ABSTRACT
CONTEXT: Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases. OBJECTIVE: The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development. MATERIALS AND METHODS: BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin. RESULTS: Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses. DISCUSSION AND CONCLUSIONS: The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.
Subject(s)
Dermatitis, Atopic , MicroRNAs , RNA, Long Noncoding , Animals , Mice , Dermatitis, Atopic/drug therapy , RNA, Long Noncoding/genetics , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Flavonoids/pharmacology , Mice, Inbred BALB C , MicroRNAs/geneticsABSTRACT
BACKGROUND: The chloroacetamide herbicides pretilachlor is an emerging pollutant. Due to the large amount of use, its presence in the environment threatens human health. However, the molecular mechanism of pretilachlor degradation remains unknown. RESULTS: Now, Rhodococcus sp. B2 was isolated from rice field and shown to degrade pretilachlor. The maximum pretilachlor degradation efficiency (86.1%) was observed at a culture time of 5 d, an initial substrate concentration 50 mg/L, pH 6.98, and 30.1 °C. One novel metabolite N-hydroxyethyl-2-chloro-N-(2, 6-diethyl-phenyl)-acetamide was identified by gas chromatography-mass spectrometry (GC-MS). Draft genome comparison demonstrated that a 32,147-bp DNA fragment, harboring gene cluster (EthRABCDB2), was absent from the mutant strain TB2 which could not degrade pretilachlor. The Eth gene cluster, encodes an AraC/XylS family transcriptional regulator (EthRB2), a ferredoxin reductase (EthAB2), a cytochrome P450 monooxygenase (EthBB2), a ferredoxin (EthCB2) and a 10-kDa protein of unknown function (EthDB2). Complementation with EthABCDB2 and EthABDB2, but not EthABCB2 in strain TB2 restored its ability to degrade chloroacetamide herbicides. Subsequently, codon optimization of EthABCDB2 was performed, after which the optimized components were separately expressed in Escherichia coli, and purified using Ni-affinity chromatography. A mixture of EthABCDB2 or EthABDB2 but not EthABCB2 catalyzed the N-dealkoxymethylation of alachlor, acetochlor, butachlor, and propisochlor and O-dealkylation of pretilachlor, revealing that EthDB2 acted as a ferredoxin in strain B2. EthABDB2 displayed maximal activity at 30 °C and pH 7.5. CONCLUSIONS: This is the first report of a P450 family oxygenase catalyzing the O-dealkylation and N-dealkoxymethylation of pretilachlor and propisochlor, respectively. And the results of the present study provide a microbial resource for the remediation of chloroacetamide herbicides-contaminated sites.
Subject(s)
Acetamides/metabolism , Acetanilides/metabolism , Cytochrome P-450 Enzyme System/metabolism , Herbicides/metabolism , Multifunctional Enzymes/metabolism , Rhodococcus/enzymology , Biodegradation, Environmental , Cytochrome P-450 Enzyme System/genetics , Dealkylation , Escherichia coli/genetics , Ferredoxins/metabolism , Genes, Bacterial , Genome, Bacterial , Kinetics , Multifunctional Enzymes/genetics , Multigene Family , Mutation , Open Reading Frames , Rhodococcus/classification , Rhodococcus/genetics , Rhodococcus/isolation & purificationABSTRACT
To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the "active ingredient-core targets" network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1, RELA) may be one of the important mechanisms of action.
Subject(s)
Drugs, Chinese Herbal , Eczema , Ephedra sinica , Drugs, Chinese Herbal/pharmacology , Humans , Molecular Docking Simulation , TechnologyABSTRACT
BACKGROUND & AIMS: The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined. METHODS: We conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates. RESULTS: Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75). CONCLUSIONS: Super-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.
