Introducing Group Open-Book Exams as a Learning and Assessment Strategy in the Clinical Biochemistry Course for Medical Students.

BACKGROUND: Teachers constantly strive to obtain reliable and appropriate teaching and assessment methods to maximize the learning experience. This study aimed to introduce combined modified team-based learning and open-book exams (TBL/OBEs) as learning and assessment strategies in clinical biochemistry for medical students and assess students' perceptions. METHODS: Second-year medical students enrolled in the clinical biochemistry course were included in this study and subjected to TBL/OBE assessment. The assessment included two parts: the open-book format for half of the questions and the closed-book format for the other as a control. Upon completing the combined TBL/OBE session, the students were required to complete a structured survey to evaluate their perception of the experience. The data were gathered and analyzed. Data were presented as mean±standard error of the mean (SEM), and a p-value ≤0.05 was considered statistically significant. RESULTS: A total of 358 students completed the TBL/OBE and closed-book exam (CBE) and responded to the survey. Of these students, 76% preferred the OBE, and 84% thought it was a suitable learning method. On the one hand, the mean difficulty of the OBE format was 92.7±1.5 SEM, while, for the CBE, the mean difficulty was 88.7±1.9 SEM (p=0.015). On the other hand, the mean discrimination factor for OBE was 0.26±0.04 and, for the CBE, 0.41±0.04 SEM (p=0.0016). Males found the OBE questions easier (p=0.025) and less stressful (p=0.01). CONCLUSION: A combined model of modified TBL and OBE is a successful learning and assessment strategy in clinical biochemistry for medical students.

Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome.

Brain insulin resistance is linked to metabolic syndrome (MetS). A low-carbohydrate, high-fat (LCHF) diet has been proposed to have a protective effect. Therefore, this study aimed to investigate the brain insulin resistance markers in a rat animal model of MetS and the protective effects of the LCHF diet. Four groups of male rats (10/group) were created. Group I (Control) was fed a regular diet. Groups II-IV were injected with dexamethasone (DEX) to induce MetS. Group II received DEX with a regular diet. Group III (DEX + LCHF) rates were fed a low-carbohydrate, high-fat diet, while Group IV (DEX + HCLF) rats were fed a high-carbohydrate, low-fat (HCLF) diet. At the end of the four-week experiment, HOMA-IR was calculated. Moreover, cerebral gene expression analysis of S-100B, BDNF, TNF-α, IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, Bax, Bcl-2, and caspase-3 was carried out. In the DEX group, rats showed a significant increase in the HOMA-IR and a decrease in the gene expression of IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, BDNF, and Bcl2, with a concomitant rise in S100B, TNF-α, Bax, and caspase-3. The LCHF diet group showed a significantly opposite effect on all parameters. In conclusion, MetS is associated with dysregulated cerebral gene expression of BDNF, S100B, and TNF-α and disturbed IGF-1 signaling, with increased apoptosis and neuroinflammation. Moreover, the LCHF diet showed a protective effect, as evidenced by preservation of the investigated biochemical and molecular parameters.

The Effect of Chronic Laxative Use on Lipid Profile and HbA1c: A Hospital-Based Retrospective Study.

BACKGROUND: Laxatives are over-the-counter medications used as a treatment for constipation. The lipid-lowering effect of the long-term use of laxatives has been proposed. AIM: To investigate the possible impact of the chronic use of laxatives on serum lipid profile, body mass index (BMI), and hemoglobin A1c (HbA1c). METHODS: An observational retrospective cohort study was conducted to analyze data related to patients who received laxatives for six or 12 months or more in the KAUH database system. BMI, weight, cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and HbA1c data were collected retrospectively from hospital records for three time points: baseline, six months, and 12 months of laxative treatment from the starting date for each patient. RESULTS: A total of 106 patients' records fulfilled the inclusion criteria, 46 (43%) males with a mean age of 66 and 60 (57%) females with a mean age of 63. A significant decrease in plasma cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels was observed in those who used laxatives for 12 months. Furthermore, an overall BMI and ALT reduction was seen in the combined. On the other hand, HbA1c levels appeared to improve in the combined group but not statistically significant. The change in the cholesterol level could be observed in patients receiving statin treatment and those without, with no statistical significance between the two groups. CONCLUSION: Chronic laxative use for 12 months or more is associated with a decreased total and LDL-C level with no significant effect on high-density lipoprotein-cholesterol (HDL-C) levels. Additionally, there was a significant reduction in BMI and ALT. This effect is more prominent with combined therapy. Further multicentric studies on larger sample sizes are recommended to confirm our findings.

Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control.

Factors such as aging, an unhealthy lifestyle with decreased physical activity, snacking, a standard Western diet, and smoking contribute to raising blood pressure to a dangerous level, increasing the risk of coronary artery disease and heart failure. Atherosclerosis, or aging of the blood vessels, is a physiological process that has accelerated in the last decades by the overconsumption of carbohydrates as the primary sources of caloric intake, resulting in increased triglycerides and VLDL-cholesterol and insulin spikes. Classically, medications ranging from beta blockers to angiotensin II blockers and even calcium channel blockers were used alone or in combination with lifestyle modifications as management tools in modern medicine to control arterial blood pressure. However, it is not easy to control blood pressure or the associated complications. A low-carbohydrate, high-fat (LCHF) diet can reduce glucose and insulin spikes, improve insulin sensitivity, and lessen atherosclerosis risk factors. We reviewed articles describing the etiology of insulin resistance (IR) and its impact on arterial blood pressure from databases including PubMed, PubMed Central, and Google Scholar. We discuss how the LCHF diet is beneficial to maintaining arterial blood pressure at normal levels, slowing down the progression of atherosclerosis, and reducing the use of antihypertensive medications. The mechanisms involved in IR associated with hypertension are also highlighted.

Association between laboratory markers and Covid-19 disease severity and outcome: a retrospective cohort study in Saudi Arabia.

Introduction: In Saudi Arabia, limited studies have evaluated factors including epidemiologic, clinical, and laboratory findings that are associated with COVID-19 disease. The aim of this paper was to identify laboratory parameters used in King Abdulaziz University Hospital which show an association with disease severity and patient outcome in the form of mortality. Methods: Age, gender, medical history, and laboratory parameters were all retrospectively assessed concerning disease severity and disease outcome in a total of 111 COVID-19 patients at King Abdulaziz University Hospital between July 2020 and August 2020. Patients were categorized into mild disease if they did not require ward admission, moderate if they met the Ministry of Health criteria for isolation ward admition, and severe if they were admitted to the ICU. Results: Age but not gender was associated with the disease severity X2 (4, N = 110) = 27.2, p <0.001. Of all laboratory parameters on admission, only the levels of Albumin appeared to be significantly associated X2 (2, N =70) = 6.6, p <0.05 with disease severity. Age but not gender was also significantly associated with disease outcome X2 (2, N = 110) = 12.8, p < 0.01. Interestingly, RBC count also showed a significant relation with disease outcome X2 (2, N = 71) = 6.1, p <0.05. Discussion: This study provides more understanding of the laboratory characteristics in our part of the world to efficiently manage the disease.

Prevalence of Gastroesophageal Reflux Disease (GERD) Among Electronic Cigarette-Smoking University Students in Jeddah, Saudi Arabia.

Background Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal tract diseases. Although there is a strong association between smoking and GERD, it is poorly understood until now. Electronic cigarettes (E-cigarettes) are widely used nowadays. So, our study aimed to investigate the prevalence of GERD among all Jeddah university students and its relation to E-cigarette smoking. Methodology A cross-sectional study was conducted among university students of all specialties in Jeddah, Saudi Arabia, using an online questionnaire to collect data distributed in a Google Form (Google LLC, Mountain View, California, United States) from August to November 2022. Results This study included 397 students, 36.5% of whom were from 18 to 20 years old, and the majority were females (69.3%). Of the participants, 43.8% were non-smokers, 13.1% were ex-smokers, and 43.1% currently smoked; of the last, 13.6% smoked tobacco cigarettes, 17.6% smoked hookah, and 35% were current E-cigarette smokers. The study found that among the participants, 19.9% had GERD based on the GerdQ, with females having a significantly higher percentage of GERD. A weak association was found between the prevalence of GERD and smoking cigarettes (p=0.49), hookah (p=0.988 ), and E-cigarettes (p=0.788 ) but this could be attributed to the high BMI. Conclusion E-cigarette smoking is more prevalent among university students in Jeddah than traditional cigarettes or hookah. However, there was no statistically significant link between E-cigarette smoking and GERD. High BMI could be a superadded factor.

