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1.
Int J Nanomedicine ; 15: 2859-2872, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368058

RESUMO

Purpose: The topical application of exosomes secreted by mesenchymal stem cells (MSC-Exos) on the skin is a very new and interesting topic in the medical field. In this study, we aimed to investigate whether marine sponge Haliclona sp. spicules (SHSs) could effectively enhance the skin delivery of human umbilical cord-derived MSC-Exos (hucMSC-Exos), and further evaluate the topical application of hucMSC-Exos combined with SHSs in rejuvenating photoaged mouse skin. Materials and Methods: SHSs were isolated from the explants of sponge Haliclona sp. with our proprietary method, and hucMSC-Exos were prepared from the conditioned medium of hucMSCs using ultracentrifugation. The effects of SHSs on the skin penetration of fluorescently labeled hucMSC-Exos were determined using confocal microscopy in vitro (porcine skin) and in vivo (mouse skin). The therapeutic effects of hucMSC-Exos coupled with SHSs against UV-induced photoaging in mice were assessed by using microwrinkles analysis, pathohistological examination and real-time RT-PCR. We also tested the skin irritation caused by the combination of hucMSC-Exos and SHSs in guinea pigs. Results: In vitro results showed that hucMSC-Exos could not readily penetrate through porcine skin by themselves. However, SHSs increased the skin absorption of exosomes by a factor of 5.87 through creating microchannels. Similar penetration enhancement of hucMSC-Exos was observed after SHSs treatment in mice. The combined use of hucMSC-Exos and SHSs showed significant anti-photoaging effects in mice, including reducing microwrinkles, alleviating histopathological changes, and promoting the expression of extracellular matrix constituents, whereas hucMSC-Exos alone produced considerably weaker effects. Skin irritation test showed that the combination of hucMSC-Exos and SHSs caused slight irritation, and the skin recovered shortly. Conclusion: SHSs provide a safe and effective way to enhance the skin delivery of MSC-Exos. Moreover, the combination of MSC-Exos and SHSs may be of much use in the treatment of photoaging.

2.
Int J Infect Dis ; 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32437933

RESUMO

Data are limited on the viral load, viral shedding patterns and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). We included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in incubation period (APIs); the other 9 patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The cycle threshold (Ct) values of APs (39.0, IQR 37.5-39.5) was significantly higher than those of APIs (34.5, IQR 32.2-37.0), which indicated a lower viral load in APs, but the duration of viral shedding remained similar between the two groups (7 days IQR 5-14 vs. 8 days IQR 5-16). The study findings demonstrated that although they have a lower viral load, APs with COVID-19 still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid tests are warranted.

3.
Stem Cell Res Ther ; 11(1): 185, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430053

RESUMO

BACKGROUND: Human induced pluripotent stem cells (hiPSCs) represent a potentially unlimited source of pancreatic endocrine lineage cells. Although insulin-producing ß cells derived from hiPSCs have been successfully induced, much work remains to be done to achieve mature ß cells. Lysine-specific demethylase 1 (LSD1) plays an important role in the regulation of hiPSC self-renewal and differentiation. We propose a new strategy to acquire insulin-producing cells (IPCs) from hiPSCs by knocking down LSD1. METHODS: Knockdown of LSD1 in hiPSCs with five shRNA. Assessment of the effects of shRNA on hiPSC proliferation, cell cycle, and apoptosis. Using knockdown hiPSCs with 31.33% LSD1 activity, we achieved a four-step differentiation into IPCs and test its differentiation efficiency, morphology, and marker genes and proteins. We implanted the IPCs into the renal subcapsular of SCID-Beige diabetic mice to evaluate the hypoglycemic effect in vivo. We tested LSD1 and HDAC1 whether they are present in the CoREST complex through IP-WB, and analyzed LSD1, CoREST, HDAC1, H3K4me2/me3, and H3K27me3 protein expression before and after knockdown of LSD1. RESULTS: Differentiated hiPSCs were 38.32% ± 3.54% insulin-positive cells and released insulin/C-peptide in response to glucose stimulus in a manner comparable to adult human islets. Most of the IPCs co-expressed mature ß cell-specific markers. When transplanted under the left renal capsule of SCID-Beige diabetic mice, these IPCs reversed hyperglycemia, leading to a significant increase in the definitive endoderm cells. IP-WB results showed that LSD1, HDAC1, and CoREST formed a complex in hiPSCs. Chip-PCR results showed that LSD1, HDAC1, and CoREST were enriched in the same district during the SOX17 and FOXA2 promoter region. Inhibition of LSD1 would not affect the level of CoREST but decreased the HDAC1 expressions. The H3K4me2/me3 and H3K9act level of SOX17 and FOXA2 promoter region increased after inhibited of LSD1, and promoted transcriptional activation. The H3K4me2/me3 and H3K9act level of OCT4 and SOX2 promoter region decreased with the transcriptional repressed. CONCLUSIONS: LSD1 regulated histone methylation and acetylation in promoter regions of pluripotent or endodermal genes. Our results suggest a highly efficient approach to producing IPCs from hiPSCs.

