Transforming Growth Factor-β1 Gene Research Articles

Роль генетических факторов в развитии гнойно-септических осложнений в акушерстве

The purpose to study the role of polymorphisms of endothelial nitric oxide synthase (eNOS3 G894T), transforming growth factor beta TGF-β (CA rs1800470) and plasminogen activator inhibitor (SERPINE-1 5G (-675)4G) in full-term pregnant women in the development of purulent-septic complications after cesarean section in the lower uterine segment. Material and methods. The authors analyzed obstetric complications after cesarean section in the lower uterine segment. Prospectively, 81 maternity patients after single-fetus delivery by caesarean section in the lower uterine segment were monitored and treated for emergency indications in order to diagnose purulent-septic complications and perform genetic analysis. The Statistica 10.0 and Eviews 12.0 software packages were used for statistical processing of the obtained results. Results. A direct correlation was established between the presence of a homozygous mutation of the transforming growth factor-β1 gene (TGF-β (CA rs1800470)), as well as the presence of a homozygous mutation of the endothelial nitric oxide synthase eNOS3 (G894T) gene, with significant risk factors for purulent-septic complications after cesarean section in full-term pregnancy: obesity 3-grade II (rs = 0.467, p < 0.001; rs = 0.461, p = 0.005) and pathological overall weight gain during pregnancy (rs = 0.660, p < 0.001; rs = 0.385, p = 0.024). Conclusion. The genetic study data allow concluding that homozygous polymorphisms of the studied genes of transforming growth factor-β1 (TGF-β (CA rs1800470)) and endothelial nitric oxide synthase eNOS3 (G894T) are associated both with the presence of purulent-septic diseases in the postpartum period after cesarean section in the lower uterine segment, and with metabolic disorders such as obesity of the 3rd degree and pathological overall weight gain during pregnancy. It is the combination of these factors that significantly increases the risks of obstetric purulent-septic complications in women with this genotype.

Association between genotyping of transforming growth factor Beta 1 with oxidative status in type 2 diabetic nephropathy Complications

Objectives: To assess the association between Transforming Growth Factor β1 gene polymorphism (T869C) and type 2 diabetes mellitus with and without nephropathy complications with endogenous antioxidant reduced glutathione levels in type 2 diabetic patients with/without nephropathy complications of Kerbala province: Iraq. Methods: A case-control study was performed at which 100 patients with diabetic nephropathy, 100 patients with only type 2 diabetic and another 100 apparently healthy individuals as control were recruited. Fasting blood glucose, HbA1c%, urea, creatinine and glutathione were measured by spectrophotometric methods using enzymatic procedures. Transforming growth factor β1 gene was genotyped for the T>C (T869C) SNP by PCR-ARMS technique. Results: The genotype and allele frequencies of TGFβ1 gene polymorphism in type 2 diabetes mellitus, type 2 diabetic nephropathy, and control were examined. The transforming growth factor β1 (T869C) C allele, TC and TC + CC genotypes were significantly higher in patients; the T allele and TT genotype were significantly higher in controls (P ≤ 0.001). Glutathione give also a significant result in diabetic patients with and without nephropathy in when compared with controls. Conclusion: The observed data indicated that TGFβ1 (T869C) codon 10, allele C, and C allele-containing genotypes may be susceptible, and the T allele / TT genotype may be protective factors for type 2diabetic nephropathy complications. The results of glutathione showed that it may be one of the causes of presence high oxidants compounds, which is lead to the damage and destruction of mutations in the DNA of the cell.

Association of Transforming Growth Factor β1 Gene Polymorphisms and Inflammatory Factor Levels with Susceptibility to Sepsis.

