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1.
J Diabetes Res ; 2022: 2552186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35036446

RESUMO

Background: Previous studies have revealed that the variation of thyroid indicators may be associated with the risk of diabetic retinopathy (DR) among euthyroid type 2 diabetes (T2D) patients. But the specific conclusions are currently inconsistent. Methods: This is a hospital-based retrospective survey. We recruited 1,145 euthyroid T2D patients and checked the thyroid function and fundus photographs. The modified Airlie House classification system was used to categorize the stages of DR. The association between thyroid indicators and different stages of DR was analyzed. Results: We divided free triiodothyronine (FT3) into tertiles and found that the prevalence of mild nonproliferative DR (NPDR) was significantly higher in T2, compared with T1 (32.0% vs. 25.2%, p < 0.05). When FT3 was within the level of T2, FT3 could be an independent risk factor for mild NPDR (OR 1.426, 95% CI (1.031, 1.971), p < 0.05). In addition, the prevalence of severe NPDR and proliferative DR (PDR) was significantly higher in thyroglobulin antibody (TgAb) positive group (8.8% vs. 4.1%, p < 0.05) and vice versa (33.3% vs. 18.4%, p < 0.05). TgAb positivity was also an independent risk factor for severe NPDR and PDR (OR 2.212, 95% CI (1.244, 3.934), p < 0.05). Conclusions: We hardly observed a significant change in DR risk with the elevation or reduction of serum TSH or thyroid hormone within the reference interval. Although the slightly elevated FT3 may be associated to mild NPDR, the extensibility of this result remains to be seen. For T2D patients with euthyroid function, there may be a significant correlation between serum TgAb positivity and severe NPDR and PDR.

2.
Front Endocrinol (Lausanne) ; 12: 746329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899598

RESUMO

Background: Hypothyroidism in the first trimester of pregnancy (T1) has great adverse effects on mothers and foetuses. However, few studies have investigated the influence on postpartum thyroid dysfunction. This study aimed to evaluate their long-term effect on postpartum thyroid function within one year after delivery. Methods: In total, 151 women were recruited from 1496 participants and were classified as newly diagnosed subclinical hypothyroidism (SCH) in T1 (ND-SCH, n=50), previously known SCH before pregnancy (PK-SCH, n=51) and previously known overt hypothyroidism (PK-OH, n=50). Their thyroid functions were dynamically monitored from pre-conception to one-year postpartum. Results: During pregnancy, the first thyroid functions' test time in T1 were 5-8 gestational weeks. After delivery, the prevalence of postpartum thyroiditis (PPT) was comparable in women with previously known and newly diagnosed hypothyroidism [ND-SCH 62.0% vs PK-SCH 64.7% vs PK-OH 64.0%, P=0.96]. For the ND-SCH group, PPT was significantly related with thyroid-stimulating hormone (TSH) >4.0 mU/L occurring at <8 gestational weeks [OR=8.06, 95% CI, 2.08-31.29] and TSH levels outside 1.0-2.5 mU/L near childbirth [OR=3.73, 95% CI, 1.04-13.41]. For patients with known hypothyroidism before pregnancy (PK-SCH and PK-OH), TSH>2.5 mU/L in T1 [OR=3.55, 95% CI, 1.43-8.81] and TPOAb≥300 µIU/mL [OR=6.58, 95% CI, 2.05-21.12] were associated with PPT. Regardless of whether SCH was diagnosed before pregnancy or in T1, the levothyroxine (LT4) treatment was discontinued at delivery. More than 50% of the patients had to face the hypothyroidism phase of postpartum and restarted LT4 treatment in the first-year follow-up. The logistic regression analysis revealed that TSH elevation occurring at <8 gestational weeks [OR=2.48, 95% CI, 1.09-5.6], TSH levels outside 1.0-2.5 mU/L near childbirth [OR=3.42, 95% CI, 1.45-8.05], and TPOAb≥300 µIU/mL [OR=6.59, 95% CI, 1.79-24.30] were the risk factors. Conclusion: TSH elevation at <8 gestational weeks was associated with PPT after delivery in women with known and newly diagnosed hypothyroidism. Especially for SCH patients who stopped LT4 treatment at delivery, unsatisfactory TSH level at <8 gestational weeks and near childbirth, TPOAb≥300 µIU/mL were the risk factors for LT4 retreatment in one-year postpartum.

