Transforming Growth Factor-β1 Levels Research Articles

Comparison of Effects of Acellular Dermal Matrix and Latissimus Dorsi Muscle Flap on Radiation-induced Peri-implant Capsular Contracture in a Rabbit Model

Abstract Background Capsular contracture of breast implants is a major complication in breast surgery. Clinically, covering a breast implant with acellular dermal matrix (ADM) or autologous tissue is considered to be the most effective technique to prevent capsular contracture. This study was designed to compare the protective effects of ADM and latissimus dorsi (LD) muscle flap placement on capsular contracture by increasing the rate of capsular contracture through controlled radiation exposure in a rabbit model. Methods Twenty New Zealand white rabbits were divided into three groups. After the implant was placed beneath the pectoralis major muscle, the lateral third of the implant was left exposed in the control group (n = 6). In the ADM group (n = 7), the exposed implant was covered with AlloDerm. In the LD flap group (n = 7), the exposed implant was covered with a pedicled LD muscle flap. All groups were irradiated 3 weeks after implant insertion. After 6 months, peri-implant tissues were harvested and analyzed. Results ADM showed markedly lower myofibroblast activity than the LD flap. However, transforming growth factor-β1 levels and the activity of collagen types I and III produced in fibroblasts were significantly lower in the ADM group than in the LD flap group. Conclusion Based on the findings of our rabbit experiments, ADM is expected to have a comparative advantage in reducing the risk of capsular contracture compared to the LD flap.

Circulating Endothelin 1 but Not Transforming Growth Factor-β Levels Are Reduced after Pulmonary Endarterectomy in Subjects Affected by Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study.

Background and objectives: Endothelin-1 (ET-1) and transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology and vascular remodeling of chronic thromboembolic pulmonary hypertension (CTEPH) which is an under-diagnosed complication of acute pulmonary embolism (PE). Currently, pulmonary endarterectomy (PEA) is still the treatment of choice for selected patients suffering from CTEPH. The aim of this study was to evaluate the preoperative and postoperative circulating levels of ET-1 and TGF-β in subjects affected by CTEPH undergoing successful surgical treatment by PEA. Methods: The data from patients diagnosed with CTEPH who underwent PEA at the Foundation IRCCS Policlinico San Matteo Hospital (Pavia, Italy) were prospectively recorded in the Institutional database. Circulating ET-1 and TGF-β levels were assessed by an ELISA commercial kit before PEA, at 3 months and 1 year after PEA. The demographic data, preoperatory mean pulmonary arterial pressure (mPAP), cardiac output (CO), and pulmonary vascular resistance (PVR) were also recorded. Univariate and multivariate analyses were performed. Results: The analysis included 340 patients with complete ET-1 measurements and 206 patients with complete TGF-β measurements. ET-1 significantly decreased both at 3 months (p < 0.001) and at 1 year (p = 0.009) after PEA. On the other hand, preoperatory TGF-β levels did not significantly change after PEA. Furthermore, ET-1, but not TGF-β, was a good predictor for increased mPAP in multivariate analyses (p < 0.05). Conclusions: ET-1 but not TGF β was significantly modulated by PEA in subjects affected by CTEPH up to 1 year after surgery. The mechanisms leading to prolonged elevated circulating TGF-β levels and their clinical significance have to be further elucidated.

Effect of Advanced Platelet-Rich Fibrin Injection on Transforming Growth Factor-β1 Level during Orthodontic Tooth Movement in Rabbits

Effect of Advanced Platelet-Rich Fibrin Injection on Transforming Growth Factor-β1 Level during Orthodontic Tooth Movement in Rabbits

Relationships of the Transforming Growth Factor β1 Level and the G/C (+915) of Its Gene Polymorphism with the Development of Atrial Fibrillation in Patients with Arterial Hypertension

Relationships of the Transforming Growth Factor β1 Level and the G/C (+915) of Its Gene Polymorphism with the Development of Atrial Fibrillation in Patients with Arterial Hypertension

Effects of selenoprotein extracts from Cardamine hupingshanensis on growth, selenium metabolism, antioxidant capacity, immunity and intestinal health in largemouth bass Micropterus salmoides.

