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ObjectiveTo explore the mechanism of Jianpi Yishen Huazhuo prescription in the improvement of ovarian function in polycystic ovary syndrome (PCOS). MethodSeventy female SD rats in SPF grade were randomly divided into 6 groups, 15 in the blank group and 15 in the model group, 10 in the metformin group (0.1 g·kg-1·d-1), and 10 in the low (1.275 g·kg-1·d-1), medium (2.55 g·kg-1·d-1), and high-dose (5.10 g·kg-1·d-1) Jianpi Yishen Huazhuo prescription groups. The blank group was given normal saline (10 mL·kg-1·d-1) by gavage and ordinary feed, and the other groups were given letrozole (1 mg·kg-1·d-1) by gavage combined with high-fat feed for 21 days to induce the model of PCOS. After modeling, the blank group and model group were given equal volume normal saline by gavage, and each drug group was given the corresponding dose of the drug by gavage for 30 days. The changes in body mass and fasting blood glucose (FPG) of rats before and after modeling were compared. Hematoxylin eosin (HE) staining was used to observe the morphological change in the ovaries of rats in each group. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-Mullerian hormone (AMH), and estradiol (E2) were measured by enzyme-linked immunosorbent assay (ELISA), and the LH/FSH ratio was calculated. Immunohistochemical staining (IHC) and Western blot were used to detect the protein expression levels of nucleoside binding oligomerization domain protein like receptor 3 (NALP3), apoptosis-associated speck-like protein (ASC), cysteine protease-1 (Caspase-1), nuclear transcription factor-κB (NF-κB), interleukin-1β (IL-1β), interleukin-18 (IL-18), and interleukin-6 (IL-6) in the rat ovaries. ResultAs compared with the blank group, large follicles with polycystic expansion were found in the ovaries of the model group, no dominant follicles were found, the granular layer of follicles decreased and arranged loosely, and the number of corpus luteum decreased significantly. Serum T, LH, AMH and LH/FSH increased in the model group (P<0.05, P<0.01), while FSH and E2 decreased (P<0.05, P<0.01). The relative protein expression levels of NALP3, ASC, Caspase-1, NF-κB, IL-1β, IL-18, and IL-6 increased (P<0.05, P<0.01) in the ovaries of the model group. Compared with the model group, the low, medium, and high-dose Jianpi Yishen Huazhuo prescription groups and the metformin group showed growing follicles and corpus luteum at all levels, the number of cystic expanding follicles decreased, the thickness of follicular granular layer increased, the number of follicular fluid increased, mature follicles were visible, and the local morphology of oocytes was complete. Serum T, LH, AMH, and LH/FSH in these groups decreased (P<0.05, P<0.01), while E2 and FSH increased (P<0.05). The relative protein expressions of NALP3, ASC, Caspase-1, NF-κB, IL-1β, IL-18, and IL-6 in the ovaries of these groups decreased (P<0.05, P<0.01). There was no significant difference among the treatment groups. ConclusionBy inhibiting the activation of NLRP3 inflammasome, Jianpi Yishen Huazhuo prescription reduces the release of NALP3, ASC, Caspase-1, NF-κB, IL-18, IL-1β, and IL-6 inflammatory factors in ovarian tissues, regulates endocrine level, and effectively reduces PCOS inflammatory statu, so as to play a role in improving ovarian function.
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Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E2 levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.
Subject(s)
AMP-Activated Protein Kinases , Animals , Cyclin D2 , Female , Follicle Stimulating Hormone/therapeutic use , Humans , Luteinizing Hormone/therapeutic use , Metformin/pharmacology , Mice , Mice, Inbred C57BL , Oogonial Stem Cells/metabolism , Ovarian Cysts/drug therapy , Ovarian Neoplasms , Polycystic Ovary Syndrome/drug therapy , Proliferating Cell Nuclear Antigen/therapeutic use , TOR Serine-Threonine KinasesABSTRACT
OBJECTIVE@#To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy.@*METHODS@#A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted.@*RESULTS@#In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period.@*CONCLUSION@#HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883).
