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WOS: 000471326300002, Background: Infantile nephrotic syndrome (INS) refers to disease that is present after the first three months of life up to one year of age. There is genetic heterogeneity and genotype-phenotype correlation is not clear. Objectives: The focus of the present study was to analyze genotypic and phenotypic features of both NPHS1 and NPHS2 genes in INS. Methods: Clinical data, mutational analysis, histology, treatments, and outcomes of 48 children with NS are evaluated. A direct sequencing of NPHS1 gene and NPHS2 gene was performed. Patients were classified into 3 groups; group 1: cases having only NPHS1 mutation; group 2: cases with only NPHS2 mutation; group 3: cases without any mutation. Results: The mean age at onset of the disease was 8.7 +/- 2.3 months, and mean follow-up time was 8.3 years. Seven familial and 41 sporadic cases of INS were found. Kidney biopsy was performed in 45 out of 48 patients and pathological investigations revealed focal segmental glomerulosclerosis in 29 (65%), IgM nephropathy in 6 (13%), and minimal change disease in 10 patients (22%). There were 5 (10.4%) cases in groups (patients having only mutations of NPHS1)and 13 cases (27%) in group 2 (patients having only mutations of NPHS2). Thirty cases (62.5%) had neither NPHS1 nor NPHS2 mutation (group 3). Conclusions: The genotypic and phenotypic features of INS were demonstrated. We found that INS with podocin mutation has poor prognosis according to exonal distribution. NPHS1 mutations caused a severe disease but with a more favorable prognosis.

WOS: 000463332100016, PubMed ID: 30968627, Brugada syndrome, an arrhythmogenic disease, occurs due to mutations involving cardiac sodium channels. It is characterized by persistent or transient ST-segment elevation in the right precordial electrocardiogram leads that could be unmasked by several circumstances, with fever particularly. Molecular and cellular mechanisms leading to Brugada syndrome have not been completely elucidated. Mutations of the SCN5A gene encoding the pore-forming alpha-subunit of the cardiac sodium channel protein have been attributed in the molecular diagnosis. Although this syndrome is well-known in adults, it is less frequently reported in infants and children. We describe a 9-year-old Turkish boy with a family history of sudden cardiac death, who presented with chest pain and fever-induced expression of the Brugada syndrome phenotype that might be associated with a mutation in SCN5A gene.

Introduction Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy, which develops as a result of defective activity of the alternative complement pathway and excessive complement activation due to genetic or acquired factors. No satisfactory responses were obtained by plasmapheresis, corticosteroids and fresh frozen plasma (FFP) transfusion. However, promising results are obtained in recent years by eculuzimab treatment, which inhibits C5 activation. Objective To evaluate the efficacy, safety and effect of eculizumab on quality of life of adult aHUS patients followed in our center. Materials and Methods Seven patients who received eculizumab treatment in single center between the years 2012 and 2016 due to aHUS diagnosis were retrospectively evaluated. Patients were diagnosed with aHUS in accordance with certain criteria, after eliminating all the other factors caused by thrombotic microangiopathy. Complement gene mutations were completed in six patients. All patients received eculizumab as recommended (900 mg/per two weeks) following plasmapheresis, FFP, corticosteroid and hemodialysis (HD) treatments. Results Four out of seven patients were men and three were women; average patient age was 51.1 (26–69) years and average duration of disease was 25.3 (2–45) months. Average period from the initial complaints of the patients up to aHUS diagnosis was 4.2 (2–13) months. Tests were implemented on six patients for complement gene mutations, and complement factor H (CFH) homozygous mutation was identified in three patients. Complete remission was observed in four patients and partial remission in two patients after eculizumab; however, one patient died. Plasmapheresis was discontinued in patients with complete remission, whereas two patients with partial remission continued the HD program, despite normalization in hematologic parameters. Significant improvement was observed in post-treatment quality of life in all six patients who currently continue eculuzimab treatment. No transfusion reaction and/or no serious infections were observed in any of the patients, while URTI (upper respiratory tract infection) was observed in one patient. Discussion Eculizumab is an effective and safety treatment option in adult aHUS patients. Early diagnosis and initializing eculizumab therapy at an early stage may decrease mortality and morbidity in patients with aHUS. New studies are required on this topic.

