BDNF Genetic Variant and Its Genotypic Fluctuation in Major Depressive Disorder

Major depressive disorder (MDD) still has an unknown etiology and mechanisms. Many studies have been conducted seeking to associate and understand the connection of different genetic variants to this disease. Researchers have extensively studied the brain-derived neurotrophic factor (BDNF) Val66Met genetic variant in MDD; yet, their findings remain inconsistent. This systematic review sought to verify the GG (Val/Val) genotype frequency fluctuation in different populations with MDD. For this, we searched in different databases and, after applying the eligibility criteria, selected 17 articles. Most studies demonstrate the higher frequency of the ancestral (wild) GG (Val/Val) genotype, although associations of the polymorphic A (Met) allele, changes in BDNF protein serum levels, or both were also found in MDD, whether related to the disease’s development or other factors. Nevertheless, despite these findings, disagreements between several studies are seen. For this reason, further BDNF Val66Met genetic variant studies should not only bridge the gap in the knowledge of this polymorphism’s role in MDD’s different facets but also analyze the genotypic and phenotypic heterogeneity in different populations to help provide a better quality of life for patients.

Evaluation of High-Sensitive C Reactive Protein Serum Level in Patients with Chronic Plaque Psoriasis before and After Treatment with Narrow Band Ultraviolet B Therapy or Methotrexate Comparative Study

Background Psoriasis is a chronic, recurring inflammatory disease affecting the skin, joints and nails that has a significant negative impact on the quality of life.Highly sensitive c reactive protein ( hsCRP) could be useful as biomarker for assessing the psoriasis severity(1). Objectives Assess the changes in high-sensitive C-reactive protein serum level in patients with chronic plaque psoriasis before and after treatment with narrow band ultraviolet B therapy and Methotrexate. Patients and Methods Our Prospective clinical study included 40 patients of both sex, aged 20-60 years old with psoriasis vulgaris recruited from dermatology outpatient clinic of Ain Shams University Hospital from January 2018 to December 2018. The study was approved by Ain Shams University ethical committee. Informed consents were taken from each Patient after full description of the study aims and procedures Results Both methotrexate and nb-uvb showed significant decrease in serum level hscrp ,PASI score and DLQI after 12 weeks of treatment ,although there were statistically significant lower PASI , DLQI scores and serum level hscrp after 12 weeks of treatment in methotrexate group of patient compared to nb-uvb group of patients Conclusion Highly sensitive C reactive protein(hscrp) is a promising inflammatory marker for monitoring psoriasis severity and efficacy of treatment respectively .Methotrexate treatment showed significant effect on psoriasis severity regarding lowering hscrp serum level ,PASI and DLQI in compared to Nb_UVB therapy .

Chronic foetal hypoxaemia does not cause elevation of serum markers of brain injury

Objectives: The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD. Methods: Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support. Results: Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein. Conclusion: Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.

↵​Clinical and Haemato-biochemical Studies on Gastro-intestinal Colic in Horses

Background: Colic is an important disease of horses. It is a multifactorial and complex disorder. Colic remains one of the common causes of death in horses therefore in present investigation, clinical and haemato-biochemical changes associated with GI colic in horses were studied. Methods: Total 105 horses were examined to study the clinical and haemato-biochemical parameters in colicky horses in southern part of Rajasthan. Result: Mean respiration rate, pulse rate and capillary refill time was found to be significantly increased in horses affected with colic than healthy control animals (P less than 0.05). In haematological indices, mean packed cell volume was significantly increased in colic affected horses (P less than 0.05) whereas mean total platelet count and mean lymphocyte count was found to be significantly decreased (P less than 0.05). In serum biochemical indices, serum aspartate amino transferase, serum alanine amino transferase, blood urea nitrogen, serum creatinine, serum glucose, serum albumin, serum total protein, serum alkaline phosphate and blood lactate were found to be significantly increased in horses affected with colic than healthy control group (P less than 0.05).

