Humans ; Infant ; Male ; Pulmonary Alveolar Proteinosis

Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
Apoptosis ; Cell Proliferation ; Dependovirus ; Genetic Vectors ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Serpins ; metabolism ; Signal Transduction ; Transfection

Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.

Objective To investigate the association of the polymorphism of rs3750344 and rs1435252 of G-protein family GABABR2 gene with obesity in population of Uygur and Han. Methods 785 Uygur subjects from Xinjiang and 425 Han subjects from Jinan Maternity and Child Care Hospital were recruited by epidemiology survey. Exposure indicators such as body mass index (BMI), total cholesterol (Tch), triglyceride (TG), fasting glucose (Glu) concentration were measured. Two single nucleotide polymorphisms (SNPs) of rs3750344 and rs1435252 of GABABR2 gene were typed with Taqman. Linkage disequilibrium and haplotype were analysed with Haploview software. Results The frequency of rs1435252 was significantly different in AA carries of Uygur subjects between overweight group (12.5%) and normal weight group (6.6%), the subject with AA genotype significantly increased risk of overweight (OR=1.43, 95% CI: 1.06~1.91). The frequency of rs1435252 was significantly different in A alleles carries of Han subjects between obesity group (80.0%) and normal weight group (65.2%), the subject with A alleles significantly increased risk of obesity (OR=2.13, 95%CI: 1.18~3.86). The C alleles of rs3750344 significantly decreased risk of obesity (OR=0.69, 95%CI: 0.49~0.97) in Uygur, but the significance disappeared after controlling for covariates of age and gender. Conclusion The rs1435252 A allele of GABABR2 gene is a risk factor for overweight or obesity in population of Uygur and Han.

Objective To clarify the role and significance of Toll?like receptor 4(TLR4)in myocardial damage following paraquat(PQ)poisoning in mice. Methods Male wild type C57BL/6J mice(WT)and male TLR4 deficient mice(TLR4?ko)were divided into four groups in the study:(1)control group(WT mice,n=6);(2)TLR4?ko group(TLR4?ko mice,n=6);(3)WT+PQ group(WT mice,n=30);(4)TLR4?ko+PQ group (TLR4?ko mice,n=30). The mice in group 1 and group 2 were injected intraperitoneally with saline;mice in group 3 and group 4 were injected in?traperitoneally with 75 mg/kg of PQ. At 2 h,4 h,8 h,16 h and 24 h after PQ administration,6 mice of WT+PQ group and TLR4?ko+PQ group were euthanized and the heart tissue specimens were harvested. All the specimens were analysed by histology,while the expression of TLR4 mRNA was only detected in samples of WT+PQ mice. The specimens at 2 h,8 h and 24 h after PQ administration were used for cytokines detection for WT+PQ group and TLR4?ko+PQ group;in addition,Western blot analysis was performed for WT+PQ group. At 8 h after treatment,control mice and TLR4?ko mice were euthanized by the same method. Mice were anesthetized for cardiac geometry and functional assessment using a 2?D guide M?mode echocardiography at 8 h following injection of either PQ or saline. Results During myocardial damage due to PQ exposure in WT+PQ mice,obvious histopathological changes were observed,as well as a noticeable decrease of heart function and increased expressions of TNF?αand IL?1β. Compared with the WT mice,TNF?αand IL?1βprotein levels,changes in heart function and histopathological changes were significantly attenuated following PQ exposure in myocardial damage in TLR4?ko mice. Conclusion The TLR4gene is involved with in heart functional injury and histopathological changes in myocardial damage following PQ poisoning in mice,which may through the regulation of TNF?αand IL?1βexpression. Our findings indi?cate that TLR4 plays an important role in mediating myocardial injury due to PQ.

