Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 19, Issue 7, 2019

Background: Osteoporosis, characterized by compromised bone quality and strength is associated with bone fragility and fracture risk. Biomarkers are crucial for the diagnosis or prognosis of a disease as well as elucidating the mechanism of drug action and improve decision making. Objective: An exhaustive description of traditional markers including bone mineral density, vitamin D, alkaline phosphatase, along with potential markers such as microarchitectural determination, trabecular bone score, osteocalcin, etc. is provided in the current piece of work. This review provides insight into novel pathways such as the Wnt signaling pathway, neuro-osseous control, adipogenic hormonal imbalance, gut-bone axis, genetic markers and the role of inflammation that has been recently implicated in osteoporosis. Methods: We extensively reviewed articles from the following databases: PubMed, Medline and Science direct. The primary search was conducted using a combination of the following keywords: osteoporosis, bone, biomarkers, bone turnover markers, diagnosis, density, architecture, genetics, inflammation. Conclusion: Early diagnosis and intervention delay the development of disease and improve treatment outcome. Therefore, probing for novel biomarkers that are able to recognize people at high risk for developing osteoporosis is an effective way to improve the quality of life of patients and to understand the pathomechanism of the disease in a better way.

Background: Arginine is considered a semi-essential amino acid in healthy adults and the elderly. This amino acid seems to improve the immune system, stimulate cell growth and differentiation, and increase endothelial permeability, among other effects. For those reasons, it has been theorized that arginine supplementation may be used as an adjuvant to conventional cancer therapy treatments. Objective: This review aims to evaluate the existing knowledge of the scientific community on arginine supplementation in order to improve the efficacy of current cancer treatment. Results: Despite the continued efforts of science to improve treatment strategies, cancer remains one of the greatest causes of death on the planet in adults and elderly people. Chemo and radiotherapy are still the most effective treatments but at the cost of significant side effects. Conclusion: Thus, new therapeutic perspectives have been studied in recent years, to be used in addition to traditional treatments or not, seeking to treat or even cure the various types of cancer with fewer side effects.

Background: Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has gained a lot of attention because of its involvement in respiratory diseases. Interleukin-17 cytokine family includes six members, out of which, IL-17A participates towards the immune responses in allergy and inflammation. It also modulates the progression of respiratory disorders. Objective: The present review is an insight into the involvement and contributions of the proinflammatory cytokine IL-17A in chronic respiratory diseases like Idiopathic Pulmonary Fibrosis (IPF), Chronic Obstructive Pulmonary Distress (COPD), asthma, pneumonia, obliterative bronchiolitis, lung cancer and many others. Conclusion: IL-17A is a major regulator of inflammatory responses. In all the mentioned diseases, IL- 17A plays a prime role in inducing the diseases, whereas the lack of this pro-inflammatory cytokine reduces the severity of respective respiratory diseases. Thereby, this review suggests IL-17A as an instrumental target in chronic respiratory diseases.

Background: The rising incidence of Clostridium difficile infection (CDI) in the general population has been recognized by health care organizations worldwide. The emergence of hypervirulent strains has made CDI more challenging to understand and treat. Inflammatory bowel disease (IBD) patients are at higher risk of infection, including CDI. Objective: A diagnostic approach for recurrent CDI has yet to be validated, particularly for IBD patients. Enzyme immunoassay (EIA) for toxins A and B, as well as glutamate dehydrogenase EIA, are both rapid testing options for the identification of CDI. Without a high index of suspicion, it is challenging to initially differentiate CDI from an IBD flare based on clinical evaluation alone. Methods: Here, we provide an up-to-date review on CDI in IBD patients. When caring for an IBD patient with suspected CDI, it is appropriate to empirically treat the presumed infection while awaiting further test results. Results: Treatment with vancomycin or fidaxomicin, but not oral metronidazole, has been advocated by an expert review from the clinical practice update committee of the American Gastroenterology Association. Recurrent CDI is more common in IBD patients compared to non-IBD patients (32% versus 24%), thus more aggressive treatment is recommended for IBD patients along with early consideration of fecal microbiota transplant. Conclusion: Although the use of infliximab during CDI has been debated, clinical experience exists supporting its use in an IBD flare, even with active CDI when needed.