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OBJECTIVE@#To clarify the significance of inflammasome NLRP3 in children with immune thrombocytopenia (ITP) by detecting its changes before and after treatment.@*METHODS@#Twenty children with ITP diagnosed and treated in Xuzhou Children's Hospital were enrolled as observation group, and 10 healthy children as control group. The mRNA levels of NLRP3, ASC, and Caspase-1 were measured by real-time quantitative PCR (RT-qPCR), the serum levels of IL-18, IL-1β, and high mobility group protein B1 (HMGB1) were detected by ELISA, and the protein level of NLRP3 was detected by Western blot.@*RESULTS@#In newly diagnosed ITP children, the serum levels of IL-18, IL-1β and HMGB1 significantly decreased after treatment (P<0.05). After treatment, NLRP3, ASC, and Caspase-1 mRNA levels in peripheral blood mononuclear cells were significantly lower than those before treatment (P<0.05). NLRP3 protein expression decreased significantly after treatment.@*CONCLUSION@#Expression of NLRP3 inflammasome and downstream inflammatory factors are decrease after treatment in children with ITP, which may be used as effective prognostic markers.
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Child , HMGB1 Protein , Humans , Inflammasomes , Leukocytes, Mononuclear , NLR Family, Pyrin Domain-Containing 3 Protein , Purpura, Thrombocytopenic, IdiopathicABSTRACT
Objective To establish a method for determining the content of Gd3+ in gadoteric acid meglumine salt injection. Methods ICP-MS was used. The separation column was a metal chelate column (1-ml Chelating Sepharose column), column temperature was normal temperature. Flow rate was 1 ml/min. Injection volume was 500 μl. Atoms were measured by ICP-MS with a molecular weight of 157 (The molecular weight of Gd was 157). The carrier gas was argon. Results The linear range of Gd3+ mass concentration was 0-500 ng/ml (r=1.000); The precision, stability and repeatability of the sample recovery test were all in accordance with the requirements. Conclusion The method was simple in operation, accurate in results and good in repeatability, which could be used to determine the content of Gd3+ in gadoteric acid meglumine salt injection.
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To a certain extent, put forward the concept of " component of traditional Chinese medicine (TCM)" simplifies the complexity of multi-component and multi-target of TCM, which provides a possibility for the clarification of the material basis of the efficacy of TCM, and also provides a new direction for promoting the modernization and industrialization of TCM, promots the high quality development of TCM. The correlation between prescription and disease syndrome has made rapid progress, both basic research and clinical application are fruitful. However, the correlation between components and disease syndrome still needs to be further studied. The syndrome of blood stasis is a common syndrome of TCM science, and it is more common in various diseases, especially cardiovascular and cerebrovascular diseases, kidney disease, diabetes and hyperlipoidemia. A large number of studies have shown that some specific components contained in TCM or TCM compound can improve the related indexes of patients or experimental animal model with blood stasis syndrome. It is manifested in reducing blood viscosity, inhibiting platelet activation and adhesion aggregation, changing erythrocyte deformability index, inhibiting thrombosis and so on. Blood stasis is not only the pathogenic factor of many diseases, but also the pathological product of many kinds of diseases, which involves a wide range of diseases. Therefore, this study will study the progress of different components of TCM in the prevention and treatment of blood stasis syndrome, focusing on saponins, flavonoids, organic acids, polysaccharides, alkaloids and other active components in improving hemorheological abnormalities, hypercoagulability, platelet activation and adhesion aggregation, thrombosis. Based on the thought of component-disease syndrome, this paper searches the relevant literature in recent 20 years, classifies and summarizes the achievements of different components in the prevention and treatment of blood stasis syndrome, and hopes to provide some ideas for the further study of the pharmacological action of TCM components, the study of compatibility of TCM components and the research of TCM components.
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Objective To establish a method for concentration determination of garlic saponins PIEB in the rat plasma and study the pharmacokinetics of PIEB.Methods The separation was performed on a reverse phase Athena C18-WP (50mm×2.1mm, 3μm), with the mobile phase consisted of elution of acetonitrile-water (contain 0.05%formic acid) at a flow rate of 0.3ml/min.After intravenous and gavage administration, the blood samples of rats were collected in different time, and measured by LC-MS/MS.The pharmacokinetics parameters were calculated by Inna Phase Kinetica2000TMpharmacokinetics software.Results There was a good linearity of the calibration curves over the concentration range of 10-2 430ng/ml (r=0.999 1), and the investigation of methodology all accorded with the demands.After intravenous administration of 50mg/kg PIEB in rats, the maximum concentration of PIEB was achieved immediately.The t1/2of PIEB was about 322minutes and the MRT was 270minutes.After oral administration of low, medium and high concentrations of garlic saponin, the AUC and cmaxincreased with the increasing of dosage, which were consistent with the features of linear pharmacokinetics.Conclusion The established method was simple, accurate and sensitive, which could be suitable for the contents determination of garlic saponins PIEB in the rat plasma.
