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1.
Artigo em Inglês | MEDLINE | ID: mdl-33810272

RESUMO

Inadequate dietary intake, poor nutritional status, heavy smoking, and alcohol consumption are associated with the risk of anemia. The objective of this study was to investigate the associations between dietary patterns, lifestyle, nutritional status, and anemia-related biomarkers among adults using a multivariable regression model. Taiwanese adults aged 20-45 years (n = 118,924, 43,055 men and 75,869 women) were obtained from the Mei Jau Health Management Institution database, between 2001 and 2015, for data analysis. The anemia-inflammation-related dietary pattern was derived by reduced rank regression analysis. Dietary patterns with high intakes of eggs, meat, organ meats, rice or flour products, fried foods, sugary beverages, and processed foods significantly increased the risk of anemia, and was associated with decreased hemoglobin, hematocrit, and red blood cells, but increased white blood cells and C-reactive protein levels. Moreover, current alcohol drinkers, as well as people who were underweight, overweight, obese, and central obese, were more likely to increase their risk of anemia by 46%, 20%, 23%, 34%, and 28%, respectively. Interestingly, participants who are current or past smokers were inversely associated with risk of anemia. In conclusion, adherence to the anemia-inflammation dietary pattern was associated with an increased risk of anemia in Taiwanese adults. Furthermore, abnormal weight status and alcohol drinking were correlated with an increased risk of anemia.

2.
Nutrients ; 13(3)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803758

RESUMO

We investigated the association between dietary patterns and serum hepatic enzyme levels in adults with dyslipidemia and impaired fasting glucose in Taiwan. A total of 15,005 subjects (5452 men and 9553 women) aged 35-69 years were selected. Two major dietary patterns were identified by principal component analysis: Western dietary pattern and Mediterranean dietary pattern. Subjects in the highest quartile (Q4) of the Western dietary pattern showed an increased risk of elevated serum alanine aminotransferase (ALT) levels (OR: 1.24, 95% CI: 1.06-1.45, p-trend = 0.01). Fur-thermore, in the highest quartile of the Western dietary pattern, subjects with high waist circum-ference were observed to have a greater risk for developing abnormal serum ALT levels compared to those in the lowest quartile (Q1) (OR: 1.43, 95% CI: 1.04-1.97, p-trend = 0.01). In the highest quartile of the Western dietary pattern, only women were at an increased risk for having abnormal serum ALT levels (OR: 1.28, 95% CI: 1.04-1.59, p-trend = 0.03). By contrast, in the highest quartile of the Mediterranean dietary pattern, only men were at a reduced risk for having abnormal serum gamma-glutamyl transferase (GGT) levels (OR: 0.72, 95% CI: 0.53-0.97, p-trend = 0.048). We report a positive association between the Western dietary pattern and abnormal serum ALT levels.

3.
Nurs Outlook ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33814158

RESUMO

OBJECTIVE: Nurse practitioners (NPs) and physicians serve in both usual source of care (USC) and supplement roles to each other in the provision of primary care to patients. Yet little is known about the care that patients receive from providers in these roles. This study examined the care individuals received when NPs and physicians served in USC and supplemental roles. DATA SOURCES: Pooled data from the Household Component of the Medical Expenditure Panel Survey 2002-2013. STUDY DESIGN: Cross-sectional, secondary data analysis using propensity score matching and multinomial logistic regression. DATA COLLECTION: Data were collected from a national subsample of households. PRINCIPAL FINDINGS: Regardless of provider role, patients reported receiving more therapeutic or preventive care from NPs but more diagnostic care and biomedical treatments from physicians. Patients reported having similar diagnoses when seen by NPs and physicians serving in USC roles, but different diagnoses when NPs and physicians served in supplemental roles. CONCLUSIONS: NPs and physicians providing different care when serving in the same role. Findings can inform policy-makers as they develop policies for serving patients and utilizing the relevant expertise of NPs and physicians.

