Objective To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes mellitus.
Methods The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion. The serum sclerostin level and bone mineral density of the anterior-posterior lumbar spine (L1-L4), femoral neck, and total hip were determined by using a quantitative sandwich ELISA kit and dual X-ray absorptiometry, respectively. Meanwhile, the clinical and laboratory indexes of bone mineral metabolism were analyzed. Associations between serum sclerostin level and bone mineral density as well as bone turnover markers were evaluated by linear regression analysis.
Results Finally, 265 postmenopausal women with type 2 diabetes and 225 non-diabetic women were recruited in the diabetic group and control group, respectively. Serum sclerostin level of the diabetic group was significantly higher than that of the control group (48.2±19.4 vs. 37.2±18.6 pmol/L, P<0.001) and was increased with age in both groups (diabetic group, r=0.374, P<0.001;control group, r=0.312, P<0.001). In type 2 diabetes patients, serum sclerostin concentration was positively correlated with hemoglobin A1c level (r=0.237; P=0.021). Biochemical bone turnover markers, intact parathyroid hormone and bone-specific alkaline phosphatase, were negatively associated with serum sclerostin level (r=?0.138, P=0.078 and r=?0.265, P<0.001). Conversely, the positive correlation between sclerostin and C-terminal cross-linking telopeptide of type I collagen was found in diabetic patients (r=0.354, P<0.001). Serum sclerostin levels of the diabetic group were positively correlated with bone mineral density of the lumbar spine, femoral neck, and total hip (r=0.324, 0.367, and 0.416, respectively;all P<0.001).
Conclusions Sclerostin might participate in the pathogenesis of bone loss of type 2 diabetes. The high sclerostin level might serve as a marker of increased osteocyte activity in postmenopausal patients with type 2 diabetes mellitus.

Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes.
Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon fatty acids treatment were analyzed.
Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake.
Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.

Animals ; Combined Modality Therapy ; Endostatins ; genetics ; Genetic Therapy ; Liver Neoplasms, Experimental ; radiotherapy ; therapy ; Mice ; Mice, Nude ; Neoplasm Transplantation

OBJECTIVEUsing doubly labeled water method to validate the colmputer science application's activity monitor (CSA) in assessing physical activity of free-living adults in Beijing, in order to develop equations to predict total daily energy expenditure (TEE) and activity related energy expenditure (AEE) from activity counts (AC) and anthropometric variables.

METHODSA total of 72 healthy adults (33 males and 39 females, mean age 43.6 +/- 4.0 yr) were monitored for 7 consecutive days by CSA. TEE was simultaneously measured using doubly labeled water method. Average AC (counts/min(-1)) was compared with TEE, AEE and physical activity level (PAL).

RESULTSPhysical activity determined by AC was significantly related to data on energy expenditures: TEE (r = 0.31, P < 0.01), AEE (r = 0.30, P < 0.05), and PAL (r = 0.26, P < 0.05). Multiple stepwise regression analysis showed that TEE was significantly influenced by gender, fat-free mass (FFM) or BMI and AC (R(2) = 0.52 - 0.70) while AEE was significantly influenced by gender, FFM and AC (R(2) = 0.25 - 0.32).

CONCLUSIONAC from CSA activity monitor seemed a useful measure in studying the total amount of physical activity in free-living adults while AC significantly contributed to the explained variation in TEE and AEE.

Activities of Daily Living ; Adult ; Anthropometry ; Body Weight ; Calorimetry, Indirect ; Energy Metabolism ; physiology ; Female ; Humans ; Male ; Monitoring, Physiologic ; instrumentation ; Motor Activity ; physiology ; Physical Fitness ; physiology

OBJECTIVETo evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes mellitus.

METHODSThe postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion. The serum sclerostin level and bone mineral density of the anterior-posterior lumbar spine (L1-L4), femoral neck, and total hip were determined by using a quantitative sandwich ELISA kit and dual X-ray absorptiometry, respectively. Meanwhile, the clinical and laboratory indexes of bone mineral metabolism were analyzed. Associations between serum sclerostin level and bone mineral density as well as bone turnover markers were evaluated by linear regression analysis.

RESULTSFinally, 265 postmenopausal women with type 2 diabetes and 225 non-diabetic women were recruited in the diabetic group and control group, respectively. Serum sclerostin level of the diabetic group was significantly higher than that of the control group (48.2±19.4 vs. 37.2±18.6 pmol/L, P<0.001) and was increased with age in both groups (diabetic group, r=0.374, P<0.001; control group, r=0.312, P<0.001). In type 2 diabetes patients, serum sclerostin concentration was positively correlated with hemoglobin A1c level (r=0.237; P=0.021). Biochemical bone turnover markers, intact parathyroid hormone and bone-specific alkaline phosphatase, were negatively associated with serum sclerostin level (r=-0.138, P=0.078 and r=-0.265, P<0.001). Conversely, the positive correlation between sclerostin and C-terminal cross-linking telopeptide of type I collagen was found in diabetic patients (r=0.354, P<0.001). Serum sclerostin levels of the diabetic group were positively correlated with bone mineral density of the lumbar spine, femoral neck, and total hip (r=0.324, 0.367, and 0.416, respectively; all P<0.001).