WOS: 000388033500006, PubMed ID: 27357501, Nucleotide binding and oligomerization domains/caspase recruitment domain-containing protein 15 (NOD2/CARD15) is a cytoplasmic molecule controlling apoptosis and inflammatory processes by recognizing some microbial components. We aimed to identify the frequencies of NOD2/CARD15 gene mutations in patients with gouty arthritis and to determine their possible correlation with the disease phenotype. The study included 93 patients with gouty arthritis and 51 healthy controls matched for age, gender, and ethnicity. The NOD2/CARD15 R702W and G908R gene mutations were explored by the polymerase chain reaction restriction fragment length polymorphism method while the 3020insC mutation was analyzed by DNA sequencing. The mean patient age was 54.2 +/- 14.2 years and mean duration of the disease was 3.1 +/- 2.9 years. The first metatarsophalangeal and finger joint involvements were detected in 72 (77.4%) and 18 (19.5%) patients, respectively. Ankle arthritis and knee arthritis were detected in 43 (46.2%) and 20 (21.5%) patients, respectively. In total, 4 (9%) heterozygous mutations were detected in the G908R and R702W genes, while no mutation was detected in the 3020insC gene. Compared to the control group, there were no significant differences in all three DNA regions (G908R, R702W, and 3020insC; p = 0.452, p = 0.583, and p = 0.350, respectively). No correlation between the NOD2/CARD15 variants and clinical or laboratory findings (p > 0.05) was found. The frequencies of the NOD2/CARD15 gene mutations in the patients were similar to healthy control group. No association between clinical or laboratory findings and the NOD2/CARD15 gene mutations was observed., scientific research project committee of Sifa University, This work was supported by the scientific research project committee of Sifa University.

Gouty arthritis is a chronic erosive autoinflammatory disease. Pyrin has anti-inflammatory effects in the regulation of inflammasome and is encoded by the MEFV gene. The relationship between different rheumatic diseases and the MEFV gene mutations was demonstrated. The aim of this study was to determine the frequency of MEFV gene mutations in patients with gouty arthritis and identify a possible correlation with disease phenotype. Ninety-three patients with gouty arthritis and 102 healthy controls, compatible with age, gender and ethnicity, were included in the study. MEFV gene mutations were investigated by PCR method. Out of 93 patients with gouty arthritis, 36 (38.7 %) showed MEFV gene mutations carriage, whereas 20.6 % in healthy control group. Distribution of mutations identified in patients with gouty arthritis was as; R202Q in 18 (19.3 %), E148Q in 5 (5.4 %), K695R in 4 (4.3 %), M680I in 2 (2.1 %), V726A in 2 (2.1 %), P369S in 2 (2.1 %), R408Q in 2 (2.1 %), M694 V in 1 (1.1 %), respectively. Three patients were identified with compound heterozygosity. Distribution of MEFV gene mutations carriage in healthy controls was; E148Q in 11 (10.7 %), M694 V in 2 (1.9 %), M694I in 1 (0.9 %), M680I in 2 (1.9 %), V726A in 1 (0.9 %), A744S in 1 (0.9 %), K695R in 2 (1.9 %), and P369S in 1 (0.9 %) patients, respectively. Higher MEFV gene mutations carrier frequency was observed in patients with gouty arthritis, compared with the control group (p = 0.009). Heterozygous R202Q was the most common mutation detected in patients with gouty arthritis, while heterozygous E148Q in healthy control group. Statistically significant difference was not detected between clinical findings of gouty arthritis and the MEFV gene mutations (p > 0.05). We determined higher prevalence of MEFV gene mutations in patients with gouty arthritis compared with the healthy control group. The most frequently detected mutation was heterozygous R202Q, whereas E148Q in healthy controls. High carriage rates of MEFV gene mutations in gouty arthritis suggest that it may play an important role in the pathogenesis of the disease and predisposition to the disease.

WOS: 000395365500020, PubMed ID: 28261298, Introduction: Chronic myeloproliferative disorders (CMPD) are chronic myeloid hematological disorders, characterized by increased myeloid cell proliferation and fibrosis. Impaired apoptotic mechanisms, increased cell proliferation, uncontrolled hematopoietic cell proliferation and myeloaccumulation may contribute to the pathogenesis of CMPD. The aim of our study was to show the possible role of FAS/FASL gene polymorphisms in CMPD pathogenesis and investigate the association with clinical parameters and susceptibility to disease. Material and methods: We included 101 (34 polycythemia vera (PV), 23 primary myelofibrosis (PMF), 44 essential thrombocythemia (ET)) CMPD patients diagnosed according to the WHO classification criteria and 95 healthy controls in this study. All the patients and the controls were investigated for FAS/FASL gene expression, allele frequencies and phenotype features, and also FAS mRNA levels were analyzed. Results: Chronic myeloproliferative disorders patients showed increased FAS-670AG + GG genotype distribution compared with the control group (p < 0.05). While the A allele was more frequent in both groups, AG genotype was more frequent in CMPD patients. There was no association between FAS-670A>G gene polymorphism and some clinical parameters such as splenomegaly and thrombosis (p > 0.05). No statistically significant difference in FASL+843C>T genotype or allele frequency was found between groups (p > 0.05). Moreover, no statistically significant difference was detected in FASL and JAK2V617F mutations (p > 0.05). FAS mRNA expression was 1.5-fold reduced in patients compared to healthy subjects. Conclusions: According to our findings, FAS/FASL gene expression may contribute to the molecular and immunological pathogenesis of CMPD. More investigations are needed to support these data.

