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The popularity of esthetic medicine is growing every year, also among patients with autoimmune inflammatory rheumatic diseases (AIRD). The objective of this study was to evaluate the safety of esthetic medicine (AM) procedures in patients with AIRD. A semi-structured, anonymous questionnaire regarding rheumatic and concomitant diseases and AM procedures was distributed among adult patients hospitalized in the rheumatology department or attending outpatient clinic in the National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw. The main outcome was the occurrence of an adverse event. A number of 512 patients took part in the survey and 15 were excluded (AM procedure preceded the diagnosis of AIRD). The study group consisted of 497 patients, of whom 47 had undergone AM procedures. The procedures performed included: tattooing (22 patients), piercing (16 patients), hyaluronic acid (7 patients), botulinum toxin (5 patients) injections, laser procedures (6 patients), plastic surgery (4 patients), mesotherapy (3 patients) and others. The vast majority of patients had these performed during remission or low disease activity. 70.2% of patients received treatment with disease-modifying antirheumatic drugs (DMARDs) during the AM procedure, with TNF-alfa inhibitors being the most common (63.6%). Adverse events occurred in 15% of patients. All were mild and transient site reactions. Most patients would like to repeat the AM procedure in the future. The use of esthetic medicine procedures in patients with AIRD, including those treated with biologic DMARDs, was associated with a risk of mild site reactions. Most of the patients expressed satisfaction with the results of the AM procedure.
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Antirreumáticos , Doenças Reumáticas , Adulto , Humanos , Antirreumáticos/efeitos adversos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inquéritos e Questionários , Doenças Reumáticas/tratamento farmacológicoRESUMO
OBJECTIVES: SMADs play one of the key roles in the TGFß signalling pathway. Therefore, through their involvement in the immune response as well as in the fibrosis process, these proteins appear to take on one of the essential functions in the pathogenesis of autoimmune connective tissue diseases such as RA. This study aimed to investigate the association of selected SNPs in SMAD2/4/7 with RA risk in the Caucasian population and disease course in RA patients. METHODS: The study was conducted on 647 patients with established RA and 496 unrelated healthy controls (HCs). All patients fulfilled the American College of Rheumatology Diagnostic classification criteria for RA (ACR 1987). The analysis has been conducted using TaqMan genotyping assay. Transcript-inferred pathogenicity score (TraP-score) has been evaluated by TrapScore. PredictSNP.2 has been used to predict the effect of amino acid substitutions. RESULTS: The present study revealed in SMAD4 a significantly higher frequency of AG rs12456284 (under codominant model OR=0.62 p=0.027 and overdominant model OR=0.59 p=0.016) and GA rs10502913 (under codominant model OR=0.65 p=0.050 and overdominant OR=0.64 p=0.033) genotypes in healthy subjects in comparison to RA patients. Additionally, very strong LD has been noted between these two genetic variants (D'=0.95 r2=0.90). Moreover, bioinformatic analysis classified rs12456284 as deleterious change with 94% prediction accuracy. SMAD2 rs1792666 and SMAD7 rs3736242 showed to have the highest association with disease course. SMAD4 rs10502913, SMAD7 rs3736242, and SMAD7 rs4464148 were associated with the concentration of creatinine. CONCLUSIONS: Our results suggested that rs12456284 and rs10502913 in SMAD4 may have a potential protective effect against RA. Particularly, SMAD2 rs1792666 and SMAD7 rs3736242 seem to be significantly associated with diseases course in RA patients in the Caucasian population.
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Artrite Reumatoide , Doenças Autoimunes , Proteína Smad2 , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Progressão da Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Proteína Smad2/genética , Proteína Smad4/genética , Proteína Smad7/genéticaRESUMO
Aging is a biological event that influences many organs and systems. Both sarcopenia and frailty syndrome refer to geriatric conditions with overlapping phenotypes. Many mechanisms are involved in the aging process such as DNA methylation telomeres which are susceptible to oxidative stress, and inflammations which result in telomere shortening, leading to chromosomal instability. The study aimed to determine the associations between these processes, frailty and sarcopenia syndrome. Global DNA methylation was analyzed using the ELISA method. Telomere length was analyzed using qPCR. Total oxidative status (TOS) was analyzed using a colorimetric method. The present study revealed that the main factor affecting methylation, telomeres length and level of total oxidant stress was age.