This study aimed to assess the impact of dietary selenoprotein extracts from Cardamine hupingshanensis (SePCH) on the growth, hematological parameters, selenium metabolism, immune responses, antioxidant capacities, inflammatory reactions and intestinal barrier functions in juvenile largemouth bass (Micropterus salmoides). The base diet was supplemented with four different concentrations of SePCH: 0.00, 0.30, 0.60 and 1.20 g/Kg (actual selenium contents: 0.37, 0.59, 0.84 and 1.30 mg/kg). These concentrations were used to formulate four isonitrogenous and isoenergetic diets for juvenile largemouth bass during a 60-day culture period. Adequate dietary SePCH (0.60 and 1.20 g/Kg) significantly increased weight gain and daily growth rate compared to the control groups (0.00 g/Kg). Furthermore, 0.60 and 1.20 g/Kg SePCH significantly enhanced amounts of white blood cells, red blood cells, platelets, lymphocytes and monocytes, and levels of hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin in the hemocytes. In addition, 0.60 and 1.20 g/Kg SePCH increased the mRNA expression levels of selenocysteine lyase, selenophosphate synthase 1, 15 kDa selenoprotein, selenoprotein T2, selenoprotein H, selenoprotein P and selenoprotein K in the fish liver and intestine compared to the controls. Adequate SePCH not only significantly elevated the activities of antioxidant enzymes (Total superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase), the levels of total antioxidant capacity and glutathione, while increased mRNA transcription levels of NF-E2-related factor 2, Cu/Zn-superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase. However, adequate SePCH significantly decreased levels of malondialdehyde and H2O2 and the mRNA expression levels of kelch-like ECH-associated protein 1a and kelch-like ECH-associated protein 1b in the fish liver and intestine compared to the controls. Meanwhile, adequate SePCH markedly enhanced the levels of immune factors (alkaline phosphatase, acid phosphatase, lysozyme, complement component 3, complement component 4 and immunoglobulin M) and innate immune-related genes (lysozyme, hepcidin, liver-expressed antimicrobial peptide 2, complement component 3 and complement component 4) in the fish liver and intestine compared to the controls. Adequate SePCH reduced the levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin 8, interleukin 1β and interferon γ), while increasing transforming growth factor β1 levels at both transcriptional and protein levels in the liver and intestine. The mRNA expression levels of mitogen-activated protein kinase 13 (MAPK 13), MAPK14 and nuclear factor kappa B p65 were significantly reduced in the liver and intestine of fish fed with 0.60 and 1.20 g/Kg SePCH compared to the controls. Histological sections also demonstrated that 0.60 and 1.20 g/Kg SePCH significantly increased intestinal villus height and villus width compared to the controls. Furthermore, the mRNA expression levels of tight junction proteins (zonula occludens-1, zonula occludens-3, Claudin-1, Claudin-3, Claudin-5, Claudin-11, Claudin-23 and Claudin-34) and Mucin-17 were significantly upregulated in the intestinal epithelial cells of 0.60 and 1.20 g/Kg SePCH groups compared to the controls. In conclusion, these results found that 0.60 and 1.20 g/Kg dietary SePCH can not only improve growth, hematological parameters, selenium metabolism, antioxidant capacities, enhance immune responses and intestinal functions, but also alleviate inflammatory responses. This information can serve as a useful reference for formulating feeds for largemouth bass.

Unraveling the complex relationship between mRNA and protein abundances: a machine learning-based approach for imputing protein levels from RNA-seq data.

The correlation between messenger RNA (mRNA) and protein abundances has long been debated. RNA sequencing (RNA-seq), a high-throughput, commonly used method for analyzing transcriptional dynamics, leaves questions about whether we can translate RNA-seq-identified gene signatures directly to protein changes. In this study, we utilized a set of 17 widely assessed immune and wound healing mediators in the context of canine volumetric muscle loss to investigate the correlation of mRNA and protein abundances. Our data reveal an overall agreement between mRNA and protein levels on these 17 mediators when examining samples from the same experimental condition (e.g. the same biopsy). However, we observed a lack of correlation between mRNA and protein levels for individual genes under different conditions, underscoring the challenges in converting transcriptional changes into protein changes. To address this discrepancy, we developed a machine learning model to predict protein abundances from RNA-seq data, achieving high accuracy. Our approach also effectively corrected multiple extreme outliers measured by antibody-based protein assays. Additionally, this model has the potential to detect post-translational modification events, as shown by accurately estimating activated transforming growth factor β1 levels. This study presents a promising approach for converting RNA-seq data into protein abundance and its biological significance.

