Publications by authors named "Zhifeng Sheng"

26 Publications

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Therapeutic Effect and Safety of Tripterygium Glycosides Combined With Western Medicine on Type 2 Diabetic Kidney Disease: A Meta-Analysis.

Clin Ther 2022 Jan 20. Epub 2022 Jan 20.

College of Traditional Chinese Medicine, Hainan Medical University, Haikou, Hainan, China. Electronic address:

Purpose: Tripterygium glycosides (TG) are widely used for the treatment of kidney disease in China. However, the application of TG in clinical practice is limited, as the therapeutic window is narrow, and the therapeutic dose is close to the toxic dose. In addition, the therapeutic effect of TG combined with Western medicine has not been fully elucidated. This study sought to explore standardized treatment, efficacy, and safety of TG combined with Western medicine for patients with type 2 diabetic kidney disease (T2DKD).

Methods: The PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature, Chinese Scientific Journal, and Wan Fang databases were searched for randomized controlled trials of TG combined with Western medicine on T2DKD from their inception until May 4, 2021. A random effects model was used to explore heterogeneity of studies.

Findings: A total of 33 studies with 2034 patients were included in the current meta-analysis. The findings showed that TG combined with Western medicine effectively reduced urinary albumin excretion rates (standardized mean difference, -2.55; 95% CI, -4.70 to -0.40; P = 0.02), 24-hour urinary protein level (mean difference, -0.79; 95% CI, -1.22 to -0.36; P = 0.0003), and serum creatinine level (mean difference, -8.23; 95% CI, -14.48 to -1.99; P = 0.01) and increased albumin level (mean difference, 4.70; 95% CI, 3.27 to 6.13; P < 0.00001) in patients with T2DKD. No serious adverse reactions occurred, and the incidence of adverse events in the TG combined with Western medicine treatment group was slightly higher than in the control group (8.14% vs 2.65%). The results were stable, and a significant publication bias was not detected (P > 0.05).

Implications: Based on our results, TG combined with Western medicine may be an effective and safe therapy for T2DKD; the best treatment duration may be 3 to 6 months. Nevertheless, larger, longer multicenter studies should be conducted for clinical application of the regimen to patients in more countries and regions. PROSPERO registration number: CRD42021259466.
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http://dx.doi.org/10.1016/j.clinthera.2021.12.006DOI Listing
January 2022

Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women With Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study.

Front Pharmacol 2021 20;12:770073. Epub 2021 Oct 20.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Subjects received SHR-1222 at 50, 100, 200, 300, and 400 mg sequentially or matching placebo subcutaneously. Totally, 50 subjects with low BMD were enrolled and randomly assigned; 10 received placebo and 40 received SHR-1222 (50 mg, n = 4; 100, 200, 300, or 400 mg, n = 9). The most common adverse events that occurred at least 10% higher in subjects with SHR-1222 treatment than those with placebo were decreased blood calcium, blood urine present, increased blood cholesterol, electrocardiogram T wave abnormal, urinary tract infection, increased blood pressure diastolic, and positive bacterial test. All the above adverse events were mild in severity and well resolved except one of increased blood cholesterol in a subject lost to follow-up. The serum SHR-1222 concentration increased in a dose-dependent manner. Administration of SHR-1222 upregulated the bone-formation markers N-terminal propeptide of type 1 procollagen, osteocalcin, and bone-specific alkaline phosphatase, while downregulated the bone-resorption marker β-C-telopeptide. The BMD at the lumbar spine notably rose after a single dose of SHR-1222. The largest increase occurred in the 400 mg cohort (3.8, 6.7, and 6.1% on day 29, 57, and 85, respectively; compared with 1.4, 0.8, and 1.0% in the placebo group). Although 10.0% of subjects receiving SHR-1222 tested positive for anti-SHR-1222 antibodies, no obvious effects of antibody formation were found on pharmacokinetics. Overall, SHR-1222 was well tolerated at doses from 50 to 400 mg and is a promising new remedy for osteoporosis. http://www.clinicaltrials.gov, NCT03870100.
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http://dx.doi.org/10.3389/fphar.2021.770073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564351PMC
October 2021

X-linked hypophosphatemic rickets caused by a de novo PHEX gene variation in a family.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Jun;46(6):658-665

National Clinical Research Center for Metabolic Diseases; Hunan Provincial Key Laboratory of Metabolic Bone Diseases; Department of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha 410011.

X-linked hypophosphatemic rickets (XLH) is caused by inactivating mutations in the PHEX gene and is the most common form of hereditary rickets. The treatment is more complicated compared with the general rickets. A family were admitted to the Department of Endocrinology, Hainan General Hospital in 2018. The proband was a 3-year-6-month-old female, Han nationality. She was admitted to hospitalization for bilateral knee valgus and walking instability. The patient's parents were not in consanguineous marrige, and there was no similar medical history in the family. The patient presented with "O" leg, bracelet sign, chicken breast, and low blood phosphorus. Typical change of rickets also appeared in her X-ray examination. The DNAs of the peripheral blood were extracted from the patient and her parents. All coding exons and flanking regions of PHEX gene in the patient were amplified by PCR, and the mutant sites of the family members were testified by a generation sequencing. A heterozygous variation (c.1482+5G>C) affecting splicing outcome was detected at the splicing region of intron 13 of PHEX gene in the patient. The variation has been included in the human gene mutation database (HGMD). No variation was found in the proband's parents, the PHEX gene in the patient was a de novo variation. Our research provided reference for the future genetic counseling for this patient and enriched the research data on the relationship between genotype and clinical manifestations.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200072DOI Listing
June 2021

Comparison of methods to improve fracture risk assessment in chinese diabetic postmenopausal women: a case-control study.