Discrimination Power of Short Essay Questions Versus Multiple Choice Questions as an Assessment Tool in Clinical Biochemistry.

Assessment is fundamental to the educational process. Multiple choice questions (MCQs) and short essay questions (SEQs) are the most widely used assessment method in medical school. The current study evaluated the discriminating value of SEQs compared to MCQs as assessment tools in clinical biochemistry and correlated undergraduate students' SEQ scores with their overall scores during the academic years 2021-2022 and 2022-2023. This is a descriptive-analytical study in which MCQ and SEQ papers of clinical biochemistry were analyzed. The mean score for SEQs in males was 66.7 ± 1.2 and for females it was 64.0 ± 1.1 SEM, with a p-value of 0.09; for MCQs, the mean score for males was 68.5 ± 0.9 SEM and for females it was 72.6 ± 0.8. When analyzing the difficulty index (DI) and discrimination factor (DF) of the questions, MCQs have a mean DI of 0.70 ± 0.01,and DF of 0.05 to 0.6. SEQs have a mean DI of 0.73 ± 0.03 and DF of 0.68 ± 0.01; there was a significant difference between the DF of MCQs and SEQs (p < 0.0001). Furthermore, there was a significant difference between SEQs and MCQs when categorizing students based on their scores, except for A-scored students. According to the current study, SEQs have a higher discriminating ability than MCQs and help differentiate high-achieving students from low-achieving students.

The Possible Effect of the Long-Term Use of Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA) on Hba1c and Lipid Profile in Type 2 Diabetes Mellitus: A Retrospective Study in KAUH, Jeddah, Saudi Arabia.

(1) Background: Type 2 diabetes (T2DM) is a chronic metabolic disease with serious health complications. T2DM is associated with many chronic illnesses, including kidney failure, cardiovascular diseases (CVD), vision loss, and other related diseases. Obesity is one of the major factors associated with insulin resistance and dyslipidemia. Recently, the development of GLP-1 Receptor agonist (GLP-1RA) showed great therapeutic potential for T2DM. Aim: To retrospectively investigate the association of the long-term use of GLP-1RA therapy in T2DM patients with HbA1c levels and dyslipidemia. (2) Methods: Retrospective data collection and analysis of demographic, clinical records, and biochemical parameters were carried out for 72 T2DM taking GLP-1RA treatments for six months. (3) Results: A total of 72 T2DM patients with a mean age = 55 (28 male and 44 female) were divided into two groups. Group 1 received statins (n = 63), and group 2 did not receive statins (n = 9). The GLP-1RA effect on BMI was significantly decreased in group 1 (p < 0.01). A significant effect was observed for HbA1c in both groups for six months of treatment duration (p < 0.05). The AST levels significantly decreased in group 2 from 25.2 to 19.4 U\L (p = 0.011). (4) Conclusions: GLP-1RA treatments were associated with weight reduction and improved glycemic control for T2DM patients. Moreover, it is suggested that it has anti-inflammatory and hepatoprotective effects. However, no direct association was found with the lipid profile in all groups of T2DM.

Low-Carbohydrate Ketogenic Diet for Improvement of Glycemic Control: Mechanism of Action of Ketosis and Beneficial Effects.

The incidence of metabolic syndrome and diabetes mellitus is increasing globally. A diet rich in carbohydrates increases the hyperglycemic state. While considering the lifestyle changes to combat life-threatening diseases, there is an effort to decrease the daily intake of carbohydrates. A low-carbohydrate diet also makes the body rely more on fat for energy, so there is less fat accumulation. A diet is considered to be low-carbohydrate ketogenic if the intake is ≤ 50 g per day. The 'low -carbohydrate ketogenic diet' (LCKD) produces ketosis. LCKD contains high-fat, moderateprotein, and low-carbohydrate components. The main objectives of the present review are to discuss insulin resistance in different viscera of the body, describe the role of adipokines in insulin resistance, understand the mechanism of ketogenesis, and determine the impact of LCKD in overcoming insulin resistance in the body. In the present review, we also highlight the beneficial effects of LCKD in metabolic, neurodegenerative, cardiovascular, and lipid disorders and discuss the effect on longevity and aging. LCKD may help in combating the morbidity and mortality arising from the above-mentioned diseases and also help in leading a better quality of life.