Objective: To study the association of transforming growth factor β1 (TGF-β1) gene single nucleotide polymorphisms (SNPs) and plasma TGF-β1 levels with susceptibility to sepsis. Methods: The genotypes of the TGF-β1 gene rs1800469, rs1800468, rs1800470, and rs1800471 loci in 285 sepsis patients (119 patients with severe sepsis and 166 patients with mild sepsis) and 285 healthy individuals (control group) were analyzed through Sanger sequencing. Enzyme-linked immunosorbent assay was used to detect the levels of plasma inflammatory factors. Results: The TGF-β1 gene SNP rs1800469 C allele was 0.56 times lower than the T allele in terms of risk of susceptibility to sepsis (95% confidence interval [CI]: 0.43-0.72, p < 0.01). Carriers of the A allele at the rs1800468 locus of the TGF-β1 were 2.82 times more susceptible to sepsis than those with the G allele (95% CI: 1.62-4.91, p < 0.01). The T allele at the rs1800470 locus of TGF-β1 produced a lower risk of sepsis than those with the C allele (odds ratio [OR] = 0.74, 95% CI: 0.57-0.94, p = 0.02). The risk of susceptibility to sepsis in the TGF-β1 rs1800471 locus G allele was 3.54 times higher than that of C allele (95% CI: 2.14-5.86, p < 0.01). The TGF-β1 gene rs1800469 T > C and rs1800470 C > T were associated with mild sepsis, whereas rs1800468 G > A and rs1800471 C > G were associated with severe sepsis (p < 0.01). The TGF-β1 gene rs1800469 T > C and rs1800470 C > T were associated with lower plasma TGF-β1 levels, whereas rs1800468 G > A and rs1800471 C > G were associated with higher TGF-β1 levels (p < 0.05). Conclusion: The alleles T > C of rs1800469 and C > T of rs1800470 of the TGF-β1 gene were associated with lower plasma TGF-β1 levels and a reduced risk of sepsis susceptibility, whereas the alleles rs1800468 G > A and rs1800471 C > G were associated with higher TGF-β1 levels and risk of susceptibility to sepsis.

Migraines and keloids: a 15-year Taiwan claim database analysis

BackgroundFibroproliferative lesions with intractable pruritus, pain and hyperesthesia that cause uncontrolled scar growth are known as keloids. Migraines are common upsetting headache disorders characterised by frequent recurrence and attacks aggravated...

Effects of Concurrent Training (Resistance-Endurance) on Interferon-γ, Interloukin-18 and Transforming Growth Factor-β Gene Expression in Women with Type 2 Diabetes

Effects of Concurrent Training (Resistance-Endurance) on Interferon-γ, Interloukin-18 and Transforming Growth Factor-β Gene Expression in Women with Type 2 Diabetes

Transforming growth factor-β1 gene polymorphism as a potential risk factor in Turkish patients with laryngeal squamous cell carcinoma.

Laryngeal cancer is the most common head-and-neck malignancies with more than 20% of all cases. The vast majority of tumors are squamous cell carcinoma (SCC). Several genes encoding different cytokines may play crucial roles in host susceptibility to cancer because cytokine production capacity varies among individuals and depends on cytokine gene polymorphisms. The association between cytokine gene polymorphisms with primary laryngeal SCC was investigated. DNA samples were obtained from a Turkish population of eighty patients with primary cancer and fifty healthy controls. All genotyping (interferon-gamma, transforming growth factor-β1 [TGF-β1], tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, and IL-10) experiments were performed using polymerase chain reaction sequence-specific primers. When compared to the healthy controls, the frequencies of TGF-β1 codon 25 (rs1800471) GC genotype and 25 C allele were significantly more common in the patient group. These results suggest that TGF-β1 gene polymorphisms may affect host susceptibility to laryngeal cancer.

Association Between Head and Neck Cancers and Polymorphisms 869T/C, 509C/T, and 915G/C of the Transforming Growth Factor-β1 Gene: A Meta-Analysis of Case-Control Studies.

BackgroundWorldwide, head and neck cancers are the eighth most common malignancy. Single nucleotide polymorphisms (SNPs) are associated with susceptibility to cancer and sensitivity to radiotherapy and chemotherapy. The inflammatory cytokine, transforming growth factor-β1 (TGF-β1), is involved in the progression of malignancy. This study aimed to systematically review the literature and undertake a meta-analysis of case-control studies on the association between 869T/C, 509C/T, and 915G/C polymorphisms of the TGF-β1 gene and head and neck cancers.Material/MethodsThe published literature in the English and Chinese languages were searched to identify relevant studies reporting TGF-β1 gene polymorphisms and head and neck cancer. The PubMed, Embase, Wanfang Data, and CNKI databases were searched. Data were extracted from eligible studies, and meta-analysis was performed using Stata version 12.0 software.ResultsTen case-control studies were identified. There was a significant association between the 869T/C polymorphism of the TGF-β1 gene and susceptibility to head and neck cancer. Subgroup analysis showed that the 869T/C polymorphism was not significantly associated with the histological type of head and neck cancer, but was significantly associated with susceptibility to head and neck cancer in the Asian population. The 509C/T polymorphism of the TGF-β1 gene was not significantly associated with susceptibility to nasopharyngeal cancer (NPC), but the 915G/C polymorphism was associated with susceptibility to oral cancer.ConclusionsData from this meta-analysis showed that the 869T/C and 915G/C polymorphisms of the TGF-β1 gene might be associated with susceptibility to head and neck cancer.