Endocrine 2021 07 1;73(1):209-216. Epub 2021 May 1.

Department of Metabolism and Endocrinology, the affiliated Zhuzhou Hospital of Xiangya School of Medicine of Central South University, 116 Changjiang South Road, Zhuzhou, 412007, Hunan, China.

Purpose: This study evaluated the predictive power of adjusted FRAX and standard FRAX models based on the actual prevalence of osteoporosis in type 2 diabetic (T2DM) postmenopausal women, and to explore the optimal strategy to better predicted fracture risk in postmenopausal women with diabetes in China.

Methods: We recruited 434 patients from community-medical centers, 217 with T2DM and 217 without T2DM (non-T2DM). All participants completed self-reported questionnaires detailing their characteristics and risk factors. Bone mineral density (BMD) and spinal radiographs were evaluated. The China FRAX model calculated all scores. The area under the receiver operator characteristic curve (ROC-AUC) evaluated the sensitivity, specificity, and accuracy for predicting 10-year risk for major (MOF) and hip (OHF) osteoporotic fractures in T2DM patients.

Results: T2DM patients had higher BMD but lower average FRAX values than non-T2DM patients. The unadjusted FRAX ROC-AUC was 0.774, significantly smaller than that for 0.5-unit femoral neck T-score-adjusted FRAX (0.800; p = 0.004). Rheumatoid arthritis (RA; AUC = 0.810, p = 0.033) and T-score (AUC = 0.816, p = 0.002) adjustments significantly improved fracture prediction in T2DM patients.

Conclusions: Femoral neck T-score adjustment might be the preferred method for predicting MOF and OHF in Chinese diabetic postmenopausal women, while RA adjustment only effectively predicted HF risk.
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http://dx.doi.org/10.1007/s12020-021-02724-yDOI Listing
July 2021

Comparison of the NOF and NOGG guidelines for spinal radiographic examination in postmenopausal Chinese women.

Arch Osteoporos 2021 01 5;16(1). Epub 2021 Jan 5.

Hospital Infection Control Center, the Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.

The aim was to compare the National Osteoporosis Foundation (NOF) and the UK National Osteoporosis Guideline Group (NOGG) guidelines for the detection of vertebral fractures in postmenopausal Chinese women. The NOF guidelines had higher accuracy than the UK guidelines for spinal radiography examination.

Purpose: To compare the National Osteoporosis Foundation (NOF) and the UK National Osteoporosis Guideline Group (NOGG) guidelines for the detection of vertebral fractures in postmenopausal Chinese women.

Methods: A cross-sectional study on 255 community-dwelling postmenopausal women was conducted in Hunan province in 2017. Demographic and clinical characteristics and risk factors were recorded through questionnaires. Height and weight were measured using standard methods, and bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Vertebral fractures were diagnosed by radiography using semi-quantitative morphometry.

Results: The prevalence of vertebral fractures was 9.4%. Women with vertebral fractures were significantly older and shorter, had higher years-since menopause and height loss values and lower BMD and T-scores at the femoral neck and total hip, and were more likely to have a history of previous fractures. The sensitivity and specificity of the NOF guidelines were 91.7% and 39.8%, respectively, while the NOGG guidelines had lower sensitivity (87.5%) and specificity (32.5%). However, a higher percentage had indications for radiography in the 50-64 years age group according to the NOGG guidelines, while a higher percentage had indications for radiography in the ≥ 65 year group according to the NOF guidelines.

Conclusions: The NOF guidelines were better than the NOGG guidelines for spinal radiography examination in the Chinese postmenopausal women.
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http://dx.doi.org/10.1007/s11657-020-00857-7DOI Listing
January 2021

Decreased lower-extremity muscle performance is associated with decreased hip bone mineral density and increased estimated fracture risk in community-dwelling postmenopausal women.

Arch Osteoporos 2020 11 3;15(1):173. Epub 2020 Nov 3.

National Clinical Research Center for Metabolic Disease, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.

The present study demonstrated that the lower-extremity muscle performance in Chinese community-dwelling postmenopausal women with lower bone mineral density (BMD) was positively associated with hip BMD and negatively associated with estimated fracture risk.

Purpose: Postmenopausal women are at high risk for osteoporotic fractures. It has been shown that decreased lower-extremity muscle performance is associated with osteoporotic fractures. However, the relationship between muscle performance and bone mineral density in postmenopausal women is inconsistent in the literature. The present study was to investigate the relationship between lower-extremity muscle performance and BMD or estimated fracture risk in community-dwelling postmenopausal women.

Methods: Two hundred forty-seven postmenopausal women aged 50-85 years were recruited in the study. The short physical performance battery (SPPB) tool including the chair stand test (CST), gait speed test (GST), and balance test (BT) was used to determine lower-extremity functioning and the CST, GST, BT, and SPPB total scores were recorded. The BMD of lumbar spine (LSBMD), femoral neck (FNBMD), and total hip (THBMD) were measured by dual-energy X-ray absorptiometry (DXA), and the vertebral fracture was confirmed by lateral spine X-rays radiographs. In addition, patients' 10-year estimated major osteoporotic fracture risk (MOFR) and hip fracture risk (HFR) were assessed by the Fracture Risk Assessment Tool (FRAX). Linear regression analysis was used to analyze the association between muscle performance and BMD.

Results: The CST, GST, and SPPB total scores were positively associated with LSBMD, THBMD, and FNBMD before adjustment for age, height, and weight. The SPPB total score was positively associated with FNBMD and THBMD, but not with LSBMD after adjustment for age, height, and weight. The BT score was positively associated with FNBMD and THBMD, but not with LSBMD before and after adjustment for age, height, and weight. Moreover, the CST, GST, BT, and SPPB scores were negatively associated with the FRAX score.