Efficacy of Agmatine Treatment in Experimental Acute Pancreatitis Rat Model.

Acute pancreatitis which is characterized by pancreatic inflammation can sometimes be difficult to treat because of limited therapeutic options. The purpose of the study was to assess the effects of agmatine in the acute pancreatitis experimental rat model. An acute pancreatitis model was created with the administration of cerulein in 40 female Sprague-Dawley rats. Agmatine was administered as a protective agent at 5 mg/kg (low dose) and 10 mg/kg (high dose). The rats were divided into 5 groups, each with 8 rats: group 1 (acute pancreatitis); group 2 (acute pancreatitis+low-dose agmatine 5 mg/kg); group 3 (acute pancreatitis+high-dose agmatine 10 mg/kg); group 4 (placebo, acute pancreatitis+saline); and group 5 (sham and saline infusion). All rats were sacrificed 24 hours after the last injection, and the levels of superoxide dismutase, interleukin-1 beta, and tumor necrosis factor-alpha were assessed in blood samples collected via cardiac puncture. Histopathological examination was performed by a pathologist, who was blind to the groups, according to the Schoenberg's pancreatitis scoring index. The amylase (16.67 and 37.89 U/L), glutathione peroxidase (13.62 and 18.44 ng/mL), tumor necrosis factor-α (39.68 and 64 ng/mL), interleukin-1 (484.73 and 561.83 pg/mL), and transforming growth factor-β (110.52 and 126.34 ng/L) levels were significantly lower and superoxide dismutase (1.29 and 0.98 ng/L) and malondialdehyde (0.99 and 0.96 nmol/mL) levels were significantly higher in group 3 compared to group 1 (P < .05). Moreover glutathione peroxidase, tumor necrosis factor-α, and transforming growth factor-β levels were lower, and malondialdehyde levels were higher in the group 3 compared to group 2 (P < .05). Although the Schoenberg's pancreatitis scoring index was not significantly different between the high- and low-dose treatment groups, rats who received high-dose treatment had significantly lower scores compared to those with acute pancreatitis group. This is the first study that evaluated the efficacy of agmatine in an experimental model of acute pancreatitis. Agmatine, an anti-inflammatory and antioxidant agent, had a protective effect in an experimental rat model of acute pancreatitis.

The Synergistic Effect of Full-Spectrum Light Therapy and Transient Immunosuppressants Prolonged Allotransplant Survival.

The lifelong administration of immunosuppressants remains the largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model. Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term antilymphocyte serum (ALS) and cyclosporine A (CsA). Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis. The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared with the control (group 1). However, in group 4, FBLT combined with short-term ALS/CsA, median composite tissue allograft survival time (266 days) was significantly prolonged compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) ( P < 0.01). Group 4 also showed a significant increase in regulatory T cells ( P = 0.04) and transforming growth factor-β1 levels ( P = 0.02), and a trend toward a decrease in interleukin-1β levels ( P = 0.03) at 16 weeks after transplantation as compared with control (group 1). FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and antiinflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival. Full-spectrum light therapy could be a potential strategy to increase vascularized composite allotransplant survival.

Research progress on the correlation between transforming growth factor-β level and depression symptoms.

Transforming growth factor (TGF)-β is a group of cytokines with anti-inflammatory effects in the TGF family, which participates in the development process of stress and depression-related mechanisms, and plays a role in the regulation of inflammatory response in depression and the recovery of various cytokine imbalances. The core symptom group of depression is associated with TGF-β level, and the psychological symptom group of depression is related to TGF-β gene polymorphism. Various antidepressants may up-regulate TGF-β level through the complex interaction between neurotransmitters and inflammatory factors, inhibiting inflammatory response and regulating cytokine imbalance to improve depressive symptoms. Studies have shown that recombinant TGF-β1 protein has beneficial effects in mouse depression models and the nasal sprays have unique advantages of fast acting, indicating TGF-β1 might be a potential therapeutic target for depression. This article reviews the research progress on dynamic changes of TGF-β level before and after depression treatment and the application of TGF-β level as an indicator for the improvement of depressive symptoms, to provide new ideas for the development of new antidepressants and the evaluation method of the efficacy of depression treatment.