Objective: For surgeons, locating parathyroid in thyroidectomy and parathyroidectomy is critical since parathyroid plays an important role in calcium balance. The fluorescence of parathyroid has already been found by researchers and the angiography equipment detecting the fluorescence of parathyroid with indocyanine green has been widely applied. Using the indocyanine green angiography and looking at the actual fluorescence of in vivo and in vitro tissues, it was possible to identify thyroid, parathyroid, lymph nodes and fat tissues during the surgical procedure. This mini-review aims to present the application of indocyanine green angiography in parathyroid detection and discusses the safety of this method. Methods: The relevant data were searched by using the keywords “Indocyanine green,” “Parathyroid,” and “Identification” and “Protection” in “Pubmed,” “Web of Science” and “China Knowledge Resource Integrated databases”, and a manual search was done to acquire peer-reviewed articles and reports about indocyanine green. Results: Indocyanine green dye along with the intraoperative fluorescence imaging system is safe in detecting parathyroid and predicting postoperative hypoparathyroidism. Conclusion: The conclusion suggests that indocyanine green angiography is a safe, effective and easy way to detect parathyroid glands. The conclusion will be of interest to surgeons regarding thyroidectomy and parathyroidectomy.

Background and Objective: APDS [Activated phosphoinositide 3-kinase (PI3K) δ Syndrome] is a newly found special form of primary immunodeficiency caused by mutations in genes encoding PI3Kδ subunits and over-activation of the PI3K signaling pathway. Gain-of-function and loss-of-function mutations in PIK3CD (encoding P110δ) and PIK3R1 (encoding p85α, p55α and p50α) lead to APDS1 and APDS2, respectively. The subsequent irregular PI3K downstream signaling cascade is associated with abnormalities in B cells and T cells and the consequent heterogeneous clinical manifestations including respiratory tract infections, autoimmunity, lymphoproliferation and not to mention primary antibody deficiency. In this study, we report a 12-year-old girl with a mutation in the PIK3R1 gene who manifested immunological phenotypes resembling hyper IgM syndrome along with a review of the literature of the previously reported patients. Methods: Whole exome sequencing was performed to detect the underlying genetic mutation in this patient. Results: A de novo heterozygous splice site mutation in the hot spot of the PIK3R1 gene within the intron 10 was found (c.1425+1G>A). Conclusion: Further investigations are required for evaluation of the underlying genetic defects and the possible associations between genetic underpinning and heterogeneous severity and features of the disease.

Background and Aims: Sexual functions are sometimes adversely affected by the therapeutic drugs delivered for treating IBD. Much attention has been focused on pregnancy/sexual issues in women. Relatively less attention has been poured in to address this issue in men. This systematic review assesses the drugs having potential detrimental effects on fertility in men. Methods: Three databases were searched by two researchers independently for potentially relevant publications between 1964 to 2015 and 249 papers were retrieved. Studies that dealt with sexual problems after IBD drugs administration were included in the purview of this review. Results: Fourteen studies with 327 human patients and 110 animals were analysed. Sulphasalazine treated patients had lower spermatozoa count, lower sperm motility and higher risk of oligospermia compared to mesalazine treated ones. Biologics seem to be safe to use while attempting to conceive however, proper clinical studies reporting male fertility problems in IBD patients are lacking. Azathioprine caused oligospermia but a meta-analytical approach was not possible due to heterogeneity in studies. Some animal studies showed methotrexate affects abnormal testis structure and spermatogenesis. Conclusion: This study summarises the current literature and safety issues affecting fertility parameters in men and animals treated with IBD therapeutic drugs, which can further assist clinicians in better management of adult male IBD patients.

