Objective To explore hemodynamic parameter changes in pulmonary arterial hypertension(PAH)treated by transplantation of bone marrow mesenchymal stem cells(MMSCs)in the experimental rats.Methods MMSCs cells were collected from bone marrow of Sprague-Dawleye(SD)rat's femoral and tibial bones,cultured and passaged in vitro,then stained by Hoechst 33342 fluorescence dye stuff.Ninety healthy male SD rats were randomly divided into 3 groups(n=30):normal control group(group N),MMSCs transplanted group(group M),PAH model group(group H).The rats in the two latter groups were given a single subcutaneous crotaline(50 mg/kg)to establish the model of PAH.The rats of group N were injected respectively a single subcutaneous 9 g/L saline water(6 mL/kg).After 21 days,5?109 L-1 MMSCs cultured in 1 mL phosphate-buffered saline were infused into the rats respectively in group M by sublingual vein and 1 mL L-DMEM was given in group H.The indexalso of right ventricle systolic pressure(RVSP),right ventricle hypertrophy index,arterial blood gas analysis and the changes of small pulmonary blood vessel were observed after 28 days.Results The administration of MMSCs 28 days after PAH nearly completely prevented the increase in RVSP with PAH alone [(32.20?2.32)mmHg vs(48.30?1.56)mmHg P

OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis, a common consequence of chronic liver injury of multiple etiology. Nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a major regulator of a celular defense system against oxidative stress. Xiaochaihutang (XCHT), a compound of seven botanical extracts used for liver diseases traditionally in East Asia. However, few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action. The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway. METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride (CCl4) over a period of 9 weeks. Starting from the 6th week, the animals in treatment groups were given the appropriate dose of XCHT granules and silybin. Biochemical parameters, histological changes of the liver and alpha-smooth muscle actin (α-SMA) were determined. The expressions of Nrf2, Keap1, Nqo1, HO-1, Gclc and Gclm were assessed by RT-PCR and Western blot. RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT (5 g·kg- 1 and 10 g·kg- 1). XCHT (5 g·kg- 1 and 10 g·kg- 1) treatment significantly decreased the number of cells labeled with α-SMA antibodies. Moreover, XCHT (5 g·kg-1 and 10 g·kg-1) significantly increase Nqo1, HO-1, Gclc and Gclm expressions in the liver. CONCLUSION These studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress, making further efforts to inhibiting the activated HSCs. Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.

Acute coronary artery syndrome (ACS) was confirmed by coronary arteriography in 398 patients,and 378 healthy persons served as the control group.Serum uric acid in ACS and control group showed normal distribution,and serum uric acid level in ACS group (322?107 )?mol/L was significantly higher than those in control group (302?77)?mol/L (P＜0.01 ).The prevalence of hyperuricemia (HUA) was 27.0% in male patients and 25.2% in female.Systolic blood pressure,diastolic blood pressure,fasting plasma glucose,total cholesterol,triglycerides,creatinine and blood urea nitrogen in ACS group were higher than those in control group (all P＜0.01 ).Muhivariable analyses adjusted for age and sex indicated that raised fasting plasma glucose,total cholesterol,uric acid and mean arterial pressure were risk factors for coronary artery stenosis in ACS,and HUA played a role in the pathogenesis of ACS.

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis(OSF),a premalignant disease that is largely induced by betel quid chewing.However,the lack of available models has challenged studies of angiogenesis in OSF.Here,we found that the expression of thrombospondin 1(THBS1),an endogenous angiostatic protein,was elevated in the stroma of tissues with OSF.Using a fibroblast-attached organoid(FAO)model,the overexpression of THBS1 in OSF was stably recapitulated in vitro.In the FAO model,treatment with arecoline,a major pathogenic component in areca nuts,enhanced the secretion of transforming growth factor(TGF)-β1 by epithelial cells,which then promoted the expression of THBS1 in fibroblasts.Furthermore,human umbilical vein endothelial cells(HUVECs)were incorporated into the FAO to mimic the vascularized component.Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs(vFAOs).Consistently,treatment with arecoline reduced the expression of CD31 in vFAOs,and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36,a receptor of THBS1.Finally,in an arecoline-induced rat OSF model,THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo.Overall,we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

Wuzhuyu Tang is a classical formula for treating migraine, but its' pharmacological ingredients is unclear yet. Present study employed the everted intestinal sac model to collect the absorption samples of 10 kinds of Wuzhuyu decoction, and then analyzed the contents of 9 ingredients in Wuzhuyu Tang and absorption samples quantitatively or semi-quantitatively by HPLC-DAD method. Reserpine was used to establish the mice model of migraine, and then the contents and activities of 5-hydroxytryptamine, noradrenaline, dopamine, nitric oxide and nitricoxide synthase in brain tissues and serums were determined respectively after oral administration of Wuzhuyu Tang. Using the partial least squares regression method to correlate the total absorption quantity of 9 ingredients and pharmacodynamics. The result shows that limocitrin-3-O-beta-D-glucoside, ginsenoside Rg1 and Rb1, rutaevine, limonin, evodiamine and rutaecarpine are the main ingredients influenced the effects in absorption samples in everted intestinal sacs, especially ginsenoside Rg1, rutaevine, evodiamine and rutaecarpine among them have obvious improving effects to most pharmacodynamics index, might be the pharmacological ingredients influenced the therapeutical effects of Wuzhuyu Tang treating migraine.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Intestinal Absorption ; drug effects ; Intestines ; drug effects ; Male ; Mice ; Mice, Inbred ICR ; Migraine Disorders ; drug therapy ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effects of saponins from Anemarrhena asphodeloides Bunge (SAaB) (Botanical Name: Anemarrhena Asphodeloidis Rhizoma) on the growth of vascular smooth muscle cells (VSMCs).