Hashimoto's disease is a polygenic disorder with complex etiopathogenesis. The imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. We aimed to evaluate the relation between 174 promoter region of the interleukin 6 rs1800795 gene polymorphism in patients with Hashimoto's thyroiditis (HT). We studied 110 HT patients and 110 healthy controls. The evaluation of genotype for interleukin 6 rs1800795 gene polymorphism were performed by using PCR-RFLP method. The genotype of IL6 distribution did differ between the control group (CC 17.3%, GC 78.2%, GG 4.5%) and the HT patients (CC 29.1%, GC 46.4%, GG 24.5%) (p 0.05). Our results indicate that interleukin 6 rs1800795 polymorphism may be associated with susceptibility to HT in Turkish Patients. It is necessary to confirm the results and determine the underlying pathogenic mechanisms in further studies.

WOS: 000459055600002, PubMed ID: 30793612, OBJECTIVES: The aim of the study was to determine the mutation of the podocin gene (NPHS2) in children with minimal changes diseases (steroid sensitive nephrotic syndrome (NS)) and steroid resistant NS. BACKGROUND: Despite the fact that the role of genetic factors is a well-known phenomenon, in NS there are still unknown aspects that are yet to be discovered. NS, type 2 is caused by NPHS2 gene and is characterised with proteinuria, minimal change disease on renal biopsy, poor response to steroid treatment, etc. METHODS: Twenty-nine children (65.5 % male, 34.5 % female) with nephrotic syndrome caused by chronic glomerulonephritis were examined and patients were tested for NPHS2 gene with Sanger technique. RESULTS: The average age was 7.2 +/- 2.65 years. 82.8 % of patients had NS with minimal changes, 17.2 % had a steroid resistant NS. The analysis of the NPHS2 gene revealed a likely pathogenic (Arg168His), uncertain significance (Pro20Ley, Leu169Pro, Val180Met, Arg229Gln, Val290Met) and benign (Gly34Gly, Ala318Ala) variants. No novel variants were detected. CONCLUSION: This is the first study investigating the nephrotic syndrome related to NPHS2 gene in Azerbaijani population. The high prevalence of uncertain significance variants emphasises the importance of population studies in this region as such data are necessary for classifications of the detected genetic variants (Tab. 1, Ref. 25). Text in PDF www.elis.sk.

WOS: 000469770400004, PubMed ID: 31144657, Background/Aims: Gastric cancers vary across countries and ethnic groups. They are the second most common type of cancer worldwide. Dietary and non-dietary factors as well as genetic and epigenetic alterations of many mechanisms are implicated in the development of gastric cancer. We aimed to determine the sequence of possible nucleotide changes, polymorphisms, and mutations, and to establish genotype and phenotype relation by performing whole DNA sequence analysis of the XRCC1 and ERCC1 genes belonging to base excision repair (BER) and nucleotide excision repair (NER) family of DNA repair genes in patients with gastric cancer. Materials and Methods: We included 50 patients of both sexes who had received diagnosis of gastric cancer and 50 healthy people who showed same demographic traits that forms the control group. We analyzed the ERCC1 and XRCC1 genes by DNA sequence analysis on both groups. After the analysis, we compared the genotype-phenotype relation. Results: Neither patients nor the control group has any nucleotide replacement in any exon of ERCC1 genes. We could not detect significant difference between patients and healthy groups when we correlated genotype contribution of mutations Arg194Trp, Arg208His, Arg399Gln detected in the XRCC1 gene and allele frequency. Conclusion: According to our study, the ERCC1 gene in Turkish population is not getting mutation in patients with gastric cancer and healthy individuals. Three mutations were detected in the XRCC1 gene, and these mutations were not associated with gastric cancer.

