Objective To evaluate the effect of hyperhomocysteinemia on ischemic diease in rats. Methods Thirty-two SD rats were randomized into two groups,control group(n=16,administered with tap water) and hyperhomocysteinemia group(HH group,n=16,administered with water containing L-methionine at 1 g/kg/d).At the 14thday of dietary modification,the left femoral artery and vein were excised,and the interventions continued for another 14 days.At the 15th day after operation,serum biochemical parameters as well as NOx and cGMP in ischemic tissues were tested,capillary vessel density of both hindlimbs were measured by histological analysis,and angiogenesis of ischemic hindlimb was observed by angiography. Results At the 15th day after operation,the level of high-density lipoprotein-cholesterol(HDL-C),blood urea nitrogen,uric acid and ratio of blood urea nitrogen to serum creatinine were significantly higher in HH group than those in control group,while the level of serum folic acid,VitB12,HDL-C and endogenous creatinine clearance rate were significantly lower in HH group than those in control group(P

Advanced technologies are used to clarify the meridian tropism theory of traditional Chinese medicine is an important part of theoretical studies of traditional Chinese medicine. In this article, modern pharmacokinetic method was used to investigate tissue distribution characteristics of psoralen and isopsoralen of Psoraleae Fructus decoction in rats, in order to provide research ideas and experimental basis for the meridian tropism theory. In this study, various tissue samples such as heart, liver, spleen, lung, kidney, brain and spermary were collected at different times after oral administration with FP decoction, in order to determine concentration of psoralen and isopsoralen by HPLC. Pharmacokinetic parameters were calculated by DAS 2.0 software. The study results showed that HPLC indexes of psoralen and isopsoralen in various tissues of rats met the determination requirements of biological samples. Both components were distributed in all of the tissues, with AUC(0-t) order of liver > lung approximately kidney > heart > brain approximately spleen > spermary. There was significant difference between liver, kidney, lung and other tissues (P < 0.05). MRT(0-t) of both psoralen and isopsoralen were about 10 h. Therefore, psoralen and isopsoralen showed stronger targeting selection in liver, kidney and lung.
Animals ; Area Under Curve ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Fruit ; chemistry ; Furocoumarins ; pharmacokinetics ; Kinetics ; Male ; Plant Extracts ; administration & dosage ; chemistry ; pharmacokinetics ; Psoralea ; chemistry ; Rats ; Tissue Distribution

Objective To analyze the molecular epidemiological characteristics on HIV infectors/AIDS patients (HIV/AIDS) under a follow-up program in Zhejiang province in 2009.Methods 303 cases were randomly sampled.Information on the cases was collected and followed by genomic DNA extraction.Gag gene fragments were amplified by nested PCR,followed by sequencing and bio-informatic analysis.Results The rate of success for sequence acquisition was 74.3％ (225/303).Distributions of HIV subtypes were as follows:CRF01_AE (58.7％),CRF07_BC (13.8％),CRF08_BC (9.8％),B' (15.1％),C (1.8％),G (0.4％) and unassigned BC (unique recombinant form 0.4％).Results from the HIV BLAST analysis showed that the sources of strains with the highest homology involved in 10 provinces/municipalities (Liaoning,Guangxi,Yunnan,Henan,etc.) and five other countries (Thailand,Vietnam,India,South Africa and Libya).The CRF01 _AE phylogenetic tree was divided into four clusters.The sequences of HIV/AIDS with homosexual transmission showed a gathering in cluster 1,and mixing with those infected through heterosexual contact.Conclusion Circulating recombinant forms of HIV seemed to play a dominant role in Zhejiang province.Unique recombinant form and new subtype of HIV were found.People living with HIV under homosexual transmission and heterosexual transmission had a trend of interwoven with each other.Increase of both the diversity and complexity of HIV strains were also noticed in Zhejiang province.

OBJECTIVETo study the effects of total alkaloids(TA) from rhizoma Coptis chinensis on alcohol-induced gastric lesion in rats and the possible mechanisms.