METHODSCell proliferation was measured by a newly developed cell proliferation reagent, WST-1. Cell apoptosis was assayed by flow cytometry through detecting annexin V. Nitric oxide production was evaluated using confocal laser scanning microscopy with diaminofluorescein diacetate (DAF-2, DA). Cell aldose reductase (AR) activity, as well as the effect of Epalrestat and interleukin-1beta were also explored.

RESULTSWST assay showed that cell proliferation induced by serum was significantly inhibited by SAaB (P<0.01). Flow cytometry analysis revealed that SAaB could enhance apoptotic rate of VSMCs (P<0.01). Nitric oxide production was significantly enhanced after administration of SAaB and interleukin-1beta. Moreover, AR activity of VSMCs was also remarkably inhibited by both SAaB and Epalrestat (P<0.01).

CONCLUSIONSAaB can inhibit proliferation and enhance apoptosis of VSMCs. It may protect vascular cells by inhibiting VSMC proliferation and augmenting apoptotic rate of VSMCs via NO-dependent pathway.

Anemarrhena ; chemistry ; Animals ; Annexin A5 ; metabolism ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Flow Cytometry ; Fluorescein ; chemistry ; Microscopy, Confocal ; Muscle, Smooth, Vascular ; cytology ; drug effects ; growth & development ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology

AIMTo report the clinical experience during collecting sperm samples in the Fragile X syndrome (FXS) male patients.

METHODSTwo different polymerase chain reaction (PCR) based methods were used for the molecular diagnosis of FXS. Sperm collection was done mostly according to the laboratory manual of the World Health Organization.

RESULTSWe failed to collect sperm samples from five Fragile X subjects aged 18-60 years as a result of an unexpected erectile dysfunction (ED). Multiple examinations of the same subject at different times, and of different subjects from different provinces examined by different physicians, showed the same result consistently in all the five subjects.

CONCLUSIONErectile reflex is an instinctive response in all healthy males. The absence of erection can be caused by hormonal, physical or neuronal malfunction. As hormonal profiles were reported to be generally normal in Fragile X men, we propose that an unknown physical factor or the neuronal circuit, or both, underlying the erection is compromised. The finding of this symptom in Fragile X patients may help better understand the clinical spectrum and pathogeneses of the disease.

Adolescent ; Adult ; Base Sequence ; DNA Primers ; Erectile Dysfunction ; Female ; Fragile X Syndrome ; physiopathology ; Humans ; Male ; Middle Aged ; Pedigree ; Polymerase Chain Reaction ; methods ; Spermatogenesis ; genetics

BACKGROUNDMultiple epiphysis dysplasia (MED) is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined cases, mutations have been identified in the gene encoding cartilage algometric matrix protein (COMP).

METHODSFive patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members.

RESULTSWe have identified a novel mutation in axon 14 of COMP gene in the family.

CONCLUSIONSThis mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.

Adolescent ; Asian Continental Ancestry Group ; Cartilage Oligomeric Matrix Protein ; genetics ; Female ; Humans ; Male ; Osteochondrodysplasias ; genetics ; Pedigree ; Point Mutation ; genetics

Purpose To investigate the clinicopathological features of primary subcutaneous lymphomatoid granulomatosis (LYG). Methods A case of primary subcutaneous LYG was observed by analysis of the clinical, histological features, immunophenotype and molecular pathology with review of the related literature. Results The male patient, 78-year-old, inadvertently found a mass of right axillary for more than 10 days. The boundary of the mass was clear, it seemed to have a capsule, the cut surface was grayish yellow and grayish red, the texture was medium. A large amount of coagulative necrosis was observed in the center of the mass under microscope. The peripheral area showed a morphological change of panniculitis, accompanied by pleomorphic lymphoid infiltration, showed central and vascular destructive infiltration, pathological mitosis was occasionally observed. Immunophenotyping showed that atypical large lymphoid cells expressed CD45 RB, CD20, CD30, while CD3, CD15, CD56, TIA-1, Granzyme B, ALK, CD21, Langerin and CD1 a, S-100 and CK (AE1/AE3) were negative. The proliferation index of Ki-67 ranged from 50％ to 60％. EBER in situ hybridization showed that positive cells were> 20/HPF.Neither acid fast staining nor TB-DNA testing supported tuberculosis. Molecular pathology found clonal Ig K gene rearrangement, TCRB + TCRG gene rearrangement showed the absence of monoclonal proliferating T cell population. Conclusion The primary subcutaneous LYG is a rare tumor. which can be diagnosed by combination of morphology, immunophenotype and molecular pathology.