Immunomodulation with romiplostim as a second-line strategy in primary immune thrombocytopenia: The iROM study.

Thrombopoietin receptor agonists (TPO-RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first-line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end-points included the sustained remission off-treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)-4, IL-9 and IL-17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor-β levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation.

The Level of Inflammatory Markers and Their Relationship with Fat Tissue Distribution in Children with Obesity and Type 2 Diabetes Mellitus.

This study aimed to determine the changes in proinflammatory and anti-inflam- matory markers in children aged 10-18, who were not diagnosed with type 2 diabetes mel- litus, were obese/overweight, and children with type 2 diabetes mellitus. In addition, we aimed to investigate whether these markers were associated with clinical and laboratory parame- ters, subcutaneous adipose tissue, preperitoneal adipose tissue, visceral adipose tissue, and hepatosteatosis. Children between the ages of 10 and 18, obese/overweight, with type 2 diabetes mellitus, and with a normal body mass index were included. Fat tissue thick- ness was measured. Tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-18, and interferon-γ as proinflammatory markers and transforming growth factor-β and interleukin-10 levels as anti-inflammatory markers were studied. Twenty-eight (31.8%) controls, 44 (50%) obese/overweight, and 16 (18.2%) patients with type 2 diabetes mellitus were included in our study. Age, sex, and puberty were similar between the groups. In the type 2 diabetes mellitus group, the subcutaneous fat tissue thick- ness was higher than that in the obese group, and the preperitoneal and visceral fat tissue thicknesses were similar to those in the obese group. Proinflammatory markers and interleu- kin-10 levels were similar in the obese/overweight, type 2 diabetes mellitus, and control groups. Transforming growth factor-β levels were significantly lower in the type 2 diabetes mellitus group than in the control group (P = .039). Transforming growth factor-β levels and other labo- ratory variables did not differ significantly in the type 2 diabetes mellitus group. While there was no change in all markers in the obese/overweight group com- pared with the control group, proinflammatory markers in the type 2 diabetes mellitus group were similar to those in the obese/overweight and control groups, and transforming growth factor-β level, an anti-inflammatory marker, was lower in the type 2 diabetes mellitus group than in the control group.

Multicenter Phase 1b/2a Clinical Trial of Radioprotectant BIO 300 Oral Suspension for Patients With Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy

Radiation therapy is part of the standard treatment regimen for non-small cell lung cancer (NSCLC). Although radiation therapy is an effective tool to manage NSCLC, it can be associated with significant dose-limiting toxicities. These toxicities can lead to treatment interruption or early termination and worsening clinical outcomes in addition to reductions in patient quality of life. Based on preclinical efficacy for radioprotection of normal tissues, we evaluated the clinical utility of BIO 300 Oral Suspension (BIO 300; synthetic genistein nanosuspension) in patients with NSCLC. In this multicenter, open-label, single-arm, ascending dose phase 1b/2a study, patients were enrolled with newly diagnosed stage II-IV NSCLC planned for 60 to 70/1.8-2.0 Gy radiation therapy and concurrent weekly paclitaxel/carboplatin. Oral BIO 300 (cohort 1, 500 mg/d; cohort 2, 1000 mg/d; cohort 3, 1500 mg/d) was self-administered once daily starting 2 to 7 days before initiating concurrent chemoradiotherapy and continued until the end of radiation therapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate, and survival. Twenty-one participants were enrolled. No dose-limiting toxicities were reported. BIO 300 dosing did not alter chemotherapy pharmacokinetics. Adverse events were not dose-dependent, and those attributable to BIO 300 (n=11) were all mild to moderate in severity (grade 1, n=9; grade 2, n=2) and predominantly gastrointestinal (n=7). A dose-dependent decrease in serum transforming growth factor β1 levels was observed across cohorts. Based on safety analysis, the maximum tolerated dose of BIO 300 was not met. Patient-reported quality of life and weight were largely stable throughout the study period. No patient had progression as their best overall response, and a 65% tumor response rate was achieved (20% complete response rate). The low toxicity rates, along with the pharmacodynamic results and tumor response rates, support further investigation of BIO 300 as an effective radioprotector.

