Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n =22), alcoholic steatosis (n =30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood mononuclear cells (PBMC) as samples the gene expression of TGF-beta 1 was examined quantitatively by reverse transcription polymerase chain reaction (RT-PCR) and dot blot. There are 34 healthy subjects served as control. RESULTS: The expression of TGF-beta 1 from all ALD patients was significantly greater than that in controls (1.320 +/- 1.162 vs 0.808 +/- 0.276, P【0.001). The differences of the expressions were significant between the patients from each groups (alcoholic steatosis, alcoholic hepatitis and alcoholic cirrhosis) and the controls (1.168 +/- 0.852, 1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.808 +/- 0.276, P【0.050). No significant differences of TGF -beta 1 mRNA expression were observed between alcohol abusers without liver impairment and controls. The expressions in patients with alcoholic hepatitis and alcoholic cirrhosis were significantly greater than that in alcohol abusers respectively (1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.841 +/- 0.706, P【0.050). No significant differences of TGF-beta 1 mRNA expression were observed between alcoholic fatty liver men and alcohol abusers. CONCLUSION: TGF-beta 1 expression level can be a risk factor for alcoholic liver disease and might be related to the inflammatory activity and fibrosis of the liver in patients.

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn's disease intestinal fibrosis

AIM To explore the role and mechanism of total flavone of Abelmoschus manihot(TFA) on epithelial-mesenchymal transition(EMT) progress of Crohn's disease(CD) intestinal fibrosis.METHODS First,CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial(IEC-6) cells and select the optimal concentrations of TFA for our further studies.Then cell morphology,wound healing and transwell assays were performed to examine the effect of TFA on morphology,migration and invasion of IEC-6 cells treated with TGF-β1.In addition,immunofluorescence,real-time PCR analysis(q RT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress.Moreover,western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways.Further,the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by q RTPCR,western blotting,morphology,wound healing andtranswell assays.RESULTS In this study,TFA promoted transforming growth factor-β1(TGF-β1)-induced(IEC-6) morphological change,migration and invasion,and increased the expression of epithelial markers and reduced the levels of mesenchymal markers,along with the inactivation of Smad and MAPK signaling pathways.Moreover,we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells.Importantly,co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.CONCLUSION These findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

Transforming growth factor β1-mediated anti-inflammation slows progression of midbrain dopaminergic neurodegeneration in Parkinson's disease?

Parkinson’s disease（PD）is characterized by the progressive loss of midbrain dopaminergic（m DA）neurons and a subsequent decrease in striatal dopamine levels,which cause the typical clinical motor symptoms such as muscle rigidity,bradykinesia and tremor.

Oral encapsulated transforming growth factorβ1 reduces endogenous levels:Effect on inflammatory bowel disease

BACKGROUND TreXTAM®is a combination of the key regulatory cytokine transforming growth factor beta(TGFβ)and all trans retinoic acid(ATRA)microencapsulated for oral delivery to immune structures of the gut.It is in development as a novel treatment for inflammatory bowel disease(IBD).AIM To measure TGFβlevels in blood and tissue after oral administration of encapsulated TGFβ.METHODS Animals were orally administered encapsulated TGFβby gavage.Levels of drug substance in blood and in gut tissues at various times after administration were measured by ELISA.RESULTS We made the surprising discovery that oral administration of TreXTAM dramatically(approximately 50%)and significantly(P=0.025)reduced TGFβlevels in colon,but not small intestine or mesenteric lymph nodes.Similarly,levels in rat serum after 25 d of thrice weekly dosing with either TreXTAM,or microencapsulated TGFβalone(denoted as TPX6001)were significantly(P<0.01)reduced from baseline levels.When tested in the SCID mouse CD4+CD25-adoptive cell transfer(ACT)model of IBD,oral TPX6001 alone provided only a transient benefit in terms of reduced weight loss.CONCLUSION These observations suggest a negative feedback mechanism in the gut whereby local delivery of TGFβresults in reduced local and systemic levels of the active form of TGFβ.Our findings suggest potential clinical implications for use of encapsulated TGFβ,perhaps in the context of IBD and/or other instances of fibrosis and/or pathological TGFβsignaling.

