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Background Hypertension is influenced by both genes and environment. At present, most studies on the relationship among occupational stress, polymorphisms of ATP binding cassette subfamily A member 1 (ABCA1) or angiotensinogen (AGT) genes, and hypertension focus on single gene or single environmental effects. Objective To investigate the relationship of potential interactions between ABCA1 and AGT gene polymorphisms and occupational stress with the prevalence of hypertension. Methods A total of 198 hypertensive patients were selected as the case group from the 1200 oilfield workers in Karamay Oilfield in 2018 with random cluster sampling method, and the control group was selected as 1∶1 matched subjects for sex, age (±3 years), and ethnicity, after excluding blood samples, questionnaires, or DNA purity (concentration) that did not meet the inclusion criteria. Finally, 153 workers in the hypertension case group and 153 workers in the control group were determined. A questionnaire was used to collect general information of the oilfield workers, and the Occupational Stress Inventory Revised Edition (OSI-R) was used to evaluate occupational stress. Polymerase chain reaction-restriction fragment length polymorphism technology was used to detect the genotypes of V825I and R219K loci of ABCA1 as well as M235T and T174M loci of AGT. The gene-gene interaction of ABCA1 and AGT and the relationship between the interaction of gene-occupational stress and the prevalence of hypertension were analyzed by generalized multi-factor dimensionality reduction method. Results The difference of reported occupational stress between the hypertension case group and the control group was statistically significant (P＝0.001), and the reporting rate of high occupational stress in the case group (65.4%) was higher than that in the control group (47.7%). The genotype and allele distributions of ABCA1 V825I, ABCA1 R219K, and AGT M235T between the hypertension case group and the control group were significantly different (P<0.05). The results of conditional logistic regression analysis showed that VI and II genotypes at V825I locus of ABCA1 (ORVI=1.682, 95%CI: 1.099-2.573; ORII=1.708, 95%CI: 1.045-2.790), TT genotype at M235T locus of AGT (OR=1.645, 95%CI: 1.022-2.647), and high occupational stress (OR=2.642, 95%CI: 1.228-5.686) increased the risks for hypertension (P<0.05). There was no significant correlation between ABCA1 R219K or AGT T174M polymorphisms and the prevalence of hypertension (P>0.05). The gene-gene interactions between ABCA1 V825I and R219K loci and AGT M235T locus were associated with hypertension (accuracy on training and test sets was 0.68 and 0.63, respectively, with a cross-validation coefficient of 10/10, P<0.05), and ABCA1 V825I locus positively interacted with AGT M235T locus. The gene-environment interactions among ABCA1 V825I and R219K loci, AGT M235T locus, and occupational stress were associated with hypertension (accuracy on training and test sets was 0.74 and 0.63, respectively, with a cross-validation coefficient of 10/10, P<0.05), and AGT M235T locus negatively interacted with occupational stress. Conclusion Genotype VI and II of V825I locus at ABCA1, genotype TT of M235T locus at AGT, and high occupational stress may be risk factors for oilfield workers’ hypertension in Karamay, and the interactions of gene-gene and gene-environment among ABCA1 and AGT gene polymorphisms and occupational stress may be associated with hypertension.
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Mitochondrion is a multifunctional organelle in cells and responsible for energy production, cell apoptosis and various life processes. Dysfunctional mitochondria are associated with hundreds of diseases. Increasing evidences have shown that extracellular mitochondria can be endocytosed by cells, directly into cells, and then play roles in cells. Mitochondria are the organelles that are extremely sensitive to oxygen content and pH of microenvironment that induces the adverse effect based on the cellular environment: mitochondria will increase cell survival and viability when they arrive in cells of physiological environment, but mitochondria will cause cell death when they enter the hypoxic and acidic tumor tissues, because they can produce a large amounts of oxygen free radicals. The pharmacological feature of environmental responsiveness of mitochondria could make them as a potential biological drug to kill cancer cells and restore the function of damaged tissues. Currently, mitochondria are used in the treatment of central nervous system diseases (Parkinson's disease, depression, schizophrenia, etc.), peripheral system diseases (ischemic myocardial injury, fatty liver, emphysema, etc.) and tumor. In this review, we summarize the research progress, medical application and challenges of mitochondrial therapy.
