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Objective: To explore the association between hair trace element and all-cause death in the elderly in Hainan Province. Methods: The subjects of the study were elderly people from China Hainan Centenarian Cohort Study, a total of 163 elderly were included. The association between hair trace element level and all-cause death was analyzed by using Cox proportional risk regression model. Results: After fully adjusting the covariates, the multiple Cox proportional hazards regression analyses showed that selenium (Se), manganese (Mn), strontium (Sr) concentrations in hair were significantly associated with all-cause mortality, the hazard ratio (HR) were 0.72 (95%CI: 0.54-0.98, P=0.035), 1.50 (95%CI: 1.07-2.11, P=0.020) and 0.54 (95%CI: 0.37-0.79, P=0.001), respectively. Subgroup and cross analysis showed that hair copper (Cu) were significant association with death in the people with anemia, the HR were 1.81 (95%CI: 1.13-2.88, P=0.013). And, hair Mn interacted with anemia, the HR was 0.46 (95%CI: 0.22-0.94, P=0.033). Conclusions: Se, Mn and Sr concentrations in hair were associated with the elevated risk for all-cause death in the elderly in Hainan. Se, Mn and Sr concentrations in hair can be used as a reference index for the prediction of the death risk of long-lived elderly in community, suggesting that the daily diet of elderly people are rich and diverse, in order to maintain normal and balanced trace element content in the body.
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Anemia , Selenio , Oligoelementos , Anciano de 80 o más Años , Humanos , Anciano , Oligoelementos/análisis , Estudios de Cohortes , Cobre , Manganeso , Cabello/químicaRESUMEN
This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs.
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Fracturas Óseas , Osteoporosis , Fracturas Osteoporóticas , Masculino , Femenino , Humanos , Anciano , Anciano de 80 o más Años , Estudios Prospectivos , Cuidados a Largo Plazo , Medición de Riesgo , Osteoporosis/complicaciones , Osteoporosis/diagnóstico , Osteoporosis/tratamiento farmacológico , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Fracturas Óseas/prevención & control , Densidad Ósea , Factores de Riesgo , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/prevención & control , Absorciometría de FotónRESUMEN
This corrects the article DOI: 10.1103/PhysRevLett.126.171801.
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The Cryogenic Underground Observatory for Rare Events (CUORE) at Laboratori Nazionali del Gran Sasso of INFN in Italy is an experiment searching for neutrinoless double beta (0νßß) decay. Its main goal is to investigate this decay in ^{130}Te, but its ton-scale mass and low background make CUORE sensitive to other rare processes as well. In this Letter, we present our first results on the search for 0νßß decay of ^{128}Te, the Te isotope with the second highest natural isotopic abundance. We find no evidence for this decay, and using a Bayesian analysis we set a lower limit on the ^{128}Te 0νßß decay half-life of T_{1/2}>3.6×10^{24} yr (90% CI). This represents the most stringent limit on the half-life of this isotope, improving by over a factor of 30 the previous direct search results, and exceeding those from geochemical experiments for the first time.
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Granisetrón , Semivida , Teorema de BayesRESUMEN
OBJECTIVE: To assess national and regional trends and causes-specific distribution of maternal mortality in India. DESIGN: Nationally representative cross-sectional surveys. SETTING: All of India from 1997 to 2020. SAMPLE: About 10 000 maternal deaths among 4.3 million live births over two decades. METHODS: We analysed trends in the maternal mortality ratio (MMR) from 1997 through 2020, estimated absolute maternal deaths and examined the causes of maternal death using nationally representative data sources. We partitioned female deaths (aged 15-49 years) and live birth totals, based on the 2001-2014 Million Death Study to United Nations (UN) demographic totals for the country. MAIN OUTCOME MEASURES: Maternal mortality burden and distribution of causes. RESULTS: The MMR declined in India by about 70% from 398/100 000 live births (95% CI 378-417) in 1997-98 to 99/100 000 (90-108) in 2020. About 1.30 million (95% CI 1.26-1.35 million) maternal deaths occurred between 1997 and 2020, with about 23 800 (95% CI 21 700-26 000) in 2020, with most occurring in poorer states (63%) and among women aged 20-29 years (58%). The MMRs for Assam (215), Uttar Pradesh/Uttarakhand (192) and Madhya Pradesh/Chhattisgarh (170) were highest, surpassing India's 2016-2018 estimate of 113 (95% CI 103-123). After adjustment for education and other variables, the risks of maternal death were highest in rural and tribal areas of north-eastern and northern states. The leading causes of maternal death were obstetric haemorrhage (47%; higher in poorer states), pregnancy-related infection (12%) and hypertensive disorders of pregnancy (7%). CONCLUSIONS: India could achieve the UN 2030 MMR goals if the average rate of reduction is maintained. However, without further intervention, the poorer states will not. TWEETABLE ABSTRACT: We estimated that 1.3 million Indian women died from maternal causes over the last two decades. Although maternal mortality rates have fallen by 70% overall, the poorer states lag behind.
