2', 3', 5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (WS070117) is a derivative compound of natural product cordycepin. It has significant lipids regulating activity and low toxicity which has been proved by in vitro and in vivo experiments. In this study, 1H NMR-based metabolomics was used to investigate the dose-related effects of WS070117 on hyperlipidemia of high-fat-fed hamsters. The hyperlipidemic hamsters were administrated with six different doses of WS070117, including 3, 12, 50, 100, 200 and 400 mg x kg(-1) x d(-1). 1H NMR spectra of hamster serum were visually and statistically analyzed using two multivariate analyses: principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). As a result, WS070117-treated groups showed dose-related regulation of metabolites associated with lipid metabolism, choline metabolism and glucose metabolism. The dose of 3 mg x kg(-1) x d(-1) of WS070117 only exhibited a little lipids regulating activity. However, the doses of 12 and 50 mg x kg(-1) x d(-1) of WS070117 both regulated the contents of metabolites to reverse significantly toward normal levels. When the dose of WS070117 reached 100 mg x kg(-1) x d(-1), it was more effective than positive control drugs. The work suggested that NMR-based metabolomics might be a valuable approach to evaluate dose-related effects of lipids regulating compounds.
Adenosine ; analogs & derivatives ; pharmacology ; Animals ; Cricetinae ; Hyperlipidemias ; metabolism ; Least-Squares Analysis ; Lipid Metabolism ; drug effects ; Magnetic Resonance Spectroscopy ; Metabolomics ; Multivariate Analysis ; Principal Component Analysis

Objective:To investigate the expressions of Mfn2(mitofusin 2) in non-small-cell lung cancer (NSCLC) tissues and non-cancerous lung tissues,and analyze its relationship with clinicopathological characteristics of lung carcinomas.Methods:The expressions of Mfn2 mRNA and protein in 92 cases of NSCLC tissues and 27 cases of non-cancerous lung tissues were detected by in situ hybridization and immunohistochemical methods. Results:The positive rates of Mfn2 mRNA and protein in pulmonary squamous cell carcinoma were higher than those in adenocarcinoma (83.33% and 89.58% vs 56.82% and 65.91%), respectively. The positive rates of Mfn2 mRNA and protein in NSCLC were higher than those in the non-cancerous lung tissues (25.93% and 29.63%) . The difference was statistically significant among the three groups (P<0.001 and P<0.01). The expressions of Mfn2 mRNA and protein in well-differentiated (93.75% and 100%) and moderately-differentiated NSCLC (91.67% and 91.67%) were higher than those in poor-diffe-rentiated NSCLC (21.43% and 42.86%). The difference was significant (P<0.001). The expressions of Mfn2 mRNA and protein had no correlation with the gender, age, tumor size, TNM stage and lymph node metastasis (P>0.05). The expression of Mfn2 mRNA was consistent with that of Mfn2 protein in NSCLC.Conclusion:Mfn2 was involved in the initiation and progression of lung cancer, and the expression of Mfn2 was related to the histological types of lung cancer and its differentiation degree.

Objective To investigate clinical feature,therapy and prognosis of 63 (rhabdomyolysis,RM) patients.Methods Retrospective analysis was used for the 63 patients who were from Nanjing from Janurary 2010 to August of 2016.Results Clinical history:the pathogenic factors mainly contained eating lobster,excessive exercise,lipid-lowering drugs,and minority patients were induced by infection,cardiac defibrillation,alcohol,and unexplained factors.Clinical features:most patients presented different degree of muscle soreness and weakness,and urine color of soy sauce;and few patients manifested a fever,respiratory distress and sound hoarse.Of which 11 RM patients concurrent acute kidney injury (AKI),there was no obvious bias of pathogenic factors among 11 patients.Clinical examination:the data was described by median,including creatine kinase 6 400 U/L,aspartate aminotransferase 399 U/L,lactate dehydrogenase 816 U/L,α-hydroxybutyric acid 445 U/L,and myoglobin 1 200 ng/ml.Creatine kinase and myoglobin were selected to measure muscle injure,there was no significant difference among the groups (P ＞ 0.05).Renal tubular injury index such as urincosmotic pressure,urine retinol-binding protein and N-acetyl-beta-D-glucosaminidase (NAG) enzyme,the abnormal percentage were 62.5％,50％,and 47.6％.Treatment:patients without complications through resting,water infusion,urine alkalization,were cured;and 11 cases of patients with AKI,1 case gave up,5 cases underwent hemodialysis,and 5 cases underwent conservative treatment,creatinine decreased to the basic level.Conclusions Among different pathogenic factors of RM,there were no obvious differences in clinlcal symptom,muscle damage degree,and whether the coexistence of AKI and prognosis.The understanding of RM,early diagnosis and treatment would prevent AKI and improve the prognosis.