4.
Biotechniques ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32336115

RESUMO

Refolding of human interleukin 17A (IL-17A) has been reported; however, the key refolding protocol was not robust enough to deliver consistent results and to be easily scaled up for crystallization. Here we report an optimized refolding method for IL-17A. Although co-crystal structures of IL-17A with ligands have been obtained with a high-affinity peptide and an anti-IL-17A Fab as stabilizers, neither the production yield nor the characterization of the IL-17A/Fab complex was reported. To facilitate co-crystallization of IL-17A with small-molecule compounds derived from our DNA encoded library, we also describe the method for yield enhancement of anti-IL-17A Fab production and characterize the IL-17A/Fab complex for the first time, providing an essential prerequisite for structure-based drug discovery targeting IL-17A.

5.
Stem Cell Res Ther ; 11(1): 163, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345350

RESUMO

BACKGROUND: Human embryonic stem cells represent a potentially unlimited source of insulin-producing cells for diabetes therapy. While tremendous progress has been made in directed differentiation of human embryonic stem cells into IPCs in vitro, the mechanisms controlling its differentiation and function are not fully understood. Previous studies revealed that lysine-specific demethylase 1(LSD1) balanced the self-renewal and differentiation in human induced pluripotent stem cells and human embryonic stem cells. This study aims to explore the role of LSD1 in directed differentiation of human embryonic stem cells into insulin-producing cells. METHODS: Human embryonic stem cell line H9 was induced into insulin-producing cells by a four-step differentiation protocol. Lentivirus transfection was applied to knockdown LSD1 expression. Immunofluorescence assay and flow cytometry were utilized to check differentiation efficiency. Western blot was used to examine signaling pathway proteins and differentiation-associated proteins. Insulin/C-peptide release was assayed by ELISA. Statistical analysis between groups was carried out with one-way ANOVA tests or a student's t test when appropriate. RESULTS: Inhibition or silencing LSD1 promotes the specification of pancreatic progenitors and finally the commitment of functional insulin-producing ß cells; Moreover, inhibition or silencing LSD1 activated ERK signaling and upregulated pancreatic progenitor associated genes, accelerating pre-maturation of pancreatic progenitors, and conferred the NKX6.1+ population with better proliferation ability. IPCs with LSD1 inhibitor tranylcypromine treatment displayed enhanced insulin secretion in response to glucose stimulation. CONCLUSIONS: We identify a novel role of LSD1 inhibition in promoting IPCs differentiation from hESCs, which would be emerged as potential intervention for generation of functional pancreatic ß cells to cure diabetes.

6.
BMC Med Genet ; 21(1): 84, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306954

RESUMO

BACKGROUND: Nephronophthisis (NPHP) is a rare autosomal recessive inherited disorder with high heterogeneity. The majority of NPHP patients progress to end-stage renal disease (ESRD) within the first three decades of life. As an inherited disorder with highly genetic heterogeneity and clinical presentations, NPHP still poses a challenging task for nephrologists without special training to make a well-judged decision on its precise diagnosis, let alone its mechanism and optimal therapy. CASE PRESENTATION: A Chinese family with NPHP was recruited in current study. The clinical characteristics (including findings from renal biopsy) of NPHP patients were collected from medical records and the potential responsible genes were explored by the whole exome sequencing (WES). A homozygous deletion of NPHP1 (1-20 exons) was found in both affected patients, which was further confirmed by quantitative PCR. CONCLUSIONS: Homozygous full gene deletion of the NPHP1 gene was identified in a Chinese family with NPHP, which was the molecular pathogenic basis of this disorder. Furthermore, identification of the pathogenic genes for those affected patients can help to have a full knowledge on NPHP's molecular mechanism and precise treatment.

