Serum Levels Of TGF-β1 Research Articles

Transforming Growth Factor-Beta is Increased in Sputum from Individuals with Rheumatoid Arthritis-Associated Pulmonary Fibrosis.

Interstitial lung disease (ILD) develops in 5-10% of patients with rheumatoid arthritis (RA) and contributes significantly to morbidity and mortality, particularly in those with a fibrotic phenotype. Yet, biomarkers to reliably identify RA patients with underlying pulmonary fibrosis are inadequate. Herein, we used sputum to identify lung-based biomarkers that distinguish RA patients with underlying pulmonary fibrosis and may better inform underlying pathogenesis in RA-ILD. We included 37 RA patients with pulmonary fibrosis (RA-PF) and 30 RA patients without ILD (RA-no-ILD). Induced sputum and serum were tested for transforming growth factor beta (TGF-β) levels by immunoassay. DNA was extracted to determine presence of the MUC5B ILD-risk allele ("T"). High resolution computed tomography (HRCT) and pulmonary function tests (PFTs) were completed within 3 months of sputum collection and quantified to determine lung disease severity. Sputum TGF-β was significantly elevated in individuals with RA-PF compared with RA-no-ILD (p< 0.001) and correlated with more fibrosis on HRCT (p= 0.005) and lower forced vital capacity (p= 0.006) and diffusion capacity of carbon monoxide (p= 0.044) on PFTs. Within RA-PF patients, sputum TGF-β was higher in those with the MUC5B ILD-risk genotype (GT/TT) (p= 0.038). There were no differences in serum levels of TGF-β between groups. We demonstrate that sputum levels of TGF-β are significantly elevated in individuals with RA-PF, correlate with lung disease severity, and are elevated in those with the MUC5B ILD-risk polymorphism. These findings could identify novel approaches to ILD screening in RA and potential targeted therapeutic strategies for RA-ILD.

Exploring the efficacy of Transcutaneous Auricular Vagus nerve stimulation (taVNS) in modulating local and systemic inflammation in experimental models of colitis

BackgroundCurrent inflammatory bowel disease (IBD) treatments often fail to achieve lasting remission and have adverse effects. Vagus nerve stimulation (VNS) offers a promising therapy due to its anti-inflammatory effects. Its invasive nature, however, has led to the development of non-invasive methods like transcutaneous auricular VNS (taVNS). This study assesses taVNS’s impact on acute colitis progression, inflammatory, anti-inflammatory, and apoptosis-related markers.MethodsMale C57BL/6 mice (11–12 weeks) were used for dextran sulfate sodium (DSS)- and dinitrobenzene sulfonic acid (DNBS)-induced colitis studies. The administration of taVNS or no stimulation (anesthesia without stimulation) for 10 min per mouse began one day before colitis induction and continued daily until sacrifice. Ulcerative colitis (UC)-like colitis was induced by administering 5% DSS in drinking water for 5 days, after which the mice were sacrificed. Crohn’s disease (CD)-like colitis was induced through a single intrarectal injection of DNBS/ethanol, with the mice sacrificed after 3 days. Disease activity index (DAI), macroscopic evaluations, and histological damage were assessed. Colon, spleen, and blood samples were analyzed via qRT-PCR and ELISA. One-way or two-way ANOVA with Bonferroni and Šídák tests were applied.ResultstaVNS improved DAI, macroscopic, and histological scores in DSS colitis mice, but only partially mitigated weight loss and DAI in DNBS colitis mice. In DSS colitis, taVNS locally decreased colonic inflammation by downregulating pro-inflammatory markers (IL-1β, TNF-α, Mip1β, MMP 9, MMP 2, and Nos2) at the mRNA level and upregulating anti-inflammatory TGF-β in non-colitic conditions at both mRNA and protein levels and IL-10 mRNA levels in both non-colitic and colitic conditions. Systemically, taVNS decreased splenic TNF-α in non-colitic mice and increased serum levels of TGF-β in colitic mice and splenic levels in non-colitic and colitic mice. Effects were absent in DNBS-induced colitis. Additionally, taVNS decreased pro-apoptotic markers (Bax, Bak1, and caspase 8) in non-colitic and colitic conditions and increased the pro-survival molecule Bad in non-colitic mice.ConclusionsThis study demonstrates that taVNS has model-dependent local and systemic effects, reducing inflammation and apoptosis in UC-like colitis while offering protective benefits in non-colitic conditions. These findings encourage further research into underlying mechanisms and developing adjunct therapies for UC.

