In chronic kidney disease (CKD), inflammatory responses during the progression of renal tissue and tissue injury related causes its progression to end-state renal disease. Among them, nuclear factor (nuclear factor, NF)-kappaB signaling pathway by regulating the corresponding nuclear expression of target gene transcription, as well as affecting the synthesis of inflammatory mediators, induction of inflammation lead to kidney damage and renal fibrosis. Some single herbs and their extracts (such as Astragali Radix, Scutellariae Radix, Ginkgo Folium) and some traditional Chinese medicine (such as Danggui Buxue decoction, Qilian decoction) can reduce the inflammatory damage induced by renal tissue NF-kappaB signaling pathway and delay the progression of CKD.
Animals ; Humans ; Kidney ; drug effects ; pathology ; Medicine, Chinese Traditional ; methods ; NF-kappa B ; metabolism ; Renal Insufficiency, Chronic ; drug therapy ; pathology ; Signal Transduction ; drug effects

OBJECTIVETo validate the hypothesis that the phenotypic transformation occurs in the smooth muscle cells in the corpus cavernosum of hypertensive rat and explore its impact on the erectile function of rats.

METHODSEighteen 16-week-old male spontaneously hypertensive rats (SHR) and 10 syngeneic normotensive rats (WKY) were used in this experiment. After measurement of systolic blood pressure of the caudal artery and examination of the erectile function with subcutaneous injection of apomorphine (APO), the rats were divided into 3 groups, namely hypertensive with erectile dysfunction (HBP-ED) group (n=6), hypertensive (HBP) group (n=12) and control group (n=10). Immunohistochemical staining and color image analysis system were used to observe expression of calponin 1 and osteopontin (OPN) in rat corpus cavernosum. Real-time quantitative RT-PCR was used to determine the expression of calponin 1 and OPN mRNAs in different groups.

RESULTSThe expressions of calponin 1 protein and mRNA were the highest in the control group and the lowest in HBP-ED group, while the expressions of OPN protein and mRNA were the highest in HBP-ED group and the lowest in the control group.

CONCLUSIONThe smooth muscle cells may transform from the contractile phenotype into synthetic phenotype in the corpus cavernosum of the hypertensive rats, resulting ultimately in erectile dysfunction.

Animals ; Calcium-Binding Proteins ; genetics ; metabolism ; Erectile Dysfunction ; etiology ; pathology ; Hypertension ; complications ; pathology ; Male ; Microfilament Proteins ; genetics ; metabolism ; Myocytes, Smooth Muscle ; pathology ; Osteopontin ; genetics ; metabolism ; Penis ; pathology ; Phenotype ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR

OBJECTIVETo evaluate the relationship between infection of Chlamydia Trachomatis(Ct) and apoptosis of spermatogenic cells.

METHODSApoptotic spermatogenic cells were examined by Wright-Giemsa staining and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate(dUTP)-biotin nick-end labeling(TUNEL) technique.

RESULTSApoptosis rate of Ct infective group was significantly higher than that of normal group(P < 0.01).

CONCLUSIONSCt infection may cause the apoptosis of spermatogenic cells, which affords an objective evidence for illustrating the mechanism of Ct-infection-induced male infertility.

Adult ; Apoptosis ; Chlamydia Infections ; complications ; pathology ; Chlamydia trachomatis ; Humans ; In Situ Nick-End Labeling ; Infertility, Male ; etiology ; Male ; Spermatocytes ; pathology ; Staining and Labeling

OBJECTIVETo investigate the main constituents absorbed in the blood after orally administrating Shuanghuanglian injection extracts of its composed crude drug and provide the foundation for optimizing the prescription of Shuanghuanglian powder for injection.

METHODThrough analysing HPLC fingerprint established based on shuanghuanglian powder for injection and extracts of it composed crude drug, the active investigation were carried out among the peaks of control plasma and plasma containing drug in rats, shuanghuanglian powder for injection and extract of its composed crude drug. And the analysis was performed about relative content of constituents in each sample. Furthermore their original drugs and the metabolites in plasma containing drug were ascertained.