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Nacimiento Vivo/epidemiología , Mortalidad Materna , Adolescente , Adulto , Femenino , Humanos , India/epidemiología , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
We measured two-neutrino double beta decay of ^{130}Te using an exposure of 300.7 kg yr accumulated with the CUORE detector. Using a Bayesian analysis to fit simulated spectra to experimental data, it was possible to disentangle all the major background sources and precisely measure the two-neutrino contribution. The half-life is in agreement with past measurements with a strongly reduced uncertainty: T_{1/2}^{2ν}=7.71_{-0.06}^{+0.08}(stat)_{-0.15}^{+0.12}(syst)×10^{20} yr. This measurement is the most precise determination of the ^{130}Te 2νßß decay half-life to date.
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The aim of the study was to assess the relationship between underweight and falls. It was a cross-sectional study in community-based participants from China Hainan Centenarian Cohort Study (CHCCS). A total of 942 centenarians (mean ages were 102.4 years in men and 102.9 years in women, 21.8% were semi-supercentenarians, and 3.2% were supercentenarians) were enrolled from July 2014 to December 2016. Height and weight were measured according to the standard protocol. Participants were interviewed face to face to self-report falls for recent 3 months. The risks of future falls were evaluated by Morse Fall Scale (MFS). The mean body mass index (BMI) was 19.04±2.79 kg/m2 in men and 18.07±3.27 kg/m2 in women. The 3-month incidences of once fall were 10.3% in men and 13.4% in women, recurrent falls were 15.4% in men and 13.4% in women, future high risks of falls were 36.6% in men and 44.3% in women. There were underweight by gender interactions on at least one fall (OR=1.39, 95% CI=1.04-1.86, P=0.026) and future high fall risk (OR=1.39, 95% CI=1.07-1.80, P=0.014). Men with underweight had higher ratios of at least one fall (OR=4.12, 95% CI=1.59-10.70, P=0.004), recurrent falls (OR=6.71, 95% CI=1.69-26.63, P=0.007) and high risk of future falls (OR=2.44, 95% CI=1.27-4.70, P=0.007), while women with underweight was only associated with high risk of future falls (OR=1.37, 95% CI=1.01-1.85, P=0.043). Compared with normal weight and overweight, underweight in men had a higher MFS Score (increased by average 7.6 points, P=0.010), yet this trend was not observed in women counterparts. Underweight was associated with incidences of 3-month and future high fall risk in centenarians, which was more pronounced in men. Underweight could be a marker in identifying potential falls in long-lived people, especially men, who need further measures to gaining weight to normal and preventing falling.