CONCLUSIONSSclerostin might participate in the pathogenesis of bone loss of type 2 diabetes. The high sclerostin level might serve as a marker of increased osteocyte activity in postmenopausal patients with type 2 diabetes mellitus.

Aged ; Alkaline Phosphatase ; blood ; Asian Continental Ancestry Group ; Biomarkers ; blood ; Bone Morphogenetic Proteins ; blood ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; blood ; epidemiology ; Female ; Genetic Markers ; Hemoglobin A ; metabolism ; Humans ; Middle Aged ; Osteocytes ; metabolism ; pathology ; Osteoporosis, Postmenopausal ; blood ; epidemiology ; Parathyroid Hormone ; blood ; Retrospective Studies

OBJECTIVETo investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine ÷ cytokines and insulin-dependent glucose uptake in human differentiated adipocytes.

METHODSAdipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes.A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine ÷ cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively.Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[³H] glucose uptake assay. Furthermore, chemokine ÷ cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon stimulation of NOD1 ligand were analyzed.

RESULTSNuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand (all P<0.01).Insulin-induced glucose uptake was decreased upon the activation of NOD1 (P<0.05).NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1,IL-6, and IL-8 release and increased insulin-induced glucose uptake (all P<0.05).

CONCLUSIONNOD1 activation in adipocytes might be implicated in the onset of insulin resistance.

Adipocytes ; metabolism ; Adult ; Cells, Cultured ; Cytokines ; biosynthesis ; Female ; Glucose ; metabolism ; Humans ; Inflammation ; etiology ; Insulin Resistance ; Ligands ; Middle Aged ; NF-kappa B ; physiology ; Nod1 Signaling Adaptor Protein ; physiology

Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Male ; Retinal Telangiectasis ; diagnosis ; therapy ; Retinopathy of Prematurity ; diagnosis

OBJECTIVETo observe the effects of Naoyikang (NYK) on expression of choline acetyltransferase (ChAT) in brain of rats with Alzheimer' s disease (AD).

METHODBilateral infusions of Ibotenic acid (IBO) into nucleus basalis of Meynert (NBM) using hamilton syringe and stereotaxic apparatus were adopted to establish the rat model of AD. After intragastrically administrated with different solution for 28 days, immunohistochemistry and Western-blot were adopted to study the expression of ChAT in frontal cortex of AD rats.

RESULTNYK could improve the morphology and increase the number of ChAT immunoreactive neurons, and significantly promote ChAT protein expression.

CONCLUSIONNYK may be able to increase the synthesis of acetylcholine (ACh) through elevating the expression of ChAT protein, thus improving the level of brain ACh so as to protect central cholinergic neurons.

Alzheimer Disease ; enzymology ; Animals ; Blotting, Western ; Brain ; drug effects ; enzymology ; Choline O-Acetyltransferase ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the direct effects of fenvalerate (Fen) on sperm motility in SD rats.

METHODSSperm were isolated from caudal epididymides of healthy adult male rats with the diffusion method. The motility parameters of the isolated sperm, such as VCL, VSL, VAP, BCF, STR and LIN, were monitored by computer-assisted sperm analysis (CASA) system after 1, 2 and 4 h Fen-exposure in vitro at concentrations of 0, 1, 4, 16 and 64 micromol/L respectively.

RESULTSAfter 1 and 2 h Fen-exposure, VSL, BCF, STR and LIN decreased significantly at 64 micromol/L compared with the control group. After 4 h Fen-exposure, the motility parameters VCL, VSL, BCF, STR and LIN dropped progressively at 64 micromol/L, and VCL declined markedly at 16 micromol/L. However, only VCL and STR showed alterations in a time-response manner.

CONCLUSIONFen may affect the caudal epididymal sperm and produce a direct toxic effect on sperm motility in SD rats.

Animals ; Dose-Response Relationship, Drug ; Insecticides ; toxicity ; Male ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; drug effects

Objective To study the expression of cyclooxygenase-2(COX-2) and survivin in children with acute leukemia(AL) and its significance.Method The expression of COX-2 and survivin were determined by immunohistochemical SABC assay.Results The expression rate of COX-2 and survivin were 52.4%(22/42 cases)and 45.2%(19/42 cases)in AL,and the expression rate of COX-2 and survivin were 46.9%(15/32 cases)and 40.6%(13/32 cases)and in acute lymphonate leukemia(ALL),both of them were higher than those in control group(Pa0.05).The positive rate of COX-2 was 84%(16/19 cases)in 19 cases with survivin positive expression,and the negative rate of COX-2 was 85%(17/20 cases)in 20 cases with survivin negative expression,and there was positive correlation between COX-2 expression and survivin expression(r=0.579 P