ABSTRACT
To explore the biological characteristics related to the pathogenesis and severity of respiratory syncytial virus (RSV) bronchiolitis by RNA sequencing of white blood cells in children with RSV bronchiolitis. This study is a case-control study. A total of 87 children diagnosed with bronchiolitis and RSV antigen positive and/or RSV nucleic acid positive in the pediatric respiratory department of the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to April 2022 were selected as the case group. The case group was divided into three groups based on the condition: mild, moderate, and severe, and there were two groups according to the presence or absence of atopic symptoms: the atopic group and the non-atopic group, forty healthy children in the same period were selected as the control group. The whole blood leukocyte RNA of the children in the case group and the control group was extracted for RNA sequencing, and the data were analyzed to obtain differentially expressed genes (DEGs). Then, the immunobiological pathways and genes related to the pathogenesis, disease condition, and atopy were screened through Gene Ontology (GO) annotation, Kyoto Gene and Genome Encyclopedia (KEGG) annotation, and protein interaction network (PPI) construction methods. Construct the weighted gene co-expression network analysis (WGCNA) module to identify potential biological indicators related to disease severity.Compared with the control group, the case group had a total of 1 782 DEGs, including 1 586 upregulated genes and 196 downregulated genes. The GO pathway enrichment of DEGs is mainly enriched in molecular functions such as peroxidase activity and oxidoreductase activity. In the cytological components, it is mainly enriched in cytoplasmic vesicle lumen and secretory granule lumen. In biological processes, it is mainly enriched in processes such as neutrophil activation involved in immune responses, neutrophil degranulation, and neutrophil activation. KEGG analysis is mainly concentrated in the signal pathway of the viral protein interaction with cytokine and cytokine receptor. A PPI network was constructed to screen four genes at the core position, including CCL2, IL-10, MMP9 and JUN. The DEGs obtained by comparing different disease groups with the control group are mainly enriched in retrograde endocannabinoid signaling and cell apoptosis pathways. WGCNA analysis showed that the brown module related to oxygen saturation was most closely related to the disease, and its gene was mainly enriched in the RNA helicase retinoic acid inducible gene-I (RIG-I) like receptor signal pathway. There are 230 specific DEGs in the atopic group and 444 in the non-atopic group. KEGG enrichment analysis results show that both groups are enriched to NF-κB signaling pathway, the characteristic does not cause significant changes in immune response and transcriptome characteristics in children with RSV bronchiolitis. In conclusion, neutrophil activation, degranulation pathway and signal pathway of interaction between viral protein and cytokine and cytokine receptor are involved in the immune response of RSV bronchiolitis host. CCL2, IL-10, MMP9 and JUN genes may be associated with the pathogenesis. They might be potential biomarkers related to disease severity in RIG-I like receptors, cell apoptosis, and endogenous cannabinoid related signaling pathways.
Subject(s)
Child , Humans , Transcriptome , Interleukin-10 , Matrix Metalloproteinase 9 , Case-Control Studies , Sequence Analysis, RNA , Respiratory Syncytial Virus Infections/genetics , Receptors, Cytokine , Viral Proteins , Respiratory Syncytial Viruses , Computational Biology/methodsABSTRACT
To explore the biological characteristics related to the pathogenesis and severity of respiratory syncytial virus (RSV) bronchiolitis by RNA sequencing of white blood cells in children with RSV bronchiolitis. This study is a case-control study. A total of 87 children diagnosed with bronchiolitis and RSV antigen positive and/or RSV nucleic acid positive in the pediatric respiratory department of the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to April 2022 were selected as the case group. The case group was divided into three groups based on the condition: mild, moderate, and severe, and there were two groups according to the presence or absence of atopic symptoms: the atopic group and the non-atopic group, forty healthy children in the same period were selected as the control group. The whole blood leukocyte RNA of the children in the case group and the control group was extracted for RNA sequencing, and the data were analyzed to obtain differentially expressed genes (DEGs). Then, the immunobiological pathways and genes related to the pathogenesis, disease condition, and atopy were screened through Gene Ontology (GO) annotation, Kyoto Gene and Genome Encyclopedia (KEGG) annotation, and protein interaction network (PPI) construction methods. Construct the weighted gene co-expression network analysis (WGCNA) module to identify potential biological indicators related to disease severity.Compared with the control group, the case group had a total of 1 782 DEGs, including 1 586 upregulated genes and 196 downregulated genes. The GO pathway enrichment of DEGs is mainly enriched in molecular functions such as peroxidase activity and oxidoreductase activity. In the cytological components, it is mainly enriched in cytoplasmic vesicle lumen and secretory granule lumen. In biological processes, it is mainly enriched in processes such as neutrophil activation involved in immune responses, neutrophil degranulation, and neutrophil activation. KEGG analysis is mainly concentrated in the signal pathway of the viral protein interaction with cytokine and cytokine receptor. A PPI network was constructed to screen four genes at the core position, including CCL2, IL-10, MMP9 and JUN. The DEGs obtained by comparing different disease groups with the control group are mainly enriched in retrograde endocannabinoid signaling and cell apoptosis pathways. WGCNA analysis showed that the brown module related to oxygen saturation was most closely related to the disease, and its gene was mainly enriched in the RNA helicase retinoic acid inducible gene-I (RIG-I) like receptor signal pathway. There are 230 specific DEGs in the atopic group and 444 in the non-atopic group. KEGG enrichment analysis results show that both groups are enriched to NF-κB signaling pathway, the characteristic does not cause significant changes in immune response and transcriptome characteristics in children with RSV bronchiolitis. In conclusion, neutrophil activation, degranulation pathway and signal pathway of interaction between viral protein and cytokine and cytokine receptor are involved in the immune response of RSV bronchiolitis host. CCL2, IL-10, MMP9 and JUN genes may be associated with the pathogenesis. They might be potential biomarkers related to disease severity in RIG-I like receptors, cell apoptosis, and endogenous cannabinoid related signaling pathways.