Elevated IL-10 serum levels are associated with slower serological response following syphilis treatment during pregnancy.

Approximately 50% of pregnant individuals treated for syphilis do not achieve a decline in non-treponemal titers by delivery. The serological response in pregnant persons is significantly slower compared to non-pregnant individuals, with unclear pathogenesis and clinical significance. This study aimed to determine the association between the host immune response and serological outcome in pregnant individuals with syphilis. Twenty-four females with early syphilis, including 14 pregnant individuals, were included. Pro-inflammatory and regulatory cytokines (IFN-γ, TNF-α, IL-4, IL-1β, IL-10, TGF-β) were measured before treatment and 6 months after penicillin injection. The median time to serological cure was 5months for pregnant individuals and 2months for non-pregnant females. Pregnant individuals had significantly higher serum levels of IL-10 and TGF-β at baseline and at 6months post-treatment compared to non-pregnant individuals (p < .05). A robust regulatory immune response to syphilis may be associated with a slower serological response to therapy during pregnancy.

Randomised Clinical Trial Study: The Combination of Vitamin D and Curcumin Piperine Attenuates Disease Activity and Pro-inflammatory Cytokines Levels Insystemic Lupus Erythematosus Patients.

Curcumin-piperine might synergise with vitamin D to induce clinical remission in patients with systemic lupus erythematosus (SLE). To observe the improvement of patients with SLE clinically and the levels of inflammatory cytokines after receiving supplements of curcumin-piperine and cholecalciferol (Vitamin D3). Forty-five female SLE patients were included in a three-month double-blind, randomized controlled trial. Participants were classified into: Group I (400 IU cholecalciferol + placebo three times daily, n = 15), Group II (600 mg curcumin + 15,800 m piperine once daily and three times daily placebo, n = 15), and Group III (cholecalciferol 400 IU three times and 600 mg curcumin + 15,800 mg piperine once a day, n = 15). Mexican SLE disease activity score (Mex- SLEDAI), fatigue severity scale (FSS), TGF-β, and IL-6 levels were measured from all patients before and after the treatments. Mex-SLEDAI, FSS, and IL-6 were reduced significantly, while TGF-β serum levels were increased in all groups after the treatments (p <0.05). Changes in Mex-SLEDAI score (p = 0.003 and p = 0.008), FSS (p = 0.001 and p <0.001), and TGF-β (p = 0.003 and p = 0.004) serum levels were significantly higher in group III compared to the group I or group II. On the other hand, changes in Mex-SLEDAI, FSS, IL-6, and TGF-β serum levels were similar between groups I and II. Although vitamin D or curcumin-piperine alone could improve the clinical outcome and cytokines levels in SLE, curcumin-piperine combined with vitamin D had the best outcome in improving the disease activity and cytokines levels among patients with SLE. (ClinicalTrials.gov number, NCT05430087).

M1 polarization of hepatic macrophages in cows with subclinical ketosis is an important cause of liver injury.