Health system and patient-level factors serving as facilitators and barriers to rheumatic heart disease care in Sudan

Background:Rheumatic heart disease(RHD)remains a leading cause of morbidity and mortality in Sub-Saharan Africa despite widely available preventive therapies such as prophylactic benzathine penicillin G(BPG).In this study,we sought to characterize facilitators and barriers to optimal RHD treatment with BPG in Sudan.Methods:We conducted a mixed-methods study,collecting survey data from 397 patients who were enrolled in a national RHD registry between July and November 2017.The cross-sectional surveys included information on demographics,healthcare access,and patient perspectives on treatment barriers and facilitators.Factors associated with increased likelihood of RHD treatment adherence to prophylactic BPG were assessed by using adjusted logistic regression.These data were enhanced by focus group discussions with 20 participants,to further explore health system factors impacting RHD care.Results:Our quantitative analysis revealed that only 32%of the study cohort reported optimal prophylaxis adherence.Younger age,reduced primary RHD healthcare facility wait time,perception of adequate health facility staffing,increased treatment costs,and high patient knowledge about RHD were significantly associated with increased odds of treatment adherence.Qualitative data revealed significant barriers to RHD treatment arising from health services factors at the health system level,including lack of access due to inadequate healthcare staffing,lack of faith in local healthcare systems,poor ancillary services,and patient lack of understanding of disease.Facilitators of RHD treatment included strong interpersonal support.Conclusions:Multiple patient and system-level barriers to RHD prophylaxis adherence were identified in Khartoum,Sudan.These included patient self-efficacy and participant perception of healthcare facility quality.Strengthening local health system infrastructure,while enhancing RHD patient education,may help to improve treatment adherence in this vulnerable population.

Transforming growth factor-β and smooth muscle differentiation

Transforming growth factor(TGF)-β family members are multifunctional cytokines regulating diverse cel- lular functions such as growth,adhesion,migration, apoptosis,and differentiation.TGF-βs elicit their effects via specific typeⅠand typeⅡserine/threonine kinase receptors and intracellular Smad transcription factors. Knockout mouse models for the different components of the TGF-β signaling pathway have revealed their critical roles in smooth muscle cell(SMC)differentia- tion.Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular disorders such as aorta aneurysm and congenital heart diseases due to SMC defects.In this review,the current understanding of TGF-β function in SMC differentiation is highlighted,and the role of TGF-βsignaling in SMC- related diseases is discussed.

Dab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling

Transforming growth factor-beta （TGF-β） type II receptor （TβRⅡ） levels are extremely low in the brain tissue of patients with Alzheimer＇s disease. This receptor inhibits TGF-β1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a specific adapter protein, protects T RII from degradation and ensures the effective conduction of TGF-β 1/SMAD signaling. In this study, we used an adenoviral vector to overexpress the Dab2 gene in the mouse hippocampus and investigated the regulatory effect of Dab2 protein on TGF-β1/SMAD signaling in a mouse model of Alzheimer＇s disease, and the potential neuroprotective effect. The results showed that the TβRⅡ level was lower.in APP/PS1 mouse hippocampus than in normal mouse hippocampus. After Dab2 expression, hippocampal TβRⅡ and p-SMAD2/3 levels were signifi- cantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor- and interleulin-6 levels and neuronal loss were significantly attenuated in APP/PS1 mouse brain tissue. These results suggest that Dab2 can exhibit neuroprotective effects in Alzheimer＇s disease by regulating TGF-β1/SMAD signaling.