Subject(s)
Hepatitis B/complications , Liver Neoplasms/epidemiology , Aged , Aged, 80 and over , Case-Control Studies , China/epidemiology , Female , Humans , Liver Neoplasms/genetics , Liver Neoplasms/virology , Male , Middle AgedABSTRACT
Although tobacco smoking has been reported as a risk factor for liver cancer, few studies have specifically explored the association among Chinese females and the potential interaction between smoking and other risk factors. A population-based case-control study was conducted and 2,011 liver cancer cases and 7,933 healthy controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data were collected, and serum hepatitis B surface antigen (HBsAg) and anti-HCV antibody were measured. Unconditional logistic regression was used to examine association and potential interaction, while semi-Bayes (SB) method was employed to make estimates more conservative. The prevalence of serum HBsAg positivity was 43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever smoking were 1.62 (95% confidence interval [CI]: 1.33-1.96) among male and 0.82 (95% CI: 0.53-1.26) among female. Age at first cigarette, duration of smoking and pack-years of smoking were all significantly associated with liver cancer among men. Compared to HBsAg-negative never smokers, the adjusted ORs were 1.25 (95% CI: 1.03-1.52) for HBsAg-negative ever smokers, 7.66 (95% CI: 6.05-9.71) for HBsAg-positive never smokers, and 15.68 (95% CI: 12.06-20.39) for HBsAg-positive ever smokers. These different odds ratios indicated super-additive (RERI: 7.77, 95% CI: 3.81-11.73) and super-multiplicative interactions (ROR: 1.64, 95% CI: 1.17-2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most associations and interactions detected remained statistically significant after SB adjustments. Tobacco smoking and HBV infection positively interact in the development of liver cancer.
Subject(s)
Hepatitis B/complications , Liver Neoplasms/etiology , Tobacco Smoking/adverse effects , Asian People , Bayes Theorem , Case-Control Studies , Female , Hepatitis B/blood , Hepatitis B Surface Antigens/blood , Hepatitis B virus/pathogenicity , Humans , Liver Neoplasms/blood , Liver Neoplasms/virology , Male , Middle Aged , Odds Ratio , Risk Factors , Smoking/adverse effectsABSTRACT
Nomenclature and classification of diseases are not only related to clinical diagnosis and treatment, but also involved in the fields such as management and exchange of medical information, medical expense payments, and medical insurance payment. In order to standardize clinical physicians' diagnostic and treatment activities, medical records, and the first page of medical records, this article elaborates on the basic principles and methods for nomenclature and classification of diseases with reference to international nomenclature of diseases and international classification of diseases. Meanwhile, in view of the problems in clinical practice, this article proposes the classification of neonatal diseases, the basic procedure and writing rules in the diagnosis of neonatal diseases, and death diagnosis principles.
Subject(s)
Infant, Newborn, Diseases/classification , International Classification of Diseases , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Terminology as TopicABSTRACT
BACKGROUND: Idiopathic renal hypouricemia (iRHUC) is an autosomal recessive hereditary disorder, characterized by impaired tubular uric acid transport, re-absorption insufficiency and/or the acceleration of secretions. Some patients present with severe complications, such as exercise-induced acute kidney injury (EIAKI) and nephrolithiasis. CASE PRESENTATION: Herein, we report the case of a girl with severe iRHUC (serum urate 0.05 mg/dL, fractional excretion of uric acid 295.99%) associated with recurrent EIAKI, in whom the disease was caused by a homozygous mutation (g.68G > A in exon 3) in the SLC2A9 gene. Her family members (father, mother and brother) carried the same mutation but were heterozygous, without any signs of severe hypouricemia. CONCLUSIONS: Our findings indicate that iRHUC is a rare disorder but that it should also be considered in patients with EIAKI, especially in those patients who manifest with moderately elevated or normal serum concentrations of uric acid during the acute phase of AKI. Mutational screening of the SLC2A9 gene is necessary for the diagnosis of iRHUC, and homozygous mutations of the SLC2A9 alleles can cause severe hypouricemia. Careful attention should be paid to any signs of hypouricemia during the recovery phase of AKI and long-term follow-up.
