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1.
J Am Med Dir Assoc ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31588027

RESUMO

OBJECTIVE: To investigate associations between leisure activities, examining each activity separately and in combination, and all-cause mortality among the Chinese oldest-old (≥80 years) population. DESIGN: Prospective cohort study. SETTING: Community-living, the oldest-old from 22 provinces in China. PARTICIPANTS: We included 30,070 Chinese individuals aged ≥80 years (mean age: 92.7 years) from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. MEASUREMENTS: Cox proportional hazards models were used to estimate relationships between leisure activities and all-cause mortality, adjusting for covariates including sociodemographic and lifestyle factors, self-reported medical history, and other potential confounders. RESULTS: During 110,278 person-years of follow-up, 23,661 deaths were documented. Participants who engaged in watching TV or listening to the radio, playing cards or mah-jong, reading books or newspapers, gardening, keeping domestic animals or pets, or attending religious activities "almost every day" had a significantly lower mortality risk (adjusted hazard ratios ranged from 0.82 to 0.89; P < .01 for all) than did participants who "never" engaged in those activities. Furthermore, engagement in multiple leisure activities was associated with a reduced risk of all-cause mortality (P for the trend < .001). CONCLUSIONS AND IMPLICATIONS: Frequent participation in leisure activities might help decrease the risk of death in the Chinese oldest-old population. This finding has important implications for public health policy and encourages the incorporation of a broad range of leisure activities into the daily lives of oldest-old individuals.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31435643

RESUMO

BACKGROUND: The aim of this study was to examine the trends in impairment regarding activities of daily living (ADL), physical performance and cognitive function among the oldest-old (those aged ≥80 years) in China between 1998 and 2014. METHODS: We used data on 34,297 oldest-old individuals from the seven waves of the Chinese Longitudinal Healthy Longevity Study. We estimated age, period and cohort effects on the prevalence of self-reported ADL impairment, tested physical performance and cognitive function impairment using the age-period-cohort (APC) model. RESULTS: Regarding age, the prevalence of ADL, physical and cognitive impairment were highest in the centenarians, but they did not increase with age in this population. Among the literate subgroup, the prevalence of cognitive impairment increased more rapidly with age than that in the illiterate subgroup. Regarding period, the prevalence of self-reported and tested physical impairment slowly increased between 1998 and 2014, but cognitive impairment remained stable. Regarding cohort, ADL impairment continuously decreased. However, physical and cognitive impairment remained stable after a brief decline in the early birth cohorts. CONCLUSIONS: The results suggest that the age effect is still the most obvious effect regarding several types of functional impairment. The likelihood of a younger person experiencing functional impairment may not change significantly, but ADL is likely to be amenable to improvement resulting from improved medical and social care. Therefore, increased care for the elderly may considerably improve their quality of life, particularly regarding their basic activities of daily living.

3.
Cancer Commun (Lond) ; 39(1): 43, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307548

RESUMO

Lung cancer is the leading cause of cancer mortality worldwide. Dendritic cells (DCs) are the key factors providing protective immunity against lung tumors and clinical trials have proven that DC function is reduced in lung cancer patients. It is evident that the immunoregulatory network may play a key role in the failure of the immune response to terminate tumors. Lung tumors likely employ numerous strategies to suppress DC-based anti-tumor immunity. Here, we summarize the recent advances in our understanding on lung tumor-induced immunosuppression in DCs, which affects the initiation and development of T-cell responses. We also describe which existing measures to restore DC function may be useful for clinical treatment of lung tumors. Furthering our knowledge of how lung cancer cells alter DC function to generate a tumor-supportive environment will be essential in order to guide the design of new immunotherapy strategies for clinical use.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30946444

