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1.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926096

RESUMO

The SOS response is induced upon DNA damage and the inhibition of Z ring formation by the product of the sulA gene, which is one of the LexA-regulated genes, allows time for repair of damaged DNA. On the other hand, severely DNA-damaged cells are eliminated from cell populations. Overexpression of sulA leads to cell lysis, suggesting SulA eliminates cells with unrepaired damaged DNA. Transcriptome analysis revealed that overexpression of sulA leads to up-regulation of numerous genes, including soxS. Deletion of soxS markedly reduced the extent of cell lysis by sulA overexpression and soxS overexpression alone led to cell lysis. Further experiments on the SoxS regulon suggested that LpxC is a main player downstream from SoxS. These findings suggested the SulA-dependent cell lysis (SDCL) cascade as follows: SulA→SoxS→LpxC. Other tests showed that the SDCL cascade pathway does not overlap with the apoptosis-like and mazEF cell death pathways.

2.
Nagoya J Med Sci ; 83(1): 183-194, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33727749

RESUMO

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P <5×10-8), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance (P <1×10-6). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SGMS2 SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of KLK3 SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future.

3.
Br J Nutr ; : 1-9, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33632354

RESUMO

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1-3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.

4.
Sci Rep ; 11(1): 2900, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536479

RESUMO

MicroRNAs (miRNAs) are cargo carried by extracellular vesicles (EVs) and are associated with cell-cell interactions. The response to the cellular environment, such as disease states, genetic/metabolic changes, or differences in cell type, highly regulates cargo sorting to EVs. However, morphological features during EV formation and secretion involving miRNA loading are unknown. This study developed a new method of EV loading using cell resealing and reconstituted the elementary miRNA-loading processes. Morphology, secretory response, and cellular uptake ability of EVs obtained from intact and resealed HeLa cells were comparable. Exogenously added soluble factors were introduced into multivesicular endosomes (MVEs) and their subsequent secretion to the extracellular region occurred in resealed HeLa cells. In addition, miRNA transport to MVEs and miRNA encapsulation to EVs followed a distinct pathway regulated by RNA-binding proteins, such as Argonaute and Y-box binding protein 1, depending on miRNA types. Our cell-resealing system can analyze disease-specific EVs derived from disease model cells, where pathological cytosol is introduced into cells. Thus, EV formation in resealed cells can be used not only to create a reconstitution system to give mechanistic insight into EV encapsulation but also for applications such as loading various molecules into EVs and identifying disease-specific EV markers.

5.
J Epidemiol ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33612706

RESUMO

BACKGROUND: Inflammation is thought to be a risk factor for kidney disease. However, discussion is controversial whether inflammatory status is either a cause or an outcome of chronic kidney disease. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using mendelian randomization (MR) approaches. METHODS: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively. RESULTS: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 95%CI: 0.000, -0.019 to 0.020 and -0.003, -0.019 to 0.014). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 95% CI: -0.005, -0.020 to 0.010 and -0.004, -0.020 to 0.012). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: -0.008, -0.058 to 0.042; IVAsian: 0.001, -0.036 to 0.036). CONCLUSIONS: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.

6.
Eur J Clin Nutr ; 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33281188

RESUMO

BACKGROUND/OBJECTIVES: Individual eating habits may be influenced by genetic factors, in addition to environmental factors. Previous studies suggested that adherence to Japanese food patterns was associated with a decreased risk of all-cause and cardiovascular disease mortality. We conducted a genome-wide association study (GWAS) in a Japanese population to find genetic variations that affect adherence to a Japanese food pattern. SUBJECTS/METHODS: We analyzed GWAS data using 14,079 participants from the Japan Multi-Institutional Collaborative Cohort study. We made a Japanese food score based on six food groups. Association of the imputed variants with the Japanese food score was performed by linear regression analysis with adjustments for age, sex, total energy intake, alcohol intake (g/day), and principal components 1-10 omitting variants in the major histocompatibility region. RESULTS: We found one SNP in the 14q11.2 locus that was significantly associated with the Japanese food score with P values <5 × 10-8. Functional annotation revealed that the expression levels of two genes (BCL2L2, SLC22A17) were significantly inversely associated with this SNP. These genes are known to be related to olfaction and obesity. CONCLUSION: We found a new SNP that was associated with the Japanese food score in a Japanese population. This SNP is inversely associated with genes link to olfaction and obesity.