Effectiveness of Azadirachta Indica Leaf Extract Against Transforming Growth Factor-β Levels in Swiss Mice Inoculated by Plasmodium berghei ANKA

Malaria is one of the health problems for the world's population in tropical and subtropical regions. Malaria infection is caused by the protozoa &lt;em&gt;Plasmodium spp&lt;/em&gt;. This study aims to determine the effectiveness of &lt;em&gt;A. indica&lt;/em&gt; Leaf extract against TGF-β&lt;em&gt; &lt;/em&gt;levels in Swiss mice inoculated with &lt;em&gt;Plasmodium berghei&lt;/em&gt; ANKA (PbA). This study used true experimental with a post-test design only control group design which used Swiss mice subjects weighing 30-35 grams as much as 24 heads and divided into four groups (K, T1, T2, T3); all groups were inoculated PbA. Group T1 (&lt;em&gt;A. indica&lt;/em&gt; leaf extract therapy at a dose of 0.25 mg/grBB), Group T2 (&lt;em&gt;A. indica&lt;/em&gt; leaf extract therapy at a dose of 0.5 mg/grBB), Group T3 (&lt;em&gt;A. indica&lt;/em&gt; leaf extract therapy at a dose of 1 mg/grBB). Data analysis using the &lt;em&gt;Anova + posthoc test&lt;/em&gt; with a significance value of p &amp;lt; 0.05 and CI of 95%. The results showed differences in TGF-β levels, both in the control and treatment groups after treatment, with a p-value of &amp;lt; 0.05. Greater increases in TGF-β levels occurred in the T3 group (average +38.46 pg/ml) compared to group K (average +14.37 pg/ml), group T1 (average +14.37 pg/ml), and group T2 (average +22.13 pg/ml)

Empagliflozin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Modulating Sesn2/AMPK/Nrf2 Signaling and Targeting Ferroptosis and Autophagy.

Pulmonary fibrosis (PF) is a life-threatening disorder that severely disrupts normal lung architecture and function, resulting in severe respiratory failure and death. It has no definite treatment. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has protective potential in PF. However, the mechanisms underlying these effects require further elucidation. Therefore, this study aimed to evaluate the ameliorative effect of EMPA against bleomycin (BLM)-induced PF and the potential mechanisms. Twenty-four male Wister rats were randomly divided into four groups: control, BLM treated, EMPA treated, and EMPA+BLM treated. EMPA significantly improved the histopathological injuries illustrated by both hematoxylin and eosin and Masson's trichrome-stained lung tissue sections, as confirmed by electron microscopic examination. It significantly reduced the lung index, hydroxyproline content, and transforming growth factor β1 levels in the BLM rat model. It had an anti-inflammatory effect, as evidenced by a decrease in the inflammatory cytokines' tumor necrosis factor alpha and high mobility group box 1, inflammatory cell infiltration into the bronchoalveolar lavage fluid, and the CD68 immunoreaction. Furthermore, EMPA mitigated oxidative stress, DNA fragmentation, ferroptosis, and endoplasmic reticulum stress, as evidenced by the up-regulation of nuclear factor erythroid 2-related factor expression, heme oxygenase-1 activity, glutathione peroxidase 4 levels, and a decrease in C/EBP homologous protein levels. This protective potential could be explained on the basis of autophagy induction via up-regulating lung sestrin2 expression and the LC3 II immunoreaction observed in this study. Our findings indicated that EMPA protected against BLM-induced PF-associated cellular stress by enhancing autophagy and modulating sestrin2/adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase 1 signaling.