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Mixed connective tissue disease (MCTD) is a very rare disorder that belongs in the rare and clinically multifactorial groups of diseases. The pathogenesis of MCTD is still unclear. The best understood epigenetic alteration is DNA methylation whose role is to regulate gene expression. In the literature, there are ever-increasing assumptions that DNA methylation can be one of the possible reasons for the development of Autoimmune Connective Tissue Diseases (ACTDs) such as systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The aim of this study was to define the global DNA methylation changes between MCTD and other ACTDs patients in whole blood samples. The study included 54 MCTD patients, 43 SSc patients, 45 SLE patients, and 43 healthy donors (HC). The global DNA methylation level was measured by ELISA. Although the global DNA methylation was not significantly different between MCTD and control, we observed that hypomethylation distinguishes the MCTD patients from the SSc and SLE patients. The present analysis revealed a statistically significant difference of global methylation between SLE and MCTD (p < 0.001), SLE and HC (p = 0.008), SSc and MCTD (p ≤ 0.001), and SSc and HC (p < 0.001), but neither between MCTD and HC (p = 0.09) nor SSc and SLE (p = 0.08). The highest % of global methylation (median, IQR) has been observed in the group of patients with SLE [0.73 (0.43, 1.22] and SSc [0,91 (0.59, 1.50)], whereas in the MCTD [0.29 (0.20, 0.54)], patients and healthy subjects [0.51 (0.24, 0.70)] were comparable. In addition, our study provided evidence of different levels of global DNA methylation between the SSc subtypes (p = 0.01). Our study showed that patients with limited SSc had a significantly higher global methylation level when compared to diffuse SSc. Our data has shown that the level of global DNA methylation may not be a good diagnostic marker to distinguish MCTD from other ACTDs. Our research provides the groundwork for a more detailed examination of the significance of global DNA methylation as a distinguishing factor in patients with MCTD compared to other ACTDs patients.
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Doenças Autoimunes , Doenças do Tecido Conjuntivo , Lúpus Eritematoso Sistêmico , Doença Mista do Tecido Conjuntivo , Escleroderma Sistêmico , Humanos , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/genética , Doenças Autoimunes/genética , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/genética , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/genética , Metilação de DNARESUMO
Prostaglandin signaling pathways are closely related to inflammation, but also muscle regeneration and processes associated with frailty and sarcopenia, whereas ß-catenin (CTNNB1 gene) as a part of Wnt signaling is also involved in the differentiation of muscle cells and fibrosis. The present study analyzed the association between selected prostaglandin pathway genes and clinical parameters in patients with sarcopenia and frailty syndrome. The present study was conducted on patients with sarcopenia, frailty syndrome, and control older patients (N = 25). Additionally, two healthy controls at the age of 25-30 years (N = 51) and above 50 years old (N = 42) were included. The expression of the PTRGER4, PTGES2 (COX2), PTGS2, and CTNNB1 genes in whole blood was checked by the qPCR method. The serum cytokine levels (IL-10, TNFα, IFN-y, IL-1α, IL-1ß) in patients and controls were checked by the Q-Plex Human Cytokine Panel. The results showed a significant effect of age on PTGER4 gene expression (p = 0.01). A negative trend between the appendicular skeletal muscle mass parameter (ASSM) and the expression of PTGER4 has been noted (r = -0.224, p = 0.484). PTGES2 and PTGS2 expressions negatively correlated with creatine phosphokinase (r = -0.71, p = 0.009; r = -0.58, p = 0.047) and positively with the functional mobility test timed up and go scale (TUG) (r = 0.61, p = 0.04; r = 0.63, p = 0.032). In the older control group, a negative association between iron levels and the expression of PTGS2 (r = -0.47, p = 0.017) was observed. A similar tendency was noted in patients with sarcopenia (r = -0.112, p = 0.729). A negative trend between appendicular skeletal muscle mass (ASMM) and PTGER4 seems to confirm the impairment of muscle regeneration associated with sarcopenia. The expression of the studied genes revealed a trend in associations with the clinical picture of muscular dystrophy and weakening patients. Perhaps PTGS2 and PTGES2 is in opposition to the role of the PTGER4 receptor in muscle physiology. Nevertheless, further, including functional studies is needed.
