Reflex sympathetic dystrophy after stroke,also called shoulder-hand syndrome(SHS),is a common complication of stroke.It is presumed that SHS is consequence of many factors,including periphery injury,effect of sympathetic never system,neurogenic inflammation,and plasticity of central nervous system.

The therapeutic effects and mechanisms of traditional Chinese kidney-tonifying drugs in treating osteoporosis have become the focus under study. Pharmacological studies have shown that traditional Chinese kidney-tonifying drugs are promoters for the proliferation of osteoblasts, inhibitors for the activity of osteoclasts, regulators for the estrogen level and its receptor, plays important roles in promoting osteogenesis and suppressing adipogenesis of marrow mesenchymal stem cells (MSCs), modulating the function of OPG/RANK/RANKL system and the metabolism of calcium and phosphorus, as well as antioxidation. The anti-osteoporotic active ingredients and pharmacological action mechanism of traditional Chinese kidney-tonifying drugs are summarized from the perspective of molecular and cell biology in this paper, so as to provide references for the study of their mechanism of anti-osteoporosis and for the development of traditional Chinese kidney-tonifying and bone-strengthening drugs.
Animals ; Bone and Bones ; drug effects ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Kidney ; drug effects ; physiopathology ; Osteoporosis ; drug therapy ; physiopathology

Animals ; Cells, Cultured ; Hepatocytes ; drug effects ; secretion ; Male ; Pancreatic Polypeptide ; pharmacology ; Rats ; Rats, Sprague-Dawley

The ABCD2 score is validated for evaluating short-term stroke risk after transient ischemic attack (TIA); however, whether it is able to predict the long-term risk of vascular outcome remains uncertain. Recently a new tissue-based definition of TIA has been proposed. The ABCD2 scores of 145 TIA patients admitted to our hospital were retrospectively calculated and stratified into two categories: ≤ 3 points (low risk); 4-7 points (moderate-high risk). At a median follow-up of 81 months, new vascular events were recorded. Follow-up data were available in 107 patients. Seventy one patients had a moderate-high ABCD2 score. Sixty six patients experienced a cerebral ischemic event; 8 a myocardial infarction; 7 died of cerebrovascular or cardiovascular cause. Moderate-high ABCD2 score was significantly associated with the further cerebral ischemic events (hazard ratio [HR], 1.755; 95% confidence interval [CI], 1.019 to 3.024) and with the combined endpoint (HR, 1.818; 95% CI, 1.079 to 3.063). Our study shows that the ABCD2 score may also be used to predict long-term vascular outcome after tissue-based definition of TIA. Moderate-high ABCD2 score is associated with an increased general vascular risk in the long-term follow-up after TIA.
Stroke

?AlM: To observe the expression of Acin1 ( apoptotic chromatin condensation inducer 1 ) in congenital cataract mouse retina during development and investigate the differences of retinal apoptosis and the connection of lens and retina development between congenital cataract mouse and normal mouse.
?METHODS: There were congenital cataract mice ( 10 female and 5 male) and normal C57BL/6 mice (10 female and 5 male) . One male and two female mice were fed in the same cage randomly. The young mice were divided into two groups: congenital cataract group and normal control group. Five young mice were treated each group on 1, 5, 9, 14, 17, 21, 26, 60d. The left eyes were fixed with 4% neutral formalin to detect AClN1 protein by immunohistochemistry and retinas from right eyes were used to detect the mRNA expression of Acin1.
?RESULTS: Acin1 had sustained expression in each group. AClN1 protein gradually expressed from the ganglion cell layer, inner nuclear layer to the outer nuclear layer following retinal development. lt mainly expressed on ganglion cell layer and inner nuclear layer, but not neuroblastoma layer. AClN1 protein positive cells on P1 ~ P14d increased in normal control group, P17d reduced, after P21d positive cells of each layers decreased. The overall trend was similar in congenital cataract group with normal control group, P1 ~ P14d positive cells count was lower than normal control group, P17-P21d positive cells were flat and higher than the normal control group. Compared with the same day of the two groups, the differences except for P17, P26, P60d were significant (P<0. 05). The overall difference was statistically significant in congenital cataract group ( Fcataract=295. 07, P<0. 01);in addition to P1 and P5, P17 and P21, the differences were statistically significant ( P< 0. 05 ) compared with each other in congenital cataract group. The overall difference was statistically significant in control group (Fnormal=214. 21, P<0. 01); in addition to P1 and P5d, the difference was statistically significant ( P<0. 05) compared with each other in control group. The expression of P17d in congenital cataract group was lower compared with that of P14d in control group, the difference was statistically significant (P<0. 05). Acin1 mRNA trends of two groups were similar with AClN1 protein. Compared with the same day of the two groups, the difference was significant except for P17, P21, P60d (P<0. 05 ) . The overall difference was statistically significant in each other of the two groups ( Fcataract=522. 29, P<0. 01;Fnormal=472. 05, P<0. 01). The difference was statistically significant compared with each day in control group ( P<0. 05). Compared with all the rest of days except for P21 and P26d, the difference was statistically significant in congenital cataract group (P<0. 05).
?CONCLUSlON: Acin1 exist differential expression of time and space in mouse retina during development, congenital cataract crystal developmental disorder may affect the expression of Acin1 and retinal cell apoptosis and development.