Subclinical ketosis (SCK) is highly prevalent and easily overlooked, with insidious and slow progression of hepatic injury, often characterized by an imbalance in immune homeostasis. In nonruminants, macrophage polarization plays an important regulatory role in hepatic lipid accumulation, fibrosis and inflammatory processes. Thus, we aimed to investigate the status of hepatic macrophage polarization in SCK cows and to corroborate its association with liver injury and inflammation. Twelve Holstein dairy cows (parity, 2-4) were selected, and liver biopsy and blood were collected on the second week postpartum (10-14 d days in milk). On the basis of serum BHBA concentrations., selected cows were categorized into healthy (n = 6; BHBA <1.0 mM) and SCK (n = 6; 1.2 mM ≤ BHBA < 3.0 mM) groups. Serum biochemical parameters were measured using an automatic biochemical analyzer, which indicated higher serum levels of BHBA and NEFA and an upregulation of liver injury indicators (AST, ALT, TP, GLB) in SCK cows compared with healthy cows. ELISA assays revealed that SCK cows displayed systemic low-grade inflammation, as demonstrated by increased serum levels of HP, SAA, TGF-β, IFN-γ, and IL-1β. Liver biopsies revealed pathological histological alterations, hepatic inflammation, and macrophage polarization status. Oil red staining indicated steatosis, while Sirius red staining demonstrated mild extracellular matrix deposition in the liver of SCK cows. The expression of inflammatory response-related proteins (TLR4, p-NFκB, p-I-κB, NLRP3, and Caspase-1) was elevated in the liver of SCK cows, with the increased mean fluorescence intensity of NFκB further confirming the activation of the inflammatory pathway. Furthermore, the levels of pro-inflammatory factors, TNF-α and IFN-γ, were elevated in the tissue homogenate. Macrophage phenotypic changes in SCK cows were further explored based on the results of liver injury and inflammation. Compared with healthy cows, the protein and mRNA abundance of the macrophage marker CD68 in the liver of SCK cows was higher, along with an increased mean fluorescence intensity of CD68. SCK cows also exhibited reduced mRNA expression of the Kupffer cell marker CLEC4F and elevated chemokine levels (CXCL1 and CCL2). As evidenced by greater protein and mRNA abundance of macrophage M1 polarization markers (iNOS, IL-1β, CD86, IL-6, IL-12b, and CCL3), higher fluorescence intensity of iNOS and CD86, and an increased number of CD68+/CD86+-positive cells observed via immunofluorescence, the macrophage polarization phenotype in the liver of SCK cows was predominantly M1. In contrast, the protein and mRNA abundances of M2 polarization markers (CD206, IL-10, and Arg1) were lower in SCK cows, accompanied by a reduced fluorescence intensity of CD206 and a lower number of CD68+/CD206+-positive cells. Overall, the present study revealed that the number of macrophages in liver is enhanced during subclinical ketosis and is dominated by pro-inflammatory macrophages (M1 macrophages). This could partly explain the increased risk of steatosis, fibrosis, and inflammatory response processes in these cows.

Menaquinone-7 and its therapeutic potential in type 2 diabetes mellitus based on a Zucker diabetic fatty rat model

BackgroundType 2 diabetes mellitus (T2DM) is marked by insulin resistance, low grade chronic inflammation, and endothelial dysfunction. Vitamin K2, especially menaquinone-7 (MK-7), might delay T2DM progression and alleviate its consequences. Hence, this study evaluated the effects of MK-7 on serum and urine markers of diabetes in an animal model of T2DM. MethodsHetero- (fa/+, control) and homozygous (fa/fa, diabetic) male Zucker diabetic fatty (ZDF) rats were supplemented or not with MK-7 for 12 weeks. After euthanasia, vitamin K1, menaquinone-4 and MK-7 serum concentrations were analyzed via reversed phase high pressure liquid chromatography. Glucose (serum), fructosamine (serum) and creatinine (serum and urine) levels were assessed photometrically, serum cystatin C and urinary total protein were turbidimetrically determined. Serum transforming growth factor beta1 (TGF-β1) and procollagen type III N-terminal peptide (PIIINP) were quantified with enzyme-linked immunosorbent assay. Urinary marker proteins were analyzed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Nephropathy was assessed histologically. ResultsSupplementation led to significantly elevated MK-7 serum levels and a significant reduction of PIIINP serum levels in both hetero- and homozygous ZDF rats. Additionally, not statistically significant reductions of TGF-β1 serum levels, proteinuria as well as the nephropathy score were observed. In vivo body mass, serum fructosamine, glucose, cystatin C and creatinine levels were unaffected. ConclusionMK-7 reduced serum markers of fibrosis, histological features of nephropathy and urinary protein excretion, but failed to affect serum markers of T2DM. The therapeutic potential of MK-7 in T2DM and its mode of action should be further investigated in more detail.