4.
Plants (Basel) ; 10(2)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672856

RESUMO

Phosphoenolpyruvate carboxylase (PEPC) is a ubiquitous cytosolic enzyme that catalyzes the irreversible ß-carboxylation of phosphoenolpyruvate (PEP) in presence of HCO3- to produce oxaloacetate (OAA) during carbon fixation and photosynthesis. It is well accepted that PEPC genes are expressed in plants upon stress. PEPC also supports the biosynthesis of biocompatible osmolytes in many plant species under osmotic stress. There are five isoforms of PEPC found in peanut (Arachis hypogaea L.), namely, AhPEPC1, AhPEPC2, AhPEPC3, AhPEPC4, and AhPEPC5. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that the gene expression patterns of these AhPEPC genes were different in mature seeds, stems, roots, flowers, and leaves. The expression of all the plant type PEPC (PTPCs) (AhPEPC1, AhPEPC2, AhPEPC3, and AhPEPC4) was relatively high in roots, while the bacterial type PEPC (BTPC) (AhPEPC5) showed a remarkable expression level in flowers. Principal component analysis (PCA) result showed that AhPEPC3 and AhPEPC4 are correlated with each other, indicating comparatively associations with roots, and AhPEPC5 have a very close relationship with flowers. In order to investigate the function of these AhPEPCs, the fragments of these five AhPEPC cDNA were cloned and expressed in Escherichia coli (E. coli). The recombinant proteins contained a conserved domain with a histidine site, which is important for enzyme catalysis. Results showed that protein fragments of AhPEPC1, AhPEPC2, and AhPEPC5 had remarkable expression levels in E. coli. These three recombinant strains were more sensitive at pH 9.0, and recombinant strains carrying AhPEPC2 and AhPEPC5 fragments exhibited more growth than the control strain with the presence of PEG6000. Our findings showed that the expression of the AhPEPC fragments may enhance the resistance of transformed E. coli to osmotic stress.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33687565

RESUMO

PURPOSE: The Prognostic Nutritional Index (PNI), Nutritional Risk Index (NRI), Geriatric Nutritional Risk Index (GNRI), and Controlling Nutritional Status (CONUT) score were devised for quantifying nutritional risk. This study evaluated their properties in detecting compromised nutrition and guiding perioperative management of esophageal cancer patients. METHODS: A prospective institutional database of esophageal cancer patients was reviewed and analyzed. Compromised nutritional status was defined as PNI < 50, NRI < 97.5, GNRI < 92, or CONUT score ≥ 4, respectively. The malnutrition diagnosis consensus established by the European Society of Clinical Nutrition and Metabolism (ESPEN 2015) was selected as reference. Multivariable logistic regression and receiver operating characteristic curve analysis were used. External validation was conducted. RESULTS: After reviewing the 212-patient database, 192 patients were finally included. Among the four nutritional indexes, the GNRI < 92 showed highest sensitivity (72.0%), specificity (78.9%), and consistency (AUC 0.754, 95% CI 0.672-0.836) with malnutrition diagnosed by ESPEN 2015. The GNRI < 92 showed comparable performance with ESPEN 2015 in recognizing decreased fat mass, fat-free mass, and skeletal muscle mass (all P < 0.01). Both the GNRI < 92 and ESPEN 2015 showed good property in predicting major complications, infectious complications, overall complications and delayed hospital discharge (all P < 0.01), better than PNI < 50, NRI < 97.5, and CONUT score ≥ 4. Regarding the external validation, a retrospective analysis of 155 esophageal cancer patients confirmed the better performance of GNRI < 92 in predicting perioperative morbidities than other 3 nutritional indexes. CONCLUSION: The GNRI was optimal in perioperative management of esophageal cancer patients among the four nutritional indexes and was an appropriate alternative to ESPEN 2015 for simplifying nutritional assessment.

