👤 Tamer Aydin

Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. The regulation of biological processes, including energy homeostasis, and control of body weight are key mechanisms that the leptin and melanocortin pathways play a role in Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. There are various risk factors for the development of gallstone disease, especially weight gain, and obesity is just one of them. This risk factor can be minimized by maintaining appetite and energy balance. Here, leptin and melanocortin pathways are the key mechanisms in maintaining appetite and energy homeostasis. The aim of this study was to investigate the relationship between the levels of LEP, LEPR, TrkB, BDNF, POMC, and MC4R proteins in patients with Cholelithiasis. This study aims to determine the relationship between LEP, LEPR, TrkB, BDNF, POMC, and MC4R protein levels, which play a role in maintaining appetite and energy homeostasis, and cholelithiasis. This study examined 44 patients diagnosed with Cholelithiasis and 44 healthy control subjects who had not previously been diagnosed with any form of Cholelithiasis. The levels of leptin (LEP), Leptin Binds To Leptin Receptors (LEPR), Tropomyosin Receptor Kinase B (TrkB), Brain-Derived Neurotrophic Factor (BDNF), Pro-OpioMelanoCortin (POMC), and Melanocortin- 4 Receptors (MC4R) molecules were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The results were analyzed using the SPSS Software (Version 22.0) program and GraphPad Prism 8.0.1 software. The study found a statistically significant decrease (p < 0.05) in MC4R, TrkB, BDNF, and POMC protein levels in Cholelithiasis patients compared to the control group. There was no statistically significant difference in LEP and LEPR concentration values between the two groups (p = 0.247, p = 0.674). The proteins MC4R, TrkB, BDNF, and POMC, which are involved in the leptin and melanocortin pathways may play a significant role in Cholelithiasis disease. However, more detailed research on the relevant proteins is needed. Nevertheless, this research will guide new studies. Show less

A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%-44%] at baseline to 42% [32%-50%] at early follow-up ( In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population. Show less

An impaired epithelial barrier integrity in the gastrointestinal tract is important to the pathogenesis of many inflammatory diseases. Accordingly, we assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID-19. Levels of bacterial DNA and zonulin family peptides (ZFP) as markers of bacterial translocation and intestinal permeability and a total of 180 immune and inflammatory proteins were analyzed from the sera of 328 COVID-19 patients and 49 healthy controls. Significantly high levels of circulating bacterial DNA were detected in severe COVID-19 cases. In mild COVID-19 cases, serum bacterial DNA levels were significantly lower than in healthy controls suggesting epithelial barrier tightness as a predictor of a mild disease course. COVID-19 patients were characterized by significantly elevated levels of circulating ZFP. We identified 36 proteins as potential early biomarkers of COVID-19, and six of them (AREG, AXIN1, CLEC4C, CXCL10, CXCL11, and TRANCE) correlated strongly with bacterial translocation and can be used to predict and discriminate severe cases from healthy controls and mild cases (area under the curve (AUC): 1 and 0.88, respectively). Proteomic analysis of the serum of 21 patients with moderate disease at admission which progressed to severe disease revealed 10 proteins associated with disease progression and mortality (AUC: 0.88), including CLEC7A, EIF4EBP1, TRANCE, CXCL10, HGF, KRT19, LAMP3, CKAP4, CXADR, and ITGB6. Our results demonstrate that biomarkers of intact or defective epithelial barriers are associated with disease severity and can provide early information on the prediction at the time of hospital admission. Show less

Alterations in skin structure and function are very common in uremic patients, but still there is no unifying hypothesis for uremic skin disorders. Fibroblast growth factor-23 (FGF-23) deficiency has been linked to skin disorders in non-uremic animals. We aimed to study alterations in FGF-23 and fibroblast growth factor-23 receptor 1 (FGFR1) expression in uremic rat skins. Wistar albino rats were divided into two groups: sham group (SG, n = 8) and uremic group (UG, n = 8). Uremia was induced by reduction of the total kidney mass in the UG. Animals were sacrificed after 14 weeks of the follow-up. Serum creatinine and blood urea nitrogen levels in the UG increased significantly, compared to the SG, at the end of the experiment (0.69 ± 0.08 vs. 0.3 ± 0.04 Mann-Whitney U test (MWU), p = 0,003 and 55.2 ± 8.9 vs. 29.6 ± 6.8 MWU, p = 0.002, respectively). Serum FGF-23 level in the UG was increased non-significantly, compared to the SG (53.5 ± 20.9 vs. 37.2 ± 9.7 MWU, p = 0.072), whereas serum 1,25(OH) This study shows increased FGF-23 levels and FGFR1 expression in uremic rat skins. It deserves further study to fully place this finding in the pathophysiology and clinical picture of uremic skin diseases. Show less