3.
Diabetes Metab Syndr Obes ; 14: 4513-4522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785920

RESUMO

Background: Some studies have reported that chronic kidney disease (CKD) or the estimated glomerular filtration rate (eGFR) is significantly associated with metabolic abnormalities. Methods: Six hundred forty-six community residents aged 45-60 years without overt renal dysfunction were recruited in this cross-sectional study. eGFR was estimated by serum creatinine measurement. The visceral fat area (VFA) and subcutaneous fat area (SFA) were assessed by magnetic resonance imaging (MRI). The body mass index (BMI) and waist-hip ratio (WHR) were also evaluated. Additionally, we tested the subjects' blood lipid levels to diagnose dyslipidemia. Results: Compared with the subjects with neither dyslipidemia nor obesity, men with both dyslipidemia and high obesity indices, such as BMI, WHR and VFA, showed a significantly lower mean eGFR; women with dyslipidemia with high WHR, VFA or SFA also showed a significantly lower mean eGFR. Although an independent association between the metabolic variables and eGFR was not found except for BMI, some of the combined effects of each variable were related to eGFR decline. Comorbidity of dyslipidemia and high WHR was significant risk factor for eGFR reduction (ß -8.805, SD 4.116, p < 0.05). Additionally, comorbidity of dyslipidemia and high obesity indices such as BMI (ß -12.942, SD 5.268, p < 0.05) and VFA (ß -7.069, SD 3.394, p < 0.05) were significant risk factors for eGFR reduction in men. Conclusion: The combined effect of dyslipidemia and high obesity indices is significantly related to the decline in eGFR. The association is more profound in men.

4.
Front Endocrinol (Lausanne) ; 12: 730279, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603208

RESUMO

Objective: Thyroid nodules (TNs) are a common thyroid disorder that can be caused by many factors. Several studies have investigated the relationship between TNs and metabolic syndrome (MetS), but the role of sex and age remains controversial. The purpose of this paper was to analyze published data from all relevant studies to reliably estimate the relationship between TNs and MetS. Methods: Thirteen articles were included in this study; articles were identified by searching for publications until July 2021 in PubMed, EMBASE, the Cochrane Library and the Web of Science. The outcomes are presented as the summary odds ratio (OR) and 95% confidence interval (CI) and the pooled prevalence and 95% CI. Results: The TNs prevalence was significantly higher in MetS patients than in controls (OR 1.88, 95% CI 1.42-2.50, P < 0.0001) and was independent of sex (male: OR 1.53, 95% CI 1.20-1.94, P = 0.0006; female: OR 1.90, 95% CI 1.54-2.33, P < 0.00001; combined: OR 2.06, 95% CI 1.31-3.25, P = 0.002) and age (< 40 years old: OR 1.62, 95% CI 1.39-1.89, P < 0.0001; 40~50 years old: OR 2.14, 95% CI 1.49-3.08, P < 0.0001;50~60 years old: OR 1.50, 95% CI 1.08-2.07, P = 0. 01; 60 years old: OR 1.70, 95% CI 1.36-2.14, P < 0.00001); the pooled TNs prevalence in MetS patients was 45% (95% CI 36-54%). However, it has not yet been considered that MetS is related to TNs in people with iodine deficiency (OR 3.14, 95% CI 0.92-10.73, P = 0.07). Conclusion: The meta-analysis results showed a strong correlation between TNs and MetS. Both male and female patients with MetS had an increased TNs prevalence. In addition, the prevalence was independent of age. However, MetS is not considered to be associated with TNs in iodine-deficient populations.

5.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3299-3310, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34658216

RESUMO

A comprehensive measurement of green economic efficiency in the Yellow River Delta region can provide a reference basis for achieving ecological protection and high-quality development. We constructed an evaluation system of green economic efficiency in counties based on multi-source remote sensing data. We adopted the Super-EBM model that considered non-expected output to make a comprehensive measurement of green economic efficiency in Yellow River Delta counties, used the kernel density function estimation method to portray the characteristics of spatial and temporal evolution, and finally used the system generalized moment estimation method to identify influen-cing factors. The results showed that the comprehensive efficiency and pure technical efficiency of the green economy in the Yellow River Delta counties showed a fluctuating upward trend from 2000 to 2015. The scale efficiency showed a rapid increase and then stayed stable in a 'Γ' type trend, while the increase in comprehensive efficiency transformed from being driven by scale-technology to being led by technology. The comprehensive efficiency and pure technical efficiency of the green economy in the Yellow River Delta counties showed an evolutionary trend from 'club convergence' to 'overall convergence', with the low efficiency counties formed a 'catch-up effect' on the high efficiency counties and the scale efficiency toward a balanced and smooth development. The comprehensive efficiency of green economy and its decomposition efficiency spatially formed a 'mountain' pattern, which was high in the middle, low in the two wings, and the high value area concentrated in the headland of the Yellow River Delta and along the coast of Laizhou Bay. The high-value area showed the characteristics of a northwest-southeast shift, and the east and west wings of the Yellow River Delta formed low-value subsidence areas. Industrial structure, population concentration level, and fixed asset investment intensity had positive effects on green economic efficiency, while population urbanization rate had negative effects on green economic efficiency. There was an obvious 'environmental Kuznets' effect between green economic efficiency and economic development level.