6.
Acupunct Med ; : 964528421996720, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33715422

RESUMO

OBJECTIVE: Interleukin (IL)-17, as a T-helper 17 cell (Th17) cytokine, plays a key role in chronic obstructive pulmonary disease (COPD) pathophysiology including chronic inflammation and airway obstruction, which lead to decreased pulmonary function. The aim of this study was to investigate the effect of acupuncture on IL-17, its receptor (IL-17R) and the mitogen-activated protein kinase (MAPK) signaling pathway, in a rat model of COPD. METHODS: The COPD model was induced in Sprague Dawley rats by exposure to cigarette smoke for 12 weeks. The model rats were treated with electroacupuncture (EA) at BL13 and ST36. The lung function and histology of the rats were observed. IL-17, tumor necrosis factor (TNF)-α, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and in plasma. The leukocytes and macrophages in the BALF were counted. The expression levels of IL-17R were assayed in lung tissue by real-time polymerase chain reaction (PCR), western blotting, and immunohistochemistry. MAPK signaling pathway molecules including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)1/2 and p38, and their phosphorylated forms, were observed in the lung by western blotting. RESULTS: Compared with the control group rats, lung function decreased and there was a severe inflammatory infiltration of the pulmonary parenchyma in the COPD rats. EA effectively improved lung function and alleviated the inflammatory infiltration in the lungs of COPD rats. EA also reversed the elevated total leukocyte and macrophage counts, the high levels of IL-17 and TNF-α, and the low IL-10 content in COPD rats. Meanwhile, EA downregulated the increased mRNA and protein expression of IL-17R, and significantly inhibited the elevated levels of phosphorylated JNK, ERK1/2, and p38 in the lungs of COPD rats. CONCLUSION: Our results suggest that the protective effects of acupuncture therapy on the lungs of COPD rats are likely related to inhibition of IL-17/IL-17R and the post-receptor MAPK signaling pathways.

7.
Prev Vet Med ; 190: 105317, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33744674

RESUMO

The coinfection of swine influenza (SI) strains and avian/human-source influenza strains in piggeries can contribute to the evolution of new influenza viruses with pandemic potential. This study analyzed surveillance data on SI in south China and explored the spatial predictor variables associated with different influenza infection scenarios in counties within the study area. Blood samples were collected from 7670 pigs from 534 pig farms from 2015 to 2017 and tested for evidence of infection with influenza strains from swine, human and avian sources. The herd prevalences for EA H1N1, H1N1pdm09, classic H1N1, HS-like H3N2, seasonal human H1N1 and avian influenza H9N2 were 88.5, 64.5, 60.3, 57.8, 12.9 and 10.3 %, respectively. Anthropogenic factors including detection frequency, chicken density, duck density, pig density and human population density were found to be better predictor variables for three influenza infection scenarios (infection with human strains, infection with avian strains, and coinfection with H9N2 avian strain and at least one swine strain) than were meteorological and geographical factors. Predictive risk maps generated for the four provinces in south China highlighted that the areas with a higher risk of the three infection scenarios were predominantly clustered in the delta area of the Pearl River in Guangdong province and counties surrounding Poyang Lake in Jiangxi province. Identification of higher risk areas can inform targeted surveillance for influenza in humans and pigs, helping public health authorities in designing risk-based SI control strategies to address the pandemic influenza threat in south China.

8.
Stem Cell Res ; : 102197, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771478

RESUMO

Excessive prostaglandin E2 (PGE2) is the key pathological basis for COVID-19 and a Celebrex treatment of hospitalized COVID-19 patients with comorbidities led to 100% discharged rate and zero death (Hong et al. 2020). It is also suggested that SARS-CoV-2 infected multiple organs and the SARS-CoV nucleocapsid (N) protein transcriptionally drives the expression of the host COX-2 gene. In order to test whether SARS-CoV-2 N protein activates COX-2 transcription in multiple human relevant cell types, an expression inducible human embryonic stem cell line was generated by piggyBac transposon system. This cell line maintained its pluripotency, differentiation potentials, normal morphology and karyotype.