7.
Sci Rep ; 10(1): 20125, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208865

RESUMO

Dietary phosphate overload induces chronic kidney disease (CKD), and calciprotein particles (CPPs), a form of nanoparticle comprising calcium phosphate and serum proteins, has been proposed to cause renal toxicity. However, the mechanism of CPP cytotoxicity in renal tubular cells is unknown. Here we show that in renal proximal tubular epithelial HK-2 cells, endocytosed CPPs accumulate in late endosomes/lysosomes (LELs) and increase their luminal pH by ~ 1.0 unit. This results in a decrease in lysosomal hydrolase activity and autophagic flux blockage without lysosomal rupture and reactive oxygen species generation. CPP treatment led to vulnerability to H2O2-induced oxidative stress and plasma membrane injury, probably because of autophagic flux blockage and decreased plasma membrane cholesterol, respectively. CPP-induced disruption of lysosomal homeostasis, autophagy flux and plasma membrane integrity might trigger a vicious cycle, leading to progressive nephron loss.

8.
Sci Rep ; 10(1): 18499, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116160

RESUMO

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B12 as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B12, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41-3.96) in men and 1.86 (95% CI 1.11-3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B12 was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B12.

9.
Phys Rev Lett ; 125(10): 106601, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32955334

RESUMO

We report the observation of the higher-order thermoelectric conversion based on a magneto-Thomson effect. By means of thermoelectric imaging techniques, we directly observed the temperature change induced by the Thomson effect in a polycrystalline Bi_{88}Sb_{12} alloy under a magnetic field and found that the magnetically enhanced Thomson coefficient can be comparable to or even larger than the Seebeck coefficient. Our experiments reveal the significant contribution of the higher-order magnetothermoelectric conversion, opening the door to "nonlinear spin caloritronics."

10.
J Epidemiol ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32963210

RESUMO

BACKGROUND: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. METHODS: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history, and collected peripheral blood samples. RESULTS: The baseline survey included 92,610 adults (mean age: 55.2 [9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. CONCLUSIONS: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

11.
Medicine (Baltimore) ; 99(38): e22370, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957414

RESUMO

BACKGROUND: Dementia among the Japanese aged 65 years or over population is estimated to approach about 700 million cases by 2025, and a corresponding rapid increase in Alzheimer disease (AD) can also be expected. The ballooning number of dementia patients, including AD, is creating major medical and social challenges. At present, only 3 drugs are recognized for the treatment of mild AD, and these are only used to alleviate symptoms. Although new therapies are needed to treat mild AD, insufficient development of disease-modifying drugs is being done. METHODS/DESIGN: The aim of this exploratory, open standard, treatment-controlled, randomized allocation, multicenter trial is to determine the efficacy of the traditional Japanese Kampo medicine hachimijiogan (HJG) on the cognitive dysfunction of mild AD.Eighty-six patients with AD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and as mild AD according to the Mini Mental State Examination (MMSE ≥21) will be included. All will already have been taking the same dose of Donepezil, Galantamine, or Rivastigmine for more than 3 months. The patients will be randomly assigned to receive additional treatment with HJG or to continue mild AD treatment without additional HJG. The primary endpoint is the change from baseline of the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version (ADAS-Jcog). ADAS-Jcog is a useful index for detecting change over time that investigates memory and visuospatial cognition injury from the early stage. The secondary endpoints are the changes from baseline of the Instrumental Activity of Daily Life, Apathy scale, and Nueropsychiatric Inventory scores. In this protocol, we will examine the Geriatric depression scale and do Metabolome analysis as exploratory endpoints. The recruitment period will be from August 2019 to July 2021. DISCUSSION: This is the first trial of Kampo medicine designed to examine the efficacy of HJG for the cognitive dysfunction of patients with mild AD. TRIAL REGISTRATION: This trial was registered on the Japan Registry of Clinical trials on 2 August 2, 2019 (jRCTs 071190018).


Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Idoso , Cognição/efeitos dos fármacos , Feminino , Humanos , Masculino , Medicina Kampo/métodos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Eur J Clin Nutr ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895509