KCl enhances the cryoablation-induced antitumor immune response: A hepatocellular carcinoma murine model research

Cryoablation is a valuable treatment for liver cancer. To investigate the effect of KCl solution on the immunological response post cryoablation, we created a tumor-bearing mice model by subcutaneously implanting Hepal-6 cells in adult Balb/c mice. Subsequently, the mice were randomly assigned to three groups: group A (sham cryoablation), group B (cryoablation), and group C (cryoablation plus KCl solution). Mice were sacrificed on days 0, 7, and 14 post-treatment. Immune cell populations were assessed using flow cytometry. Blood samples were analyzed for serum IL-4, HSP70, and TGF-β1 levels with ELISA assays. Ablated tissues stained with immunohistochemistry were utilized to evaluate Ki67 expression at the margins of the ablation site. Our findings revealed higher HSP70 expression levels in groups B and C compared to group A. Cryoablation triggered an immune response, which was enhanced by KCl. On days 0, 7, and 14, the percentages of CD4+ T cells, CD8+ T cells, and NK cells in the spleen of group C were significantly increased compared with groups A and B. Additionally, the Th1/Th2 ratio was significantly increased in group C. Serum TGF-β1 expression was elevated after cryoablation, but KCl solution reduced the high TGF-β1 expression after cryoablation and decreased the invasiveness of cancer cells. Finally, the proliferative activity of untreated tumor tissue was significantly reduced in group C compared to groups A and B. In summary, Cryoablation triggered a systemic immune response in tumor-bearing mice, which was further boosted by combining cryoablation with a KCl solution.

Correlation of biochemical markers and inflammatory cytokines in autism spectrum disorder (ASD)

IntroductionAutism Spectrum Disorder (ASD) is a disorder that severely affects neurodevelopment, and its underlying causes are not yet entirely understood. Research suggests that there may be a connection between the occurrence of ASD and changes in immune responses. This study aims to know if some biochemical and inflammatory cytokines are promising biomarkers for ASD and whether they are involved in the pathogenesis of ASD.MethodsThe serum levels of CRP, TNF-α, TGF-β, IL-1β, IL-10, 1 L-8, and IL-6 were measured in all of the patients (n = 22) and in the healthy (n = 12) children using ELISA method.ResultsThe serum concentrations of IL-10 and IL-8 were significantly lower in the ASD patients compared to the control group (p < 0.05) and there were not significant differences between CRP, TNF-α, TGF-β, IL-6 and IL-1β levels in two groups. There were positive correlations between CRP and IL-10, also CRP and IL-8, in ASD group. In contrast to the ASD patients, the correlations of IL-8, IL-10, and CRP were not significant in the control group.ConclusionIn conclusion, this study highlights the potential role of certain biochemical markers and inflammatory cytokines in ASD. Specifically, the lower levels of IL-10 and IL-8 in ASD patients, along with the significant correlations between CRP and these cytokines, suggest an altered immune response in individuals with ASD. These findings support the hypothesis that immune dysregulation may be involved in ASD pathogenesis. Further research is needed to explore these biomarkers and their mechanistic links to ASD, which could lead to improved diagnostics or therapeutic strategies.

Profiling of Toll-like Receptors and Related Signaling Mediators in the Pathogenesis of Morphea.

Morphea, also known as localized scleroderma, is a rare fibrosing inflammatory disease of unknown pathogenesis. Although the genetic basis for morphea is important, reports on the evaluation of Toll-like receptors (TLR) in this disease is quite limited. We aimed to evaluate TLR expression levels and serum IL-6, IL-17A, TGF-β1, FGF, and VEGF levels in patients with morphea and compare these results with healthy controls. The expression levels of TLRs in the lesional and non-lesional adjacent skin of patients with morphea and in normal skin of healthy controls were evaluated by RT-PCR, whereas serum levels of IL-6, IL-17A, TGF-β1, FGF, and VEGF were evaluated by ELISA. Based on our findings, TLR1 gene expression increased 34.3-fold in the lesional skin of patients with morphea. In addition, IL-6, IL-17A, TGF-β, FGF, and VEGF were found to be higher in the blood samples of the patient group than in the healthy group. TLRs are important parts of the pathogenesis of morphea, and a better understanding of them will lead to more directed, effective treatments. We believe that this study will be important for pioneering TLR-targeted therapeutic approaches in the treatment of morphea in the future.

Correlation of T Regulatory Cells, Cytotoxic T-lymphocyte-associated Antigen 4, and Transforming Growth Factor-β1 with Treatment Response in Patients with Chronic Myeloid Leukemia Receiving Dasatinib Therapy.

