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Objective To explore the possible mechanisms by which fibroblast growth factor (FGF) 23 promoted atrial fibrosis in circulation of chronic kidney disease (CKD) by binding to atrial tissue fibroblast growth factor receptor (FGFR) 4. Methods Twenty-two healthy male Sprague-Dawley (SD) rats were selected. Rats were randomly selected to undergo 5/6 nephrectomy and fed for 15 weeks to establish a CKD model (n=14). The remaining 8 rats were used as the sham group. The sham group (n=8) underwent the same surgery without removing renal tissue. Body weight, blood pressure, renal function, cardiac ultrasound, epicardial electrocardiography and pathological indices were monitored in both groups. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the circulating levels of FGF23 in the two groups of rats. Transcriptomic analysis of left atrial tissue was performed to search for differentially expressed genes. Rat atrial fibroblasts were divided into the control group, the FGFR inhibitor group, the transforming growth factor- β (TGF-β) group and the TGF- β +FGFR inhibitor group. The expression levels of α -smooth muscle actin (α -SMA), collagen Ⅰ (Col Ⅰ) and phosphorylated protein kinase B (p-AKT) protein were detected by Western blot assay. Results Systolic blood pressure, blood urea nitrogen and creatinine were elevated in the CKD group of rats. Cardiac electrophysiological study showed that CKD could promote the occurrence of atrial fibrillation (AF) and atrioventricular block. Cardiac ultrasound suggested that the internal diameter of the left atrium was significantly increased in rats of the CKD group. Pathological findings showed that the left atrium in the CKD group underwent significant fibrosis, and epicardial electrical markers showed that left atrial electrical conduction velocity was significantly slower and conduction heterogeneity was significantly increased in the CKD group. These changes were accompanied by higher circulating FGF23. Western blot results showed that FGFR4 expression was upregulated in the CKD group. After blocking the FGF23/FGFR4 signaling pathway in atrial fibroblasts, the fibrosis-related proteins α-SMA, Col Ⅰ and p-AKT/AKT were decreased. Conclusion CKD promotes the occurrence of AF by inducing both structural and electrical remodeling. Increased circulating FGF23 promotes atrial fibrosis by activating the downstream AKT pathway binding to FGFR4 in atrial tissue. [ABSTRACT FROM AUTHOR]

Objective: To investigate the application value of Pelvic Inflammation No. 1 formula of transdermal meridian pointtargeted drug delivery therapy in the treatment of patients with chronic pelvic inflammatory disease (damp-heat stasis type). Methods: All patients with chronic pelvic inflammatory disease (damp-heat stasis type) visited Danzhou Hospital of Traditional Chinese Medicine from August 2017 to March 2021 and were randomly grouped, 57 patients in the control group were treated with simple Western medicine, and 57 patients in the observation group were combined with Pelvic Inflammation No. 1 formula transdermal meridian targeted transdermal medication, and the therapeutic efficacies were compared after 3 months of treatment. Results: After treatment, serum matrix metalloproteinase-9 （MMP-9）, D dimer （D-D）, IL-6 and other indexes in the observation group were lower than those in the control group, and IL-10 was higher than that in the control group, the difference was statistically significant （P<0.05）. After treatment, the carbohydrate antigen CA125 in the observation group was lower than that in the control group, and the CD4+/CD8+ and CD4+ cells in the observation group were higher than those in the control group （P<0.05）. After treatment, the score of summary of health status surveys （SF-36） in the observation group was higher than that in the control group, and the total score of TCM symptoms was lower than that in the control group （P<0.05）. The total effective rate in the observation group was 96.49%（ 55/57）, which was higher than 82.46% （46/57） in the control group （P<0.05）. Conclusion: For patients with chronic pelvic inflammatory disease （damp-heat stagnation type）, combined with Pelvic Inflammation No. 1 formula transdermal via acupoints targeted drug therapy can help to regulate inflammatory factors, regulate immune function, and improve clinical efficacy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have shown that salidroside has an ameliorative effect on multi-organ fibrosis. However, the protective effect of salidroside on angiotensin ii-induced fibrosis in cardiac fibroblasts is unclear OBJECTIVE: To investigate the protective effects of salidroside on angiotensin ii-induced oxidative stress and extracellular matrix deposition in cardiac fibroblasts of Sprague-Dawley rats and its mechanism of action. METHODS: Angiotensin II was used to induce fibrosis in cardiac fibroblasts, and there were five experimental groups: normal control group, model group (final concentration of angiotensin II in culture medium was 1 μmol/L), salidroside low and high dose groups (treatment with salidroside 50, 100 μmol/L for 2 hours, followed by co-incubation with angiotensin II for 48 hours), SIRT1 inhibitor group (treatment with SIRT1 inhibitor EX527 10 μmol/L for 2 hours, followed by high dose of salidroside for 2 hours and then co-incubation with angiotensin II for 48 hours). The cell viability was detected using the cell counting kit-8 method, the cell migration rate was detected by Transwell, the intracellular reactive oxygen species level was detected by DCFH-DA fluorescent probe, and the intracellular malondialdehyde content, superoxide dismutase and catalase activities were detected by relevant kits. The protein and mRNA expression levels of SIRT1, LOXL2, α-SMA, type I collagen and type III collagen were detected by western blot and qRT-PCR, respectively. RESULTS AND CONCLUSION: The cells were identified as cardiac fibroblasts by Vimentin fluorescence. Compared with the normal control group, cell viability, cell migration rate, reactive oxygen species level, and malondialdehyde content were significantly increased, superoxide dismutase and catalase activities were significantly decreased, LOXL2, α-SMA, type I collagen, type III collagen mRNA and protein expression were significantly increased, and SIRT1 protein expression level was significantly decreased in the model group (all P < 0.01). Compared with the model group, the above indexes showed opposite changes in the salidroside low and high dose groups (all P < 0.05). Moreover, salidroside showed dose-dependent regulation. Compared with salidroside groups, cell migration rate and α-SMA protein expression level were significantly increased in the SIRT1 inhibitor group (both P < 0.001). To conclude, salidroside has a protective effect on angiotensin II-induced cardiac fibroblasts and can dose-dependently inhibit oxidative stress and extracellular matrix deposition. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease （NAFLD） has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma. However, the pathogenesis of NAFLD remains unclear, and there is still a lack of specific treatment measures. Sterol regulatory element-binding proteins （SREBP） are an important nuclear transcription factor, which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol, fatty acids, and triglycerides, and therefore, SREBP are a target for the treatment of metabolic diseases. This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD. It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage. Therefore, excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD. In conclusion, SREBP is a promising therapeutic target for NAFLD； the molecular mechanism of SREBP in lipid metabolism is regulated by many factors, and these factors are being deeply explored and analyzed, which has an important clinical significance for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Copyright of Traditional Chinese Drug Research & Clinical Pharmacology is the property of Traditional Chinese Drug Research & Clinical Pharmacology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the role and molecular mechanism of connexin 43 (Cx43) in rats with myocardial injury induced by common bile duct ligation (CBDL). Methods A total of 18 Sprague-Dawley rats were randomly divided into sham-operation group, CBDL group, and Cx43 inhibitor group, with 6 rats in each group. The rats in the sham-operation group were given isolation of the common bile duct, those in the CBDL group were given isolation, ligation, and cutting of the common bile duct, and those in the Cx43 inhibitor group were given a single injection of 25 mg/kg Gap 26 via the caudal vein at 24 h before surgery, followed by the isolation, ligation, and cutting of the common bile duct. The rats in all three groups were reared to day 14 after surgery, and echocardiography was used to evaluate ejection fraction (EF), fractional shortening (FS), and heart rate (HR); the three groups were measured in terms of serum total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) activity, and malondialdehyde (MDA); HE staining and Masson staining were performed for heart tissues samples collected from the three groups; Western blotting was used to measure the levels of Cx43, Wnt 3α, and β-catenin in heart tissue. Results Echocardiography showed that the CBDL group and the Cx43 inhibitor group had significantly lower cardiac EF, FS, and HR than the sham-operation group (F=22.95-43.55,t=5.10-9.32,P