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OBJECTIVE@#To explore the role and the mechanism of NLRP3 inflammasome in children's immune thrombocytopenia (ITP).@*METHODS@#Twenty-one children suffered from ITP were enrolled in ITP group, 10 healthy children were selected in control group. Peripheral blood mononuclear cells (PBMNC) were isolated from ITP children and healthy controls. The mRNA levels of NLRP3, ASC, and Caspase-1 in PBMNCs were measured by quantitative real-time PCR. Moreover, the protein level of NLRP3 in PBMNCs was detected by Western blot. The plasma IL-18 level was detected by ELISA.@*RESULTS@#The expression level of NLRP3, ASC and Caspase-1 mRNA in newly-diagnosed ITP children was dramatically higher than that in control. The plasma IL-18 level was higher than that in healthy control. Furthermore, the level of NLRP3 protein was up-regulated in ITP children.@*CONCLUSION@#The NLRP3 inflammasome and up-regulated level of IL-18 have been found in newlydiagnosed ITP patients, and they may involve in the pathogenesis of ITP.
Subject(s)
Caspase 1 , Child , Humans , Inflammasomes , Leukocytes, Mononuclear , NLR Family, Pyrin Domain-Containing 3 Protein , Purpura, Thrombocytopenic, IdiopathicABSTRACT
·AIM:To compare the application effect on patients with retinopathy of prematurity (ROP) screened by wide-angle digital retinal imaging system (RetCam) and binocular indirect ophthalmoscope (BIO). ·METHODS:Totally 1624 cases(3248 eyes) of premature infants were detected by RetCam and BIO in our hospital from May 2014 to May 2017. The screening results of ROP and occurrence of adverse events were compared between two checking methods. ·RESULTS: In the 1 624 cases (3248 eyes) of premature infants,196 cases (392 eyes) of premature infants were detected by RetCam and 189 cases (378 eyes) of premature infants were detected by BIO, there was no statistical significance on staging results and partition pathological results between RetCam and BIO (P>0.05). Taking inspection result of BIO as standard, the sensibility, specificity, false positive rate and positive predictive value was 100. 00%, 99. 51%, 3. 57% and 96.43%, respectively. The adverse event rate of RetCam and BIO was 0.18% and 0.22%, respectively, there was no statistical significance (P>0.05). ·CONCLUSION:RetCam and BIO have similar application efficacy for screening ROP, and RetCam could take the place of BIO as the screening method of ROP.
