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This review article studies the complex field of noncoding RNAs (ncRNAs) in cancer biology, focusing on their potential use as biomarkers and therapeutic targets. NcRNAs include circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs). We discuss how ncRNAs affect gene expression in cancerous cells, the spread of cancer, and metastasis. The article illustrates the complex pathways through which ncRNAs can affect oncogenesis, tumor suppression, and therapeutic resistance. It also assesses the potential clinical uses of non-coding RNAs (ncRNAs), including their utility in cancer diagnosis, and prognosis. Besides, their potential for personalized cancer therapy is documented. Finally, it is concluded that understanding the role of ncRNA is of clinical importance regarding carcinogenesis, cancer diagnosis, and personalized therapy.

BackgroundEndothelial dysfunction (ED) is induced by insulin resistance, mediated by endoplasmic reticulum (ER) stress and disturbed autophagy. This study investigates the protective role of a low-carbohydrate, high-fat (LCHF) diet on ED, ER stress, and autophagy dysregulation in an experimental animal model of metabolic syndrome.MethodsForty male Sprague–Dawley rats were divided into four groups: a Control group (standard diet) and three Dexamethasone (DEX) treated groups. Group II continued the standard diet, Group III received an LCHF diet, and Group IV received a high-carbohydrate, low-fat (HCLF) diet. At the end of the experiment, aortic tissue samples were obtained and used for histological, immunohistochemical (Endothelin and PCNA, biochemical MDA, TCA, NO, 8-OH-dG, and Nrf2/ARE protein) and molecular (Endothelin, eNOS, Nrf-2 α, p62, LC3, BECN-1, PINK1, CHOP, BNIP3, PCNA) analysis.ResultsOxidative stress, autophagy markers, and ED markers are increased in the metabolic syndrome group. LCHF diet mitigates the adverse effects of DEX on endothelial dysfunction and oxidative stress, as evidenced by reduced BMI, HOMA-IR, and improved histological and molecular parameters.ConclusionOxidative stress, autophagy dysregulation, and ER stress play crucial roles in the pathogenesis of insulin resistance-induced endothelial dysfunction. An LCHF diet offers protective benefits against insulin resistance and related comorbidities, including endothelial dysfunction.

The study aims to identify the gifted students in basic interior design courses by utilizing new teaching strategies to support their capabilities and their intellectual growth within the interior design program. This research used a descriptive correlational study design to recruit the gifted students studying at Ajman University during the academic year 2018-2019, where the female students were 77% and 23%, male students -- percentages based on a total of 130 students - with no statistically significant difference for teaching strategies based on gender variable. The results also showed that 66% of these students joined the interior design program due to their passion, and 95% had learned how to determine the requirements of a successful interior design project effectively. The findings have shown a significant and positive difference for teaching strategies based on 3rd level students (F=11.895, p=0.007). The study concluded that the use of creative and critical thinking strategies needs the exclusion of conventional teaching methods, which include monocratic and memorizing techniques to aid, precisely the gifted students' GS, to reach the same motivational level as their counterparts.

IntroductionIn 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.MethodsAge, 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.ResultsAge but not gender was associated with the disease severity X2 (4, N = 110) = 27.2, p

This preliminary study investigates the emission characteristics of formaldehyde (HCHO) and total volatile organic compounds (TVOC) in indoor environments, comparing the effects of eco-friendly materials and general materials. The study analyzes the concentration changes over time in the living rooms of experimental units to assess the effectiveness of eco-friendly materials in reducing indoor air pollutants. The results show that eco-friendly materials exhibit lower initial emissions of TVOC than general materials, gradually decreasing over time. Compared to the eco-friendly material unit, the general material unit takes longer to reach acceptable TVOC concentrations. The emission pattern of HCHO differs from TVOC, with the highest peak occurring on the seventh day. Major individual VOCs, except for benzene, exhibit a similar decreasing trend for TVOC over time. Eco-friendly materials demonstrate significant reductions in emissions compared to general materials in various material applications, including parquet flooring, wallpaper, built-in furniture, and kitchen furniture. However, the difference in emissions for door and window frames using eco-friendly materials is minimal. These findings emphasize the effectiveness of eco-friendly materials in reducing indoor air pollutants and provide valuable insights for creating healthier living environments. Further research is needed to optimize the application of eco-friendly materials in specific components and investigate their long-term impact on indoor air quality and occupant health.

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.

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.