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Accidentes por Caídas/estadística & datos numéricos , Peso Corporal/fisiología , Delgadez/complicaciones , Anciano de 80 o más Años , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Incidencia , MasculinoRESUMEN
Objective: To investigate the types and distribution of blood-sucking insects and arboviruses in Inner Mongolia autonomous region, and provide basic data for the prevention of arbovirus transmitted disease. Methods: Blood-sucking insects were collected by lamp trapping method in nature. Mosquito samples were classified according to morphologic characteristics and then stored at liquid nitrogen. Viruses were isolated in cell culture and characterized, using molecular biological methods. Results: A total of 24 240 mosquitoes and 17 110 aphids were collected from 2 sites of 5 counties (Flags) in Inner Mongolia in 2014 and during 2017-2018. Among them, Japanese encephalitis virus gene was detected in Culex pipiens pallens, and 4 virus strains isolates which could be stably passaged. The isolates were identified as Getah virus and densonucleosis virus by molecular biology identification. Phylogenetic analysis on the E2 gene of the Getah virus (NMDK1813-1) showed that it belonged to the same evolutionary branch of the Gansu isolates (GS10-2) and having six common amino acid variation sites. Conclusions: The emergence of Japanese encephalitis virus and Getah virus from specimen of mosquitoes in Inner Mongolia indicated the new challenges on the prevention and control of arbovirus and related diseases. The results pf this study provided basic data for the prevention and control stretagies of arbovirus transmitted diseases in Inner Mongolia.
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Alphavirus/aislamiento & purificación , Culicidae/virología , Virus de la Encefalitis Japonesa (Especie)/genética , Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Encefalitis Japonesa , Mosquitos Vectores/virología , ARN Viral/genética , Animales , China , Filogenia , ARN Viral/aislamiento & purificaciónRESUMEN
Objective: To understand the types and distribution of Arboviruses in Hainan province. Methods: Blood-sucking insects were collected in Hainan province from 2017 to 2018. After laboratory treatment, BHK-21 cells and C6/36 cells were inoculated with grinding supernatant of all blood-sucking insects to isolate all of involving virus. Arbovirus genes in blood-sucking insects were detected in parallel by RT-PCR method. Results: A total of 15 062 mosquitoes were classified into four genera (Culex, Armigeres, Aedes, Anopheles) and 11 360 midges were collected. Culex tritaeniorhynchus was in the majority and accounted for 92.88% (13 990/15 062) of all the mosquitoes collected. Four strains of virus isolates were notified by tissue culture method. Three strains of viruses belonged to Japanese encephalitis virus (JEV), with the other one as Getah virus (GETV). Five pools of JEV gene amplification were positive, from Culex tritaeniorhynchus. Results from the phylogenetic analysis showed that they belonged to genotype JEV-â . The minimum infection rate of JEV was 0.57 (8/13 990). A total of 5 pools of Akabane virus (AKV) gene amplification were positive. The minimum infection rate of AKV was 0.44 (5/11 360). Based on the S gene and M gene sequences of the virus, data from the phylogenetic analysis showed that the five AKV strains carried by midges in Hainan province were in a separate evolutionary branch and with formed unique geographical distribution. Conclusions: JEV and GETV had been isolated again from the mosquito specimens in this survey, since the 1980s. AKV was detected from the midge specimens in Hainan province. These results showed the needs of strengthening the programs on detection and monitor of JEV, GETV and AKV that were related to animal and human diseases in order to reduce the risks of related diseases in this area.
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Arbovirus/genética , Arbovirus/aislamiento & purificación , Culicidae/virología , Alphavirus/genética , Alphavirus/aislamiento & purificación , Animales , China , Culex/virología , Virus de la Encefalitis Japonesa (Especie)/genética , Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Humanos , FilogeniaRESUMEN
Objective: To investigate the distribution patterns of mosquitoes, midges and related arboviruses in Sichuan province. Methods: Blood-sucking insects were collected from houses and pens, using the ultraviolet lights. Mosquito samples were classified according to morphologic characteristics and then stored at liquid nitrogen. All samples were incubated with BHK-21 and C6/36 cells for virus isolation and then detected for their viral genes. Sequences of the virus were identified and analyzed by molecular biological software, such as BioEdit 7.0.5.3, MEGA 6.0. Results: In total, 17 019 mosquitoes from 3 genera and 4 species and 12 700 midges were collected from the southeast regions of Sichuan province in 2016 and 2017. Among them, 79.4% (13 519/17 019) belonged to Culex tritaeniorhynchus with 11.1% (1 897/17 019) as Armigeres subalbatus, 5.5% (930/17 019) were Anopheles sinensis and 4.0% (673/17 019) were Anopheles sinensis 3 virus strains that isolated from Culex tritaeniorhynchus were identified as typeâ Japanese encephalitis virus. Seven pools of mosquitoes isolated from Hejiang county were identified Japanese encephalitis virus gene positive through PCR amplification. With 4 pool midges were detected positive for Akabane virus through PCR gene amplification while midges samples didn't have virus isolates. Conclusions: Culex tritaeniorhynchus appeared the predominant species in the southeast regions of Sichuan. Japanese encephalitis virus transmitted by mosquitoes and Akabane virus by midges were prevalent in southeast Sichuan province.