Subject(s)
Acute Kidney Injury/etiology , Exercise , Glucose Transport Proteins, Facilitative/genetics , Mutation , Renal Tubular Transport, Inborn Errors/complications , Urinary Calculi/complications , Acute Kidney Injury/genetics , Child , Female , Humans , Pedigree , RecurrenceABSTRACT
Alcohol drinking is a major risk factor for esophageal cancer (EC) and the metabolism of ethanol has been suggested to play an important role in esophageal carcinogenesis. Epidemiologic studies, including genomewide association studies (GWAS), have identified single nucleotide polymorphisms (SNPs) in alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) to be associated with EC. Using a population-based case-control study with 858 EC cases and 1,081 controls conducted in Jiangsu Province, China, we aimed to provide further information on the association of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms with EC in a Chinese population. Results showed that ADH1B (rs1229984) was associated with EC with odds ratios (ORs) of 1.34 [95% confidence interval (CI): 1.08-1.66] for G-allele carriers compared to A/A homozygotes. No heterogeneity was detected on this association across different strata of alcohol drinking and tobacco smoking. Statistical interaction between ALDH2 (rs671) and alcohol drinking on EC susceptibility in both additive and multiplicative scales was observed. Compared to G/G homozygotes, A-allele carriers were positively associated with EC among moderate/heavy drinkers (OR = 1.64, 95% CI: 1.12-2.40) and inversely associated with EC among never/light drinks (OR = 0.75, 95% CI: 0.54-1.03). In addition, statistical interaction between ALDH2 and ADH1B polymorphisms on EC susceptibility among never/light drinkers was indicated. We did not observe association of ADH1C polymorphism with EC. In conclusion, our findings indicated that ADH1B (rs1229984) was associated with EC independent of alcohol drinking and tobacco smoking status and alcohol drinking interacted with ALDH2 (rs671) on EC susceptibility in this high-risk Chinese population.
Subject(s)
Alcohol Dehydrogenase/genetics , Aldehyde Dehydrogenase/genetics , Esophageal Neoplasms/genetics , Polymorphism, Single Nucleotide , Aged , Aldehyde Dehydrogenase, Mitochondrial , Case-Control Studies , China , Esophageal Neoplasms/epidemiology , Female , Humans , Male , Middle Aged , Population SurveillanceABSTRACT
The collembolan Folsomia candida Willem, 1902, is widely distributed throughout the world and has been frequently used as a test organism in soil ecology and ecotoxicology studies. However, it is questioned as an ideal "standard" because of differences in reproductive modes and cryptic genetic diversity between strains from various geographical origins. In this study, we obtained two high-quality chromosome-level genomes of F. candida, for a parthenogenetic strain (named FCDK, 219.08 Mb, 25,139 protein-coding genes) and a sexual strain (named FCSH, 153.09 Mb, 21,609 protein-coding genes), reannotated the genome of the parthenogenetic strain reported by Faddeeva-Vakhrusheva et al. in 2017 (named FCBL, 221.7 Mb, 25,980 protein-coding genes) and conducted comparative genomic analyses of the three strains. High genome similarities between FCDK and FCBL based on synteny, genome architecture, mitochondrial and nuclear gene sequences suggest that they are conspecific. The seven chromosomes of FCDK are each 25%-54% larger than the corresponding chromosomes of FCSH, showing obvious repetitive element expansions and large-scale inversions and translocations but no whole-genome duplication. The strain-specific genes, expanded gene families and genes in nonsyntenic chromosomal regions identified in FCDK are highly related to the broader environmental adaptation of parthenogenetic strains. In addition, FCDK has fewer strain-specific microRNAs than FCSH, and their mitochondrial and nuclear genes have diverged greatly. In conclusion, FCDK/FCBL and FCSH have accumulated independent genetic changes and evolved into distinct species after 10 million years ago. Our work provides important genomic resources for studying the mechanisms of rapidly cryptic speciation and soil arthropod adaptation to soil ecosystems.