Background: Respiratory distress syndrome [RDS] is among the most common diseases in preterm infants. Numerous causes of RDS have been recently diagnosed and researchers have identified the presence of low serum carnitine in preterm infants with RDS.The aim of this study: to evaluate serum carnitine levels in preterm infants with RDS.Patients and methods: Eighty preterm infants were divided into two groups; group 1 consisted of 50 preterm with RDS in the first 6h of life constituted Group [A] as they were preterm infants with RDS with normal serum carnitine levels while Group [B] represented infants with carnitine deficiency. Control group 2 consisted of 30 preterm infants without RDS in the first 6 h of life. All cases and their mothers included in the study were subjected to a thorough history taking, thorough clinical examination and measurement of serum carnitine.Results: The cases groups had significantly lower serum L-carnitine than the controls group [25.56 ± 11.14 vs. 34.53 ± 2.54], and carnitine deficiency in RDS cases [32%]. Concerning weight, cases with carnitine deficiency had higher weight than cases with normal carnitine and control. With regard to clinical manifestations, there was a statistically significant difference between the cases subgroups in Down score indicting severe RDS in cases with carnitine deficiency. There was a statistically significant difference among cases subgroups regarding radiological findings. The cases with carnitine deficiency had worse X-ray, more need for surfactant therapy and MV than the cases with normal carnitine.Conclusion: Preterm neonates with RDS were demonstrated to be associated with a significant reduction in carnitine level compared to RDS- free preterm ones.

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.

Background: Bronchiolitis is the most common lower respiratory tract infection in children. The management guidelines recommend only supportive measures; however, there is an increasing burden for bronchiolitis especially in developing countries. The use of nebulized hypertonic saline may aid in decreasing hospital stay and decrease the global burden of the disease.Objective: To compare between the efficacy of hypertonic saline versus normal saline in reducing duration of hospital admission and improving symptoms of acute bronchiolitis.Patients and methods: A randomized comparative clinical trial included 90 children with acute bronchiolitis, conducted at Al-Azhar University Hospital (New Damietta) during the period from October 2019 till June 2020. Patients were randomly assigned into 2 groups; 45 patients received 3% hypertonic saline nebulization (group 1), and 45 patients received 0.9% normal saline nebulization (group 2). Efficacy of treatment was assessed through duration of hospitalization and oxygen supplementation, and severity of respiratory distress.Results: there was no significant difference between both groups as regard to age, sex, baseline clinical severity score and O2 saturation. After treatment, patients who received nebulized hypertonic saline showed less duration of hospitalization (62.3±20.8 hours vs 76.8± 26.1 hours; p=0.001), less duration of O2 therapy (16.2±6.0 hours vs 25.3±5.4 hours; p=0.01). As regard to severity clinical score, patients received nebulized hypertonic saline showed significant improvement started within 24 hours from admission (P=

Background: Febrile seizures are non-epileptic types of seizure that occur frequently during early childhood. Multiple factors are implicated in the pathogenesis of these types of seizures. Iron deficiency might play as an etiological or, at least, augmenting factor in the development of febrile seizures. Objective: To study iron status among children with simple febrile seizures, and to estimate the prevalence of iron deficiency between them. Patients and methods: A case-control study included 100 febrile children aged 6 months to 60 months, and were ascribed to 2 groups; 50 children with simple febrile seizures [case group], and 50 children who had febrile disease without occurrence of seizures [control group]. Venous samples were obtained for the analysis of complete blood count, and iron indices [serum ferritin, serum iron and total iron binding capacity]. Results: The peak temperature was significantly elevated among the case group [P=0.03]. Regarding iron profile, compared to controls, the case group had significantly lower iron [54.24±16.04 vs. 62.6±16.02; P=0.011], and lower ferritin [37.612±19.85 vs. 80.624±31.57; P

(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.

Abstract Background At King Abdulaziz University, medical and health science schools depend on admission exams (aptitude and achievement) and preparatory year scores in their students’ selection. However, with the growing number of applicants and the drastic changes in teaching and assessment in these colleges, continuous assessment and development of admission criteria are needed. In this study, we aimed to evaluate the correlation of admission exam scores, in addition to the preparatory year Grade Point Average (GPA), with academic performance in the basic science subjects such as Clinical Biochemistry and Clinical Pharmacology in health science colleges. Methods The study was conducted on four cohort studies, two faculty of nursing cohorts; nursing students (2017-2018, n=146) nursing students (2018-2019, n=81), and two faculty of applied medical sciences cohorts, clinical nutrition students (2017-2018, n=33), and clinical nutrition students (2018-2019, n=28). The students’ scores of General Aptitude Test (GAT), Scholastic Achievement Admission Test (SAAT), and preparatory year GPA were all recorded at the beginning of each semester before the beginning of courses. Clinical Biochemistry and Clinical Pharmacology exam results were recorded at the end of the semester. Correlation was done for each cohort and all cohorts pooled. Results Results showed only a weak correlation detected between SAAT and the overall achievement in Clinical Biochemistry (r= 0.192, P= 0.042) in nursing students (2017-2018), but no correlation was seen with SAAT or preparatory year scores. There was also no significant correlation between admission exams scores and the students’ academic achievement in Clinical Biochemistry or Clinical Pharmacology. On the other hand Clinical Pharmacology exam results showed a significant positive correlation with Clinical Biochemistry results (r=0.688, P=0.000). Conclusion Our results could indicate the need to revisit the admission criteria for these colleges. Furthermore, specific preparatory year tracks for health science colleges can ensure that students improve the specific skills and knowledge required for their future college years3