Conclusion: The lower-extremity muscle performance in community-dwelling postmenopausal women is positively associated with FNBMD and THBMD and negatively associated with the FRAX score.
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http://dx.doi.org/10.1007/s11657-020-00835-zDOI Listing
November 2020

The Value of Historical Height Loss for Detecting Vertebral Fractures in Postmenopausal Women in China.

Endocr Res 2021 Feb 12;46(1):14-19. Epub 2020 Oct 12.

Department of Metabolism & Endocrinology, The Affiliated Zhuzhou Hospital of XiangYa School of Medicine, Central South University , Zhuzhou, HN, People's Republic of China.

Objectives: The diagnosis and management of osteoporosis and osteoporotic fractures are challenging in rural and underdeveloped areas of China because medical resources are inaccessible; thus, a simple and accurate method is essential for the detection of vertebral fractures. We aimed to examine the relationship between historical height loss (HHL) and vertebral fractures in postmenopausal Chinese women.

Material And Methods: A cross-sectional study of 255 postmenopausal women aged 50 years or older was conducted in September 2017. Demographic data, including self-reported tallest historical height and current height were analyzed. Vertebral fractures were assessed using X-ray radiography and HHL thresholds were examined using specificity and sensitivity testing.

Results: The average age of the 255 participants was 66.3 ± 9.0 years and their mean HHL was 3.5 ± 2.8 cm. The 24 women who were found to have vertebral fractures were older, had more years since menopause (YSM), and a larger HHL compared to those without vertebral fractures. Logistic regression analysis showed that age was a better predictor of vertebral fractures than HHL was, and the cutoff age for detecting vertebral fractures was 71 years, with an area under the receiver operating characteristic curve of 0.750.

Conclusions: Although the women in this study with vertebral fractures had a greater height loss than those without fractures, it was apparent that age, rather than HHL, is the best way to determine who is most likely to develop vertebral fractures.
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http://dx.doi.org/10.1080/07435800.2020.1827263DOI Listing
February 2021

Association between renal function and bone mineral density in healthy postmenopausal Chinese women.

BMC Endocr Disord 2019 Dec 26;19(1):146. Epub 2019 Dec 26.

Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan, 410011, People's Republic of China.

Background: The relationship between renal function and bone mineral density (BMD) is controversial. The aim of this study was to determine the relationship of renal function with BMD and osteoporosis risk in healthy postmenopausal Chinese women.

Methods: A cross-sectional study was conducted in 776 healthy postmenopausal Chinese women. Dual-energy X-ray absorptiometry was used to measure BMDs. Clinical, demographic, and biochemical data were obtained at the time of image acquisition. Estimated glomerular filtration rate (eGFR) was calculated using a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Results: Women with eGFR levels of at least 90 ml/min/1.73m had a lower prevalence of osteoporosis compared with women with decreased eGFR levels (60 ml/min/1.73 m ≤ eGFR < 90.0 ml/min/1.73 m). BMDs at femoral neck and total hip were significantly lower in the lower eGFR class than the higher class (0.717 ± 0.106 vs 0.744 ± 0.125 g/cm, P < 0.01; 0.796 ± 0.116 vs 0.823 ± 0.129 g/cm, P < 0.01, respectively). eGFR was positively correlated with BMDs at femoral neck and total hip in unadjusted analysis (P < 0.05). After controlling for age, menopausal duration and body mass index (BMI), decreased eGFR was not associated with osteoporosis risk.

Conclusions: After adjustments for age, menopausal duration and BMI, the decline in renal function was not independently associated with osteoporosis risk in healthy postmenopausal Chinese women.
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http://dx.doi.org/10.1186/s12902-019-0476-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933739PMC
December 2019

25-Hydroxyvitamin D and Vitamin D Binding Protein Levels in Patients With Primary Hyperparathyroidism Before and After Parathyroidectomy.

Front Endocrinol (Lausanne) 2019 27;10:171. Epub 2019 Mar 27.

Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, United States.

To evaluate vitamin D binding protein and free 25-hydroxyvitamin D [25(OH)D] levels in healthy controls compared to primary hyperparathyroidism (PHPT) patients, and to examine PHPT before and after surgery. Seventy-five PHPT patients and 75 healthy age, gender, and body mass index (BMI) -matched control subjects were examined. In addition, 25 PHPT patients underwent parathyroidectomy and had a 3-month follow up visit. Levels of total and free 25(OH)D, DBP, and intact parathyroid hormone (iPTH) were determined before and 3 months after surgery. There was no significant difference in age and BMI between PHPT patients and controls. Levels of 25(OH)D and DBP were lower in PHPT patients compared to controls ( < 0.01). There was no significant difference in calculated free and bioavailable 25(OH)D levels between PHPT patients and controls. Calcium and iPTH levels decreased to normal but DBP and DBP-bound-25(OH)D increased ( < 0.001) after parathyroidectomy. Levels of DBP were inversely correlated with iPTH ( = -0.406, < 0.001) and calcium levels ( = -0.423, < 0.001). Serum DBP levels were lower in patients with PHPT and parathyroidectomy restored DBP levels. We suggest that lower DBP levels is one of contributing mechanisms of low total 25(OH)D in PTHP patients and the total 25(OH)D levels might not reflect true vitamin D status in PHPT patients.
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http://dx.doi.org/10.3389/fendo.2019.00171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446311PMC
March 2019

Comparison of Initial Clinical Presentations between Primary Hyperparathyroidism Patients from New Brunswick and Changsha.

Int J Endocrinol 2018 18;2018:6282687. Epub 2018 Sep 18.

Division of Endocrinology and Metabolism, Rutgers-RWJMS, New Brunswick, NJ 08901, USA.