Effect of Tadalafil in Comparison with Clobetasol ointment in induced Psoriasis in Mice Male

Psoriasis is an immune-mediated chronic inflammatory skin disease. It is define as a clinical entity, affecting the skin, nails, mucous membranes, and joints. The psoriasis pathogenesis primarily shares the combined influence of several gene susceptibilities and incorrect of the immune system together with pervasive risk factors of environment. Tadalafil is a strong phosphodiesterase- 5 blocker that relaxes smooth muscle and prevents the breakdown of the cyclic guanosine monophosphate. The aim is to evaluate the possible beneficial effect of oral tadalafil plus tadalafil gel in comparison with clobetasol in induced psoriasis in mice. Accordingly, forty male BALB/c Albino mice animal experiments in the stage of age 8-11 weeks and body mass ranged 25-40 g; were divided equally into four groups (ten mice/group) after their skin of the dorsal back and right ear being shaved for topical application: Group I (normal control) healthy mice without treatment. Group II (Induction group) in which mice experiment administered topical dose of a limited dose of imiquimod cream (5%) for seven days. The following groups (III and IV), after being received imiquimod cream (5%) as mentioned in the induction group, mice were treated for a further two weeks with either clobetasol ointment (0.05%) topically once daily (clobetasol group), tadalafil gel (0.05%) topically once daily plus oral tadalafil in a dose of 5 mg/kg once daily (tadalafil gel + oral group). This study demonstrated a highly significant reduction in pro-inflammatory tumor necrosis factor-α and interlukin-23 profile, with no significant decrease in the level of interlukin-17 and vascular endothelial growth factor, and significantly elevation in transforming growth factor-β level in tadalafil gel plus oral group in comparison to the induction group.ConclusionThis study conclude the possible effect of anti-inflammatory activity of oral and gel of tadalafil on skin homogenate parameters in comparison with clobetasol in induced psoriasis in mice.

Sodium butyrate attenuates peritoneal fibroproliferative process in mice.

What is the central question of this study? Peritoneal injury can result in a persistent fibroproliferative process in the abdominal cavity, causing pain and loss of function of internal organs. This study aimed to demonstrate the use of sodium butyrate (NaBu) as a potential agent to attenuate peritoneal fibrosis induced by a synthetic matrix. What is the main finding and its importance? Our findings provide the first evidence that NaBu attenuates the inflammatory, angiogenesis and fibrogenesis axes involved in the formation of peritoneal fibrovascular tissue, indicating the potential of this compound to ameliorate peritoneal fibrosis. The aim of this study was to identify the bio-efficacy of sodium butyrate (NaBu) on preventing the development of peritoneal fibrovascular tissue induced by implantation of a synthetic matrix in the abdominal cavity. Polyether-polyurethane sponge discs were implanted in the peritoneal cavity of mice, which were treated daily with oral administration of NaBu (100mg/kg). Control animals received water (100μl). After 7 days, the implants were removed for assessment of inflammatory, angiogenic and fibrogenic markers. Compared with control values, NaBu treatment decreased mast cell recruitment/activation, inflammatory enzyme activities, levels of pro-inflammatory cytokines, and the proteins p65 and p50 of the nuclear factor-κB pathway. Angiogenesis, as determined by haemoglobin content, vascular endothelial growth factor levels and the number of blood vessels in the implant, was reduced by the treatment. In NaBu-treated animals, the predominant collagen present in the abdominal fibrovascular tissue was thin collagen, whereas in control implants it was thick collagen. Transforming growth factor-β1 levels were also lower in implants of treated animals. Sodium butyrate downregulated the inflammatory, angiogenesis and fibrogenesis axes of the fibroproliferative tissue induced by the intraperitoneal synthetic matrix. This compound has potential to control/regulate chronic inflammation and adverse healing processes in the abdominal cavity.

Sinomenine promotes differentiation of induced pluripotent stem cells into immature dendritic cells with high induction of immune tolerance.

