vitamin D status on postural stability. MATERIALS AND METHODS: A cross-sectional study of 704 healthy young adult males were enrolled in this study. Dynamic balance was measured as overall stability index (OSI) using biodex balance system (BBS). Vitamin D deficiency was defined when its serum level <20 ng mL-1. The effect size was measured for vitamin D, parathyroid hormone (PTH) and the interaction between vitamin D and PTH (VTD*PTH) with respect to the OSI values. Correlations between variables were examined according to the beta standardised coefficient (ß) and the effect size was measured using the partial eta-squared (η2) test. RESULTS: About 95, 3.8 and 1.2% of individuals had deficient, insufficient and normal vitamin D levels, respectively. Vitamin D had no significant effect to OSI, but PTH exhibited a significant correlation with OSI (adjusted ß = 0.095, p = 0.038). A significant effect size was observed between OSI and PTH (adjusted partial η2 = 0.012, p = 0.038) and between OSI and VTD*PTH (adjusted partial η2 = 0.034, p<0.001). CONCLUSION: A significant interaction of vitamin D deficiency and high PTH on postural stability is detected among healthy adult males.

Prevalence of hypovitaminosis D, and its association with hypoadiponectinemia and hyperfollistatinemia, in Saudi women with naïve polycystic ovary syndrome.

AIMS: The association between vitamin D and polycystic ovary syndrome (PCOS) is an active area of growing research. However, data in Saudi Arabia are scarce. This study aimed to define serum 25-hydroxyvitamin D (25(OH)D) levels among Saudi women with naïve PCOS, and to investigate the associations of their 25(OH)D status with their serum adiponectin and follistatin levels, along with indices of insulin resistance and hormonal deteriorations. METHODS: In this case-control observational study, 63 women with PCOS and 65 age-and body mass index (BMI)-matched control women were assessed. PCOS was diagnosed based on the revised criteria of Rotterdam. Fasting serum levels of 25(OH)D, adiponectin, follistatin, insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), androgen (Δ4-androstenedione), estradiol, progesterone, along with fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid profile were measured in both groups. RESULTS: The prevalence of hypovitaminosis D (serum 25(OH)D <30 ng/ml) was higher in PCOS group than control group (77.8% vs. 12.3%). Serum adiponectin and FSH concentrations were significantly lower, while serum follistatin, LH, TT, Δ4-androstenedione and insulin levels, as well as FPG and HOMA-IR were significantly higher in PCOS group than control group. In addition, 25(OH)D levels of PCOS women were significantly correlated positively with adiponectin and FSH levels, but negatively with follistatin, HOMA-IR, FPG, LH, testosterone, and Δ4-androstenedione levels. CONCLUSION: Hypovitaminosis D, coexisted and correlated with hypoadiponectinemia and hyperfollistatinemia, is being an alarming risk factor in Saudi women with PCOS. Further investigational and explanatory studies in large size samples are warranted to realize these findings and to improve both diagnostic and treatment tools in Saudi women with PCOS.

Pharmacotherapy with Thymoquinone Improved Pancreatic ß-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats.

AIMS: This study is aimed at evaluating the antidiabetic effects of thymoquinone (TQ) on streptozotocin (STZ)-induced diabetes in rats, and exploring the possible underlying mechanisms. METHODS: Diabetes was induced in adult male Wistar rats by intraperitoneal injection of freshly prepared STZ (65 mg/kg). After disease induction, 42 rats were equally assigned to: controls, STZ-diabetic group, and STZ-diabetic group treated with oral TQ (35 mg/kg/day) for 5 weeks. Fasting blood glucose levels were determined weekly, and the animals were euthanized at day 38 post-STZ injection. Blood samples were assessed for glucose-insulin homeostasis parameters (plasma glucose, glycated hemoglobin, serum insulin, homeostatic model assessment of insulin resistance, and insulin sensitivity index) and lipid profile. Resected pancreases were subjected to histological examination and immunohistochemical or enzyme-linked immunosorbent assay assessment to determine the pancreatic expression of insulin sensitizing ß-cells, anti-apoptotic protein "survivin," apoptosis-inducer "caspase-3," prototypic angiogenic factors (vascular endothelial growth factor [VEGF] and endothelial cluster of differentiation 31 [CD31]), pro- and anti-inflammatory cytokines (interleukin-1beta [IL-1ß] and interleukin-10 [IL-10], respectively), thiobarbituric acid reactive substances (TBARS), total glutathione (GSH), and superoxide dismutase (SOD). The hepato-renal statuses were assessed biochemically and histologically. RESULTS: Therapy with TQ markedly improved the integrity of pancreatic islets, glucose-insulin homeostasis-related parameters, lipid profile parameters, and hepato-renal functional and histomorphological statuses that collectively were severely deteriorated in untreated diabetic group. Mechanistically, TQ therapy efficiently increased insulin producing ß-cells, upregulated survivin, VEGF, CD31, IL-10, GSH and SOD, and downregulated caspase-3, IL-1ß, and TBARSs in the pancreatic tissues of STZ-diabetic rats. CONCLUSIONS: These findings prove the anti-diabetic potential of TQ and its efficacy in regenerating pancreatic ß-cells and ameliorating pancreatic inflammation and oxidative stress, and highlight its novelty in repressing apoptosis of ß-cells and enhancing islet revascularization in STZ-diabetic rats. Further studies are required to support these findings and realize their possible clinical significance.