The melanocortin system is an important neural system underlying the control of body weight and food intake. This system has recently received great attention as a potential target for obesity treatment. Therefore, the objective of this study was to find out the leptin-melanocortin pathway before and after Laparoscopic Sleeve Gastrectomy (LSG) in obese patients. The study was carried out with a total of 144 individuals in 3 groups [control, obese group before LSG and obese group after LSG (who underwent LSG one year ago)]. The amount of leptin (LEP), leptin receptor (LEPR), tropomyosin receptor kinase receptor B (TrkB), brain-derived neurotrophic factor (BDNF), pro-opiomelanocortin (POMC) and melanocortin-4 receptors (MC4R) molecules were measured by using Enzyme-Linked Immunosorbent Assays. A statistically significant difference was found between the groups in terms of body mass index (BMI) values (p = 0.001). There was also statistically significant difference present between obese before LSG group and obese after LSG group regarding the levels of LEP, TrkB, BDNF and proteins (p < 0.05). A decline was determined in the LEP and BDNF levels one year follow-up after LSG. The evidence suggests that the leptin melanocortin pathway strictly regulates food intake and BMI before and after LSG surgery. This pathway should be kept under control for effectively reducing food intake and body weight in the treatment of obesity. Show less

This study aimed to investigate the effect of using high-quality colostrum in addition to paromomycin on the treatment outcomes and serum proteomes of calves naturally affected by cryptosporidiosis. Thirty Holstein calves infected with only Cryptosporidium spp. were divided into three equal groups. Calves in the PC group received paromomycin orally at a dose of 100 mg/kg once daily for 5 days. Calves in PCOL and PBCOL groups received 250 ml colostrum 3 h after feeding twice a day for 3 days. The PBCOL group was also given 6 g of sodium bicarbonate 15 min before colostrum administration. While the fecal scores of all calves were evaluated daily for 10 days from the initiation of the treatment, fecal oocyst counts were determined on the 0, 1, 2, 3, 5, 7, and 10th days. Brix%, total protein (TP), immunoglobulin G (IgG), gamma-glutamyltransferase (GGT) levels, and proteomic analyses were performed on the 0 and 3rd days' sera. Considering pretreatment values, fecal scores (8th, 2nd, and 2nd day), and fecal oocyst counts (10th, 3rd, and 2nd day) improved in a significantly (p < 0.05) shorter time in the colostrum groups than in the control group. By serum proteomic analysis, 99, 93, and 83 proteomes were detected in PC, PCOL, and PBCOL groups, respectively. Although the significant changes in any protein in Group PC were absent, significant changes were observed in Alpha-1B-glycoprotein (A1BG), Zinc transporterZIP11 (S39AB), Cathelicidin-1 (CTHL1), Actin_ cytoplasmic-1 (ACTB), and Apolipoprotein A-IV (APOA4) proteins in Group PCOL and Alpha-1-antiproteinase (A1AT), Serum amyloid A protein (SAA), Actin-cytoplasmic-2 (ACTG), Protein HP-20 homolog (HP20) proteins in Group PBCOL with colostral treatment, which indicated that the use of colostrum had an effect on calf serum proteomes. The more pronounced healing and shorter clinical improvement time in the colostrum groups especially colostrum with sodium bicarbonate revealed that these proteomes have positive effects in the treatment with their systemic and local effects in the intestines. Show less

Membranous nephropathy (MN) is characterized by the deposition of immune complexes along glomerular basement membranes. M-Type phospholipase A Multicenter retrospective cohort study. 177 consecutive patients with MN unrelated to lupus erythematosus, identified after screening of 3,875 native kidney biopsies performed in the Belgian UCLouvain Kidney Disease Network from 2000 through 2018. Positive immunostaining for podocyte antigens on archived kidney biopsy samples. Association with different phenotypes (baseline characteristics of patients and pathologic findings on kidney biopsy), time to cancer and to kidney failure. Kaplan-Meier estimates and Cox regression analyses to assess time to cancer and kidney failure. 177 patients were followed up for a median of 4.0 (IQR, 1.3-8.0) years. Diagnosis of PLA Retrospective design; small number of patients in the THSD7A group; lack of evaluation of immunoglobulin G subclasses deposition. Our real-world data describe the relative prevalence of subgroups of MN and support the hypothesis that a novel classification of MN based on podocyte antigen staining may be clinically relevant. Show less