Assuntos
Desenvolvimento Econômico , Rios , China , Indústrias , Urbanização
6.
Arch Anim Breed ; 64(2): 375-386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34584939

RESUMO

Litter size is an important component trait of doe reproduction. By improving it, production efficiency and economic benefits can be significantly provided. Genetic marker-assisted selection (MAS) based on proven molecular indicators could enhance the efficacy of goat selection, as well as litter size trait. Many molecular markers have been identified that they can be used to improve litter size in different goat breeds. However, the presence and value of these markers vary among goat breeds. In the present study, we used the reported loci on other breeds of goat as candidate loci to detect whether these loci appear in this Nubian goat population; then we proceed to genotype and detect surrounding loci (50 bp) by multiplex PCR and sequencing technology. As a result, 69 mutations (59 SNPs and 10 indels) were screened out from 23 candidate genes in Nubian goat population, 12 loci were significantly associated with the litter size of first-parity individuals; 5 loci were significantly associated with the litter size of second-parity individuals; 3 loci were significantly associated with the litter size of third-parity individuals. In addition, five loci were significantly associated with the average litter size. The additive effect value of KITLG: g.18047318 G > A in first parity, KITLG: g.18152042G > A in third parity, KISS-1: g.1341674 C > G in first parity, and GHR: g.32134187G > A in second parity exceed more than 0.40, and the preponderant alleles are G, C, A and G, respectively. Further, linkage disequilibrium analysis of 21 mutation loci shows that 3 haplotype blocks are formed, and the litter size of combination type AACC in KISS-1 gene and AAGG in KITLG gene are significantly lower than that of other combinations genotype in first parity ( P < 0.05 ). These findings can provide effective candidate DNA markers for selecting superior individuals in Nubian goat breeding.

7.
Int J Nanomedicine ; 16: 6497-6530, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588777

RESUMO

The complex drug delivery barrier in the eye reduces the bioavailability of many drugs, resulting in poor therapeutic effects. It is necessary to investigate new drugs through appropriate delivery routes and vehicles. Nanotechnology has utilized various nano-carriers to develop potential ocular drug delivery techniques that interact with the ocular mucosa, prolong the retention time of drugs in the eye, and increase permeability. Additionally, nano-carriers such as liposomes, nanoparticles, nano-suspensions, nano-micelles, and nano-emulsions have grown in popularity as an effective theranostic application to combat different microbial superbugs. In this review, we summarize the nano-carrier based drug delivery system developments over the last decade, particularly review the biology, methodology, approaches, and clinical applications of nano-carrier based drug delivery system in the field of ocular therapeutics. Furthermore, this review addresses upcoming challenges, and provides an outlook on potential future trends of nano-carrier-based drug delivery approaches in ophthalmology, and hopes to eventually provide successful applications for treating ocular diseases.


Assuntos
Nanopartículas , Oftalmologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Lipossomos , Nanotecnologia
8.
Front Endocrinol (Lausanne) ; 12: 660277, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140930