Background: Natural killer cells (NKC) are a major component of the innate immune response to HCV, mediating their effects through TRAIL and IFN-γ. However, their function is diminished in chronic HCV patients (HCVp). Prolactin is an immunomodulatory hormone capable of activating NKC. Objective: The study aims to explore if hyperprolactinemia can activate NKC in HCVp. Methods: We treated twelve chronic HCVp (confidence level =95%, power =80%) for 15 days with Levosulpiride plus Cimetidine to induce mild hyperprolactinemia. Before and after treatment, we determined TRAIL and NKG2D expression on peripheral blood NKC, along with cytokine profiles, viral loads and liver function. We also evaluated in vitro effects of prolactin and/or IL-2 on NKC TRAIL or NKG2D expression and IFN-γ levels on cultured blood mononuclear cells from 8 HCVp and 7 healthy controls. Results: The treatment induced mild hyperprolactinemia and increased TRAIL expression on NKC as well as the secretion of IL-1ra, IL-2, PDGF and IFN-γ. Viral loads decreased in six HCVp. IL-2 and TRAIL together explained the viral load decrease. In vitro, prolactin plus IL-2 synergized to increase TRAIL and NKG2D expression on NKC from HCVp but not in controls. Conclusion: Levosulpiride/Cimetidine treatment induced mild hyperprolactinaemia that was associated with NKC activation and Th1-type cytokine profile. Also, an increase in TRAIL and IL-2 was associated with viral load decrease. This treatment could potentially be used to reactivate NKC in HCVp.

Objective: We aimed to investigate the etiology and prevalence of anemia in patients with diabetic foot ulcers and the relationship between both microvascular complications and related conditions and anemia. Methods: We retrospectively collected and evaluated the data of 225 patients with diabetic foot ulcer followed at our clinic. The demographic characteristics of the patients were analyzed. Complete blood count for those with anemia, serum iron, iron-binding capacity, ferritin, transferrin saturation index, vitamin B12, folic acid and thin blood film were performed. The diabetic microvascular complications and related conditions such as osteomyelitis, peripheral artery disease, and amputations were also determined. IBM SPSS Statistics Version 20.0 package software was used for the statistical analysis of the data. Results: Of 225 patients were 67 (29%) female and 158 (70.2%) male. The mean age of the patients was 62 ± 10.5 years (30-87). Duration of diabetes was 16.2 ± 6.7 years (2-31). Of the 225 patients, 41 had hypertension, 14 had chronic kidney failure, and 34 had coronary artery disease. Anemia was found in 192 (85.3%) of the 225 patients. Of 192, 126 (56%) had iron deficiency anemia, 50 had folate- deficiency anemia, and the remaining 16 had anemia of chronic disease. Iron deficiency anemia was significantly found to be higher in women. There was no significant difference between patients with and without anemia in terms of diabetic microvascular complications (neuropathy, retinopathy, nephropathy) and the related conditions. Conclusion: We have found that the most common cause of anemia was iron deficiency anemia. However, in our study, the prevalences of microvascular complications did not vary between patients with and without anemia. On the other hand, since all of our patients are having DFU and the high rates of microvascular complications and correlation with the presence of anemia could not be clearly portrayed.

Objective: The effect of dietary incorporation of ethanolic extracts of single and combinatorial formulations of Acanthus montanus (ACMO), Asystaciagangetica (ASGA), Gongronemalatifolium (GOLA) and Solanummelongena (SOME) on glucose tolerance was studied in normoglycaemicWistar rats. Methods: A total of 128 Wistar rats were used for the research work. The rats were divided into 32 groups of 4 rats each. One group was the normal control group and 15 groups were orally administered 200mg/kg body weight extract(s) for the single and combinatorial formulations. Another group (negative control) was given oral glucose load (4g/100ml) of 200mg/kg body weight alone and the remaining 15 groups were given oral glucose load (4g/100ml) of 200mg/kg body weight before giving the test extract(s) of 200mg/kg body weight. Results: Post-prandial serum glucose response at 30 minutes interval was plotted and the area under the curve (AUC) used to determine glycaemic index (GI) of each herbs. The herbs (ACMO, ASGA, GOLA and SOME) resulted in a marked improvement in oral glucose tolerance in rats after 10 days of treatment at an interval of 2 days. Blood glucose concentration (mmol/l) of rats administered with the combinations; ACMO+GOLA, ACMO+SOME, SOME+GOLA, ACMO+SOME+GOLA+GLU, ACMO+ASGA+GOLA, ACMO+SOME+GOLA and ACMO+ASGA+GOLA+SOME was found to belowered, with ACMO+ASGA+GOLA combination having the best result. This might be a result of hypoglycaemic synergy promoted by the various bioactive principles present in the combined extracts thereby lowering the GI. These findings revealed that the listed combinations have hypoglycaemic potentials and habitual consumption could positively modulate oral glucose tolerance. Conclusion: The herbs could be useful in the dietary management of diabetes as they could help regulate blood glucose level when consumed with normal meals and could also be incorporated into meals to prevent or delay the onset of diabetes or reverse the same in its early stages.

