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Objective:To explore the value of serum activin A (ACT-A) level in early identification of moderate and severe acute pancreatitis (AP).Methods:A prospective case control study was conducted. A total of 120 patients with AP admitted to department of hepatobiliary surgery of Affiliated Nanhua Hospital of Hengyang Medical College of University of South China between October 2020 and April 2022 were recruited. According to the revised Atlanta classification, all patients were classified into mild AP group and moderate-to-severe AP group. The blood samples within 24 hours of onset were drawn, and the serum ACT-A and C-reactive protein (CRP) levels were detected by enzyme-linked immunosorbent assay (ELISA). The Ranson score and the modified CT severity index (MCTSI) were performed. Pearson correlation method was used to analyze the correlation of various parameters. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of ACT-A and CRP for moderate-to-severe AP.Results:A total of 120 patients with AP were enrolled, including 83 patients with mild AP and 37 patients with moderate-to-severe AP. Serum ACT-A and CRP levels within 24 hours of onset in the moderate-to-severe AP group were significantly higher than those in the mild AP group [ACT-A (ng/L): 140.4±37.7 vs. 53.9±30.5, lg CRP: 1.42±0.91 vs. 0.77±0.70, both P < 0.01], and the Ranson score and MCTSI score were also significantly higher than those in the mild AP group (Ranson score: 5.3±1.3 vs. 1.8±1.6, MCTSI score: 5.5±1.0 vs. 2.7±1.2, both P < 0.01). Correlation analysis showed that the serum ACT-A level was positively correlated with serum CRP level, Ranson score and MCTSI score ( R2 value was 0.272, 0.841, 0.616, respectively, all P < 0.05). ROC curve analysis showed that the serum ACT-A, CRP and Ranson score had predictive value for moderate-to-severe AP. The area under the ROC curve (AUC) was 0.948 [95% confidence interval (95% CI) was 0.909-0.986], 0.711 (95% CI was 0.606-0.815), 0.946 (95% CI was 0.910-0.982), respectively. When serum ACT-A > 112.6 ng/L, the sensitivity and specificity of predicting moderate-to-severe AP were 78.38% and 96.39%, respectively, which was better than serum CRP with sensitivity and specificity of 72.92% and 66.27%, respectively, and the specificity was better than Ranson score (71.08%). Conclusion:ACT-A can be detected in the early stage of AP, and it is positively correlated with the disease severity, which can early identify moderate-to-severe AP.
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Abstract Objective The aim is to evaluate the diagnostic value of Activin A levels in serum and pleural fluid on Parapneumonic Pleural Effusion (PPE). Methods The authors collected serum and pleural fluid from 86 PPE and 37 Non-PPE (NPPE) patients. Including Activin A, levels of biomarkers such as Lactate Dehydrogenase (LDH), Procalcitonin (PCT), and C-Reactive Protein (CRP) were measured. All factors were calculated for association with days after admission. The diagnostic potential of biomarkers on PPE was considered by Receiver Operating Characteristic (ROC) curve analysis. Results Levels of Activin A in serum and pleural fluid of PPE patients were significantly higher than those of the NPPE patients. Moreover, concentrations of Activin A in pleural fluid showed a more obvious relevant days after admission. ROC curve analysis found that Activin A in pleural fluid had AUCs of 0.899 with 93% sensitivity and 84% specificity for PPE diagnosis. Conclusion Activin A in pleural fluid correlated with disease severity could act to diagnose PPE.