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Arbovirus , Culicidae , Virus de la Encefalitis Japonesa (Especie)/genética , Animales , Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Encefalitis Japonesa/diagnóstico , Genes Virales , Técnicas de Amplificación de Ácido Nucleico , Filogenia , Reacción en Cadena de la PolimerasaRESUMEN
Objective: To understand the evolution characteristics of Banna viruses (BAVs) isolated worldwide from 1980 to 2012. Methods: In this study, a phylogenetic analysis using Bayesian Markov Chain Monte Carlo simulations was conducted on all available 12th segment of genes of BAVs isolated worldwide from 1980 to 2012 to investigate the evolutionary and epidemiologic dynamics of BAVs. Results: The Bayesian phylogenetic analysis of BAVs revealed that the common ancestor of BAVs appeared 315 (95%HPD: 63-619) years ago. The evolutionary rate of BAV based on the 12th segment gene was estimated to be 2.33×10-3 (95%HPD: 2.84× 10-4-8.52×10-3) substitution per site per year, indicating BAV belong to an emerging arbovirus with rapid evolution. Conclusion: The evolution of emerging BAVs is rapid and the distribution of BAVs has expanded with new variant being detected, so it is necessary to enhance the surveillance to fully understand the natural distribution and pathogenicity of BAVs.
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Coltivirus/genética , Filogenia , Teorema de Bayes , Coltivirus/patogenicidad , Evolución Molecular , Humanos , Cadenas de Markov , Método de MontecarloRESUMEN
UNLABELLED: This is the first study to investigate the association between the use of selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) and the risk of fractures using a nationwide representative cohort of ethnic Chinese. Current use of SSRI/SNRI and the co-morbidity, especially osteoporosis and history of falling, play an important role in the increased risk of fractures. INTRODUCTION: This nested case-control study examines the association between the timing, intensity, and individual components of serotonergic antidepressant (including SSRIs and SNRIs) use and the risk of all-cause fracture. METHODS: Using the 2002-2011 Taiwan National Health Insurance Research Database, we identified patients who received at least three prescriptions of antidepressants between January 1st 2002 and December 31st 2010 as our study cohort. In the study cohort, we identify 8250 patients who had first admission for fracture and 33,000 matched controls (1:4, matched by age, sex, and cohort entry date). Multivariate conditional logistic regression was used to estimate the association between the use of serotonergic antidepressants and the risk of fracture. RESULTS: Current users of serotonergic antidepressants were associated with an increased risk of fracture (adjusted odds ratio (aOR) 1.16 [95 % confidence interval 1.07-1.25]). Furthermore, a higher risk of fractures was found in patients with osteoporosis (aOR 3.05 [2.73-3.42]) or a history of falling (aOR 6.13 [3.41-11.0]). The risks of fracture between SSRI and SNRI users were comparable. CONCLUSION: Current use of SSRI/SNRI is associated with an increased risk of all caused fractures. Additionally, the co-morbidity, especially osteoporosis and a history of falling, plays an important role in the risk of fractures.