Aim: Mesenchymal stem cells (MSCs) are strong immunomodulatory cells and a component of the tumor microenvironment. In this study, we aimed to investigate the effects of MSCs derived from adipose tissue on the expressions of immune evasive molecules indoleamine 2,3-dioxygenase (IDO), human leukocyte antigen G (HLA-G) and programmed death-ligand 1 (PD-L1) of breast tumor cell lines MDA-MB-231 and MCF-7. Methods: For this purpose, MSCs, MDA-MB-231 and MCF-7 cells were cultured with increased doses of interferon gamma (IFN-g). In another plate, tumor cells were cultured in transwell inserts using the same IFN-g stimulation to evaluate the effect of MSCs. At the end of the culture period, the HLA-G and PD-L1 expression was detected by flow cytometry, and IDO expression by the Luminex method. Results: We found that in low-dose IFN-g stimulation (10 ng/mL), MSCs led to a significant increase in the HLA-G and PD-L1 expression of MCF-7 cells. On the contrary, at a high dose of IFN-g (50 ng/mL), their expression significantly decreased in both tumor cells. In addition, we observed that the IDO expression of MDA-MB-231 cells was significantly increased in the presence of MSCs, but MCF-7 cells were not affected. Conclusion: In conclusion, for MDA-MB-231 cells, MSCs may play a protective role because they reduce the expression of HLA-G and PD-L1 that are involved in the suppression of cytotoxic cells and exhaustion of T cells. On the other hand, MSCs may be an important source of high IDO levels, and therefore may negatively affect the antitumor immune response. However, our data should be supported by further studies. Amaç: Mezenkimal kök hücreler (MKH) güçlü immünomodülatör hücreleridir ve ayrıca tümör mikroçevresinin bir bileşenidir. Bu çalışmada meme tümör hücre hatları MDA-MB-231 ve MCF-7’nin immün evazif moleküller olan Indoleamine 2,3-dioxygenase (IDO), Human Leukocyte Antigen G (HLA-G) and Programmed Death-Ligand 1 (PD-L1) ifadelerine yağ dokusu kökenli mezenkimal kök hücrelerin etkilerini araştırmayı amaçladık. Yöntemler: Bu amaçla MKH, MDA-MB-231 ve MCF-7 hücrelerini artan dozlarda interferon gama (IFN-g) ile kültüre edildi. Başka bir kültür kabında MKH’ler ile tümör hücreleri trans-well insertler ve aynı IFN-g uyarımı ile kültür edildi. Kültür süresinin bitiminde HLA-G ve PD-L1 ifadeleri flow-sitmotetri yöntemi ile IDO ifadeleri Luminex yöntemi ile analiz edildi. Bulgular: Düşük dozlu IFN-g uyarımında (10 ng/mL), MSC'lerin MCF-7 hücrelerinin HLA-G ve PD-L1 ekspresyonunda önemli bir artışa yol açtığını bulduk. Aksine, yüksek doz IFN-g ile (50 ng/mL) bu ifadelerin her iki tümör hücresinde de önemli ölçüde azaldığını gördük. Ek olarak, MDA-MB-231 hücrelerinin IDO ekspresyonunun MSC'lerin varlığında anlamlı şekilde arttığını, ancak MCF-7 hücrelerinin etkilenmediği gördük. Sonuç: Sonuç olarak, MDA-MB-231 hücreleri için MSC'ler, sitotoksik hücrelerin baskılanmasında ve T hücrelerinin tükenmesinde önemli bir rol oynayan HLA-G ve PD-L1 ekspresyonunu azalttığı için koruyucu bir rol oynayabilir. Öte yandan, MSC'ler yüksek IDO seviyeleri için önemli bir kaynak olabilir ve bu nedenle anti-tümör immün yanıtı olumsuz yönde etkileyebilir. Bununla birlikte, verilerimiz diğer çalışmalarla desteklenmelidir.

52nd Conference of the European-Society-of-Human-Genetics (ESHG) -- JUN 15-18, 2019 -- Gothenburg, SWEDEN, WOS: 000489313907095, [No abstract available], European Soc Human Genet