RESUMO

Objective: The aim of our study was to compare the reference intervals (RIs) [median (2.5th-97.5th percentiles)] for thyroid-stimulating hormone (TSH) between subgroups stratified by ethnicity and iodine status in a global context. Design and Methods: Primary data were derived from a recently published cross-sectional study in mainland China. Secondary data were obtained from online databases. The RIs for TSH were calculated in the reference population according to the National Academy of Clinical Biochemistry (NACB) standard and in the disease-free population. A meta-analysis of ethnicity- and iodine status-specific TSH RIs was performed. Results: The primary data showed that the TSH RI (mU/L) in the disease-free population was 2.33 (0.67, 7.87), which is wider than the published RI [2.28 (0.74, 7.04)] in the reference population. The meta-analysis showed that whether in the reference or disease-free population, the RIs in Yellows were much higher than those in Caucasians. In the reference population, the median and 2.5th percentile in the iodine-sufficient subgroup were both lower than the iodine-deficient or more-than-adequate subgroup, while the 97.5th percentile showed a positive trend with increasing sufficiency of iodine. However, in the disease-free population, the iodine-sufficient subgroup had a lower median and 97.5th percentile but higher 2.5th percentile than the iodine-deficient subgroup. Conclusion: Yellows have a higher TSH RI than Caucasians. In the reference population, both the median and 2.5th percentile TSH in the iodine-sufficient population were the lowest among the different iodine status subgroups, while the 97.5th percentile of TSH showed an upward trend with increasing iodine sufficiency.

9.
Vaccine ; 39(25): 3428-3434, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33965257

RESUMO

BACKGROUND: The widespread use of pneumococcal conjugate vaccines (PCVs) has significantly decreased pneumococcal disease worldwide. However, China has not adopted PCVs in their national immunization schedules and had only approved these vaccines for children aged 2-15 months by 2020. METHODS: In an open-label trial, enrolled healthy children aged 2-5 years old were randomized 1:1 and divided into a 7-valent pneumococcal conjugate vaccine (PCV7) group and a Haemophilus influenzae type b conjugate vaccine (Hib) group. Children in the PCV7 group received a single dose of PCV7, and the Hib group received a single dose of Hib vaccine. Blood samples were collected before and 6 months after vaccination. Immunogenicity and safety of PCV7 were assessed at prespecified time points. RESULTS: Six months after a single dose of PCV7, children in the PCV7 group for all 7 serotypes, IgG mean concentrations (GMCs) and opsonophagocytic geometric mean titres (GMTs) were significantly higher (P < .001) than at baseline, and the proportion of IgG ≥ 0.35 µg/mL ranged from 90.0% to 100%. Although the antibody level increased with age, preexisting antibodies did not induce hyporesponsiveness to PCV7. In the Hib group, the antibody levels were not significantly different or had changed slightly at 6 months. PCV7 was well tolerated in all age groups, and no serious adverse events (AEs) emerged during this study. CONCLUSIONS: A single dose of PCV7 was immunogenic and safe for Chinese children aged 2-5 years, and the preexisting antibodies against the PCV7 serotypes did not change the response to vaccination. The findingssupported the effectiveness of PCV7 in this age group. PCVs with broader serotype coverage are expected to expand pneumococcal disease protection.


Assuntos
Infecções Pneumocócicas , Vacinas Pneumocócicas , Anticorpos Antibacterianos , Criança , Pré-Escolar , China , Humanos , Esquemas de Imunização , Lactente , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/efeitos adversos , Vacinas Conjugadas/efeitos adversos
10.
Front Immunol ; 12: 609762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968014

RESUMO

Cancer is one of the leading causes of death and a major public health problem all over the world. Immunotherapy is becoming a revolutionary clinical management for various cancer types. Restoration of aberrant immune surveillance on cancers has achieved markable progress in the past years by either in vivo or ex vivo engineering of the immune cells. Here, we summarized the central roles of immune cells in tumor progression and regression, and the existing and emerging strategies for different immune cell-based immunotherapies. In addition, the current challenges and the potential solutions in translating the immunotherapies into the clinic are also discussed.


Assuntos
Reprogramação Celular/imunologia , Imunomodulação , Neoplasias/imunologia , Neoplasias/terapia , Animais , Reprogramação Celular/genética , Engenharia Genética , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
11.
Food Res Int ; 143: 110306, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33992326

RESUMO

Sunlight conditions around grape clusters vary with their positions, and can have a significant effect on grape berry compounds. This study investigated the influence of cluster positions in the canopy (interior and two exterior canopy sides) and vineyard row orientation (north-south and east-west) on flavonoid and volatile compound profiles of Vitis vinifera L. cvs 'Cabernet franc' (CF) and 'Chardonnay' (CH) berries in two consecutive years. The experimental vineyard was located in Jiaodong Peninsula of China, which is characterized by a temperate monsoon-type climate and relatively short sunlight duration. Clusters located in the interior of the canopy received less sunlight irradiation than the exterior positions, and the average temperature around clusters located in different positions differed slightly. The results showed that over two years, the positions of clusters in the canopy had no consistent impact on cluster weight, berry weight, juice total soluble solids or titratable acidity for either cultivar. For both cultivars, the interior clusters had lower total flavonol concentrations than the exterior clusters, while the position of clusters in the canopy had no major impacts on the composition of anthocyanins and flavan-3-ols. The volatile compounds were somewhat influenced by the positions of clusters in the canopy, while some bound norisoprenoids and terpenoids had lower levels in interior clusters than in exterior clusters. These results will help winegrowers make decisions regarding harvest strategies.