RESUMO

Little is known about the role of specific leisure activities in affecting cognitive functions. We aim to examine the associations of specific leisure activities with the risk of cognitive impairment among oldest-old people in China. This community-based prospective cohort study included 10,741 cognitively normal Chinese individuals aged 80 years or older (median age 88 years) from the Chinese Longitudinal Healthy Longevity Survey. Cognitive function was assessed using the Mini-mental State Examination (MMSE). Cox proportional hazards models were utilized to estimate the effects of specific leisure activities on cognitive impairment outcome. During a median follow-up time of 3.4 years (41,760 person-years), 2,894 participants developed cognitive impairment. Compared to those who 'never' engaged in watching TV or listening to radio, reading books or newspapers, and playing cards or mah-jong, those who engaged in such activities 'almost every day' reduced their risk of cognitive impairment, the fully adjusted HRs were 0.56 (0.51-0.61), 0.64 (0.53-0.78), and 0.70 (0.56-0.86), respectively. The association between the risk of cognitive impairment and watching TV and listening to the radio, playing cards or mah-jong, and reading books or newspapers were stronger among those who had 2 or more years of education. Moreover, the association between risk of cognitive impairment and watching TV and listening to radio was stronger in men than in women. In conclusion, a greater frequency of TV watching or radio listening, reading books or newspapers and playing cards or mah-jong may decrease the risk of cognitive impairment among the oldest-old.

5.
J Nutr ; 149(6): 1056-1064, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30949685

RESUMO

BACKGROUND: High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear. OBJECTIVE: We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y. DESIGN: The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs. RESULTS: The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases. CONCLUSIONS: A higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.

6.
J Clin Endocrinol Metab ; 104(8): 3345-3354, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30896760

RESUMO

CONTEXT: The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear. OBJECTIVE: To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes. DESIGN, SETTING, AND PATIENTS: This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality. RESULTS: A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was <5.6% or >7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was <5.0%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 5.4%. However, we did not observe a statistically significant elevated risk of all-cause mortality above an HbA1c level of 5.4%. CONCLUSIONS: A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.

7.
Cancer Epidemiol ; 60: 67-76, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30925282

RESUMO

BACKGROUND: Differential microRNA (miRNA) expression profiles in plasma or serum were identified, providing foundation for studying their potentially diagnostic role in colorectal cancer (CRC). METHODS: We performed S-poly(T) Plus PCR assay to select and validate differentially expressed plasma miRNAs from a sample set including 101 CRC patients, 20 patients with colorectal noncancerous polyps (NCP), and 134 healthy controls. And bioinformatics methods was used to integrated predicted or validated targets of the differentially dysregulated miRNAs and analyzed their overrepresented pathways. RESULTS: After the two-phase selection and validation process, we identified a miRNA panel (miR-144-3p, miR-425-5p, and miR-1260b) with high diagnostic efficiency for CRC; the panel distinguished CRC patients from controls with 93.8% sensitivity and 91.3% specificity. Results indicated that the dysregulated miRNAs in CRC were functionally involved in several key cancer-related pathways, such as axonal guidance, PI3K, and calcium signaling pathways. CONCLUSIONS: Our study demonstrated that a plasma 3-miRNA panel may serve as a novel noninvasive biomarker to diagnose CRC. This plasma 3-miRNA panel may be related to CRC development. However, further studies are needed to highlight its theoretical strengths.

8.
J Clin Endocrinol Metab ; 104(8): 3370-3378, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30869791

RESUMO

CONTEXT: The patterns of the association between high-density lipoprotein cholesterol (HDL-C) concentrations and mortality among the elderly are still unclear. OBJECTIVE: To examine the association of HDL-C concentrations with mortality and to identify the optimal HDL-C concentration range that predicts the lowest risk of all-cause mortality among the elderly. DESIGN: This was a nationwide, community-based, prospective cohort study. PARTICIPANTS: This study included 7766 elderly individuals (aged ≥65 years; mean age: 74.4 years) from the Health and Retirement Study. Cox proportional hazards models and Cox models with penalized smoothing splines were used to estimate hazard ratios (HRs) with 95% CI for all-cause and cause-specific mortality. RESULTS: During a median follow-up of 5.9 years, 1921 deaths occurred. After a full adjustment for covariates, a nonlinear (P < 0.001 for nonlinearity) association was found between HDL-C and all-cause mortality [minimum mortality risk at 71 mg/dL (1.84 mM)]; the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration <61 mg/dL (1.58 mM; HR: 1.18; 95% CI: 1.05 to 1.33) and with HDL-C concentration >87 mg/dL (2.25 mM; HR: 1.56; 95% CI: 1.17 to 2.07) than in the group with HDL-C concentrations ranging from 61 to 87 mg/dL (1.58 to 2.25 mM). Nonlinear associations of HDL-C concentrations with both cardiovascular and noncardiovascular mortality were also observed (both P < 0.001 for nonlinearity). CONCLUSIONS: Among the elderly, nonlinear associations were found between HDL-C and all-cause and cardiovascular mortality. The single optimal HDL-C concentration and range were 71 mg/dL and 61 to 87 mg/dL, respectively.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(6): 1746-1751, 2018 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-30501715