7.
Thorac Cancer ; 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32314522

RESUMO

BACKGROUND: Previous studies have reported that cancer stem cells (CSCs) play a key role in tumorigenesis, metastasis, and recurrence. CSC-based vaccination confers better protection in tumor cells. However, isolation and cultivation of CSCs are difficult. This study aimed to explore the similarities between CSCs and induced pluripotent stem cells (iPSCs). METHODS: ALDH1+ cancer stem cells were isolated from lung adenocarcinoma patients and their gene expression patterns compared with human induced pluripotent stem cells (hiPSCs). In addition, a tumor vaccine was developed using hiPSC and unmethylated cytosine-guanine (CpG). Finally, the antitumor properties of the vaccine were evaluated in a humanized mouse model. RESULTS: Preimmunization of iPSC+CpG elicited stronger antigen presentation and cytotoxic T cell response which suppressed the growth of tumors. Adoptive transfer of spleen T cells from the vaccine preimmunized mice inhibited tumor growth in unvaccinated recipients without any side effects. CONCLUSIONS: This study suggests a universal strategy for tumor therapy which simplifies future clinical procedures. Therefore, the application of hiPSC elicits tumor protective responses.

8.
Ann Rheum Dis ; 79(6): 829-836, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32253185

RESUMO

OBJECTIVES: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. METHODS: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables. RESULTS: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080). CONCLUSIONS: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

10.
J Transl Med ; 18(1): 108, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122370

RESUMO

BACKGROUND: Commonly used miRNA detection methods cannot be applied for high-throughput analyses. However, this study was aimed to performed a liquid bead array detection system (LBAS) to detect tissue 6 miRNAs in non-small cell lung cancer (NSCLC). METHODS: In this study, evaluation of LBAS was performed to observe the precision, specificity, limitation and stability. Then, a total of 52 primary NSCLC patients who received resection operation without preoperative radiotherapy and chemotherapy between June 2013 and March 2014 were selected, and then the total RNA of the tissues were extracted. We prepared six NSCLC-related miRNAs for LBAS. After optimization and evaluation, LBAS was verified by detecting the relative expression levels of 6 microRNAs in the pathological tissues and corresponding normal tissues of 52 NSCLC patients. RESULTS: The results of evaluation of LBAS showed that the Mean Fluorescence Intensity (MFI) of the reaction only added with chimeric probes and beads showed no significant change after 180 days (P > 0.05). And the intra-assay Coefficient of Variation (CV) was between 1.57 and 3.5%, while the inter-assay CV was between 4.24 and 11.27%, indicating this system was ideal for diagnostic reagents. In addition, only the beads corresponding to the additional miRNAs showed high MFIs from 8426 to 18,769, whereas the fluorescence values of the other beads were under background levels (MFIs = 20 to 55) in each reaction, indicating no cross reactivity among the miRNAs. The limit of detection of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 were 5.27, 1.39, 1.85, 2.01, 1.34, and 2.73 amol/µL, respectively, showing that the lowest detection limit of miRNA by this system was under pM level. Then, the relative expression levels of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 by using this system were significantly correlated with NSCLC (P < 0.05). And the results of AUC method indicated that specific of the LBAS system was 94.2%. CONCLUSIONS: Our findings suggest that LBAS was simple, high-throughput, and freely combined with absolute quantification. Thus, this system could be applied for tumor miRNAs detection.

11.
Int J Biol Sci ; 16(4): 633-643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32025211

RESUMO

DC vaccine-based immunotherapy is emerging as a novel therapeutic strategy for cancer treatment, however, antitumor effect of DC vaccines based on tumor cell lysates (TCLs) remains unsatisfactory due to poor immunogenicity of tumor antigens. Although tumor-associated exosomes (TAEs) have been reported as a promising antigen for DC vaccines, it remains unclear how TAE-based DC vaccine induced antitumor immunity in lung cancer. Methods: In the present study, we extracted TAEs from the supernatant of tumor cell culture medium, and compared the effect of TAEs with TCLs on DCs. To further evaluate the therapeutic effect of DCTAE, we used immunofluorescence and flow cytometry to evaluate the apoptosis of tumor tissue, tumor-infiltrating CD8+ T cells and Tregs in TDLNs and spleen. Then the levels of cytokines of IL-12, IFN-γ, L-10 and TGF-ß were quantified by ELISA assays. Results: Our data showed that TAEs were more potent than TCLs to promote DC maturation and enhance MHC cross presentation, which directly contributed to more robust tumor-specific cytotoxic T lymphocyte (CTL) response. More importantly, TAEs reduced the expression of PD-L1 of DCs, thereby led to down-regulated population of Tregs in vitro. Moreover, DCTAE remarkably suppressed the tumor growth and prolonged survival rate in vivo, due to participance of CD8+ T cells and decreased Tregs in TDLNs and spleen. Conclusion: TAEs could serve to improve vaccine-elicited immunotherapy by triggering stronger DC-mediated immune responses and decreasing Tregs in the tumor microenvironment.