The Role of Transforming Growth Factor-β1 Gene Polymorphism and Its Serum Levels in Hashimoto's Thyroiditis.

TGF-β1 gene (TGFB1) is one of the target genes involved in genetic predisposition to autoimmune diseases, particularly Hashimoto's thyroiditis (HT). In the present study, we attempted to investigate whether -509C/T SNP (rs1800469) in the promoter of TGFB1 is associated with the genetic susceptibility and clinical characteristics of Bulgarian patients with HT. We also analyzed serum TGF-β1 levels in different stages of the disease and its association with the -509C/T polymorphism in the TGFB1 promoter. The study recruited 121 female out-patients with autoimmune thyroiditis and 250 agematched healthy women (HC). Genotyping of the rs1800469 was performed by restriction fragment length polymorphism (RFLP)-PCR assay. The serum concentrations of latent acid-activated TGF-β1 protein were determined by the quantitative sandwich ELISA method. Upon testing different types of inheritance, a significant risk was found for heterozygotes (CT) with OR=1.640; p=0.05 under the codominant model. The significantly higher risk for developing Hypothyroidism was calculated again for CT-genotype patients with OR=1.789. According to the hormone reference values, a significant association of CT genotype with decreased TSH (75.4%) simultaneously with increased free T4 hormone (94%) levels was also calculated. When patients were stratified by genotype and compared to the same genotype in HC, we observed that the decreased levels in serum TGF-b1 were significant for patients who carried the C-allele in their genotype. We suggest that heterozygous genotype CT is a genetic risk factor for developing more severe HT due to enhanced free T4 serum level at the onset of the disease, before developing the hypothyroid stage.

Transforming growth factor-β1 gene promoter -509C/T polymorphism in association with expression affects colorectal cancer development and depends on gender.

It is widely known that sporadic colorectal cancer (CRC) is age-related diseases with higher incidence rate among men. Transforming growth factor-β1 (TGF-β1) is a major immune regulatory cytokine with a great impact and dual role in gastrointestinal carcinogenesis. In this context, the aim of the study was to explore the role of circulating TGF-β1 and the -509C/T functional promoter polymorphism (rs1800469) within the TGF-β1 gene (TGFB1) in the susceptibility, progression, and prognosis of CRC among Bulgarian male and female patients. Patients with sporadic CRC and healthy controls were genotyped by polymerase-chain reaction–restriction fragment length polymorphism. Serum TGF-β1 levels before and after curative surgery were determined by ELISA. Total RNA was extracted from paired tumor, normal mucosa and distant metastasis samples and was used for quantitative detection of TGFB1 mRNA by TaqMan qPCR.We observed that TGF-β1 serum levels depend on the -509C/T genotype in combination with gender. TGF-β1 serum levels in CRC patients were decreased compared to controls, but statistical significance was reached only for men. In the stratified analysis by gender and genotype, a significant association was found for the CC genotype. Overall, our results indicate that the -509C allele increased the cancer risk, particularly for advanced stages (OR = 1.477; p = 0.029). The results from the relative mRNA quantification showed a significant upregulation of TGFB1 in distant metastases compared to primary tumor tissues and higher TGFB1 mRNA levels in men (RQ = 4.959; p = 0.022). In conclusion, we present data that diminished circulating TGF-β1 due to the CC genotype could be a possible risk factor for tumor susceptibility and progression. This association is more pronounced in males than in females. Colorectal cancer tissue expression of TGFB1 gene mRNA correlates with tumor progression and metastasis.

Transforming growth factor β1 gene play a novel role in innate immune response in Pelteobagrus fulvidraco

Transforming growth factor-beta 1 (TGF-β1) as a member of TGF-β superfamily plays crucial roles in regulation of immune responses. Yellow catfish, Pelteobagrus fulvidraco , is one of the most important freshwater aquaculture species in China, but little is known about its genes related to immune response. The present study cloned cDNA encoding TGF-β1 from P. fulvidraco . The results showed the full-length cDNA of TGF-β1 is 2,816 bp and encodes 461 amino acids. The homology of P. fulvidraco TGF-β1 depicted 83% and 81% similarity to the TGF-β1 in Stegastes partitus and Pundamilia nyererei respectively. The phylogenetic tree construction revealed that P. fulvidraco is closely related to Astyanax mexicanus . Analysis of mRNA expression of TGF-β1 in different tissues (gonads, brain, liver, kidney, spleen, intestine, blood, gills, muscle and heart) revealed that TGF-β1 is predominantly expressed in liver and brain, followed by gill and spleen. TGF-β1 gene in gill and spleen up-regulated for 48h after Edwardsiella ictaluri and Flavobacterium columnare injection, then the expression showed a significant decrease (p P. fulvidraco.