RESUMO

OBJECTIVE: To detect the expression of JAK2/STAT3 mRNA in peripheral blood T cells from the patients with chronic idiopathic thrombocytopenic purpura(CITP), and to explore the relationship between JAK2/STAT3 mRNA and CITP. METHODS: CITP group and healthy control group were set in this study, The JAK2/STAT3 mRNA expression level in peropheral blood T cells of 2 groups was detected with the RT-PCR and agarose gel electrophoresis. RESULTS: JAK2 mRNA expression level in CITP group was significantly higher than that in control group(P<0.01), the STAT3 mRNA expression level in CITP group was also higher than control group(P<0.01), The JAK2/STAT3 mRNA expression level of CITP patiants increased obviously compared with control group. CONCLUSION: The expression level of JAK2/STAT3 mRNA increases signficanlty in chronic ITP patients, which involves in pathogenesis of CITP.

10.
Mikrochim Acta ; 185(12): 552, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30443680

RESUMO

A multiplexed graphene oxide (GO) fluorescent nanoprobe is described for quantification and imaging of messenger RNAs (mRNAs) in living cells. The recognizing oligonucleotides (with sequences complementary to those of target mRNAs) were labeled with different fluorescent dyes. If adsorbed on GO, the fluorescence of the recognizing oligonucleotides is quenched. After having penetrated living cells, the oligonucleotides bind to target mRNAs and dissociate from GO. This leads to the recovery of fluorescence. Using different fluorescent dyes, various intracellular mRNAs can be simultaneously imaged and quantified by a high content analysis within a short period of time. Actin mRNA acts as the internal control. This GO-based nanoprobe allows mRNA mimics to be determined within an analytical range from 1 to 400 nM and a detection limit as low as 0.26 nM. Up to 3 intracellular mRNAs (C-myc, TK1, and actin) can be detected simultaneously in a single living cell. Hence, this nanoprobe enables specific distinction of intracellular mRNA expression levels in cancerous and normal cells. It can be potentially applied as a tool for detection of cancer progression and diagnosis. Graphical abstract A multiplexed graphene oxide (GO)-based fluorescent nanoprobe is described for quantification and imaging of intracellular messenger RNAs. After penetrating living cells, the recovered fluorescence of the dissociated recognizing oligonucleotides can be analyzed , and this allows for simultaneous detection of up to 3 intracellular messenger RNAs.

11.
Chem Commun (Camb) ; 54(15): 1909-1912, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29393313

RESUMO

We developed a microplate-based enhanced chemiluminescence system for the direct detection of circulating miRNAs. The system exhibited a high target sensitivity and specificity, with a detection limit of 3.02 fM.


Assuntos
Técnicas Biossensoriais , MicroRNA Circulante/sangue , Luminescência , Hibridização de Ácido Nucleico , Humanos
12.
Sleep Breath ; 22(3): 815-824, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28612266