BACKGROUNDImmature dendritic cells (imDCs) play an important role in the induction of donor-specific transplant immunotolerance. However, these cells have limitations, such as rapid maturation and a short lifespan in vivo. In previous studies, induced pluripotent stem cells (iPSCs) differentiated into imDCs, and sinomenine (SN) was used to inhibit the maturation of imDCs. AIMTo study the capacity of SN to maintain iPSC-derived imDCs (SN-iPSCs-imDCs) in an immature state and the mechanism by which SN-iPSCs-imDCs induce immunotolerance.METHODSIn this study, mouse iPSCs were induced to differentiate into imDCs in culture medium without or with SN (iPSCs-imDCs and SN-iPSCs-imDCs). The imDC-related surface markers, endocytotic capacity of fluorescein isothiocyanate-Dextran and apoptosis were analyzed by flow cytometry. The effects of iPSCs-imDCs and SN-iPSCs-imDCs on T-cell stimulatory function, and regulatory T (Treg) cell proliferative function in vitro were analyzed by mixed lymphocyte reaction. Cytokine expression was detected by ELISA. The apoptosis-related proteins of iPSCs-DCs and SN-iPSCs-DCs were analyzed by western blotting. The induced immunotolerance of SN-iPSCs-DCs was evaluated by treating recipient Balb/c skin graft mice. Statistical evaluation of graft survival was performed using Kaplan–Meier curves.RESULTSBoth iPSCs-imDCs and SN-iPSCs-imDCs were successfully obtained, and their biological characteristics and ability to induce immunotolerance were compared. SN-iPSCs-imDCs exhibited higher CD11c levels and lower CD80 and CD86 levels compared with iPSCs-imDCs. Reduced major histocompatibility complex II expression, worse T-cell stimulatory function, higher Treg cell proliferative function and stronger endocytotic capacity were observed with SN-iPSCs-imDCs (P < 0.05). The levels of interleukin (IL)-2, IL-12, interferon-γ in SN-iPSCs-imDCs were lower than those in iPSCs-imDCs, whereas IL-10 and transforming growth factor-β levels were higher (P < 0.05). The apoptosis rate of these cells was significantly higher (P < 0.05), and the expression levels of cleaved caspase3, Bax and cleaved poly(ADP-ribose) polymerase were higher after treatment with lipopolysaccharides, but Bcl-2 was reduced. In Balb/c mice recipients immunized with iPSCs-imDCs or SN-iPSCs-imDCs 7 d before skin grafting, the SN-iPSCs-imDCs group showed lower ability to inhibit donor-specific CD4+ T-cell proliferation (P < 0.05) and a higher capacity to induce CD4+CD25+FoxP3+ Treg cell proliferation in the spleen (P < 0.05). The survival span of C57bl/6 skin grafts was significantly prolonged in immunized Balb/c recipients with a donor-specific pattern. CONCLUSIONThis study demonstrated that SN-iPSCs-imDCs have potential applications in vitro and in vivo for induction of immunotolerance following organ transplantation.

Urethral monopolar cauterization: alternative infravesical obstruction model in male rats.

SUMMARYOBJECTIVE:We aimed to determine which method gives the most consistent results between urethral monopolar cauterization and standard urethral partial ligation methods for the urethral obstruction model.METHODS:Thirty male rats were randomly divided into control, partial ligation, and monopolar cauterization groups. Six weeks after experimental procedures, the experimental groups were evaluated cystometrically, biochemically, and histologically.RESULTS:According to the cystometric results, bladder capacity, baseline bladder pressure, and compliance data of the monopolar cauterization group were higher than those of the partial ligation and monopolar cauterization groups (p<0.05 and p<0.01, respectively). As a biochemical evaluation, malondialdehyde levels in bladder tissues of group control were higher than partial ligation and monopolar cauterization groups (p<0.05 and p<0.01, respectively). The collagen type I level of the control group was higher than the partial ligation and monopolar cauterization groups (p<0.01 and p<0.05, respectively). Collagen type III levels of the monopolar cauterization group were higher than those of the control group (p<0.01), but the Collagen type I/Collagen type III and transforming growth factor-β levels of the monopolar cauterization group were significantly lower than those of the control group (p<0.001). As a histological evaluation (hematoxylin and eosin), fibrosis in the lamina propria was more prominent in the monopolar cauterization group than in the control group (p<0.05). In addition, the muscular thickness was higher in the monopolar cauterization group compared with control and partial ligation groups (p<0.001 and p<0.01, respectively).CONCLUSION:The needle-tipped monopolar cauterization of the posterior urethra may be the method of choice for creating a chronic infravesical obstruction model of infravesical obstruction in male rats.