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Objective:To evaluate the effect of Activin-A on spinal inflammatory response in rats with incisional pain and the relationship with p38 mitogen-activated protein kinase (MAPK) signaling pathway.Methods:Forty-eight SPF healthy male Sprague-Dawley rats, aged 1 month, weighing 100-150 g, were divided into 4 groups ( n=12 each) by the random number table method: sham operation group (S group), incisional pain group (I group), sham operation + antagonist group (SA group) and incisional pain + antagonist group (IA group). The rat model of incisional pain was prepared in group I and group IA.At the first 30 min of model preparation, the antagonist follicle statin 5 μg/kg was intraperitoneally injected in SA and IA groups, and the normal saline 5 μg/kg was intraperitoneally injected in S and I groups.At 24 h before model preparation (T 0) and 2, 6 and 24 h after model preparation (T 1-3), 3 rats in each group were randomly selected to measure the thermal paw withdrawal latency (TWL). Then 3 rats in each group were randomly sacrificed, and the spinal cord L 4-6 segments were taken for determination of the expression of Activin-A and p38 MAPK mRNA (by quantitative real-time polymerase chain reaction) and contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β (by enzyme-linked immunosorbent assay). Results:Compared with group S, the TWL was significantly shortened, the contents of TNF-α and IL-1β were increased, and the expression of Activin-A and p38 MAPK mRNA was up-regulated at T 1-3 in I and IA groups ( P<0.05), and no significant change was found in each parameter in group SA ( P>0.05). Compared with group SA, the TWL was significantly shortened, the contents of TNF-α and IL-1β were increased, and the expression of Activin-A and p38 MAPK mRNA was up-regulated at T 1-3 in I and IA groups ( P<0.05). Compared with group I, the TWL was significantly prolonged, the contents of TNF-α and IL-1β were decreased, and the expression of Activin-A and p38 MAPK mRNA was down-regulated at T 1-3 in group IA ( P<0.05). Conclusions:Activin-A is involved in spinal inflammatory response through activating the p38 MAPK signaling pathway in rats with incisional pain.
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@#Malaria infection still remains as one of the most prominent parasitic diseases afflicting mankind in tropical and subtropical regions. The severity of malaria infection has often been associated to exuberant host immune inflammatory responses that could possibly lead to severe immunopathological conditions and subsequent death of host tissues. Activin A is a protein belonging to the transforming growth factor-beta (TGF-β) family that regulates multiple physiological processes and pathological-associated diseases. The biological roles of activin A have been associated with manipulation of inflammation-related processes and modulation of host immune responses. This implies that activin A protein could play a role in malaria pathogenesis since malaria infection has been closely linked to severe immune responses leading to death, However, the actual in vivo role of activin A in malaria infection remains elusive. Hence, this study was undertaken to investigate the involvement of activin A in malaria infection as well as to assess the modulating effects of activin A on the cytokine releases (TNF-α, IFN-γ and IL-10) and histopathological changes in major affected organs (kidney, liver, lung, brain and spleen) in malarial mice infected with Plasmodium berghei ANKA. Our results showed that the concentrations of plasma activin A were significantly increased in malarial mice throughout the study periods. Also. the systemic activin A level was positively correlated with malaria parasitemia. This indicates that activin A could play a role in malaria pathogenesis and malaria parasitemia development. Plasma TNF-α, IFN-γ and IL-10 cytokine levels were significantly increased in malarial mice at day-5 post infection, suggesting that these cytokines attributed to severe malaria pathogenesis. Histopathological features such as sequestration of parasitized red blood cells (pRBCs) and hemozoin formation were amongst the most common pathological conditions observed in tissues of major affected organs (kidney, liver, lung, brain and spleen) in malarial mice. Neutralization of activin A production via recombinant mouse activin RIIA Fc chimera (rmActivin RIIA Fc chimera) had significantly reduced the parasitemia levels in malarial mice. The release of TNF-α cytokine was significantly reduced as well as the sequestration of parasitized pRBCs and hemozoin formation in major affected organs in malarial mice were also alleviated following inhibition of activin A production. Overall, this preliminary study suggests that activin A could play an immune modulation role in malaria pathogenesis through modulation of TNF-α release that benefits host from severe pathological destructions provoked by intensified inflammatory responses. Further studies are warranted to elucidate the precise mechanism of immune modulation mediated by activin A and its associated immune-modulation mediators in regulating the inflammatory responses elicited during the course of malaria infection.