METHODThe experimental gastric damges were established by intragastric(ig) absolute ethanol, and possible protective effects of TA given orally previously were evaluated by following parameters: gastric damage indexes, gastric juice volume, acidity, and mucus quantity. The contents of NO, MDA, *OH, and SOD activity were also measured in gastric mucosa.

RESULTTA showed significantly inhibitive effects on gastric damages induced by ig ethanol in a dose dependent manner. The effects of TA (120 mg x kg(-1)) were stronger than that of both cimitidine(70 mg x kg(-1)) and berberine(100 mg x kg(-1)), the quantity of later was equal to TA as calculated with berberine. TA significantly suppressed secretion of gastric acid caused by ethanol without clear influences on gastric juice volume and mucus secretion. TA obviously blunted ethanol-induced elevation of MDA and *OH, as well as decrease of NO level and SOD activity from gastric mucosa.

CONCLUSIONIt is suggested that the TA is a potent protective agent against ethanol-induced gastric damages. The mechanism of actions may be related with inhibiting the secretion of gastric acid and blunting the increase of MDA and *OH, as well as the decrease of NO level and SOD activity from gastric mucus.

Alkaloids ; isolation & purification ; pharmacology ; Animals ; Coptis ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Ethanol ; Female ; Gastric Mucosa ; metabolism ; pathology ; Male ; Plants, Medicinal ; chemistry ; Protective Agents ; isolation & purification ; pharmacology ; Rats ; Rats, Wistar ; Rhizome ; chemistry ; Stomach Ulcer ; chemically induced ; metabolism ; pathology

OBJECTIVETo detect mutations of guanosine triphosphate cyclohydrolase I (GCH1) gene in Chinese patients with dopa responsive dystonia (DRD).

METHODSSix sporadic patients with DRD were examined. GCH1 gene mutations were detected using polymerase chain reaction (PCR), DNA sequence analysis and restriction enzyme digestion analysis. One hundred normal people were detected using PCR and restriction enzyme digestion analysis.

RESULTSA new point mutation, 151(G-->A) in exon one was found in a patient. It lead to substitution of a methionine for isoleucine at amino acid 1(M1I). This mutation was not found in normal control people.

CONCLUSIONThe authors report a new heterozygotic point mutation 151(G-->A) in GCH1 gene. There are GCH1 gene mutations in Chinese sporadic patients with DRD.

Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; DNA ; genetics ; DNA Mutational Analysis ; Dihydroxyphenylalanine ; therapeutic use ; Dystonia ; drug therapy ; genetics ; Exons ; genetics ; Female ; GTP Cyclohydrolase ; genetics ; Humans ; Male ; Point Mutation ; genetics ; Polymerase Chain Reaction

Aim To study the protective effect of fluoxetine hydrochloride on brain tissues of rats with simulated high altitude cerebral edema(HACE)and its mechanism.Methods The optimal dosage and time of fluoxetine hydrochloride were determined by the hypoxia tolerance test of mice under normal pressure.The rat model of brain edema at high altitude was established by large-scale low-pressure oxygen chamber.HE staining was used to observe the pathological changes of brain tissues in rats.Microplate reader was used to detect the corresponding indexes of oxidative stress such as malondialdehyde(MDA)level and superoxide dismutase(SOD)activity.The expressions of hypoxia-related proteins HIF-1α,VEGF,MMP-9,AQP4 and SERT were detected by Western blot.Results Compared with the hypoxia model group,after the intervention of fluoxetine hydrochloride,the survival time of mice was prolonged,and the middle dose of fluoxetine(14 mg·kg-1)had the best effect,with an extension rate of 17.78%.The pathological damage of brain was improved,the water content of brain decreased,and the permeability of blood-brain barrier decreased.MDA content in rat brain decreased and SOD activity increased.Western blot results showed that HIF-1α,VEGF,MMP-9,AQP4,SERT protein were significantly down-regulated.Conclusions Fluoxetine has protective effect on rats with brain edema at high altitude,and its mechanism may be related to improving oxidative stress,activating HIF-1α/VEGF/MMP-9 signaling pathway and affecting the expression of SERT protein.SERT may be a potential target for treating brain edema at high altitude.

OBJECTIVETo detect parkin gene mutation of early-onset parkinsonism (EOP) by denaturing high performance liquid chromatography (DHPLC).