Low-Carbohydrate High-Fat Diet: A SWOC Analysis.

Insulin resistance (IR) plays a role in the pathogenesis of many diseases, such as type 2 diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, obesity, and neurodegenerative diseases, including Alzheimer's disease. The ketogenic diet (KD) is a low-carbohydrate/high-fat diet that arose in the 1920s as an effective treatment for seizure control. Since then, the KD has been studied as a therapeutic approach for various IR-related disorders with successful results. To date, the use of the KD is still debatable regarding its safety. Some studies have acknowledged its usefulness, while others do not recommend its long-term implementation. In this review, we applied a SWOC (Strengths, Weaknesses, Opportunities, and Challenges) analysis that revealed the positive, constructive strengths of the KD, its potential complications, different conditions that can make used for it, and the challenges faced by both physicians and subjects throughout a KD. This SWOC analysis showed that the KD works on the pathophysiological mechanism of IR-related disorders such as chronic inflammation, oxidative stress and mitochondrial stress. Furthermore, the implementation of the KD as a potential adjuvant therapy for many diseases, including cancer, neurodegenerative disorders, polycystic ovary syndrome, and pain management was proven. On the other hand, the short and long-term possible undesirable KD-related effects, including nutritional deficiencies, growth retardation and nephrolithiasis, should be considered and strictly monitored. Conclusively, this review provides a context for decision-makers, physicians, researchers, and the general population to focus on this dietary intervention in preventing and treating diseases. Moreover, it draws the attention of scientists and physicians towards the opportunities and challenges associated with the KD that requires attention before KD initiation.

Modulation of Dyslipidemia Markers Apo B/Apo A and Triglycerides/HDL-Cholesterol Ratios by Low-Carbohydrate High-Fat Diet in a Rat Model of Metabolic Syndrome.

Metabolic syndrome (MetS) risks cardiovascular diseases due to its associated Dyslipidemia. It is proposed that a low-carbohydrate, high-fat (LCHF) diet positively ameliorates the MetS and reverses insulin resistance. Therefore, we aimed to investigate the protecting effect of the LCHF diet on MetS-associated Dyslipidemia in an experimental animal model. Forty male Sprague-Dawley rats were divided into four groups (10/group): the control group, dexamethasone-induced MetS (DEX) (250 µg/kg/day), LCHF-fed MetS group (DEX + LCHF), and High-Carbohydrate-Low-Fat-fed MetS group (DEX + HCLF). At the end of the four-week experiment, fasting glucose, insulin, lipid profile (LDL-C, HDL-C, Triglyceride), oxidized-LDL, and small dense-LDL using the ELISA technique were estimated. HOMA-IR, Apo B/Apo A1 ratio, and TG/HDL were calculated. Moreover, histological examination of the liver by H & E and Sudan III stain was carried out. In the DEX group, rats showed a significant (p < 0.05) increase in the HOMA-IR, atherogenic parameters, such as s-LDL, OX-LDL, Apo B/Apo A1 ratio, and TG/HDL. The LCHF diet significantly improved the parameters of Dyslipidemia (p < 0.05) by decreasing the Apo B/Apo A1 and TG/HDL-C ratios. Decreased steatosis in LCHF-fed rats compared to HCLF was also revealed. In conclusion, the LCHF diet ameliorates MetS-associated Dyslipidemia, as noted from biochemical results and histological examination.

Endoplasmic reticulum stress and mitochondrial injury are critical molecular drivers of AlCl3-induced testicular and epididymal distortion and dysfunction: protective role of taurine.