Objective To examine the expression of toll-like receptor 2(TLR2)in peripheral blood monocytes and explore its association with disease stages and clinical manifestations and to explore the patho- genesis of rheumatoid arthritis(RA).Methods The expression of toll-like receptor 2 in peripheral blood monocytes from 47 RA patientis(27 in active stage and 20 in stable stage)and 18 normal individuals were de- tected by flowcytometry and RT-PCR.Results The expression of toll-like receptor 2 in peripheral blood monocytes in patients with active disease was significantly increased compared to non-active patients and nor- mal individuals,The expression was found to correlate with the Disease Active Score(DAS),serum C-reactive protein(CRP)level and the erythrocyte sedimentation rate(ESR),but not correlate with rheumatoid factor (RF)and the anti-cyclic citrullinated peptide(CCP)antibody.Conclusion The expression of toll-like recep- tor 2 in peripheral blood monocytes of patients with active RA is significantly increased.And the expression is correlated with disease activity index.The innate immune system is activated in patients with active disease. And the increased expression may promote the activities of monocytes.

Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×10⁴, and the effective concentration of the positive drug was 1-100 µmol·L^-1. In addition, pretreated with 10 µmol·L^-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L^-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.

The poor survival of mesenchymal stem cells (MSCs) compromises the efficacy of stem cell therapy.Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell therapy.In this study,the aim was to evaluate the effect of serum deprivation on the cell death of MSCs and to investigate the underlying mechanisms.Apoptosis of MSCs was evaluated with Hoechst 33342/PI staining.Signaling pathways involved in serum-deprivation induced apoptosis were analyzed using Western blotting.The results revealed that serum deprivation induced apoptosis in MSCs within 72 h of treatment.Serum deprivation was shown to lead to protein expression alterations in Bax,Bcl-2,casepase-3,casepase-8,GRP78,and CHOP during experiments.The data suggested that the mitochondria death pathway,the extrinsic apoptotic pathway and the endoplastic reticulum(ER) stress pathway were all involved in MSCs apoptosis.The increase in expression of CHOP and the simultaneous decrease in Bcl-2 expression suggest a synergistic effect in apoptosis induction in both the mitochondrion and the ER.

OBJECTIVETo observe application value of multispectral animal living imaging technology in rats model of osteoarthritis.

METHODSFifteen male SD rats weighed (180 +/- 20) g (3 months old) were received intra-articular injection of iodoacetic acid for establishing osteoarthritis. Articular cavity of left knee of rats were injected into 50 microl iodoacetic acid. The same volume of sterile saline was injected into right knee articular cavity as control. X-ray living imaging and bone mineral density were observed at 2 and 4 weeks after establishment of model. After 4 weeks,rats were sacrificed and their bilateral joints were collected and determined histologically based on Collins classification and Kellgren-Lawrence classification.

RESULTSOsteoarthritis model was successfully established, compared with control group, model group showed typical manifestation of osteoarthritis, including irregular cartilage surface,osteophyte formation,joint deformity and cartilage defect,and combined with significant decrease of bone density (P < 0.01), while the decrease was not obvious in proximal tibia (P < 0.05). After 2 weeks, knee joints in model group was classified as Collins grade 1 and Kellgren-Lawrence grade 2,then classified as Collins grade 4 and Kellgren-Lawrence grade 3 after 4 weeks,control group showed smooth articular surface,normal joint space and intact cartilage surface, knee joints was classified as Collins and Kellgren-Lawrence grade 0, and bone density of distal femur and proximal tibia were normal.

CONCLUSIONMultispectral animal living imaging technology could be used in dynamic observation of living imaging and detection of bone density in the animal model of osteoarthritis, and it is significant for evaluation of osteoarthritis model, and its realted tesearch.

Animals ; Bone Density ; Disease Models, Animal ; Humans ; Knee Joint ; diagnostic imaging ; Male ; Osteoarthritis ; diagnosis ; diagnostic imaging ; physiopathology ; Radiography ; Rats ; Rats, Sprague-Dawley

The study aims to investigate the embryo-fetus development toxicity of the novel PPAR-δ agonist HS060098 on SD rats. The pregnant rats that were randomly divided into the solvent control group (1% hydroxypropyl methyl cellulose water solution) and HS060098 suspension groups (10, 30 and 100 mg x kg(-1) xd(-1)) were orally administered with HS060098 suspension or vehicle during the gestation of 6 -15 days (GD6-15). At termination (GD20), female rats were sacrificed. The pregnant females were evaluated by corpora lutea count, implantation sites, existence and death of embryos. Fetal sex, weight, externals, variations and malformations of viscus and skeleton were observed. The results show that there were no significant abnormality in maternal general conditions and fetal appearance as well as viscera, but in the 100 mg x kg(-1) x d(-1) group, the maternal weight gain decreased greatly (P < 0.01) and the skeletal ossification delayed remarkably (P < 0.01); in the 30 mg x kg(-1) xd(-1) group, the fatal and litter number of incompletely ossified sternebrae II was higher than those of the control group (P < 0.05); the skeletal malformations occurred in all dose groups, which indicate that the novel PPAR-δ agonist HS060098 had maternal toxicity and adversely effected fetal skeletal development under the experimental conditions.
Animals ; Bone and Bones ; drug effects ; Embryonic Development ; drug effects ; Female ; Fetal Weight ; PPAR delta ; agonists ; Pregnancy ; Rats ; Toxicity Tests