BACKGROUND: Overweight or obesity is the most significant risk factors for knee osteoarthritis. Time-restricted diet shows an effective effect in preventing overweight or obesity. Whether infrapatellar fat pad, an important component of the knee joint, is affected by time-restricted diet and thus influences knee osteoarthritis remains unclear. OBJECTIVE: To employ a high-fat diet-induced rat model to investigate the effect of weight loss by time-restricted diet on infrapatellar fat pad, thereby providing evidence for early prevention and treatment of obesity-related knee osteoarthritis. METHODS: Fifteen male Sprague-Dawley rats were randomly divided into three groups (n=5 per group). Rats in the control group were allowed to eat at will for 24 hours and were fed the defined control diet (12% fat); rats in the high-fat diet group were allowed to eat at will for 24 hours and were fed the high-fat diet (45% fat); and rats in the high-fat diet with time-restricted diet group were fed the high-fat diet only from 9:00 (2 hours after the light) to 17:00 (2 hours before the dark). After 8 weeks of feeding, mDixon-Quant sequence was used to assess proton density fat fraction in the infrapatellar fat pad and subcutaneous adipose tissue in the right inguinal region. ELISA was used to quantify differences adipokine. Sirius red staining was used to evaluate changes in fibrosis of the infrapatellar fat pad. The expressions of uncoupling protein-1 in the infrapatellar fat pad and subcutaneous adipose tissue in the right inguinal region as well as leptin, adiponectin and tumor necrosis factor-α in the infrapatellar fat pad were detected by immunohistochemistry staining. RESULTS AND CONCLUSION: After 8 weeks of feeding, compared with the high-fat diet group, the body mass of rats in the control group (P=0.036) and the high-fat diet with time-restricted diet group (P=0.003) was significantly reduced. The proton density fat fraction in the infrapatellar fat pad in the high-fat diet group was significantly higher than that in the control group (P < 0.001) and the high-fat diet with time-restricted diet group (P=0.004), while there was no significant difference in the proton density fat fraction of the subcutaneous adipose tissue among the three groups. The serum leptin levels of rats in the highfat diet group were significantly higher than those in the control group (P=0.030) and the high-fat diet with time-restricted diet group (P=0.018). Compared with the high-fat diet group, the infrapatellar fat pad fibrosis characterized by Sirius red staining in the control group (P < 0.001) and the time-restricted diet group (P=0.003) was significantly decreased. The expression of leptin in IFP of the high-fat diet group was significantly higher than that of the control group (P < 0.001) and the high-fat diet with time-restricted diet group (P < 0.001). The expression of adiponectin in the infrapatellar fat pad of the high-fat diet group was significantly lower than that of the control group (P=0.004) and the high-fat diet with time-restricted feeding group (P=0.048). However, there was no positive expression of uncoupling protein-1 in the infrapatellar fat pad and subcutaneous adipose tissue of all the three groups, and no positive expression of tumor necrosis factor-α in the infrapatellar fat pad. To conclude, time-restricted diet could retard the fibrosis of the infrapatellar fat pad, reduce the proton density fat fraction of the infrapatellar fat pad, and affect the level of adipokine in serum and infrapatellar fat pad. Time-restricted diet may become a simple and effective option for the treatment and prevention of obesity-related knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of baicalein on myocardial fibrosis in experimental autoimmune myocarditis (EAM) mice and its mechanism. Methods Twenty BalB/C mice were divided into blank group, EAM group, baicalein group, and dexamethasone group, with 5 mice in each group. On days 0 and 7, all the mice except those in the blank group were subcutaneously injected with 200 μL of complete Freund’s adjuvant and α-MyHC peptide emulsion. Starting from day 8, the mice in the EAM group, baicalein group, and dexamethasone group were intragastrically administered sodium carboxymethyl cellulose, baicalein, and dexamethasone, respectively. Echocardiography was performed on day 21 of administration to determine left ventricular ejection fraction (LVEF), shortening fraction (LVFS), left ventricular end-diastolic internal diameter (LVIDd), and left ventricular end-systolic internal diameter (LVIDs) in mice across all groups. On day 21, the mice from all groups were euthanized by cervical dislocation and their heart tissues were collected for HE staining and Masson staining. Flow cytometry was used to detect the proportion of Th17/Treg cells among the splenocytes. Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot were used to analyze the mRNA and protein expression of Collagen Ⅰ, matrix metalloproteinase-1 (MMP-1), interleukin 17A (IL-17A), Treg transcription factor (FOXP3), and IL-10 in the cardiac tissue of mice. Results Echocardiographic results showed that the LVEF and LVFS of mice in baicalein group were significantly higher than those in the EAM group (F=51.55,35.38,q=8.08,5.97,P

BackgroundLong-term exposure to free silica particles will lead to fibrosis of lung tissue, and abnormal expression of microRNA (miRNA) may affect the occurrence and process of fibrosis. ObjectiveTo observed possible intervention effect of miR-204-3p overexpression adenovirus on silicosis fibrosis induced by silica dust using a silicosis rat model via non-exposed intratracheal instillation. MethodsForty SD rats were randomly divided into four groups: control group, silicosis model group, miRNA-NC group, and miR-204-3p intervention group. Under ether anesthesia, rats in the silicosis model group, miRNA-NC group, and miR-204-3p intervention group were injected with 1 mL (50 mg·mL−1) of free silica dust suspension into the trachea, while the control group was injected with the same volume of normal saline. After 30 d of dust exposure, the miR-204-3p intervention group was injected with rno-mir-204 adenovirus vector to overexpress miR-204-3p, and the miRNA-NC group was given empty virus vector. After 30 d of normal feeding, the animals were sacrificed by chloral hydrate anesthesia, and the lung tissue was taken for subsequent experiments. The relative expression level of miR-204-3p in lung tissue of rats in each group was detected by real-time fluorescence quantitative PCR (RT-qPCR). HE staining, Masson staining, and Sirius red staining were used for pathological observation. Immunohistochemistry was used to detect the expression of Fibronectin and Collagen I in lung tissue of rats in each group. RT-qPCR was used to detect the relative gene expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Western blot was used to detect the protein expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. ResultsThe anatomical features of lung tissue in the control group were pink lung tissue with soft texture and smooth surface, while those in the silicosis model were grayish white tissue with hard texture and scars and grayish white silicon nodules on the surface. Compared with the silicosis model group, the color of lung tissue in the miR-204-3p intervention group became ruddy, the surface was smooth, and the texture became soft. The staining results showed that the alveolar wall of the control group was thin, there were a small number of capillaries in the alveoli, and the alveolar structure was clear and complete. In the silicosis model group, the alveolar wall became thicker, the pulmonary septum was partially broken, the alveolar structure was defective, and a large amount of collagen fibers were deposited. The alveolar structure of the miR-204-3p intervention group was relatively clear and there was a small amount of collagen fiber deposition. RT-qPCR results showed that compared with the control group, the relative expression levels of miR-204-3p in lung tissue of the silicosis model group and the miRNA-NC group were decreased (P

Cellular senescence and fibrosis are two biological processes that are closely related to the development of many diseases. Cellular senescence can occur through mechanisms such as telomere shortening, DNA damage, and oxidative stress, leading to degradation of cell function and decreased ability to repair damage. More and more studies have shown that fibrosis and cell senescence are closely related, and cell senescence has been confirmed to be involved in the occurrence and development of scar fibrosis diseases. An in-depth understanding of the relationship between cellular senescence and scar fibrosis is helpful to find new therapeutic strategies and develop targeted drugs to reduce the process of scar fibrosis. [ABSTRACT FROM AUTHOR]

AIM: To explore the roles and associations of hepatocyte nuc lear factor 4 alpha (HNF4A) and mu-protocadherin (MUCDHL) in the kidney of diabetic mice. METHODS: (1) A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks. The protein levels of fibronectin (FN), collagen type III (Col-III), E-cadherin, a-smooth muscle actin (a-SMA), HNF4A, Snail and MUCDHL in renal tissues were scrutinized using Western blot. Immunohistochemical staining was conducted to observe the distribution and expression of FN, HNF4A and MUCDHL. (2) Mouse renal tubular epithelial cells (mRTEC) were cultured in vitro and categorized into groups: normal glucose (NG) group, high glucose (HG) group, overexpression control groups (NG+vector and HG+vector), overexpression groups (NG+OE-MUCDHL, HG+OE-MUCDHL, NG+OE-HNF4A and HG+OE-HNF4A), knockdown control groups (NG+control and HG+control), and knockdown groups (NG+si-MUCDHL, HG+si-MUCDHL, NG+si-HNF4A and HG+si-HNF4A). The relevant protein levels were also detected by Western blot. RESULTS: (1) In db/db group, elevated body weight, blood glucose and urine albumin-to-creatinine ratio (UACR) indicated significant renal injury. Compared with db/m group, the mice in db/db group exhibited increased expression of FN, Col-III, a -SMA and Snail, and decreased expression of E-cadherin, HNF4A and MUCDHL. MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells, FN in the tubular mesenchyme, and HNF4A in the plasma and nucleus of renal tubular cells. (2) In HG group, there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin, HNF4A and MUCDHL compared with NG group. Overexpression of MUCDHL led to a decrease in the expression of FN, Col-III, a-SMA and Snail proteins, an increase in the expression of E-cadherin and MUCDHL proteins, and unaltered expression of HNF4A. Knockdown of MUCDHL resulted in a reversal of the aforementioned effects, with HNF4A expression remaining unaltered. Overexpression of HNF4A led to an increased expression of MUCDHL, and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL. Knockdown of HNF4A reversed the aforementioned effects. MUCDHL may represent a downstream target gene of HNF4A. CONCLUSION: The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease (DKD). HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL. [ABSTRACT FROM AUTHOR]

Copyright of Traditional Chinese Drug Research & Clinical Pharmacology is the property of Traditional Chinese Drug Research & Clinical Pharmacology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: In recent years, the incidence of hyperuricemia caused by purine metabolism disorders has been increasing, which can induce inflammatory responses and lead to renal injury. OBJECTIVE: To explore the role and mechanism of solute carrier family 2 member 12 (SLC2A12) in hyperuricemia-related renal injury. METHODS: Renal tubular cells (HK2 cells) were divided into five groups: HK2 group, HK2+uric acid group, HK2+uric acid+NC group, HK2+uric acid+siSLC2A12 group, and HK2+uric acid+siSLC2A12+MK-2206 group. HK2 cells were treated with uric acid and transfected with siRNA SLC2A12, followed by MK-2206 treatment to inhibit AKT expression. Cell proliferation was detected by CCK-8 assay. Apoptosis was detected by TUNEL assay. qRT-PCR and western blot assay were used to detect fibrogenic factors as well as activation of the AKT/FOXO3a pathway. The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION: (1) Uric acid treatment inhibited cell proliferation and promoted cell apoptosis in the HK2+uric acid group compared with the HK2 group. The proliferative ability of cells in the HK2+uric acid+siSLC2A12 group was further decreased and apoptotic cells were further increased compared with the HK2 group. Compared with the HK2+uric acid+siSLC2A12 group, the HK2+uric acid+siSLC2A12+MK-2206 group showed an increase in cell proliferation and a decrease in apoptotic cells. (2) Compared with the HK2 group, the connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA) and transforming growth factor beta (TGF-β) expressions increased in the HK2+uric acid group; CTGF, α-SMA and TGF-β expression further increased in the HK2+uric acid+siSLC2A12 group. Compared with the HK2+uric acid+siSLC2A12 group, the CTGF, α-SMA and TGF-β expressions decreased. (3) Compared with the HK2 group, the expression of p-AKT, FOXO3a, and p-FOXO3a elevated in the HK2+uric acid group; the expression of p-AKT further increased, while the expression of FOXO3a and p-FOXO3a decreased in the HK2+uric acid+siSLC2A12 group. Compared with the HK2+uric acid+siSLC2A12 group, p-AKT expression decreased; FOXO3a and p-FOXO3a expression increased in the HK2+uric acid+siSLC2A12+MK-2206 group. (4) Compared with the HK2 group, interleukin-6, interleukin-1 β, and tumor necrosis factor α levels increased in the HK2+uric acid group; interleukin-6, interleukin-1 β, and tumor necrosis factor α levels further increased in the HK2+uric acid+siSLC2A12 group. Compared with the HK2+uric acid+siSLC2A12 group, interleukin-6, interleukin-1 β, and tumor necrosis factor α levels diminished in the HK2+uric acid+siSLC2A12+MK-2206 group. (5) These findings indicate that SLC2A12 may protect against hyperuricemia-induced renal injury by counteracting uric acid-induced tubular fibrosis and inflammation through activation of the FOXO3a pathway. [ABSTRACT FROM AUTHOR]