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<p><b>OBJECTIVE</b>To investigate the expression of vasoactive intestinal peptide (VIP) in peripheral blood of children with hand, foot and mouth disease and its significance.</p><p><b>METHODS</b>According to the condition of the disease, 86 children with hand, foot and mouth disease were classified into phase 1 group (19 children) and phase 2 group (67 children). ELISA was used to measure the concentrations of plasma VIP, interferon-γ (IFN-γ), and interleukin-4 (IL-4) in peripheral blood. Flow cytometry was used to measure CD3, CD4, and CD8T lymphocyte subsets. RT-PCR was used for qualitative detection of enterovirus 71 (EV71) RNA in stool.</p><p><b>RESULTS</b>Compared with the phase 1 group, the phase 2 group had a significantly higher positive rate of EV71-RNA (P<0.05) and significantly higher serum levels of IgG, IgA, IgM, and C3 (P<0.05). The phase 2 group had significantly lower proportions of peripheral CD3, CD4, and CD8T lymphocyte subsets than the phase 1 group (P<0.05), as well as significantly lower proportion of peripheral B cells and CD4/CD8ratio than the phase 1 group (P<0.05). The phase 2 group also had a significantly lower concentration of VIP in peripheral blood than the phase 1 group (P<0.05). In the 86 children with hand, foot and mouth disease, the concentration of VIP in peripheral blood was positively correlated with the proportion of CD4T lymphocyte subset and CD4/CD8ratio (r=0.533 and 0.532 respectively; P<0.05).</p><p><b>CONCLUSIONS</b>VIP may be an important marker of the severity of hand, foot and mouth disease.</p>
Subject(s)
Biomarkers , CD4-CD8 Ratio , Child, Preschool , Female , Hand, Foot and Mouth Disease , Allergy and Immunology , Humans , Infant , Interferon-gamma , Blood , Interleukin-4 , Blood , Male , Severity of Illness Index , Vasoactive Intestinal Peptide , BloodABSTRACT
<p><b>OBJECTIVE</b>To identify the causative mutations in two Chinese Han families featuring triphalangeal thumbs (TPT) and preaxial polydactyly (PPD).</p><p><b>METHODS</b>Blood samples were collected from 9 members (2 affected) from family 1 and 14 members (7 affected) from family 2. After genomic DNA was extracted, the ZPA regulatory sequence (ZRS) region was analyzed with real-time quantitative PCR (qPCR) and Sanger sequencing. For family 1, haplotypes compassing the ZRS were also analyzed with short tandem repeats (STR) and single nucleotide changes.</p><p><b>RESULTS</b>No copy number mutation around the ZRS region was found in both families. Two heterogeneous mutations in the ZRS (406A>G and 105C>G) were found to co-segregate with the TPT/PPD malformation in family 1 and 2, respectively. Neither mutation was detected in 200 healthy individuals. Haplotype analysis and Sanger sequencing of family 1 indicated that the first TPT/PPD patient in the family was both germline and somatic mosaic for the 406A>G mutation.</p><p><b>CONCLUSION</b>Two pathogenic ZRS mutations, 105C>G and 406A>G, have been identified in two Chinese Han families with TPT/PPD, among which the 406A>G mutation was de novo.</p>
Subject(s)
Asian People , Genetics , Female , Hand Deformities, Congenital , Genetics , Haplotypes , Humans , Male , Mutation , Polydactyly , Genetics , Regulatory Sequences, Nucleic Acid , Thumb , Congenital AbnormalitiesABSTRACT
Objective To optimize the synthesis of photosensitizer chlorine e6‐C15 monomethyl ester (1) .Methods Tar‐get compound 1 was synthesized through E ring cracking of pheophorbide a (3) in methanol solution of potassium hydroxide followed by adding H2 O for ester hydrolysis with“one‐pot” process .Four main factors that influencing the synthetic yield of target compound 1 are ring cleavage reaction time (A) ,reflux hydrolysis reaction time (B) ,alkali concentration (C) and weight ratio of material 3 to alkali (D) .Each of the four factors was chosen at three levels and evaluated by the orthogonal ex‐perimentaldesignofL9(34).Results Theoptimizationtermsofthesynthesisoftargetcompound1wereB1C2A2D1 .Theyield of compound 1 was raised from 43 .0% to 56 .5% .Conclusion The developed process has the advantages of simple operation , good safety and high reaction yield ,and is suitable for industrial production .