Objective To evaluate the histocompatibility of novel manufactured xenogenic tendon matrix materials by an animal experimental study.Methods The study was conducted on 15 dogs,weighing 10-13 kg.The prepared xenogenic tendon matrix materials were implanted into the bilateral area of spine in dogs subcutaneously (experimental group),and the implantation of silicon served as control group.The animals were killed 14,30,60 days after surgery and the specimens were processed in laboratory to receive gross and histology observation.The histological sections were stained with hematoxylin-eosin and analyzed by light microscopy.Scores were assigned to the inflammatory process and statistically compared by two related samples with non-parametric test.Results All dogs survived well during the embedded test.There was no tissue necrosis,effusion or inflammation at all implantation sites in both groups during the test.The xenogenic implant materials promoted slight to moderate inflammation process after 14 days,with no statistically significant difference compared to the control.However,after 30 days,there was a regression of inflammation.After 60 days,it was observed the presence of well-organized connective tissue,and few inflammatory cells.Score evaluation of inflammation response at different time after operation of two groups showed no statistically significant difference (P＞0.05).Conclusions The new xenogenic tendon matrix materials are considered biocompatible with subcutaneous tissue.

Objective To investigate the effects of EMP exposure to male BABL/c mice on the reproduction and its sex ratio.Methods Thirty-three male BALB/c mice were randomly divided into sham-exposed group,10 000 pulses/d exposed group,and 100 000 pulses/d exposed group with 50 Hz static magnetic field of 35 kV/m for 2 weeks consecutively,then the male mice were mated with unexposed females (1 male vs.2 female).Mated males were sacrificed to examine the exposure effects on sperm number and testis index after 7 days of mating.The sex ratio of embryos collected from unexposed mated females was investigated by PCR.Results The sex ratio of offspring was 0.298 (14/47) in the 10 000 pulses/d exposed group,significantly lower than 0.871 (27/31) in the sham-exposed group.No statistical changes were observed in the sex ratio of offspring,sperm number,the weights of testis and testis index after 100 000 pulses/d exposure.Conclusions The exposure of male mice to 35 kV/m EMP at 10 000 pulses/d for 2 weeks consecutively may change the sex ratio of mice's offspring.

12E7 Antigen ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Diagnosis, Differential ; Fibrosarcoma ; metabolism ; pathology ; Heart Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Humans ; Male ; Mesothelioma ; genetics ; metabolism ; pathology ; Middle Aged ; Mucin-1 ; metabolism ; Oncogene Proteins, Fusion ; metabolism ; Pericardiectomy ; Pericardium ; pathology ; Sarcoma ; metabolism ; pathology ; Sarcoma, Synovial ; genetics ; metabolism ; pathology ; surgery ; Translocation, Genetic ; Vimentin ; metabolism

Objective: To investigate the effects of Chinese herbal drug-containing serum, prepared by administration of Chinese herbal medicine for activating blood (Xiongshao Capsule, XS) or for activating blood and detoxifying (Xiongshao Capsule plus Huanglian Capsule, XSHL) in rats, on cell viability, oxidative damage and apoptosis of human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL). Methods: Thirty-two rats were randomly divided into 4 groups: control group, positive control group (simvastatin 1.8 mg/kg), activating blood (XS, 0.135 g/kg) group, and activating blood and detoxifying (XS Capsule 0.135 g/kg and Huanglian Capsule 0.135 g/kg, XSHL) group. Corresponding drugs were continuously administered to the rats for 7 days and then drug-containing serum was harvested 1 hour after the last administration. HUVECs isolated from newborn children by collagenase digestion were stimulated by ox-LDL (100 μg/L) and incubated with corresponding drug-containing serum for 24 hours. Untreated HUVECs were also used as a normal control. The morphology and structure of HUVECs were observed by an inverted microscope. Cell viability was measured by methyl thiazolyl tetrazolium method, and cell membrane damage was determined by lactate dehydrogenase (LDH) leakage. Activity of superoxide dismutase (SOD) was examined by spectrophotometry, and content of malondialdehyde (MDA) in the cell lysate was examined by thiobarbituric acid assay. HUVECs were stained with Annexin V-fluorescein isothiocyanate and propidium iodide and analyzed on a flow cytometry to determine apoptosis. Results: Compared with the normal HUVECs, the cell viability and the activity of SOD were significantly decreased while the content of MDA and apoptosis rate were significantly increased after 24-hour ox-LDL stimulation (P<0.01, P<0.05). Simvastatin-, XS-, and XSHL-containing serum significantly promoted the ox-LDL-stimulated HUVEC viability and inhibited early apoptosis (P<0.01, P<0.05), while had no significant effect on LDH leakage. Simvastatin-containing serum and XS-containing serum also showed significant decrease in MDA content and increase in SOD activity, while XSHL-containing serum showed no significant effects. There was no significant difference between the XS-containing serum group and the XSHL-containing serum group. Conclusion: Both sera containing XSHL and XS show protective action against the oxidative damage and apoptosis of HUVECs induced by ox-LDL.

OBJECTIVETo investigate the anti-motion sickness efficacy and influence on the blood level of some hormones of a Chinese prescription composed of 10 herbs such as spina date seed.