Hermle, Tobias/0000-0002-0441-7749, WOS: 000508269600010, PubMed: 31732614, Background Mutations in about 50 genes have been identified as monogenic causes of nephrotic syndrome, a frequent cause of CKD. These genes delineated the pathogenetic pathways and rendered significant insight into podocyte biology. Methods We used whole-exome sequencing to identify novel monogenic causes of steroid-resistant nephrotic syndrome (SRNS). We analyzed the functional significance of an SRNS-associated gene in vitro and in podocyte-like Drosophila nephrocytes. Results We identified hemizygous missense mutations in the gene TBC1D8B in five families with nephrotic syndrome. Coimmunoprecipitation assays indicated interactions between TBC1D8B and active forms of RAB11. Silencing TBC1D8B in HEK293T cells increased basal autophagy and exocytosis, two cellular functions that are independently regulated by RAB11. This suggests that TBC1D8B plays a regulatory role by inhibiting endogenous RAB11. Coimmunoprecipitation assays showed TBC1D8B also interacts with the slit diaphragm protein nephrin, and colocalizes with it in immortalized cell lines. Overexpressed murine Tbc1d8b with patient-derived mutations had lower affinity for endogenous RAB11 and nephrin compared with wild-type Tbc1d8b protein. Knockdown of Tbc1d8b in Drosophila impaired function of the podocyte-like nephrocytes, and caused mistrafficking of Sns, the Drosophila ortholog of nephrin. Expression of Rab11 RNAi in nephrocytes entailed defective delivery of slit diaphragm protein to the membrane, whereas RAB11 overexpression revealed a partial phenotypic overlap to Tbc1d8b loss of function. Conclusions Novel mutations in TBC1D8B are monogenic causes of SRNS. This gene inhibits RAB11. Our findings suggest that RAB11-dependent vesicular nephrin trafficking plays a role in the pathogenesis of nephrotic syndrome., Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [HE 7456/3-1]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK076683, U54HG006504]; MOTI-VATE program of the Medical Faculty of theUniversity of Freiburg; National Human Genome Research InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [UM1HG008900]; National Eye InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI); National Heart, Lung, and Blood InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI); T32 Ruth L. Kirschstein Institutional National Research Service AwardUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK007527]; Charite-Universitatsmedizin Berlin; Berlin Institute of Health; German Research FoundationGerman Research Foundation (DFG) [RO4341/2-1]; Excellence Initiative of the German Research FoundationGerman Research Foundation (DFG) [EXC 294]; Ministry of Science, Research and the Arts of Baden-Wurttemberg [Az: 33-7532.20]; Deutsche Forschungsgemeinschaft Collaborative Research CentreGerman Research Foundation (DFG) [KIDGEM1140]; Federal Ministry of Education and ResearchFederal Ministry of Education & Research (BMBF) [01GM1515C]; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [UM1HG008900, UM1HG008900, UM1HG008900, UM1HG008900, UM1HG008900] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [T32DK007527, T32DK007527, T32DK007527, T32DK007527, T32DK007527] Funding Source: NIH RePORTER, This research was supported by grants from the Deutsche Forschungsgemeinschaft to Dr. Hermle (HE 7456/3-1) and the National Institutes of Health to Dr. Hildebrandt (DK076683), and to the Yale Center for Mendelian Genomics (U54HG006504). Ms. Kampf was supported by the MOTI-VATE program of the Medical Faculty of theUniversity of Freiburg. the Broad CMG was funded by a grant from the National Human Genome Research Institute (UM1HG008900), the National Eye Institute, and the National Heart, Lung, and Blood Institute. A. Onuchic-Whitford acknowledges support from the T32 Ruth L. Kirschstein Institutional National Research Service Award (DK007527). Dr. Schrezenmeier is participant in the BIH-Charite Clinician Scientist Program funded by the Charite-Universitatsmedizin Berlin and the Berlin Institute of Health. Dr. Romer acknowledges the support by the German Research Foundation (grant RO4341/2-1), the Excellence Initiative of the German Research Foundation (EXC 294), and the Ministry of Science, Research and the Arts of Baden-Wurttemberg (Az: 33-7532.20). Dr. Bergmann acknowledges support from the Deutsche Forschungsgemeinschaft Collaborative Research Centre (KIDGEM1140) and the Federal Ministry of Education and Research (01GM1515C).

PubMed: 31705748, 2-s2.0-85074726532, Introduction. Atypical hemolytic uremic syndrome (aHUS) is associated with mutations or antibodies that affect the regulation of the alternative complement pathway. Several studies were published recently, describing these mutations. We present the initial clinical findings, treatments, and long-term follow-up results of 19 patients hospitalized with the diagnosis of aHUS. Methods. Nineteen patients who were diagnosed as aHUS were enrolled from January 2010 to March 2017. Initial clinical signs and clinical follow-up of patients with aHUS were evaluated. The reasons for complement factor H (CFH) mutations were investigated. Results. CFH mutations were detected in 5 of the 19 aHUS cases. Of these, one was novel, while four were previously reported. We reported here the clinical course of aHUS patients with CFH previously defined mutations (p.Glu936Asp, Val 1197Ala) and a novel mutation (Glu927Lys), which caused previously defined aHUS. Two of the CFH mutation cases developed end-stage kidney disease that required hemodialysis, and one patient developed chronic kidney disease. Two cases were in remission; one of them under supportive therapy and the other one in remission with eculizumab treatment. Conclusions. Morbidity rates are higher in children with aHUS. However, renal prognosis and morbidity rates are higher in children with CFH mutations than other children with aHUS. Poor prognosis in aHUS-children with CFH mutation depends on the genetic background. © 2019, Iranian Society of Nephrology.