12.
Gene Expr Patterns ; 35: 119096, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32027977

RESUMO

Glomerular capillary formation is one of the fundamental mysteries in renal developmental biology. However, there are still debates on this issue, and its detailed formation process has not been clarified. To resolve this problem, we performed antibody staining with ultra-thick section on embryonic and postnatal mouse kidneys. We obtained the expression patterns of several genes that play an important role in the development of glomerular capillaries. We found that blood vessel of the fetal kidneys expanded through proliferation and sprouting. During the comma-stage and S-shaped stage, 3-4 capillaries began to bud and migrate into the glomerular cleft, forming a capillary bed in the Bowman's capsule. Then, the capillary bed expanded into mature glomerular capillary by intussusceptive angiogenesis. The afferent and efferent arterioles were formed through pruning. The distribution of VEGFA in the nephron epithelial cells but not only in podocytes, induced multiple capillaries sprouted into the glomerular cleft. And CXCR4 played an important role in the differentiation and expansion of capillary bed into glomerular capillary. Immunofluorescence performed with ultra-thick section allowed us to investigate the development of complex structure tissues systematically and comprehensively.

13.
Neurosci Lett ; 720: 134780, 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-31978497

RESUMO

OBJECTIVE: Methamphetamine (METH) dependence, especially among women, is a serious global health problem. Kick-boxing exercise can be used to reduce cue-induced craving and develop a healthy lifestyle for female with METH dependencies. This study aimed to assess acute kick-boxing related changes in effective connectivity (EC) in the brain of females with METH dependencies by using functional near-infrared spectroscopy (fNIRS) signals. METHODS: The fNIRS signals were continuously recorded from the left and right prefrontal cortices (LPFC/RPFC) and left and right motor cortices (LMC/RMC) of 30 female subjects with methamphetamine dependencies (METH group) and 30 age-matched controls (control group) during resting and kick-boxing exercise (training) periods. EC was calculated in the frequency range of 0.01-0.08 Hz. RESULTS: In both resting and training state, the EC levels of METH group were significantly lower than the control group (p < 0.05). The EC levels of control group showed more significantly increased connection types than that of the METH group. CONCLUSION: Acute kick-boxing exercise altered EC in the brain of females with METH dependencies. Furthermore, the efficiency of the information flow between different brain regions in the control group was significantly higher than that in the METH group. This study provides a novel and portable assessment technique for METH rehabilitation in females on the basis of fNIRS signals.

14.
Ecotoxicol Environ Saf ; 189: 110010, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31787381

RESUMO

Nitrogen (N) forms not only affect cadmium (Cd) accumulation in plants, but also affect plant resistance to Cd toxicity. However, few researches have been reported underlying the mechanism of the relationship between nitrogen forms and plant resistance under Cd exposure. Here, we explored the mechanism on how different NO3-/NH4+ ratios affect antioxidase system and the glutathione-ascorbate cycle under five different ratios of NO3-/NH4+ (1:0, 2:1, 1:1, 1:2, 0:1) and three dosages of Cd exposure (0, 1, 5 µmol L-1 Cd) in rice (Oryza sativa L.). The results showed that high NO3- and high Cd exposure both significantly inhibited tissue growth of rice plants, and this inhibiting trend was mitigated with increasing NH4+ ratios as proved by the increased biomass and the decreased concentrations of malonaldehyde (MDA) and hydrogen peroxide (H2O2), as well as the levels of Cd contents in rice tissues. Additionally, high NH4+ ratios elevated the SOD activities in rice tissues, especially at high Cd treatment. However, other two antioxidases (CAT and APX) were insensitive to changes of NO3-/NH4+ ratios (except the full NO3-). Furthermore, high NH4+ ratios induced increasing of the efficiency of glutathione-ascorbate cycle (GSH-AsA) under two levels of Cd exposure, as evidenced by increasing concentrations of GSH and AsA and the activities of GR and DHAR in rice tissues. Overall, these results revealed that ammonium nutrition caused an enhancement resistance to Cd stress in rice plants was responsible for increasing of partial antioxidase system and the efficiencies of GSH-AsA cycle.

15.
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.