Subject(s)
Child , Humans , Transcriptome , Interleukin-10 , Matrix Metalloproteinase 9 , Case-Control Studies , Sequence Analysis, RNA , Respiratory Syncytial Virus Infections/genetics , Receptors, Cytokine , Viral Proteins , Respiratory Syncytial Viruses , Computational Biology/methodsABSTRACT
Objective: To investigate the morbidity of chronic obstructive pulmonary diseases (COPD) in residents aged 30 years and above in Sichuan Province, and analyze the effect of smoking on the risk of morbidity on COPD. Methods: From 2004 to 2008, people were randomly selected from Pengzhou, Sichuan Province. All the local people aged 30-79 years were asked to receive questionnaire survey, physical examination and pulmonary function testing, and long-term follow-up to determine the morbidity of COPD. Cox proportional hazard regression model was used to analyze the relationship between smoking and COPD. Results: In 46 540 participants, the current smoking rates were 67.31% in males and 8.67% in females, there were 3 101 new cases of COPD, with a cumulative incidence of 6.66%. Adjusted for age, gender, occupation, marriage, income level, educational level, BMI, daily total physical activity, current cooking frequency, whether there was smoke exhaust device at present and frequency of passive smoking exposure, multivariate Cox proportional hazard regression analysis showed that compared with the non-smoking population, current smoking and quitting smoking increased the risk of COPD, with HR of 1.42 (95%CI:1.29-1.57) and 1.34 (95%CI:1.16-1.53). Compared with people who never or occasionally smoke, the risk of morbidity on COPD increased with the increase of average daily smoking volume, mixed smoking at present, mixed smoking at the beginning increased the risk of COPD, with HR of 1.79 (95%CI: 1.42-2.25) and 2.12 (95%CI: 1.53-2.92), started smoking at the age of <18 years old and ≥18 years old increased the risk of COPD, with HR of 1.61 (95%CI:1.43-1.82) and 1.34 (95%CI: 1.22-1.48), inhaling into the mouth, throat and lung during smoking increased the risk of COPD, with HR of 1.30 (95%CI: 1.16-1.45), 1.63 (95%CI: 1.45-1.83) and 1.37 (95%CI: 1.21-1.55). Adjusted for multiple confounding factors and adjusted for regression dilution bias, the average daily smoking volume, the age of starting smoking and the depth of smoking inhalation had an impact on the incidence of COPD, and the gender difference was particularly prominent. Conclusions: Smoking increased the risk of morbidity on COPD, which was related to the average daily smoking volume, the type of smoking, the age of starting smoking and the depth of smoking inhalation. Tobacco control should comprehensively consider the specific characteristics of smoking, so as to prevent COPD.