Tyrosine kinase inhibitors improve chronic myeloid leukemia (CML) outcomes. Dasatinib inhibits breakpoint cluster region-Abelson 1 proto-oncogene tyrosine kinase better than imatinib in CML. T-regulatory cells prevent autoimmune diseases and aberrant immune responses by reducing oncoprotein antigen reactivity. They also reduce self-antigen-induced immune responses to maintain peripheral tolerance. In this study, T-regulatory cells in peripheral blood of chronic myeloid leukemia-chronic phase patients were measured, together with serum levels of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and transforming growth factor (TGF)-β1 at diagnosis and 3 months postdasatinib therapy. The Pathology and Clinical Haematology Departments at King George's Medical University, Lucknow, India, conducted this prospective analytical study. Forty CML-chronic patients and 10 healthy controls were analyzed. Flow cytometry was used to determine T-regulatory cell percentage in peripheral blood mononuclear cells of newly diagnosed CML patients before and after 3 months of dasatinib treatment; ELISA was used to measure serum levels of CTLA-4 and TGF-β1. T-regulatory cells, CTLA-4, and TGF-β1 significantly decreased in CML-chronic phase patients after 3 months of dasatinib therapy compared to the initial diagnosis. No significant change in T-regulatory cell, CTLA-4, or TGF-β1 percentages were seen between responders and poor responders. However, responders had a lower percentage of T-regulatory cells than suboptimal responders. The study concluded that dasatinib treatment improved response in CML patients with decreased Treg cells. Dasatinib reduces Treg-mediated immunological suppression, reducing CTLA-4 and TGF-β1 levels.

Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma.

Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear. To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC). Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1β, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-β, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing. TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-β, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1β, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora. TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.

Accuracy of Transforming Growth Factor-Beta in Serum and Synovial Fluid as Rheumatoid Arthritis Prognostic Factors

Background: Rheumatoid arthritis (RA) An autoimmunity of the joints which is now seen as a major public health concern. Therefore, finding new biomarkers is crucial to improve RA sufferers' quality of life. Several cytokines increased the inflammatory cascade which linked to pathophysiology of RA. This investigation aimed to determine the validity of transforming growth factor-beta-1 (TGF-β1) in synovial fluid and serum as prognostic factor and which one is better for rheumatoid arthritis disease follow up. Material and Methods: In Al-Saddar Medical City Rheumatology Unit in the Najaf governorate, 80 patients were included in case-control research. These patients were identified by specialized who classified the patients according to stages of disease into mild stage (stage 1 and 2) and aggressive (stage 3 and 4 who had knee effusion and synovial fluid separation). Venous blood samples (3ml) drawn from patients and controls were transferred to a gel tube for serum separation that used to measure the TGF-β1 level in accordance (BT LAB/China), RF level and anti-CCP level by ELISA assay. knee synovial fluid was collected from RA patients in aggressive stage and from patient suffering from knee trauma as control group which included 18 patients not have RA. The result demonstrated that Females and aged individuals in AL-NAJAF province more incidence with RA disease. TGF-β1 serum level increased significantly with disease severity and positive correlated with ACCP autoantibody, according to ROC prognosis analysis AUC of TGF-β1 serum level was excellent 0.9 with 100% sensitivity and specificity. While ROC analysis for TGF-β1 synovial fluid was 0.8 with 77.8% sensitivity and 86.7% specificity Conclusion: Using ROC analysis, which supported good TGF level in both serum and synovial fluid diagnosis accuracy and enabled more sensitive and precise discrimination in RA disease. Instead of using synovial fluid separation as a diagnostic for excellent prognosis in RA disease, TGF-β1 and ACCP blood levels can help patients avoid discomfort and stress.

Effect of anesthetic technique on antitumor immunity in patients undergoing surgery for gall bladder cancer: A prospective randomized comparative study.