Purpose: To compare the initial clinical features, laboratory values, and bone mineral density among patients with primary hyperparathyroidism (PHPT) in Changsha (China) and New Brunswick (USA).

Methods: In this retrospective study, we reviewed 169 PHPT patients who presented at Robert Wood Johnson University Hospital and 133 PHPT patients who presented at the Second Xiangya Hospital of Central South University in the same time period. The following characteristics were compared between the groups: age, gender, BMI, serum calcium, alkaline phosphatase (AKP), albumin, intact PTH (iPTH), 25-hydroxyvitamin D (25 (OH) D), fasting blood glucose levels, and bone mineral density (BMD). All these parameters were also compared according to gender and menopausal status. iPTH associations were also assessed along with several other parameters.

Results: PHPT patients from Changsha had higher serum calcium, iPTH, and AKP levels but lower 25 (OH) D levels than the patients from New Brunswick ( < 0.05). Patients in Changsha had lower -scores and -scores in both the lumbar spine and hip regions than those in New Brunswick ( < 0.05). Patients in New Brunswick had lower percentages of parathyroid adenoma and kidney stones. Serum iPTH level was positively correlated with serum calcium and serum AKP levels in both Changsha and New Brunswick ( < 0.05).

Conclusions: There are distinct biochemical and clinical differences between patients with PHPT in China and the United States. Our study revealed that Asian PHPT patients from Changsha presented more severe PHPT profiles, lower bone mineral density, and higher incidence of renal stones.
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http://dx.doi.org/10.1155/2018/6282687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186333PMC
September 2018

Positive effects of total and dairy protein intakes on peripheral skeleton bone strength.

Am J Clin Nutr 2017 07;106(1):322

From the Department of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China (DX; ZS, e-mail:

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http://dx.doi.org/10.3945/ajcn.117.154450DOI Listing
July 2017

Low-Level Cadmium Exposure and Bone Health.

J Bone Miner Res 2017 02 10;32(2):419. Epub 2017 Jan 10.

Department of Metabolism and Endocrinology, the 2nd Xiangya Hospital, Central South University, Changsha, Hunan, China.

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http://dx.doi.org/10.1002/jbmr.3049DOI Listing
February 2017

Serum myostatin in central south Chinese postmenopausal women: Relationship with body composition, lipids and bone mineral density.

Endocr Res 2016 Aug 4;41(3):223-8. Epub 2016 May 4.

c Institute of Metabolism and Endocrinology, the Second Xiang-Ya Hospital , Central South University , Changsha , PR China.

Aims: Previous data suggest that myostatin has direct effects on the proliferation and differentiation of osteoprogenitor cells. The relationships between serum myostatin, body composition lipids and bone mineral density in postmenopausal women remain unclear. The aim of this study is to elucidate the relationships between serum myostatin, body composition, lipids and bone mineral density in central south Chinese postmenopausal women.

Methods: A cross-sectional study was conducted in 175 healthy postmenopausal women, aged 51-75 years old. Bone mineral density (BMD) and body composition were measured by double energy X-ray absorptiometry (DXA). Serum myostatin, 25-dihydroxyvitamin D(25OH-D), parathyroid hormone (PTH), bone alkaline phosphatase (BAP) and carboxy-terminal telopeptide of type I collagen (CTX) were measured by enzyme-linked immunoabsorbent assay (ELISA).

Results: In contrast to the osteoporotic women, the women without osteoporosis had higher BMI, fat mass and lean mass (P<0.01). The osteoporotic women were older than women without osteoporosis (P<0.01). There were no differences between two groups with regard to serum BAP, CTX, (25OH-D), PTH, lipids and myostatin after adjusted by age. BMD at each site was positively correlated with age at menopause, fat mass and lean mass, and also negatively correlated with age and serum BAP. Serum myostatin was positively correlated with tryglicerides, not correlated with either body composition or BMD at each site.

Conclusions: Our data indicated that serum myostatin concentration did not correlate with muscle and bone mass. Further studies are needed to demonstrate the role of myostatin in regulating the bone metabolism.
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http://dx.doi.org/10.3109/07435800.2015.1044609DOI Listing
August 2016

Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats.

Int J Endocrinol 2015 27;2015:252503. Epub 2015 Jul 27.

Comprehensive Cancer Center and Urology, University of Michigan, E Medical Center Drive, Ann Arbor, MI 48109, USA ; Research & Development and Radiology, VA Southern Nevada Healthcare System, 6900 N. Pecos Road, North Las Vegas, NV 89086, USA.

Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (-27%) and at tissue level (-12%), Tb bone volume fraction (-29%), Tb thickness (-14%), and Tb number (-17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties-nanoindentation hardness, elastic modulus, and plastic deformation-nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se.
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http://dx.doi.org/10.1155/2015/252503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530249PMC
August 2015

Relationships of serum lipid profiles and bone mineral density in postmenopausal Chinese women.

Clin Endocrinol (Oxf) 2015 Jan 7;82(1):53-8. Epub 2014 Nov 7.

Department of Metabolism and Endocrinology, the Second Xiang-Ya Hospital, Central South University, Changsha, China.

Objectives: Recent studies suggest that serum lipid profiles are related to bone mineral density (BMD). But data about this relationship on Chinese population are scarce. We investigated the relationships between serum lipid and BMD in postmenopausal Chinese women.

Methods: A cross-sectional study was conducted in 790 Chinese postmenopausal women. BMDs were measured by dual X-ray absorptiometry. Serum lipid profiles were obtained after a 12-h fasting.