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Fragilidade , Sarcopenia , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Sarcopenia/genética , beta Catenina/genética , Ciclo-Oxigenase 2/genética , Idoso Fragilizado , Citocinas , MúsculosRESUMO
Circulating free-cell miRNAs are increasingly important as potential non-invasive biomarkers due to the easy accessibility of clinical materials. Moreover, their epigenetic role may provide insight into the mechanisms of pathogenesis. Nevertheless, these aspects are mostly studied in the area of oncological diseases. Therefore, this research aimed to find the potential association of selected miRNAs in serum with the expression of Th17/Treg transcription factors and clinical features in RA patients. Accordingly, experiments was conducted on rheumatoid arthritis (RA), osteoarthritis (OA) and healthy subjects (HC). Analysis of miRNAs level in serum was performed using LNA miRNA PCR assays. mir-10 was detected only in RA patients. Furthermore, its expression was correlated with IL-35 serum concentration and the mRNA level of STAT5a in whole blood in RA. Additionally, a tendency of the raised level of miR-10 was noted in RA patients with high activity disease. miR-326 was significantly upregulated in RA patients with rheumatoid factor presence. In HC the correlation between miR-26 and IL-21 serum levels and expression of SMAD3 have been found. In OA patients, correlations between miR-126 and HIF1 expression and between miR-146 and RORc have been noted. The differential association of transcription factor expression with serum miRNA levels may be important in the diagnosis and progression of RA and OA.
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Artrite Reumatoide , MicroRNAs , Osteoartrite , Humanos , MicroRNAs/metabolismo , Osteoartrite/diagnóstico , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
Background and aims: Systemic sclerosis (SSc) is an autoimmune, rare multisystem chronic disease that is still not well-understood aetiologically and is challenging diagnostically. In the literature, there are ever-increasing assumptions regarding the epigenetic mechanisms involved in SSc development; one of them is circulating microRNAs. Many of them regulate TLR pathways and are significant in autoimmune balance. The aim of this study was to determine profile expression of selected microRNAs in SSc patients, including miR-126, -132, -143, -145, -155, -181a, -29a and -3148, in comparison to healthy controls. Methods: Serum microRNAs were isolated from 45 patients with SSc and 57 healthy donors (HC). Additionally, SSc patients were considered in the aspect of disease subtype, including diffuse systemic sclerosis (dcSSc) and limited systemic sclerosis (lcSSc). Results: miR-3148 was detected neither in the serum of HC nor in SSc patients. All of the rest of the analyzed microRNAs, excluding miR-126, miR-29a and miR-181a, were significantly upregulated in SSc patients in comparison to HC. However, miR-181a has been revealed only in the serum of patients with lcSSc but not dcSSc. Moderate positive correlations between the transfer factor of the lung for carbon monoxide (TLCO) and miR-126 and miR-145 were observed. A significant correlation has been found between serum miR-143 level and forced vital capacity (FVC). SSc patients with FVC ≤ 70% were characterized by significantly lower levels of miR-143 compared to patients with normal FVC. Additionally, the expression of miR-132 was significantly higher in dcSSc subgroup with detected active lung lesions compared to dcSSc patients with fibrotic lesions. Patients with an early scleroderma pattern of microangiopathy seen on nailfold video-capillaroscopy (NVC) revealed higher expression of miR-155 in serum than those with a late pattern. Conclusions: The expression profile of circulating cell-free miRNAs is significantly changed in the serum of SSc patients compared to healthy individuals. Downregulation of miRNA-181a and overexpression of miR-132, miR-143, miR-145 and miR-155 in serum may be significant in SSc in the context of biomarkers.