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Objective To investigate the influence of non-dipper blood pressure rhythm on peripheral atherosclerosis in elderly hypertensive patients.Methods The 199 elderly hypertensive patients with 24-hour average systolic blood pressure<140 mmHg were selected.Body mass index (BMI),glycosylated hemoglobin,blood lipids,uric acid,creatinine,Brachial ankle pulse wave velocity (baPWV),ankle arm index(ABI) and 24-hour ambulatory blood pressure monitoring were tested and calculated.The elderly patients were divided into dipper hypertensive group (n=95),and non-dipper hypertensive group (n=104).The relationships of arteriosclerosis with lifestyle and the circadian rhythm of blood pressure (non-dipper hypertension) were analyzed.Results Circadian blood pressure rhythm,age,levels of total cholesterol,triglyceride and serum creatinine,nocturia times,and smoking index were significantly related with atherosclerosis.There was a relationship between circadian blood pressure rhythm and baPWV,with the greatest standardized regression coefficient of 0.439.There were obviously linear relationships between levels of serum creatinine,nocturia times,age and ABI.There were significant differences in baPWV,ABI and smoking index between dippers and non-dippers groups [(1746.0±246.9) vs.(2115.7±321.8),(1.14±0.10) vs.(1.11±0.18),(251.8±272.8) vs.(368.5±339.9),P<0.05 or 0.001].The multiple linear regression analysis showed that smoking index was significantly correlated with baPWV,but not correlated with blood pressure rhythm.In the ROC curve of MAP difference percentage and baPWV diagnosis result,the area under the curve was 0.8188,the optimal cut-off was 10.9%,the sensitivity was 62.5% and the specificity was 85.7%.In the ROC curve of MAP difference percentage and AMI diagnosis result,the area under the curve was 0.7589,the optimal cut-off was 8.1%,the sensitivity was 88%,and the specificity was 61%.These results reflected that there were better consistences between MAP difference percentage and baPWV,ABI,and indirectly indicted that there was a relationship between MAP difference percentage and atherosclerosis.Conclusions We advise the elderly patients to give up the bad habits,help them control the systolic blood pressure,and advise them to adjust the medication time according to the circadian rhythm of blood pressure of every elderly hypertensive patient in order to restore the normal circadian blood pressure rhythm and delay the atherosclerotic process.
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BacKground:Lymphocyte function-associated antigen-1( LFA-1 ) pIays a cruciaI roIe in the pathogenesis of infIammatory boweI disease by reguIating the activation and function of T ceIIs. Aims:To investigate the effect of LFA-1 deficiency( LFA-1-/-)on differentiation of mice na?ve T ceIIs into Th17 ceIIs in vitro. Methods:LFA-1-/- mice were breeded and the progeny genome DNA was extracted from the taiIs for genotyping by PCR. CD4+CD62L+ na?ve T ceIIs were separated from spIenic mononucIear ceIIs of LFA-1-/- progeny mice and wiId type ( WT ) C57BL/6J mice, respectiveIy,by magnetic-activated ceII sorting( MACS),and then the purity of separated ceIIs was determined. Na?ve T ceIIs obtained were cuItured in different inducing systems[ transforming growth factor-β( TGF-β),TGF-β + interIeukin-6 (IL-6),and TGF-β + IL-6 + IL-23]in vitro for Th17 ceII differentiation;ceIIs in each inducing system were coIIected for anaIyzing the ratio of Th17 ceIIs by fIow cytometry,and the expressions of Th17-specific transcription factor ROR-γt and Th17-specific marker IL-17A were measured by qRT-PCR and ELISA methods. Results:AII fifteen progeny mice were identified as LFA-1-/- genotype. Purity of CD4+CD62L+ na?ve T ceIIs separated by MACS was above 95%. Th17 ceIIs couId be induced by Iow-dose TGF-βcombined with IL-6,and the differentiation ratio was increased obviousIy when IL-23 was added. In inducing system containing TGF-β,IL-6 and IL-23,na?ve T ceIIs from LFA-1-/- mice produced more Th17 ceIIs than those from WT mice(17. 2% ± 1. 4% vs. 5. 7% ± 0. 2%,P<0. 001),expressions of ROR-γt mRNA and IL-17A mRNA were up-reguIated(P<0. 001),and IL-17A concentration in ceII cuIture supernatant was increased(P<0. 01). Conclusions:Deficiency of LFA-1 promotes the differentiation of mice na?ve T ceIIs into Th17 ceIIs in vitro.