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Objective: To observe the effect of type 1 bone morphogenetic protein (BMP) receptor activin A receptor type 1 ( ACVRl) on the morphology, proliferation and differentiation of the mandibular condylar cartilage (MCC) cells in the postnatal mice, and to provide the reference for the study on etiology and treatment of MCC-related disease. Methods: The C57BL/6J mouse model of conditional deletion of ACVRl gene was constructed by using the Cre-LoxP system. The female and male mice with Acvrl1" ; RS/RS and Acvrl ; Osterix (+)/( ) genotypes were paired off with each other; the offspring Osterix-Cre ( + ); Acvrl'∗ ; RS/+ genotype mice were selected as experiment group, and the Osterix-Cre ( + ); Acvrl1" ; RS/+ mice were selected as control group. The newborn (n-3). postnatal day 21 (n=4) and PN42 (n=5) male mice were selected. X-gal staining was used to detect the expressions of Osterix-Cre in MCC tissue of the mice in two groups. micro-CT was used to detect the condylar widths and condylar head lengths of mandible of the mice in two groups. HE and Toluidine blue staining were used to analyze the morphology of MCC cells and the thickness of caritilage in each layer of MCC tissue of the mice in two groups, immunohistochemical (1HC) staining was used to detect the number of proliferating cell nuclear antigen (PCNA)-positive cells and the level of type X collagen in MCC tissue of the mice in two groups. Results: The X-gal staining and 1HC results showed that the mouse model of ACVRl gene conditional deletion was successfully constructed. At PN21. compared with control group, the condylar width and the condylar head length of mandible of the mice in experiment group were significantly shortened ( P<0. 05); the morphology of the MCC cells of the mice in two groups had no significant difference. Compared with control group, the number of PCNA-positive cells in the MCC cells of hypertrophic chondrocyte zone (Hy) and chondroblastic zone (Ch) and single Hy of the mice in experiment group were significantly increased ( P<0. 05 or P-<0. 01). At PN42. compared with control group, the shape of parts of the mandibular condylar cartilage cells of the mice in experiment group was abnormal, and the arrangement of some condylar chondrocytes was disordered, the cell thickness of the Ar. Pr and Ch in intermediate part and Hy in anterior part of the condylar cartilage of the mice in experiment group were significantly increased ( P<0. 05 or P<.0. 01); compared with control group, the number of PCNA-positive cells in each zone and the level of type X collagen in Ch of MCC tissue of the mice in experiment group were incresed. Conclusion: ACVRl affects the morphology of MCC cells and structure of MCC tissue by inhibiting the proliferation of MCC cells and the differentiation of chondroblasts into hypertrophic chondrocytes.
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OBJECTIVE: Muscle wasting contributes to the reduced quality of life and increased mortality in chronic obstructive pulmonary disease (COPD). Muscle atrophy in mice with cachexia was caused by Activin A binding to ActRIIB. The role of circulating Activin A leading to muscle atrophy in COPD remains elusive. METHODS: In the present study, we evaluated the relationship between serum levels of Activin A and skeletal muscle wasting in COPD patients. The expression levels of serum Activin A were measured in 78 stable COPD patients and in 60 healthy controls via ELISA, which was also used to determine the expression of circulating TNF-α levels. Total skeletal muscle mass (SMM) was calculated according to a validated formula by age and anthropometric measurements. The fat-free mass index (FFMI) was determined as the fat-free mass (FFM) corrected for body surface area. RESULTS: Compared to the healthy controls, COPD patients had upregulated Activin A expression. The elevated levels of Activin A were correlated with TNF-α expression, while total SMM and FFMI were significantly decreased in COPD patients. Furthermore, serum Activin A expression in COPD patients was negatively associated with both FFMI and BMI. CONCLUSION: The above results showed an association between increased circulating Activin A in COPD patients and the presence of muscle atrophy. Given our previous knowledge, we speculate that Activin A contributes to skeletal muscle wasting in COPD.