RESUMO

BACKGROUND/OBJECTIVE: Although benefits of fish consumption for health are well known, a significant percentage of individuals dislike eating fish. Fish consumption may be influenced by genetic factors in addition to environmental factors. We conducted a genome-wide association study (GWAS) to find genetic variations that affect fish consumption in a Japanese population. METHODS: We performed a two-stage GWAS on fish consumption using 13,739 discovery samples from the Japan Multi-Institutional Collaborative Cohort study, and 2845 replication samples from the other population. We used a semi-quantitative food frequency questionnaire to estimate food intake. Association of the imputed variants with fish consumption was analyzed by separate linear regression models per variant, with adjustments for age, sex, energy intake, principal component analysis components 1-10, and alcohol intake (g/day). We also performed conditional analysis. RESULTS: We found 27 single nucleotide polymorphisms (SNPs) located in 12q24 and 14q32.12 that were associated with fish consumption. The 19 SNPs were located at 11 genes including six lead SNPs at the BRAP, ACAD10, ALDH2, NAA25, and HECTD4 regions on 12q24.12-13, and CCDC197 region on 14q32.12. In replication samples, all five SNPs located on chromosome 12 were replicated successfully, but the one on chromosome 14 was not. Conditional analyses revealed that the five lead variants in chromosome 12 were in fact the same signal. CONCLUSION: We found that new SNPs in the 12q24 locus were related to fish intake in two Japanese populations. The associations between SNPs on chromosome 12 and fish intake were strongly confounded by drinking status.

13.
Nutrients ; 12(6)2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32486113

RESUMO

The association between dietary acid load and metabolic syndrome (MetS) has not been fully investigated. A cross-sectional study was performed on 14,042 men and 14,105 women (aged 35-69 years) who participated in a baseline survey of the Japan Multi-Institutional Collaborative Cohort study. Dietary acid load was assessed using the net-endogenous-acid-production (NEAP) score that is closely correlated with the rate of renal net acid excretion. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009 using body-mass index instead of waist circumference. After adjusting for potential confounders, higher NEAP scores were associated with a significantly increased odds ratio (OR) of MetS, obesity, high blood pressure, and high fasting blood glucose. These associations remained significant after further adjustment for carbohydrate intake or two nutrient-pattern scores significantly associated with MetS. After adjustment for fiber, iron, potassium, and vitamin pattern scores, the OR of MetS for the highest quartile of NEAP scores, relative to the lowest quartile, was 1.25 (95% confidence interval 1.12-1.39). There was no significant interaction between sex, age, or body-mass index and NEAP. Higher dietary acid load was associated with a higher prevalence of MetS and several of its components, independently of carbohydrate intake or nutrient patterns.

14.
J Atheroscler Thromb ; 27(10): 1108-1122, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32281547

RESUMO

AIM: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan. METHODS: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression. RESULTS: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C <100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend=0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population. CONCLUSIONS: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

15.
J Atheroscler Thromb ; 27(10): 1097-1107, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32269208

RESUMO

AIM: Accumulating evidence reveals that sedentary behavior is associated with mortality and cardiometabolic disease; however, there are potential age and sex differences in sedentary behavior and health outcomes that have not been adequately addressed. This study aimed to determine the association of sedentary behavior with cardiometabolic diseases such as hypertension, dyslipidemia, diabetes mellitus, and its risk factors in a large Japanese population according to age and sex. METHODS: Using data from the Japan Multi-Institutional Collaborative Cohort Study obtained from baseline surveys, data of 62,754 participants (27,930 males, 34,824 females) were analyzed. This study uses a cross-sectional design and self-administered questionnaires to evaluate sedentary time and anamnesis. For the logistic regression analysis, sedentary time <5 h/day was used as the reference and then adjusted for age, research areas, leisure-time metabolic equivalents, and alcohol and smoking status. From the analysis of anthropometric and blood examinations, 35,973 participants (17,109 males, 18,864 females) were analyzed. RESULTS: For hypertension and diabetes, sedentary time was associated with a significantly higher proportion of male participants. Both sexes were associated with a significantly higher proportion of participants with dyslipidemia. Participants who had longer sedentary time tended to have increased levels of blood pressure, triglycerides, and non-high-density lipoprotein cholesterol (HDL-C), and decreased levels of HDL-C, especially in the 60-69 years group. CONCLUSIONS: Independent of leisure-time physical activity, sedentary time was associated with cardiometabolic diseases in a large Japanese population classified by age and sex. Our findings indicate that regularly interrupting and replacing sedentary time may contribute to better physical health-related quality of life.

16.
Sci Rep ; 10(1): 4382, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32127621

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

17.
J Epidemiol ; 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32147644

RESUMO

BACKGROUND: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. METHODS: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20) and change in BMI (BMI change), among 11 586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. RESULTS: We found a significant association (P < 0.05/282 = 1.77×10-4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained even after additional adjustment for dietary energy intake. CONCLUSIONS: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.