Subject(s)
Arthropods , Ecosystem , Animals , Arthropods/genetics , Genome , Synteny , Soil , Evolution, Molecular , Genetic SpeciationABSTRACT
BACKGROUND: Cyclosporine A (CsA) and tacrolimus (TAC) are often alternative treatment choices for patients with nephrotic syndrome. METHODS: In this prospective study, the efficacy and safety of CsA and TAC in inducing and maintaining remission in 74 children with idiopathic nephrotic syndrome (INS) were evaluated. RESULTS: In terms of short-term efficacy, TAC was more effective than CsA in children with steroid-resistant nephrotic syndrome (χ(2) = 13.75, P = 0.001), although no significant difference in number of episodes of relapse were found in patients with complete remission between the two treatment groups (first year: χ(2) = 0.261, P = 0.88; second year: χ(2) = 2.685, P = 0.26). In patients with frequently relapsing or steroid-dependent nephrotic syndrome, no significant difference in short-term remission (χ(2) = 1.908, P = 0.39) or in relapse frequency during follow-up (within first year: χ(2) = 1.046, P = 0.59; within second year: χ(2) = 0.587, P = 0.75) were found between the two groups. There was a difference in the rate of adverse effects between the two treatment groups [nephrotoxicity: 4/24 (CsA) vs .0/50 (TAC), P = 0.002; hirsutism: 8/24 (CsA) vs. 0/50 (TAC), P < 0.001]. CONCLUSIONS: In our pediatric patient cohort, the treatment of steroid-resistant nephrotic syndrome with tacrolimus was associated with higher efficacy and lower renal toxicity in comparison to CsA, although no favorable outcome in relapse rate during long-term follow-up was seen. On the other hand, tacrolimus was not always the better choice to replace CsA in the treatment of severe frequently relapsing or steroid-dependent nephrotic syndrome.
Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Nephrotic Syndrome/congenital , Tacrolimus/therapeutic use , Adolescent , Chi-Square Distribution , Child , Child, Preschool , Cyclosporine/adverse effects , Female , Humans , Immunosuppressive Agents/adverse effects , Male , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/drug therapy , Prospective Studies , Recurrence , Remission Induction , Tacrolimus/adverse effects , Time Factors , Treatment OutcomeABSTRACT
Atmospheric concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) were measured in Taizhou, a large electronic equipment waste (e-waste) recycling area in East China. The mean concentrations (in summer and winter) of PCDD/Fs (0.45 and 0.39 pg WHO-TEQ m⻳, where WHO-TEQ is the toxic equivalent set by the World Health Organisation), PBDD/Fs (0.22 and 0.18 pg WHO-TEQ m⻳), and PBDEs (270 and 225 pg m⻳) in this region have declined compared with those in 2005, due to regulations on primitive e-waste recycling activities. However, these concentrations remain higher than the historically highest levels in Europe and North America. The congener profiles of 2,3,7,8-substituted PCDD/Fs were similar, with OCDD, 1,2,3,4,6,7,8-HpCDF, OCDF, and 1,2,3,4,6,7,8-HpCDD being the most abundant congeners at all sites. The PCDD/F homologue profiles in the present study were different from those typically observed at non-e-waste locations, indicating a distinct source in this region. Seasonal differences were found in the lower brominated PBDE profiles. These differences indicate that the PBDE emission sources in summer (e.g., strong evaporation sources) differed from those in winter. However, the relatively steady congener profiles of the highly brominated PBDEs suggest that these PBDEs were controlled primarily by similar emission mechanisms. The lifetime excess cancer risks from exposure to PCDD/Fs and PBDD/Fs via inhalation ranged from 0.7 × 10â»5 to 5.4 × 10â»5, or approximately 80 cancer cases in the Taizhou population.