Transforming growth factor-β1 gene polymorphisms with liver cirrhosis risk: A meta-analysis

Although several epidemiological studies have investigated the association of transforming growth factor-β1 (TGF-ß1) gene polymorphisms with the susceptibility to liver cirrhosis (LC), controversial results exist. Consequently, we performed a meta-analysis to accurately evaluate the relationship of TGF-ß1-509C/T and codon 10T/C polymorphisms with the risk of LC introduced by chronic hepatitis B/V virus (HBV/HCV) infection. A total of 9 case-control studies, involving 985 LC patients and 909 controls, were recruited for meta-analysis. The results suggested a significant association between the -509C/T polymorphism and LC risk in the total population. Stratification by ethnicity revealed similar associations in Egyptian and Caucasian populations, but not in Asian populations. Subgroup analyses by different etiologies also showed similar associations in HCV-induced LC, but not in HBV-induced LC. However, the overall data failed to show a significant association between codon 10T/C polymorphism and the risk of LC in the study. We concluded that TGF-ß1-509C/T polymorphism was significantly associated with LC susceptibility, while the codon 10T/C polymorphism seemed to have a limited role in predicting the occurrence of LC induced by HBV/HCV infection.

Transforming Growth Factor-β1 gene polymorphism and osteoporosis in postmenopausal egyptian women.

Transforming growth factor-β1 (TGF-β1) is a wide spread bone matrix protein that affect the function, formation and cell-cell interactions of osteoclasts and osteoblasts to regulate bone remodeling and sustain adequate bone mass. The aim of this study is to evaluate the role of the two polymorphism of transforming growth factor-β1 T869C and C-509T in developing osteoporosis in postmenopausal Egyptian women. This study was performed on 138 postmenopausal osteoporosis/osteopenic women and 128 postmenopausal female control group. There was a significant statistical difference in the CC, CT and TT (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value &lt;0.001). There was a non-significant statistical difference in the CC, CT and TT (T-509C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value &lt;0.082). There was a significant statistical difference between TT,CT and CC of (T869C) and T score, Z score and calcium of osteopenia/osteoporosis group (p value &lt;0.001). There was a non-significant statistical difference between TT, CT and CC of (T-509C) and T score, Z score of osteopenia/osteoporosis group (p value 0.32,0.31),but there was a statistically significant difference between the three genotyping and serum calcium and creatinine (p value 0.04). Multivariate regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis (OR 3.57, 95% CI= 1.56-5.67). We concluded that T869C polymorphism of the TGF-β1 gene has an impact on bone mineral density and enhancement of the susceptibility to osteopenia/osteoporosis in Egyptian women.

Role of Galectin-3 in the pathophysiology underlying allergic lung inflammation in a tissue inhibitor of metalloproteinases 1 knockout model of murine asthma.

Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyperresponsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Using a tissue inhibitor of metalloproteinases 1 (TIMP-1) knockout murine allergic asthma model, we previously showed that TIMP-1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation and T helper type 2 cytokine gene and protein expression following sensitization with ovalbumin. In the current study, we compared the expression of Galectins and other key cytokines in a murine allergic asthma model using wild-type and TIMP-1 knockout mice. We also examined the effects of Galectin-3 (Gal-3) inhibition on a non-T helper type 2 cytokine interleukin-17 (IL-17) to evaluate the relationship between Gal-3 and the IL-17 axis in allergic asthma. Our results showed a significant increase in Gal-3, IL-17 and transforming growth factor-β1 gene expression in lung tissue isolated from an allergic asthma murine model using TIMP-1 knockout. Gal-3 gene and protein expression levels were also significantly higher in lung tissue from an allergic asthma murine model using TIMP-1 knockout. Our data show that Gal-3 may regulate the IL-17 axis and play a pivotal role in the modulation of inflammation during experimental allergic asthma.

Association between transforming growth factor-beta 1 gene single nucleotide polymorphisms and knee osteoarthritis susceptibility in a Chinese Han population.

