Elevated serum Activin A in chronic obstructive pulmonary disease with skeletal muscle wasting

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.

Study on the association between maternal urinary phthalate metabolites and testicular steroid hormones in the cord blood in a Chinese population / 中华预防医学杂志

<p><b>OBJECTIVE</b>The purposes of our study were to investigate the association between maternal urinary phthalate metabolites and the levels of inhibin B (INHB) and insulin-like factor 3 (INSL3) in the cord blood in a Chinese pregnant population.</p><p><b>METHODS</b>Maternal urine samples in the third trimester of pregnancy of 69 participants were collected and stored, and the samples of cord blood (10 ml) were collected at delivery between June 2011 and September 2012 in a comprehensive hospital of gynecology and obstetrics in Tianjin, China.Four phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and mono-2-ethylhexyl phthalate (MEHP) were measured in the urine samples using liquid chromatography-tandem mass spectrometry. The levels of INHB, INSL3 in the cord blood were tested by ELISA. Associations of phthalate exposure with INHB and INSL3 levels were determined by spearman correlation and multiple regression model analysis.</p><p><b>RESULTS</b>The median concentrations of observed metabolites in descending order were 49.74 µg/L for MMP, 24.96 µg/L for MEHP, 19.52 µg/L for MEP and 17.73 µg/L for MBP. The median concentrations of INHB and INSL3 were 89.09 and 106.21 ng/L.Significant negative associations between INHB and MMP(β' = -0.252), MEP(β' = -0.363) or the sum value (∑PAEs) (β' = -0.346) were found by the multiple regression model analysis. For INSL3, only the sum value (β' = -0.313) was inversely significantly associated with the levels of INSL3 in the cord blood.</p><p><b>CONCLUSIONS</b>Maternal urinary phthalate metabolites were associated with INHB and INSL3 in the cord blood in a Chinese population.</p>

Potential detrimental effect of soy isoflavones on testis sertoli cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of soy isoflavones on cell proliferation and the transcription levels of follicle-stimulating hormone receptor (FSHR), inhibin α (INHα), INHβB, androgen binding protein (ABP), transferrin (Tf) and vimentin in testis sertoli cells in SD rats.@*METHODS@#Sertoli cells were cultured in vitro, exposed to daidzein at 0.03, 0.3, 3, and 30 μmol/L and genistein at 0.05, 0.5, 5 and 50 μmol/L, respectively. MTT was used to detect the proliferation of sertoli cells. Real-time PCR was used to detect the relative mRNA expressions of FSHR, INHα, INHβB, ABP, Tf and vimentin.@*RESULTS@#Compared with control groups, cell proliferation and the relative mRNA expression levels of INHβB and ABP in the treated cells showed no significant alternation. The INHα mRNA expression levels were increased in 0.3 and 3 μmol/L Dai and 0.05 μmol/L Gen, while the mRNA expression levels of FSHR were downregulated in 30 μmol/L Dai and Gen at all concentrations. Tf mRNA expression levels were downregulated in 30 μmol/L Dai and 5 μmol/L and 50 μmol/L Gen, and the mRNA expression levels of vimentin were downregulated in 3 and 30 μmol/L Dai and 50 μmol/L Gen.@*CONCLUSION@#Soy Isoflavones may have potential detrimental effect on the male reproductive system, as they may impact the function of sertoli cells by downregulating the transcription levels of some important proteins.

Expression of inhibin B betaB subunits in the testicular tissues of azoospermia patients with different pathological alterations / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the expression of inhibin B betaB subunits in human testicular tissues.</p><p><b>METHODS</b>Eighty-three cases of the azoospermia underwent testicular biopsy. In accordance with the pathological alterations of spermatogenesis, the samples were divided into four groups: Sertoli-cell-only syndrome (n = 21); hypospermatogenesis (n = 20), maturation arrest (n = 24) and almost normal spermatogenesis (n = 18). Immunohistochemical staining for inhibin B betaB subunits was conducted on the paraffin-embedded sections of different spermatogenesis to localize inhibin B betaB subunits in the seminiferous tubules.</p><p><b>RESULTS</b>Immunohistochemically, positive products of inhibin B betaB subunits were found in both the seminiferous tubules and interstitial tissues of the testis as brown or yellow particles in the cytoplasm. Leydig cells and early intermediate spermatogenic cells showed a very strong positivity; Sertoli cells in the seminiferous tubules were mostly positive; peritubular myoid cells showed a weak positive staining; but no positive expression of inhibin B betaB subunits was found in late spermatids and mature sperm.</p><p><b>CONCLUSION</b>Inhibin B may be produced by both Sertoli cells and early spermatogenic cells in the seminiferous tubules.</p>

The expression and localization of inhibin isotypes in mouse testis during postnatal development