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Antidepresivos/efectos adversos , Fracturas Osteoporóticas/inducido químicamente , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Accidentes por Caídas/estadística & datos numéricos , Adulto , Anciano , Estudios de Casos y Controles , Comorbilidad , Bases de Datos Factuales , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Medición de Riesgo/métodos , Taiwán/epidemiologíaRESUMEN
AIMS/HYPOTHESIS: Recent reports indicate that B lymphocyte-induced maturation protein 1 (BLIMP-1), encoded by the Prdm1 gene, expands its control over T cells and is associated with susceptibility to colitis in mice with T cell-specific BLIMP-1 deficiency. In this study, we aimed to investigate the potential role of BLIMP-1 in regulating autoimmune diabetes and T helper type 17 (Th17) cells. METHODS: We generated T cell-specific Blimp1 (also known as Prdm1) transgenic (Tg) or conditional knockout (CKO) NOD mice, in which Blimp1 is overexpressed or deleted in T cells, respectively. By side-by-side analysing these Tg or CKO mice, we further dissected the potential mechanisms of BLIMP-1-mediated modulation on autoimmune diabetes. RESULTS: Overproduction of BLIMP-1 in T cells significantly attenuated insulitis and the incidence of diabetes in NOD mice. Consistent with these results, the diabetogenic effect of splenocytes was remarkably impaired in Blimp1 Tg mice. Moreover, overproduction of BLIMP-1 repressed the proliferation and activation of lymphocytes and enhanced the function of regulatory T cells (Tregs) in NOD mice. In contrast, mice lacking BLIMP-1 in T cells markedly increased Th1 and Th17 cells, and developed highly proliferative and activated lymphocytes. Strikingly, overexpansion of Th1 and Th17 cells in CKO mice was significantly reduced by introducing a Blimp1 transgene, reinforcing the emerging role of BLIMP-1 in autoimmunity. CONCLUSIONS/INTERPRETATION: We conclude that BLIMP-1 orchestrates a T cell-specific modulation of autoimmunity by affecting lymphocyte proliferation and activation, Th1 and Th17 cell differentiation, and Treg function. Our results provide a theoretical basis for developing BLIMP-1-manipulated therapies for autoimmune diabetes.
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Autoinmunidad , Diabetes Mellitus Tipo 1/prevención & control , Terapia de Inmunosupresión , Páncreas/inmunología , Células TH1/inmunología , Células Th17/inmunología , Factores de Transcripción/biosíntesis , Animales , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Cruzamientos Genéticos , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Femenino , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Ratones Transgénicos , Páncreas/patología , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Organismos Libres de Patógenos Específicos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Células TH1/patología , Células Th17/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Interleukin-1beta (IL-1beta)-mediated early islet graft dysfunction and loss of islet mass can occur in different phylogenic types of islet transplantation. Large quantities of interleukin-1 receptor antagonist (IL-1RA) have been demonstrated to impede IL-1beta-mediated adverse effects on islet grafts in allo- and xenotransplantation. To clarify the influence of IL-1RA on early function and mass change, as well as long-term hypoglycemic effects of islet isografts, we studied streptozotocin-induced diabetic C57BL/6 mice infected with replication-defective adenovirus carrying the mouse IL-1RA cDNA gene. This vector increased the mean serum level of IL-1RA to 8 ng/mL, approximately three times greater than for mice receiving adenovirus carrying the beta-galactosidase (beta-Gal) gene. The blood glucose levels declined faster and the insulin content of the graft was significantly higher on day 10 following transplantation among mice receiving mIL-1RA gene than the controls. Nevertheless, the insulin content of the pancreatic remnant did not differ among mice in the IL-1RA, beta-Gal, and vehicle control groups. Serum levels of nitrite and osteopontin before and 3 days after islet transplantation did not differ considerably among the IL-1RA, beta-Gal, and vehicle groups. Compared with the beta-Gal group, temporary posttransplantation hyperglycemia was significantly shortened in the IL-1RA group mice. Removal of graft-bearing kidneys at 13 weeks following transplantation caused recurrence of hyperglycemia in all treated diabetic mice. The insulin content of pancreatic remnants removed at 15 weeks following transplantation was similar in the IL-1RA and beta-Gal groups. In conclusion, a mildly elevated serum concentration of IL-1RA protected and enhanced engraftment of islet isografts immediately after transplantation.