Thymoquinone potentiates chemoprotective effect of Vitamin D3 against colon cancer: a pre-clinical finding.

Prevention of colon cancer among high-risk group has been long lasting research goal. Emerging data have evidenced the anticancer activities of Vitamin D3 (Vit.D) and Thymoquinone (TQ). The aim of the current study was to evaluate the synergistic potential of Thymoquinone and Vitamin D3 in the control of colon cancer progression using azoxymethane-induced rat model. Vit.D and TQ were given individually or in combination 4 week prior to induction and continued for a total of 20 week. At the end of the study, all animals were euthanized and their resected colons were examined macroscopically and microscopically for tumor growth. Colonic tissue preparations were used for measuring gene expression and/or protein levels of selected pro and anti-tumor biomarkers using quantitative RT-PCR, ELISA and immunohistochemistry. Compared with their individual supplementation, combined Vit.D/TQ showed prominent anti-tumor effect manifested by significant reduction (P < 0.05) of the numbers of grown tumors and large aberrant crypts foci. Mechanistically, gene expression and/or protein quantification studies revealed that combined Vit.D/TQ supplementation induced significant reduction (P < 0.01 and P < 0.05) of pro-cancerous molecules (Wnt, ß-catenin, NF-κB, COX-2, iNOS, VEGF and HSP-90) as well as significant increase (P < 0.01 and P < 0.05, respectively) of anti-tumorigenesis biomarkers (DKK-1, CDNK-1A, TGF-ß1, TGF-ß/RII and smad4) as compared to un-supplemented or individually supplemented groups, respectively. In conclusion, TQ augmented the chemopreventive effect of Vit.D during the initiation phase of colon cancer in rat model, with the potential to suppress progression of pre-neoplastic lesions in colon carcinogenesis.

Association of the body mass index with the overall stability index in young adult Saudi males.

OBJECTIVES: Studies have focused on obesity-induced balance instability in the older population, which has been understudied in young adults. This study aimed to determine the impact of obesity on dynamic balance in young adult Saudi males. METHODS: A cross-sectional study of 704 young adult males aged between 18 and 35 years from Umm Al-Qura University, Makkah, KSA, was performed. The obesity-induced balance was evaluated with a Biodex Balance System apparatus with a movable platform, and the overall stability index (OSI) was measured as an indicator of dynamic balance. Participants with a body mass index (BMI) ≥30 kg/m2 were considered obese. RESULTS: The mean age and BMI of the participants was 20 years and 25.6 kg/m2, respectively. The mean OSI of the entire sample was 0.9, and the OSI values increased significantly (p < 0.001) with increasing BMI. The adjusted correlation between OSI and BMI was 0.487 (p < 0.001). Logistic regression showed that for each one-unit increment in BMI, there was an expected rise of 0.115 units in the OSI value. The receiver operating characteristic curve showed that the optimal threshold of the weight and BMI cutoff points that optimized the OSI values were 18.8 kg/m2 and 54.5 kg, respectively, with high sensitivity and specificity values. In addition, BMI affected approximately 23% of the total variability on balance (partial eta squared = 0.227, p < 0.001). CONCLUSION: Obesity has a clear impact on dynamic balance in the selected young males. Weight management programs for obese subjects should be encouraged to optimize BMI and weight, which can attenuate balance stability.

Activins and their related proteins in colon carcinogenesis: insights from early and advanced azoxymethane rat models of colon cancer.