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Apoptosis , MitochondriaABSTRACT
Polypeptide fragment of rabies virus glycoprotein(RVG)has become one of the most popular polypeptides in drug delivery field,because of its advantages of neurotropiam,penetration of blood-brain barrier and biosafety.Polypeptide fragment of RVG can directly deliver proteins and nucleic acids into brain.Additionally,when polypeptide fragment of RVG couples with drug-loading polymers,nanoparticles or liposomes,it can mediate the latters into brain.The application of the RVG polypeptide fragment provides a safe and effective approach for the treatment of brain diseases with biomolecules,such as chemicals,proteins.plasmids,siRNA,miRNA.
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Aim To analyze the antibiotic activity and mechanism of a polypyridyl ruthenium complex. Meth-ods The antibacterial activity of [ ( Phen ) 2 Ru ( dp-pz) ] ( PF6 ) 2 was determined by MIC and MBC value. Based on a fluorescent activity of this complex, the flu-orescent emission spectra was used to analyze the com-bination of complex to DNA. Then the competition combination was analyzed between complex and Gold View to DNA. Lastly, gel electrophoresis of DNA was applied to detect the combination situation between complex and DNA. Results This kind of polypyridyl ruthenium complex showed a significant antibacterial activity with a minimum antibacterial conentration of 0. 2~0. 4 g · L-1 . That was caused by the combina-tion and distortion of DNA due to the activity of this complex. Conclusion The antibacterial activity and the mechanism of antibacterial activity about [ ( Phen) 2 Ru( dppz) ] ( PF6 ) 2 are confirmed in this re-search, which provides a good foundation for the devel-opment of such class of compound.
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Mitochondrial DNA (mtDNA)genome mutations and defects are the essential mechanism of a various of mitochondrial dysfunction associated with diseases. The studies of targeting de-livery nucleic acid into mammalian mitochondria can thoroughly correct mtDNA mutation, rescue mtDNA impairment and then reverse the progress of diseases. There’s obvious differences be-tween nucleic acid import pathway of mammalian mitochondria and gene transfection of nuclei. In this paper, the effective strat-egies of delivering DNA and RNA(tRNA,rRNA,mRNA and an-tisense RNA)into mitochondria have been reviewed, as well as the challenges and development.
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Aim Targeted drug delivery in the brain is the necessary way for the treatment of brain diseases. In our study, a new peptide derived from the rabies vi-rus glycoprotein ( RVG-derived peptide, RDP ) was used as a targeted carrier to modify the curcumin stealth liposomes, and their characteristics and brain targeting effect were studied. Methods The curcumin liposomes were prepared by thin film dispersion. The release test in vitro was conducted to investigate their drug release. Curcumin distribution in several organs of mice was investigated by caudal vein injection of curcumin suspension liquid ( CUR ) , curcumin lipo-somes ( CUR-L) , RDP modified curcumin stealth lipo-somes ( RDP-CUR-L) via HPLC assay at different time points. Results The prepared stealth nano liposomes had a size of around 100 nm, and also had a good dis-persion and reproducibility. The entrapment efficiency was larger than 85%. After caudal vein injection of CUR, CUR-L and RDP-CUR-L in mice respectively, no curcumin was detected in brain of CUR group, and only a little was detected in CUR-L group. Neverthe-less, high concentration of curcumin was detected in RDP-CUR-L group. Conclusion RDP can deliver li-posome into the brain, which may provide a new meth-od for the treatment of brain diseases.
