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Purpose: It is known that the decrease in estrogen level in women's life has negative effects on the cardiovascular system. In this study, it was aimed to elucidate the changes in the clinical status and treatment requirement of patients with heart failure (HF) during the menopausal transition period. Materials and Methods: A total of 26 patients followed up in the HF outpatient clinic between 2015-2020 were included in this retrospective, single-center study. Demographic data of the patients, New York Heart Association class, echocardiographic findings, routine biochemical parameters and HF signs, symptoms and therapies were examined. Data at the beginning of the menopause period and after 12 months were compared. Results: At the end of the 12-month follow-up, a statistically significant increase was found in the daily dose of furosemide (50.5 mg/day vs. 72.4 mg/day). While the mean heart rate of the patients was 80.4±20.1 beats/min at the beginning, it was 69.3±10.1 beats/min in the control visit. Echocardiographically measured left ventricular (LV) systolic diameters of the patients were significantly increased compared to baseline in the control visit (41.2±7.4 mm vs 45.8±7.0 mm,). Conclusion: The menopausal period caused an increase in the need for treatment in patients followed up with HF. Therefore, in evaluation of the patients with HF, it would be a useful approach to question the menopausal status in detail and to follow the patients more closely during the menopausal transition period. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to compare the anti-HAV IgG and Anti-HAV IgM seropositivity in children aged 0-18 in Erzurum with studies in our country and other countries, and also to evaluate the effect of seasons on hepatitis A infection. Material and Methods: The study was conducted on the serum samples of 5086 patients aged 0-18 years, who were considered to have Hepatitis A or who applied with different complaints as a result of the examination of family physicians in Erzurum between 2015 and 2018. The results of these patients, obtained from Anti-HAV IgM and Anti-HAV IgG analysis by ELISA method in the Public Health Microbiology Laboratory, were evaluated retrospectively. Pearson chi-square test was used to analyze the categorical data such as gender, age and seasonal differences in anti-HAV IgM and Anti-HAV IgG positivity rates and p <0.05 was considered significant. Results: Anti-HAV IgG seropositivity was 69.0% (3510/5086) and Anti-HAV IgM positivity was 0.7% (33/5063). Anti-HAV IgM was positive in 1.1% of girls and 0.1% of boys. Anti-HAV IgG positivity was 89.9%, 83.3%, 62.5% 61.9% and 74.5% in the 0-3 age group, 4-7 age group, 8-11 age group, 12-15 age group and 16-18 age groups, respectively. Anti-HAV IgM positivity was 0, 0.2%, 0.2%, 1.0%, 0.9% in the 0-3 age group, 4-7 age group, 8-11 age group, 12-15 age group and 16-18 age groups, respectively. The highest anti-HAV IgM positivity was found in November (1.7%). Conclusion: Total anti-HAV IgG seropositivity rate in our province showed many similarities with studies in Turkey and developing countries. The prevalence of anti-HAV IgM was the highest in November. [ABSTRACT FROM AUTHOR]

The PI3K signaling cascade in APCs has been recognized as an essential pathway to initiate, maintain, and resolve immune responses. In this study, we demonstrate that a cell type-specific loss of the PI3K antagonist phosphatase and tensin homolog (PTEN) in myeloid cells renders APCs toward a regulatory phenotype. APCs deficient for PTEN exhibit reduced activation of p38 MAPK and reduced expression of T cell-polarizing cytokines. Furthermore, PTEN deficiency leads to upregulation of markers for alternative activation, such as Arginase 1, with concomitant downregulation of inducible NO synthase in APCs in vitro and in vivo. As a result, T cell polarization was dysfunctional in PTEN-/- APCs, in particular affecting the Th17 cell subset. Intriguingly, mice with cell type-specific deletions of PTEN-targeting APCs were protected from experimental autoimmune encephalomyelitis, which was accompanied by a pronounced reduction of IL-17- and IL-22-producing autoreactive T cells and reduced CNS influx of classically activated monocytes/macrophages. These observations support the notion that activation of the PI3K signaling cascade promotes regulatory APC properties and suppresses pathogenic T cell polarization, thereby reducing the clinical symptoms and pathology of experimental autoimmune encephalomyelitis. [ABSTRACT FROM AUTHOR]