Results: Women with serum high-density lipoprotein cholesterol (HDL-C) levels of at least 1·55 mmol/l had a greater prevalence of osteoporosis compared with women with lower HDL-C (≤1·54 mmol/l). After controlling for age, menopausal duration, body mass index, serum creatinine levels, outdoor activity, smoking and alcohol intake, high HDL-C levels were associated with osteoporosis (OR = 1·64, 95%CI 1·16-2·33, P < 0·01). BMD at femoral neck and total hip was significantly lower in the higher HDL-C class than the lower class (0·722 ± 0·118 vs 0·744 ± 0·120 g/cm(2) , P < 0·01; 0·800 ± 0·126 vs 0·824 ± 0·125 g/cm(2) , P < 0·01, respectively). No association was found between total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) with BMD.

Conclusions: In Chinese postmenopausal women, elevated levels of serum HDL-C had a greater probability of being osteoporosis than the lower HDL-C levels. Our analysis showed higher HDL-C level that is favourable for cardiovascular diseases should be regarded as a risk factor for osteoporosis.
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http://dx.doi.org/10.1111/cen.12616DOI Listing
January 2015

Vitamin D status and its relationship with body composition, bone mineral density and fracture risk in urban central south Chinese postmenopausal women.

Ann Nutr Metab 2014 13;64(1):13-9. Epub 2014 Mar 13.

Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, PR China.

Aims: This study was designed to assess vitamin D (25(OH)D) status and its relationship with bone mineral density (BMD) and fracture risk, which was determined using the FRAX algorithm, among postmenopausal central south Chinese women, and to identify the risk factors for vitamin D deficiency and osteoporosis.

Methods: This cross-sectional study involved 578 healthy postmenopausal central south Chinese women. Fat mass and BMD at lumbar spine (L1-L4), femur neck and total hip were measured with dual X-ray absorptiometry. Serum levels of 25(OH)D, parathyroid hormone and creatinine were measured. The 10-year probabilities of hip and major osteoporotic fracture were calculated by the FRAX model.

Results: Approximately 72.1% women were vitamin D deficient (25(OH)D <50 nmol/l). Serum 25(OH)D levels did not correlate with body mass index (BMI), fat mass and weight. They positively correlated with all BMDs (p < 0.05) and negatively correlated with both 10-year fracture probabilities (p < 0.05). BMI ≤19 and age ≥65 years were risk factors for osteoporosis at all sites.

Conclusions: Vitamin D deficiency was prevalent among postmenopausal central south Chinese women. Serum 25(OH)D levels were correlated with all BMDs and negatively correlated with both 10-year fracture probabilities.
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http://dx.doi.org/10.1159/000358340DOI Listing
February 2015

RNF20 promotes the polyubiquitination and proteasome-dependent degradation of AP-2α protein.

Acta Biochim Biophys Sin (Shanghai) 2014 Feb 26;46(2):136-40. Epub 2013 Dec 26.

Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Science, Hunan Normal University, Changsha 410081, China.

Transcription factor activator protein 2α (AP-2α) is a negative regulator of adipogenesis by repressing the transcription of CCAAT/enhancer binding protein (C/EBPα) gene. During adipogenesis, AP-2α is degraded, leading to transcriptional up-regulation of C/EBPα. However, the mechanism for AP-2α degradation is not clear. Here, using immunoprecipitation assay and mass spectrometry, we identified ring finger protein 20 (RNF20) as an AP-2α-interacting protein in 3T3-L1 preadipocytes. RNF20 has been proved to be an E3 ubiquitin ligase for both histone H2B and tumor suppressor ErbB3-binding protein 1 (Ebp1). In this study, we demonstrated that RNF20 co-localized and interacted with AP-2α, and promoted its polyubiquitination and proteasome-dependent degradation. Over-expression of RNF20 inhibited the activity of AP-2α and rescued the C/EBPα expression which was inhibited by AP-2α. These results suggested that RNF20 may play roles in adipocyte differentiation by stimulating ubiquitin-proteasome-dependent degradation of AP-2α.
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http://dx.doi.org/10.1093/abbs/gmt136DOI Listing
February 2014

How to decide intervention thresholds based on FRAX in central south Chinese postmenopausal women.

Endocrine 2014 Mar 22;45(2):195-7. Epub 2013 Oct 22.

Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, 139 Renmin-Zhong Rd, Changsha, 410011, Hunan, People's Republic of China.

The FRAX tool has been used to determine possible thresholds for therapeutic intervention; however, there are no FRAX-based intervention thresholds available for China, we proposed that the 10-year probability of major osteoporotic fracture and hip fracture of about 4.0 and 1.3%, respectively, may be acceptable intervention thresholds for central south Chinese postmenopausal women.
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http://dx.doi.org/10.1007/s12020-013-0076-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924028PMC
March 2014

Age-related changes in body composition and their relationship with bone mineral density decreasing rates in central south Chinese postmenopausal women.

Endocrine 2013 Jun 19;43(3):643-50. Epub 2012 Nov 19.

Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, 139 Renmin-Zhong Rd, Changsha, 410011, Hunan, People's Republic of China.

The purpose of this work is to investigate the age-related changes in body composition and their relationship with bone mineral density decreasing rates (BDR) in central south Chinese postmenopausal women. BDR is the percentage of bone mineral density (BMD) decreasing value relative to the peak bone mass. A cross-sectional study was conducted on 779 healthy postmenopausal women, aged 50-77. Lumbar spine, total hip, and femoral neck BMD and body composition were measured by dual-energy X-ray absorptiometry. In women under 65, lean mass levels showed a stable downward trend, and were significantly higher than those of the 65-70 and >70 age groups; however, the fat mass levels showed no significant difference between the age groups. After controlling for age, age at menopause, and height, both fat mass and lean mass positively correlated with BDR at the lumbar1-4 spine, the femoral neck and the total hip. When BDR at the lumbar1-4 spine was used as the dependent variable, a higher R (2) change and partial R (2) were seen in fat mass than the age, age at menopause or lean mass, indicating that fat mass was the most significant determinant of BDR at this site. When BDR at the femoral neck or total hip was used as the dependent variable, respectively, lean mass was a more significant determinant than that of fat mass. We found that with advancing age, lean mass begins to decrease in women aged over 65 years, but fat mass levels show no significant difference between the age groups. Both fat mass and lean mass positively correlate with BDR, with site-specific differences. Fat mass is the most significant determinant of BDR at the lumbar spine, whereas lean mass is the most significant determinant of BDR at the femoral neck and total hip.
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http://dx.doi.org/10.1007/s12020-012-9833-6DOI Listing
June 2013

The relationship between body composition and fracture risk using the FRAX model in central south Chinese postmenopausal women.