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Aim Through identification of the difunc-tionality of neuroprotection and passage of blood-brain barrier ( BBB) for RDP-BDNF fusion protein to offer a new strategy to treat brain diseases. Methods BDNF was conjugated to a novel cell penetrating peptide known as RDP which was derived from rabies virus gly-coprotein ( RVG) . The fusion protein RDP-BDNF was expressed in E. coli BL21 ( DE3 ) . After the intrave-nous injection of RDP-BDNF, the time effect curve of RDP-BDNF in the brains and serum was examined. Additionally , Morris water maze test was used to evalu-ate the effect of RDP-BDNF on scopolamine-induced amnesic mice, and the mechanism was also studied. Results RDP-BDNF could cross the BBB and exhibi-ted neuroprotective effects on the treatment of cognitive deficit induced by scopolamine in dementia model mice. Conclusions Delivery of protein therapeutics using RDP might offer a new and exciting strategy to treat brain diseases.
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OBJECTlVE To establish Tg(-6.3CYP3A65∶EGFP) transgenic zebrafish for quick, intuitive detection of heavy metals ( copper, cadmium and zinc) , dioxin-like PCBs ( PCB126) and other environmental pollutants. METHODS Tol2 transposon system was used to generate transgenic zebrafish lines Tg(-6.3CYP3A65∶EGFP) in which CYP3A65 promoter regualated labeled fluorescence. The effect of heavy mentals ( copper, cadmium and zinc ) and PCB126 on the relative amounts of CYP3A65 gene expression was determined by observing the change in fluorescence intensity. RESULTS The relative gene expression of CYP3A65 was significantly increased after 96 h exposure to copper 0.1 and 0.2μmol·L-1 , cadmium 0.35 and 0.7μmol·L-1 , zinc 1.5 and 3μmol·L-1 , and PCB126 2-32μmol·L-1 , respectively ( P<0.01) , but decreased after 96 h exposure to copper 0. 9 μmol·L-1 , cadmium 2. 7 and 5.4 μmol·L-1 , and zinc 24μmol·L-1 , respectively( P<0.01) . CYP3A65 gene expression was significantly increased after 168 h exposure to copper 0.1 and 0.2 μmol·L-1 , cadmium 0.35 and 0.7 μmol·L-1 , zinc 1.5 and 3 μmol·L-1, and PCB126 2-32 μmol·L-1, respectively(P<0.01), but decreased after 168 h exposure to copper 0.9 μmol·L-1, cadmium 2.7 and 5.4 μmol·L-1, and zinc 12 and 24 μmol·L-1( P<0.05) , in a concentration-dependent manner. CONCLUSlON The results suggest that zebrafish CYP3A65 gene expression and the CYP3A65 labeled fluorescence lines can be another candidate biomarker for detecting environmental pollutants.
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Blood-brain barrier (BBB) is the major obstacle for drug delivery into the central nervous system (CNS). However, there is no ideal model animal for the study of BBB permeability till now. Currently zebrafish (Danio rerio) has emerged as a powerful model organism for the study of vertebrate biology. In this study, the feasibility of using zebrafish as model animal was investigated for BBB permeability by comparing the results of administration of BBB-penetrating peptide and protein to mouse and zebrafish. The results showed that the BBBs of mouse and zebrafish were similar in molecular permeability. Additionally, zebrafish has advantageous features as a model animal, such as small size, fertile and easy to breed. Therefore, it is suggested that zebrafish may be a favored model for the study of BBB permeability.
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OBJECTIVE To investigae the gene resistant to quaternary ammonium compounds of multiple drug resistant Acinetobacter baumannii(MDR-ABA).METHODS The quaternary ammonium compounds qacE?1 gene in 20 MDR-ABA strains were detected by PCR.RESULTS The 20 MDR-ABA strains showed multiple resistance,its sensitivity to imipenm was 65% only.Among twenty strains of MDR-ABA qacE?1 gene were all positive.CONCLUSIONS The results indicate that qacE?1 gene were all carred class 1 integron.The chlorhexidine usage in prevnting hospital infection after surgery should be reevaluated.