18.
Appl Microbiol Biotechnol ; 104(2): 475-488, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31781815

RESUMO

Among the so-called non-conventional yeasts, Kluyveromyces marxianus has extremely potent traits that are suitable for industrial applications. Indeed, it has been used for the production of various enzymes, chemicals, and macromolecules in addition to utilization of cell biomass as nutritional materials, feed and probiotics. The yeast is expected to be an efficient ethanol producer with advantages over Saccharomyces cerevisiae in terms of high growth rate, thermotolerance and a wide sugar assimilation spectrum. Results of comprehensive analyses of its genome and transcriptome may accelerate studies for applications of the yeast and may further increase its potential by combination with recent biotechnological tools including the CRISPR/Cas9 system. We thus review published studies by merging with information obtained from comprehensive data including genomic and transcriptomic data, which would be useful for future applications of K. marxianus.


Assuntos
Biotecnologia/métodos , Perfilação da Expressão Gênica/métodos , Genômica/métodos , Microbiologia Industrial/métodos , Kluyveromyces/genética , Kluyveromyces/metabolismo , Engenharia Metabólica/métodos
19.
Biochim Biophys Acta Gen Subj ; 1864(2): 129329, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30914205

RESUMO

BACKGROUND: Cell-based assays are essential for analyzing molecular functions and spatiotemporal information. The cell resealing technique, in which pore-forming toxins are used to permeabilize cell membranes, enables the delivery of various membrane-impermeable molecules inside cells. SCOPE OF REVIEW: We review the basics of the resealed cell system, including optimized protocols, assessment of cellular damage, and recovery following permeabilization of the membrane. Additionally, we introduce the streptolysin O (SLO)-type and listeriolysin O (LLO)-type resealing techniques. In SLO, the formation of larger pores (~30 nm) enables the passage of a wider range of molecules. Then, we discuss the advantages and applications of the semi-intact cell system, in which ongoing permeabilization is selected to maintain and analyze a specific cellular environment. MAJOR CONCLUSIONS: As confirmed by the effective use of quantitative image analysis, the SLO-type resealing system is successful for establishing and phenotyping diabetic model cells by introducing cytosol from diabetic mice. The LLO-type resealing technique enables the delivery of mid-sized molecules with high efficiency and low damage. As each technique has specific advantages, understanding the characteristics of LLO and SLO is necessary for choosing the appropriate technique. GENERAL SIGNIFICANCE: SLO-type resealing is optimal for creating disease model cells and drug screening, especially lifestyle-related diseases. LLO-type resealing is expected to be suitable for screening mid-sized biological drugs. Semi-intact cells can contribute to elucidating various cellular phenomena that have remained intractable due to their complexity.


Assuntos
Toxinas Bacterianas/química , Permeabilidade da Membrana Celular/efeitos dos fármacos , Técnicas Citológicas , Proteínas de Choque Térmico/química , Proteínas Hemolisinas/química , Estreptolisinas/química , Animais , Proteínas de Bactérias/química , Produtos Biológicos , Membrana Celular/metabolismo , Citosol/metabolismo , Diabetes Mellitus Experimental , Fluoresceína/química , Edição de Genes , Genótipo , Células HEK293 , Humanos , Membranas/metabolismo , Camundongos , Fenótipo
20.
J Infect Chemother ; 26(1): 28-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31279522

RESUMO

Occult hepatitis B virus (HBV) infection (OBI) is hepatitis B surface antigen (HBsAg) negative but with detectable HBV DNA. Although HIV infection has been reported to be a risk factor for OBI, the prevalence and clinical features of OBI in Japanese HIV infected patients have not been documented. This retrospective, single-center study was conducted to determine the prevalence and characteristic of OBI in Japanese antiretroviral therapy (ART) naïve HIV infected patients. OBI was defined as the presence of serum HBV DNA but without detectable HBsAg. Of the 147 ART naïve HIV infected patients, OBI was detected in 9 (6.1%) patients; 2 (4.3%) of 47 with both anti-HBs and anti-HBc positive, 6 (27.3%) of 22 with anti-HBc alone, and 1 (2.0%) of 50 with both anti-HBs and anti-HBc negative. The mean HBV DNA level was low at 28.7 ± 18.2 IU/mL. The proportion of OBI patients with anti-HBc alone was significantly higher than that of non-OBI patients (66.7% vs 14.5%, P = 0.001). In addition, the prevalence of AIDS (acquired immunodeficiency syndrome)-defining illnesses in the OBI group was significantly higher than in the non-OBI group (77.8% vs 35.5%, P = 0.001). No significant difference was found in the CD4 count or alanine aminotransferase levels of these two groups. This is the first study to reveal the prevalence and clinical features of OBI in Japanese HIV-infected patients. The persistence of anti-HBc alone and AIDS-defining illnesses were associated with the occurrence of OBI in these patients.


Assuntos
Infecções por HIV , Hepatite B , Adulto , DNA Viral/sangue , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
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