Subject(s)
Air Pollutants/analysis , Benzofurans/analysis , Dioxins/analysis , Electronic Waste/analysis , Halogenated Diphenyl Ethers/analysis , Neoplasms/epidemiology , Polychlorinated Dibenzodioxins/analogs & derivatives , Air Pollutants/toxicity , Air Pollution/statistics & numerical data , Benzofurans/toxicity , Bromine Compounds/analysis , Bromine Compounds/toxicity , China/epidemiology , Dioxins/toxicity , Electronic Waste/statistics & numerical data , Environmental Exposure/statistics & numerical data , Environmental Monitoring , Halogenated Diphenyl Ethers/toxicity , Humans , Polychlorinated Dibenzodioxins/analysis , Polychlorinated Dibenzodioxins/toxicity , Polymers/analysis , Polymers/toxicity , Risk AssessmentABSTRACT
A population-based case-control study on esophageal cancer has been conducted since 2003 in Jiangsu Province, China. The aim of this analysis is to provide further evidence on the relationship between family history of cancer in first-degree relatives (FH-FDRs) and the risk of esophageal cancer, and to explore the joint effects for FH-FDR with major lifestyle risk factors. A total of 1,520 cases and 3,879 controls were recruited. Unconditional logistic regression was applied for evaluating independent association as well as potential interactions between FH-FDR and lifestyle risk factors on the risk of esophageal cancer. Population attributable fraction (PAF) was calculated to quantify the proportion of cases attributable to risk factors. Results showed that with a FH-FDR of any malignant tumor or esophageal cancer, there is a 1.64- and 2.22-fold risk of esophageal cancer, respectively. Association was increased when there was more than one affected FDR (OR = 3.14) and younger age at diagnosis of relatives. Exposure of both FH-FDR and lifestyle risk factors strongly associated with esophageal cancer. Significant superadditivity interaction was found for FH-FDR with fast eating speed and diets low in fruits and vegetables. The estimation of PAF indicated that the majority of cases were attributed to lifestyle risk factors. In conclusion, it was found that FH-FDR significantly increases the risk of esophageal cancer and could modify the effect of certain lifestyle risk factors. If comprehensive lifestyle interventions are carried out within high-risk populations, there is a high probability of curbing occurrences of esophageal cancer.
Subject(s)
Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/etiology , Genetic Predisposition to Disease , Life Style , Adult , Aged , Aged, 80 and over , Alcohol Drinking/adverse effects , Case-Control Studies , China/epidemiology , Diet , Female , Humans , Male , Middle Aged , Risk Factors , Smoking/adverse effectsABSTRACT
Although the association for esophageal cancer with tobacco smoking and alcohol drinking has been well established, the risk appears to be less strong in China. To provide more evidence on the effect of smoking and alcohol consumption with esophageal cancer in China, particularly among Chinese women, a population-based case-control study has been conducted in Jiangsu, China, from 2003 to 2007. A total of 1,520 cases and 3,879 controls were recruited. Unconditional multivariate logistic regression analysis was applied. Results showed that the odds ratio (OR) and confidence interval (CI) for ever smoking and alcohol drinking were 1.57 (95% CI: 1.34-1.83) and 1.50 (95% CI: 1.29-1.74). Dose-response relationships were observed with increased intensity and longer duration of smoking/drinking. Risk of smoking and alcohol drinking at the highest joint level was 7.32 (95% CI: 4.58-11.7), when compared to those never smoked and never drank alcohol. Stratifying by genders, smoking and alcohol drinking increased the risk among men with an OR of 1.74 (95% CI: 1.44-2.09) and 1.76 (95% CI: 1.48-2.09); however, neither smoking nor alcohol consumption showed a significant association among women. In conclusion, smoking and alcohol drinking were associated with esophageal cancer risk among Chinese men, but not among Chinese women.
Subject(s)
Alcohol Drinking/adverse effects , Asian People/statistics & numerical data , Carcinoma/etiology , Esophageal Neoplasms/etiology , Sex Characteristics , Smoking/adverse effects , Aged , Alcohol Drinking/epidemiology , Carcinoma/epidemiology , Carcinoma/ethnology , Case-Control Studies , China/epidemiology , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/ethnology , Female , Geography , Humans , Male , Middle Aged , Population , Risk Factors , Smoking/epidemiologyABSTRACT
A malate dehydrogenase (MDH) from Streptomyces avermitilis MA-4680 (SaMDH) has been expressed and purified as a fusion protein. The molecular mass of SaMDH is about 35 kDa determined by SDS-PAGE. The recombinant SaMDH has a maximum activity at pH 8.0. The enzyme shows the optimal temperature around 42 °C and displays a half-life (t(1/2)) of 160 min at 50°C which is more thermostable than reported MDHs from most bacteria and fungi. The k(cat) value of SaMDH is about 240-fold of that for malate oxidation. In addition, the k(cat)/K(m) ratio shows that SaMDH has about 1,246-fold preference for oxaloacetate (OAA) reduction over L-malate oxidation. The recombinant SaMDH may also use NADPH as a cofactor although it is a highly NAD(H)-specific enzyme. There was no activity detected when malate and NADP(+) were used as substrates. Substrate inhibition studies show that SaMDH activity is strongly inhibited by excess OAA with NADH, but is not sensitive to excess L-malate. Enzymatic activity is enhanced by the addition of Na(+), NH(4)(+), Ca(2+), Cu(2+) and Mg(2+) and inhibited by addition of Hg(2+) and Zn(2+). MDH is widely used in coenzyme regeneration, antigen immunoassays and bioreactors. The enzymatic analysis could provide the important basic knowledge for its utilizations.