Assuntos
Vitis , Antocianinas , China , Flavonoides , Frutas
12.
Food Chem ; 361: 130064, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34029895

RESUMO

In this study, black geotextile inter-row mulch, a weed control practice, was applied under a semi-arid climate to attenuate solar reflection in 2015-2017, and it concurrently increased soil temperature and fruit-zone high temperature duration and decreased low temperature duration. Inter-row mulch decreased anthocyanins concentrations in grapes in 2015-2016, and consistently inhibited flavonols accumulation in 2015-2017. Correlation analysis between microclimate parameters and flavonoids concentrations reflected the importance of solar reflection, fruit-zone high and low temperature duration, heat accumulation and soil temperature to flavonoids accumulation. Basal leaf removal, a widely applied practice to increase fruit-zone light exposure, was applied to mulch-treated grapevines to investigate if increasing incident light could mitigate the impact of inter-row mulch on flavonoids, and it had limited influence on anthocyanins whereas compensated the loss of flavonols in grapes caused by inter-row mulch. Notably, inter-row mulch wines showed less red and more yellow color than controls because of lower anthocyanins concentrations.


Assuntos
Flavonoides/metabolismo , Vitis/química , Antocianinas/análise , Antocianinas/metabolismo , Cromatografia Líquida de Alta Pressão , Clima Desértico , Flavonoides/análise , Flavonóis/análise , Flavonóis/metabolismo , Frutas/química , Frutas/efeitos da radiação , Humanos , Luz , Espectrometria de Massas , Microclima , Solo/química , Vitis/efeitos da radiação , Vinho/análise , Vinho/efeitos da radiação
13.
J Clin Endocrinol Metab ; 106(10): e4251-e4259, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-33754627

RESUMO

CONTEXT: The association between serum thyrotropin (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established. OBJECTIVE: This work aimed to determine and analyze the causal association between serum TSH level and obesity-related traits (body mass index [BMI] and obesity). METHODS: The latest genome-wide association studies (GWASs) on TSH, BMI, and obesity were searched to obtain full statistics. Bidirectional 2-sample mendelian randomization (MR) was performed to explore the causal relationship between serum TSH and BMI and obesity. The inverse variance-weighted (IVW) and MR-Egger methods were used to combine the estimation for each single-nucleotide variation (formerly single-nucleotide polymorphism). Based on the preliminary MR results, free thyroxine (fT4) and free 3,5,3'-triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them. BMI and obesity were treated as the outcomes to evaluate the effect of serum TSH on them, and TSH was set as the outcome to estimate the effect of BMI and obesity on it. RESULTS: IVW and MR-Egger results both indicated that genetically driven serum TSH did not causally lead to changes in BMI or obesity. Moreover, the IVW method showed that the TSH level could be significantly elevated by genetically predicted high BMI (ß = .038, SE = 0.013, P = .004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (ß = 10.123, SE = 2.523, P < .001) while not significantly affecting the fT4 level. CONCLUSION: Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.


Assuntos
Obesidade/epidemiologia , Obesidade/genética , Tireotropina/sangue , Índice de Massa Corporal , Causalidade , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Testes de Função Tireóidea
14.
Bioact Mater ; 6(9): 2870-2880, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33718668

RESUMO

Immune suppressive microenvironment in tumor emerges as the main obstacle for cancer immunotherapy. In this study, we identified that HIF1α was activated in the tumor associated macrophages and acted as an important factor for the immune suppressive microenvironment. Epigenetically silencing of Hif1α via histone H3 methylation in the promoter region was achieved by CRISPR/dCas9-EZH2 system, in which histone H3 methylase EZH2 was recruited to the promoter region specifically. The Hif1α silenced macrophage, namely HERM (Hif1α Epigenetically Repressed Macrophage) manifested as inheritable tumor suppressing phenotype. In the subcutaneous B16-F10 melanoma syngeneic model, intratumoral injection of HERMs reprogrammed the immune suppressive microenvironment to the active one, reducing tumor burden and prolonging overall survival. Additionally, HERMs therapy remarkably inhibited tumor angiogenesis. Together, our study has not only identified a promising cellular and molecular target for reverting immune suppressive microenvironment, but also provided a potent strategy for reprogramming tumor microenvironment via epigenetically reprogrammed macrophages.