The activation of innate immune cells triggers numerous intracellular signaling pathways, which require tight control to mount an adequate immune response. The PI3K signaling pathway is intricately involved in innate immunity, and its activation dampens the expression and release of proinflammatory cytokines in myeloid cells. These signaling processes are strictly regulated by the PI3K antagonist, the lipid phosphatase, PTEN, a known tumor suppressor. Importantly, PTEN is responsible for the elevated production of cytokines such as IL-6 in response to TLR agonists, and deletion of PTEN results in diminished inflammatory responses. However, the mechanisms by which PI3K negatively regulates TLR signaling are only partially resolved. We observed that Arginase I expression and secretion were markedly induced by PTEN deletion, suggesting PTEN 7' macrophages were alternatively activated. This was mediated by increased expression and activation of the transcription factors C/EBPβ and STAT3. Genetic and pharmacologic experimental approaches in vitro, as well as in vivo autoimmunity models, provide convincing evidence that PI3K/ PTEN-regulated extracellular Arginase .1 acts as a paracrine regulator of inflammation and immunity. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine the relationship between pelvic floor functions and sexual functions in women with fibromyalgia. The study included 204 women with fibromyalgia, mean aged 43.43 ± 8.61 years. All patients who met the inclusion criteria and applied to the rheumatology outpatient clinic were included in the study. The study was conducted between September 2020 and June 2022. The Female Sexual Function Scale (FSFI) was used to evaluate sexual function, Pelvic Floor Distress Scale-20 (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7) and Pelvic Organ Prolapse/Incontinence Sexual Function Assessment (PSIQ-12) were used to evaluate pelvic floor problems. The relationship between sexual dysfunction and other parameters was analyzed using Spearman correlation analysis. There was a weak negative correlation between many sub-parameters of FSFI and scores of PFDI-20, PFIQ-7, PSIQ-12 (r:−0.165–−0.377 p: 0.02–0.00). According to the results of this study, sexual dysfunction was negatively affected by pelvic floor dysfunction and symptoms related to bladder, bowel, and pelvic organs in women with fibromyalgia. These results may suggest that sexual function and pelvic floor problems in women with fibromyalgia should be considered together and an approach should be planned for such problems in treatment programs. [ABSTRACT FROM AUTHOR]

Abstract: Crude enzyme extracts were prepared from Armillaria mellea (A. mellea), Lepista nuda (L. nuda) and Hypholoma fasciculare (H. fasciculare), which were harvested from the Lişer High Plateau-Maçka (Trabzon, Turkey). The crude polyphenol oxidase (PPO) extracts from each mushroom were highly active against 4-methylcatechol. Native polyacrylamide gel electrophoresis, stained by L-3,4-dihydroxyphenylalanine, showed the polyphenol oxidase potentials. The optimum pH value, for each enzyme, was 7.0. When enzyme extracts were incubated at pH 7.0 for 24h at 4°C, it was observed that L. nuda and H. fasciculare enzyme activities decreased by about 26% and 18%, respectively, but, A. mellea enzyme activity increased by about 11%. The temperature optima of A. mellea, L. nuda and H. fasciculare were, respectively, 30, 30 and 20°C. Cr3+ and Cu2+ ions inhibited each activity. Also, sodium metabisulphite and ascorbic acid were strong inhibitors of the enzyme activities. [Copyright &y& Elsevier]

Multiple sclerosis (MS) is the most common autoimmune disease affecting the central nervous system. It is characterized by autoreactive T cells that induce demyelination and neuronal degradation. Treatment options are still limited and several MS medications need to be administered by parenteral application but are modestly effective. Oral active drugs such as fingolimod have been weighed down by safety concerns. Consequently, there is a demand for novel, especially orally active therapeutics. Nature offers an abundance of compounds for drug discovery. Recently, the circular plant peptide kalata B1 was shown to silence T-cell proliferation in vitro in an IL-2-dependent mechanism. Owing to this promising effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1 using the MS mouse model experimental autoimmune encephalomyelitis (EAE). Treatment of mice with the cyclotide resulted in a significant delay and diminished symptoms of EAE by oral administration. Cyclotide application substantially impeded disease progression and did not exhibit adverse effects. Inhibition of lymphocyte proliferation and the reduction of proinflammatory cytokines, in particular IL-2, distinguish the cyclotide from other marketed drugs. Considering their stable structural topology and oral activity, cyclotides are candidates as peptide therapeutics for pharmaceutical drug development for treatment of T-cell-mediated disorders. [ABSTRACT FROM AUTHOR]