Subject(s)
Female , Male , Humans , Adolescent , Prospective Studies , Smoking , Morbidity , Pulmonary Disease, Chronic Obstructive , ChinaABSTRACT
Objective: Rehmanniae Radix has been traditionally used to treat diabetes. Catalpol (CAT) and stachyose (STA) are two of the main bioactive compounds in Rehmannia Radix and found to have similar therapeutic effects on diabetes and its complications. In this paper, we aimed to investigate whether there were synergistic therapeutic effects of CAT and STA on diabetes. Methods: Streptozotocin (STZ) with the feeding of high-sugar-high-fat diet (HFD) was applied to induce diabetic C57BL/6 mice. STZ-HFD induced diabetic mice were then divided into model and six medical-treated groups: metformin (MET), STA, CAT, and three combinations of CAT:STA (1:1, 1:2, 2:1). Blood, liver, and kidney samples were isolated after six-week oral administration for biochemical assays of serum lipids, the indicators of kidney and liver functions and HE staining for liver tissues. Results: It turned out that CAT, STA and their three combinations (1:1, 1:2, 2:1) could effectively control body weight, blood glucose, kidney weight and liver weight index, and well regulate levels of TC, HDL-c, TG, ALT, and TBA. In addition, CAT and its combination with STA at the ratio of 2:1 could significantly improve albumin content, compared to that in model group. STA and CAT and their combinations showed the improvements on kidney function in terms of urinary creatinine (Ucr). However, there were no such consistent observations on serum creatinine (Scr) and creatinine clearance rate (Ccr). The combination of CAT and STA at the ratio of 1:1 exhibited the better adjusting effects on kidney weight and liver weight indexes and the levels of ALT, Ucr, Scr, and Ccr. Our results demonstrated that the combinations of CAT and STA especially 1:1 showed similar or better improvements on diabetes-associated complications, compared to the sole CAT or STA treatment. Conclusion: Thus, we concluded that there were synergistic therapeutic effects between CAT and STA on STZ/HFD-induced type 2 diabetes. This project provided insights and technical supports for the innovation of discovering bioactive constituents in Rehmannia Radix and studying its integrative mechanism in curing diabetes.
ABSTRACT
BACKGROUND: Induced pluripotent stem cells hold enormous potential as a tool to generate cells for disease therapy and modeling. However, the lower efficiency of cell reprogramming using exogenous transcription factors limits the clinical use of induced pluripotent stem cells. Recent studies have indicated that microenvironmental cues can promote the production of pluripotent cells. Further summarization on these reports will provide new strategies to enhance the safety and efficiency of the reprogramming technology. OBJECTIVE: To summarize the effect of microenvironmental cues on the reprogramming of somatic cells to induced pluripotent stem cells and the maintenance of pluripotency. METHODS: Scientific papers from 2006 to present included in Web of Science were searched by the first author. Eighty papers focusing on the effect of microenvironmental cues on the reprogramming of somatic cells to induced pluripotent stem cells and the maintenance of pluripotency were included. RESULTS AND CONCLUSION: Cell-matrix interaction and cell-cell adhesion regulate gene expression and have effects on the epigenetic states of the chromatin through a direct connection between actin cytoskeletons and the nuclear membrane; thus, manipulation of the cell-matrix interaction and cell-cell adhesion can improve the induction of pluripotency. In addition, other environmental factors including hypoxia, dynamic culture and electrical stimulation can also promote cell reprogramming.
ABSTRACT
OBJECTIVE@#To find out the prevalence of respiratory syncytial virus (RSV) genotypes in southern Zhejiang Province, China, and to study the genetic characteristics of G protein from subtype A of RSV.@*METHODS@#The lower respiratory tract secretions of children under 5 years of age who were hospitalized for pneumonia and bronchiolitis in three hospitals in southern Zhejiang Province from July 2009 to June 2014 were collected. Direct immunofluorescence assay was used to detect RSV antigens from the collected secretions. A total of 200 samples were randomly selected from RSV-positive specimens in each prevailing year (from July of a specific year to June of the next year). RT-PCR was used to determine RSV subtypes, and the near-full length gene sequence of G protein from subtype A was amplified and sequenced to identify the genotype.@*RESULTS@#A total of 25 449 samples of lower respiratory tract secretions were collected from 2009 to 2014, among which 6 416 (25.21%) samples were RSV-positive. Among the 1 000 RSV-positive specimens randomly sampled, 462 strains (46.2%) were subtype A, and 538 strains (53.8%) were subtype B. Subtype A accounted for 22.5%, 74.5%, 84.5%, 19.0%, and 30.5% of the total strains in each year from 2009 to 2014. A total of 25 RSV subtype A strains were randomly sampled and sent out for bidirectional sequencing in each year, which confirmed 52 positive subtype A strains. Four genotypes of subtype A strains were obtained from the above strains, including NA1 (39 strains), NA4 (1 strain), ON1 (10 strains), and GA2 (2 strains). NA1 was the dominant genotype between 2009 and 2012, and ON1 was the only genotype of subtype A during 2013-2014. The nucleotide homology and amino acid homology between the G protein of subtype A and the prototype strain A2 were 80.7%-89.3% and 74.4%-82.6%, respectively. The nucleotide homology and amino acid homology between the isolates of subtype A were 81.5%-100% and 80.2%-100%, respectively.@*CONCLUSIONS@#In southern Zhejiang Province from 2009 to 2014, there was a co-circulation of RSV subtypes A and B, as well as a co-circulation of several different genotypes of RSV subtype A, which had highly variable G protein genes.