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MicroRNAs , Esclerodermia Difusa , Escleroderma Sistêmico , Doenças Vasculares , Biomarcadores , Monóxido de Carbono , Humanos , Pulmão/metabolismo , MicroRNAs/genética , Fator de TransferênciaRESUMO
Methotrexate (MTX) is the first-line therapy for rheumatoid arthritis. Nevertheless, MTX resistance is quite a common issue in clinical practice. There are some premises that aryl hydrocarbon receptor (AhR) gene battery may take part in MTX metabolism. In the present retrospective study, we analyzed genes expression of AHR genes battery associated with MTX metabolism in whole blood of RA patients with good and poor response to MTX treatment. Additionally, sequencing, genotyping and bioinformatics analysis of AHR repressor gene (AHRR) c.565C > G (rs2292596) and c.1933G > C (rs34453673) have been performed. Theoretically, both changes may have an impact on H3K36me3 and H3K27me3. Evolutionary analysis revealed that rs2292596 may be possibly damaging. Allele G in rs2292596 and DAS28 seems to be associated with a higher risk of poor response to MTX treatment in RA. RA patients with poor response to MTX treatment revealed upregulated AhR and SLC19A1 mRNA level. Treatment with IL-6 inhibitor may be helpful to overcome the low-dose MTX resistance. Analysis of gene expression revealed possible another cause of poor response to MTX treatment which is different from that observed in the case of acute lymphoblastic leukemia.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Receptores de Hidrocarboneto Arílico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Artrite Reumatoide/genética , Resistência a Medicamentos/genética , Feminino , Genes/genética , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Proteína Carregadora de Folato Reduzido/genética , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Tissue factor (TF) and Human apolipoprotein H (APOH) seem to be significantly associated with a clinical manifestation in systemic lupus erythematosus (SLE) patients with or without APS, mostly because of thrombotic events and coagulation processes. Additionally, according to recent studies, these two factors appear to be an important part of immune response and inflammation. METHODS: The objective of this study was to investigate three SNPs of APOH (rs4581, rs8178835 and rs818819) and three of TF (rs958587, rs3917615, rs1361600) in SLE patients and healthy subjects using TaqMan genotyping assay and their association with inflammatory cytokines level in serum and selected clinical parameters. RESULTS: Present study revealed that TF rs3917615 and rs958587 and APOH rs4581 possibly predispose to joint involvement in SLE. CONCLUSIONS: Analysed genetic variants of TF and APOH may have an impact on inflammatory processes and clinical relevance in SLE patients in the Caucasian population.
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Lúpus Eritematoso Sistêmico , Tromboplastina , beta 2-Glicoproteína I/genética , Estudos de Casos e Controles , Citocinas/genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Tromboplastina/genéticaRESUMO
Environmental factors contribute to autoimmune disease manifestation, and as regarded today, AhR has become an important factor in studies of immunomodulation. Besides immunological aspects, AhR also plays a role in pharmacological, toxicological and many other physiological processes such as adaptive metabolism. In recent years, epigenetic mechanisms have provided new insight into gene regulation and reveal a new contribution to autoimmune disease pathogenesis. DNA methylation, histone modifications, chromatin alterations, microRNA and consequently non-genetic changes in phenotypes connect with environmental factors. Increasing data reveals AhR cross-roads with the most significant in immunology pathways. Although study on epigenetic modulations in autoimmune diseases is still not well understood, therefore future research will help us understand their pathophysiology and help to find new therapeutic strategies. Present literature review sheds the light on the common ground between remodeling chromatin compounds and autoimmune antibodies used in diagnostics. In the proposed review we summarize recent findings that describe epigenetic factors which regulate AhR activity and impact diverse immunological responses and pathological changes.
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Doenças Autoimunes/patologia , Autoimunidade/imunologia , Metilação de DNA , Epigênese Genética , Regulação da Expressão Gênica , Imunomodulação , Receptores de Hidrocarboneto Arílico/genética , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Humanos , Receptores de Hidrocarboneto Arílico/metabolismoRESUMO
MicroRNAs regulate gene expression of transcriptional factors, which influence Th17/Treg (regulatory T cells) balance, establishing the molecular mechanism of genetic and epigenetic regulation of Treg and Th17 cells is crucial for understanding rheumatoid arthritis (RA) pathogenesis. The study goal was to understand the potential impact of the selected microRNAs expression profiles on Treg/Th17 cells frequency, RA phenotype, the expression profile of selected microRNAs, and their correlation with the expression profiles of selected transcriptional factors: SOCS1, SMAD3, SMAD4, STAT3, STAT5 in RA; we used osteoarthritis (OA) and healthy controls (HCs) as controls. The study was conducted on 14 RA and 11 OA patients, and 15 HCs. Treg/Th17 frequency was established by flow cytometry. Gene expression analysis was estimated by qPCR. We noticed correlations in RA Th17 cells between miR-26 and SMAD3, STAT3, SOCS1; and miR-155 and STAT3-and in RA Treg cells between miR-26 and SOCS1; miR-31, -155 and SMAD3; and miR-155 and SMAD4. In RA Tregs, we found a negative correlation between miR-26, -126 and STAT5a. The expression level of miR-31 in Th17 cells from RA patients with DAS28 ≤ 5.1 is higher and that for miR-24 is greater in Tregs from patients with DAS28 > 5.1. MiR-146a in Tregs is higher in rheumatoid factor (RF) positive RA patients.