METHODSAccording to the report by Cramptom and Lucot, SD rats and Beagle dogs were rotated around a horizontal axis, and the rat behavior of pica for Kaolin and the latency to vomit in dog were observed. In addition, guinea pigs were rotated around a vertical axis, and the nystagmus was recorded. Blood levels of corticosterone, adrenocorticotrophic hormone (ACTH), corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) in rats were measured with radioimmunoassay. The influences of the extracted mixture of herbs on these variables were simultaneously investigated.

RESULTSCompared with control group, oral administration of the extracted mixture of herbs: (1) significantly inhibited the rat behavior of pica for Kaolin and prolonged the latency to vomit in dog dose-dependently; (2) decreased the frequency of nystagmus and mean slow phase speed in rat; (3) reduced the elevation of corticosterone, ACTH, CRH and AVP in rat blood induced by rotatory stimulation; and (4) these effects of the extracted mixture of herbs were almost identical to dimenhydrinate.

CONCLUSION(1) The extracted mixture of Chinese Medicinal Herbs we used could inhibit motion sickness effectively. (2) This drug could reduce the blood levels of hormones of hypothalamic-pituitary-adrenocortical axis and AVP elevated by provocative rotatory stimulation.

Adrenocorticotropic Hormone ; blood ; Animals ; Arginine Vasopressin ; blood ; Corticosterone ; blood ; Corticotropin-Releasing Hormone ; blood ; Dogs ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Guinea Pigs ; Male ; Motion Sickness ; blood ; drug therapy ; Phytotherapy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo examine the hypothesis that periodontitis was one of the sources of inflammation in preterm low birth weight (PLBW) mothers and investigate the relationship between PLBW and inflammatory factors.

METHODSThe samples of saliva and gingival crevicular fluid (GCF) were collected from 83 PLBW mothers (PLBW group) and 44 normal birth weight (NBW) mothers (NBW group). The levels of IL-1beta and IL-6 were analyzed by enzyme-linked immunosorbent assay. The concentrations of cytokines in saliva and GCF were compared between the two groups.

RESULTSIL-1beta level in saliva of PLBW group was higher than which of NBW group significantly [(78.32+/-11.81) ng/L vs. (39.66+/-11.89) ng/L, P<0.05]. There was no statistically significant difference on IL-6 level in saliva [(17.45+/-3.13) ng/L vs. (16.28+/-0.66) ng/L], IL-1beta level in GCF [(93.58+/-13.22) ng/L vs. (81.38+/-9.28) ng/L] and IL-6 level in GCF [(15.35+/-0.28) ng/L vs. (14.87+/-0.37) ng/L) between two groups, but those of PLBW group were higher than NBW group. Significant negative correlations existed between gestational age at delivery and probing depth. It was also found significant negative correlations between gestational age at delivery and IL-6 (r=-0.274, P<0.01), between the weight of the new born infants and IL-6 levels in saliva (r=-0.424, P<0.01), IL-1beta level in GCF (r=-0.231, P<0.01).

CONCLUSIONSThere was a tendency presenting the higher inflammatory cytokine in GCF and saliva, the shorter gestation period and the lower birth weight. The levels of cytokine in saliva and GCF were higher in PLBW mothers. The correlation may be exist between maternal periodontitis and PLBW.

Adolescent ; Adult ; Female ; Gestational Age ; Gingival Crevicular Fluid ; chemistry ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Periodontal Attachment Loss ; metabolism ; Periodontal Index ; Periodontitis ; metabolism ; Premature Birth ; Saliva ; chemistry ; Young Adult

The interaction among collagen, von Willebrand factor (vWF) and glycoprotein Ib axis is the first step in hemostasis and thrombosis, especially under high shear condition. To develop a new remedy of anti-thrombosis, mRNA from endothelial cells was extracted, and reverse transcription PCR was adopted to amplify DNA of interest. After sequencing, recombinant expression vector was constructed. The amplified DNA fragment of vWF domain A3 was inserted into expression vector with 6 x his taq, pET20b(+), the recombinant was transformed into E coli (strain DE3) and induced by IPTG. Recombinant vWF-A3 was designated as a recombinant fragment comprising residues 918 - 1114 of mature vWF subunit. It was purified through Ni-NTA resin column and refolded in Tris buffer containing GSH and GSSG. The results showed that rvWF-A3 was expressed successfully in E coli (strain DE3), accounting for 46% of total bacterial protein with its purity of over 95%. It was identified that rvWF-A3 is capable to bind collagen and inhibit the wild vWF binding to collagen by competition. It is concluded that rvWF-A3 fragment might be an effective antithrombotic agent for preventing arterial thrombosis.
Cloning, Molecular ; Collagen ; metabolism ; Escherichia coli ; genetics ; Humans ; Protein Structure, Tertiary ; Recombinant Proteins ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; von Willebrand Factor ; chemistry ; genetics ; metabolism