Subject(s)
Child, Preschool , Humans , Infant , Infant, Newborn , China , Epidemiologic Studies , Genotype , Phylogeny , Respiratory Syncytial Virus Infections , Epidemiology , Respiratory Syncytial Virus, HumanABSTRACT
A large number of epidemiological data have shown that the high-density lipoprotein cholesterol level is negatively related to atherosclerotic cardiovascular disease, suggesting that high-density lipoprotein may have the effect of anti-atherosclerosis. It may play the role of anti-atherosclerosis, through the promotion of cholesterol reverse transport, anti-inflammatory, antioxidant, and against thrombosis and fibrinolysis and so on. Among them, reverse cholesterol transport which is mainly regulated by apolipoprotein A-I, ATP-binding cassette transporter 1, liver X receptor and cholesteryl ester transfer protein, may play a major role in the maintenance of cholesterol homeostasis and reversing the course of atherosclerosis. These regulatory factors may be potential targets in high density lipoprotein-based drug discovery. In this review, these key proteins are discussed for the current status of small molecule drugs against atherosclerosis.
ABSTRACT
Objective: To investigate the water-soluble phenolic acids from Clerodendranthus spicatus of Dai medicine. Methods: The chemical constituents were separated and purified by D101, Sephadex LH-20, MCI, and preparative HPLC column chromatographies. Their structures were determined by physicochemical properties and spectral data analyses. Results: Sixteen constituents were isolated and elucidated as protocatechualdehyde (1), protocatechuic acid (2), 3, 5-dihydroxybenzaldehyde (3), 4-hydroxybenzoic acid (4), 4-hydroxybenzaldehyde (5), vanillic acid (6), danshensu methyl ester (7), 3, 5-O-dimethyl gallic acid (8), helisterculins A (9), lithospermic acid (10), methyl lithospermate (11), dimethy lithospermate (12), helisterculins B (13), ethyl dihydrocaffeate (14), ferulic acid (15), and dihydroferulic acid (16). Conclusion: Compounds 3, 6-9, and 13-16 are obtained from Clerodendranthus Kudo for the first time.
ABSTRACT
<p><b>BACKGROUND</b>Few studies have addressed whether abnormalities in the lenticular nucleus (LN) are characteristic transcranial sonography (TCS) echo features in patients with primary dystonia. This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia.</p><p><b>METHODS</b>cross-sectional observational study was performed between December 2013 and December 2014 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects. TCS was performed in patients and control subjects. Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups.</p><p><b>RESULTS</b>Thirteen individuals were excluded due to poor temporal bone windows, and two subjects were excluded due to disagreement in evaluation by sonologists. Totally, 70 patients (cervical dystonia, n = 30; blepharospasm, n = 30; oromandibular dystonia, n = 10) and 50 normal controls were included in the final analysis. LN hyperechogenicity was observed in 51% (36/70) of patients with primary focal dystonia, compared with 12% (6/50) of controls (P < 0.001). Substantia nigra hyperechogenicity did not differ between the two groups. LN hyperechogenicity was observed in 73% (22/30) of patients with cervical dystonia, a greater prevalence than in patients with blepharospasm (33%, 10/30, P = 0.002) and oromandibular dystonia (40%, 4/10, P = 0.126). LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls (73% vs. 12%, P < 0.001); however, no significant difference was detected in patients with blepharospasm (33% vs. 12%, P = 0.021) or oromandibular dystonia (40% vs. 12%, P = 0.088).</p><p><b>CONCLUSIONS</b>LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls. It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Blepharospasm , Diagnostic Imaging , Corpus Striatum , Diagnostic Imaging , Cross-Sectional Studies , Dystonic Disorders , Diagnostic Imaging , EchoencephalographyABSTRACT
<p><b>OBJECTIVE</b>To compare the epidemiological and clinical features of lower respiratory tract infection (LRTI) caused by influenza virus A (IVA) and influenza virus B (IVB) in children.</p><p><b>METHODS</b>The clinical data of 366 children with LRTI caused by influenza virus (IV), who were hospitalized in Yuying Children′s Hospital of Wenzhou Medical University between 2010 and 2014, were analyzed retrospectively, and there were 272 cases caused by IVA and 94 cases caused by IVB.</p><p><b>RESULTS</b>IV was mainly prevalent from December to March of the next year, with the predominance of IVA. There were small peaks of IVA prevalence in July or September every other year, and IVB was prevalent from December to March of the next year every other year. The children with LRTI caused by IVA alone had a significantly higher white blood cell (WBC) count and significantly higher percentages of children with increased WBC, abnormal serum sodium, and abnormal serum potassium than those caused by IVB alone (P<0.05). However, there were no significant differences in age, sex, underlying diseases, clinical manifestations, and co-infection rate with bacteria or atypical pathogens between the two groups (P>0.05). The rate of co-infection with respiratory syncytial virus (RSV) was significantly higher in the IVB group than in the IVA group (P<0.01).</p><p><b>CONCLUSIONS</b>IVA is prevalent in winter and spring every year and has small peaks in summer every other year, while IVB is prevalent in winter and spring every other year. Compared with IVB, IVA causes more cases of increased WBC and electrolyte disturbance. The children infected with IVB are more likely to be co-infected with RSV. The children with LRTI caused by IVA and IVB have similar clinical manifestations.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , China , Epidemiology , Influenza A virus , Genetics , Physiology , Influenza B virus , Genetics , Physiology , Influenza, Human , Diagnosis , Epidemiology , Virology , Respiratory Tract Infections , Diagnosis , Epidemiology , Virology , Retrospective Studies , SeasonsABSTRACT