BACKGROUND: Activin-A may exert pro- or anti-tumorigenic activities depending on cellular context. However, little is known about its role, or the other mature activin proteins, in colorectal carcinoma (CRC). This study measured the expression of activin ßA- & ßB-subunits, activin type IIA & IIB receptors, smads 2/3/4/6/7 and follistatin in CRC induced by azoxymethane (AOM) in rats. The results were compared with controls and disseminated according to the characteristics of histopathological lesions. METHODS: Eighty male Wistar rats were allocated into 20 controls and the remaining were equally divided between short 'S-AOM' (15 weeks) and long 'L-AOM' (35 weeks) groups following injecting AOM for 2 weeks. Subsequent to gross and histopathological examinations and digital image analysis, the expression of all molecules was measured by immunohistochemistry and quantitative RT-PCR. Activin-A, activin-B, activin-AB and follistatin were measured by ELISA in serum and colon tissue homogenates. RESULTS: Colonic pre-neoplastic and cancerous lesions were identified in both AOM groups and their numbers and sizes were significantly (P < 0.05) greater in the L-AOM group. All the molecules were expressed in normal colonic epithelial cells. There was a significantly (P < 0.05) greater expression of ßA-subunit, IIB receptor and follistatin in both pre-neoplastic and cancerous tissues. Oppositely, a significant (P < 0.05) decrease in the remaining molecules was detected in both AOM groups. Metastatic lesions were only observed within the L-AOM group and were associated with the most significant alterations of all molecules. Significantly higher concentrations of activin-A and follistatin and lower activin-AB were also detected in both groups of AOM. Tissue and serum concentrations of activin-A and follistatin correlated positively, while tissue activin-AB inversely, and significantly with the numbers and sizes of colonic lesions. CONCLUSIONS: Normal rat colon epithelial cells are capable of synthesising, controlling as well as responding to activins in a paracrine/autocrine manner. Colonic activin systems are pathologically altered during tumorigenesis and appear to be time and lesion-dependent. Activins could also be potential sensitive markers and/or molecular targets for the diagnosis and/or treatment of CRC. Further studies are required to illustrate the clinical value of activins and their related proteins in colon cancer.

Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats.

Colorectal cancer (CRC) is one of the most prevalent cancers and has a high mortality rate. Insensitivity and the limited therapeutic efficacy of its standard chemotherapeutic drug, 5-fluorouracil (5-FU), represents an important challenge in CRC treatment. The robust antitumor properties of thymoquinone (TQ), the main bioactive constituent of Nigella sativa, have recently been demonstrated on different cancers. We investigated whether TQ could potentiate the chemopreventive effect of 5-FU to eradicate the early stages of CRC and elucidated its underlying mechanisms. An intermediate-term (15 weeks) model of colorectal tumorigenesis was induced in male Wistar rats by azoxymethane (AOM), and the animals were randomly and equally divided into five groups: control, AOM, AOM/5-FU, AOM/TQ, and AOM/5-FU/TQ. TQ (35 mg/kg/d; 3 d/wk) was given during the seventh and 15th weeks post-AOM injection, while 5-FU was given during the ninth and tenth weeks (12 mg/kg/d for 4 days; then 6 mg/kg every other day for another four doses). At week 15, the resected colons were subjected to macroscopic, histopathological, molecular, and immunohistochemical examinations. Interestingly, 5-FU/TQ combination therapy resulted in a more significant reduction on AOM-induced colorectal tumors and large aberrant crypts foci than treatment with the individual drugs. Mechanistically, 5-FU and TQ remarkably cooperated to repress the expression of procancerous Wnt, ß-catenin, NF-κB, COX-2, iNOS, VEGF, and TBRAS and upregulate the expression of anti-tumorigenesis DKK-1, CDNK-1A, TGF-ß1, TGF-ßRII, Smad4, and GPx. Overall, our findings present the first report describing the in vivo enhancement effect of combined TQ and 5-FU against early stages of CRC; however, further studies are required to determine the value of this combination therapy in an advanced long-term model of CRC and also to realize its clinical potential.

Nutritional status of low birth weight infants in Makkah region: Evaluation of anthropometric and biochemical parameters.

OBJECTIVE: To assess the nutritional status of low birth weight infants from Makkah area immediately after birth. METHODS: The prospective study was conducted between October and December 2012 at Al-Noor Speciality Hospital, Makkah, Saudi Arabia, and comprised low birth weight infants who were divided into three equal groups according to their birth weight: group A (low birthweight1501-2500gm), group B (very low birthweight1001-1500gm), and group C (extremely low birth weight < 1000gm). Mothers who had delivered low birth weight infants were enrolled. Weight, length, head circumference, complete blood count, and blood tests were performed for all the infants under investigation. RESULTS: There were 300 infants in the study; 100(33.3%) in each of the 3 groups. Group C showed the lowest gestational age, length, and head circumferences (p< 0.05 each). No significant discrepancies were found in complete blood count results among the three groups (p>0.05). Normal serum phosphorus, potassium and magnesium levels and mild hypocalcaemia were observed in all infants. However, hypernatraemia was significantly evident (p< 0.05) for group C. All infants had hyperglycaemia and hyperbilirubinaemia. Albumin content decreased significantly (p< 0.05) as birth weight decreased. Groups B and C infants showed higher serum urea than group A infants (p< 0.05). CONCLUSIONS: Low newborn birth weight was related to the deteriorated nutritional status in terms of low anthropometric and abnormal biochemical measures. It was not possible to correlate the birth weight of the neonates to the parameters of the complete blood tests.