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OBJECTIVE To investigate the aminoglycoside modifying enzymes genes of multi-drug resistant Acinetobacter baumannii(MDR-ABA).METHODS The four kinds aminoglycoside modifying enzymes genes(aac(6′)-Ⅰad,aac(6′)-Ⅰb,aac(3)-Ⅰ,ant(3″)-Ⅰ) of 20 strains MDR-ABA were detected by PCR.RESULTS Among 20 MDR-ABA strains,12 strains of aac(3)-Ⅰ,15 strains of aac(6′)-Ⅰb,18 strains of ant(3″)-Ⅰwere positive,and aac(6′)-Ⅰad was negative.The new subtype aac(6′)-Ⅰad gene has not been found.CONCLUSIONS Twenty strains MDR-ABA aminoglycoside modifying enzymes genes are found in all the 20 MDR-ABA strains.The genotype is in accordance with antibiotics resistance.It can induce clone transmitting hospital infection.It is first time to study the aac(6′)-Ⅰad gene of A.baumannii in China.
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OBJECTIVE To investigate the ?-lactamases gene of multi-drug resistant Acinetobactor baumannii(MDR-ABA).METHODS The blaTEM,blaSHV,blaPER,blaGES,blaIMP,blaVIM,blaSIM,blaOXA-23,blaADC and blaDHA genes of 20 MDR-ABA strains were detected by PCR.RESULTS Among 20 MDR-ABA strains,18 strains were with positive blaADC,11 strains were with positive blaTEM;the others were negative.Totally 19 strains were with genes correlated to ?-lactam antibiotics.The results indicated that the blaADC DNA sequence was a new subtype type compared with the blaADC sequence which had registered on America GenBank.CONCLUSIONS blaADC Gene and blaTEM gene have spread in the MDR-ABA group and a new blaADC subtype has been found.
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OBJECTIVE To test and analyze the new drug-resistant characteristics of Acinetobacter baumannii.METHODS The bacteria identification was determined by the routine method.Antimicrobial susceptibility was detected by K-B test.RESULTS In 95 A.baumannii strains,in addition to imipenem,the drug-resistant incidence was above 49%.There were two A.baumannii strains resistant to imipenem,and were seen panresistant strains The new characteristics of drug-resistance were found.CONCLUSIONS A new drug-resistant mode about A.baumannii to amikacin is found.The high drug-resistant incidence of A.baumannii becomes a very important problem.
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Some basic nuclear localization signals(NLS) have the capability of penetrating cell membrane and deliverying recombinant proteins, DNA, oligonucleotide into living cells. NLS based delivery system prohaps can satisfy most of major requirement in cargoing exogenous macromolecules or charged compounds. Different internalization mechanisms were found for different NLSs. Endocytosis or electrostatic binding of the anionic membranes and cationic NLSs probably induce celluar uptake.
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AIM: The changes of myocardial nuclear membrane Ca 2+ -ATPase function was investigated in ischemia/reperfusion injury. METHODS: The model of myocardial ischemia/reperfusion injury was established in rats. Myocardial nuclei were purified with sucrose density centrifugation,the activity of Ca 2+ -ATPase was measured and calcium uptake was assayed with [ 45 Ca 2+ ] . RESULTS: Plasma levels of malondialdehyde (MDA) and free fatty acid (FFA) in myocardial ischemia/reperfusion injury increased significantly( P
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Small interfering RNA (siRNA) is emerging as a powerful tool for in vivo research and for use as potential therapeutic agents. This review demonstrates the examples of the applications of siRNA as a new modality in gene therapy which can elicit down-regulation of gene expression and has prodigious potential in the treatment of diseases in mammals. Before siRNA technique is used in vivo, efficient strategies of delivery must be designed, such as vectors and routes of delivery. The problems that should be considered before applying this technology are outlined.