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Artrite Reumatoide/genética , MicroRNAs/genética , Osteoartrite/genética , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , MicroRNAs/imunologia , Pessoa de Meia-Idade , Osteoartrite/imunologia , Osteoartrite/patologia , Fenótipo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/imunologia , Índice de Gravidade de Doença , Proteína Smad3/genética , Proteína Smad3/imunologia , Proteína Smad4/genética , Proteína Smad4/imunologia , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/imunologia , Linfócitos T Reguladores/patologia , Células Th17/patologiaRESUMO
Systemic sclerosis (SSc) is a rare autoimmune disorder with a high mortality rate. There are still many unknowns concerning the pathophysiology of this disease, due to its clinical heterogeneity. Since there is still no curative treatment, researchers focus on finding novel methods to help the patients. One of the valid options is cellular therapy, and mesenchymal stem cells (MSCs)-based therapy yields great expectations. These cells possess especially valuable attributes regarding key points of SSc. Nevertheless, the effectiveness and safety of this therapy must undergo a rigorous process of verification. In preclinical trials, animal models proved to be a valuable source of scientific knowledge regarding SSc. Because of that, it has been possible to test autologous or allogeneic MSCs from various sources in many clinical trials. A lot of aspects still have to be determined to assess their potential in the management of SSc, probably in association with other therapies.
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OBJECTIVES: U1-70K, encoded by the SNRNP70 gene, is a key early immunogen in connective tissue disease. The aim of the study was the genetic analysis of the SNRNP70 gene in mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) patients. METHODS: SNRNP70 genetic variants were detected using 3730 DNA Analyzer. SNRNP70 rs560811128 G/A (c.476-252 G/A), rs78616533delCT (c.475+130_475+131delCT) and rs117167710 T/C (c.393+326 T/C) variants were genotyped using the technique of sequence-specific hybridisation probe binding assays. SNRNP70 393_47 G/A mutation was detected using TaqMan SNP genotyping assay. RESULTS: We found one novel c.393+47G>A and three, c.476-252 G/A, c.475+130_475+131delCT and c.393+326 T/C, previously recorded variants. The present study revealed that T-G-CT-G haplotype demonstrated significantly higher frequencies in MCTD patients than in SLE and SSc patients. In MCTD patients c.475+130_475+131delCT distribution of genotype was gender-dependent and showed association with thrombo-/leukocytopenia. Mutation at position c.476-252G>A was predicted to possibly have an impact on splicing of the SNRNP70 transcript and it was present only in one MCTD patient. CONCLUSIONS: Our results demonstrated that the T-G-CT-G SNRNP70 haplotype is another proof that MCTD may be distinct from SLE and SSc. The novel c.476-252G>A mutation in SNRNP70 gene created a new acceptor splice site and may potentially alert of splicing of the SNRNP70 transcript.