ObjectiveTo investigate associations between single polymorphisms (SNPs) rs1800469 and rs1982073 in the transforming growth factor-β1 gene (TGF-β1) and knee osteoarthritis (OA) susceptibility in a Chinese Han population.MethodsTGF-β1 rs1800469 and rs1982073 were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. The association was further analyzed according to gender and age.ResultsA total of 765 patients with knee OA and 780 controls were included. CT and CT + CC genotypes of rs1982073, and variant C, were associated with a significantly increased risk of knee OA. Stratification analysis showed that the association between the OA risk and rs1982073 CT heterozygotes compared with TT homozygotes was stronger in females and those aged >65 years. In contrast, CT, TT, and CT + TT genotypes of rs1800469 were not significantly associated with the risk of knee OA, even after further stratification analysis for gender and age.ConclusionsThe TGF-β1 rs1982073 T to C change and the variant C genotype may contribute to knee OA risk in the Chinese Han population.

New insights into the role of dietary spermine on inflammation, immune function and related-signalling molecules in the thymus and spleen of piglets

ABSTRACTThis study aimed to determine the effects of dietary spermine supplementation on the inflammatory response and immune function of the thymus and spleen in piglets. Eighty suckling piglets were randomly assigned to receive adequate nutrients supplemented with spermine (0.4 mmol/kg body weight) or restricted nutrient intake supplemented with normal saline for 7 h or 3, 6 and 9 days in pairs. Regardless of treatment time, spermine supplementation decreased (p < 0.05, compared with the controls) the following: (1) tumour necrosis factor α (TNF-α), interleukin (IL)-1β, 2 and 6, and interferon (IFN)-γ levels in serum; (2) gene expression of cluster of differentiation 8 and integrin beta-2 in the thymus and spleen and the lymphocyte function-associated antigen 1 in the thymus; (3) mRNA levels of TNF-α, IL 1β, 2, 6, and 12, IFN-γ and inducible nitric oxide synthase in the thymus and spleen, as well as IL-8 in the spleen; and (4) eukaryotic IF4E-binding protein 1, Janus kinase 2, signal transducer and activator of transcription 3, and nuclear factor-kappa B P65 gene transcriptions in the thymus and spleen. By contrast, spermine supplementation increased (p < 0.05) the following: (1) immunoglobulin M, IL-10, and transforming growth factor β1 gene expression, as well as (2) relative mRNA levels of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase 1 in the thymus and spleen. These effects were also observed upon prolonged spermine administration (p < 0.05). In summary, dietary spermine supplementation can alleviate inflammatory response, enhance the immune function and regulate the gene expression of signalling molecules related to inflammation.

Novel copy number variation of the TGFβ3 gene is associated with TGFβ3 gene expression and duration of fertility traits in hens.

Improvements in the duration of fertility (DF) could increase the interval between successive artificial inseminations, thereby decreasing the cost associated with production of hatching eggs. The molecular mechanisms involved in DF in hens remains under-explored. In this study, expression levels of the transforming growth factor-β genes (TGFβs: TGFβ1, TGFβ2, TGFβ3) were investigated in utero-vaginal junctions (UVJs) of hens with long DF (Group L, n = 10) and short DF (Group S, n = 10). TGFβ1 and 2 tended to exhibit higher expression levels in UVJs from Group L hens. The expression levels of TGFβ3 mRNA and protein were significantly increased in UVJs of hens from Group L compared to hens in Group S. Consistently, six TGFβs downstream genes (DAXX, MEKK1, T-BET, GATA-3, TAK1, and FOXP3) associated with the immune response were found to be significantly differentially expressed in UVJs of Group L than Group S hens. In addition, four SNPs were identified in intron 1 of TGFβ3, and these SNPs were significantly associated with DF traits (P < 0.05). Furthermore, we identified multi-copy and copy number variants (CNVs) in chicken TGFβ3 and later determined significant associations between TGFβ3 CNVs and DF traits in hens. Specifically, TGFβ3 copy number exhibited a significant positive correlation with its expression (P < 0.05). Collectively, our results suggest that chicken DF traits may be regulated by the expression of TGFβ3 in UVJ. Meanwhile, the copy number variation in the TGFβ3 gene identified in this study seems to be one marker for DF traits.