This study was purposed to investigate the proliferation, differentiation and apoptosis of human promyelocytic leukemia HL-60 cells induced by proanthocyanidin (PAC). HL-60 cells were incubated with 20 mg/L PAC for 24 h, the cell growth was evaluated by CCK-8 assay. the effect of PAC on HL-60 cells was evaluated and the cells morphology was observed by optical microscopy. Expression of CD14 and CD11b, and cell cycle were analyzed by flow cytometry. The results showed that the growth of HL-60 cells was inhibited after treatment with PAC of different concentration in a dose-dependent manner (P < 0.05). 20 mg/L PAC displayed significant effect on HL-60 cells with inhibition ratio (72.3 ± 1.8)% for 24 h. Microscopy displayed that some cells differentiated to relative mature cells after treating for 48 h. Expression of CD14 increased and the expression of CD11b increased a little after treating with 20 mg/L PAC for 24 h, the ratio of cells in G0/G1 phase increased, but the ratio of cells in S phase decreased. The mRNA and protein expression of P21 gene increased, but the protein expression of CDK4 and Cyclin D1 decreased. It is concluded that PAC may inhibit the proliferation of HL-60 cells in vitro, induces the differentiation of HL-60 cells, and arrests the cells in G0/G1 phase. The possible mechanism may be related to up-regulation of P21 gene expression and down-regulation of the protein expression of CDK4 and Cyclin D1.
Subject(s)
Humans , Cell Cycle Checkpoints , Cell Differentiation , Cyclin D1 , Metabolism , Cyclin-Dependent Kinase 4 , Metabolism , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Gene Expression Regulation, Leukemic , HL-60 Cells , Proanthocyanidins , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To search the effect of PPARgamma agonists for infection of RSV in vitro.</p><p><b>METHODS</b>The CPE of Hep-2 and A549 cells induced by RSV infection were observed. The effects of 15d-PGJ2 and rosiglitazone on change of CPE of A549 cells induced by RSV infection for 48 h were observed, too. MTT assay was used to detect the rate of viral suppression, and the protective effects of 15d-PGJ2 and rosiglitazone on A549 cells induced by RSV infection for 48 h.</p><p><b>RESULTS</b>A549 cells interfered by 15d-PGJ2 (5 -25 micromol/L) and rosiglitazone (10-50 micromol/L) did not show obvious CPE, MTT assay also showed that the survival rate of A549 cells induced by RSV infection with PPARgamma agonists added, was significantly higher than that of RSV infection without PPARgamma agonists added, the difference was statistically significant (P < 0.01), but comparision between the two drugs showed no statistical significance. The optimal concentrations of 15d-PGJ2 and rosiglitazone were 5 micromol/L and 10 micromol/L respectively.</p><p><b>CONCLUSIONS</b>PPARgamma agonist can reduce the CPE of A549 cells after RSV infection and improve the survival rate of A549 cells. PPARgamma agonist can counteract the infection of RSV in A549 cells.</p>
Subject(s)
Humans , Cells, Cultured , PPAR gamma , Prostaglandin D2 , Pharmacology , Respiratory Syncytial Viruses , Thiazolidinediones , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the chemopreventive effects of boswellic acid and curcumin on 7,12-dimethyl benzanthracene(DMBA)-induced oral carcinogenesis in the hamster cheek pouch model.</p><p><b>METHODS</b>Male Syrian golden hamsters (6 - 8 weeks old, 80 - 130 g in weight) were randomly divided into seven groups, with group A serving as the untreated negative control. The left cheek pouch of the remaining hamsters was topically treated with 0.5% DMBA in mineral oil three times a week for 6 weeks. They were then randomized to six groups with group B serving as a positive control and receiving no further treatment. Groups C-G were treated topically with 5, 10 mg/L boswellic acid, 5, 10 µmol/L curcumin, or the combination of 5 mg/L boswellic acid and 5 µmol/L curcumin three times per week for 18 weeks. The animals were injected with bromodeoxyuridine intraperitoneally at 50 mg/kg 2 h prior to killing. At the 25 th week all the hamsters were sacrificed and cheek pouch tissue was harvested. One half of the tissue was snap frozen in liquid nitrogen for analysis of arachidonic acid metabolites, and the other half was fixed in 10% phosphate-buffered saline(PBS)-buffered formalin for histopathological examination.</p><p><b>RESULTS</b>Six-weeks of DMBA followed by 18-weeks of topical application of boswellic acid and curcumin, both boswellic acid (5, 10 mg/L) and curcumin (5, 10 µmol/L) significantly inhibited the incidence from 93.8% to 73.9% (P > 0.05), numbers from 2.19 ± 0.98 to 1.13 ± 0.81 (P < 0.01) and size of visible tumors. Microscopically the incidence of squamous cell carcinoma and BrdU index were also significantly suppressed by boswellic acid and curcumin.</p><p><b>CONCLUSIONS</b>Both boswellic acid and curcumin were effective in preventing oral carcinogenesis in DMBA-induced hamster cheek pouch model.</p>