Myocardial fibrosis is a common pathological manifestation of various heart diseases, with hidden onset and the possibility of evolving into irreversible heart failure. Currently, there is still insufficient diagnosis and treatment of myocardial fibrosis. Traditional Chinese medicine can regulate myocardial fibrosis at multiple levels, targets, and pathways, and has significant advantages in treating myocardial fibrosis. Its underlying mechanisms are worth further exploration. The theory of "yang generating qi, yin constituting the body" in Huangdi Neijing embodies the meaning of yin and yang, containing a profound outlook on life and disease. Pathological changes in the initial, progressive, and final stages of myocardial fibrosis conform to the yin-yang theory of "yang generating qi, yin constituting the body". Insufficient yang generating qi and excessive yin constituting the body constitutes the core pathogenesis of myocardial fibrosis. This article proposes a treatment approach for myocardial fibrosis by tonifying yang and abating yin. The treatment of warming yang, unblocking yang, removing blood stasis, resolving phlegm, detoxifying, and promoting diuresis is applied to broaden the clinical treatment approach for myocardial fibrosis. [ABSTRACT FROM AUTHOR]

Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy (DCM). Methods The technology platform of Chinese medicine system pharmacology (TCMSP) and the small molecule drug target prediction (Swiss Target Prediction) platform were used to excavate the active components of Scutellariae Radix and the target of its response. DCM related disease gene targets were screened using GeneCards, Disgene, UniPort and OMIM databases, and intersecting genes were imported into the String 11. 5 database to construct a drug-disease-protein interaction network diagram. Cytoscape 3. 9. 1 software was adopted to visualize the key target network. Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM, and draw pathway maps through the KEGG database. H9c2 and AC16 cardiomyocytes were stimulated with 5. 5 mmol/L D-glucose as the normal glucose control group, 35 mmol/L D-glucose as the high glucose group, and 10 μmol/L Baicalin was used for intervention. The levels of TGF-β1, collagen Ⅰ (COLⅠ) and collagenⅢ (COLⅢ) mRNA were detected by RT-qPCR, and the expression of Smad2/3, p-Smad2/3, COLⅠ and COLⅢ protein were detected by Western blot, TGF-β1 level in supernatant was assessed by ELISA. Results Through the above platform, a total of 33 effective ingredients including Baicalin, 441 core targets, and 1 884 DCM disease genes were retrieved, 150 core genes for treating DCM with Scutellariae Radix were obtained. The drug-disease interacted genes such as TGF-β1, TP53, MMP-9 and IL-6 were obtained through String PPI, KEGG signaling pathways such as MAPK and PI3K/Akt were enriched. In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1, COLⅠ and COLⅢ mRNA levels, p-Smad2/3, COLⅠ and COLⅢ protein levels, and significantly increased the content of TGF-β1 in the supernatant, while Baicalin weakened its expression. Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets, among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM. [ABSTRACT FROM AUTHOR]

Background Atherosclerosis (AS) causes cardiovascular diseases such as myocardial infarction and myocardial fibrosis. Incidence of the population gradually increases with the aging of the global population. The inflammatory response is a key factor in myocardial fibrosis, and regular aerobic exercise can reduce inflammation and protect myocardial function. However, the protective mechanism of aerobic exercise against AS myocardial fibrosis is unclear. Objective To investigate the mechanism of the effect of aerobic exercise on myocardial fibrosis in AS mice. Methods From February to August 2022, twenty-seven 8-week-old male ApoE-/- mice were selected as the experimental subjects and randomly divided into the control group, model group and aerobic exercise group, with 9 mice in each group. The mouse model of AS was prepared, and the mice were trained with exercise. The myocardial tissue was observed by hematoxylin-eosin (HE) and Masson staining. The protein expressions of NOD receptor 3 (NLRP3), interleukin1β (IL-1β) and transforming growth factor β1 (TGF-β1) in myocardial tissue were detected by Western blotting. The expressions of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected. Results Masson staining results showed that myocardial fibrosis in the model group was significantly worse than that in the control group. Myocardial fibrosis in the aerobic exercise group was significantly improved compared with the model group. HE staining showed that myocardial cells in the model group were disorganized, with abnormal cell morphology and size, enlarged cell gaps and inflammatory cell infiltration. Cardiomyocytes of mice in the aerobic exercise group were still neatly arranged, with abnormal cell morphology and size, and the cell gap was basically normal. The expressions of NLRP3, IL-1β and TGF-β1 in the model group were higher than those in the control group, while the expressions of NLRP3, IL-1β and TGF-β1 in the aerobic exercise group were lower than those in the model group, and higher than the control group (P

Objective To study the effect of marein on myocardial fibrosis in diabetic mice. Methods Ten leptin receptor gene defective heterozygous (db/m) mice aged 5-6 weeks were selected as the control group and 30 diabetic mice with leptin receptor gene defective db/db were divided into: db/db group (db/db,n=10), metformin (Met) positive group (280 mg/kg daily,n=10) and marein drug intervention group (50 mg/kg,n=10). After continuous administration for 8 weeks, the cardiac morphological changes were observed by HE staining and Masson staining. The distribution and expression of vimentin were detected by immunohistochemistry method. The expression of fibronectin, vimentin, and transforming growth factor-β1(TGF-β1)protein in cardiac tissue was detected by Western blot. Results Myocardial fiber hypertrophy was observed in db/db group, and myocardial structural damage was improved in metformin group and marein group. Compared with db/m group, the expression of myocardial collagen fiber in db/db group increased (P＜0.01), while the expression of myocardial collagen fiber in metformin group and marein group decreased (P＜0.01). Compared with the control group, the expression of vimentin in myocardial tissue of db/db group was significantly increased(P＜0.01), while the expression of vimentin in metformin group and marein group was significantly decreased (P＜0.01). The expression of fibronectin, vimentin and TGF-β1 in db/db group was significantly increased as compared with those in db/m group (P＜0.01), while the expression of fibronectin, vimentin and TGF-β1 in metformin group and marein group were significantly decreased (P＜0.01). Conclusions Marein improves myocardial fibrosis in diabetic db/db mice.

BACKGROUND: Abnormal extracellular matrix accumulation and excessive proliferation of fibroblasts are the main manifestations of pathological scars. Excessive proliferation of fibroblasts leads to the production of large amounts of collagen-based extracellular matrix. Therefore, to investigate the role of fibroblast fibrosis in the formation of pathological scar will provide a new idea for revealing the mechanism of pathological scar and biological therapy. OBJECTIVE: To investigate the effect of RAS-selective lethal small molecule 3 (RSL3) on the fibrosis of human pathological scar fibroblasts. METHODS: Then cases of pathological scar tissue and normal skin tissue samples from the same individuals, provided by the Department of Burn Plastic Surgery, General Hospital of Ningxia Medical University, were collected. Fibroblasts of human pathological scar and human normal skin were extracted and used in the following experiments. The general condition of the pathological scar tissue and the normal skin tissue was detected by hematoxylin-eosin staining. The appearance of fibroblasts from pathological scar and normal skin were observed by inverted microscope. The fibroblasts were verified by immunofluorescence assay. The cells were treated with different concentrations of RSL3 (1, 3, 5, 7, 9, 11, 13 μmol/L). The inhibitory concentration of RSL3 on fibroblasts was detected by cell counting kit-8. Control group (without treatment) and RSL3 intervention group (treated with 7 μmol/L RSL3 for 24 hours) were set up. The mRNA and protein expressions of glutathione peroxidase 4, type I collagen, type III collagen and α-smooth muscle actin were detected by qRT-PCR and western blot, respectively. Level of malondialdehyde in cells was detected. The residual scratch area was measured by cell scratch test after 24 hours to calculate the percentage of residual scratch area. RESULTS AND CONCLUSION: The expression of glutathione peroxidase 4 in the pathological scar group was higher than that in the normal skin group (mRNA: t=3.252, P < 0.01; protein: t=5.075, P < 0.01). The expression of glutathione peroxidase 4 in the pathological scar fibroblast group was higher than that in the normal skin fibroblast group (mRNA: t=10.32, P < 0.01; protein: t=26.22, P < 0.01). Compared with the control group, the expression of glutathione peroxidase 4 was decreased (mRNA: t=2.798, P < 0.05; protein: t=4.643, P < 0.01), the content of malondialdehyde was increased (t=2.917, P < 0.05), the expression of type I collagen (mRNA: t=15.84, P < 0.01; protein: t=4.610, P < 0.01), type III collagen (mRNA: t=28.86, P < 0.01; protein: t=7.713, P < 0.01) and α-smooth muscle actin (mRNA: t=2.671, P < 0.05; protein: t=7.417, P < 0.01) were decreased in the RSL3 intervention group. Compared with the control group, the migration ability was weakened in the RSL3 intervention group (t=14.06, P < 0.01). To conclude, RSL3 can inhibit the expression of glutathione peroxidase 4 and then inhibit the ability of fibrosis and migration of pathological scar fibroblasts. [ABSTRACT FROM AUTHOR]