Subject(s)
Malate Dehydrogenase/metabolism , Prokaryotic Cells/cytology , Prokaryotic Cells/enzymology , Streptomyces/cytology , Streptomyces/enzymology , Amino Acid Sequence , Biocatalysis/drug effects , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Enzyme Activation/drug effects , Enzyme Stability/drug effects , Hydrogen-Ion Concentration/drug effects , Ions , Kinetics , Malate Dehydrogenase/chemistry , Malate Dehydrogenase/isolation & purification , Malates/pharmacology , Metals/pharmacology , Molecular Sequence Data , Oxaloacetic Acid/metabolism , Prokaryotic Cells/drug effects , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Streptomyces/drug effects , TemperatureABSTRACT
A monomeric NADP-dependent isocitrate dehydrogenase from the multicellular prokaryote Streptomyces avermitilis MA-4680 (SaIDH) was heteroexpressed in Escherichia coli, and the His-tagged enzyme was further purified to homogeneity. The molecular weight of SaIDH was about 80 kDa which is typical for monomeric isocitrate dehydrogenases. Structure-based sequence alignment reveals that the deduced amino acid sequence of SaIDH shows high sequence identity with known momomeric isocitrate dehydrogenase, and the coenzyme, substrate and metal ion binding sites are completely conserved. The optimal pH and temperature of SaIDH were found to be pH 9.4 and 45°C, respectively. Heat-inactivation studies showed that heating for 20 min at 50°C caused a 50% loss in enzymatic activity. In addition, SaIDH was absolutely specific for NADP+ as electron acceptor. Apparent Km values were 4.98 µM for NADP+ and 6,620 µM for NAD+, respectively, using Mn2+ as divalent cation. The enzyme performed a 33,000-fold greater specificity (kcat/Km) for NADP+ than NAD+. Moreover, SaIDH activity was entirely dependent on the presence of Mn2+ or Mg2+, but was strongly inhibited by Ca2+ and Zn2+. Taken together, our findings implicate the recombinant SaIDH is a divalent cation-dependent monomeric isocitrate dehydrogenase which presents a remarkably high cofactor preference for NADP+.
Subject(s)
Gene Expression , Isocitrate Dehydrogenase/metabolism , Prokaryotic Cells/enzymology , Streptomyces/enzymology , Amino Acid Sequence , Electrophoresis, Polyacrylamide Gel , Enzyme Activation/drug effects , Gene Expression/drug effects , Hydrogen-Ion Concentration/drug effects , Indicators and Reagents/pharmacology , Ions , Isocitrate Dehydrogenase/chemistry , Isocitrate Dehydrogenase/isolation & purification , Kinetics , Metals/pharmacology , Molecular Sequence Data , Molecular Weight , Prokaryotic Cells/drug effects , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Streptomyces/drug effects , TemperatureABSTRACT
Henoch-Schönlein purpura (HSP) is one of the most common causes of systemic vasculitis in children. The incidence of HSP nephritis (HSPN) among HSP patients has been reported to be 15-62%. Even so, what constitutes severe HSPN is controversial. In the study reported here, we retrospectively reviewed the clinical features and prognosis of 101 children with HSPN, ISKDC grade IIIa/IIIb, from January 1992 to November 2008. Patients with isolated hematuria and/or proteinuria <50 mg/kg/day received triptolide alone, and those with nephrotic range proteinuria received a combination therapy of prednisone and triptolide. Nephrotic syndrome was the most common clinical manifestation (45.5%). There were no significant differences in the clinical features (χ(2) = 2.756, P = 0.252), the side effects related to treatment (χ(2) = 2.259, P = 0.894), prognosis between IIIa and IIIb (χ(2) = 3.013, P = 0.222), or prognosis in grade IIIa patients receiving triptolide alone or triptolide and prednisone (χ(2) = 1.207, P = 0.272) and grade IIIb patients (χ(2) = 1.158, P = 0.282). No significant difference in clinical manifestations and long-term prognosis of our HSPN patients with grade IIIa or grade IIIb were found, implying that our patients with International Study and Kidney Disease in Children (ISKDC) grade IIIb were not the most severe cases of HSPN. Our results may also suggest that treatment with steroid may not alter the clinical outcome of such grade IIIa or IIIb patients.