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Humans , Male , Female , Adult , Middle Aged , Aged , Muscular Atrophy/etiology , Pulmonary Disease, Chronic Obstructive/complications , Activins/blood , Cachexia/metabolism , Muscular Atrophy/metabolism , Muscular Atrophy/blood , Body Mass Index , Case-Control Studies , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/blood , Muscle, Skeletal/physiopathology , Pulmonary Disease, Chronic Obstructive/blood , Activins/metabolism , Inhibin-beta SubunitsABSTRACT
Objective To investigate the clinical value of serum activin A,endoglin combined with uterine artery pulsatility index in predicting preeclampsia.Methods One hundred cases pregnant women who were admitted to the obstetrics clinic of Longhua New District People′s Hospital in Shenzhen from December 2016 to July 2017 were selected ,50 cases of preeclampsia were in the observation group,and another 50 cases of healthy pregnant women were in the control group.Serum activin A,endoglin and uterine artery pulsatility index ( UAPI ) were measured at 11 ～ 13 weeks respectively.Receiver operating characteristic curve was used to analyze the diagnostic value of activin A,endoglin and UAPI in different gestational weeks separately and jointly in predicting preeclampsia.Results At 11～13 weeks of pregnancy, the serum activin A((379.98±153.80)ng／L],endoglin((9.87 g±1.62)μg／L) and UAPI (0.97±0.09) in the observation group were significantly higher than in the control group ((205.45±93.29)ng／L,(6.61 ±1.54)μg／L, ( 0.82 ± 0.15 )), and the difference was statistically significant ( all P＜ 0.05 ).The multivariate Logistic regression analysis showed that serum activin A, endoglin level and UAPI in early pregnancy were the risk factors for preeclampsia ( all P＜0.05).ROC curve analysis showed that the joint prediction of activin A, endoglin and UAPI in different gestational weeks was better than that in single detection.The maximum area (AUC) of the joint prediction of activin A,endoglin and UAPI at pregnant 11～13 weeks was 0.969, the sensitivity was 82.0%, and the specificity was 100.0%.Conclusion The combined detection of serum activin A, endothelial factor and uterine artery pulsation index in early pregnancy can be used to predict preeclampsia with high sensitivity and specificity,and can be used as a clinical index to predict preeclampsia.
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OBJECTIVE: To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model.METHODS: The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; 3.0 μg, 6.0 μg, or 10.0 μg of rhBMP2 with osteon; and 1.0 μg, 3.0 μg, 6.0 μg, or 10.0 μg of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry.RESULTS: Bone fusion scores were significantly higher for 10.0 μg AB204 and 10.0 μg rhBMP2 than for osteon only or 1.0 μg AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and 10.0 μg, but, the properties of AB204 at doses of 3.0 μg exhibited better than the properties of rhBMP2 at doses of 3.0 μg.CONCLUSION: AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.
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Animals , Humans , Male , Rats , Activins , Bone Morphogenetic Proteins , Chimera , Haversian System , Immunohistochemistry , Osteoblasts , Palpation , Rats, Sprague-Dawley , Spinal FusionABSTRACT
OBJECTIVE: To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model. METHODS: The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; 3.0 μg, 6.0 μg, or 10.0 μg of rhBMP2 with osteon; and 1.0 μg, 3.0 μg, 6.0 μg, or 10.0 μg of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry. RESULTS: Bone fusion scores were significantly higher for 10.0 μg AB204 and 10.0 μg rhBMP2 than for osteon only or 1.0 μg AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and 10.0 μg, but, the properties of AB204 at doses of 3.0 μg exhibited better than the properties of rhBMP2 at doses of 3.0 μg. CONCLUSION: AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.
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Animals , Humans , Male , Rats , Activins , Bone Morphogenetic Proteins , Chimera , Haversian System , Immunohistochemistry , Osteoblasts , Palpation , Rats, Sprague-Dawley , Spinal FusionABSTRACT
It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a "dose effect". Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development.