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Lúpus Eritematoso Sistêmico , Doença Mista do Tecido Conjuntivo , Ribonucleoproteína Nuclear Pequena U1 , Escleroderma Sistêmico , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Lúpus Eritematoso Sistêmico/genética , Doença Mista do Tecido Conjuntivo/genética , Ribonucleoproteína Nuclear Pequena U1/genética , Ribonucleoproteína Nuclear Pequena U1/imunologia , Escleroderma Sistêmico/genética , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: The aim of the study was to explore whether TGF-ß and IL-6 gene polymorphisms may be associated with SLE and assess the frequency of HLA-DRB1 alleles in Polish systemic lupus erythematosus (SLE) patients. METHODS: 216 SLE patients and 552 healthy individuals were examined for TGF-ß rs1800469 and rs1800470 by TaqMan SNP genotyping assay and for and IL-6(rs2069827 and rs1800795 using the PCR- RFLP method. RESULTS: An increased frequency of TT genotype and T allele of the TGF ß -509 C/T was found in SLE patients (p=0.02). The TGF-ß 869 C allele was more frequent in SLE patients. The genotype-phenotype analysis showed association between the TGF ß -509 C/T and mean value of CRP, ESR, haemoglobin, APTT, Pt and INR (p=0.05, p=0.03, p<0.001, p=0.03, p=0.03 and p=0.05, respectively) as well as anti-SSA and anti-Sm presence (p=0.04 and p=0.03, respectively); the TGF- ß 869 T/C and mean value of APTT and INR (p=0.01 and p=0.05, respectively); the IL-6 -174 G/C and SLICC (p=0.05), anti-SSA (p=0.05) and anti-SSB (p=0.05). A higher TGF-ß and IL-6 serum level were found in SLE patients compared to controls (both p<0.0001). In SLE patients with the TGF-ß -509 TT genotype have shown positive association with the TGF-ß serum levels. Polish SLE patients have strong positive association with HLA-DRB1*52.1, and negative with the HLA-DRB1*07:01 allele. HLA-DRB1*52.1 was also associated with higher TGF-ß serum levels in the Polish population. CONCLUSIONS: Our results suggested that the TGF ß -509 C/T variant may be considered as a genetic marker for SLE in the Polish population.
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Interleucina-6 , Lúpus Eritematoso Sistêmico , Polimorfismo Genético , Fator de Crescimento Transformador beta , Alelos , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Cadeias HLA-DRB1 , Humanos , Interleucina-6/sangue , Interleucina-6/genética , Lúpus Eritematoso Sistêmico/genética , Polônia , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta/genéticaRESUMO
OBJECTIVES: Inflammatory processes in rheumatic diseases spread via various types of immune system cells and tissues with the aid of inflammatory cytokines and growth factors and the participation of vascular endothelium. Research is still conducted to determine the role of individual factors in the pathophysiology of rheumatic diseases. The task is complicated because the multiplane network of cytokines is characterized by complex correlations manifesting as positive and negative feedback, which impedes the definitive interpretation of the role of specific cytokines. Therefore, it seems justified to perform a comparative analysis of the expression of at least several molecules in one study, which may help reveal their role in the pathogenesis of rheumatic diseases and have prognostic value. MATERIAL AND METHODS: The aim of the study involves the assessment and comparative analysis of the concentrations of interleukin 35 (IL-35), tumour necrosis factor α (TNF-α), B-cell-activating factor (BAFF), and vascular endothelial growth factor (VEGF) in peripheral blood serum in patients with rheumatoid arthritis (RA) (n = 43), systemic lupus erythematosus (SLE) (n = 28), antiphospholipid syndrome (APS) (n = 24), and mixed connective tissue disease (MCTD) (n = 9). The main intention is to search for biomarkers for specific rheumatic diseases. Cytokine and growth factor levels were determined using specific ELISA kits. RESULTS: Statistically significant differences in VEGF and IL-35 concentrations occurred between patients with APS vs. RA and SLE vs. RA. There was a significant high positive correlation between the concentration of BAFF and TNF-α (r = 0.77, p < 0.0000) in patients with APS, as well as in patients with SLE (r = 0.55, p = 0.00). CONCLUSIONS: BAFF and TNF-α may be promising biomarkers in patients with APS and VEGF in patients with RA. Additionally, IL-35 may be a useful marker for the diagnosis of APS. Positive correlation of BAFF and TNF-α concentrations in APS and SLE potentially indicates much more similar etiopathogenesis of these diseases than it could be previously predicted.