Background: Over the past 15 years, 300 out of 6000 breeds of all farm animal species identified by the Food and Agriculture Organization of the United Nations (FAO) have gone extinct. Among cattle, many Podolian breeds are seriously endangered in various European areas. Podolian cattle include a group of very ancient European breeds, phenotypically close to the aurochs ancestors (Bos primigenius). The aim of the present study was to assess the genetic diversity of Podolian breeds and to reconstruct their origin. Methodology: The mitochondrial DNA (mtDNA) control-regions of 18 Podolian breeds have been phylogenetically assessed. Nine non-Podolian breeds have been also included for comparison. Conclusion: The overall analysis clearly highlights some peculiarities in the mtDNA gene pool of some Podolian breeds. In particular, a principal component analysis point to a genetic proximity between five breeds (Chianina, Marchigiana, Maremmana, Podolica Italiana and Romagnola) reared in Central Italy and the Turkish Grey. We here propose the suggestive hypothesis of a dual ancestral contribution to the present gene pool of Podolian breeds, one deriving from Eastern European cattle; the other arising from the arrival of Middle Eastern cattle into Central Italy through a different route, perhaps by sea, ferried by Etruscan boats. The historical migration of Podolian cattle from North Eastern Europe towards Italy has not cancelled the mtDNA footprints of this previous ancient migration. [ABSTRACT FROM AUTHOR]

Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo . Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation. In addition, loss of miR-146a shifts the metabolic state of fibroblasts towards glycolysis and augments the ability of synovial fibroblasts to support the generation of osteoclasts by controlling the balance of osteoclastogenic regulatory factors receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). Bone marrow transplantation experiments confirmed the importance of miR-146a in the radioresistant mesenchymal compartment for the control of arthritis severity, in particular for inflammatory joint destruction. This study therefore identifies microRNA-146a as an important local epigenetic regulator of the inflammatory response in arthritis. It is a central element of an anti-inflammatory feedback loop in resident synovial fibroblasts, who are orchestrating the inflammatory response in chronic arthritis. MiR-146a restricts their activation, thereby preventing excessive tissue damage during arthritis. [ABSTRACT FROM AUTHOR]

Background & Aims Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects of 24- nor -ursodeoxycholic acid ( nor UDCA) in Abcb4/Mdr2 −/− mice with cholestatic liver injury and biliary fibrosis, we hypothesized that nor UDCA improves inflammation-driven liver fibrosis in S. mansoni infection. Methods Adult NMRI mice were infected with 50 S. mansoni cercariae and after 12 weeks received either nor UDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4 weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of nor UDCA on primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro . Results UDCA as well as nor UDCA attenuated the inflammatory response in livers of S. mansoni infected mice, but exclusively nor UDCA changed cellular composition and reduced size of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo . Moreover, nor UDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro , whereas UDCA had no effect. Conclusions This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of nor UDCA compared to UDCA in S. mansoni induced liver injury, and indicates that nor UDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro . Therefore, nor UDCA represents a promising drug for the treatment of this important cause of liver fibrosis. [ABSTRACT FROM AUTHOR]

Sepsis still remains a major cause for morbidity and mortality in patients. The molecular mechanisms underlying the disease are still enigmatic. A great number of therapeutic approaches have failed and treatment strategies are limited to date. Among those few admitted for clinical intervention, intensive insulin treatment has proven to be effective in the reduction of disease related complications in critically ill patients. Insulin effectively reduces glucose levels and thereby contributes to protection. On the other hand insulin is a potent signaling pathway activator. One of those is the PI3K signaling axis. Activation of PI3K is known to limit pro-inflammatory gene expression. Here we can show that in a mouse model of insulin hypersensitivity induced by the deletion of the PI3K antagonist PTEN, specifically in hepatic tissue, significant protection is conferred in murine models of lethal endotoxemia and sepsis. Acute inflammatory responses are diminished, glucose metabolism normalized and vascular activation is reduced. Furthermore we investigated the hepatic gene expression profile of relevant anti-inflammatory genes in PTEN deficient mice and found marked upregulation of PPARγ and HO-1. We conclude from our data that insulin hypersensitivity via sustained activation of the PI3K signaling pathway exerts protective effects in acute inflammatory processes. [ABSTRACT FROM AUTHOR]