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Animals , Mice , Activins , Metabolism , Cells, Cultured , Embryonic Development , Germ Layers , Metabolism , Pluripotent Stem Cells , Cell Biology , MetabolismABSTRACT
Objective To explore influence of antibiotics and Jiuyi Dan combined with incision-thread-drawing procedure on perianal abscess patients' level of activin A (ACTA) and C-reactive protein (CRP).Methods120 cases of perianal abscess patients in our hospital during March 2015 to December 2016 Coloproctology were selected, they were divided into the experiment group and the control group by random number method.All of patients were taken incision-thread-drawing procedure.Then the experimental group were given nine one antibiotics and Jiuyi Dan, the control group were given antibiotics.The cure rate, 6months after the recurrence rate, average healing time of the wound, and wound edema rate of two groups were observed.Levels of ACTA and CRP expression levels of two groups of patients before and after operation were analyzed.ResultsPatients in the experimental group cure rate was 96.7% higher than that of the control group (P<0.05), the recurrence rate of patients in the experimental group than in the control group, the difference was not statistically significant;the patients in the experimental group the average healing time was (20.67±3.22) d shorter than the average healing time of patients in the control group (29.48±3.15) d, patients in the experimental group wound edema rate of 5% was significantly lower than in the control group 20% (P<0.05);3D ACTA, the expression level of CRP was significantly higher than the preoperative 7 d levels after operation in the two groups (P<0.05);after 7d, the expression level of the two groups of patients with ACTA and CRP were significantly lower than the preoperative level of expression of 7d (P<0.05), experimental group levels of ACTA were significantly lower than the control group, the difference was statistically significant (P<0.05);postoperative 14d patients, ACTA levels of two groups were significantly lower than the levels before operation (P<0.05).ConclusionPerianal abscess can be treated effectively and patients levels of Acta and CRP were obviously dereased by Jiuyi Dan combined with incision-thread-drawing procedure combined, postoperative inflammatory reaction could be importantly alleviated, it was worth clinical promotion.
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Objective:To investigate the effects of telmisartan on the expressions of activin A and its receptors in non-infarction area of left ventricle in the heart failure rats after myocardial infarction,and to clarify the mechanism of improvement effect of telmisartan on myocardial collagen deposition.Methods:A total of 27 rats were divided into sham operation group(n=9),model group(n=20) and telmistartan group(n=10).The left anterior descending coronary arteries of the rats in model group and telmisartan groupwere ligated,and the left anterior descending coronary arteries of the rats in sham operation group were not ligated.After 5 weeks,there were 6 surviving rats in each group.The rats in sham operation group were treated with 0.5%CMC(10 mL·kg-1),the rats in model group were treated with 0.5%CMC (10 mL·kg-1),and the rats in telmisartan group were treated with telmisartan (30 mg·kg-1).All the rats were treated with medicines by intragastric administration for 4 weeks.The whole cardiac hypertrophy index and left ventricular hypertrophy index of the rats were measured;the mRNA expression levels of activin A,ActRⅡA,ActRⅡB,ColⅠ,and ColⅢ in the non-infarction areaof the rats were detected by RT-PCR and the ratio of ColⅠ/ ColⅢ was calculated;the expression intensities of activin A protein in the myocardium tissue in non-infarction area of the rats in various groups were observed by immunohistochemical staining.Results:Compared with sham operation group,the whole cardiac hypertrophy index and left ventricular hypertrophy index of the rats in model group were significantly increased (P<0.01);the mRNA expression levels of activin A,ActRⅡA and ActRⅡB,ColⅠ,ColⅢ and the ratio of ColⅠ/ColⅢ were also increased (P<0.01).The immunohistochemical staining results showed that the expression level of activin A protein in noninfarction area of left ventricle of the rats in sham operation group was lower,and the expression level of activin A protein in non-infarction area of left ventricle of the rats in model group was higher.Conclusion:Telmisartan may improve the myocardial collagen deposition by inhibiting the expressions of activin A and its receptors during heart failure.