Lower-Body Resistance Training Reduces Interleukin-1β and Transforming Growth Factor-β1 Levels and Fatigue and Increases Physical Performance in Breast Cancer Survivors.

Martins, FM, Santagnello, SB, de Oliveira Junior, GN, de Sousa, JdFR, Michelin, MA, Nomelini, RS, Murta, EFC, and Orsatti, FL. Lower-body resistance training reduces interleukin-1β and transforming growth factor-β1 levels and fatigue and increases physical performance in breast cancer survivors. J Strength Cond Res 37(2): 439-451, 2023-This article ascertains whether resistance training (RT) improves inflammatory markers, fatigue (sensations and fatigability), and physical performance in breast cancer survivors (BCS) and investigates whether the changes in the inflammatory markers, fatigue, and physical performance are associated with each other. Volunteers were randomly divided into 2 groups: control group (n = 11) and RT group (n = 11). Resistance training (3 sets of 8-12 repetitions with 80% 1 repetition maximum (1RM) on 4 exercises-leg extension, leg curl, 45° leg press, and calf raise) was performed 3 times a week for 12 weeks. Self-reported fatigue (SRF), fatigability (critical torque [CT] and W prime [W']), muscle strength, and circulating inflammatory markers were assessed using the Brief Fatigue Inventory, iDXA, 1RM test, protocol of 60 maximal voluntary isometric contractions, and enzyme-linked immunosorbent assay, respectively. Resistance training reduced interleukin (IL)-1β, transforming growth factor (TGF)-β1, and SRF score and increased muscle strength, 6-minute walk test (6MWT), CT, and W'. In the RT group, the changes in SRF were positively associated with the changes in IL-1β. The changes in muscle strength were associated with the changes in CT and W', and the changes in the 6MWT were associated with the changes in CT, W', muscle strength, and SRF. Resistance training improved fatigue and physical performance and reduced IL-1β, and TGF-β1 in BCS. Although improvement in fatigability seems to be dependent on the increase in muscle strength, improvement in the sensation of fatigue seems to be dependent on the reduction in IL-1β after RT. Increase in physical performance seems to be dependent on improvement in muscle strength and fatigue.

De-sialylated and sialylated IgG anti-dsDNA antibodies respectively worsen and mitigate experimental mouse lupus proteinuria and possible mechanisms

BackgroundThe role of sialylated and de-sialylated (de-SIA) IgG anti-dsDNA antibodies in experimental mouse lupus remains unclear. Aim of the studyTo examine how sialylated and de-SIA IgG anti-dsDNA antibodies affect lupus mouse proteinuria and possible mechanisms. MethodsBlood was serially obtained from pristane-induced female BALB/c lupus mice to assess correlations between alpha-2,6-sialic cid (SIA) ratios of serum IgG anti-dsDNA and proteinuria. Kidney C3 staining was correlated with blood IgG anti-dsDNA. Sialylated IgG anti-dsDNA with its de-SIA form was administered to determine the effect on lupus proteinuria and in vitro consequences. ResultsWe observed that the SIA contents of IgG anti-dsDNA were lower in Week 16/1+ (Week 16 with 1 + proteinuria) and W24/2 + mice than those in W16 (no proteinuria) and W24/1 + mice, respectively (P < 0.005 for both). C3 staining densities in the kidney correlated inversely with the α-2,6-SIA content of plasma IgG anti-dsDNA (r = -0.660). Highly sialylated A52L1 IgG anti-dsDNA injection mitigated lupus proteinuria significantly from PBS injection; however, its de-SIA form worsened proteinuria (aggravation of proteinuria: the latter vs. the former [sialylated A52L1 IgG anti-dsDNA] with an infinite odds ratio). Highly sialylated A52L1 IgG anti-dsDNA resulted in higher interleukin (IL)-10/IL-12 ratios, higher transforming growth factor-β1 levels, and lower tumor necrosis factor-α levels in sera than its de-SIA from. ConclusionWe concluded that a low SIA/serum IgG anti-dsDNA ratio indicated a high severity of nephritis in pristane-induced lupus mice. Highly sialylated IgG anti-dsDNA, in contrast to the de-SIA form, alleviated the severity of lupus proteinuria.