Subject(s)
Diterpenes/therapeutic use , IgA Vasculitis/drug therapy , Immunosuppressive Agents/therapeutic use , Nephritis/drug therapy , Phenanthrenes/therapeutic use , Prednisone/therapeutic use , Adolescent , Biopsy , Chi-Square Distribution , Child , Child, Preschool , China , Diterpenes/adverse effects , Drug Therapy, Combination , Epoxy Compounds/adverse effects , Epoxy Compounds/therapeutic use , Female , Hematuria/drug therapy , Hematuria/etiology , Humans , IgA Vasculitis/complications , IgA Vasculitis/diagnosis , Immunosuppressive Agents/adverse effects , Male , Nephritis/diagnosis , Nephritis/etiology , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/etiology , Phenanthrenes/adverse effects , Prednisone/adverse effects , Proteinuria/drug therapy , Proteinuria/etiology , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
Standing yoga poses strengthen a person's legs and helps to achieve the goal of musculoskeletal rehabilitation, but inadequate exercise planning can cause injuries. This study investigated changes in the electromyogram and joint moments of force (JMOFs) of lower extremities during common standing yoga poses in order to explore the feasibility and possible injury risk in dealing with musculoskeletal problems. Eleven yoga instructors were recruited to execute five yoga poses (Chair, Tree, Warrior 1, 2, and 3). The results revealed significant differences in hip, knee, and ankle JMOFs and varying degrees of muscle activation among the poses. Among these poses, rectus femoris muscle activation during the Chair pose was the highest, Warrior 2 produced the highest muscle activation in the vastus lateralis of the front limb, while Warrior 1 had the highest muscle activation in the vastus medialis of the back limb. Therefore, all three poses can possibly be suggested as a therapeutic intervention for quadriceps strengthening. Warrior 1 was possibly suggested as a therapeutic intervention in order to reduce excessive lateral overload of the patella, but the possible adverse effects of Warrior 2 with the highest knee adductor JMOF in the back limb could raise joint reaction forces across the medial condyles. In single-leg balance postures, Warrior 3 had unique training effects on the hamstring, and is therefore suggested as a part of hamstring rehabilitation exercises. The Tree pose induced low lower-extremity JMOFs and a low level of thigh muscle activations when it was performed by senior instructors with excellent balance control; however, for yoga beginners with insufficient stability, it will be a useful training mode for strengthening the muscles that help to keep one upright. This study quantified the physical demands of yoga poses using biomechanical data and elucidated the structures and principles underlying each yoga movement. This is crucial for yoga practitioners.