Aluminum, the third most plentiful metal in the Earth's crust, has potential for human exposure and harm. Oxidative stress plays an essential role in producing male infertility by inducing defects in sperm functions. We aimed to investigate the role of endoplasmic reticulum (ER) stress and mitochondrial injury in the pathogenesis of aluminum chloride (AlCl3)-induced testicular and epididymal damage at the histological, biochemical, and molecular levels, and to assess the potential protective role of taurine. Forty-eight adult male albino rats were separated into four groups (12 in each): negative control, positive control, AlCl3, and AlCl3 plus taurine groups. Testes and epididymis were dissected. Histological and immunohistochemical (Bax and vimentin) studies were carried out. Gene expression of vimentin, PCNA, CHOP, Bcl-2, Bax, and XBP1 were investigated via quantitative real-time polymerase chain reaction (qRT-PCR), besides estimation of malondialdehyde (MDA) and total antioxidant capacity (TAC). Light and electron microscopic examinations of the testes and epididymis revealed pathological changes emphasizing both mitochondrial injury and ER stress in the AlCl3 group. Taurine-treated rats showed a noticeable improvement in the testicular and epididymal ultrastructure. Moreover, they exhibited increased gene expression of vimentin, Bcl-2, and PNCA accompanied by decreased CHOP, Bax, and XBP1 gene expression. In conclusion, male reproductive impairment is a significant hazard associated with AlCl3 exposure. Both ER stress and mitochondrial impairment are critical mechanisms of the deterioration in the testes and epididymis induced by AlCl3, but taurine can amend this.

Integrative system biology and mathematical modeling of genetic networks identifies shared biomarkers for obesity and diabetes.

Obesity and type 2 and diabetes mellitus (T2D) are two dual epidemics whose shared genetic pathological mechanisms are still far from being fully understood. Therefore, this study is aimed at discovering key genes, molecular mechanisms, and new drug targets for obesity and T2D by analyzing the genome wide gene expression data with different computational biology approaches. In this study, the RNA-sequencing data of isolated primary human adipocytes from individuals who are lean, obese, and T2D was analyzed by an integrated framework consisting of gene expression, protein interaction network (PIN), tissue specificity, and druggability approaches. Our findings show a total of 1932 unique differentially expressed genes (DEGs) across the diabetes versus obese group comparison (p≤0.05). The PIN analysis of these 1932 DEGs identified 190 high centrality network (HCN) genes, which were annotated against 3367 GO terms and functional pathways, like response to insulin signaling, phosphorylation, lipid metabolism, glucose metabolism, etc. (p≤0.05). By applying additional PIN and topological parameters to 190 HCN genes, we further mapped 25 high confidence genes, functionally connected with diabetes and obesity traits. Interestingly, ERBB2, FN1, FYN, HSPA1A, HBA1, and ITGB1 genes were found to be tractable by small chemicals, antibodies, and/or enzyme molecules. In conclusion, our study highlights the potential of computational biology methods in correlating expression data to topological parameters, functional relationships, and druggability characteristics of the candidate genes involved in complex metabolic disorders with a common etiological basis.

Integrative global co-expression analysis identifies key microRNA-target gene networks as key blood biomarkers for obesity.

BACKGROUND: Obesity is associated with the quantitative changes in miRNAs and their target genes. However, the molecular basis of their dysregulation and expression status correlations is incompletely understood. Therefore, this study aims to examine the shared differentially expressed miRNAs and their target genes between blood and adipose tissues of obese individuals to identify potential blood-based biomarkers. METHODS: In this study, 3 gene expression datasets (two mRNA and one miRNA), generated from blood and adipose tissues of 68 obese and 39 lean individuals, were analyzed by a series of robust computational concepts, like protein interactome mapping, functional enrichment of biological pathways and construction of miRNA-mRNA and transcription factor gene networks. RESULTS: The comparison of blood versus tissue datasets has revealed the shared differential expression of 210 genes (59.5% upregulated) involved in lipid metabolism and inflammatory reactions. The blood miRNA (GSE25470) analysis has identified 79 differentially expressed miRNAs (71% downregulated). The miRNA-target gene scan identified regulation of 30 shared genes by 22miRNAs. The gene network analysis has identified the inverse expression correlation between 8 target genes (TP53, DYSF, GAB2, GFRA2, NACC2, FAM53C, JNK and GAB2) and 3 key miRNAs (hsa-mir-940, hsa-mir-765, hsa-mir-612), which are further regulated by 24 key transcription factors. CONCLUSIONS: This study identifies potential obesity related blood biomarkers from large-scale gene expression data by computational miRNA-target gene interactome and transcription factor network construction methods.

The Interplay of Vitamin D Deficiency and Cellular Senescence in The Pathogenesis of Obesity-Related Co-Morbidities.