Objective To investigate the therapeutic effect of total flavonoids of Sarsaparilla on chronic pelvic inflammatory disease (CPID) model rats. Methods CPID rat model were performed by injecting phenol mucilage into the right uterus. The SD rats were divided into the model control group, the high dose group [32. 4 g/ (kg·d)], the medium dose group [16. 2 g/ (kg·d)], the low dose group [8. 1 g/ (kg·d)], the Jingangteng capsule group, the dexamethasone group according to the random number table method, with ten animals each. Rats treated with sham operation were divided into the sham operation group and the background control group according to the random number table method, with ten animals each. In addition, the blank control group (ten animals) was estabished without any treatment. The hemorheology and routine blood indexes of each group were detected 14 days after administration. The morphological changes of the left and right sides of the uterus were observed, the swelling rate and swelling inhibition rate of the uterus were calculated, and the pathological changes of the uterus were observed by hematoxylin-eosin (HE) and Masson staining. The expression of interleukin-1β (IL-1β), IL-4, IL-6 and IL-10 in uterine tissue of rats was detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the model control group and the Jingangteng capsule group, all dose groups of total flavonoids from Sarsaparilla can significantly reduce the number of white blood cells, lymphocytes, neutrophils, and various hemorheological indicators in the blood of CPID model rats, reduce the rate of uterine swelling in rats, and inhibit the expression of L-1β and IL-6 in rat uterine tissue, and promote the expression of IL-4 and IL-10 and can significantly reduce uterine congestion and edema, reduce inflammatory cell infiltration, alleviate fibrous connective tissue proliferation around glands, and improve endometrial hyperplasia and fibrosis, with statistical significance (P＜0. 01). Conclusion Total flavonoids of Sarsaparilla can improve the symptoms of CPID model rats, enhance blood flow, improve local blood circulation, and inhibit uterine inflammation and fibrotic hyperplasia in CPID model rats. [ABSTRACT FROM AUTHOR]

Skeletal muscle injury is a common disease in clinical practice, and an in-depth understanding of its repair mechanisms is crucial for the development of effective therapeutic strategies. This paper focuses on the key role of TGF-β in skeletal muscle injury repair, introduces the diversity of its family members and signaling pathways, explores the expression and regulation part of TGF-β after skeletal muscle injury, analyzes its early expression dynamics and regulatory factors, and thoroughly investigates the effects of TGF-β on skeletal muscle repair, revealing its inflammatory regulation, cellular activation and proliferation as well as fibrosis. Key role. Special attention was paid to its mechanism of action in muscle regeneration and its regulatory mechanism at the cellular level. In addition, the potential clinical applications of TGF-β in the repair of skeletal muscle injury were discussed, and the development and application of it as a therapeutic target and modulator were explored. However, controversies and shortcomings still exist in the current study, such as the dual roles of TGF-β and the impact of individual differences on treatment. Future research directions should include digging deeper into the details of signaling pathways and biomarker discovery. By overcoming these challenges, the potential clinical application of TGF-β in skeletal muscle injury repair is expected to usher in new breakthroughs and provide patients with more individualized and effective treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of Smurf1 on fibrosis process in hypertrophic scar formation and its molecular mechanism. Methods: Hypertrophic scar tissue and normal skin tissue samples of 12 patients who underwent hyperplastic scar resection in the department of burn and plastic surgery of the Second Affiliated Hospital of Air Force Medical University from June 2021 to June 2022 were collected. And the pathological examination was performed by HE and Masson staining. After sterile treatment of hypertrophic scar tissue, human hypertrophic scar fibroblasts (HSF) were isolated and cultured by tissue block method. HSF cells were divided into some groups according to the experimental scheme, (1) Smurf1 overexpression treatment group, control group 1 (Con-1 group), empty vector group (Vector group) and Smurf1 overexpression group (OE-Smurf1 group), (2) Smurf1 interference expression treatment group, control group 2 (Con-2 group), negative group (si-NC group) and Smurf1 interference expression group (si-Smurf1 group). Then pcDNA3.1 empty plasmid, pcDNA3.1+Smurf1 plasmid, si-NC and si-Smurf1 were transfected into HSF cells in Vector group, OE-Smurf1 group, si-NC group and si-Smurf1 group, respectively. Smurf1 mRNA expression level was detected by qRT-PCR. Protein expression level was detected by Western blot. Cell proliferation level was detected by CCK-8. Cell apoptosis level was detected by flow cytometry. Cell invasion level was detected by Transwell assay and cell migration level was detected by cell scratch assay. Results: The results of HE staining and Masson staining showed that compared with normal skin tissue, the dermis thickness of hypertrophic scar tissue increased significantly, and there were a large number of blue-dyed collagen fibers in the dermis, which were disordered and dense. Compared with normal skin tissue, the protein expression levels of TGF-β1, α-SMA, COL1, COL3, TβR-I, p-Smad3 and Smad7 in hypertrophic scar tissue were increased (P<0.05), while the expression level of Smurf1 was decreased (P<0.05). Compared with Con-1 or Vector groups, the expression levels of TGF-β1, α-SMA, COL1, COL3, TβR-I, p-Smad3 and Smad7 proteins in HSF cells of OE-Smurf1 group were decreased (P<0.05), and the proliferation, invasion and migration levels of HSF cells were decreased (P<0.05), the apoptosis level was increased (P<0.05). Compared with Con-2 group or si-NC group, the expression levels of TGF-β1, α-SMA, COL1, COL3, TβR-I, p-Smad3 and Smad7 proteins in HSF cells of si-Smurf1 group were increased (P<0.05), and the proliferation, invasion and migration levels of HSF cells were increased (P<0.05), the apoptosis level was decreased (P<0.05). Conclusion: Smurf1 may inhibit the fibrotic process of hypertrophic scars by inhibiting TGF-β1/Smad pathway. [ABSTRACT FROM AUTHOR]

Fibrotic diseases have brought great clinical challenges due to their extensiveness and complexity. It is imperative to explore the mechanism of fibrosis and seek more effective treatments. Adipose derived stem cells (ADSC) are ideal stem cells for regenerative medicine and can be used as an alternative treatment for many diseases. Recent studies have shown that ADSC has significant anti⁃fibrosis potential. This article reviews the potential intervention targets involved in the anti⁃fibrosis process of ADSC, such as epithelial ⁃ mesenchymal transition, fibroblast activation, anti⁃inflammatory and immune regulation, in order to provide new ideas for the prevention and treatment of fibrosis. [ABSTRACT FROM AUTHOR]

[Objective] CRISPR/Cas9 technology was used to construct Pmepa1 knockdown TCMK1 mouse renal tubular epithelial cell lines and to explore the effect of Pmepa1 knockdown on TGF-β-stimulated TCMK1 cell fibrosis, which provides a cell model for studying the role of Pmepa1 in fibrosis models. [Method] The pX333 vector was created and transfected into TCMK1 cells in accordance with the CRISPR/Cas9 design principle. Flow sorting of mCherry-positive cells, monoclonal cell expansion, and sequencing were used to identify the Pmepa1 knockout cells, and Western blot was used to confirm the knockout status of the Pmepa1 gene. Pmepa1 knockdown was confirmed using a Western blot. By using RT-PCR and Western blot, the effects of Pmepa1 knockdown on TGF-1-induced R-Smad activation and fibrosis were examined. [Result] The sgRNA was designed in exon 2 of Pmepa1 48 h after transfection of TCMK1 cells with pX333-Pmepa1 plasmid, the expression of mCherry fluorescent protein was observed, and flow cytometric analysis of the transfection efficiency was about 17%. pX333-Pmepa1 plasmid transfection-positive cells were cultured by flow sorting and monoclonal amplification to obtain 19 cell clones. PCR amplification sequencing analysis of the sgRNA target sequence at the PMEAP1 gene locus revealed 2 double allele shift mutant cells, and Western blot verified the absence of Pmepa1 protein expression, indicating that the Pmepa1 knockdown TCMK1 cell line was successfully constructed, compared with the non-knockdown cells, the Pmepa1 knockdown cells were stimulated by TGF-β, p-Smad2 and p-Smad3 expression was significantly elevated in Pmepa1 knockout cells compared with non-knockout cells, and the expressions of the fibrogenic genes Fibronectin and Collagen I were promoted. [Conclusion] CRISPR/Cas9 technique was used to construct the renal tubular epithelial cell line of PMEPA1 knockout TCMK1 mice successfully, which established the cell model for the functional study of PMEPA1 protein and the important role of PMEPA1 in fibrosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects and underlying mechanism of cryptotanshinone (CTS) on pulmonary fibrosis in rats with hyperoxia⁃induced bronchopulmonary dysplasia (BPD) . Methods: 50 newborn male Sprague⁃Dawley rats were randomly divided into air group, hyperoxia group, low⁃dose CTS (7.5 mg/kg) group, medium⁃dose CTS (15.0 mg/kg) group and high⁃dose CTS (30 mg/kg) group. Rats in hyperoxia and three CTS treatment groups were exposed to 95% oxygen (O2) for 7 d after birth, and the air group were exposed to a room environment (21% O2) . 7 days later, all rats were euthanized. The alveolar morphology and lung fibrosis were evaluated using hematoxylin⁃eosin (HE) staining and Masson staining. The mRNA levels of transforming growth factor beta1 (TGF⁃β1) and alpha⁃smooth muscle actin (α⁃SMA) were detected by RT⁃qPCR. The protein expression of cell signaling molecules small mother against decapentaplegic (Smad) 2/3 and p ⁃Smad2/3 was detected by Western blot. In vitro experiments: Human fetal lung fibroblasts (HFL ⁃ 1) cells were selected and divided into air group, hyperoxia group and CTS intervention group according to the culture conditions. The air group was cultured under conventional conditions, while the hyperoxia and intervention groups were incubated in a 95% O2 incubator for 24 h. 10 μmol/L CTS was added to the intervention group. Cell viability was measured by CCK ⁃ 8 assay, and protein expression of TGF⁃β1, α⁃SMA, p⁃Smad2/3 and Smad2/3 were detected by Western blot. Results: Compared with the control group, rats in the hyperoxia group had disorderd alveolar morphology, widened alveolar septa, decreased RAC values and increased fibrosis scores (P < 0.05) ；increased the mRNA levels of TGF⁃β1 and α⁃SMA (P < 0.05) ；and up⁃regulated p⁃Smad2/3 expression (P < 0.05) . Different doses of CTS could improve the above indicators (P < 0.05) . Meanwhile, CTS also reduced TGF⁃β1, α⁃SMA, p⁃Smad2/ 3, and Smad2/3 protein expression levels in HFL⁃1 cells after hyperoxia (P < 0.05) . Conclusion: CTS ameliorates the fibrotic process of hyperoxia⁃induced lung injury via the TGF⁃β/Smad pathway. [ABSTRACT FROM AUTHOR]