15.
Aging Cell ; 20(3): e13323, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657282

RESUMO

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10-15 ) and TMEM43/XPC (rs1043943; p = 3.59 × 10-8 ), were identified in a case-control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10-15 ) and BMPER (rs17169634; p = 1.45 × 10-10 ) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex-stratified analyses identified sex-specific longevity genes. Notably, sex-differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not-longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.


Assuntos
/genética , Loci Gênicos , Predisposição Genética para Doença , Longevidade/genética , Estudos de Coortes , Feminino , Genoma Humano , Humanos , Masculino , Metanálise como Assunto , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Fatores de Risco , Caracteres Sexuais , Análise de Sobrevida
16.
Cell Stress Chaperones ; 26(3): 563-574, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33743152

RESUMO

Heat stress (HS) results in health problems in animals. This study was conducted to investigate the effect and the underlying mechanism of HS on the proliferation and differentiation process of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated at 37 °C or 41.5 °C. HS up-regulated the mRNA and protein expression level of heat shock protein 70 (HSP70). Furthermore, the proliferation of 3T3-L1 preadipocytes were significantly inhibited after HS treatment for 2 days. A large number of accumulated lipid droplets were observed under the microscope after HS treatment for 8 days. Notably, the result of oil red O staining showed that the number of lipid droplets increased significantly and the differentiation ability of the cells was enhanced after HS. Moreover, after 2 and 8 d of differentiation, HS increased the transcription levels of fat synthesis genes including peroxisome proliferators activated receptor γ (PPARγ), fatty acid binding protein 2 (AP2), fatty acid synthase (FAS) and CCAAT enhancer binding protein α (CEBPα) genes, while decreasing the transcription levels of lipid decomposition genes including ATGL and HSL genes. In addition, HS reduced the expression of AMPK and PGC-1α, as well as the dephosphorylation of AMPK. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) can eliminate HS induced lipogenesis by activating AMPK. These results indicated that HS inhibited the proliferation of 3T3-L1 preadipocytes and promoted lipid accumulation by inhibiting the AMPK-PGC-1α signaling pathway in 3T3-L1 preadipocytes. This work lays a theoretical foundation for improving the effect of HS on meat quality of livestock and provides a new direction for the prevention of obesity caused by HS.

17.
J Extracell Vesicles ; 9(1): 1816710, 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-33133429

RESUMO

Therapeutically intervening the function of RNA in vivo remains a big challenge. We here developed an exosome-based strategy to deliver engineered RNA-binding protein for the purpose of recruiting specific RNA to the lysosomes for degradation. As a proof-of-principle study, RNA-binding protein HuR was fused to the C-terminus of Lamp2b, a membrane protein localized in both exosome and lysosome. The fusion protein was able to be incorporated into the exosomes. Moreover, exosomes engineered with Lamp2b-HuR successfully decreased the abundance of RNA targets possibly via lysosome-mediated degradation, especially when the exosomes were acidified. The system was specifically effective in macrophages, which are lysosome enriched and resistant to routine transfection mediated RNAi strategy. In the CCl4-induced liver injury mouse model, we found that delivery of acidified exosomes engineered with Lamp2b-HuR significantly reduced liver fibrosis, together with decreased miR-155 and other inflammatory genes. In summary, the established exosome-based RNA-binding protein delivery strategy, namely "exosome-mediated lysosomal clearance", takes the advantage of exosome in targeted delivery and holds great promise in regulating a set of genes in vivo.