METHODSThe blood cell genomic DNA of 82 EOP patients was isolated. Exons of parkin gene were amplified by PCR. The PCR products were detected by DHPLC. The sample with abnormal peak shape was sequenced.

RESULTSThree point mutations were identified in 82 EOP patients compared with 100 healthy controls. Mutations in intron include IVS1-39 G --> T and IVS9 +18 C --> T. The T1422C mutation was in coding region and resulted in 441 Cys --> Arg.

CONCLUSIONThree heterozygous mutations are found in sporadic EOP patients and genetic diagnosis of parkin gene by DHPLC is applicable in EOP patients.

Adult ; Base Sequence ; Chromatography, High Pressure Liquid ; methods ; DNA Mutational Analysis ; Humans ; Middle Aged ; Mutation ; Parkinson Disease ; diagnosis ; genetics ; Polymerase Chain Reaction ; Ubiquitin-Protein Ligases ; genetics

OBJECTIVETo observe the cellular expression of (R127W) HSPB1 and its influence on neurofilament light chain (NFL) self-assembly and co-localization with NFL.

METHODSEukaryotic expression vectors pEGFPN1-(wt) HSPB1 and pEGFPN1- (R127W) HSPB1 were constructed. Hela cells were transiently transfected with pEGFPN1-(wt) HSPB1 or pEGFPN1- (R127W) HSPB1 and observed under a confocal microscope. Hela cells were also transiently co-transfected with Pcl-NFL and pEGFPN1-(wt)HSPB1, or pCL-NFL and pEGFPN1-(R127W)HSPB1. The self-assembly of NFL was observed and the co-localization study of HSPB1/ (R127W)HSPB1 with NFL was carried out in these two cell models by immunofluorescence technique.

RESULTSThe aggregates formed by EGFP-(R127W)HSPB1 predominantly located around the nucleus, and EGFP-(wt)HSPB1 showed diffusion pattern in Hela cells. When co expressed with EGFP-(wt)HSPB1, NFL formed homogeneous structure in cytosol. When co-expressed with EGFP-(R127W)HSPB1, however, NFL had amorphous staining pattern predominantly consisting of NFL aggregates, and NFL co-localized with (R127W)HSPB1 in these aggregates.

CONCLUSIONThe R127W mutant of HSPB1 may have reduced capacity to serve as a chaperone to prevent aggregate formation, and fail to correctly organize the neurofilament network. Dysfunction of the axon cytoskeleton and axon transport may be the primary mechanism of R127W mutation of HSPB1 in the pathogenesis of Charcot-Marie-Tooth disease.

Base Sequence ; Charcot-Marie-Tooth Disease ; genetics ; metabolism ; Gene Expression Regulation ; Genetic Vectors ; genetics ; HSP27 Heat-Shock Proteins ; genetics ; metabolism ; HeLa Cells ; Humans ; Intracellular Space ; metabolism ; Mutant Proteins ; genetics ; metabolism ; Neurofilament Proteins ; metabolism ; Protein Binding ; genetics ; Protein Transport ; Transfection

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.
Humans ; Salmonella enterica/genetics* ; Serogroup ; Anti-Bacterial Agents/pharmacology* ; Multilocus Sequence Typing ; Cities ; London ; Clonidine ; Phylogeny ; Genomics ; Drug Resistance ; Electrophoresis, Gel, Pulsed-Field ; Microbial Sensitivity Tests

Cell death occurs in various tissues and organs in the body. It is a physiological or pathological process that has different effects. It is of great significance in maintaining the morphological function of cells and clearing abnormal cells. Pyroptosis, apoptosis, and necrosis are all modes of cell death that have been studied extensively by many experts and scholars, including studies on their effects on the liver, kidney, the heart, other organs, and even the whole body. The heart, as the most important organ of the body, should be a particular focus. This review summarizes the mechanisms underlying the various cell death modes and the relationship between the various mechanisms and heart diseases. The current research status for heart therapy is discussed from the perspective of pathogenesis.
Apoptosis ; Autophagy ; Cardiovascular Diseases ; Humans ; Necrosis ; Pyroptosis