This scoping review aims to clarify the interplay between obesity, vitamin D deficiency, cellular senescence, and obesity-related metabolic consequences, mainly subclinical atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Obesity is a significant global health problem that involves cellular, environmental, behavioral, and genetic elements. The fundamental cause of obesity throughout all life stages is an energy imbalance, and its consequences are countless and, foremost, very common. Obesity has been comprehensively studied in the literature given its association with low serum vitamin D, with many proposed mechanisms linking the two conditions. Moreover, markers of exaggerated cellular senescence have been proven to accumulate in obese individuals. Subclinical atherosclerosis initiates an early stage that ends in serious cardiac events, and obesity, low vitamin D, and senescent cells largely contribute to its associated chronic low-grade inflammation. Furthermore, NAFLD signifies the hepatic manifestation of metabolic syndrome, and studies have highlighted the important role of obesity, vitamin D deficiency, and cellular senescence in its development. Therefore, we outlined the most important mechanisms tying these conditions to one another.

An Overview of the Perspective of Cellular Autophagy: Mechanism, Regulation, and the Role of Autophagy Dysregulation in the Pathogenesis of Diseases.

Autophagy is a cellular process that eliminates unnecessary cytoplasmic materials, such as long-age proteins, destroyed organelles, and foreign microorganisms. Macroautophagy (MaA), chaperone-mediated autophagy, and microautophagy are the three main types of autophagy. It is regulated by the integration of signaling from the AMPK and mTOR-ULK1 pathways. Autophagy plays a physiological role in health, and its dysregulation could be a pathophysiologic mechanism in different disease conditions. In the current study, we reviewed papers of Google Scholar database, PubMed, PubMed Central, Cochrane Database of Systematic Reviews, MEDLINE, and MedlinePlus with no time limitation and a recent World Health Organization report. In the current review, it could be concluded that autophagy plays many physiological functions, including immune system modulation, and regulates different cellular processes such as metabolism, protein synthesis, and cellular transportation. Dysregulation of autophagy is implicated in tumorigenesis, aging, age-related neurodegeneration, and endothelial dysfunctions. Autophagy dysregulation is also implicated in the newly discovered CoV-COVID-19 pathogenesis.

Methylation degree of metalloproteinase inhibitor RECK gene: Links to RECK protein level and hepatocellular carcinoma in chronic HCV infection patients.

The RECK gene, a tumor suppressor gene, inhibits angiogenesis, invasion, and tumor metastasis. Epigenetic regulation of the RECK gene constitutes a potent approach to the molecular basis of liver malignancy. This study aims to evaluate the promoter methylation status of the RECK gene and its serum level in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and the potential association of RECK gene methylation with clinical criteria of HCC. One hundred and fifty-five subjects were included (healthy control [55], chronic HCV patients [55], HCV-related HCC patients [45]). The methylation status of the RECK gene promoter and serum RECK level were investigated by methylation-specific PCR and enzyme-linked immunosorbent assay techniques, respectively. RECK gene promoter hypermethylation was recorded in 46.7% of HCC patients, and 10.9% of HCV patients, but not in control subjects (0%). It was related to RECK protein level, varices, edema, ascites, lymph node metastasis, vascular invasion, and the largest diameter of focal lesions. Meanwhile, it was not associated with focal lesion number nor distant metastasis of HCC. In conclusion, RECK gene promoter hypermethylation is linked to HCV genotype-4-related HCC. Moreover, different degrees of RECK gene promoter methylation are associated with serum RECK level, lymph node metastasis, and vascular invasion, which could prove its pathogenic role in hepatocarcinogenesis in chronic HCV-infected patients.

MTHFR C677T Polymorphism and Serum Homocysteine Level as Risk Factors of Coronary Heart Disease in Patients with Androgenetic Alopecia: A Case Control Study.