18.
Food Res Int ; 137: 109688, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33233263

RESUMO

In this study, fruit-zone microclimate was modified by three treatments, including inter-row mulch (M), the combination of leaf removal applied at the onset of veraison and inter-row mulch (MLR-BV), and the combination of leaf removal applied at complete veraison and inter-row mulch (MLR-EV), in a semi-arid climate in three consecutive years (2015-2017). M decreased fruit-zone reflected solar radiation from vineyard floor and low temperature (10-20 °C) duration, whereas it increased soil temperature and high temperature (> 30 °C) duration. MLR-BV and MLR-EV increased fruit-zone incident photosynthetically active radiation while decreased the duration of 20-25 °C compared to M. Notably, M significantly decreased grape total norisoprenoid concentrations in 2015-2017, and total terpenoid concentrations in 2015-2016. Applying leaf removal applied at the onset of veraison could compensate the decreases of total norisoprenoids and terpenoids caused by M when two treatments were applied together. Besides, M significantly increased grape total C6/C9 compound concentrations, besides, (Z)-3-hexen-1-ol concentrations were significantly higher in grapes of M than those of MLR-BV in 2015-2017. Light exposure and high temperature duration after veraison had strong positive correlations with total norisoprenoids and terpenoids, besides, low temperature duration was positively correlated with total norisoprenoids. In addition, light exposure after veraison had strong negative correlations with total C6/C9 compounds. With respect to the volatile compounds in wines, M significantly decreased the concentrations of isopentanol and ethyl acetate, and the concentrations of ethyl cinnamate, phenylacetaldehyde, phenylethyl alcohol and 3-methylthio-1-propanol were significantly lower in MLR-BV and MLR-EV than in M. The outcome of this study can assist winegrowers to properly adjust vineyard managements to optimize the concentrations of desired volatile compounds in grapes and wines.


Assuntos
Vitis , Vinho , Fazendas , Frutas/química , Norisoprenoides/análise , Vinho/análise
19.
Am J Transl Res ; 12(10): 6723-6739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194068

RESUMO

The mechanisms that regulate hematopoietic stem cell (HSC) regeneration after myelosuppressive injury are not well understood. Here, we showed that disruption of Notch signaling aggravated chemotherapy-induced myelosuppression in inducible genetic mice. Conversely, Notch activation correlated positively with clinical HSC engraftment. We used endothelial-targeted chimeric Notch ligand Delta-like 1 (D1R) to activate Notch signaling in hematopoietic stem/progenitor cells through micro-environmental cellular contact. Recombinant protein D1R contributed to the recovery of the HSC pool and sustained HSC vitality in response to various chemotherapeutic agents in vivo. Mechanistically, D1R treatment promoted HSC proliferation transiently, prevented HSC exhaustion, correlated with activation of the downstream phosphoinositide 3-kinase (PI3K)/extracellular-signal-regulated kinase (ERK)/BCL2 associated agonist of cell death (BAD) signaling axis during regeneration, and partially mediated upregulation of c-Myc in HSCs. These data reveal an unrecognized role for Notch signaling in promoting HSC repopulation after myelosuppressive chemotherapy and offer a new therapeutic approach to mitigate chemotherapy-induced injury.

20.
Food Res Int ; 137: 109388, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33233090

RESUMO

Differences in key odor-active volatile compounds among the head, heart, and tail fractions of freshly distilled spirits from Spine grape (Vitis davidii Foex) wine were identified for the first time by gas chromatography-olfactometry and gas chromatography-mass spectrometry. Results from aroma extract dilution analysis (AEDA) showed that there were 34, 45, and 37 odor-active compounds in the head, heart and tail fractions, respectively. Besides, 20, 22, and 17 quantified compounds, respectively, showed odor activity values (OAVs) > 1. The head fraction was characterized by fruity, fusel/solvent notes owing to higher concentrations of higher alcohols and esters, while the tail fraction had more intense smoky/animal, sweaty/fatty attributes due to higher concentrations of volatile phenols and fatty acids. Finally, the heart fraction was characterized by ethyl octanoate, ethyl hexanoate, ethyl 3-phenylpropanoate, ethyl cinnamate, isoamyl alcohol, guaiacol, 4-ethylguaiacol, 4-vinylguaiacol, 2,3-butanedione, and (E)-ß-damascenone. Furthermore, observation of the distillation progress indicated that different volatiles with various boiling points and solubilities followed diverse distillation patterns: concentrations of most esters, higher alcohols, terpenes and C13-norisoprenoids decreased, while concentrations of volatile phenols, fatty acids and some aromatic compounds increased during distillation. As a result, their final concentrations in the three distillate fractions varied significantly.


Assuntos
Vitis , Compostos Orgânicos Voláteis , Vinho , Cromatografia Gasosa-Espectrometria de Massas , Odorantes/análise , Olfatometria , Compostos Orgânicos Voláteis/análise , Vinho/análise
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