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Objective To evaluate the predictive value of pre-eclampsia with the combination of inhibin A,activin A and uterine artery doppler.Methods The single pregnant pregnant women were divided into 9-12 week of pregnancy groups and 13-16 week of gestation group based on examination of gestational age.According to the outcome of further follow-up the women are divided into normal pregnancy (9-12 week pregnant or 13-16 week pregnant normal group) and the PE group (9-12 weeks pregnant or pregnant 13-16 PE group).Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of inhibin A and activin A.Doppler ultrasound were used to examine UAPI.The results were converted to MoM values to calculate the combined detection specificity and sensitivity.Results The concentration of serum inhibin A and activin A and UAPI in 9-12 week pregnant PE group were significantly higher than that in 9-12 week normal pregnant (P ＜0.05).The concentration of serum inhibin A and activin A and UAPI in 13-16 week pregnant PE group were significantly higher than that in 13-16 week normal pregnant (P ＜0.05).When the maximum area under the curve of three indicator combined application (AUC =0.836) in 9-12 week pregnant,the specificity was 72％ and the sensitivity was 83％.When the maximum area under the curve of three indicators combined application (AUC =0.912) in 13-16 week pregnant,the specificity was 87％ and the sensitivity was 86％.Conclusion The combined application of peripheral blood inhibin A,activin A and UAPI could predict PE.The combined application of three indicator detection index provides a high degree of specificity,sensitivity and predictive value in 13-16 week pregnant.
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Objective:To investigate the expression of activin A in paraventricular nucleus (PVN)of the WKY rats and its influence in arterial blood pressure,and to clarify the mechanism of activin A in the regulation of arterial blood pressure by PVN.Methods:The WKY rats were selected.The expressions of activin A,ActRⅡA,ActRⅡB,and Smads mRNA in PVN of the WKY rats were measured by RT-PCR.The expression of ActRⅡA protein in PVN was detected by immunohistochemical staining.The microinjection of exogenous activin A into PVN was used to observe the changes of arterial blood pressure.The primary cultured PVN neurons from the WKY rats were divided into control group and activin A group.The mRNA expression levels of ActRⅡA,ActRⅡB,and Smads in the PVN neurons were analyzed by RT-PCR.Results:Activin A,ActRⅡA,ActRⅡB,Smad2 and Smad3 mRNA were expressed in PVN of the WKY rats.The ActRⅡ A protein expression in PVN was further confirmed by immunohistochemical staining.After microinjection of activin A or angiotensin Ⅱ (AgⅡ)into PVN,the mean arterial blood pressure was increased obviously compared with before treatment (P <0.05).Moreover,compared with control group,the expression levels of ActRⅡA and Smad3 mRNA in primary cultured PVN neurons of the rats in vitro were significantly increased (P <0.05).Conclusion:Activin A can regulate the arterial blood pressure in PVN in an autocrine or paracrine manner,which is related to ActRⅡA-Smad3 signal pathway.
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Objective:To investigate the effect of activin A and nerve growth factor ( NGF) NGF on stimulating neurite outgrowth of dorsal root ganglia(DRG)of the embryonic chicken.Methods:In this study,we observed that activin A and NGF together induced neurite outgrowth of DRG and kept survival of DRG neurons by the primary cultured DRGs from embryonic day 8 ( E8 ) chicken.calcitonin gene-related peptide(CGRP)CGRP mRNA expressions were analyzed by RT-PCR.Results: The DRG treated with activin A +NGF had obvious neurite outgrowth ,compared with only NGF group on day 3,and the number of living DRG neurons also increased.Activin A +NGF up-regulated the mRNA expressions of CGRP in DRG.Conclusion:The Data demonstrated that activin A with NGF can synergistically stimulate DRG neurite outgrowth and maintain the DRG neurons survival , suggesting that it is more effective that NGF and activin A together treat the associated disease of nerve system.