Subject(s)
Animals , Cricetinae , Male , 9,10-Dimethyl-1,2-benzanthracene , Antineoplastic Agents , Therapeutic Uses , Bromodeoxyuridine , Carcinogenesis , Carcinogens , Carcinoma, Squamous Cell , Pathology , Cheek , Pathology , Curcumin , Therapeutic Uses , Hyperplasia , Leukotriene B4 , Metabolism , Mesocricetus , Mouth Neoplasms , Pathology , Precancerous Conditions , Pathology , Random Allocation , Triterpenes , Therapeutic UsesABSTRACT
This study was aimed to prepare the polypeptide of N-terminal heparin-binding domain of fibronectin(rhFNHN-29 polypeptide) with pichia expression system, to detect biological activity of recombinant polypeptide and investigate its effect on disseminated intravascular coagulation (DIC) in rats. The sequence of N-terminal heparin-binding domain of fibronectin was amplified from FNcDNA by PCR. The aim gene was cloned into T vector for selection. Then it was cloned into pAo815SM and pPIC9K vectors.Lined pPIC9K vectors were transformed into GS115 Pichia cells so as to express the aim polypeptide in Pichia expression system. The fermentation liquid were precipitated by 80% ammonium sulfate, and the further dissolved sediment were purified using S-100 column and SP column. Its activity of binding with heparin were detected by Western-blot. The established DIC rats (40 rats) were randomly divided into two groups. One group was treated with rhFNHN-29 polypeptide, and the other was treated with normal saline. The rats in the former group were injected with rhFNHN-29 polypeptide (10 mg/kg) through tail vein at 0.5 hour before, 2 hours and 4 hours after injection of LPS respectively. The rats in latter group were injected with equal volume saline. In addition, 20 normal rats injected with normal saline were as normal controls. 500 microl blood was taken from the rat vein, at 6 hours after the injection of LPS. White blood cell (WBC), hemoglobin (Hb) and platelets were tested from 50 microl blood. The rest 450 microl blood was used to isolate plasma for detecting TNFa level and coagulogram. The rats were killed at 24 hours after injection with LPS. Their livers, lungs, hearts, kidneys, and brain tissues were taken for histopathologic examination. The results showed that the aim polypeptide was successfully expressed in Pichia expression system. The expression level reached approximately 30 mg/L. The polypeptide had activity of binding with heparin antibody. In the experiment study of polypeptide effect on DIC in rats, the plasma TNFa level in polypeptide-treated group was lower than that in saline control group, the hemogram, coagulogram and histopathology were more obviously improved in polypeptide-treated group as compared with saline control group. It is concluded that the rhFNHN-29 polypeptide is successfully prepared, this polypeptide can antagonize DIC induced by endotoxin in rats.
Subject(s)
Animals , Female , Male , Rats , Disseminated Intravascular Coagulation , Therapeutics , Endotoxins , Fibronectins , Genetics , Allergy and Immunology , Therapeutic Uses , Heparin , Metabolism , Peptides , Genetics , Therapeutic Uses , Pichia , Metabolism , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To study the viral etiology of acute respiratory infection (ARI)in children from Wenzhou, Zhejiang between 2007 and 2008.</p><p><b>METHODS</b>The nasopharyngeal aspirate samples were obtained from 5 097 hospitalized children with ARI. Seven common respiratory viruses, including respiratory syncytial virus (RSV), influenza virus A and B, parainfluenza viruses 1, 2 and 3 and adenovirus, were detected using direct immunofluorescence.</p><p><b>RESULTS</b>Viral agents were identified in 2 209 cases (43.3%).Of the 2 209, RSV was the most frequent (78.1%), followed by parainfluenza 3 (12.4%), influenza virus A (3.0%), adenovirus (2.8%), parainfluenza 1 (1.7%), influenza B (0.5%) and parainfluenza 2 (0.3%). The infants at ages of <3 months and <6 months had higher detection rate of viruses (53.6% and 49.2%, respectively). A highest detection rate of viruses was found in winter.</p><p><b>CONCLUSIONS</b>RSV is the leading pathogen of ARI in children from Wenzhou, Zhejiang between 2007 and 2008. The children at age of less than 6 months are susceptible to respiratory viruses. The viral activity peaks in winter.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Acute Disease , Adenoviruses, Human , Age Factors , Nasopharynx , Virology , Orthomyxoviridae , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Virology , Seasons , Time FactorsABSTRACT
A series of novel quinolinone acid-containing compounds were designed and synthesized. Their structures were confirmed with 1H NMR and MS. The target compounds were tested for anti-HIV-1 integrase activities in vitro with enzyme linked immunosorbent assay (ELISA). The result showed that D-2, D-4 and D-7 have anti-integrase activity with IC50 < 100 micromol L(-1).