RESUMO

PURPOSE: Prospective studies reported inconsistent findings on the relationship between daytime napping and risk of type 2 diabetes (T2D). Categorized and dose-response meta-analyses were performed to quantify this relation. METHODS: Potentially eligible studies were identified by searching PubMed and Embase databases. Dose-response effects were assessed by the generalized least squares trend estimation and study-specific summary relative risks (RRs) with 95% confidence intervals (CIs) were computed with a random-effects model. RESULTS: Seven prospective studies including one US, four European, and two Chinese cohorts involving 249,077 participants and 13,237 cases of T2D were included. The overall analyses showed a 17% increased risk of T2D when comparing habitual nappers with non-nappers (RR = 1.17, 95% CI 1.08-1.27). By region, the summary RR was 1.21 (95% CI 1.17-1.26), 1.15 (95% CI 1.03-1.30) and 1.23 (95% CI 0.87-1.73) for the US, European, and Chinese studies, respectively. Limiting to five studies that excluded subjects with known major chronic disorders yielded a summary RR of 1.16 (95% CI 1.03-1.30). A dose-response analysis suggested an 11% (95% CI 7-16%) increased T2D risk for each increment in daytime napping of 30 min/day and, despite no evidence for nonlinearity (P nonlinearity = 0.65), the increased risk of T2D for short nap (<50 min/day) was dominated by the US study. CONCLUSIONS: This meta-analysis suggests that daytime napping is associated with an increased risk of T2D. Given the limited number of cohorts and inconsistency in terms of methodological and population characteristics across these cohorts, residual confounders and/or reverse causality cannot be fully addressed, and our findings should be interpreted with great caution. Future well-designed prospective studies are still warranted.

13.
Int J Cardiol ; 250: 240-246, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29066151

RESUMO

BACKGROUND: Treatments of type B aortic dissection (TBAD) include thoracic endovascular aortic repair (TEVAR), best medical treatment (BMT) and open surgery (OS). This meta-analysis was to compare these three strategies to evaluate which provides best outcomes. METHODS: We searched clinical trials that compared treatment strategies for TBAD. The outcomes measures were 30-day/in-hospital mortality, long-term survival rate, paraplegia or paraparesis, renal failure, rupture, stroke, late re-intervention, late rupture and aneurismal dilatation/expansion. RESULTS: Sixteen control trials covering 10,307 patients were evaluated. Meta-analysis showed that TEVAR provides preferable long-term survival rate (HR=0.71; 95% CI: 0.52-0.95), lower rate of late re-intervention (OR=0.33; 95% CI: 0.13-0.85), late rupture (OR=0.21; 95% CI: 0.10-0.43) and late aneurismal dilatation/expansion (OR=0.15; 95% CI: 0.04-0.63) compared with BMT. However, TEVAR seemed to be associated with higher stroke rate than BMT (OR=1.65; 95% CI: 1.21-2.23). 30-day/in-hospital mortality appeared to be lower in TEVAR (OR=0.49; 95% CI: 0.29-0.81) when compared with OS. In addition, OS induced higher 30-day/in-hospital mortality compared with BMT (OR=3.95, 95% CI: 1.56-10.02). CONCLUSIONS: Our study shows that TEVAR may be favorable in long-term outcomes and effectively provide morphologic advantages compared to BMT. However, there is a need for prophylactic measures against stroke in TEVAR. OS seems to be inferior to TEVAR both in short-term and long-term outcomes. Further studies especially randomized clinical trials are needed to comprehensively compare the efficacy between TEVAR and BMT.


Assuntos
Aneurisma Dissecante/diagnóstico , Aneurisma Dissecante/cirurgia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Aneurisma Dissecante/mortalidade , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/mortalidade , Procedimentos Endovasculares , Mortalidade Hospitalar/tendências , Humanos , Resultado do Tratamento
14.
Exp Ther Med ; 14(3): 2568-2576, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28962196