RESULTEight compounds were detected in plasma after oral administration of Shuanghuanglian, four of them were the original compounds contained in Shuanghuanglian powder for injection and three of them were relative metabolites. It has also found that contents of original compounds such as baicalin and chlorogenic acid fell off gradually, but their metabolites increased in rat plasma in vivo. With increasing time the main components of forsythia have not been detected obviously in rats plasma.

CONCLUSIONIn some extent, the compounds absorbed into blood from Shuanghuanglian powder for injection and their metabolites are the effective constituents, and its plasma pharmacochemistry should be subject to illuminate the pharmacological effects and the active mechanism.

Administration, Oral ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; Injections ; Male ; Plasma ; chemistry ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo compare the stability of baicalin and baicalein in buffered aqueous solutions and mouse plasma in order to discuss the degradation mechanism and the method of disposing samples.

METHODHPLC-ECD was used to determine baicalin and baicalein in different conditions, and the disposing samples methods were selected to stabilize them.

RESULTBaicalin and baicalein in the buffered aqueous solution at pH 7.4 was more stable than that in the mouse plasma. After adding Vit C in the buffered aqueous solution, the stability of baicalin and baicalein could be improved obviously and their remained percents were 102% and 100%. The stability of baicalin and baicalein could be enhanced distinctly in the mouse plasma only when adding Vit C and 1 mol x L(-1) HCl, and furthermore their remained percentage was up to 98% and 103%.

CONCLUSIONThe stability of baicalin and baicalein is related to the oxidation and enzyme degradation and it can be improved by adding Vit C and 1 mol x L(-1) HCl in the solution.

Animals ; Chromatography, High Pressure Liquid ; methods ; Flavanones ; blood ; pharmacokinetics ; Flavonoids ; blood ; pharmacokinetics ; Hydrogen-Ion Concentration ; Male ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results

OBJECTIVETo research effect of Wuzhuyu on Huanglian intestinal absorption and to provide some basic principle of match-pair of huanglian-rougui.

METHODThe rat everted gut sac method as well as non everted gut sac method was applied to investigate the influence of Wuzhuyu on Huanglian intestinal absorption.

RESULTThe content of each alkalis in Huanglian was decreasing with the comptibale ration increase, and the intestinal absorption had been improved in some degree. The intestinal absorption of Huanglian alkalis reached the highest level when match-pair ration of huang Lian-rougui was 6: 1.

CONCLUSIONThe chemical reaction in the progress of extraction and the intestinal absorption of huanglian alkalis were the key factors of match-pair of huanglian-wuzhuyu.

Animals ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; In Vitro Techniques ; Intestines ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo detect the mutations of Krit-1 gene that cause familial cerebral cavernous malformation (CCM) in the Han ethnic origin.

METHODSThe subjects were hospitalized in the Department of Neurosurgery, Tiantan Hospital affiliated to Capital University of Medical Sciences. Two families (A and B) and 8 apparently sporadic individuals affected with CCM were screened for mutations of Krit-1 gene. Members of the family CCM have a wide range in age of onset with seizures, headaches and skin lesions. The gene was screened by PCR amplification of 16 exons and mutation was detected by direct sequencing.

RESULTSIn family A samples, analysis of the Krit-1 gene revealed a new point mutation in exon 14 [a heterozygous C to G transition at nucleotide 1 289 (counting from the start codon or nt 2 308 counting from the first nt of the mRNA, aligned according to Gene Bank AF388384)] which predicts the substitution of a premature termination codon for Serine at codon 430 (S430X), belonging a nonsense point mutation. No mutation was identified in one of family A members as well as in any of the sporadic individuals with the exception of a single nucleotide polymorphism.