Plasma HGF and OPN as Potential Biomarkers of Pulmonary Arterial Hypertension in Congenital Heart Disease

Objectives:Pulmonary arterial hypertension in congenital heart disease(PAH-CHD)is the most common type of PAH and increases morbidity and mortality in patients with CHD.Right heart catheterization(RHC)is the standard method to diagnose PAH.However,RHC is an invasive and complicated method with relatively high cost.Noninvasive,feasible,and cost-efficient methods are urgently needed.The objective of this study was to evaluate three potential biomarkers of PAH-CHD:Hepatocyte growth factor(HGF),osteopontin(OPN),and suppression of tumorigenicity 2(ST2).Methods:Plasma samples were collected from patients with CHD(n=46)and healthy individuals(n=22)and divided into four groups according to the severity of PAH.The levels of HGF,OPN,and ST2 were then analyzed using an enzyme-linked immunosorbent assay.Correlations between HGF,OPN,ST2,and clinical parameters of PAH-CHD were analyzed.Results:The plasma HGF levels in the moderate to the severe group were significantly higher than those in the mild group,nonPAH group,and healthy control group(p<0.05).Derived from a receiver operating characteristic(ROC)curve analysis,a cut-off value of 356.75 ng/ml for the HGF concentration was able to predict PAH-CHD with 53%sensitivity and 89%specificity.The HGF level was positively related to pulmonary arterial systolic pressure(PASP)(r=0.36,p<0.05)and pulmonary vascular resistance(PVR)(r=0.36,p<0.05).Plasma OPN levels in the mild group were significantly higher than other groups and positively correlated with the pulmonary-systemic shunt ratio(Qp/Qs)(r=0.33,p<0.05).There was no statistically significant between-group difference in plasma soluble ST2(sST2)levels.Conclusion:The plasma HGF level was elevated in PAH-CHD patients and can be used as a potential biomarker.The plasma OPN level was positively correlated with the Qp/Qs.

Effects of trimetrazine combined with Rhodiolarosea on patients with coronary heart disease combined with heart failure and RDW and GDF-15 levels

Objective: To investigate the effect of Rhodiola sachalinensis combined with trimetazidine on patients with coronary heart disease complicated with heart failure and the influence of RDW (Red Blood Cell Distribution Width), GDF-15 (Growth and Differentiation Factor 15) level. Methods: A total of 104 patients with coronary heart disease and heart failure treated in our hospital from March 2016 to November 2018 were randomly divided into control group and observation group, 52 cases in each group. After admission, patients in the control group were given routine symptomatic treatment according to the course of the disease, including angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, diuretics, beta-blockers and other drugs. The observation group was treated with Dazhu Hongjingtian injection combined with trimetazidine on the basis of the treatment measures of the control group. At the end of the course of treatment, the therapeutic effects of the two groups were evaluated, and the indexes of cardiac function before and after treatment were tested, including:left ventricular end-diastolic diameter (LEVDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF, Left Ventricular End-Diastolic Dimension), left ventricular ejection fraction (Left Ventricular Enje). The changes of RDW and GDF-15 levels before and after treatment were analyzed and compared between the two groups. Results: The total effective rate of the observation group was 95.00%, which was significantly higher than that of the control group. After treatment, the LVEF value of the observation group was significantly higher than that of the control group, but the LVESD and LVEDD of the observation group were significantly lower than that of the control group. After treatment, the content of GDF-15 in the observation group was significantly lower than that of the control group;the RDW of the observation group was lower than that of the There was no significant difference. Conclusion: Trimetazidine combined with Rhodiola sachalinensis can effectively treat patients with coronary heart disease and heart failure, and can effectively reduce the levels of RDW and GDF-15. It has good clinical application prospects.

Osler’s Subacute Infective Endocarditis on Rheumatic Heart: A Complicated Clinical Case That Reflects Four (4) Major Public Health Issues in Sub-Saharan Africa

Endocarditis is an inflammation of the endocardium and its structures (valves), most often of infectious origin, described by William Osler in 1885. In the 21st century, infective endocarditis remains a reality in our countries. We report a complicated case of infective endocarditis (IE). This is a 53-year-old woman, obese and passive smoker who died on the 5th day of her hospitalization following an infective endocarditis (IE) with bacterial strains resistant to the usual antibiotics: daughter of acute lithiasic cholecystitis, mother of major mitral valve perforation, brain abscess, ischemic stroke and atrial fibrillation. All were responsible for septic shock and fatal coma. Surgical management of the infective endocarditis in the first hours of her admission could have improved her prognosis. To conclude, in addition to its interests and its clinical particularities, our present observation has highlighted major public health problems specific to our sub-Saharan African countries, namely: The problem of the double health burden, the problem of delays in seeking care, the problem of resistance to antibiotics and the problem of the insufficiency of reference health technical platforms.

The correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease

Objective:To study the correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease.Methods: A total of 80 patients with coronary heart disease who were treated in our hospital between January 2013 and April 2016 were collected as the observation group, and 50 healthy subjects who received medical examination in our hospital during the same period were selected as the normal control group. Serum PDGF and Ang-2 contents of two groups of patients were detected, and the observation group were further divided into the high PDGF group and low PDGF group (n = 40) as well as the high Ang-2 group and low Ang-2 group (n = 40) according to the median of PDGF and Ang-2 contents. Ultrasonic contrast technology was used to assess the atherosclerotic plaque characteristics in patients with coronary heart disease.Results: Serum PDGF and Ang-2 contents of observation group were significantly higher than those of control group;ultrasound parameters P and AUC levels of high PDGF group were higher than those of low PDGF group while Tp and MTT levels were lower than those of low PDGF group;ultrasound parameters P and AUC levels of high Ang-2 group were higher than those of low Ang-2 group while Tp and MTT levels were lower than those of low Ang-2 group.Conclusion:Serum PDGF and Ang-2 contents increase in patients with coronary heart disease and are negatively correlated with the atherosclerotic plaque stability.

Pathophysiology of fistula formation in Crohn's disease

Fistulae represent an important complication in patient suffering from Crohn's disease(CD). Cumulative incidence of fistula formation in CD patients is 17%-50% and about one third of patients suffer from recurring fistulae formation. Medical treatment options often fail and also surgery frequently is not successful. Available data indicate that CD-associated fistulae originate from an epithelial defect that may be caused by ongoing inflammation. Having undergone epithelial to mesenchymal transition(EMT), intestinal epithelial cells(IEC) penetrate into deeper layers of the mucosa and the gut wall causing localized tissue damage formation of a tube like structure and finally a connection to other organs or the body surface. EMT of IEC may be initially aimed toimprove wound repair mechanisms since "conventional" wound healing mechanisms, such as migration of fibroblasts, are impaired in CD patients. EMT also enhances activation of matrix remodelling enzymes such as matrix metalloproteinase(MMP)-3 and MMP-9 causing further tissue damage and inflammation. Finally, soluble mediators like TNF and interleukin-13 further induce their own expression in an autocrine manner and enhance expression of molecules associated with cell invasiveness aggravating the process. Additionally, pathogen-associated molecular patterns also seem to play a role for induction of EMT and fistula development. Though current knowledge suggests a number of therapeutic options, new and more effective therapeutic approaches are urgently needed for patients suffering from CD-associated fistulae. A better understanding of the pathophysiology of fistula formation, however, is a prerequisite for the development of more efficacious medical anti-fistula treatments.

Effects of single nucleotide polymorphisms 869 T/C and 915 G/C in the exon 1 locus of transforming growth factor-β1 gene on chronic obstructive pulmonary disease susceptibility in Chinese

Background The main risk factor for chronic obstructive pulmonary disease （COPD） is cigarette smoking. However, only 10%-20% of chronic heavy smokers develop systematic COPD. We hypothesized that the inheritance of gene polymorphisms could influence the development of COPD, which was investigated by studying two single nucleotide polymorphisms （SNP） in exon 1 of the transforming growth factor-β1 （TGF-β1） gene. Methods We enrolled 219 patients with COPD as the research group and 148 healthy people as the control group, all of whom were Chinese Han people. The polymorphisms of the TGF-β1 gene, 869T/C and 915G/C, were analyzed using the method of amplification refractory mutation system-polymerase chain reaction （ARMS-PCR）. Results The occurrence of the TGF-β1 gene 869T/C polymorphism in patients with COPD was significantly different from the control group （P 〈0.05）, in which the relative risk of this disease increased in cases who had the C allele （OR： 1.131, 95% CI： 1.101-1.539）. There was no increased frequency of TGF-β1 915G/C gene in COPD patients compared with control subjects （P 〉0.05）. Conclusions The polymorphism 869T/C in TGF-β1 gene has a significant association with disease occurrence in COPD patients and the C allele might be a risk factor. The homozygous wild-type CC of 869T/C on TGFβ1 could be a predisposing factor in COPD and those who carry the C allele might have particularly susceptibility to developing COPD.