Aim: Mesenchymal stem cells (MSCs) are strong immunomodulatory cells and a component of the tumor microenvironment. in this study, we aimed to investigate the effects of MSCs derived from adipose tissue on the expressions of immune evasive molecules indoleamine 2,3-dioxygenase (IDO), human leukocyte antigen G (HLA-G) and programmed death-ligand 1 (PD-L1) of breast tumor cell lines MDA-MB-231 and MCF-7. Methods: For this purpose, MSCs, MDA-MB-231 and MCF-7 cells were cultured with increased doses of interferon gamma (IFN-g). in another plate, tumor cells were cultured in transwell inserts using the same IFN-g stimulation to evaluate the effect of MSCs. At the end of the culture period, the HLA-G and PD-L1 expression was detected by flow cytometry, and IDO expression by the Luminex method. Results: We found that in low-dose IFN-g stimulation (10 ng/mL), MSCs led to a significant increase in the HLA-G and PD-L1 expression of MCF-7 cells. on the contrary, at a high dose of IFN-g (50 ng/mL), their expression significantly decreased in both tumor cells. in addition, we observed that the IDO expression of MDA-MB-231 cells was significantly increased in the presence of MSCs, but MCF-7 cells were not affected. Conclusion: in conclusion, for MDA-MB-231 cells, MSCs may play a protective role because they reduce the expression of HLA-G and PD-L1 that are involved in the suppression of cytotoxic cells and exhaustion of T cells. on the other hand, MSCs may be an important source of high IDO levels, and therefore may negatively affect the antitumor immune response. However, our data should be supported by further studies., Amaç: Mezenkimal kök hücreler (MKH) güçlü immünomodülatör hücreleridir ve ayrıca tümör mikroçevresinin bir bileşenidir. Bu çalışmada meme tümör hücre hatları MDA-MB-231 ve MCF-7’nin immün evazif moleküller olan Indoleamine 2,3-dioxygenase (IDO), Human Leukocyte Antigen G (HLA-G) and Programmed Death-Ligand 1 (PD-L1) ifadelerine yağ dokusu kökenli mezenkimal kök hücrelerin etkilerini araştırmayı amaçladık. Yöntemler: Bu amaçla MKH, MDA-MB-231 ve MCF-7 hücrelerini artan dozlarda interferon gama (IFN-g) ile kültüre edildi. Başka bir kültür kabında MKH’ler ile tümör hücreleri trans-well insertler ve aynı IFN-g uyarımı ile kültür edildi. Kültür süresinin bitiminde HLA-G ve PD-L1 ifadeleri flow-sitmotetri yöntemi ile IDO ifadeleri Luminex yöntemi ile analiz edildi. Bulgular: Düşük dozlu IFN-g uyarımında (10 ng/mL), MSC'lerin MCF-7 hücrelerinin HLA-G ve PD-L1 ekspresyonunda önemli bir artışa yol açtığını bulduk. Aksine, yüksek doz IFN-g ile (50 ng/mL) bu ifadelerin her iki tümör hücresinde de önemli ölçüde azaldığını gördük. Ek olarak, MDA-MB-231 hücrelerinin IDO ekspresyonunun MSC'lerin varlığında anlamlı şekilde arttığını, ancak MCF-7 hücrelerinin etkilenmediği gördük. Sonuç: Sonuç olarak, MDA-MB-231 hücreleri için MSC'ler, sitotoksik hücrelerin baskılanmasında ve T hücrelerinin tükenmesinde önemli bir rol oynayan HLA-G ve PD-L1 ekspresyonunu azalttığı için koruyucu bir rol oynayabilir. Öte yandan, MSC'ler yüksek IDO seviyeleri için önemli bir kaynak olabilir ve bu nedenle anti-tümör immün yanıtı olumsuz yönde etkileyebilir. Bununla birlikte, verilerimiz diğer çalışmalarla desteklenmelidir.