Objective: To compare the efficacy of different treatment protocols in treating transient synovitis of the hip (TSH) in children and to optimize the clinical treatment strategy for this condition. Methods: Ninety kids with TSH were divided into a control group, a chiropractic group and a chiropractic plus foot bath group using the random number table method, with 30 cases in each group. The control group was treated with conventional traction; the chiropractic group was given chiropractic treatment based on the control group; the chiropractic plus foot bath group was given Chinese medicine foot bath based on the chiropractic group. Traction and foot bath were conducted once daily while chiropractic was done once every other day, all with 14 d as a treatment course for a total of two courses. Changes in the visual analog scale (VAS) score and range of motion (ROM) of the hip joint in the three groups were observed, and the efficacy was compared. Results: The total effective rate was 93.3％ in the chiropractic plus foot bath group, versus 76.7％ in the chiropractic group and 66.7％ in the control group, and the total effective rate was notably higher in the chiropractic plus foot bath group than in the other two groups (both P<0.05). Respectively after the first and second treatment course, the VAS score decreased significantly in each of the three groups compared with that before treatment (all P<0.01), and the ROM of the hip joint in flexion increased significantly (all P<0.01). After two treatment courses, the VAS score was lower in the chiropractic plus foot bath group than in the other two groups (both P<0.05), and its ROM of the hip joint in flexion was larger than that in the other two groups (both P<0.05). Conclusion: Based on traction, chiropractic plus Chinese medicine foot bath can effectively reduce pain and improve motor function of the hip joint in treating TSH.

ObjectiveTo investigate the long term effect of different antihypertensive agents on renal hemodynamics with ultrasound Doppler.Methods52 essential hypertensive patients were divided into three groups according to the antihypertensive agent they took: angiotensin-converting-enzyme inhibitor (ACEI), calcium channel blocker (CCB) and β-adrenoceptor blocker (βB). The blood pressures of right upper arms were measured with mercury column blood pressure gauge using Korotkoff method. Renal hemodynamics were examined with ultrasound Doppler before and after treatment with agents. ResultsSystolic blood pressure (SBP) and diastolic blood pressure (DBP) of all patients were decreased significantly. An significant correlation was found between the deceases of blood pressure and the betterment of renal homodynamic parameters in ACEI and CCB groups, but not in βB group. ConclusionTo a degree, the betterment of renal hemodynamics is correlation with the reduction of systemic blood pressure and mechanism of action of antihypertensive agents.

OBJECTIVETo observe the effect of Chinese herbs for stasis removing and collaterals dredging (CHSRCD) upon angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis in the renal cortex of diabetic nephropathy rats.

METHODSTotally 89 male Sprague-Dawley rats were randomly divided into the blank control group (C group, n=22), the high-glucose high-fat control group (H group, n=10), and the streptozotocin (STZ)-injecting group (n=57). The diabetes rat model (n=50) was induced by feeding high-glucose high-fat diet in combination with intraperitoneal injection of STZ, which were further divided into the model group (M group, n=24), the irbesartan group (I group, n=13), and the CHSRCD (Z group, n=13). Rats in I and Z groups were intragastrically fed with suspension of irbesartan and CHSRCD, once daily for 16 weeks. Equal volume of drinking water was administrated to rats in the rest groups. Blood glucose and 24 h urine protein quantitation were tested at four time points. And the mRNA expression of ACE2 and Mas at various time points was detected by Real-time PCR, immunohistochemical assay, and Western blot. Quantitative analyses of ACE2 and Mas protein expression were performed at the end of week 16.

RESULTSCompared with the C group, blood glucose increased in the H and M groups (P < 0.01). It was higher in the H group (P < 0. 01). 24 h urine protein quantitation at different time points increased in the M group, and it was higher than that in the H group (P < 0.05). Compared with the M group, 24 h urine protein quantitation decreased at the end of week 8 in the I group, and at the end of week 8 and 16 in the Z group (P < 0.05). It was lower in the Z group than in the I group at the end of week 16 (P < 0.05). Compared with the C and H groups, the expression of ACE2 mRNA in the renal cortex was lower in the M group at the end of week 16 (P < 0.01). Compared with the M group, it was higher in the Z group (P < 0. 01). There was no statistical difference in the expressions of Mas mRNA at the end of week 16 between the C group and the M group (P > 0.05). It was lower in the M group than in the H group (P < 0.05). It was higher in the Z group than in the M group (P < 0.05), and higher than in the I group (P < 0.05). The expression of ACE2 and Mas protein in the M group decreased as time went by. The expression quantitation of ACE2 and Mas protein at the end of week 16 was lower in the M group than in the C group (P < 0.05). Compared with the M group, ACE2 expression of the Z group and Mas of the I and Z groups increased more significantly (P < 0. 05).

CONCLUSIONCHSRCD could play a role in renal protection for diabetic nephropathy rats by up-regulating the mRNA and protein expression of ACE2 and Mas, promoting the ACE2-Ang-(1-7)-Mas axis, and lowering urinary protein.