RESUMO

Mesenchymal stem cells (MSCs) are able to differentiate into hepatocytes, promote the regeneration of hepatic cells and inhibit the progression of hepatic fibrosis. Transforming growth factor (TGF)-ß1 is one of the key factors in the development of liver fibrosis, which also promotes extracellular matrix (ECM) formation. Drosophila mothers against decapentaplegic 7 (Smad7) is an essential negative regulator in the TGF-ß1/Smad signaling pathway. In the present study, bone mesenchymal stem cells (BMSCs) were isolated from rat bone marrow and transfected with lentiviral vectors carrying the Smad7 gene. Smad7-enhanced green fluorescent protein (EGFP)-BMSCs stably expressing Smad7 were subsequently co-cultured with hepatic stellate cells (HSCs) for 48 h. Smad7 and TGF-ß1 levels in the culture medium were detected using ELISA, and the levels of collagen (Col) I, Col III, laminin (LN) and hyaluronic acid (HA) were measured using immunoassays. The early apoptosis rates of HSCs were determined via flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to evaluate the mRNA and protein expression profiles, respectively. The results indicated that Smad7-EGFP-BMSCs stably expressing Smad7 were successfully constructed. Upon co-culturing with rat Smad7-EGFP-BMSCs, the early apoptotic rate of HSCs was significantly increased (P<0.05). Levels of Smad7 in the culture medium were also significantly increased (P<0.05), whereas the levels of TGF-ß1, Col I, Col III, LN and HA were significantly decreased (P<0.05). Furthermore, the mRNA and protein levels of Smad7 and matrix metalloproteinase 1 were significantly increased (P<0.05), whereas those of TGF-ß1, α-SMA, Smad2, smad3, TGF-ß receptor I, Col I, tissue inhibitors of metalloproteinase-1 and Col III were significantly decreased. The results of the present study suggest that rat BMSCs overexpressing Smad7 may inhibit the fibrosis of HSCs by regulating the TGF-ß1/Smad signaling pathway. This provides a novel insight into future treatments for liver fibrosis.

15.
Nutrients ; 9(9)2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28850090

RESUMO

Findings on the association between long-term intake of fish or long-chain n-3 polyunsaturated fatty acids (PUFAs) and risk of atrial fibrillation (AF) are inconsistent in observational studies. We conducted a meta-analysis of prospective studies to separately examine the associations between fish consumption and dietary intake of n-3 PUFAs with the risk of AF. A systematic search was conducted in PubMed and Embase to identify relevant studies. Risk estimates were combined using a random-effect model. Seven prospective cohort studies covering 206,811 participants and 12,913 AF cases were eligible. The summary relative risk of AF for the highest vs. lowest category of fish consumption and dietary intake of n-3 PUFAs was 1.01(95% confidence interval: 0.94-1.09) and 1.03 (95% confidence interval: 0.97-1.09), respectively. These null associations persisted in subgroup and dose-response analyses. There was little evidence of publication bias. This meta-analysis suggests that neither long-term intake of fish, nor of n-3 PUFAs were significantly associated with lower risk of AF.


Assuntos
Fibrilação Atrial/prevenção & controle , Inquéritos sobre Dietas , Ácidos Graxos Ômega-3 , Peixes , Análise de Alimentos , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
Exp Ther Med ; 13(4): 1456-1464, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28413492

RESUMO

Mesenchymal stem cells (MSCs) have been considered as hypo-immunogenic and immunosuppressive. However, a thorough understanding of the immunological properties after MSC differentiation in vitro and in vivo has not been reached. We asked whether it would be immunogenic after differentiation or influenced by the immune microenvironment after transplantation. In different disease models, the immunological changes of MSCs after differentiation greatly varied, with contradicting results. In order to clarify this, we used a modified four-step induction method to induce human umbilical cord MSCs (hUCMSCs) to differentiate into insulin-producing cells (IPCs), and investigate the immunological changes after differentiation and immune reactions after transplantation into diabetic mice. We found that the induced IPCs are hypo-immunogenic, lacking HLA-DR, CD40 and CD80 expression. Of note, we observed immune cell infiltration to peritoneal cavity and left kidney capsule after local transplantation of induced IPCs. This indicated that hUCMSC-derived IPCs maintained hypo-immunogenic in vitro, but became immunogenic after transplanting to the host, possibly due to the changes of immune microenvironment and thereafter immunological enhancement and immune cell infiltration.