WOS: 000492798700005, Introduction. Atypical hemolytic uremic syndrome (aHUS) is associated with mutations or antibodies that affect the regulation of the alternative complement pathway. Several studies were published recently, describing these mutations. We present the initial clinical findings, treatments, and long-term follow-up results of 19 patients hospitalized with the diagnosis of aHUS. Methods. Nineteen patients who were diagnosed as aHUS were enrolled from January 2010 to March 2017. Initial clinical signs and clinical follow-up of patients with aHUS were evaluated. the reasons for complement factor H (CFH) mutations were investigated. Results. CFH mutations were detected in 5 of the 19 aHUS cases. of these, one was novel, while four were previously reported. We reported here the clinical course of aHUS patients with CFH previously defined mutations (p.Glu936Asp, Val 1197Ala) and a novel mutation (Glu927Lys), which caused previously defined aHUS. Two of the CFH mutation cases developed end-stage kidney disease that required hemodialysis, and one patient developed chronic kidney disease. Two cases were in remission; one of them under supportive therapy and the other one in remission with eculizumab treatment. Conclusions. Morbidity rates are higher in children with aHUS. However, renal prognosis and morbidity rates are higher in children with CFH mutations than other children with aHUS. Poor prognosis in aHUS-children with CFH mutation depends on the genetic background.

Atypical hemolytic uremic syndrome (aHUS) is associated with mutations or antibodies that affect the regulation of the alternative complement pathway. In the recent years several studies have been published describing these mutations. In this study, the initial clinical findings, treatments and long-term follow-up results of 19 patients who were hospitalized with the diagnosis of aHUS were presented.Nineteen patients who were diagnosed as aHUS were enrolled from January 2010 to March 2017. Initial clinical signs and clinical follow-up of patients with aHUS were evaluated. Disease causing complement factor H (CFH) mutations were determined. Results. CFH mutations were detected in 5 of 19 aHUS cases. Of these, one was novel and 4 were previously reported. We reported here the clinical course of aHUS patients with CFH mutations (p.Glu936Asp, Val 1197Ala) and a novel mutation (Glu927Lys) which caused previously defined aHUS. Two of the CFH mutation cases developed end stage kidney disease that required hemodialysis, 1 case developed chronic kidney disease. Two cases were in remission, one of them with supportive therapy and the other case was in remission with eculizumab treatment.Morbidity rate is higher in children with aHUS. The renal prognosis and morbidity rate is higher in children with CFH mutations than other children with aHUS. Poor prognosis in aHUS children with CFH mutation depends on the genetic background.

WOS: 000438380400011, PubMed ID: 29745120, Complement mediated hemolytic uremic syndrome which is caused by excessive activation of the alternative complement system is a thrombotic microangiopathy. The disease frequently occurs as a result of mutations in the genes that regulates complement proteins. Complement factor H gene has the most common mutations. A nine-month-old male patient was transferred to pediatric intensive care unit with the diagnosis of hemolytic uremic syndrome. Nonsense heterozygous p.Arg1215X mutation in the complement factor H gene was detected. The patient who had pulmonary, intestinal and hepatic involvement accompanying acute renal failure was successfully treated with therapeutic plasma exchange and eculizumab. Nonsense heterozygous p.Arg1215X mutation is extremely rare and can cause severe hemolytic uremic syndrome. As far as we know, our patient is the third case with this mutation in the literature.

Background: Severe combined immunodeficiency (SCID) syndromes are a heterogenous group of diseases characterized by impairment in both cellular and humoral immunity with a range of genetic disorders. Complete recombinase activating gene (RAG) deficiency is associated with classical T - B - NK + SCID which is the most common phenotype of Turkish SCID patients. There is a broad spectrum of hypomorfic RAG mutations including Omenn syndrome, leaky or atypical SCID with expansion of γδ T cells, autoimmunity and cytomegalovirus (CMV) infections. Methods: Twenty-one (44%) patients had RAG1 deficiency of all 44 SCID patients followed up by pediatric immunology department. A retrospective analysis was conducted on the medical records of all SCID patients with RAG1 deficiency. Results: Eight patients were classified as T - B - NK + SCID, five patients as T + B - NK + SCID (three of these were Omenn phenotype), and eight patients as T + B + NK + SCID phenotype. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were 87.7 ± 73.8 (12 - 256), 4.4 ± 8.2 (1 - 36) and 29.1 ± 56.8 (1 - 244) months, respectively. Consanguinity was present in 11 (52%) of 21 patients. Autoimmunity was found in six patients (28%). Ten patients (47%) had CMV infection, four (19%) had Epstein-Barr virus (EBV) infections and three (14%) had Bacillus Calmette-Guerin (BCG) infections. Seven patients who had refractory cytopenia (two pancytopenia and five bicytopenia) underwent bone marrow biopsy, three of whom had bone marrow fibrosis. Future evaluations must be considered about bone marrow fibrosis in RAG1 deficiency patients. Eosinophilia was observed in 10 patients, seven of whom did not have Omenn phenotype. Conclusion: Non-Omenn phenotype RAG1 deficiencies can also present with eosinophilia. This report is presented to emphasize that RAG1 mutations may lead to diverse clinical phenotypes. J Clin Med Res. 2016;8(5):379-384 doi: http://dx.doi.org/10.14740/jocmr2316w