Clin Endocrinol (Oxf) 2012 Oct;77(4):524-30

Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, China.

Objectives: To assess the relationship between body composition and fracture risk as determined by the FRAX(®) model in postmenopausal women in central south China.

Methods: A cross-sectional study was conducted in 779 women. Bone mineral density (BMD) of the left femur and total body composition were measured by dual X-ray absorptiometry. All clinical information was available for incorporation into the FRAX model to assess the 10-year fracture probability.

Results: In the FRAX model, when BMD values were included, the 10-year probability of major osteoporotic fractures and hip fractures was 3·4% and 1·0%, respectively, which was significantly higher than the probability rates of 2·7% and 0·8%, respectively, for the same events when BMD values were not included (P < 0·01). Both fat mass and lean mass were negatively correlated with the predicted 10-year probability of fracture (P < 0·01), and femoral neck BMD was the most significant determinant of the predicted 10-year fracture probability. Compared with fat mass, lean mass had more impact on the 10-year probability of both major and hip osteoporotic fractures.

Conclusion: In postmenopausal women in central south China, both fat mass and lean mass were negatively correlated with the predicted 10-year fracture probability. The effect of lean mass and fat mass on fracture risk may be mediated through their impact on BMD. Compared with fat mass, lean mass had more of an impact on the risk of both major osteoporotic and hip fractures, showing that physical activity is an important component in the prevention of osteoporotic fracture.
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http://dx.doi.org/10.1111/j.1365-2265.2012.04399.xDOI Listing
October 2012

Serum sclerostin levels were positively correlated with fat mass and bone mineral density in central south Chinese postmenopausal women.

Clin Endocrinol (Oxf) 2012 Jun;76(6):797-801

Key Laboratory of Protein Chemistry and Developmental Biology of Education Ministry of China, College of Life Science, Hunan Normal University, Hunan, China.

Objectives: To investigate the relationship between serum sclerostin level, body composition, and bone mineral density (BMD) in central south Chinese postmenopausal women.

Methods: A cross-sectional study was conducted on 260 healthy central southern Chinese postmenopausal women with vs without osteoporosis, aged 50-76 years old. Dual X-ray absorptiometry was used to measure the bone mineral content and BMD of the whole body, lumbar spine and left femur, and total body soft tissue composition. Serum sclerostin levels were measured by a quantitative sandwich enzyme-linked immunosorbent assay.

Results: Compared with women without osteoporosis, osteoporotic women had a significantly lower level of serum sclerostin (P = 0.001). Serum sclerostin levels were positively correlated with body weight, Ponderal index and fat mass. There was a positive correlation with the BMD of both the whole body and at various sites (P < 0.05), even after controlling for age, age at menopause, height and body weight. Multiple linear stepwise regression analysis showed that serum sclerostin level was the most significant determinant of both whole-body and lumbar spine BMD, compared with age, age at menopause, fat mass and lean mass. Age had similar impact as serum sclerostin on hip BMD.

Conclusions: This study showed that in central south Chinese postmenopausal women, serum sclerostin is lower in women with osteoporosis than without. Serum sclerostin is positively correlated with fat mass and BMD for the whole body, lumbar spine and hip.
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http://dx.doi.org/10.1111/j.1365-2265.2011.04315.xDOI Listing
June 2012

Relationship of body composition with prevalence of osteoporosis in central south Chinese postmenopausal women.

Clin Endocrinol (Oxf) 2011 Mar;74(3):319-24

Institute of Metabolism and Endocrinology, the Second Xiang-Ya Hospital, Central South University, Changsha, China.

Objectives: To elucidate the relationship between body composition and bone mineral density (BMD) and the prevalence of osteoporosis in central south Chinese postmenopausal women.

Methods: A cross-sectional study was conducted on 954 healthy central southern Chinese postmenopausal women, aged 50-82. Total body, lumbar spine and left femur BMD and total body soft tissue composition were measured by dual X-ray absorptiometry.

Results: Among the study population, 578 (60.5%) subjects were without osteoporosis and 376 (39.4%) subjects were osteoporotic. The osteoporotic women were older, shorter and thinner, had an earlier age at menopause, a lower BMD and bone mineral content (BMC) of the total body and at different sites, and had lower body mass and body mass components than the women without osteoporosis. Both fat mass and lean mass were positively correlated with age at menopause, height, weight, body mass index (BMI) and BMD at all sites. Fat mass and lean mass were also inversely correlated with age and years since menopause (P<0.05). After controlling for age, age at menopause and height, both fat mass and lean mass were positively correlated with BMD at the lumbar(1-4) spine, the femoral neck and the total hip. Fat mass was the most significant determinant of BMD at the lumbar(1-4) spine with a higher R(2) change and a partial R(2) compared with that of lean mass, while lean mass had more impact on the total hip values. Either a fat mass below 18.4 kg or a lean mass below 33.9 kg was correlated with a higher prevalence of osteoporosis at the lumbar spine or total hip.