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Diabetes Mellitus Experimental/cirugía , Nefropatías Diabéticas/cirugía , Trasplante de Islotes Pancreáticos/métodos , Trasplante de Islotes Pancreáticos/fisiología , Trasplante de Riñón/métodos , Adenoviridae/genética , Animales , ADN Complementario/genética , Insulina/sangre , Proteína Antagonista del Receptor de Interleucina 1/antagonistas & inhibidores , Proteína Antagonista del Receptor de Interleucina 1/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Nitritos/sangre , Osteopontina/sangreRESUMEN
We co-transplanted silica gel-entrapping 4H-1,3-Thiazin-2-amine,5,6-dihydro-6-methyl monohydrochloride (AMT) with islets to evaluate the effects of AMT on early graft dysfunction in a syngeneic mouse model. The mean diameter of AMT-embedding silica gel particles was 595 +/- 275 nm. The cumulative release of AMT was 29% at 1 hour and 45% at 72 hours. Sixteen streptozotocin-induced diabetic mice were separated into 3 groups. Group A received 50 islets (n = 4). Group B received 50 islets and blank silica gel (n = 6). Group C received 50 islets plus silica-gel containing 6.4 microg AMT (n = 6). Mice in group C required significantly less time for temporary posttransplantation hyperglycemia than those in groups A and B (A, 39 +/- 7 vs B, 40 +/- 5 vs C, 24 +/- 2 days; P < .05). The insulin contents of grafts retrieved at 13 weeks were 1.17 +/- 0.11 (n = 4), 1.01 +/- 0.16 (n = 6), and 1.68 +/- 0.30 microg (n = 6) for mice in groups A, B, and C, respectively. Pancreatic remnant insulin did not differ significantly between the 3 groups (A, 0.32 +/- 0.04 [n = 4] vs B, 0.29 +/- 0.06 [n = 6] vs C, 0.40 +/- 0.05 microg [n = 6]; P > .05). In vitro study revealed that 4 and 20 nmol/L of sol-gel-embedded AMT protected 87% and 96% RIN-m5F cells from 1 ng/mL interleukin-1beta-mediated destruction, respectively. Silica-gel-entrapped AMT protects islet graft from a nonspecific inflammatory destruction, which is partly mediated via interleukin-1beta.
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Diabetes Mellitus Experimental/cirugía , Proteína Antagonista del Receptor de Interleucina 1/fisiología , Trasplante de Islotes Pancreáticos/métodos , Animales , ADN Complementario/genética , Insulina/sangre , Proteína Antagonista del Receptor de Interleucina 1/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Nitritos/sangre , Osteopontina/sangreRESUMEN
To study effects of glucose on growth-related proteins of adult islets, we cultured mice islets in medium containing either 5.5 mmol/L (LG) or 20 mmol/L (HG) glucose. Total islet proteins were processed for sodium dodecyl sulfate polyacrylamide gel and Western blotting using antibodies against beta-actin (housekeeping), p27kip1 (G1/G0 checkpoint), cyclin D1 (G1/S), cyclin B1 (G2/M), and FoxM1. At day 1, protein levels p27, B1, D1, and FoxM1 of islets on LG and HG were 0.48- and 0.63-fold; 7.09- and 11.58-fold; 1.25- and 1.38-fold; and 1.75- and 1.75-folds, the value of day 0, determinations respectively. At day 3, the proteins of p27, B1, D1, and FoxM1 of islets in LG and HG were 0.84- and 0.84-fold; 3.08- and 17.17-fold; 1.41- and 1.54-fold; and 0.83- and 1.17-fold of those on day 0, respectively. On day 7 the values were 1.19- and 1.09-fold; 3.15- and 14.81-fold; 0.86- and 1.44-fold; and 2.75- and 3.42-fold that of day 0, respectively. At day 1, the ratios of protein in islets after HG verse LG were 1.25, 2.38, 0.94, and 1.00 for p27, B1, D1, and FoxM1, respectively. At days 3 and 7, the protein ratios of HG/LG were 0.81 and 0.82, 5.47 and 2.64, 0.81 and 1.51, and 1.11 and 1.24 for p27, B1, D1, and FoxM1, respectively. In conclusion, adult mouse islets rapidly respond to cultivation by reducing p27 and increasing B1; HG attenuates p27 elevation but enhances B1 and D1 elevations, which favor islet entry into the cell cycle.