CONCLUSIONSReport the first family in the Han with CCM having a novel mutation in the CCM1 gene on the continent of Asia. The newly identified mutation creates a premature termination codon and is predicted to produce a truncated Krev1 interaction-trapped 1 protein, KRIT1. This result allows efficient presymptomatic molecular diagnosis.

Adult ; Base Sequence ; Child ; Child, Preschool ; Female ; Hemangioma, Cavernous, Central Nervous System ; genetics ; pathology ; Humans ; KRIT1 Protein ; Male ; Microtubule-Associated Proteins ; genetics ; Middle Aged ; Molecular Sequence Data ; Mutation ; Proto-Oncogene Proteins ; genetics

OBJECTIVETo investigate P2Y purinergic receptor activated PI-3K/Akt signaling pathway in the regulation of growth and invasion of prostate cancer in vitro.

METHODSWestern blot was used to detect phosphorylation of Akt (a downstream target molecule of PI-3K) by P2Y receptor agonist in 1E8 cells (a highly metastatic subclone derived from PC-3 prostatic cancer cell line). Cell counts, flow cytometry, Matrigel invasion assay, wound healing assay and gelatin zymography were used to detect changes of biological behaviors of 1E8 cells after P2Y receptor activation.

RESULTSAMP-PNP, one non-hydrolysis ATP analogue and P2Y receptor agonist, induced significant phosphorylation of Akt in a time- and dose-dependent manner in IE8 cells. LY294002, a specific inhibitor of PI-3K, effectively blocked Akt phosphorylation induced by AMP-PNP. Continuous exposure to AMP-PNP induced significant growth inhibition of 1E8 cells (inhibition rate at 50.2% at the 8th day), and this inhibition was mainly due to an arrest at S phase of the cell cycle (the S phase fraction of AMP-PNP treated cells was 22.3% higher than that of the control). Application of LY294002 did not reverse the growth inhibition effect of AMP-PNP. Matrigel invasion assay showed that AMP-PNP stimulation increased invasive ability of 1E8 cells, and this effect was effectively blocked by LY294002. No significant changes in the activation of MMP-2 and MMP-9 were detected by gelatin zymography, although wound healing assay showed 21.2% increase in cell migration after AMP-PNP treatment.

CONCLUSIONSPI-3K/Akt signaling pathway participates in P2Y receptor-stimulated prostate cancer invasion by enhancing cell motility, rather than up-regulating MMP-2 and MMP-9 activities. PI-3K signaling pathway plays an important role in prostate cancer proliferation, but is not involved in P2Y receptor mediated growth inhibition.

Adenylyl Imidodiphosphate ; pharmacology ; Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Chromones ; pharmacology ; Humans ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Mice ; Mice, Nude ; Morpholines ; pharmacology ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Phosphorylation ; Prostatic Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Purinergic P2 Receptor Agonists ; S Phase ; drug effects ; Signal Transduction ; drug effects

OBJECTIVETo investigate the prevalence of common psychosomatic symptoms among Chinese adolescents and the influence on 6 months later suicide and self-injurious behavior.

METHODSBased on the cluster sampling method, the participants who were recruited from 8 cities from 3 areas in China, including Eastern areas (Beijing, Shaoxing and Guangzhou), Middle areas (Ezhou, Harbin and Taiyuan) and Western areas (Guiyang and Chongqing), were administered by multidimensional sub-health questionnaire of adolescents (MSQA) in March 2008. Demographics, life style, psychosomatic symptoms, suicide and self-injurious behavior were also assessed. A total of 17 622 questionnaires were valid at baseline. Six months later, 14 407 questionnaires were eligible for two waves investigation. Analysis of Pearson chi-square and logistic model regression analysis were employed to compare the incidence of psychosomatic symptoms, suicide and self-injurious behaviors among different areas and to explore the possible risk factors of those symptoms and behaviors.