BACKGROUND: Androgenetic alopecia (AGA) is associated with a risk of coronary heart disease (CHD), although the causes underlying this association are not clear. Serum homocysteine (SH) is a known risk factor for CHD, and methylene tetrahydrofolate reductase enzyme (MTHFR) plays a crucial role in the remethylation of homocysteine to methionine. The polymorphism C677T that affects the catalytic domain of the MTHFR protein leads to a high levels of SH. Our hypothesis was that this polymorphism and SH level are risk factors for CHD in patients with AGA. MATERIALS AND METHODS: A total of 106 patients with AGA and 100 well-matched healthy controls were enrolled in the study. SH levels were estimated. DNA was extracted and polymerase chain reaction amplification, followed by restriction enzyme digestion for MTHFR (C677T) gene, was conducted. RESULTS: SH levels were significantly higher in the patient group and highest in those with the TT genotype. The mutant T allele was associated with hyperhomocysteinemia and an increased risk of CHD in patients with AGA. CONCLUSIONS: AGA is associated with a higher risk of developing CHD due to the associated higher level of SH that, in turn, depends on and is correlated with mutant MTHFR genotypes. Cardiac evaluation and follow-up of patients with AGA is recommended for early detection and treatment of CHD to avoid an overall detrimental course.

Cellular Senescence and Vitamin D Deficiency Play a Role in the Pathogenesis of Obesity-Associated Subclinical Atherosclerosis: Study of the Potential Protective Role of Vitamin D Supplementation.

The exact link between obesity, vitamin D deficiency, and their relation to cellular senescence in the pathogenesis of subclinical atherosclerosis is still under debate. Therefore, the current study aims to verify the possible role of vitamin D deficiency and cellular senescence in the pathogenesis of obesity-related subclinical atherosclerosis. Moreover, it aims to investigate the possible protective role of vitamin D supplementation. Fifty-seven male albino rats were enrolled in the study and classified into four groups: negative (10) and positive control groups (10), an obese model group (24), and a vitamin-D-supplemented obese group (13). Aortic tissue samples and fasting blood samples were collected. The following biochemical investigations were performed: serum cholesterol, triglycerides, HDL-C, LDL-C, ALT, AST, CPK, CK-MB, and hs-cTnt. HOMA-IR was calculated. Moreover, serum SMP-30, 25 (OH)Vitamin D3, and eNOS were determined by the ELISA technique. Aortic gene expression of eNOS, SMP-30, and P53 was estimated by real-time qRT-PCR. Serum 25(OH) D3 and SMP-30 were lower in the obese group. In addition, the obese group showed higher serum lipid profile, HOMA-IR, eNOS, ALT, AST, CPK, CK-MB, and hs-cTnt than the control groups, while decreased levels were found in the vitamin-D-treated obese group. Gene expression of eNOS and SMP-30 were in accordance with their serum levels. A positive correlation was found between vitamin D level and SMP-30. In conclusion, obesity is associated with vitamin D deficiency and enhanced cellular senescence. They could play a role in the pathogenesis of obesity-associated subclinical atherosclerosis and endothelial dysfunction. Vitamin D supplements could play a protective role against such obesity-related comorbidity.

Study of Cellular Senescence and Vitamin D Deficiency in Nonalcoholic Fatty Liver Disease and The Potential Protective Effect of Vitamin D Supplementation.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a pathological process characterized by excessive hepatic fatty deposition with possible involvement of vitamin D deficiency and cellular senescence. The aim of this study is to investigate the pathophysiologic role of vitamin D deficiency and cellular senescence in NAFLD development. Moreover, it aims to investigate the potential protective role of vitamin D supplementation. METHODS: This is an experimental Case/Control study. Forty-five male albino rats were enrolled in this study. Animals were divided into four groups: negative and positive control groups (10 for each group), a model of NAFLD (11) and vitamin D-treated NAFLD groups (14). At the end of the experiment, all rats were subjected to the following investigation; biochemical estimation of serum 25 hydroxycholecalciferol, senescence marker protein-30 (SMP-30), lipid profile and calculation of homeostatic model of insulin resistance (HOMA-IR). RESULTS: NAFLD group shows a significant increase in glucose, insulin levels, and HOMA- IR compared with both normal controls. This finding indicates the intimate association between insulin resistance and NAFLD pathogenesis. Moreover, it was found that NAFLD group shows a significant decrease in SMP-30 level compared with normal controls. While vitamin D-treated NAFLD group shows significant increased SMP-30 and decrease in HOMA-IR in comparison with nontreated NAFLD group. CONCLUSION: Vitamin D deficiency and increased cellular senescence are key features of NAFLD. Vitamin D supplementation could play a protective role, which needs further investigation including clinical human study.