There is a paucity of literature regarding the effect of anesthetic techniques on antitumor immunity, especially in gall bladder malignancies. We designed a study to compare the effect of propofol-based total intravenous anesthesia and sevoflurane-based general anesthesia-on antitumor immunity, including tumor growth factor-β (TGF-β), T-helper cell profile, and inflammatory markers. A pilot prospective randomized trial was conducted in 64 patients undergoing surgery for gall bladder malignancy under general anesthesia in a tertiary specialty cancer hospital. Adult cancer patients of ASA physical status I-III fulfilling the inclusion criteria were randomized to either group S (sevoflurane-based general anesthesia) or group T (propofol-based total intravenous anesthesia). Preoperative (morning of surgery) and postoperative (24 h and 1 month after surgery) blood samples were obtained. Demographic profile and preoperative parameters were comparable between both groups. There was a statistically significant difference in the postoperative value of TGF-β (higher in group T). There was a statistically significant difference in postoperative interleukin-17A value (indicative of TH17 cells), and it was found to be higher in group S. Propofol-based TIVA increases serum TGF-β levels. At the same time, Sevoflurane modulates T-helper cells-based immunity to increase TH17 cells in patients with gall bladder cancer. Multiple larger studies will be required to validate the results and provide useful recommendations.

Exploring the role of TNF-α, TGF-β, and IL-6 serum levels in categorical and noncategorical models of mood and psychosis

Psychotic and mood disorders are discussed as part of the same continuum. The potential role of immune dysregulation in defining their clinical presentations, however, remains unclear. Differences in TNF-α, IL-6 and TGF-β levels were investigated in 143 patients with schizophrenia (SCH = 63) and bipolar disorder (BD = 80), in remission. Cytokines were evaluated against the dimensional assessment of psychosis and affective symptoms using the schizo-bipolar scale, together with the severity of the same symptom domains measured by the brief psychiatric rating scale (BPRS). Lower TGF-β was associated with more lifetime episodes, family risk for psychosis, and more severe mood and psychotic symptoms in all patients. BPRS Affect symptoms domain correlated with lower TGF-β levels in BD, and higher TGF-β levels in SCH patients. Using moderated mediation analysis, TGF-β was a relevant predictor only in the setting of non-categorical symptom distribution, with familial risk for psychosis confirmed as a significant moderator. Severity of BPRS Affect symptoms domain was an independent predictor of inclination towards the psychosis spectrum. The underlying immune dysregulation may be shared by the disorders, rather than a unique characteristic of each, having significant implications for our understanding of the continuum vs. categorical approach to psychosis and mood disorders.

Diagnoses Bacterial Wound Infection and Detection of Some Immune Parameters in its

This study aims to diagnoses bacterial wound infection and to estimate the serum levels of TLR-3, CXCL8, TGF-β1, IL-8, IL-17 and IL-22 in wound patients. This study had been included 140 samples (blood and swab) obtained from patients found in Baquba-Teaching Hospital from 15/ 6 /2023 to 20 /3 /2024. Swab samples taken from wound were culture on the blood agar and MacConkey agar, and then Bacteria diagnoses was done by using an automatic VITEK 2 system. The serum levels of immune parameters done by ELISA. The results shown that sixty isolates were grow in culture, the results indicated of 38(63.3%) isolates of gram-negative bacteria, represented by: 12 (20%) isolates E. coli, 18 (30%) Pseudomonas aeruginosa, 6 (10%) Protus spp., 2 (3.3%) Acinetobacter spp. the results indicated of 22 (36.6%) isolates of gram-positive bacteria, represented by: 16 (26.6%) isolates Staphylococcus aureus, 4 (6.6 %) another Staphylococcus spp., 2 (3.3%) Enterococcus spp. The study also shown the a increase in the concentration of TLR-3 , CXCL8 , IL-2 , IL-17 and IL-22 in the serum of bacterial patients compared with the healthy, Where the results of the current study show decreases in the concentration of TGF-β1 among compared with healthy. In conclusion, it was discovered that the infection of bacteria in wound infection was lower in females than males. Pseudomonas aeruginosa and S. aureus were found to be the highly isolated bacteria wound infection, with increases levels of TLR-3, CXCL8, IL-17 and IL-22 in serum in patients and decreases level of TGF-β1 in serum of patients.