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Introduction: The aim of our study was to assess the values of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides before and after treatment with metformin in lean patients with polycystic ovary syndrome (PCOS). Material and Methods: 32 patients received metformin 1500 mg per day in three divided doses. Lipids measurements were performed twice: before and after 6 months of treatment with metformin. Results: In lean patients with PCOS after treatment with metformin we observed: statistically significant lower LDL-C levels (4.16±0.79 mmol/l vs 3.4±0.86 mmol/l, p<0.05) and triglycerides levels (1.8±0.53 mmol/l vs 1.12±0.64 mmol/l, p<0.05). We observed an increase in HDL values and a decrease in total cholesterol values, but these changes were not statistically significant (1.5±0.71 mmol/l vs 1.71±0.69 mmol/l, p=0.09; 5.87±0.92 mmol/l vs 5.69±0.97 mmol/l, p=0.11). Conclusion: Our study showed that treatment of 1500 mg metformin for about six months among PCOS women results in an improvement in serum lipid profiles. We observed a significant decrease in LDL-C and triglycerides values after metformin therapy.
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Lipídeos/sangue , Metformina/uso terapêutico , Síndrome do Ovário Policístico/sangue , Adulto , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Feminino , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Estudos Retrospectivos , Triglicerídeos/sangueRESUMO
Spermatogenesis is a process where an important contribution of genes involved in folate-mediated one-carbon metabolism is observed. The aim of the present study was to investigate the association between male infertility and the MTHFR (677C > T; 1298A > C), MTR (2756A > G) and MTRR (66A > G) polymorphisms in a Polish population. No significant differences in genotype or allele frequencies were detected between the groups of 284 infertile men and of 352 fertile controls. These results demonstrate that common polymorphisms in folate pathway genes are not major risk factors for non-obstructive male infertility in the Polish population.
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In this paper, we study synthesis and characteristics of mesoporous silica nanotubes modified by titanium dioxide, as well as their antimicrobial properties and influence on mitochondrial activity of mouse fibroblast L929. Nanocrystalized titania is confined in mesopores of silica nanotubes and its light activated antibacterial response is revealed. The analysis of the antibacterial effect on Escherichia coli. (ATCC 25922) shows strong enhancement during irradiation with the artificial visible and ultraviolet light in respect to the commercial catalyst and control sample free from the nanomaterials. In darkness, the mesoporous silica/titania nanostructures exhibited antibacterial activity dependent on the stirring speed of the suspension containing nanomaterials. Obtained micrograph proved internalization of the sample into the microorganism trough the cell membrane. The analysis of the mitochondrial activity and amount of lactate dehydrogenase released from mouse fibroblast cells L929 in the presence of the sample were determined with LDH and WST1 assays, respectively. The synthesized silica/titania antibacterial agent also exhibits pronounced photoinduced inactivation of the bacterial growth under the artificial visible and UV light irritation in respect to the commercial catalyst. Additionally, mesoporous silica/titania nanotubes were characterized in details by means of high resolution transmission electron microscopy (HR-TEM), XRD and BET Isotherm.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Nanopartículas/química , Nanotubos/química , Dióxido de Silício/química , Titânio/química , Titânio/farmacologia , Animais , Antibacterianos/toxicidade , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Camundongos , Processos Fotoquímicos , Porosidade , Titânio/toxicidadeRESUMO
Nuclear receptors and transcription factors regulate the functions of many genes involved in cellular physiology and pathology (e.g. tumorigenesis and autoimmune diseases). The present study was performed to define the expression and the regulation of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), and nuclear factor E2-related factor 2 (Nrf2) in the rat parotid gland. Constitutive expression, as well as expression after stimulation with specific inducers for AhR [2,3,7,8-tetrachloro-dibenzylo-p-dioxin (TCDD)], Nrf2(oltipraz), PXR (dexamethasone), and CAR (phenobarbital), was evaluated using the quantitative PCR. Cellular localization of the nuclear receptors and the transcription factor was visualized by immunohistochemical staining. The study revealed constitutive expression of AhR as well as Nrf2, and their induction by TCDD andoltipraz, respectively. Immunohistochemical analysis revealed constitutive, predominantly cytoplasmic, expression of the AhR receptor, especially in interlobular striated duct cells, with nuclear shift upon exposure to TCDD. Inducible expression of Nfr2 was found mainly in the cytoplasm of intralobular striated duct cells. Constitutive expression of PXR and CAR was not found. Bearing in mind the involvement of AhR and Nrf2 in the regulation of many genes, it seems that these factors may play also a role in salivary gland physiology and pathology.