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This study was aimed to clone the gene coding mouse CXC chemokine receptor 4 (CXCR4), to construct the recombinant lentiviral vector carrying enhanced green fluorescence protein (EGFP) and to explore its expression in eukaryotic cells (293FT cells). The full length CXCR4 gene was cloned by RT-PCR using bone marrow cells from C57BL/6 mouse as template and inserted into PCR-Blunt vector. CXCR4 fragment was generated by digestion with restriction endonuclease and subcloned into a lentiviral vector to generate recombinant lentiviral vector LV-IRES-EGFP-CXCR4, which was co-transfected into 293FT cells together with envelope plasmid and packaging plasmid by lipofectamine 2000. Viruses were gathered and concentrated using ultracentrifuge, and then transfected into 293FT cells. Expression of EGFP was detected by fluorescent microscopy and flow cytometry (FCM). And the expression of CXCR4 protein was detected by Western blot. The results demonstrated that mouse CXCR4 gene was cloned and the lentiviral vector was successfully constructed. The lentiviral particles were correctly packaged, and the virus titers were above 10(8) TU/ml in the supernatant after concentration. Expression of EGFP was detected by fluorescent microscopy in the transfected 293FT cells, and the transfection efficacy > 95% was determined by FCM. Expression of CXCR4 protein detected by FCM and Western blot was significantly higher than that in control group. It is concluded that the CXCR4 gene along with the gene coding EGFP is successfully inserted into a lentiviral vector to construct a recombinant lentiviral vector, which can be expressed in eukaryotic cells.
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Animals , Cell Line , Gene Expression , Genetic Vectors , Green Fluorescent Proteins , Genetics , Humans , Lentivirus , Genetics , Mice , Mice, Inbred C57BL , Plasmids , Receptors, CXCR4 , Genetics , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To determine the role of chemokine receptor 2 (CCR2) in the development of salt-sensitive hypertension-induced renal damage.</p><p><b>METHODS</b>We investigated the renal damage induced by uninephrectomy and deoxycorticosterone acetate (DOCA)-salt in mice treated with or without a selective CCR2 antagonist RS504393 for 4 weeks. Sham mice underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, creatinine clearance, glomerulosclerosis, renal tubulointerstitial injury, and renal monocyte/macrophage infiltration were measured.</p><p><b>RESULTS</b>DOCA-salt treatment led to increased systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, decreased creatinine clearance, glomerulosclerosis, renal tubulointerstitial injury, and renal monocyte/macrophage infiltration compared with the sham mice (P<0.05). All of them were prevented by CCR2 inhibition (P<0.05).</p><p><b>CONCLUSION</b>Blockade of CCR2 prevents renal damage induced by DOCA-salt treatment, suggesting that CCR2-mediated monocyte/macrophage infiltration may contribute to salt-sensitive hypertension-induced renal injury.</p>
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Animals , Disease Models, Animal , Hypertension , Kidney , Male , Mice , Mice, Inbred C57BL , Receptors, CCR2 , Metabolism , Sodium Chloride, Dietary , ToxicityABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effects of oxysophoridine (OSR) on primary cultured hippocampus neurons subjected to anoxia injury in neonatal rats and its mechanism.</p><p><b>METHOD</b>The model of anoxia injury of hippocampus neurons in neonatal rats were primarily cultured in vitro by physical oxygen deficiency using glucose-free culture fluid. The survival rate of neurons, the leaking rate of lactate dehydrogenase (LDH), the intracellular contents of malondialdehyde (MDA) and nitric oxide (NO), the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and nitric oxide synthase (NOS) were measured. The intracellular free calcium concentration ([Ca2+]i) in hippocampus neurons were detected with Ca(2+)-sensitive dual wavelength fluorescence spectrophotometer.</p><p><b>RESULT</b>Neuron death occurred in the anoxia injury model group with increase of LDH leaking rate, the contents of NO, MDA, intracellular [Ca2+] and the elevated activity of NOS while decreased activities of SOD and GSH-PX. The hippocampus neurons subjected to anoxia injury were alleviated in OSR (0.625, 5, 10 microg x L(-1)) group.</p><p><b>CONCLUSION</b>OSR has significant protective effects on hippocampus neurons subjected to anoxic injury. The mechanism of its protective effect may relate to its reduction of calcium overload and against oxidation injury.</p>
Subject(s)