Blood serum TGF-β1 content in children with new coronavirus infection

Impaired serum TGF-β1 production is one of the proposed mechanisms for coronavirus disease 2019 (COVID-19).Study objective: to study blood serum TGF-β1 content in children with new coronavirus infection.Materials and methods: a one-stage study was conducted in 119 patients with COVID-19 and compared with 118 healthy children of the same age and sex as a control group. The age range in both groups was 11.0 years. Preschoolers (0–6 years old) and schoolchildren (7–17 years old) in the group with COVID-19 were 21 (18%) and 98 (82%), respectively. Children with COVID-19 were divided into asymptomatic (n=23), mild (n=61), and moderate (n=35) subgroups. Serum samples for TGF-β1 concentration analysis were taken from all patients and tested by flow fluorimetry. The data were processed using the IBM SPSS Statistics Version 25.0 software package (International Business Machines Corporation, license No Z125-3301-14, USA).Results: median serum TGF-β1 levels of children 0–17 years old with COVID-19 regardless of the form of severity were significantly higher than in the control group. The serum concentration of TGF-β1 in children with COVID-19 of preschool age was increased comparing to schoolchildren. Children 0-6 years old with a moderate form of coronavirus infection had high serum TGF-β1 values when compared with school-age patients.Conclusion: elevated serum TGF-β1 levels were found in children both without clinical manifestations and with symptoms of coronavirus infection, reaching maximum values in the moderate form in children 0–6 years old.

Pancreatitis pain quality changes at year 1 follow-up, but GP130 remains a biomarker for pain

Background/objectivesDebilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). CP pain is dynamic due to multiple underlying mechanisms. The objective of this study was to 1) evaluate changes in pain phenotype at one year follow-up and 2) validate putative pain biomarkers in a prospective cohort study. MethodsThe Neuropathic and Nociceptive PROMIS-PQ questionnaires were used to classify pain for participants with in the PROCEED study. Putative serum biomarkers were measured via immunoassay. ResultsAt enrollment, 17.6 % (120/681) subjects with CP reported no pain in the previous year. Of those, 29 % experienced pain during the 1 yr follow-up whereas 18 % of those with pain prior to enrollment reported no pain during the 1 yr follow-up period. Of the 393 subjects with PROMIS-PQ data at enrollment, 212 also had follow-up data at 1 yr. Approximately half (53.3 %) of those individuals changed pain phenotype between baseline and follow-up. At 1 yr, serum TGFβ1 level was negatively correlated with nociceptive T-scores (p = 0.006). GP130 was significantly correlated with both nociceptive (p = 0.012) and neuropathic T-scores (p = 0.043) at 1 yr, which is consistent with the previously published findings. ConclusionsThe positive association between TGFβ1 and pain is not maintained over time, suggesting it is a poor pain biomarker. However, serum GP130 is a consistent biomarker for mixed-type pain in CP. Preclinical studies show that targeting TGFβ1 or IL-6 (ligand for GP130) is sufficient to inhibit CP pain supporting further investigation of this as a potential therapeutic target.

Efficacy and safety of compound glycyrrhizin combined with topical minoxidil for alopecia areata: a systematic review and meta-analysis of randomized controlled trials

Introduction Alopecia areata (AA) is a common autoimmune skin disease. Our study aimed to systematically evaluate the efficacy and safety of compound glycyrrhizin (CG) combined with topical minoxidil therapy in treating AA. Methods We searched the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Randomized controlled trials (RCTs) on CG combined with topical minoxidil therapy compared with topical minoxidil therapy alone for AA were included. The Cochrane Collaborative Network Tool was used to assess the risk of bias. Statistical analysis was completed using RevMan5.3 software and Stata 15.0 software. The GRADE system was used to evaluate the quality of evidence for outcomes. Result 11 RCTs and 1189 patients were included. Compared with topical minoxidil therapy alone, CG combined with topical minoxidil therapy was more effective at improving the clinical efficacy (RR = 1.36, 95% CI [1.27, 1.45], p < 0.00001). The SALT score (MD = −10.09, 95% CI [−12.89, −7.30], p < 0.00001), serum TNF-α levels (MD = −0.99, 95% CI [−1.19, −0.39], p < 0.00001), serum IL-12 levels (MD = −8.84, 95% CI [−11.20, −6.47], p < 0.00001) and serum IFN-γ levels (MD = −7.44, 95% CI [−11.51, −3.37], p = 0.0003) were reduced, and the serum TGF-β1 levels (MD = 2.40, 95% CI [1.24, 3.57], p < 0.0001) were increased. There were no significant differences in reported adverse events, including irritant contact dermatitis (RR = 0.51, 95% CI [0.25, 1.01], p = 0.05),’ gastrointestinal reactions (RR = 2.47, 95% CI [0.49, 12.55], p = 0.28), lower limb edema (RR = 2.60, 95% CI [0.61, 11.06], p = 0.20), facial edema (RR = 2.33, 95% CI [0.61, 8.93], p = 0.22), or localized itching (RR = 0.56, 95% CI [0.18, 1.75], p = 0.32), between the two groups. Conclusion The current evidence indicates that CG combined with topical minoxidil therapy is effective and safe for AA. However, owing to the suboptimal quality of the included studies, more high-quality and large-scale RCTs are needed for comprehensive analysis and further validation.