Conclusions: In central south Chinese postmenopausal women, both fat mass and lean mass are correlated with BMD at the lumbar spine and hip. Fat mass was the most significant determinant of BMD at the lumbar spine, while lean mass had more impact on the total hip value. Both lower values of fat mass and lean mass are related to a higher prevalence of osteoporosis at either the lumbar spine or the total hip. Thus, it is important to maintain a reasonable body weight to balance bone health and other metabolic disorders.
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http://dx.doi.org/10.1111/j.1365-2265.2010.03941.xDOI Listing
March 2011

Relationship between body composition and age, menopause and its effects on bone mineral density at segmental regions in Central Southern Chinese postmenopausal elderly women with and without osteoporosis.

Arch Gerontol Geriatr 2011 Sep-Oct;53(2):e192-7. Epub 2010 Sep 28.

Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, 139 Renmin-Zhong Rd., Changsha, Hunan 410011, PR China.

We aimed at evaluating the relationship between lean mass and fat mass with age, menopausal age (MA) and years since menopause (YSM) and their effects on bone mineral density (BMD) at segmental regions in postmenopausal elderly women with and without osteoporosis. After using a dual-energy X-ray absorptiometry (DXA) methodology to measure body composition and BMD at posteroanterior spine and hip in 244 postmenopausal elderly non-osteoporotic (Non-OP) women (65.5 ± 4.3 years) and 298 postmenopausal elderly osteoporotic (OP) women (67.1 ± 4.4 years), we found that in postmenopausal elderly Non-OP women, there was no correlation between lean mass with age, MA, and YSM, as well as no correlation between fat mass with age (all, p > 0.05); leg fat (LF) mass (r = 0.187; p<0.01), whole body fat (WF) mass (r = 0.151; p < 0.05), and trunk fat (TRF) mass (r = 0.141; p < 0.05) were positively correlated with MA; LF (r = -0.131; p < 0.05) and WF (r = -0.127; p < 0.05) were negatively associated with YSM; WF and whole body lean (WL) mass were the most important body composition components influencing BMD at the third lumbar spine (L3), total first to fourth lumbar spine (L1-4) and hip, respectively; TRF was the most significant determinant of BMD at both L2 and L4. In postmenopausal elderly OP women, there was no relationship between body composition with MA (p > 0.05); Trunk lean (TRL) mass (r = -0.183; p < 0.05), leg lean (LL) mass (r = -0.136; p < 0.01), and WL mass (r = -0.162; p < 0.01) were negatively correlated with age; TRL mass (r = -0.132; p < 0.05), LL mass (r = -0.152; p < 0.01), WL mass (r = -0.170; p < 0.01) were also negative with YSM; WF was the most important factor influencing BMD at lumbar spine and hip. These data suggest in postmenopausal elderly Non-OP women, fat mass (TRF, LF, and WF) was more related with MA; WF and WL mass were the most important body composition components influencing BMD at L1-4 and hip, respectively; in postmenopausal elderly OP women, body composition was not correlated with MA; lean mass (TRL, LL, and WL) was more age-related negatively; WF mass was the most significant factor affecting BMD at lumbar spine and hip.
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http://dx.doi.org/10.1016/j.archger.2010.09.002DOI Listing
December 2011

Effects of genistein on vertebral trabecular bone microstructure, bone mineral density, microcracks, osteocyte density, and bone strength in ovariectomized rats.

J Bone Miner Metab 2008 4;26(4):342-9. Epub 2008 Jul 4.

Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, 139 Renmin-Zhong Rd, Changsha, 410011 Hunan, China.

Until now, the effects of phytoestrogen on bone in both women and ovarian hormone-deficient animal models of osteoporosis have remained uncertain. We have aimed here to investigate the effect of genistein (GEN) on trabecular bone quality in ovariectomized (OVX) rats. Forty 7-month-old female Sprague-Dawley rats were randomly divided into the following four groups: OVX, sham-operated (SHAM), treated with 17beta-estradiol (EST, 10 microg x kg(-1) x day(-1)), and GEN (5 mg x kg(-1) x day(-1)). At 15 weeks postoperation, the compressive test was performed on the L5 vertebral body; additionally, microcomputed tomography (micro-CT) assessment was performed to estimate the bone mineral density (BMD) and microstructure parameters of the L6 vertebral body. After fatigue damage testing, the L6 vertebral body was bulk-stained in 1% basic fuchsin and embedded in methylmethacrylate. The L4 vertebral body was embedded in methylmethacrylate for dynamic histomorphometry analysis without staining. Mounted bone slices were used to measure microcrack parameters, empty osteocyte lacuna density (e.Lc.Dn), and osteocyte density (Ot.N/T.Ar). Maximum loading (ML) and Ot.N/T.Ar were significantly lower in the OVX group than in the other groups. E.Lc.Dn was significantly decreased in GEN and EST groups compared to the OVX group. ML was significantly decreased in the GEN group compared to the SHAM group. Microcrack density, microcrack surface density, and microcrack length were significantly increased in the OVX group compared to the other groups. Mineral apposition rate was significantly decreased in the OVX group compared to the SHAM and GEN groups. Bone formation rate was significantly decreased in the OVX group compared to other groups. There were no significant differences with regard to mineralizing surface among the four groups. Volumetric BMD at organ was significantly lower in OVX, EST, and GEN groups than in the SHAM group. Bone mineral content was significantly lower in the OVX group than in the SHAM group. Bone volume fraction and trabecular number were significantly decreased in OVX, EST, and GEN groups compared to the SHAM group. Structure model index was significantly lower in the SHAM group than in OVX, EST, and GEN groups. Trabecular separation was significantly increased in the OVX group compared to SHAM and EST groups. There were no significant differences with regard to the trabecular thickness (Tb,Th) between SHAM, GEN, and OVX groups. Tb.Th was significantly lower in the EST group than in the SHAM group. Connectivity density (Conn.D) was significantly lower in the OVX group than in SHAM and GEN groups, and Conn. D was significantly lower in the EST group than in GEN. In conclusion, the present study demonstrates that GEN preserved the biomechanical quality of the trabecular bone regardless of the microstructure and BMD.
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http://dx.doi.org/10.1007/s00774-007-0830-4DOI Listing
September 2008

Comparison of the effects of genistein and zoledronic acid on the bone loss in OPG-deficient mice.