17.
Endocr J ; 64(3): 291-302, 2017 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-28100871

RESUMO

Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet ß cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice. We found that hepatocytes could be directly reprogrammed into insulin-producing cells after PNM gene transfection by non-viral hydrodynamics injection, and fasting blood glucose was reduced to normal, and lasted until 100 days after transfection. Intraperitoneal glucose tolerance test (IPGTT) showed that glucose regulation ability was improved gradually and the serum insulin level approached to the level of normal mice with time. Insulin-positive cells were found in the liver tissue, and the expression of various islet ß-cell-specific genes were detected at the mRNA level, including islet mature marker gene Ucn3. In conclusion, we provide a new approach for the treatment of diabetes by in vivo direct reprogramming of liver cells to insulin producing cells through non-viral methods.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Transdiferenciação Celular , Hepatócitos/patologia , Proteínas de Homeodomínio/metabolismo , Células Secretoras de Insulina/patologia , Fatores de Transcrição Maf Maior/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transativadores/metabolismo , Regulação para Cima , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores/sangue , Biomarcadores/metabolismo , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Técnicas de Transferência de Genes/efeitos adversos , Hepatócitos/metabolismo , Proteínas de Homeodomínio/genética , Hidrodinâmica , Injeções Intravenosas , Insulina/sangue , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Fatores de Transcrição Maf Maior/genética , Masculino , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Plasmídeos/administração & dosagem , RNA Mensageiro/metabolismo , Organismos Livres de Patógenos Específicos , Cauda , Transativadores/genética , Urocortinas/genética , Urocortinas/metabolismo
18.
Immunol Cell Biol ; 95(2): 189-197, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27616751

RESUMO

Donor-reactive memory T (Tm)cells mediate accelerated rejection, which is known as a barrier to the survival of transplanted organs. Selective interference with the anti-CD45RB monoclonal antibody (α-CD45RB) reliably induces donor-specific tolerance. In this study, pre-sensitization to female C57BL/6 mice with the skin of female BLAB/c mice generated a large number of Tm cells and resulted in rapid rejection of the secondly transplanted allografts. α-CD45RB did induce the tolerance to skin allograft primarily transplanted but failed to induce tolerance in the pre-sensitized mice. Donor-specific spleen cell transfusion (DST) alone also failed to induce the tolerance in the pre-sensitized recipients. Interestingly, combination of α-CD45RB with DST inhibited the rejection induced by memory T cells in the pre-sensitized mice. CD25+ T-cell depletion in α-CD45RB combined with DST therapy recipients could prevent skin allograft tolerance from establishing. In addition, adoptive transfer of donor-primed memory T cells into the tolerant recipients markedly broke the established tolerance. Our findings indicate that α-CD45RB and DST can synergistically inhibit the accelerated rejection mediated by memory T cells and induce long-term skin allograft acceptance in mice.


Assuntos
Aloenxertos/imunologia , Rejeição de Enxerto/imunologia , Memória Imunológica , Antígenos Comuns de Leucócito/metabolismo , Transplante de Pele , Baço/citologia , Linfócitos T/imunologia , Doadores de Tecidos , Animais , Apoptose , Proliferação de Células , Feminino , Sobrevivência de Enxerto/imunologia , Inflamação/patologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Depleção Linfocítica , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Análise de Sobrevida , Linfócitos T Reguladores/imunologia
20.
Biosens Bioelectron ; 86: 8-13, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27318104

RESUMO

To date, few effective fluorescent biosensors based on RNA aptamers have been developed because the intrinsic instability of RNA in the presence of nucleases precludes the application of RNA aptamers for the analysis of biological fluids. In this study, we developed a simple, sensitive, selective turn-on fluorescent aptasensor for theophylline detection in serum, utilizing ligand-induced self-assembling RNA aptamers and two different interaction stages of the aptamer fragments with graphene oxide (GO). A single strand of the theophylline RNA aptamer (33-mer) was split at the end loop region into two shorter fragments, one of which was labeled with a fluorophore (FAM). In the absence of theophylline, the adsorption of the two individual fragments on GO brought the fluorophore in close proximity to the GO surface, resulting in highly efficient quenching of fluorescence. The system showed very low background fluorescence. Conversely, the fragments self-assembled into an RNA aptamer/theophylline complex and were dissociated from GO. The quenched fluorescence was significantly recovered, and theophylline could be detected at a wide range of concentrations from 1 to 100µM, with a detection limit of 0.155µM and good selectivity in serum. Moreover, because of the shorter RNA fragments and the effective protection ability of GO from nuclease cleavage, the RNA sequences remained stable during the experiments. This design may serve as an example for the application of RNA aptasensors in the clinical setting.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/instrumentação , Grafite/química , Espectrometria de Fluorescência/instrumentação , Teofilina/sangue , Análise Química do Sangue/instrumentação , Broncodilatadores/sangue , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Óxidos/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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