Inhibin, which is important for normal gonadal function, acts on the pituitary gonadotropins to suppress folliclestimulating hormone (FSH) secretion. The level and cellular localization of the inhibin isotypes, alpha, beta(A) and beta(B), in the testis of mice were examined during postnatal development in order to determine if inhibin expression is related to testicular maturation. Mouse testes were sampled on postnatal days (PNDs) 1, 3, 6, 18, 48 and 120, and analyzed by Western blotting and immunofluorescence. Western blot analysis showed very low levels of inhibin alpha, beta(A) and beta(B) expression in the testes at days 1 to 6 after birth. The levels then increased gradually from PND 18 to 48-120, and there were significant peaks at PND 48. Inhibin alpha, beta(A) and beta(B) were detected in testicular cells during postnatal development using immunohistochemistry. The immunoreactivity of inhibin alpha was rarely observed in testicular cells during PND 1 to 6, or in the cytoplasmic process of Sertoli cells surrounding the germ cells and interstitial cells during PND 18 to 120. Inhibin beta(A) and beta(B) immunoreactivity was rarely observed in the testis from PND 1 to 6. On the other hand, it was observed in some spermatogonial cells, as well as in the interstitial space between PND 48 and PND 120. We conclude that the expression of inhibin isotypes increases progressively in the testis of mice with increasing postnatal age, suggesting that inhibin is associated with a negative feedback signal for FSH in testicular maturation.

Effects of Fructus lycii and Radix astragali on the function of sertoli cells in rat testes / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of the Chinese herbal medicines Fructus Lycii and Radix Astragali on the function of the Sertoli cells in the rat testis and their mechanisms.</p><p><b>METHODS</b>Sertoli cells from the testes of the SD rats aged 18 - 22 days were isolated and cultured. The effects of Fructus Lycii, Radix Astragali and the combined administration of the two on the proliferation of Sertoli cells in vitro were detected by MTT assay, and their effects on the level of INHbetaB mRNA transcription in Sertoli cells in vitro were investigated in both normal environment and peroxide-damaging environment by RT-PCR.</p><p><b>RESULTS</b>The proliferation of Sertoli cells was promoted by either Fructus Lycii or Radix Astragali at high concentration (P < 0.05), and significantly promoted by the combined administration at high concentration (P <0.01). Sertoli cell INHbetaB transcription was significantly up-regulated by Fructus Lycii, Radix Astragali and their combined administration in vitro (P < 0.01). When the level of INHbetaB mRNA in Sertoli cells significantly dropped (P < 0.01) in the presence of injury induced by peroxide (H2O2), it could be elevated by Radix Astragali (P < 0.05) and significantly up-regulated by Fructus Lycii or the combined administration in vitro (P < 0.01).</p><p><b>CONCLUSION</b>Fructus Lycii, Radix Astragali and the combined administration of the two could promote and protect INHbetaB mRNA in Sertoli cells in vitro.</p>

Day 3 serum inhibin-B level is not predictive of ovarian assisted reproductive technologies outcome

The ability of the ovary to respond to exogenous gonadotrophin stimulation and development of several follicles is essential in assisted reproductive technology. Neither age and regularity of menses nor follicular phase FSH and estradiol concentrations are reliable predictors of ovarian response. Day 3 serum inhibin-B level, during induction ovulation, has been proposed as a predictor of ovarian response. To determine day 3 serum inhibin-B as a predictor of ovarian response to induction ovulation in IVF/ ICSI cycles. Seventy one infertile patients under 40 years old were enrolled in this study. All women have both ovaries, basal FSH level under 15 mIU/ml, and no evidence of endocrine disorders. Day 3 FSH, estradiol, inbibin-B concentrations and ovarian volume were measured before treatment. All patients underwent standard long GnRH agonist protocol. The number of oocytes retrieved, fertilization rate, clinical pregnancy rate, days of stimulation and number of HMG ampoules were determined. The patients were divided into two groups, normal responders and poor responders [number of oocytes retrived <4]. The mean inhibin-B level in normal responders was 166.9 +/- 141 pg/ ml versus 115.8 +/- 87 pg/ml in poor responders, which the difference was not statistically significant [p=0.24]. We could not find a cut off between normal and poor responders. The use of day 3 inhibin-B level as a predictive marker of ovarian response in IVF/ICSI cycles is not reliable

Use of ovarian reserve markers to predict ovarian response in A.R.T: a prospective study

Our study is conducted in order to evaluate the correlation between ovarian reserve markers such as antral follicular count, baseline FSH, LH, E2 as well as Inhibin-B, with the prognosis of IVF/ICSI cycles, demonstrated by the number of eggs retrieved. Through a prospective comparative study, 50 patients undergoing IVF/ICSI cycles were recruited in the study. Ovarian reserve markers, as well as the number of eggs retrieved were evaluated for all cases, and correlations were evaluated. Demonstrated that all of the ovarian reserve markers showed significant correlations with the number of eggs retrieved, duration of stimulation, rate of cancelled cycles for non response. Yet the antral follicular count showed the strongest correlation, followed by the bseline Estradiol, and baseline FSH. Antral follicular count can be used with high accuracy to evaluate and predict response to controlled ovarian stimulation in IVF/ICSI cycles, with comparable accuracy to other classic ovarian reserve markers, such as baseline hormone values