Objective: To investigate the therapeutic effect of Qidantongmai tablet (QDTM) on adriamycin-induced dilated cardiomyopathy (DCM) in rats and its effect on the expression of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST). Methods: Rats were divided into Con group (n=12), DCM group (n=13), L-QDTM group (n=13), M-QDTM group (n=13), and H-QDTM group (n=13). Rats in Con group rats were normal control, and rats in other groups were doxorubicin-induced dilated cardiomyopathy model rats. Rats in Con group and DCM group were given normal saline, rats in L-QDTM group, M-QDTM group and H-QDTM group were given QDTM extractum powder of 500, 1000 and 2000 mg/kg/d, respectively. The rats of each group were given the drug once a day for 4 weeks. After treatment, The cardiac function parameters, serum myocardial injury indexes and myocardium tissue oxidative stress indicators of each group were detected, respectively. Myocardial morphology, fibrosis and apoptosis were observed by hematoxylin eosin (HE), Masson tricolor and TUNEL staining. The transcription levels of XIST, collagen I, collagen Ⅲ, TGF-β1, Bax and Bcl-2 in myocardial tissue were detected by RT-qPCR. Results: Compared with Con group, left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (FS) in DCM group decreased, left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVIDs) increased, lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac troponin I (cTnI) increased,myocardial injury was obvious, fibrosis area increased, collagen I, collagen Ⅲ and TGF-β1 m RNA levels increased, TUNEL positive rate increased, Bax m RNA level increased, Bcl-2 m RNA level decreased, superoxide dismutase (SOD) and catalase (CAT) levels decreased, malondialdehyde (MDA) level increased, and XIST level increased (all P＜0.05). Compared with DCM group, LVEF and FS in L-QDTM group, M-QDTM group and H-QDTM group increased, LVIDd and LVIDs decreased, LDH, CK and cTnI decreased, myocardial injury was alleviated, fibrosis area decreased, collagen I, collagen Ⅲ and TGF-β1 m RNA levels decreased, TUNEL positive rate decreased, Bax m RNA level decreased, Bcl-2 m RNA level increased, SOD and CAT levels increased, MDA level decreased, and XIST level decreased (all P＜0.05). Conclusion: This study indicates that Qidantongmai tablet is effective in the treatment of doxorubicin-induced dilated cardiomyopathy in rats, and the mechanism may be related to the inhibition of lncRNA XIST. [ABSTRACT FROM AUTHOR]

Objective To study the effect of marein on myocardial fibrosis in diabetic mice. Methods Ten leptin receptor gene defective heterozygous (db/m) mice aged 5-6 weeks were selected as the control group and 30 diabetic mice with leptin receptor gene defective db/db were divided into: db/db group (db/db,n=10), metformin (Met) positive group (280 mg/kg daily,n=10) and marein drug intervention group (50 mg/kg,n=10). After continuous administration for 8 weeks, the cardiac morphological changes were observed by HE staining and Masson staining. The distribution and expression of vimentin were detected by immunohistochemistry method. The expression of fibronectin, vimentin, and transforming growth factor-β1(TGF-β1)protein in cardiac tissue was detected by Western blot. Results Myocardial fiber hypertrophy was observed in db/db group, and myocardial structural damage was improved in metformin group and marein group. Compared with db/m group, the expression of myocardial collagen fiber in db/db group increased (P＜0.01), while the expression of myocardial collagen fiber in metformin group and marein group decreased (P＜0.01). Compared with the control group, the expression of vimentin in myocardial tissue of db/db group was significantly increased(P＜0.01), while the expression of vimentin in metformin group and marein group was significantly decreased (P＜0.01). The expression of fibronectin, vimentin and TGF-β1 in db/db group was significantly increased as compared with those in db/m group (P＜0.01), while the expression of fibronectin, vimentin and TGF-β1 in metformin group and marein group were significantly decreased (P＜0.01). Conclusions Marein improves myocardial fibrosis in diabetic db/db mice. [ABSTRACT FROM AUTHOR]

BackgroundSilicosis is one of the most serious occupational diseases in China, requiring new treatment targets and therapies. The effects and mechanisms of integrated stress response inhibitors (ISRIB) on silicosis are still unknown. ObjectiveTo observe the effects of ISRIB on silicosis fibrosis and its possible mechanisms. Methods The study was divided into two parts: in vivo and in vitro experiments. For the in vivo part, 40 SPF grade male C57BL/6J mice were randomly divided into four groups: control group, ISRIB group, silicotic model group, and ISRIB treatment group, with 10 mice in each group. A silicotic mouse model was established by using a single tracheal infusion of 50 μL 200 mg·mL−1 SiO2 suspension. After one week of perfusion with SiO2 (the control group and the ISRIB group were perfused with an equal amount of sodium chloride solution), the ISRIB group and the ISRIB treatment group were intraperitoneally injected with 200 μL 2.5 mg·kg−1 ISRIB for four weeks, and mice of other groups were injected with equal amounts of sodium chloride solution. A micro-CT instrument was used to observe the lung field clarity and lung texture of each group; hematoxylin eosin (HE) staining was used to observe the histopathology morphology of the lung and the formation of silicon nodules; Van Gieson (VG) staining was used to observe the deposition of collagen in silicotic nodules; immunofluorescence assay was used to detect the expression and localization of p-protein kinase RNA-like ER kinase (PERK) in lung tissue; immunoblotting was used to detect the expression of collagen I (Col I) and endoplasmic reticulum stress signal related proteins p-PERK, p-inositol-requiring enzyme-1α (p-IRE-1α), p-eukaryotic initiation factor 2α (p-eIF-2α), activating transcription factor 4 (ATF4), and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). For the in vitro part, mouse alveolar macrophages MH-S cells were cultured in vitro and divided into a control group, an ISRIB (1 μg·mL−1) group, a SiO2 induction group (100 μg·mL−1), and an ISRIB treatment group (1 μg·mL−1 ISRIB treatment for 1 h, followed by 100 μg·mL−1 SiO2 induction). Immunofluorescence assay was used to detect the expression of p-PERK in MH-S cells; immunoblotting was used to determine expressions of endoplasmic reticulum stress signal related proteins p-PERK, p-IRE-1α, p-eIF-2α, and ATF4. ResultsThe CT images showed that the lung markings of the silicotic model group mice were thickened, and several high-density shadows of varying sizes were observed in the lung field, mainly distributed around the bronchi. Compared with the silicotic model group, the ISRIB treatment group showed a decrease in the number and volume of high-density shadows. The HE staining results showed that lung tissues in the silicotic model group lost their normal structure, with the formation of silicon nodules, around which were thickened alveoli around the silicon nodules, and infiltration of inflammatory cells; the area and number of silicon nodules in the ISRIB treatment group were significantly reduced, and the range of silicon nodules was limited. The results of VG staining showed that the proportion of collagen fiber area in the lung tissue of the silicotic model group was 21.47%±2.59%, and it decreased to 9.34%±1.06% in the ISRIB treatment group, with a statistically significant difference (P

BackgroundOsteoclast stimulatory transmembrane protein (OC-STAMP) is involved in silicosis fibrosis induced by silicon oxide (SiO2) exposure. Its role in silicosis fibrosis by inducing ferroptosis of alveolar type II epithelial cells and its related mechanism remain unclear. ObjectiveTo explore the effect and possible mechanism of OC-STAMP on ferroptosis of alveolar type II epithelial cells and silicosis fibrosis in rats under SiO2 exposure. MethodsTwenty male Wistar rats of SPF grade were randomly divided into two groups: control (Sham) group and SiO2 group, 15 rats in each group. Rats in the SiO2 group were given 1 mL of 50 mg·L−1 SiO2 suspension at one time through the non-exposed intratracheal instillation method to establish an animal model of silicosis, and rats in the Sham group were give 1 mL of 0.9% sodium chloride solution in the same way. Rats were sacrificed after 8 weeks. Samples of lung tissue were fixed in glutaraldehyde or paraformaldehyde for observing ultrastructure of mitochondria by transmission electron microscopy; HE, Masson, VG, and Prussian blue were used to observe changes in lung tissue structure and iron deposition. The expression level of OC-STAMP and the degree of lung fibrosis were evaluated by immunohistochemistry and immunofluorescence. The expression level of OC-STAMP in rat lung tissue was detected and the transfection effect of OC-STAMP was verified by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Overexpression (OCS group) and inhibition expression (SI-OC group) models were constructed by OC-STAMP plasmid and OC-STAMP small interfering RNA (siRNA) transfection to cultured MLE-12 cells, respectively. The relative expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and other proteins in lung tissue and MLE-12 were detected by Western blotting. ResultsThe results of HE, Masson, and VG staining showed that the silicosis modeling was successful after 8 weeks of SiO2 exposure. The immunofluorescence results showed that OC-STAMP and ATP binding cassette subfamily A member 3 (ABCA3) co-localized in alveolar type II epithelium. The immunohistochemical results showed that the levels of OC-STAMP and collagen I in the SiO2 group were significantly higher than those in the Sham group (P