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Objective:To study the role of activin A in regulation of neutrophil function by detecting activin receptor expression and cellular activities.Methods:Peritoneal neutrophils were isolated in mouse.After the neutrophils were stimulated with activin A,the expression of ActRⅡA on neutrophils was examined by immunofluorescence and flow cytometry.Expression of Smad3 in neutrophils was analyzed by Western blot.Assays of neutrophils function were performed by detecting respiratory burst, production of NO and phagocytosis.Results:The isolated cells were composed of more than 90% peritoneal neutrophils.ActRⅡA was expressed on mouse neutrophils and Gr-1/ActRⅡA double-positive cells were 41.1%.Activin A promoted Smad3 phosphorylation in neutrophils,increased the production of ROS and O2-(P<0.05),enhanced secretion of NO and phagocytosis of mouse neutrophils(P<0.01),and promoted fluorescent microsphere phagocytosis of neutrophils by flow cytometry ( P<0.01 ) .Conclusion: Activin receptor and activin signaling protein were expressed on mouse neutrophils,activin A might play an important regulatory role in activation and function of neutrophils.
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Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.
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Animals , Male , Activins/metabolism , Exercise Therapy , Follistatin/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Obesity/therapy , Physical Exertion , Body Weight , Blood Glucose/analysis , Disease Models, Animal , Diet, High-Fat/adverse effects , Fatty Liver/metabolism , Fatty Liver/pathology , Gene Expression , Non-alcoholic Fatty Liver Disease/therapy , Obesity/metabolism , Random Allocation , Rats, Wistar , RNA, Messenger/metabolism , SwimmingABSTRACT
Objective To explore the relationship between urinary activin A and neonatal hypoxic-ischemic encephalopathy(HIE).Methods 50 full-term neonatal with HIE were selected as the observation group,48 normal full-term neonatal in the same period were selected as the normal control group randomly.Within 7 days after birth,the observation group was divided into the group of 30 patients with mild HIE and the group of 20 patients with moderate and severe HIE,according to diagnostic criteria and clinical grading of neonatal HIE.The levels of urinary activin A in two groups after birth at different time(2,12,24,48,72h)was determined by using ELISA method.Results The levels of urinary activin A in moderate and severe HIE group was significantly higher than than in the normal control group(P＜0.01)and mild HIE group(P＜0.01);The levels of urinary activin A in the normal control group and mild HIE group showed no significant differences(P＞0.05).Urinary activin A level＞70 ng/L for the critical value to determine the occurrence of moderate and severe HIE,the sensitivity and specificity of 2 h urinary activin A levels were separately 86％ and 99％;The sensitivity and specificity of 12～72 h urinary activin A levels were separately 100％ and 98％.Conclusion The correlation between the level of urinary activin A and the severity of HIE was positive,the level of urinary activin A had a high degree of sensitivity and specificity for determine the incidence of moderate and severe HIE,it provided an important basis for diagnosis of moderate and severe HIE.
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Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis(TM), we identified genes (up- or down-regulated, > or = 1.5 fold, P < or = 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 microg/ml) in UtLM cells. Downregulation of TGF-beta signaling pathway genes, activin A, activin B, Smad3, TGF-beta2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-beta pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.
Subject(s)
Female , Humans , Activins/genetics , Anticarcinogenic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin-Dependent Kinase Inhibitor p15/genetics , Down-Regulation , Genistein/pharmacology , Leiomyoma/metabolism , Oligonucleotide Array Sequence Analysis , Signal Transduction/drug effects , Smad3 Protein/genetics , Transforming Growth Factor beta/genetics , Up-Regulation , Uterine Neoplasms/metabolismABSTRACT
BACKGROUND: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. METHODS: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. RESULTS: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. CONCLUSION: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.