Mammals have three HP1 protein isotypes HP1 beta (CBX1), HP1 alpha (CBX3) and HP1 alpha (CBX5) that are encoded by the corresponding genes Cbx1, Cbx3 and Cbx5. Recent work has shown that reduction of CBX3 protein in homozygotes for a hypomorphic allele (Cbx3hypo) causes a severe postnatal mortality with around 99 percent of the homozygotes dying before weaning. It is not known what the causes of the postnatal mortality are. Here we show that Cbx3hypo/hypo conceptuses are significantly reduced in size and the placentas exhibit a haplo-insufficiency. Late gestation Cbx3hypo/hypo placentas have reduced mRNA transcripts for genes involved in growth regulation, amino acid and glucose transport. Blood vessels within the Cbx3hypo/hypo placental labyrinth are narrower than wild-type. Newborn Cbx3hypo/hypo pups are hypoglycemic, the livers are depleted of glycogen reserves and there is almost complete loss of stored lipid in brown adipose tissue (BAT). There is a 10-fold reduction in expression of the BAT-specific Ucp1 gene, whose product is responsible for nonshivering themogenesis. We suggest that it is the small size of the Cbx3hypo/hypo neonates, a likely consequence of placental growth and transport defects, combined with a possible inability to thermoregulate that causes the severe postnatal mortality. Show less

Atrioventricular nodal reentrant tachycardia (AVNRT) may coexist with Brugada syndrome (BrS). The present study was designed to determine the prevalence of drug-induced type 1 Brugada ECG pattern (concealed BrS) in patients presenting with clinical spontaneous AVNRT and to investigate their electrocardiographic, electrophysiological, and genetic characteristics. Ninety-six consecutive patients without any sign of BrS on baseline electrocardiogram undergoing electrophysiological study and ablation for symptomatic, drug-resistant AVNRT and 66 control subjects underwent an ajmaline challenge to unmask BrS. Genetic screening was performed in 17 patients displaying both AVNRT and BrS. A concealed BrS electrocardiogram was uncovered in 26 of 96 patients with AVNRT (27.1%) and in 3 of 66 control subjects (4.5%) (P ≤ .001). Patients with concealed BrS were predominantly female patients (n=23 [88.5%] vs n=44 [62.9%], P = .015), had higher prevalence of chest pain (n=10 [38.5%] vs n=13 [18.6%], p=0.042), migraine headaches (n=10 [38.5%] vs n=10 [14.2%], p=0.008), and drug-induced initiation and/or worsening of duration and/or frequency of AVNRT (n=4 [15.4%] vs n=1 [1.4%], p=0.006) as compared to patients with AVNRT without BrS. Genetic screening identified 19 mutations or rare variants in 13 genes in 13 of 17 patients with both AVNRT and BrS (yield = 76.5%). Ten of these 13 genotype-positive patients (76.9%) harbored genetic variants known or suspected to cause a loss of function of cardiac sodium channel current (SCN5A, SCN10A, SCN1B, GPD1L, PKP2, and HEY2). Our results suggest that spontaneous AVNRT and concealed BrS co-occur, particularly in female patients, and that genetic variants that reduce sodium channel current may provide a mechanistic link between AVNRT and BrS and predispose to expression of both phenotypes. Show less

Dyggve-Melchior-Clausen syndrome (DMC) (MIM #223800) is a rare autosomal-recessive type of skeletal dysplasia accompanied by variable degrees of intellectual disability (ID). It is characterized by progressive spondyloepimetaphyseal dysplasia leading to disproportionate short stature, microcephaly, and coarse facies. The radiographic appearance of generalized platyspondyly with double-humped end plates and the lace-like appearance of iliac crests are pathognomonic in this syndrome. The disorder results from mutations in the dymeclin (DYM) mapped to the 18q12-12.1 chromosomal region. Here, we report two cases with DMC: one with disproportionate short stature, developmental delay, and severe ID with a novel frameshift mutation (c.1028₁₀₅₆del29) leading to a premature stop codon, and the second patient with classical clinical and radiological features of DMC with mild ID and rectal prolapse, which is very rare. The clinical diagnosis was confirmed with molecular analysis of DYM with a known mutation at c.580C>T (p.R194X). The parents and sibling of the second patient were heterozygous carriers with mild skeletal changes and short stature. Show less