BackgroundThe pathogenesis of silicosis is complex and treatment methods are limited. SiO2-induced increase of transforming growth factor-β1 (TGF-β1) can activate fibroblasts to promote collagen deposition, ultimately leading to fibrosis. Previous studies have confirmed that lipid metabolism plays an important role in the progression of silicosis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) mediates mitochondrial dysfunction and lipid metabolism pathways in diabetic models, but its role in silicosis has not been elucidated. ObjectiveTo investigate the effect of PGC1α on lipid metabolism disorder of macrophages induced by SiO2 and its effect on the progression of silicosis fibrosis. Methods(1) Macrophages were divided into four groups by transfecting and silencing PGC1α and its control sequence in macrophages and followed by SiO2 stimulation: negative control group (transfected with si-NC for 48 h), si-PGC1α group (transfected with si-PGC1α for 48 h), SiO2 stimulation group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-NC for 48 h), and si-PGC1α+SiO2 group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-PGC1α for 48 h). Western blot and cell immunofluorescence were used to test PGC1α expression, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and total cholesterol (TC) and free cholesterol (FC) kits were used to test lipid accumulation, and the Oroboros2k-Oxygraph respiratory test system (O2K) was used to assess the effects of PGC1α on mitochondrial respiratory chain. ELISA kits were used to test TGF-β1 expressed in the macrophage supernatant. (2) Lung fibroblasts were divided into the same four groups as above, and stimulated with the supernatant of macrophages in the above groups. The expression of collagen Ι (COL Ι), E-cadherin (Eca), and fibronectin (FN) were detected by cell immunofluorescence and Western blot to further evaluate the effect of silencing PGC1α on fibrosis. ResultsThe protein expression level of PGC1α stimulated by SiO2 was decreased, and the relative expression level of PGC1α was 0.78 times that of the control group (P

Objective To investigate the expression of transforming growth factor-beta 1 in endometrial fibrosis in rats and related mechanisms. Methods Sprague-Dawley female rats were randomly divided into sham operation group (n=12) and model group (n=12). Uterine tissues were collected on days 7, 14 and 18 after surgery. HE staining and Masson staining were measured the number of endometrial glands and degree of endometrial fibrosis. The protein expression of TGF-β1 and α-SMA were measured by immunohistochemistry. Results Compared with the sham operation group, the uterine structure of the rats in the model group was significantly disrupted; there was a significant increase in TGF-β1 expression in the model group at 7 days,14 days, and 28 days of modeling; the number of endometrial glands decreased, the fibrotic area of endometrium increased and the expression of α-SMA was significantly higher at 14 days and 28 days of modeling. Conclusions TGF-β1 may promote endometrial fibrosis by activating myofibroblasts.

Objective We aim to investigate the impact of HeiBu Ointment on transforming growth factor- P1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human immortalized epidermal cells (HaCaT) and elucidate the mechanism underlying HeiBu Ointment's efficacy in treating chronic skin ulcers with abnormal fibrosis. Methods We employed a TGF-β1-induced EMT model using HaCaT. HaCaT cells were categorized into five groups: the blank control group, the model group, and the HeiBu Ointment high-, medium-, and low-dose groups. All the groups were cultured in DMEM high-glucose medium (4.00 mmol/L L-glutamine, 4.5 g/L glucose). The model group was treated with TGF-β1 (0. 01 mg/L), while the HeiBu Ointment high-, medium-, and low-dose groups received TGF-β1 (0.01 mg/L) in combination with varying doses of HeiBu Ointment extract (0.5 mg/L, 0.25 mg/L, and 0.125 mg/L). The CCK-8 method was used to detect the effect of HeiBu Ointment on HaCaT cell activity; the effect of HeiBu Ointment on the migration ability of HaCaT cells was determined by scratch test; the effects of HeiBu Ointment on the expression of the epithelial marker protein E-cadherin and the mesenchymal marker proteins N-cadherin and vimentin in HaCaT cells were observed by immuno fluorescence method; the expression of Smad and ERIK signaling pathway-related proteins was detected by Western blotting. Results HeiBu Ointment below 0. 5 mg/L had no effect on HaCaT cell activity. Compared with the model group, HeiBu Ointment significantly inhibited the migration of HaCaT cells after TGF-β1 stimulation (P< 0. 05), promoted the expression of the epithelial marker protein E-cadherin, inhibited the expression of the mesenchymal marker proteins N-cadherin and vimentin, and inhibited TGF-β1-induced phosphorylation of Smad2, Smad3, and ERIK1/2 in HaCaT cells (P < 0.05). Conclusion HeiBu Ointment may promote healing of chronic skin ulcers with abnormal fibrosis by inhibiting excessive trausition of epidermal cells to mesenchymal cells through inhibition of the Smad and ERIK signaling pathways. [ABSTRACT FROM AUTHOR]

A small proportion of nephropathy patients administered gadolinium contrast agents for nuclear magnetic resonance have been reported to develop nephrogenic systemic fibrosis (NSF). This paper introduces the mechanism of the transformation and deposition of NSF, aiming to reveal the chemical nature of the gadolinium phosphate bioparticles in nephrogenic system fibrosis. This research will provide an important theoretical basis for future studies on the occurrence, development, and formation of nephrogenic system fibrosis and the removal of sediment residues. Moreover, a new idea for introducing a biocompatible second chelating agent into the gadolinium contrast agent system has been proposed, which aims to improve the safe use of gadolinium contrast agent. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical significance of monitoring neuron specific enolase (NSE), carbohydrate antigen 125 (CA125), and carbohydrate antigen 199 (CA199) in patients with pneumoconiosis. Methods A retrospective analysis was conducted among 222 patients with pneumoconiosis admitted to this hospital from January 2018 to December 2022. The patients were divided into three groups according to the stage of pneumoconiosis (stage I, II, and III). The serum levels and abnormal rates of NSE, CA125, and CA199 among these groups were compared. Results Among the 222 patients with pneumoconiosis, 51 (22.97%) were in stage I, 52 (23.42%) were in stage II, and 119 (53.61%) were in stage III. There were statistically significant differences in serum NSE and CA125 levels among pneumoconiosis patients at different stages (P < 0.001), and serum NSE and CA125 levels in patients at stage III were higher than those in stage I and stage II (P < 0.001). There was no statistically significant difference in serum CA199 level among pneumoconiosis patients at different stages (P = 0.163). The abnormal rates of serum NSE, CA125, and CA199 levels among 222 patients were 45.05%, 27.93%, and 2.70%, respectively. There were statistically significant differences in serum NSE and CA125 abnormal rates among pneumoconiosis patients at different stages (both P < 0.001), and both showed an increasing trend with the increase of stage. Conclusions Monitoring serum NSE and CA125 in patients with pneumoconiosis can indicate the progression of their condition and provide references for the treatment plan. [ABSTRACT FROM AUTHOR]

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nscription factor-κB (NF-κB) signaling pathway, and its effect on renal fibrosis in diabetic nephropathy (DN) rats. Methods: A rat DN model was established, and the renal tubular epithelial cells (NRK-52E) were cultured with high sugar to simulate an in vitro DN model, qRT-PCR was used to detect the expression level of miR-203, Western blot was used to detect the expressions of PEG3 and NF-κB proteins. Dual luciferase reporter gene technology was used to detect the targeting relationship between miR-203 and PEG3. The miR-203 mimic (miR-203 mimic) and negative control (mimic NC), PEG3 high expression recombinant vector (pcDNA-PEG3) and negative control (pcDNA-NC) were constructed, and injected and transfected into DN rats and DN model cells respectively to set the control group, model group, miR-203 mimic group, mimic NC group, miR-203 mimic+pcDNA-PEG3 group, and miR-203 mimic+pcDNA-NC group. The 24 h urine protein, blood sugar, serum creatinine (SCr) and urea nitrogen (BUN) in rats were detected, electron microscopy and Masson staining were used to detect renal tissue lesions and fibrosis changes; ELISA was used to detect the contents of IL-6, IL-1β, Collagen Ⅰand TGF-β1 in cells； Western blot was used to detect the protein expressions of IL-6, IL-1β, Collagen Ⅰ，α-SMA and TGF-β1 in kidney tissue. Results: The expressions of miR-203 in kidney tissue and renal tubular epithelial cells of DN rats were decreased (P<0.05), the expression of PEG3/NF-κB was increased in kidney tissue and renal tubular epithelial cells of DN rats (P<0.05). There was a targeted binding site between miR-203 and PEG3. Up-regulating the expression of miR-203 could inhibit the activation of PEG3/NF-κB in DN rats and cell models, reduce the expression of inflammation-fibrosis related factors, and alleviate the pathological symptoms of DN such as renal tissue structural damage and decreased renal function in rats (P<0.05). pcDNA-PEG3 could partially reverse the above effects of miR-203(P<0.05). Conclusion: miR-203 can target to negatively regulate the PEG3/NF-κB pathway and up-regulate the expression of miR-203, which can target to inhibit the activation of the PEG3/NF-κB pathway and play the role of anti-inflammatory-fibrosis in the kidney of DN rats. [ABSTRACT FROM AUTHOR]

Copyright of Science & Technology of Food Industry is the property of Science & Technology of Food Industry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acute myocardial infarction is a serious ischemic disease. In response to myocardial infarction, cardiac remodeling takes place by means of cardiac structural and functional changes. This remodeling including three continuous cellular pathophysiological stages: Inflammation, proliferation and scar maturation. The first stage is characterized by infiltration of great amount of inflammatory cells induced by injured, necrotic, apoptotic cells and cellular debris. The latter two stages represent a repair process, which caused by anti-inflammatory cells and cytokines, as well as fibroblasts, which altogether contribute to inflammation regression, new blood vessel formation and fibrous scar maturation. Immune system plays an important and complex role in process of cardiac remodeling, among which macrophages provide a pivotal impact in this pathological change, which is one of research hotspots in recent years. In this paper, we mainly reviews cellular behavior of macrophages in cardiac remodeling after myocardial infarction and research progress of traditional Chinese medicine in modulating macrophages. [ABSTRACT FROM AUTHOR]