Background : Direct Antiretroviral Agents (DAAs), sofosbuvir-based therapies, have opened a new era in the treatment of chronic HCV infection. The aim of the study was to investigate the potential use of baseline and in serial serum, AFP levels as a predictor for response to DAAs in patients with Chronic Hepatitis C. Methods: This multicenter observational study was carried out on 1716 chronic hepatitis C virusinfected patients who received direct anti-viral drugs for 12 weeks. The primary end point was sustained virological response at 12 weeks after the end of treatment determined by quantitative PCR for HCV RNA. Serum AFP was quantitatively assessed at baseline then after 12week after stoppage of treatment (SVR12). Results: SVR12 rate was 97.8%. Elevated serum AFP was significantly higher in non -SVR group p value (<0.001). There was a significantly marked decrease in AFP after treatment in comparison to pretreatment values. The multivariate logistic regression analysis on the resulting significant variable from the univariate analysis revealed that only AFP was significantly related to the response to direct antiviral therapy in patients with chronic hepatitis C with p <0.001, OR 1.10 (95% CI 1.07:1.12). Other sociodemographic (e.g. Age, gender, BMI, ..) or laboratory factors (Hb, ANC, WBCs, …) did not show any significant association with the patients’ response to treatment. Conclusions: Serum AFP levels were a predictor for response in patients with chronic HCV with the administration of direct antiviral drugs.

Objective: Hashimoto’s Thyroiditis (HT) is an autoimmune disease, characterized by chronic inflammation of the thyroid gland with unknown etiologies. Recently, interleukin-33/ST2 (IL- 33/ST2) pathway reveals its participation in the process of several autoimmune diseases. In this study, the role of IL-33/ST2 pathway in the development of HT is investigated. Methods: The levels of plasma IL-33, sST2 and the frequency of circulating CD4+ST2L+T cells in 30 HT patients and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry respectively. The mRNA expressions of related molecules in IL-33/ST2 pathway in thyroid tissues (12 HT patients and 10 controls) were detected by real-time quantitative PCR (RTqPCR). The protein expressions of IL-33 and ST2 were determined by Western blot and immunohistochemistry staining. Results: The mRNA expressions of plasma IL-33 and sST2 were elevated in HT patients, with an increased ratio of IL-33/sST2. The number of CD4+ST2L+ T cells in PBMCs of HT group was significantly increased when compared to the control group (CON) by Flow cytometry assay. MRNA Expression of IL-33 and ST2 in thyroid tissue and the level of IL-1β and IL-18 were significantly upregulated in HT patients, while IL-5 was down-regulated in HT patients, compared to CON. The expression of IL-1β and IL-18 were positively correlated with the expression of IL-33. Results of western blot and immunohistochemical staining were consistent with qPCR. Conclusion: IL-33/ST2 pathway participates in HT via affecting the production of inflammatory cytokines.