16.
BMJ Open ; 9(10): e026513, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601581

RESUMO

PURPOSE: The Chinese Longitudinal Healthy Longevity Survey Biomarkers Cohort (Healthy Ageing and Biomarkers Cohort Study (HABCS)) was established to investigate the determinants of healthy aging and mortality among the oldest old in China. Besides collecting health status, behavioural and sociodemographic circumstances, the present study also gathers comprehensive data for the elderly by simultaneously collecting, detecting, analysing blood and urine, respectively. PARTICIPANTS: HABCS is a community-based longitudinal multiwave study of older men and women aged 65 or above. Baseline survey and the follow-up surveys with replacement for deceased elderly were conducted in eight longevity areas in China, which cover the northern, middle and southern parts of China. Between 2008 and 2017, 6333 participants were included in HABCS, comprising 1385 centenarians, 1350 nonagenarians, 1294 octogenarians, 1577 younger elderly (aged 65-79). FINDINGS TO DATE: We have found that higher baseline levels of (1) total cholesterol, (2) low-density lipoprotein cholesterol (LDL-C) and (3) superoxide dismutase activity were associated with greater cognitive decline. While (4) higher LDL-C level was associated with lower risk of all-cause mortality. There was a reverse association between (5) plasma vitamin D and cognitive impairment in cross-sectional and prospective study. FUTURE PLANS: We are currently exploring the relationships between various biomarkers and different outcomes such as cognitive function and mortality. This longitudinal cohort study will be continued in the future.

17.
Chem Asian J ; 14(23): 4328-4336, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31650678

RESUMO

Surface-modified thermally expandable microcapsules (TEMs) hold potential for applications in various fields. In this work, we discussed the possible surface coating mechanism and reported the properties of TEMs coated with polyaniline (PANI) and polydisperse graphene oxide sheets (ionic liquid-graphene oxide hybrid nanomaterial (ILs-GO)). The surface coating of PANI/ ILs-GO increased the corresponding particle size and its distribution range. The morphologies analyzed by scanning electron microscopy indicated that no interfacial gap was observed between the microspheres ink and substrate layer during the substrate application. The thermal properties were determined by thermogravimetric and differential thermal analyses. The addition of ILs-GO to the polyaniline coating significantly improved the thermal expansion and thermal conductivity of the microcapsules. The evaporation of hexane present in the core of TEMs was not prevented by the coating of PANI/ ILs-GO. The printing application of TEMs showed excellent adaptability to various flexible substrates with great 3D appearance. By incorporating a flame retardant agent into TEMs coated by PANI/ILs-GO, finally, these TEMs also demonstrated a great flame retardant ability. We expect that these TEM-coated PANI/ ILs-GO are likely to have the potential to improve the functional properties for various applications.

18.
Nutr Metab (Lond) ; 16: 66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528185

RESUMO

Background: Current evidence remains equivocal as to whether and how consumption of coffee may be associated with risk of bladder cancer, and potential influence of confounding by smoking on this association is yet to be elucidated. We conducted an updated meta-analysis of prospective studies to address these issues. Methods: Relevant studies were identified by searching PubMed and EMBASE databases from inception to April 2019. A random-effects model was used to estimate summary relative risk (RR) with corresponding 95% confidence interval (CI) of bladder cancer associated with coffee consumption. Results: The final analysis included 16 prospective studies comprising 2,122,816 participants and 11,848 bladder cancer cases. Overall, coffee consumption was not associated with risk of bladder cancer (RR high-vs-low = 1.07, 95% CI: 0.96-1.20). The lack of association persisted in the strata defined by sex or participants' smoking status. Meta-regression analyses identified the number cases (P difference = 0.06) and the degree of adjustment for smoking (P difference = 0.04) as potential sources of heterogeneity. There was an increased risk of bladder cancer related to higher coffee consumption among studies with fewer cases (RR high-vs-low = 1.38, 95% CI: 1.05-1.81) and among those with poorer adjustment for smoking (RR high-vs-low = 1.48, 95% CI: 1.14-1.93). Results were similar in the dose-response analyses (RR 1 cup/d = 1.01, 95% CI: 0.98-1.03). Conclusion: Best evidence available to date does not support an independent association between coffee consumption and bladder cancer risk. Some direct associations observed in individual studies may be a result of residual confounding by smoking. Supplementary information: Supplementary information accompanies this paper at 10.1186/s12986-019-0390-3.

19.
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.

20.
Cancer Commun (Lond) ; 39(1): 43, 2019 07 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.

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