Fibrosis is an abnormal repair process of the organism activated by tissue injury, with the typical pathological manifestation of excessive deposition of extracellular matrix, ultimately leading to the destruction of normal tissue structure as well as organ hypofunction or even failure. The development of targeted anti-fibrotic drugs has been hampered by the fact that the specific mechanism is not yet clear. There is growing evidence that interleukin-36 （IL-36） has an important role in the development of fibrotic diseases. Aberrant expression of IL-36 cytokines is observed in idiopathic pulmonary fibrosis, liver fibrosis, renal interstitial fibrosis, inflammatory bowel disease-associated intestinal fibrosis, and cardiac fibrosis. Inhibition or knockdown of IL-36 can effectively prevent or even reverse fibrotic lesions, and its mechanism is closely related to the regulation of immune cell responses, the activation of fibroblasts, and the regulation of related enzyme activity. In this paper, we review the recent research progress of IL-36 and its expression and pro-fibrotic mechanisms in different fibrotic diseases in order to provide a reference for further research. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of proto-oncogene c-SKI（ cellular Sloan-Kettering Institute） expression on hypertensive myocardial fibrosis induced by angiotensin II （Ang II） in mice. METHODS: Twelve male C57BL/6 mice were randomly divided into PBS group（ n=6） and Ang II group（ n=6）. The mice were subcutaneously implanted with osmotic pressure micropumps to receive equal volume of PBS and Ang II for 4 weeks, and the blood pressure was monitored. The histopathological characteristics of mouse heart tissue slices were detected by HE and Masson staining. The protein levels of c-SKI, CD31, smooth muscle protein 22（ SM22）, collagen type I（ Col I） and α-smooth muscle actin（ α -SMA） were detected by immunohistochemical and Western blot. Additionally, human coronary artery endothelial cells （HCAECs） were treated with various concentrations of Ang II. The morphological changes of the cells were observed under a microscope, and the cell viability was determined by CCK-8 assay. The HCAECs were treated with the lowest effective dose of Ang II, and the expression levels of c-SKI, CD31, α-SMA, Col I, and epithelial-mesenchymal transition （EMT） pathway proteins were detected by immunofluorescence staining and Western blot. Moreover, after overexpression of c-SKI combined with Ang II treatment in HCAECs, the cell viability and apoptosis were detected by CKK-8 assay and flow cytometry, and the expression levels of α-SMA, c-SKI, CD31, Col I, EMT pathway proteins and EMT markers were detected by immunofluorescence staining and Western blot. RESULTS: After Ang II treatment, the systolic blood pressure of the tail artery in mice increased（ P<0. 01）, accompanied by thickening of the cardiac ventricular wall. The expression levels of Col I and α-SMA were significantly increased （P<0. 01）, while c-SKI, CD31 and SM22 were significantly down-regulated（ P<0. 01）. After treatment with Ang II at 10 μmol/L, the HCAEC morphology changed, and cell viability decreased significantly at 48 h （P<0. 01）. The protein levels of Col I, α-SMA, Twist, Snail and p-Smad2/3 were significantly up-regulated in Ang II group（ P<0. 01）, while c-SKI and CD31 were significantly down-regulated（ P<0. 01）. Overexpression of c-SKI significantly increased cell vaibility （P<0. 01） and significantly decreased the apoptosis rate （P< 0. 01）. The levels of c-SKI, CD31 and E-cadherin were significantly increased （P<0. 01）, while α-SMA, Col I, Twist, Snail, p-Smad2/3, N-cadherin and vimentin were significantly down-regulated （P<0. 01）. Compared with Ang II+vector group, the viability of HCAECs was improved after overexpression of c-SKI combined with Ang II treatment（ P<0. 01）, accompanied by inhibited cell apoptosis （P<0. 01）, up-regulated c-SKI, CD31, and E-cadherin expression （P<0. 05）, and down-regulated α-SMA, Col I, Twist, Snail, p-Smad2/3, N-cadherin and vimentin expression （P<0. 01）. CONCLUSION: Angiotensin II may promote hypertensive myocardial fibrosis in mice through the regulation of c-SKI expression. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of transforming growth factor-beta 1 in endometrial fibrosis in rats and related mechanisms. Methods Sprague-Dawley female rats were randomly divided into sham operation group (n=12) and model group (n=12). Uterine tissues were collected on days 7, 14 and 18 after surgery. HE staining and Masson staining were measured the number of endometrial glands and degree of endometrial fibrosis. The protein expression of TGF-β1 and α-SMA were measured by immunohistochemistry. Results Compared with the sham operation group, the uterine structure of the rats in the model group was significantly disrupted; there was a significant increase in TGF-β1 expression in the model group at 7 days,14 days, and 28 days of modeling; the number of endometrial glands decreased, the fibrotic area of endometrium increased and the expression of α-SMA was significantly higher at 14 days and 28 days of modeling. Conclusions TGF-β1 may promote endometrial fibrosis by activating myofibroblasts. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the efficacy of compound Danhuang formula in the treatment of cholestatic liver disease of liver-gallbladder dampness-heat pattern, and to further analyze its potential mechanism based on the synthesis, transport and metabolism, fibrosis, inflammation and oxidative stress of bile acid. METHODS: Totally 128 patients with cholestatic liver disease of liver-gallbladder dampness-heat pattern admitted into the hepatology department of the hospital from Mar. 2020 to Oct. 2022 were enrolled for study, the patients were divided into control group and observation group via random number table method, with 64 cases in each group. The control group was given Western expectant treatment, the observation group was given compound Danhuang formula based on the control group, both groups were treated for 4 weeks. The syndrome integrals, liver function and incidences of adverse drug reactions were compared between two groups, its effects on related parameters of the synthesis, transport and metabolism, fibrosis, inflammation and oxidative stress of bile acid were further analyzed. RESULTS: During research, 2 cases in the control group and 1 case in the observation group were loss to follow-up. After treatment, the syndrome integrals of lateral thorax pain, abdominal distension, fatigue and cutaneous pruritus of both groups were lower than those before treatment, and those of the observation group were lower than the control group; the alkaline phosphatase and glutamyl transpeptidase of both groups were lower than those before treatment, and those of the observation group were lower than the control group, with statistically significant differences ( P < 0. 05 ). The incidences of adverse drug reactions of control group and observation group were respectively 8. 06% ( 5 / 62) and 4. 76% (3 / 63), the difference had no statistical significance (P> 0. 05). After treatment, the total bile acid and fibroblast growth factor-19 of both groups were lower than those before treatment, and those of the observation group were lower than the control group; the Ⅲ-type procollagen, hyaluronic acid, laminin and Ⅳ-type collagen of both groups were lower than those before treatment, and those of the observation group were lower than the control group, with statistically significant differences (P<0. 05). After treatment, the interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were lower and the superoxide dismutase (SOD) was higher in both groups than those before treatment, the IL-6 and TNF-α were lower and the SOD was higher in the observation group than those in the control group, with statistically significant differences ( P < 0. 05 ). CONCLUSIONS: Patients with cholestatic liver disease of livergallbladder dampness-heat pattern can obtain definite efficacy by receiving compound Danhuang formula based on Western expectant treatment, which can improve lover function, with few adverse drug reactions. The compound Danhuang formula can play a positive role in the synthesis, transport and metabolism, anti-fibrosis, anti-inflammatory reaction and oxidative stress of bile acid. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and mechanism of micheliolide on renal lesions of unilateral ureteral obstruction (UUO) mice. Methods Male C57BL/6J mice were randomly divided into the sham group, the UUO (model) group and the UUO+micheliolide (administration) group. Mice in the UUO+ micheliolide group were given micheliolide by gavage at 25 mg/kg body weight after the establishment of the animal model. Renal tissue samples were collected 8 days after operation, and the renal tissue was stained with HE, Masson and TUNEL staining. The protein expressions of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and (phosphorylation)- nuclear transcription factor (NF)-κB p65 were detected by immunohistochemistry and Western blot assay. Results HE staining showed that there were no pathological changes in renal tissue in the sham group. Mice in the UUO group had progressive renal tubule dilation and interstitial edema with a small amount of inflammatory cell infiltration. The renal lesions were significantly improved in the UUO+MCL group compared with those of the UUO group. Masson staining showed that compared with the sham group, the collagen volume fraction (CVF) was significantly increased in the UUO group, while CVF was significantly reduced in the UUO+MCL group than that in the UUO group. TUNEL staining showed that compared with the sham group, the apoptosis rate was increased in the UUO group, and the apoptosis rate was significantly decreased in the UUO+MCL group than that of the UUO group. Western blot assay and immunohistochemistry result showed that the expression levels of NLRP3, caspase-1, IL-1β, TNF-α and p-NF-κB p65 were increased in kidney tissue of the UUO group compared with those of the sham group. Compared with the UUO group, NLRP3, caspase-1, IL-1β, TNF-α and p-NF-κB p65 were significantly decreased in the UUO+MCL group. Conclusion The expression of NLRP3 inflammasome and related inflammatory factors in renal tissue of mice with unilateral ureteral obstruction are increased. Micheliolide can reduce the inflammatory response of renal tubule interstitium by inhibiting NF- κB pathway and NLRP3 inflammasome activation, thereby improving renal fibrosis. [ABSTRACT FROM AUTHOR]