Idiopathic nephrotic syndrome (NS) is one of the most common primary glomerular diseases in children. In this study, we investigate the association of single-nucleotide polymorphisms of nephrin gene and glucocorticoid receptor gene (NR3C1) and susceptibility to develop NS and the response to steroid therapy in 100 Egyptian children with NS using polymerase chain reaction-restriction fragment length polymorphism. We also analyzed the correlation between the genotypes and clinicopathologic features of the patients. Thirty-four patients (34%) were initial steroid nonresponders, renal biopsy findings of those patients were available, of which 22 (64.7%) showed minimal change NS and 12 (35.3%) had focal segmental glomerulosclerosis. The distribution of the genotypes was comparable between the patient and control groups, allele frequencies showed no significant difference between the patient’s group and the control group. The genotypes showed no correlation with the age of onset of NS, initial steroid responsiveness, renal pathologic findings, estimated glomerular filtration rate (eGFR), and serum albumin. However, 24-h protein in urine showed a significant association with the NR3C1 gene. These data suggested that the nephrin gene and NR3C1 gene SNPs do not affect the development of NS, initial steroid responsiveness, renal pathological lesion, eGFR, and serum albumin. However, 24-h protein in urine showed a significant association with the NR3C1 gene in Egyptian children with NS.

Infectious cutaneous diseases are very common, especially in certain geographic and tropical regions. Sometimes they may simulate other dermatoses, ordering verification of diagnosis with particular investigations. Dermoscopy is among one of the most important tools readily available in the outpatient setting for the dermatologist to confirm the diagnosis. In this up-to date review, literature concerning the various dermoscopic features of parasitic, viral, dermatophytic and bacterial cutaneous infections is composed. In addition artefacts as well as practical issues in dermoscopy usage are discussed; with the aim to empower dermatologists to promptly and non-invasively diagnose and manage cutaneous infections and infestations.

Background: Transient tachypnea of the newborn [TTN] is a common physiologic lung disorder. Stimulation of β-adrenergic receptors could alleviate the condition. Aim of the work: The study was undertaken to assess the efficacy and safety of inhaled salbutamol in reduction of TTN, oxygen treatment and hospitalization. Patients and Methods:This clinical study included 150 [50 control group, 50 single dose of salbutamol and 50 double-doses of salbutamol] infants between 35th-39th week's gestation. Inhaled salbutamol was given and comparison between the three groups was carried out. Results: Treatable and control groups were comparable as regard neonatal and maternal characteristics. Heart rate was significantly increased in group B when compared to control group half and one hour after treatment. In addition, respiratory rate was significantly increase in group B when compared to group A at half hour after treatment and continued till 8 hours after treatment. The TTN score after treatment was significantly lower in group B when compared to group A at one hour after nebulized salbutamol and continued till 8 hours. Furthermore, time before initiation of feeding was significantly reduced in group B when compared to group A [26.72[±3.68] vs [39.66[±4.7] and also there was significant reduction of hospitalization days in group B when compared to group A [3.78 [±1.25] vs [7.36[±1.28]. Conclusion: Inhalational salbutamol reduced duration of supplemental oxygen therapy, the duration of hospitalization and time before initiation of feeding, and no adverse effects were reported. Thus, inhaled salbutamol seems to be effective and safe in TTN.

Background: The most common cause of hospital admission in the first month of life is the neonatal jaundice. Some factors [e.g., prenatal, neonatal factors, maternal factors, and environmental factors (such as zinc) influence the frequency of neonatal jaundice. In terms of neonates, it is proposed that there is a correlation between serum zinc quality and hyperbilirubinemia. Aim of the work: To evaluate the level of serum zinc in term neonates with indirect hyperbilirubinemia. Patients and Methods: A case control study carried out at the neonatal intensive care unit (NICU) and pediatric outpatient clinic of New Damietta, Al-Azhar University Hospital, from June 2018 to February 2019. It included 75 neonates with neonatal jaundice as cases group and 75 healthy neonates of matched age and sex as a control group. All were assessed clinically and serum zinc levels were determined and documented. Results: Level of serum zinc in neonates with non-hemolytic hyperbilirubinemia (103.3±36.56 ug/dl) was significantly lower than healthy neonates without jaundice (128.62 ± 40.83 ug/dl) and zinc deficiency in jaundiced neonates (25.3%) was statistically significant more than healthy neonates) 6.7%). There was no significant relation between the level of serum zinc and other factors like the maternal age, parity, pattern of feeding, gender and weight, but there was significant correlation with maternal zinc intake during pregnancy. Conclusion: We concluded that serum zinc level in term neonates with neonatal jaundice was statistically significant decreased than healthy term neonates.