Subject(s)
Yoga , Electromyography , Humans , Knee Joint , Lower Extremity , Muscle, Skeletal , Quadriceps MuscleABSTRACT
AIM: To determine the relationship between birth size and later QOL for Chinese people. METHODS: Birth data of 1074 subjects were obtained from obstetric birth records of Peking Union Medical College Hospital. All subjects are interviewed face to face with the 36-Item Short-Form Health Survey scale by trained investigators. Linear regression model was used to analyse the relationship between QOL and birth head circumference of the subjects after adjusting for the childhood and adulthood characteristics. The relationship was described with regression coefficients (B) and its 95% confidence interval (CI). RESULTS: The mean weighted score of QOL was 88.1 ± 9.1, ranging from 76.8 to 100. Larger birth head circumference meant higher adulthood QOL total score (P= 0.001). After controlling the adulthood confounders, as compared to larger head circumference (≥33 cm), small (<31 cm) and medium head circumferences (31-33 cm) meant lower adulthood QOL scores (B=-2.356, P= 0.005 and B=-1.645, P= 0.014, respectively). The increase of head circumference by 1 cm was associated with 0.480 (95% CI: 0.141, 0.820) increase of QOL score after adjusting adulthood confounders (P= 0.006). CONCLUSIONS: This study validated the relationship between birth head circumference and QOL in later life. Smaller head circumference at birth could predict worse adulthood QOL at above 50 years old.
Subject(s)
Cephalometry , Quality of Life , Birth Certificates , Birth Weight , China , Chronic Disease , Female , Health Surveys , Humans , Infant, Newborn , Linear Models , Male , Middle Aged , Risk Factors , TimeABSTRACT
Epidemiological studies suggested drinking green tea is inversely associated with esophageal cancer but results remain inconclusive. Moreover, inconsistent observations found high temperature drinks are associated with esophageal cancer. A population-based case-control study was conducted in a high-risk area (Dafeng) and a low-risk area (Ganyu) of esophageal cancer in Jiangsu province China from 2003 to 2007. It aimed to explore green tea drinking and tea temperature with the risk of esophageal cancer, and to compare the difference between different risk regions. Using identical protocols, 1,520 cases and 3,879 healthy controls were recruited as study subjects in 2 regions. Detailed information was collected to assess green tea drinking habits. Unconditional logistic regression was used to obtain OR and 95% CI. Results showed that ever drinking green tea elevated OR in both counties (Dafeng OR = 1.2, 95% CI = 0.9-1.5; Ganyu: OR = 1.9, 95% CI = 1.4-2.4). Drinking tea at high temperature was found to increase cancer risk in both areas (Dafeng: OR = 1.9, 95% CI = 1.2-2.9; Ganyu OR = 3.1 95% CI = 2.2-4.3). However, after further adjustment for tea temperature, ever drinking tea was not related to cancer in either county (Dafeng: OR = 1.0, 95% CI = 0.7-1.3; Ganyu: OR = 1.3, 95% CI = 0.9-1.7). For dose-response relationships, we observed positive relationship with monthly consumption of tea (p for trend = 0.067) and tea concentration (p for trend = 0.006) after further adjustment for tea temperature. In conclusion, green tea drinking was not inversely associated with esophageal cancer in this study. However, drinking tea at high temperatures significantly increased esophageal cancer risk. There was no obvious difference of green tea drinking between low- and high-risk areas.
Subject(s)
Esophageal Neoplasms/epidemiology , Tea , Adult , Aged , Aged, 80 and over , Alcohol Drinking , Case-Control Studies , China , Esophageal Neoplasms/etiology , Female , Hot Temperature , Humans , Male , Middle Aged , Smoking , TemperatureABSTRACT
OBJECTIVE: To examine the epidemiologic characteristics of major cancers in Dafeng City, Jiangsu Province. METHODS: The cancer registry data 1999 - 2007 of Dafeng were analyzed retrospectively. RESULTS: Over the 9 years, the crude incidence of cancers was 244.99 persons per 100 thousand and the standard incidence ratio (SIR) was 175.48 persons per 100 thousand. The crude incidence and SIR of cancers of the males was 299.22 persons per 100 thousand and 214.41 persons per 100 thousand respectively, 1.57 and 1.76 times as high as those of the females (190.92 per 100 thousand and 137.34 per 100 thousand respectively). The incidence of cancers increased remarkably since the age group of 509, peaked at the age groups 70 and 80, and decreased remarkably since the age group of 85. Stomach cancer ranked first for incidence among the males while esophageal cancer ranked first for the females. CONCLUSION: The incidence of cancers, especially the lung cancer, shows a trend to increase in both the males and females in Dafeng. Priority should be paid to prevention and treatment of cancers of the digestive and respiratory systems.