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Glucosa/farmacología , Hiperglucemia/fisiopatología , Islotes Pancreáticos/fisiopatología , Actinas/genética , Animales , División Celular/efectos de los fármacos , Ciclina B/genética , Ciclina B1 , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead/genética , Islotes Pancreáticos/citología , Islotes Pancreáticos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Antígeno Nuclear de Célula en Proliferación/genética , Regulación hacia ArribaRESUMEN
This study examined the combinatory effect on graft survival of neonatal pig pancreatic cell clusters (NPCC) with nordihydroguaiaretic acid (NDGA), a 5-lipoxygenase inhibitor, with systemic CTLA4Ig expression, with local CTLA4Ig and with interleukin-1 (IL-1) receptor antagonist (IL-1ra) expression using a pig to mouse model. About 2000 NPCCs, which were infected with both adenoviruses carrying CTLA4Ig and IL1-1ra genes (each 500 pfu/NPCC), were transplanted beneath the kidney capsule of diabetic BALB/c mice. Two days before transplantation, the recipient mice were either injected with (group C, n = 4; group D, n = 6) or without (group A, n = 7; group B, n = 9) 1 x 10(13) pfu/kg body weight of adenovirus carrying the CTLA4Ig gene. Mice in groups B and D received daily injections of NDGA (20 mg/kg body weight) subcutaneously for 4 weeks. Blood glucose levels less than 200 mg/dL were defined to be normoglycemic and the transplant termed as a functioning graft for the purpose of calculating mean graft function time (MFT). Four weeks posttransplantation, an intraperitoneal glucose tolerance test (IPGTT) was performed to calculate the area under the curve (AUC). Blood glucose levels in groups C and D were significantly lower than groups A and B at 1, 2, and 3 weeks after transplantation. Graft MFT and AUC of IPGTT in group D were significantly different from those in groups A and B. Our data suggested that a high dosage of systemic expression of CTLA4Ig was effective to enhance xenograft survival and that in it was reinforced by a combination with the macrophage inhibitor NDGA.
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Inmunoconjugados/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Islotes Pancreáticos/inmunología , Masoprocol/uso terapéutico , Trasplante Heterólogo/inmunología , Abatacept , Animales , Animales Recién Nacidos , Diabetes Mellitus Experimental/cirugía , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Ratones , Ratones Endogámicos BALB C , Modelos Animales , PorcinosRESUMEN
BACKGROUND: To sequence and analyze the complete nucleotide sequence of the Japanese encephalitis virus (JEV) strain 02-76, newly isolated in 2002 in China and to provide information for the genomic structure of JEV and the characteristics of virulence. METHODS: Overlapping primers were designed according to the full-length genomes from GenBank. RT-PCR was used to amplify the fragments, sequencing was performed and all the nucleotides were connected to acquire the full-length genome. Computer software was used to analyze the nucleic acid data, deduced amino acid sequence and phylogenetic trees including Clustal X(1.8), DNASTAR, GENEDOC(3.2). RESULTS: The result of sequence analysis showed that the genome of 02-76 strain was 10,977 nucleotides long. An open reading frame from 95 to 10,391 including 10,296 bases was found capable of coding for a 3432 amino acid polyprotein. Compared with the Beijing 1 strains isolated in 1949 in China, there was a 248 nucleotide divergence and 16 amino acid divergence. Comparison of the complete genome sequences of different JEV isolates showed a 0.6%-15.1% nucleotide sequence divergence among them, which resulted in 0.2%-4.6% amino acid sequence divergence. Phylogenetic analysis through PrM/C,E,3'NTR and full-length genome showed that the 02-76 strain belonged to genotype 3. CONCLUSION: Analysis based on the complete genome sequences of different JEV isolates showed that the 02-76 isolate in 2002 belonged to genotype 3 and was close to the old Chinese isolates SA-14.