The expression of activin A and transforming growth factor-beta 1 during rabbit mandibual distraction osteogenesis / 中华整形外科杂志

<p><b>OBJECTIVE</b>To examine the expression of activin A (ACT A) and transforming growth factor-beta 1 (TGF-beta 1) during mandibular lengthening and elucidate the difference between the role of ACT A and TGF-beta 1 during mandibular distraction osteogenesis.</p><p><b>METHOD</b>Skeletally mature white new zealand rabbits were established right mandibular distraction osteogenesis model. The regenerating tissue of animals' lengthened mandibes were harvested at different time points to have immunohistochemistric research of ACT A, TGF-beta 1 protein and analysis ACT A, TGF-beta 1 mRNA by using RT-PCR semiquantitative mean.</p><p><b>RESULTS</b>AT the end of latency period day, positive stain of ACT A were found in the osteoblasts while positive stain of TGF-beta 1 was found in mesenchymal cells. At the end of distraction phase, fibrosis tissue had no stain of ACT A, but had strong stain of TGF-beta 1. At the period of fixation days of 20 days, both cytoplasm of osteoblasts and extracellular matrix in primary mineralization front were strongly stained of ACT A. The osteoblasts, osteoid and osteocytes in peripheral new bone zone were moderately stained of ACT A. TGF-beta 1 had strongly positive stained in fibrosis zone and weekly positive stained in primary mineralization front and peripheral new bone zone. There were also broad activin A stains in cytoplasm of osteoblasts, osteoid and cytoplasm of ACT A, TGF-beta 1 in osteocytes after distraction for 30 days. Activin A mRNA began to express at the end of latency period. Expression for activin A mRNA increased gradually along with the beginning of distraction and at the peak in distraction of 10 days and 20 days, while TGF beta 1 mRNA increased at the peak at the end of latency period.</p><p><b>CONCLUSION</b>ACT A and TGF beta 1 have different role during rabbit mandibular distraction osteogenesis.</p>

Expression of activins, follistatin mRNA in the development of hepatic fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To examine the expression changes of activin beta A, beta C, beta E and follistatin mRNA in the development of rat hepatic fibrosis induced by carbon tetrachloride (CCl(4)).</p><p><b>METHODS</b>Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. After carbon tetrachloride injection of 1, 2, 3, 4, 5, 6, and 7 weeks, the 6-12 rats were killed every time. The kinetics of activin beta A, beta C, beta E and follistatin mRNA expression were assessed by the semi-quantity RT-PCR.</p><p><b>RESULTS</b>Activin beta A, beta C, beta E and follistatin mRNA could be detected in normal rat livers. After CCl(4) injection for 2 or 3 weeks, beta A mRNA was transiently decreased and became undetectable, then increased gradually. After CCl injection for 6 and 7 weeks, beta A mRNA level was significantly higher than controls (P<0.01). beta C mRNA could be detected after CCl(4) injection for 1 to 4 weeks and was significantly increased after 5 weeks over controls (P<0.05). beta E mRNA could not be detected after CCl(4) injection for 1 to 5 weeks, but significantly increased after CCl(4) injection for 6 or 7 weeks compared with controls (P<0.01). Except for normal rat liver, no follistatin mRNA was detected in rats after CCl(4) injection.</p><p><b>CONCLUSIONS</b>Activins and follistatin have different expression changes in the development of hepatic fibrosis and the imbalance of activins and follistatin expression may involve in the formation of hepatic fibrosis.</p>

Differentiation and malignant suppression induced by mouse erythroid differentiation and denucleation factor on mouse erythroleukemia cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the roles of mouse erythroid differentiation and denucleation factor (MEDDF), a novel factor cloned in our laboratory recently, in erythroid terminal differentiation.</p><p><b>METHODS</b>Mouse erythroleukemia (MEL) cells were transfected with eukaryotic expression plasmid pcDNA-MEDDF. Then we investigated the changes on characteristics of cell growth by analyzing cells growth rate, mitotic index and colony-forming rate in semi-solid medium. The expressions of c-myc and beta-globin genes were analysed by semi-quantitative RT-PCR.</p><p><b>RESULTS</b>MEL cells transfected with pcDNA-MEDDF showed significant lower growth rate, mitotic index, and colony-forming rate in semi-solid medium (P<0.01). The percentage of benzidine-positive cells was 32.8% after transfection. The expression of beta-globin in cells transfected with pcDNA-MEDDF was 3.43 times higher than that of control (MEL transfected with blank vector, pcDNA3.1), and the expression of c-myc decreased by 66.3%.</p><p><b>CONCLUSIONS</b>MEDDF can induce differentiation of MEL cell and suppress its malignancy.</p>