Background: Toll-like receptors (TLRs) are an important family of receptors that constitute the first line of defense system against microbes. They can recognize both invading pathogens and endogenous danger molecules released from dying cells and damaged tissues and play a key role in linking innate and adaptive immunity. TLRs are widely distributed in both immune and other body cells. The expressions and locations of TLRs are regulated in response to specific molecules derived from pathogens or damaged host cells. The binding of ligands to TLR activates specific intracellular signaling cascades that initiate host defense reactions. Such binding is liganddependent and cell type-dependent and leads to production of pro-inflammatory cytokines and type 1 interferon. TLR-dependent signaling pathways are tightly increased during innate immune responses by a variety of negative regulators. Overactivation of TLRs can ultimately lead to disruption of immune homeostasis and thus increase the risk for inflammatory diseases and autoimmune disorders. Antagonists/inhibitors targeting the TLR signaling pathways have emerged as novel therapeutics to treat these diseases. Aim of work: The present review summarizes the structure, characterizations, and signaling of TLRs and their regulators, as well as describes the implication of TLRs in many diseases with a brief idea about the inhibitors that target TLR signaling pathways. Conclusion: We conclude that TLRs are the main elements of our immune system, and they should be maintained functioning to keep the integrity of innate immunity. Targeting of TLR signaling represents a new challenge for treatment of many diseases.

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BACKGROUND:The rapidly increasing prevalence of childhood obesity became a major burden on health worldwide, giving an alarm to clinicians and researchers. Adipocytes act as an active endocrine organ by releasing plenty of bioactive mediators (adipokines) that play a major role in regulating metabolic processes. Apelin is a recently identified adipokine that is expressed in adipocytes.AIM:The current work aimed to uncover the relation between serum apelin and childhood obesity and its related complications as hypertension and hyperglycemiaMETHOD:A group of 50 obese and 31 non-obese; sex- and age-matched children were enrolled in our study with a mean age of (9.5 ± 2.1) and (8.7 ± 1.3) respectively. Anthropometric measurements, blood pressure, were assessed in all studied participants, we also determined the lipid profile, serum insulin, fasting blood glucose (FBG) level, HOMA-IR and serum apelin.RESULTS:Obese children had higher levels of HbA1c, FBG, serum insulin, HOMA-IR, total cholesterol, triglycerides, low-density lipoprotein (LDL) and diastolic blood pressure (DBP Z-score); compared to controls (all P < 0.05). Apelin was significantly higher in obese children versus controls and correlated positively with BMI Z-Score (P = 0.008), DBP Z-Score (P = 0.02), cholesterol, TG (both P = 0.02), serum insulin (P = 0.003), FBG and HOMA-IR (both P = 0.001). Linear regression analysis showed that FBG was the most effective factor in predicting the level of serum apelin (P = 0.04).CONCLUSION:This work supports the hypothesis that apelin may have a crucial role in the pathogenesis of health hazards related to obesity in children including insulin resistance, hypertension and a higher risk of occurrence of metabolic syndrome.

Background: Toll-like receptors (TLRs) are type I integral transmembrane receptors involved in recognition and conveying of pathogens to the immune system. These receptors are located either on cell surfaces or within endosomes. They are activated by specific ligand leading to the release of cytokines via signal transduction pathway. The excess production of these cytokines leads to disrupt the immune homeostasis. There are several factors regulating TLR expression and consequently affecting their functions. Among these are inflammation, cytokines, some cellular process, air pollution, depression, stress, some drugs, genetic polymorphism, nutrition, and micronutrients. Some micronutrients (vitamins and trace elements) may be considered as important TLR regulators, as they have immunomodulatory functions. Vitamins D, B12, and A; zinc; copper; and iron have important role on innate immune responses. Aim of work: This review gives a brief idea on TLR family and attempts to cover the factors affecting the physiological functions of them. Conclusion: Of many factors affecting TLRs functions are micronutrients. There is a shortage of researches concerning the effect of micronutrients deficiency on the function of TLRs, all of which focused on vitamin D but other vitamins have not got the same importance that they deserve. This orients our efforts to work at this point in the future.