Endothelial mesenchymal transition promotes pannus formation in ankylosing spondylitis byactivation of TGF-β/SMAD signalling pathway.

To explore the role of endothelial-mesenchymal transition (EndMT) mediated by the TGF-β/SMAD signalling pathway in the pathogenesis of ankylosing spondylitis (AS). Serum levels of TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA) in 48 patients with AS and 15 healthy subjects. The expression levels of TGF-β1, SMAD7, CTGF, CD34 and EndMT-related markers (α-SMA, vimentin, FSP-1, VE-cadherin) in the sacroiliac joint (SIJ) of three AS patients were detected by immunohistochemistry, and three non-spondyloarthritis (SpA) autopsy samples were used as controls. Serum TGF-β1 level of AS patients was significantly higher than that of healthy controls (22971 ± 7667 pg/ml vs. 14837±4653 pg/ml, p<0.01). Compared with the non-SpA control group, the microvascular density (MVD) at the pannus formation site of SIJ in AS patients was significantly increased, accompanied by respectively increased expressions of TGF-β1, CTGF, α-SMA, vimentin, and FSP-1 (all p<0.05), whereas respectively decreased expressions of VE-cadherin and SMAD7 (p<0.01). The expression level of FSP-1 was positively correlated with levels of TGF-β1 and MVD, and negatively correlated with SMAD7. Our findings show that EndMT is involved in the promotion of pannus formation by TGF-β/SMAD signalling pathway activation in AS.

Impacts of circulating cytokine levels and gene polymorphism predisposition on type 1 diabetes mellitus.

A wide range of cytokines has been demonstrated to be involved in the etiology of type 1 diabetes mellitus (T1DM). Gene polymorphisms may potentially contribute to a hereditary predisposition toward circulating cytokine levels as (high, intermediate, or low) since they can affect cytokine production or function. The aim of this study was to investigate the roles of cytokine levels and the association of single-nucleotide polymorphisms (SNPs) within cytokine genes with T1DM in Saudi children. Totals of 91 well-characterized T1DM patients and 91 T1DM-free control subjects were enrolled in this study. The levels of 3 circulating cytokines (transforming growth factor [TGF]-β1, interleukin [IL]-10, and IL-6) and 6 SNPs in 3 cytokine genes (TGF-β1 [rs1800470 and rs1800471], IL-10 [rs1800896, rs1800871, and rs1800872], and IL-6 [rs1800795]) that contribute to genetic susceptibility were measured by enzyme-linked immunosorbent assay and polymerase chain reaction with sequence-specific primers. Our fn dings show that TGF-β1 serum levels were signifcantly lower in the children with T1DM than in the control participants. The TGF-β1 genotypes with a high-production phenotype were signifcantly less frequent and those with a lowproduction phenotype were signifcantly more frequent in the children with T1DM compared to the control participants. respectively. Furthermore, the IL-6 genotype frequency with low level of IL-6 production were signifcantly increased in the T1DM group compared to the control group. Moreover, our data demonstrated no appreciable diferences in circulating serum level or genotype and phenotype of IL- 10 between the patients and controls. This kind of measurement, which considers the prediction of T1DM, may be useful in assessing the severity of T1DM and susceptibility to T1DM among Saudi children.