Angiotensin I ; metabolism ; Animals ; Diabetes Mellitus, Experimental ; metabolism ; Diabetic Nephropathies ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney Cortex ; metabolism ; Male ; Peptide Fragments ; metabolism ; Peptidyl-Dipeptidase A ; metabolism ; Proto-Oncogene Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism

We used metabolomics to investigate the ability of a traditional Mongolian medicine called modified Tabusen-2 (MT-2) to improve kidney yang deficiency (KYD) in rats. All animal experiments were conducted under the guidance and standards of the Medical Ethics Committee of Inner Mongolia Medical University. SD rats were divided into 6 groups of six rats: a normal group, a model group, Jinkuishenqi pill administration group (1.26 g·kg^-1), and MT-2 administration in high-, medium- and low-dose groups (1.512, 0.756, and 0.378 g·kg^-1). KYD was established by intramuscular injection of hydrocortisone (HC) and biochemical indicators and clinical characterization was used to confirm that KYD was established. All groups received intragastrically administered drug (Jinkuishenqi pill or MT-2) or saline. Serum from each group was collected after 8 weeks and analyzed by UPLC-Q-exactive-MS to measure various biochemical indicators. The biomarkers affected by MT-2 were identified and the metabolic pathways of KYD regulated by MT-2 were analyzed by metabolomic analysis. The results show that MT-2 can decrease serum creatinine (Cr) in KYD rats and significantly increase (P<0.05) the content of thyroid stimulating hormone (TSH) and luteinizing hormone (LH). In serum samples, 38 biomarkers such as corticosterone, L-phenylalanine, and DL-tryptophan were measured as possible indicators for disease development in KYD rats. MT-2 lowered 18 biomarkers of KYD, including corticosterone, deoxycorticosterone, and L-phenylalanine, and altered 13 related metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and steroid hormone biosynthesis, resulting in an overall improvement in KYD. MT-2 appears to be important in improving KYD in rats mainly by regulating metabolites such as amino acids, steroids and lipids.

ObjectiveTo investigate the relationship between the serum concentration of IL-6,S100β,NT-3 and the cognitive functions in first-episode schizophrenia characterized by positive or negative symptoms.Methods44 first-episode schizophrenic patients characterized by positive symptoms (positive group),36 first-episode schizophrenic patients characterized by negative symptoms (negative group) and 50 healthy controls (controls) were collected.The serum levels of IL-6,S100β and NT-3 were measured by enzyme-linked immunosorbent assay (ELISA).The systematic evaluation tool-MCCB was applied to assess cognitive function in patients and controls.ResultsNT-3 serum levels in positive or negative groups were lower than those in controls and the differences were significant((118.39±37.50) ng/L,(112.55±32.29) ng/L vs (141.18±29.67) ng/L) (P<0.01).IL-6 and S100β serum levels in positive or negative groups were higher than those in controls and the differences were statistically significant((5.74±1.00)ng/L,(5.07±1.17)ng/L vs (4.23±0.91)ng/L),((132.98±46.71)ng/L,(124.99±43.14)ng/L vs (103.63±31.57)ng/L)(P<0.01).IL-6 serum levels in the positive group ((5.07±1.17)ng/L) were lower than those in the negative group ((5.74±0.99)ng/L) and the difference was statistically significant (P<0.05).In MCCB test,the TMT scores in patients characterize by positive symptoms or patients characterize by negative symptoms were higher than those in healthy control group (P<0.01).BACS SC,HVLT-R WMS-Ⅲ,SS,NAB,BVMT-R,CF in patients characterize by positive symptoms or by negative symptoms were lower than those in healthy control group(P<0.01).There were no statistical difference in the MCCB scores between the patients with positive symptoms and negative symptoms.In positive group,there was a positive correlation between the IL-6 serum concentration and the general symptom scores in PANSS (P<0.05).In positive group,NT-3 serum concentration was positively correlated with the general symptom scores or total scores of PANSS (P<0.05).BVMT-R scores in MCCB were also positively correlated with IL-6 or NT-3 serum concentration in positive group (P<0.05).ConclusionThe impairment of part of cognitive functions for schizophrenic patients may be related to the serum protein factors.There may be different in pathophysiology between the first-episode schizophrenic patients characterized by positive symptoms and those characterized by negative symptoms.