Background: Many neurological disorders lead to institutionalization and can be accompanied in their advanced stages by functional impairment, and progressive loss of mobility, and cognitive alterations. Objective: We analyzed the relationship between functional impairment and cognitive performance and its related subdomains in individuals with Parkinson’s disease, Alzheimer’s disease accompanied by motor dysfunction, and with other neurological disorders characterized by both motor and cognitive problems. Methods: All participants lived in nursing homes (Valencia, Spain) and underwent cognitive evaluation with the Mini-Mental State Examination; functional assessment of independence in activities of daily living using the Barthel score and Katz index; and assessment of mobility with the elderly mobility scale. Results: The mean age of the subjects was 82.8 ± 0.6 years, 47% of the sample included individuals with Parkinson’s disease, and 48 % of the sample presented severe cognitive impairment. Direct significant relationships were found between the level of cognitive impairment and functional capacity (p < 0.01) and mobility (p < 0.05). Among the different domains, memory impairment was not associated with altered activities of daily living or mobility. The functional impairment and the risk of severe cognitive impairment were significantly (p<0.05) higher in female compared to male patients. Among comorbidities, overweight/obesity and diabetes were significantly (p < 0.05) associated with poor cognitive performance in those individuals with mild/moderate cognitive impairment. Conclusion: In institutionalized individuals with movement disorders there is an association between functional and cognitive impairment. Reduction of over-weight and proper control of diabetes may represent novel targets for improving cognitive function at such early stages.

Background: Research studies that holistically investigated the effect of administration of Virgin Coconut Oil (VCO) on diabetic humans or animals are limited in literature. Objective: To investigate the effect of administration of VCO on lipid profile, markers of hepatic and renal dysfunction, and hepatic and renal antioxidant activities of alloxan induced diabetic rats. Methods: Twenty-four male albino rats were used, and they were divided into four groups of six rats each. Group 1 (Normal Control, NC) received distilled water (1 mL/kg); Group 2 (VCO Control) received VCO (5 mL/kg); Group 3 (Diabetic Control, DC) received distilled water (1 mL/kg); Group 4 (Test Group, TG) received 5 ml/kg of VCO. Results: There were no significant differences in blood glucose, body weights, relative liver weights, relative kidney weights, hepatic and renal Superoxide Dismutase (SOD) activities, Malondialdehyde (MDA), albumin, aspartate Amino Transaminase (AST), alanine Amino Transaminase (ALT), Alkaline Phosphatase (ALP), urea, creatinine, uric acid, total cholesterol, triacylglycerol, Very Low Density Lipoprotein cholesterol (VLDL) and Low Density Lipoprotein cholesterol (LDL) concentrations; significant increases in renal Glutathione (GSH), hepatic catalase, Glutathione Peroxidase (GPx) and GSH but significant reduction in renal GPx and catalase activities of VCO control group compared with NC group. There were significant increases in blood glucose, relative liver and kidney weights, hepatic GPx, hepatic and renal MDA concentration, ALP, AST, ALT, urea, creatinine, uric acid, triacylglycerol, total cholesterol, LDL and VLDL concentrations; and significant decreases in body weight, hepatic SOD and GSH activities and albumin concentration but no significant difference in hepatic catalase activity of DC group compared with NC group. Administration of VCO to diabetic rats positively modulated these parameters compared with the diabetic control. Conclusion: The study showed the potentials of VCO in the management of hyperlipidemia, renal and hepatic dysfunctions imposed by hyperglycemia and by oxidative stress in diabetic rats.

Objective: Laser Ablation (LA) is a therapeutic modality for reducing the volume of large benign thyroid nodules. This retrospective study was aimed at assessing the outcome of LA in patients with benign nonfunctioning thyroid nodules in a 5-years follow-up. Methods: Sixty-two patients (47 females; mean age 54.7±12 yr) with benign cold thyroid nodules underwent LA from July 2009 to March 2012. Nodule volume, thyroid function test, and ultrasound were monitored at baseline, and at 3, 6 and 12 months after the procedure, then annually. After dividing nodules in solid and spongiform, we evaluated unfavourable outcomes: 1) nodule’s volume reduction <50%; 2) need for surgery; 3) need for additive LA session (due to nodule re-growth with persistence of cosmetic concern or compressive symptoms). Results: Baseline volume did not differ between solid and spongiform nodules as well as energy delivered and the number of needles used. Unfavourable outcomes occurred in 24 patients (38.7%). Nineteen/ 24 (79.2%) patients who experienced unfavourable outcomes belonged to the solid nodules group (P<0.01). When considering only those who benefited from LA, the 5-years reduction was 59.7% for solid and 78.6% for spongiform nodules (P<0.05). One/6 patients who underwent surgery (solid nodules group) had a final diagnosis of Follicular Variant of Papillary Thyroid Cancer (FVPTC). Conclusion: Large solid nodules, unlike spongiform, submitted to LA are characterized by a long-term unfavourable outcome and entail a potential risk of false negative cytologic results.