RESULTSAt baseline, rates of total common physiological and psychological symptoms were 24.1% (4255/17622) and 30.9% (5447/17622), respectively, with the highest being eating and drinking too much (6.4%, 1130/17622) and hardly feel ease to learn at home (11.8%, 2087/17 622). In males, the rate of common psychological symptoms (30.7%, 2637/8599) was higher than physiological symptoms (24.0%, 2061/8599) (P < 0.05); in females, the rate of common psychological symptoms (31.1%, 2810/9023) was higher than physiological symptoms (24.3%, 2194/9023) (P<0.05). The rate of the common psychosomatic symptoms in senior high school students (46.8%, 2905/6208) were significantly higher than those in middle high school students (37.3%, 2337/6262) and college students (33.2%, 1711/5152) (all P values <0.05). Students from Western areas had the highest incidences of the common physiological and psychological symptoms (30.2%, 1471/4871; 40.6%, 1979/4871), higher than students from Middle areas (22.4%, 1443/6453; 27.0%, 1743/6453) and Eastern areas (21.3%, 1341/6298; 27.4%, 1725/6298) (all P values <0. 05). Results from multiple logistic regression showed that physical symptoms > or = 2 at baseline were shared risk factors for suicidal ideation (RR = 1.44, 95% CI:1.16 - 1.79), attempted suicide (RR = 1.79, 95% CI: 1.22 - 2.61) and self-injurious behaviors (RR = 1.39, 95% CI: 1.17 - 1.66) 6 months later. Psychopathological symptoms > or = 4 at baseline was the shared risk factors for suicide ideation (RR = 1.74, 95% CI: 1.39 -2.17), attempted suicide (RR = 2.08, 95%CI: 1.39 - 3.11) and self-injurious (RR = 1.90, 95%CI: 1.59 - 2.28) 6 months later.

CONCLUSIONIt is common in Chinese adolescents who have multiple psychosomatic symptoms simultaneously. What's important is that those common psychosomatic symptoms are shared risk factors of later suicidal and self-injurious behaviors.

Adolescent ; China ; epidemiology ; Female ; Humans ; Male ; Psychophysiologic Disorders ; epidemiology ; Self-Injurious Behavior ; epidemiology ; psychology ; Suicidal Ideation ; Suicide ; psychology ; statistics & numerical data ; Surveys and Questionnaires

BACKGROUNDStudies have shown that abnormal activation of the sonic hedgehog pathway is closely related to tumorigenesis in central nervous system. This study aimed to investigate the role of the sonic hedgehog signaling pathway in the occurrence of brainstem and supratentorial glioma.

METHODSReal-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to detect the expression of sonic hedgehog-related components in 5 specimens of normal brain tissue, 10 of grade II brainstem glioma, and 10 of grade II supratentorial glioma. The significance of differences between two groups was determined using the Mann-Whitney U test or the two-sample test according to the results of normality distribution tests.

RESULTSThe mRNA expression levels of sonic hedgehog-related genes were higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue. The level of protein patched homolog 1 (PTCH1) was significantly higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue (P < 0.01). Immunohistochemistry semi-quantitative analysis was consistent with the qRT-PCR result that PTCH1 expression was increased significantly in brainstem astrocytomas at the protein level (P < 0.05).

CONCLUSIONSEnhanced PTCH1 expression and activation of the sonic hedgehog pathway are involved in brainstem glioma. This may be related to the difference in malignant biological behavior between brainstem and hemispheric glioma, and could be an ideal therapeutic target in brainstem glioma.

Adolescent ; Adult ; Astrocytoma ; genetics ; metabolism ; Brain Stem Neoplasms ; genetics ; metabolism ; Female ; Glioma ; genetics ; metabolism ; Hedgehog Proteins ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Patched Receptors ; Patched-1 Receptor ; Real-Time Polymerase Chain Reaction ; Receptors, Cell Surface ; genetics ; metabolism ; Signal Transduction ; genetics ; physiology ; Supratentorial Neoplasms ; genetics ; metabolism ; Young Adult