Bone 2008 May 8;42(5):950-9. Epub 2008 Feb 8.

Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.

Unlabelled: Using osteoprotegerin (OPG)-knockout mice, we demonstrated that in vivo the effects of both genistein and 17beta-estradiol (E2) on bone metabolism were completely abolished. In contrast, zoledronic acid could effectively suppress bone resorption and prevent bone loss.

Introduction: The anti-resorptive effects of E2 on bone metabolism are considered to be mediated via modulation of the osteoblast-derived paracrine factor OPG. Recently, the phytoestrogen genistein was found to suppress bone resorption by enhancing osteoblastic production of OPG. However, the mechanism underlying the in vivo effects of E2 and genistein on bone is not entirely understood, and a central question in this regard is whether E2 regulates bone metabolism via an OPG-dependent pathway.

Methods: After mating heterozygous (OPG+/-) mice, homozygous (OPG-/-) and wild-type (WT) with a mixed C57BL/6J x 129/SV background were obtained. The study involved 6-week-old female OPG-/- (n=40) and WT mice (n=8). The OPG-/- mice were randomly divided into 5 groups (n=8 per group) as follows: (1) genistein-treated mice (Gen) that were subcutaneously injected with genistein at a maximal dose (0.8 mg/day); (2) E2-treated mice (E2) that were subcutaneously injected with E2 at a dose (0.03 microg/day); (3) DMSO control mice (DMSO) that were subcutaneously injected with a mixture of dimethylsulfoxide (DMSO) and polyethyleneglycol-300; (4) zoledronic acid-treated mice (Zol) that were subcutaneously injected with zoledronic acid at a dose of (150 microg/kg) twice per week; and (5) H2O control mice that were subcutaneously injected with sterilized water twice per week. The doses of genistein, estrogen and zoledronic acid were selected based on the results of dose-response effect of agents on bone versus uterus in OPG-/- mice. The mice were sacrificed 6 weeks after this intervention. The microarchitecture of the trabecular and cortical bone was assessed by performing microcomputed tomography (micro-CT) for the right proximal tibia. The bone mineral density (BMD) of the left femur was measured by dual-energy X-ray absorptiometry (DXA). The biomechanical parameters of the right femur were determined by a three-point bend testing. Serum levels of bone alkaline phosphatase (B-ALP), tartarate-resistant acid phosphatase-5b (TRACP-5b), and receptor activator of nuclear factor kappaB ligand (RANKL) were determined by performing ELISA.

Results: DXA analysis revealed that the total BMD of the femur was not significantly altered in the Gen, E2, H2O, and DMSO groups. The three-point bending test revealed no significant differences in the biomechanical parameters, including ultimate loading, ultimate stress, stiff index, and elastic modulus, and micro-CT analysis revealed that the microarchitectural parameters of the trabecular bone (vBMD, tBMD, BVF, BSF, SMI, Tb.N, Conn.D, Tb.Sp, and Tb.Th) and cortical bone (Ct.Th, Mm, In.Pm, Ot.Pm, Ma.Ar, Ct.Ar, Tt.Ar, Ct.BMD, and Ct.BMC) did not differ among the groups. Genistein and E2 treatment did not alter the serum TRACP-5b, B-ALP, or RANKL levels. However, in addition to increasing the bone mass, zoledronic acid could effectively improve biomechanical parameters and could completely prevent deterioration of the bone architecture in the OPG-/- mice.

Conclusions: The effects of genistein and E2 on bone metabolism in vivo were lost completely in OPG-deficient mice, suggesting that the effect of these agents on bone metabolism seems to be entirely dependent on OPG. In contrast, zoledronic acid could effectively suppress bone resorption and completely prevent the bone loss in the OPG-/- mice--an effect that is likely to be independent of the OPG pathway.
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http://dx.doi.org/10.1016/j.bone.2008.01.010DOI Listing
May 2008

Prolactin may be a promising therapeutic target for myasthenia gravis: hypothesis and importance.

Med Hypotheses 2008 22;70(5):1017-20. Epub 2007 Oct 22.

Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, 86# Middle Renmin Road, Changsha, Hunan 410011, PR China.

Myasthenia gravis (MG) is an autoimmune disease that affects the transmission signals from nerves to muscles. The basic pathology is the production of anti-acetylcholine receptor (AChR) antibodies (AChRAb) which is the consequence for the generation of autoreactive T lymphocytes responsing to AChR. However, the molecular mechanism of MG and the production of autoreactive T lymphocytes remain elusive. Recently beside its pivotal role in reproduction, the pituitary hormone prolactin (PRL) has been attributed to an immunomodulatory function. Furthermore it has been shown to be expressed in T cells and conversely it also affects the function of T cells, such as directly stimulating the proliferation and survival of T lymphocytes. In addition, elevated PRL levels frequently are described in autoimmune diseases, such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). So we hypothesized that the stimulating effect of PRL on T-cells function may be implied in the pathogenesis of MG and, perhaps, prolactin may be a promising therapeutic target for MG.
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http://dx.doi.org/10.1016/j.mehy.2007.06.044DOI Listing
July 2008
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