INTRODUCTION:Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children that may be complicated by micro or macrovascular complications. Measurement of the carotid intima-media thickness (CIMT) allows the early detection of atherosclerotic alterations of blood vessels that may complicate T1DM.SUBJECTS AND METHODS:This study is a case-control study. Participants were classified into two groups. The first group included 40 children with T1DM and the second group included 30 matched healthy controls. The studied cases were recruited from Endocrinology and Diabetology Unit, Pediatric Hospital, Ain Shams University. Serum apelin, cholesterol, TG, LDL were measured for every case. Also, albumin level was analyzed in urine. Measurement of the carotid intima-media thickness (CIMT) was done for all cases.RESULTS:Comparison between T1DM patients and controls revealed that serum apelin, cholesterol, TG, LDL and albuminuria were significantly increased in cases compared to controls. Significant positive correlations were detected between HbA1C, albuminuria and lipid profile with apelin in the diabetic group (p < 0.05). CIMT has significant positive correlation with serum apelin levels (r = 0.36, p = 0.05). Also, this study found positive correlations between CIMT and some variables as LDL, SBP z-score and duration of the illness.CONCLUSION:Increased levels of serum apelin in T1DM patients may be considered as predicting factor for the ongoing development of vascular sequels. This study highlighted the possible validity of apelin assay as an early predictor of atherosclerosis in T1DM children. Evaluating CIMT in these patients is of at most important for early detection of subclinical atherosclerosis.

Background: Adipose tissue is a type of connective tissue composed of adipocytes. Recently, this tissue has been recognized as a major endocrine organ. The physiological process of fat loss occurs when fats are liberated from adipocytes into circulation to supply the needed energy. Nutrition supplements that increase fat metabolism, impair fat absorption, increase weight loss, and increase fat oxidation during exercise are known as fat burners. A good fat burner must burn the stored fats, break down the fat cells, and increase the metabolic rate. Eating thermogenic foods helps burn fats. Fat flush diet comes to repair the damage that resulted from ingested and environmental toxins stored in adipocytes. Aim of work:This review will focus on the recent advances in fat burning supplements, fat burning foods, and fat flash diet. Conclusion:The human body can act as a fat-burning machine by depending on low-calorie foods instead of high-calorie foods in addition to doing regular exercise, avoiding toxins and processed food, and applying any fat flush dietary program under the approval of a professional doctor. What's new in this review is that it may orient our attention to the importance of using natural fat burners in the fat burning process in an attempt to avoid medications that have many side effects by targeting other organs and it also gives an idea of the importance of increasing the brown adipose tissue content because its activation could be linked to a feeling of being full. We need further studies in this context.

BACKGROUND: Chronic malnutrition is a long-term health condition that has threatening effects on children’s health. Environmental enteric dysfunction (EED) is a subclinical disorder affecting the small intestine that may occur due to exposure to environmental pathogens and toxins. AIM: The present research was intended to detect the value of fecal biomarkers of intestinal epithelial damage alpha-1anti-trypsin (AAT) and intestinal inflammation Myeloperoxidase (MPO) and Neopetrin (NEO), also to quantify their association with faltering growth in stunted and underweight children. PATIENTS AND METHODS: This case–control study included 105 children with moderate malnutrition as a case group and 100 children of normal body weight and height as a control group. Quantification of fecal markers levels of intestinal permeability AAT and intestinal inflammation (NEO and MPO) along with serum micronutrients levels (iron and zinc) in children with malnutrition in comparison to controls. RESULTS: Fecal markers of intestinal permeability AAT and intestinal inflammation NEO had statistically significant higher levels in children with malnutrition, while serum micronutrients (iron and zinc) had statistically significant lower levels in children with malnutrition. CONCLUSION: Faltering growth is associated with elevated fecal markers of intestinal permeability AAT and intestinal inflammation NEO. EED may be a cause for faltering growth.

AIM:There are no reports regarding the influence of vitamin D on thymosin ß4 and the cluster of differentiation CD4 levels which are important for maintaining a healthy immune system. Consequently, we aimed to explore this relationship through a study.MATERIAL AND METHODS:The study was carried out on 35 subjects, screened for 25-hydroxy vitamin D[25 (OH) D] using ELISA method and they were divided into two groups: Group 1 consists of 10 healthy subjects with sufficient vit. D level > 24.8 ng/ml. Group 2 consists of 25 subjects suffering, severely, from vitamin D deficiency at level < 11.325 ng/ml. Also, Thymosin ß4, CD4 and zinc levels were performed.RESULTS:There were significant differences between the two groups in the concentration levels of thymosin β4, as the group 1 has shown higher levels (P = 0.005). Whereas, CD4 and zinc levels didn’t show any significant difference between the two groups. At the same time, a significant positive correlation has been observed between vitamin D, thymosin β4, and CD4 at (r = 0.719; P = 0.001), and (r = 0.559, P = 0.001) respectively.CONCLUSION:We concluded that vitamin D may be an essential factor that influence or determine the level of thymosin β4. This study is the first that focused on demonstrating that sufficient level of vitamin D may have the ability to influence the thymic hormone thymosin β4 levels. Further studies on large scale of subjects are needed to explore the positive correlation we had found between vitamin D and thymosin β4 and CD4.