Objective This study aimed to investigate the expression of CD73 in colonic tissues in Crohn's disease (CD) and its significance and possible mechanism of action. Methods Thirty male BALB/c mice were randomly divided into normal control group, model group and intervention group. The control group was fed normally, and the model group was treated with TNBS+40% alcohol enema to establish a mouse model of Crohn's disease induced by chronic inflammation. The intervention group was treated with AB-680 intraperitoneally on the second day of each enema based on the model group. Mice body weight, fecal traits and fecal occult blood were recorded for disease activity index (DAI) score of inflammatory bowel disease. The animals were sacrificed at 7th week, their colonic tissues were removed, weighed and measured. The tissue inflammation was observed by standard hematoxylin-eosin (HE) staining. Masson staining was used to measure the area of collagen in colon tissue of mice. CD73 was detected by fluorescence quantitative PCR and immunohistochemistry. The expression levels of TGF-β, TNF-α and IL-6 in colon tissue of mice were determined by ELISA. Results The DAI score was (0.10±0.16) in the control group, (2.80±0.79) in the model group, and (3.07±0.34) in the intervention group. Compared with the control group, the DAI scores of the model and intervention groups were increased significantly (P<0.05). Compared with the model group, the DAI score of the intervention group was significantly increased (P<0.05). HE staining showed that there was no inflammation in the colon of the control group, while the colon of the model group and the intervention group showed typical inflammatory manifestations such as edema and congestion, inflammatory cell infiltration, and mucosal ulcer. The area ratio of collagen in the control group was (4.95±0.82)%, in the model group was (24.62±1.46)%, and in the intervention group was (54.47±2.75)%. Compared with the control group, the area ratio of collagen in the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the area ratio of collagen in the intervention group was significantly increased (P<0.05). Compared with the control group, the expression of CD73 in colon tissue of the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the expression of CD73 in colon tissue of the intervention group was decreased (P<0.05). Compared with the control group, the expressions of TGF-β, TNF-α and IL-6 in the model group and the intervention group were significantly increased (P<0.05). Compared with the model group, the expression of TGF-β, TNF-α and IL-6 in the intervention group decreased (P<0.05). Conclusions CD73 is upregulated in colon tissue of CD mice, it can inhibit inflammatory reaction and improve fibrosis by up-regulating TGF-β expression. On the other hand, CD73 can aggravate the inflammatory response in CD intestinal inflammation and fibrosis by upregulating the expression of IL-6 and TNF-α. Therefore, CD73 may play a bidirectional regulatory role in intestinal inflammation and fibrosis of CD. [ABSTRACT FROM AUTHOR]

BackgroundOccupational and environmental particulate matter may cause fibrosis, accompanied by RNA m6A modification changes. Neodymium oxide (Nd2O3) can cause mouse lung fibrosis, which contains a large number of fibroblasts. ObjectiveTo investigate m6A modification of tumor necrosis factor receptor-associated protein 6/nuclear factor-κB (TRAF6/NF-κB) signaling pathway in fibrosis of human embryonic lung fibroblasts induced by Nd2O3, and identify the key m6A modification sites of TRAF6. MethodsDesigned concentrations of Nd2O3 (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100, and 200 mg∙L−1) were infected with HELF cells for 24 and 48 h, and cell viability was detected to determine exposure time and dose. Measurements included indicators of fibrosis [hydroxyproline (HYP) and transforming growth factor-β1 (TGF-β1)], m6A methylation level, methyltransferases (METTL3 and METTL14), demethylases (FTO and ALKBH5), reading proteins (YTHDC2 and YTHDF2), fibrosis-associated genes (collagen-І, vimentin, and α-SMA), and proteins related to signaling pathway (TRAF6, NFKB1, P65, and P-P65). The enrichment of m6A in TRAF6 mRNA was measured by methylated RNA immunoprecipitation-quantitative real-time PCR (MeRIP-qPCR). ResultsThe results of cell viability indicated that 6.25, 12.5, 25 mg∙L−1 Nd2O3 and 48 h exposure time were used for subsequent experiments. After 48 h exposure, compared with the control group, the HYP level in the 25 mg∙L−1 Nd2O3 group was increased, and the levels of TGF-β1 in the 6.25, 12.5, and 25 mg∙L−1 Nd2O3 groups were increased (P

BACKGROUND: The foreign body reaction induced by implanted biomaterials leads to the formation of surface fibrosis (also known as implant fibrosis), that is, biomaterials are wrapped by fibrous tissue, making them lose their functionality and producing serious clinical complications, which is a major problem in the field of tissue regeneration and repair. The key cells involved in implant fibrosis are macrophages. However, the effects and mechanism of macrophages on the process of implant fibrosis and the strategy of inhibiting fibrosis remain unclear. OBJECTIVE: To review the effects of macrophage polarization and differentiation events on material fibrosis, including fibrogenic signal pathways, and strategies to inhibit biomaterial fibrosis based on specific regulation of macrophages. METHODS: The relevant articles up to 2022 were searched on PubMed, Wiley, EBSCOhost, ScienceDirect, and Elsevier databases using English search terms “macrophages, biological materials, fibrosis, foreign body reaction, myofibroblasts, inflammation, regulation, surface topology, mechanical properties, chemical signals”, and 60 articles were finally included for the further analysis. RESULTS AND CONCLUSION: (1) Both M1 and M2 macrophages may participate in the formation of biomaterial fibrosis. Maybe strategies that regulate macrophage polarity alone cannot inhibit the formation of fibrosis in biomaterials. (2) As a key cellular event in the regulation of macrophage-mediated biomaterial fibrosis, the differentiation of macrophages into myofibroblasts can induce the expression of marker α-smooth muscle actin, indicating that this process has a direct effect on fibrosis. (3) In terms of the signaling pathway of macrophages promoting fibrosis, the analysis suggests that there may be differences in the signaling pathway of macrophages with different phenotypes. (4) Two main pathways are involved in the regulation of macrophage-induced inflammation using the physical properties of biomaterials. First, based on the biomaterial surface topology, the construction of patterning surface less than 100 nm or the enhancement of surface roughness of biomaterial is expected to reduce macrophage fusion and expression of inflammatory factors, reducing fibrosis caused by macrophages. Second, researchers prefer to design and prepare biomaterials with smaller modulus of elasticity to reduce the stress transfer induced by the implant to the injured tissue, reduce macrophage-induced inflammation, and improve the fibrosis during tissue repair. (5) Regarding the use of chemical signals to regulate the expression of macrophage-induced inflammation, regulatory strategies can be implemented mainly in macrophage-derived inflammatory factors, as well as chemical signals for macrophage recruitment, fusion, and differentiation; therefore, effective use of inhibitors and antioxidants can achieve reverse regulation of transforming growth factor β1, reactive oxygen species, nuclear transcription factor κB, and miRNA-21 through the above pathways, thus delaying fibrosis induced by macrophages. [ABSTRACT FROM AUTHOR]

Pancreatic fibrosis is the main irreversible pathological change during the progression of chronic pancreatitis，and at present，there is still a lack of effective drugs for the treatment of pancreatic fibrosis in clinical practice. This article summarizes the application of traditional Chinese medicine (TCM) in the treatment of pancreatic fibrosis in recent years from the aspects of clinical strategies and research advances. The TCM syndrome differentiation of pancreatic fibrosis involves the liver， gallbladder， spleen， and stomach， and pathological factors are associated with fire， blood stasis， and phlegm dampness. The research on the anti－pancreatic fibrosis effect of TCM extracts mainly involves spleen－strengthening， dampness－resolving，and blood stasis－resolving drugs，and intervention against the activation of pancreatic stellate cells is the main signaling pathway involved in the mechanism of TCM prescriptions in the treatment of pancreatic fibrosis. The above studies provide a reference for in－depth research on the application of TCM in the prevention and intervention of pancreatic fibrosis and the prevention and treatment of related complications. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury, rejection, nephrotoxicity caused by calcineurin inhibitors and other factors cause excessive accumulation of renal extracellular matrix after kidney transplantation, which gradually induce renal fibrosis and eventually lead to renal failure. In recent years, the mechanism of macrophages in renal allograft fibrosis has gradually captivated widespread attention. Studies have shown that some drugs like mammalian target of rapamycin inhibitors may mitigate renal allograft fibrosis through the macrophage. In this article, the main pathogenesis and pathophysiological mechanism of renal allograft fibrosis, the role of different macrophages in the progression of renal allograft fibrosis, the infiltration of peripherally-recruited macrophages and renal resident macrophages into renal injury areas, the induction of myofibroblasts by macrophages and potential treatment regimens of macrophage-associated renal allograft fibrosis were reviewed, aiming to provide reference for investigating the role of macrophages in renal allograft fibrosis. [ABSTRACT FROM AUTHOR]

Objective: The current study aims to investigate the effect and molecular mechanism of dapagliflozin on epithelial⁃mesenchymal transformation and fibrosis of renal tubular epithelial cells in diabetic kidney disease. Methods: Human renal tubular epithelial cells HK⁃2 were cultured in vitro and divided into control group, high glucose group, low dose dapagliflozin + high glucose group and high dose dapagliflozin+high glucose group. The expression levels of Rffl were detected by Western blot and RT⁃PCR, respectively. The expression levels of epithelial cadherin (E⁃cadherin), α⁃smooth muscle actin (α⁃SMA), Fibronectin, transforming growth factor β1 (TGF⁃β1) and signal transducer and activator of transcription 1 (STAT1) were detected by Western blot. After Rffl was overexpressed in HK⁃2 cells, the expression levels of E⁃cadherin, α⁃SMA, Fibronectin, TGF⁃β1 and STAT1 were detected by Western blot. Results: The expression level of Rffl was significantly lower in the high glucose group than in the control group, and the expression of Rffl was increased after adding dapagliflozin. Compared with the control group, the expression level of E⁃Cadherin in the high glucose group was decreased, while the expression level of Fibronectin and α⁃SMA was increased. After Rffl was overexpressed in cells, the expression level of E⁃Cadherin was increased, while the expression levels of Fibronectin and α⁃SMA were decreased. Compared with high glucose group, the expression levels of E⁃Cadherin in low⁃dose dapagliflozin+high glucose group and high⁃dose dapagliflozin+high glucose group were increased, but the expression levels of Fibronectin and α⁃SMA were decreased in a dose⁃dependent manner. Compared with the control group, the expression levels of STAT1 and TGF⁃β1 were increased in the high glucose group, but significantly decreased after overexpression of Rffl or addition of dapagliflozin. Conclusion: Dapagliflozin inhibits STAT1/ TGF⁃β1 signaling pathway by up⁃regulating Rffl expression, and improves epithelial⁃mesenchymal transformation and fibrosis of renal tubular epithelial cells in diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Background and objective Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. Methods Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. Results A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microen-vironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. Conclusions This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Sichuan University (Medical Science Edition) is the property of Editorial Board of Journal of Sichuan University (Medical Sciences) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)