Higher NDUFS8 Serum Levels Correlate with Better Insulin Sensitivity in Type 1 Diabetes

Aim: The aim of the study was to evaluate the function of Complex I by measuring NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 serum level and the relationship with insulin resistance in type 1 diabetes. T1DM causes adverse changes in the mitochondria, which can influence the development of chronic complications. The NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 (NDUFS8 protein) is a subunit of NADH dehydrogenase and plays an important role in the mitochondrial function. NDUFS8 serum concentration probably reflects the function of mitochondria. Methods: All of 36 people suffer from T1DM. All participants were treated with functional intensive insulin therapy. NDUFS8 protein serum concentration was measured using the ELISA test. Insulin resistance was evaluated with indirect marker estimated glucose disposal rate (eGDR). The group was divided on the base of median value of eGDR (higher eGDR – less IR). Results: The study group consisted of 12 women and 24 men, aged 39.5 (28.0-46.5) years with the duration of the disease 22 (15-26) years. Medians of eGDR and NDUFS8 protein concentration were 7.6 (5.58-8.99) mg/kg/min and 2.25 (0.72-3.81) ng/ml, respectively. The group with higher insulin sensitivity had higher NDUFS8 protein serum concentration, lower WHR, BMI and they were younger. A negative correlation was observed between NDUFS8 protein serum concentration and WHR (rs=-0.35,p=0.03), whereas a positive correlation was observed between NDUFS8 protein serum concentration and eGDR (rs=0.43,p=0.008). Multivariate linear regression confirmed a significant association between insulin sensitivity and better mitochondrial function (beta=0.54,p=0.003), independent of age, duration of diabetes and smoking. Conclusions: Higher NDUFS8 protein serum concentration is associated with higher insulin sensitivity among people with T1DM and might reflects better mitochondrial function.

MiR-384 is associated with renal damage in lupus nephritis via regulation of TET3 expression

Purpose: To investigate the correlations between miR-384 expression and renal damage in lupus nephritis (LN).Methods: Lupus nephritis and normal tissues were collected during surgery. The relative miR-384 expression was evaluated by extracting RNA and performing quantitative real time PCR (qRT-PCR) assays. Expression of ten-eleven translocation (TET3) mRNA and protein were measured by qRT-PCR and western blotting, respectively. The 24-h urine protein, serum complement C3, and serum creatinine were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. TargetScan and luciferase assays were used to validate the binding site for miR-384 and its target mRNA. Relationships among miR-384, TET3, and renal damage were analyzed by Spearman rank-order correlation coefficients.Results: MiR-384 expression increased in LN tissues and was positively correlated with the activity index (AI) and chronicity index of LN, whereas miR-384 expression and serum complement C3 were negatively correlated. Positive correlations were observed between miR-384 expression and 24-h urine protein, serum creatinine, and systemic lupus erythematosus disease AI. TargetScan and luciferaseassays indicated that the TET3 3′-UTR was the direct target of miR-384. MiR-384 upregulation inhibited TET3 mRNA and protein expression, and was negatively associated with renal damage in LN.Conclusion: MiR-384 upregulation contributes to renal damage in LN by targeting the 3′-UTR of TET3 mRNA, suggesting that miR-384 is a potential biomarker and therapeutic target in LN. Keywords: MiR-384, Renal damage, Lupus nephritis, Ten-eleven translocation, TET3

Neutralization of viruses with European, South African, and United States SARS-CoV-2 variant spike proteins by convalescent sera and BNT162b2 mRNA vaccine-elicited antibodies

The increasing prevalence of SARS-CoV-2 variants with mutations in the spike protein has raised concerns that recovered individuals may not be protected from reinfection and that current vaccines will become less effective. The B.1.1.7 isolate identified in the United Kingdom and B.1.351 isolate identified in the Republic of South Africa encode spike proteins with multiple mutations in the S1 and S2 subunits. In addition, variants have been identified in Columbus, Ohio (COH.20G/677H), Europe (20A.EU2) and in domesticated minks. Analysis by antibody neutralization of pseudotyped viruses showed that convalescent sera from patients infected prior to the emergence of the variant viruses neutralized viruses with the B.1.1.7, B.1.351, COH.20G/677H Columbus Ohio, 20A.EU2 Europe and mink cluster 5 spike proteins with only a minor decrease in titer compared to that of the earlier D614G spike protein. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus and neutralized virus with the B.1.351 spike with, on average, a 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). The reduction in titer was attributable to the E484K mutation in the RBD. The B.1.1.7 and B.1.351 viruses were not more infectious than D614G on ACE2.293T cells in vitro but N501Y, an ACE2 contacting residue present in the B.1.1.7, B.1.351 and COH.20G/677H spike proteins caused higher affinity binding to ACE2, likely contributing to their increased transmissibility. These findings suggest that antibodies elicited by primary infection and by the BNT162b2 mRNA vaccine are likely to maintain protective efficacy against B.1.1.7 and most other variants but that the partial resistance of virus with the B.1.351 spike protein could render some individuals less well protected, supporting a rationale for the development of modified vaccines containing E484K.