Association of serum levels of transforming growth factor β1 with disease severity in patients with hepatocellular carcinoma

Aim: Transforming growth factor (TGF) is overexpressed by tumor cells like other proteins and growth factors. TGF-β1 is then activated in the extracellular compartment but is unable to control cell proliferation because of the absence or low level of TGF-β1 receptors on the plasma membrane of malignant hepatocytes. This potential mechanism might interrupt the autocrine regulation loop of TGF-β1 and its blocking effect on cell proliferation. TGF-β1 is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. This study aimed to evaluate the association of serum levels of TGF-β1 with disease severity. Methods: A total of 180 subjects were classified into 6 groups according to Barcelona clinic liver cancer (BCLC) classification, 30 patients each:early (BCLC 0 and A), intermediate (BCLC B), advanced stage (BCLC C), and terminal stage (BCLC D) of hepatocellular carcinoma as well as 1 group of patients with cirrhosis only and 1 control group. Serum levels of TGFβ1 were measured. Results: Serum levels of TGF-β1 were significantly higher in patients with HCC (1,687.47 ± 1,462.81 pg/mL) than cirrhotics (487.98 ± 344.23 pg/mL, P < 0.001) and controls (250.16 ± 284.61 pg/mL, P <0.001). Conclusion: TGF-β1 may have a role in tumor growth and progression.

Increased duodenal expression of mi R-146a and-155 in pediatric Crohn's disease

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn&#x02019;s disease (CD) and the effect of transforming growth factor-&#x003b2; (TGF-&#x003b2;) on these miRs in duodenal epithelial and fibroblast cells.METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-&#x003b2; (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well.RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 &#x000b1; 0.50 vs CD intact: 0.62 &#x000b1; 0.26, P &#x02264; 0.01) and to the control group (CD inflamed: 3.21 &#x000b1; 0.50 vs C: 1.00 &#x000b1; 0.33, P &#x02264; 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 &#x000b1; 1.02 vs Control: 1.00 &#x000b1; 0.40, P &#x02264; 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-&#x003b2; treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-&#x003b2;: 0.7 &#x000b1; 0.083 vs Control: 1 &#x000b1; 0.09, P &#x02264; 0.05) and also the expression of miR-146a (TGF-&#x003b2;: 0.67 &#x000b1; 0.04 vs Control: 1 &#x000b1; 0.15, P &#x02264; 0.01) and miR-155 (TGF-&#x003b2;: 0.72 &#x000b1; 0.09 vs Control: 1 &#x000b1; 0.06, P &#x02264; 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-&#x003b2; treatment did not influence the expression of miR-122.CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-&#x003b2; plays an important role in the regulation of the expression of these miRs.

Role of IL-10 in the progression of kidney disease

Interleukin-10(IL-10), a cytokine with anti-inflammatory and immunomodulatory functions, regulates the biology of B and T cells. The present review describes the role of IL-10 in normal renal physiology, during acute kidney injury and in the development of chronic renal failure. We further discuss IL-10-induced cellular and molecular pathways and their link to the progression of kidney injury.