Background: Obese patients are more sensitive to myocardial ischemia, which has been linked with high mortality rates. The following study investigates the effects of impaired macrophage Migration Inhibitory Factor (MIF)/AMP-Activated Protein Kinase (AMPK) activation on increased susceptibility to myocardial ischemia/reperfusion (I/R) in high-fat diet-induced obesity. Methods: Male C57BL/6J mice were fed with a normal diet (10% kcal as fat, lean group) or a high-fat diet (60kcal as fat, obese group) for 12 consecutive weeks. To detect the MIF expression and AMPK activation in response to I/R in isolated hearts from lean and obese mice, myocardial samples were collected from left ventricular areas at different time points. To determine whether MIF supplementation is protective against I/R injury, recombined MIF (10 ng/mL) was applied before ischemia. Myocardial infarct size was estimated by triphenyltetrazolium staining. Western blot was used to detect myocardial MIF expression, AMPK activation and membrane glucose transporter 4 (Glut4) expression. Results: The expression of MIF was remarkably higher in obese group compared to lean group. Ischemia increased myocardial MIF expression and phosphorylation of AMPK in lean mice, whereas it had no significant effect on obese mice. Furthermore, administration of recombinant MIF increased ischemic AMPK activation and membrane Glut4 expression in both lean and obese mice, while it reduced the infarct size in lean mice only. Conclusion: An impaired MIF/AMPK activation response and consequent reduced membrane Glut4 expression may play an important role in increasing myocardial susceptibility to I/R in obesity.

Background: Although the pathogenetic mechanism of Diabetic Kidney Disease (DKD) has not been elucidated, an inflammatory mechanism may be a potential contributor. Monocyte chemotactic protein-1 (MCP-1) is suggested to be implicated in the development of DKD by playing a role in the infiltration of monocyte/macrophage. The aim of this study was to investigate the expression of MCP-1 under high glucose conditions, as well as the effects of microRNA-192 (miR-192) under these conditions, and to study the regulatory mechanism of MCP-1 in DKD. Methods: Rat glomerular mesangial cells were cultured in high glucose or isotonic mannitol. The messenger RNA(mRNA) expression of miR-192, miR-200b, miR-200c, E-box-binding homeobox 1 (Zeb1), and MCP-1 was then detected by real-time PCR, and the protein expression of Zeb1 and MCP- 1 was assessed by western blotting. The rat mesangial cells were transfected with an miR-192 inhibitor, NC inhibitor , and transfected with siRNA Zeb1, siNC. The cells were then cultured in high glucose to detect the mRNA expression of miR-192, miR-200b, miR-200c, Zeb1, and MCP-1 using realtime PCR, and Zeb1 and MCP-1 protein expression were determined by western blotting. Results: MiR-192, miR-200b, miR-200c, and MCP-1 were overexpressed, whereas Zeb1 was downregulated when cultured in high glucose (P < 0.05). After transfection with an miR-192 inhibitor, the expression of miR-192, miR-200b, miR-200c, and MCP-1 was downregulated, whereas Zeb1 was increased, and these differences were statistically significant (P < 0.05). The observed changes in the expression in the NC inhibitor transfection group were similar to that of non-transfected cell lines. Silencing the expression of Zeb1 resulted in a significant increase in the expression of miR-192, miR- 200b, miR-200c, and MCP-1 (P < 0.05). The observed changes in the SiNC transfection group were similar to those of non-transfected cell lines. Conclusions: MiR-192 expression was upregulated to increase the expression of inflammatory factor MCP-1 by inhibiting the expression of Zeb1, which was mediated by breaking the regulatory loop of Zeb1 and miR-200b/c in rat mesangial cells cultured in high glucose.