Introduction Several studies have attempted to define the diagnostic criteria of the geriatric syndrome sarcopenia. Studies of sarcopenia prevalence in Turkey are limited; one reason for this is the absence of standard diagnostic reference values. The aim of this study was to investigate the prevalence of sarcopenia and its influencing factors in the local elderly nursing home residents in accordance with the EWGSOP consensus report. Materials and methods The study included a total of 211 nursing home residents. Anthropometric measurements, muscle mass, muscle strength and physical performance were examined. Muscle mass of the nursing home residents was compared to an 18–45-year-old healthy control group. Descriptive values for numerical variables are given as mean, standard deviation; categorical variables are shown as frequency and percentage. Results A total of 211 nursing home residents were included in the study. The average age was 77.30 ± 7.20; the participants were 58.8% women and 37.4% young-old. The prevalence of sarcopenia in Turkish nursing home residents was found to be 33.6%. Among sarcopenic participants, 32.4% were women and 67.6% were men. In our study, sarcopenia was more prevalent in men, the young-old, and patients with Parkinson's or chronic obstructive lung disease, while sarcopenia was seen less in obese patients. No relationship was found between the Barthel index and sarcopenia. Conclusions Sarcopenia prevalence was 33.6% when the diagnostic criteria described by the EWGSOP were used. Sarcopenia prevalence was higher in men and the young-old age groups. Sarcopenia was more frequent in nursing home residents with malnutrition or risk of malnutrition.

WOS: 000219054200003, Aim: Glycogen storage disease type 1 is characterized with hypertriglyceridemia which does not lead to atherosclerosis. The human intercellular adhesion molecule-1 gene has been shown to be affected in atherosclerosis and postprandial hypertriglyceridemia. Materials and Methods: In the present paper, the authors genotyped the Glu241Arg polymorphism in the intercellular adhesion molecule-1 gene in 35 patients with Glycogen storage disease type 1 and 108 healthy controls. Results: The results indicated a significant decrease in the frequency of the GG genotype in Glycogen storage disease type I patients compared to healthy controls. In addition, a significant correlation between the GG genotype and triglyceride levels was seen in Glycogen storage disease type 1 patients. Conclusion: It is thus concluded that the GG genotype could protect Glycogen storage disease type I patients from the development of atherosclerosis.

WOS: 000443041100012, Arthrogryposis, renal tubular dysfunction and cholestasis (ARC) syndrome is a rare, autosomal recessive multisystem disorder. Severe growth retardation, ichthyosis, recurrent febrile disease, platelet abnormalities, sensorineural hearing loss, hypotonia and corpus callosum dysgenesis were later included as further features of this syndrome. We present a case of ARC syndrome diagnosed by genetic analysis.

WOS:000443998400353, [No Abstract Available]

Serdaroglu, Erkin/0000-0002-6863-8866, WOS:000443998400339, [No Abstract Available]

SENOL, Ozgur/0000-0002-1062-3290, WOS:000443998400400, [No Abstract Available]

BACKGROUND The aim of the study was to investigate the effects of colchicine on cytokine production, apoptosis, alveolar bone loss, and oxidative stress in an experimental model of periodontitis in rats. METHODS Forty-eight rats were divided equally into four groups: healthy (H); periodontitis (P); periodontitis+colchicine low dose (CL, 30 μg/kg/day), and periodontitis+colchicine high dose (CH, 100 μg/kg/day). After 11 days, interleukin (IL) -1β, IL-8, and IL-10 were analyzed in gingival samples using Enzyme-Linked ImmunoSorbent Assay. Receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), total oxidative stress (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured in gingiva and serum. Alveolar bone volume was evaluated via micro-CT. Apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in histological sections. RESULTS Colchicine treatment significantly reduced IL-1β, IL-8, RANKL, RANKL/OPG, TOS, OSI, and bone volume ratio levels, and increased TAS levels compared to group P (p