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.

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.

Fibromyalgia (FM) is a common chronic pain syndrome that affects 1% to 5% of the population. We aimed to investigate the role of endothelial dysfunction and autophagy in fibromyalgia-related vascular and cerebral cortical changes in a reserpine-induced rat model of fibromyalgia at the histological and molecular levels and to study the ameliorative effect of fisetin. Forty adult female albino rats were divided into four groups (10 each): two control groups, the reserpine-induced fibromyalgia group, and the fisetin-treated group. The carotid arteries and brains of the animals were dissected. Frozen tissue samples were used for total RNA extraction and qPCR analysis of eNOS, caspase-3, Bcl-2, LC-3, BECN-1, CHOP, and TNF-α expression. Histological, immunohistochemical (eNOS), and ultrastructure studies were conducted. The carotid arteries revealed excessive autophagy and endothelial, vascular, and apoptotic changes. The cerebral cortex showed similar findings apart from endoplasmic reticulum stress. Additionally, there was decreased gene expression of eNOS and Bcl-2 and increased expression of caspase-3, LC-3, BECN-1, CHOP, and TNF-α. In the fisetin-treated rats, improvements in the histological and molecular results were detected. In conclusion, oxidative stress, enhanced apoptosis, and excessive autophagy are fundamental pathophysiologic mechanisms of reserpine-induced fibromyalgia. Moreover, fisetin has an ameliorative effect against fibromyalgia.

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.

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.

Abstract Background This is the first study to investigate spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentations in the spermatozoa of men diagnosed with metabolic syndrome (MS) who have normal seminograms with unexplained infertility, and to correlate these parameters with seminal glucose concentration. Methods This study included 120 participants: 75 male subjects with MS (38 fertile and 37 infertile), and a control group of 45 fertile males without MS. HOMA-IR, semen analysis, and biochemical measurement of seminal plasma insulin and glucose levels were carried out. Spermatozoal insulin gene and CIDEA gene expressions were performed by the RT-PCR method. The percentage of spermatozoal DNA fragmentation was also estimated. Results The spermatozoal insulin and CIDEA gene expression, as well as the DNA fragmentation, were significantly higher in the infertile MS group than in the fertile MS group, and significantly higher in both the MS groups than in the control group. Seminal glucose concentration showed significant positive correlations with seminal insulin level, spermatozoa insulin, CIDEA gene expression, and DNA fragmentation. Moreover, there was a positive correlation between spermatozoa CIDEA gene expression and DNA fragmentation. Conclusions It can be concluded that MS may affect male fertility at the molecular level, through its possible inducing effect of spermatozoa CIDEA and insulin gene expression, DNA fragmentation, and increased seminal glucose.

Background: Sodium valproate (VPA) is an antiepileptic drug (AED) licensed for epilepsy and used during pregnancy in various indications. Alpha-lipoic acid (ALA) is a natural compound inducing endogenous antioxidant production. Our study aimed to investigate the effect of prenatal administration of VPA on the pancreas of rat offspring and assess the potential protective role of ALA co-administration during pregnancy. Methods: Twenty-eight pregnant female albino rats were divided into four groups: group I (negative control), group II (positive control, ALA treated), group III (VPA-treated), and group IV (VPA-ALA-treated). The pancreases of the rat offspring were removed at the fourth week postpartum and prepared for histological, immune-histochemical, morphometric, molecular, and oxidative stress marker studies. Results: In group III, there were pyknotic nuclei, vacuolated cytoplasm with ballooning of acinar, α, and β cells of the pancreas. Ultrastructural degeneration of cytoplasmic organelles was detected. Additionally, there was a significant increase in oxidative stress, a decrease in insulin-positive cell percentage, and an increase in glucagon positive cells in comparison to control groups. Moreover, VPA increased the gene expression of an apoptotic marker, caspase-3, with a decrease in anti-apoptotic Bcl2 and nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional factor. Conversely, ALA improved oxidative stress and apoptosis in group VI, and a consequent improvement of the histological and ultrastructure picture was detected. Conclusion: ALA co-administration with VPA significantly improved the oxidative stress condition, histological and morphometric picture of the pancreas, and restored normal expression of related genes, including Nrf2, caspase-3, and Bcl-2. Administration of α-lipoic acid has a protective effect against VPA-induced pancreatic oxidative damage via its cytoprotective antioxidant effect.