Transforming growth factor β1 is a differentially expressed candidate protein of congestive heart failure with Qi-deficiency-blood-stasis syndrome

OBJECTIVE: To investigate the role of tongue coating fluid protein in regulation of congestive heart failure(CHF) in Qi-deficiency-blood-stasis syndrome.METHODS: We studied patients with CHF(3 patients with Qi-deficiency-blood-stasis syndrome and 3 without Qi-deficiency-blood-stasis syndrome) to investigate differentially expressed proteins. We also included a control group. A biotin label-based antibody array was used for testing tongue coating fluid samples from patients. Net-work analysis of these differentially expressed proteins was conducted using the STRING database,which can predict the relations between differentially expressed proteins and CHF with Qi-deficiency-blood-stasis syndrome.RESULTS: A total of seven differentially expressed proteins were identified, and among these, transforming growth factor β1(TGF-β1) gets a particular attention for us has drawn specific attention.Network analysis showed a homologous relationship of TGF-β1 with bone morphogenetic protein15, which is associated with myocardial fibrosis.CONCLUSION: Occurrence and development of CHF may result from certain DE-proteins and associated signaling pathways. TGF-β1 protein may be a candidate marker for assessing the risk of CHF in Qideficiency-blood-stasis syndrome.

Relation between connective tissue growth factor rs9399005 gene single nucleotide polymorphism and coronary heart disease

Objective To investigate the relationship between connective tissue growth factor(CTGF)rs9399005 gene polymorphism and serum CTGF level,coronary heart disease(CHD).Methods The serum CTGF levels were de-tected by enzyme linked immunosorbent assay in 214 cases of CHD and 64 cases of normal control group.CTGF gene rs9399005 single nucleotide polymorphism(SNP)was analyzed by Sanger method.Baseline clinical data,serum CTGF and genotype distribution frequencies

Paeoniflorin Attenuates Myocardial Fibrosis in Isoprenaline-induced Chronic Heart F ailure Rats via Inhibiting P38 MA PK Pathway

Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic heart failure(CHF)remain unclear.This study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF rats.Pae(20 mgkg)was intragastrically administrated to CHF rats for 6 weeks.Cardiac structure and function were assessed.The protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF rats.The levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,P<0.001)and perivascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso group.The expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso group.The expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso group.Pae could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.

Shenqihuatan formula(参七化痰方) reduces inflammation by inhibiting transforming growth factor-beta-stimulated signaling pathway in airway smooth muscle cells

OBJECTIVE:To study the effects and mechanism of Shenqihuatan formula(参七化痰方,SQHT)of the transforming growth factor-beta(TGF-β)-stimulated cell processes in airway remodeling.METHODS:The current study examined cell viability using a Cell Counting Kit-8 assay.Furthermore,a Transwell assay was conducted to detect the ability of cell migration,and apoptosis was detected via flowcytometry.Western Blot and quantitative real-time polymerase chain reaction(q RT-PCR)were used to determine the expression levels of apoptosis or inflammation-related factors,such as TGF-β,Interleukin-1β(IL-1β),B cell lymphoma 2(Bcl-2),Bcl-2-Associated X(Bax),Ras homolog gene family,member A(Rho A),recombinant rho associated coiled coil containing protein kinase 1/2(ROCK1/2),extracellular regulated protein kinases 1/2(ERK1/2),Snail,and Slug.Finally,the expression levels of matrix metalloproteinase-9(MMP-9)and Tissue inhibitor of metalloproteinase(TIMP-1)were admeasured by enzyme-linked immuno sorbent assay.RESULTS:The results demonstrated that SQHT inhibited the viability and migration,as well as the the F-actin formation and cytoskeletal reorganization of airway smooth muscle cells(ASMCs)stimulated by TGF-β.By monitoring the changes of critical regulators in the presence of the formula,it was observed that the expression levels of TGF-β,IL-1β,Bcl-2,Rho A,ROCK1/2,ERK1/2,Snail,and Slug were markedly suppressed,whereas Bax expression exhibited the opposite effect.Compared with a well-characterized Rho A pathway inhibitor,Fasudil,SQHT generated equivalent or even higher inhibitory effects on these processes in ASMCs.CONCLUSIONS:Collectively,these suggested that SQHT can reduce airway inflammation by inhibiting TGF-β-stimulated signaling pathways in ASMCs.These findings may provide a novel remedy for treating ASMC inflammation,which causes thickening and obstruction of the airway in chronic obstructive pulmonary disease.