An updated meta-analysis of transforming growth factor-β1 gene: Three well-characterized polymorphisms with asthma

The association between TGF-β1 polymorphisms and asthma risk has been widely reported, but results were controversial. We performed this meta-analysis based on the Preferred Reporting Items for Systematic Reviews and meta-analyses statement (PRISMA). Electronic database of Pub Med, Web of Science, CBM, and CNKI were searched for eligible articles published up to September, 2013. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Finally, a total of 20 articles were identified, 17 studies with 3694 cases and 5613 controls for C-509T polymorphism, 7 studies with 1109 cases and 1098 controls for T869C polymorphism and 5 studies with 849 cases and 829 controls for G915C polymorphism. For C-509T, significant associations with asthma were found in Asians (TT+TC vs. CC: P=0.004, OR=1.43, 95%CI=1.12–1.81, Pheterogeneity=0.001) and in Caucasians (P=0.05, OR=1.16, 95%CI=1.00–1.34, Pheterogeneity=0.36). With respect to T869C, a small significant association was observed in overall analysis of allele contrasts(C vs. T: OR=1.14, 95%CI: 1.01–1.29, P=0.03) and homozygote comparison (CC vs. TT: OR=1.29, 95%CI: 1.00–1.65, P=0.05), but no significant risks were found among Caucasian population and Asian population. For G915C polymorphism, no significant association with asthma risk was demonstrated in overall analysis and subgroup analyses according to ethnicity for all genetic models. This meta-analysis suggested that TGF-β1 C-509T and T869C polymorphisms may be risk factors for asthma.

Association of genetic polymorphisms in interferon-γ, interleukin-6 and transforming growth factor-β1 gene with oral lichen planus susceptibility.

BackgroundOral lichen planus (OLP) is a premalignant mucocutaneous disease in which genetic factors and immune responses play a major role. Cytokines play an important role in the pathogenesis and disease progression of OLP. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-β1 on OLP susceptibility in a Saudi cohort.MethodsForty two unrelated patients with OLP and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms.ResultsThe frequency of genotype AT of IFN-γ (874A/T) was significantly higher while genotype AA was lower in OLP patients as compared to controls (P < 0.05). The frequency of T containing genotypes (AT + TT) was also higher in OLP patients as compared to that in controls (P = 0.003). The frequencies of allele T was higher while that of allele A lower in patients than the controls however the difference was not statistically significant (P = 0.07). There was no significant difference in the frequencies of alleles and genotypes of IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms between patient and control groups. These results indicated that genotype AT of IFN-γ (874A/T) polymorphism is associated with OLP risk and genotype AA is protective to OLP. On the other hand the polymorphisms IL-6 (174G/C) and TGF-β1 (509C/T) may not be associated with OLP risk in our population.ConclusionIt is concluded that IFN-γ (874A/T) polymorphism is associated with the susceptibility of OLP, however further studies with large sample size involving different ethnic populations should be conducted to strengthen our results.

Transforming Growth Factor-β1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level

BackgroundFamilial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome.MethodsOverall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1.ResultsTwo transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16–3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls.ConclusionTransforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome.

Pentoxifylline inhibits liver fibrosis via hedgehog signaling pathway

Infection of schistosomiasis japonica may eventually lead to liver fibrosis, and no effective antifibrotic therapies are available but liver transplantation. Hedgehog (HH) signaling pathway has been involved in the process and is a promising target for treating liver fibrosis. This study aimed to explore the effects of pentoxifylline (PTX) on liver fibrosis induced by schistosoma japonicum infection by inhibiting the HH signaling pathway. Phorbol12-myristate13-acetate (PMA) was used to induce human acute mononuclear leukemia cells THP-1 to differentiate into macrophages. The THP-1-derived macrophages were stimulated by soluble egg antigen (SEA), and the culture supernatants were collected for detection of activation of macrophages. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of the culture supernatant and PTX on the LX-2 cells. The LX-2 cells were administered with activated culture supernatant from macrophages and(or) PTX to detect the transforming growth factor-β gene expression. The mRNA expression of shh and gli-1, key parts in HH signaling pathway, was detected. The mRNA expression of shh and gli-1 was increased in LX-2 cells treated with activated macrophages-derived culture supernatant, suggesting HH signaling pathway may play a key role in the activation process of hepatic stellate cells (HSCs). The expression of these genes decreased in LX-2 cells co-cultured with both activated macrophages-derived culture supernatant and PTX, indicating PTX could suppress the activation process of HSCs. In conclusion, these data provide evidence that PTX prevents liver fibrogenesis in vitro by the suppression of HH signaling pathway.