Alkaloids , Animals , Cells, Cultured , Drugs, Chinese Herbal , Female , Glutathione Peroxidase , Metabolism , Hippocampus , Cell Biology , Metabolism , Humans , Hypoxia , Drug Therapy , Metabolism , Malondialdehyde , Metabolism , Neurons , Cell Biology , Metabolism , Nitric Oxide Synthase , Metabolism , Protective Agents , Rats , Rats, Sprague-Dawley , Sophora , Chemistry , Superoxide Dismutase , MetabolismABSTRACT
<p><b>BACKGROUND</b>Glycoprotein non-metastatic melanoma protein B (GPNMB) plays an important role in the pathogenesis of inflammatory and malignant diseases. We investigated the expression of GPNMB in benign and malignant skin diseases.</p><p><b>METHODS</b>Tissue microarray was performed in the skin tissues of 102 cases including malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and benign dermatosis. The expression of GPNMB in the tissues was detected by immunohistochemistry. Twenty cases of normal skin and adjacent neoplastic normal skin tissues were selected as controls.</p><p><b>RESULTS</b>GPNMB was positively stained in skin malignancies (38/50, 76%), which was significantly higher than that in the control and the benign skin tissues (P = 0.001 and < 0.001 respectively). GPNMB was positively stained in MM (13/15, 87%) and SCC (16/20, 80%) (P < 0.001). Significant higher expression of GPNMB was observed in patients aged ≥ 65 years than those less than 65 years (n = 11 and n = 9 respectively, P = 0.027). No significant difference of the expression rates was observed between normal control and BCC; however, stronger intensity was detected in the latter. Negative or weak expression was observed in the controls.</p><p><b>CONCLUSION</b>Over-expression of GPNMB correlated strongly and might play an important role in the pathogenesis of MM and SCC.</p>
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Adolescent , Adult , Aged , Carcinoma, Basal Cell , Metabolism , Carcinoma, Squamous Cell , Metabolism , Female , Humans , Immunohistochemistry , Male , Melanoma , Metabolism , Membrane Glycoproteins , Metabolism , Middle Aged , Skin , Metabolism , Pathology , Skin Diseases , Metabolism , Skin Neoplasms , Metabolism , Tissue Array Analysis , Methods , Young AdultABSTRACT
A case of hereditary benign telangiectasia without family history was reported. A 39-year-old woman presented with small and tiny telangiectases on the face, neck, upper trunk and forearms at birth. The numbers and sizes of the lesions increased gradually and she had no hemorrhagic diathesis and systemic diseases. No similar patients were found in her family. Upon physical examination, telangiectases were found on the face, neck, upper trunk and forearms; and a telangiectatic erythema was found on the right forearm 25 mm × 40 mm in size. Histopathology examination showed a normal epidermis and dilation of the capillaries at upper dermis. Hereditary benign telangiectasia without family history was diagnosed.
Subject(s)
Adult , China , Female , Genetic Diseases, Inborn , Diagnosis , Humans , Telangiectasis , DiagnosisABSTRACT
Objective To explore the correlation of the operation effects of the miorovascular decompression(MVD) and the findings on magnetic resonance tomographic angiography(MRTA) in patients of neurovascular compression of the cranial nerves.Methods Two hundred and twenty three patients treated with the microvascular decompression were analyzed retrospectively.They were grouped and graded according to the vessel compression on the cranial nerves.The compression were grouped as none, moderate and severe, and the operation effects were graded as Ⅰ ( complete relief), Ⅱ ( partial relief) and Ⅲ ( no relief).The operation effects grades were correlated according to the compression groups by Kruskal-Wallis test and the operation effects between each two of the groups were compared using Nemenyi test.P < 0.05 was defined as statistic significant.Results Of the 53 cases of non-compression group, 31 cases were graded as Ⅰ , 13 cases were graded as Ⅱ and 9 cases were graded as Ⅲ, according to the operation-effects of the decompression.Of the 110 cases of moderate group,95 cases were grade as Ⅰ , 11 cases were graded as Ⅱ and 4 cases were graded as Ⅲ.Of the 60 cases of severe group, 48 cases were graded as Ⅰ, 7 cases were graded as Ⅱ and 5 cases were graded as Ⅲ.There were statistic significance among the three groups,where χ2= 16.84 and P <0.05.The mean rank of the non-compression, the moderate and the severe group was 134.21,102.37 and 110.4 ,respectively.The difference of the mean ranks between the non-compression group and the moderate group was 31.84, and between the non-compression and the severe group was 24.17, respectively, where P < 0.05 both.Conclusions There was close relationship between the findings on magnetic resonance tomographic angiography and the operation effects of the MVD.The operation effects of patients with moderate and severe vessel compression were much better than the non-compression group.MRTA is helpful for MVD surgical indication and its prognosis.