Background: Ovulatory PCOS (OPCOS) is the mildest form of the polycystic ovarian syndrome among all four determined phenotypes. Though the females with OPCOS are ovulating, hyperandrogenism and polycystic ovarian morphology increase the susceptibility of cardiovascular diseases, insulin resistance, hyperlipidemia and metabolic syndrome in these females. Objectives: The aim of the study was to identify the significance associated with OPCOS phenotype through serum proteomic profiling of OPCOS females and normal age-matched healthy ovulating females. Methods: One and two-dimensional gel-based proteomic approaches were adopted to fractionate the complex serum proteome. Differential protein profiles generated were analyzed with PD-QUEST Software. Protein spots differing in intensity by >2-fold were selected and identified further by MALDI-TOF MS. Validation of identified protein was carried out by Biolayer Interferometry. Results: One and two-dimensional gel profiles revealed a differential expression pattern of proteins. 10 selected spots were identified as GMP synthase [glutamine hydrolyzing], zinc finger protein 518A, pericentriolar material 1 protein, BCLAF1 and THRAP3 family member 3, MAP/microtubule affinityregulating kinase 4, H/ACA ribonucleoprotein complex subunit 1, Melanoma-associated antigen B3 and Zinc finger protein 658B. Expression of MAP/microtubule affinity-regulating kinase 4 (MARK4) was found to be downregulated in OPCOS females as compared to controls on validation. Conclusion: Reduced expression of MARK4 protein in OPCOS increases the associated risk of hyperlipidemia, hyperandrogenism and metabolic syndrome, thus the protein holds strong candidature as a drug target for the syndrome.

Objective: The aim of this randomized controlled trial was to investigate the effects of a polyherbal compound consisting of Aloe vera, black seed, fenugreek, garlic, milk thistle, and psyllium on diabetic patients with uncontrolled dyslipidemia. Methods: Fifty patients with type 2 diabetes who had dyslipidemia in spite of statin therapy were randomly allocated to two groups: control group (n = 25) receiving a conventional therapy with hypolipidemic and hypoglycemic drugs and intervention group (n = 25) receiving both the conventional therapy and the herbal compound (one sachet twice daily) for 12 weeks. Each sachet contained 300 mg of Aloe vera leaf gel, 1.8 g of black seed, 300 mg of garlic, 2.5 g of fenugreek seed, 1 g of psyllium seed, and 500 mg of milk thistle seed. Results: The levels of serum triglyceride, total cholesterol, low-density lipoprotein, and HbA1c showed a significant in-group improvement in the intervention group. However, the effects of the herbal compound on fasting blood glucose remained insignificant. The compound had no unwanted effect on the kidney function parameters (urea, creatinine) and serum liver enzymes (alanine aminotransferase and aspartate transaminase). Conclusion: The tested herbal compound, as an add-on to statin therapy, was effective in lowering the serum lipids in diabetic patients with uncontrolled dyslipidemia.

Background: The relationship between atopic dermatitis and allergic contact dermatitis is frequently debated, particularly in children. The impaired skin barrier of atopic subjects can facilitate the penetration of exogenous agents and its mutations in the filaggrin gene might be implicated in an increased risk to develop contact dermatitis. Moreover, atopic children are protractedly exposed to chemical substances contained in skin care products from an early age. Patients And Methods: The aim of this retrospective study is to determine if atopic children are more prone to allergic contact dermatitis and which substances are more frequently related to this disease. From 2014 to 2016, a total of 268 children under 14 years with a history of eczematous dermatitis, of whom 141 (52.6%) were affected, and 127 (47.4%) were not affected by AD, underwent patch testing with the baseline S.I.D.A.P.A standard series. Results: Based on the results of our study, the prevalence of contact allergy in atopic children is comparable to that noted in non-atopic children. The most frequent causes of contact allergy in children are fragrances, and their prevalence is significantly higher in atopic children (19.9%) than in non-atopic ones, (11.8%; p < .05). Conclusion: Our study highlights the importance of patch testing in atopic children for continuously monitoring the trends and changes of contact allergies that are a common disease and is even significantly increasing for some allergens, as fragrances. We may speculate that the protracted use of skincare products, associated with the impaired skin barrier of atopic children, enhances the risk of sensitization to the ingredients of these products.