Subject(s)
HIV Integrase , Metabolism , HIV Integrase Inhibitors , Chemistry , Pharmacology , Inhibitory Concentration 50 , Quinolones , Chemistry , Pharmacology , Structure-Activity RelationshipABSTRACT
<p><b>OBJECTIVE</b>A deficient interferon-gamma (IFN-gamma) response has been involved in the pathogenesis of severe respiratory syncytial virus (RSV) infection. Gene polymorphisms in IFN-gamma/A+874T have been associated with the susceptibility to asthma and might be related to disease severity of RSV infection. This study investigated the single nucleotide polymorphisms (SNPs) of IFN-gamma/A+874T in Han children in Wenzhou area and to explore the correlation between gene polymorphisms of IFN-gamma/A+874T and the susceptibility and disease severity of RSV bronchiolitis, as well as the effect of SNPs upon nasopharyngeal secretions (NPS) IFN-gamma and total serum IgE levels.</p><p><b>METHODS</b>One hundred and fourteen hospitalized children with RSV bronchiolitis and 90 healthy controls were recruited. Sequence analysis was used for detecting the SNPs of IFN-gamma/A+874T. NPS IFN-gamma levels were measured using ELISA. Total serum IgE levels were assayed using the chemiluminescence method.</p><p><b>RESULTS</b>IFN-gamma/A+874T gene polymorphisms were present in both the patient and the control groups. AA and AT genotypes were found in both groups, with a AA frequency of 82.5% vs 77.8% and a AT frequency of 17.5% vs 21.1% (p>0.05). The frequency of allele was 90.4% (A) and 9.6% (T) in the patient group, and 88.3% (A) and 11.7% (T) in the control group, respectively. There were no significant differences in the allele frequency between the two groups. Moreover, no difference was found both in NPS IFN-gamma and total serum IgE levels between AA and AT genotypes in the patient group. There were no significant differences in the variation of IFN-gamma/+874 between mild and moderate to severe cases.</p><p><b>CONCLUSIONS</b>IFN-gamma/A+874T gene polymorphisms were present in Han children in Wenzhou area. Gene variations were not associated with the susceptibility and disease severity of RSV bronchiolitis as well as IFN-gamma and total serum IgE levels.</p>
Subject(s)
Female , Humans , Infant , Male , Bronchiolitis , Genetics , Allergy and Immunology , Genetic Predisposition to Disease , Immunoglobulin E , Blood , Interferon-gamma , Genetics , Nasopharynx , Allergy and Immunology , Polymorphism, Single Nucleotide , Respiratory Syncytial Virus Infections , Genetics , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>To study the association of tumor necrosis factor (TNF)-alpha-308G/A and interleukin (IL)-6-174G/C gene polymorphisms with the susceptibility of respiratory syncytial virus (RSV) bronchiolitis.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) was used to identify the polymorphisms at position 308 of the TNF-alpha promoter and -174 of the IL-6 promoter in 150 children with RSV bronchiolitis and 120 healthy children (control group).</p><p><b>RESULTS</b>The frequency of GG, GA and AA genotypes of TNF-alpha-308 was 68.0%, 28.0% and 4.0% respectively in the RSV group, while that was 80.8%, 19.2% and 0 respectively in the control group. There were significant differences in the genotype frequencies between the two groups (chi2=5.665, p<0.05). The frequency of G and A alleles in the RSV group was 82.0% and 18.0% respectively, while that was 90.4% and 9.6% respectively in the control group. The frequency of A allele in the RSV group was significantly higher than that in the control group (chi2=7.726, p<0.05). Compared to the children carrying G allele, the children with A allele demonstrated a 2.071-fold increased risk of RSV bronchiolitis (OR=2.071, p<0.05). Only GG genotype was detected at position -174 of IL-6 in both groups.</p><p><b>CONCLUSIONS</b>TNF-alpha-308A is associated with the susceptibility of RSV bronchiolitis and it might be an important candidate gene for the development of RSV bronchiolits. IL-6-174G/C gene polymorphism is not found in children in Wenzhou area.</p>
Subject(s)
Female , Humans , Infant , Male , Bronchiolitis , Genetics , Genetic Predisposition to Disease , Interleukin-6 , Genetics , Polymorphism, Genetic , Respiratory Syncytial Virus Infections , Genetics , Tumor Necrosis Factor-alpha , GeneticsABSTRACT
Objective To study the epidemiological characteristics of Keshan disease(KD) and its fiend so as to provide evidences for further research,prevention and treatment of the disease in Sichuan province.Methods Based on KD related data from 1990 to 2008,descriptive method was used to analyze the epidemiological characteristics of KD.Results 87 KD cases were identified during the 19 years.All cases were children from the countryside,with majority of them were Yi nationality.Age of the patients ranged from 5 months to 18 years,with majority at 2-6 year-olds.The annual incidence rates Were from 0/100 000 to 1.73/100 000 with 1999 the highest(1.73/100 000).A total number of 310 preclinical or chronic KD cases were identified and the total detection rates were between 0.28% and 2.8%.with 1992 the highest.As for levels of blood selenium during the 19 years:1995 appeared the lowest(0.1345 μg/g),followed by 1990-2000(0.1558 μg/g) but all of them fell in to the level in the KD epidemic areas.Conclusion There were 5 stages in the development trend of KD disease in Sichuan province,with 2 ascending and 3 descending.The differences between any of the two stages were statistically significant.The 3 descending stages all appeared right after the selenium supplement intervention was taken.Our data showed that the program of selenium supplement was closely related to the incidence of KD,suggesting that a long term mechanism of Selenium supplement in the epidemic areas should be taking into account.
ABSTRACT
<p><b>OBJECTIVE</b>Airway remodeling in asthma makes treatment of asthma very difficult, and study of its pathogenesis becomes very important. The present study aimed to explore the role of external signal regulated kinase (ERK) signal transduction pathway in airway remodeling in rats asthma model and regulatory effects of glucocorticoids on ERK signal transduction pathway and airway remodeling.</p><p><b>METHODS</b>Totally 80 male Sprague-Dawlay rats (6-8 weeks old, weighing about 120 g) were randomly divided into control groups (30 rats), asthma groups (30 rats) and treated groups [including a group intervened with dexamethasone (DM group) and budesonide (BUD group), each had 10 rats]. The rats were sensitized for inducing asthma by intraperitoneal injection of ovalbumin and Al (OH)(3) and were repeatedly exposed to aerosolized ovalbumin for 4, 8, or 12 weeks [respectively called 4, 8 or 12 wk asthma group (A4, A8 or A12 group), each had 10 rats]; and correspondingly control rats were intraperitoneally injected with 0.9% NaCl, then were repeatedly exposed to 0.9% NaCl for 4, 8, or 12 weeks [respectively called 4, 8 or 12 wk control group (C4, C8 or C12 group), each had 10 rats]; DM group rats were repeatedly exposed to aerosolized ovalbumin for 8 wk, and BUD group rats for 12 wk. Total bronchial wall thickness (Wat) and smooth muscle thickness (Wam) were measured by an image analysis system. Concentrations of PDGF-AB in serum were measured by sandwich ELISA. Phospho-ERK (P-ERK) and c-Fos were detected by immunohistochemical technique; lung tissue extracts were analyzed for phosphorylation of ERK by Western blotting.</p><p><b>RESULTS</b>Wat and Wam in all asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), those of the treated groups were significantly lower than asthma groups (P < 0.01). The concentrations of PDGF-AB in serum of asthma groups [(228 +/- 18) pg/ml, (293 +/- 77) pg/ml, (225 +/- 66) pg/ml for A4, A8, A12 groups, respectively] were all significantly higher than those of the control groups [(160 +/- 14) pg/ml, (165 +/- 29) pg/ml and (164 +/- 27) pg/ml for C4, C8, C12 group, respectively] (P < 0.01 or P < 0.05); the value of DM group [(157 +/- 46) pg/ml] was significantly lower than that of the group A8 (P < 0.01), no significant difference was found when the values of BUD group [(208 +/- 40) pg/ml] was compared with that of A12 group (P > 0.05). Mean absorbance values (by immunohistochemistry) of P-ERK and c-Fos in asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), DM group had a significantly lower value than group A8 (P < 0.01), BUD group had a significantly lower value than group A12 (P < 0.01); absorbance (by Western blot) of P-ERK in A4, A8, A12 group was significantly higher than that in C4 and C8 group, the value of DM group was significantly lower than that of group A8 (P < 0.01), and that of BUD group (1.8 +/- 0.2) was significantly lower than that of group A12 (P < 0.01).</p><p><b>CONCLUSION</b>Asthmatic rats have higher concentrations of PDGF-AB in serum and phosphorylation of ERK and c-Fos; glucocorticoids inhibit phosphorylation of ERK and c-Fos in asthmatic rats, and to some extent also inhibit Wat and Wam.</p>