9.
Sheng Wu Gong Cheng Xue Bao ; 37(2): 604-614, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33645158

RESUMO

Proton-pumping rhodopsin (PPR) is a simple photosystem widely distributed in nature. By binding to retinal, PPR can transfer protons from the cytoplasmic to the extracellular side of the membrane under illumination, creating a proton motive force (PMF) to synthesize ATP. The conversion of light into chemical energy by introducing rhodopsin into nonphotosynthetic engineered strains could contribute to promoting growth, increasing production and improving cell tolerance of microbial hosts. Gloeorhodopsin (GR) is a PPR from Gloeobacter violaceus PCC 7421. We expressed GR heterologously in Escherichia coli and verified its functional activity. GR could properly function as a light-driven proton pump and its absorption maximum was at 539 nm. We observed that GR was mainly located on the cell membrane and no inclusion body could be found. After increasing expression level by ribosome binding site optimization, intracellular ATP increased, suggesting that GR could supply additional energy to heterologous hosts under given conditions.


Assuntos
Cianobactérias , Rodopsina , Cianobactérias/genética , Cianobactérias/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Bombas de Próton , Rodopsina/genética , Rodopsina/metabolismo , Rodopsinas Microbianas/genética , Rodopsinas Microbianas/metabolismo
10.
Zhongguo Zhong Yao Za Zhi ; 46(4): 1000-1009, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645106

RESUMO

To systematically evaluate the clinical efficacy and safety of Lianhua Qingwen in the treatment of adult pneumonia. The randomized controlled trial of Lianhua Qingwen combined with conventional Western medicine in the treatment of pneumonia were retrieved from PubMed, EMbase, Wanfang database, VIP database, and CNKI from the establishment of database to March 2020. Two researchers independently conducted literature screening and data extraction, and the third researcher was in charge of arbitration in case of any disagreement. Outcome indicators included total clinical effective rate, symptom improvement time, and incidence of adverse events. R 3.6.1 was used for Meta-analysis, and RevMan 5.3 was used for quality evaluation. Twenty-two studies were included, with a total of 2 007 patients, including 1 017 patients in the experimental group and 990 patients in the control group. The results showed that the total clinical effective rate of the experimental group was higher than that of the control group(RR=1.11, 95%CI[1.08, 1.15], P<0.001), and the antifebrile time(MD=-1.81, 95%CI[-2.42,-1.21], P<0.001), cough duration(MD=-2.32, 95%CI[-2.89,-1.76], P<0.001), rale duration(MD=-2.19, 95%CI[-2.74,-1.63], P<0.001), imaging recovery time(MD=-2.17, 95%CI[-2.76,-1.58], P<0.001) and post-treatment CRP(MD=-4.07, 95%CI[-6.39,-1.75], P<0.001] were all significantly lower than those of the control group. However, it did not proved that the experimental group was safer than the control group(RR=0.84, 95%CI[0.57, 1.24], P=0.382). The results confirmed that Lianhua Qingwen combined with conventional Western medicine in the treatment of pneumonia could improve the clinical treatment efficiency, shorten the time of fever, cough, rale disappearance and imaging recovery, improve CRP index and accelerate the recovery of pneumonia patients. However, the literatures included in this study had a low quality, and the conclusions still need to be further confirmed by more high-quality, multi-center, rigorously designed randomized controlled trial.


Assuntos
Medicamentos de Ervas Chinesas , Pneumonia , Adulto , Tosse , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Pneumonia/tratamento farmacológico , Resultado do Tratamento
11.
Bioengineered ; 12(1): 763-778, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33660570

RESUMO

Interleukin (IL)-18 has a clear antitumor effect; however, its mechanisms of action are not understood in patients with colorectal cancer (CRC). Here, we investigated the potential mechanism of IL-18 in CRC. The results showed that IL-18 treatment alone had no effect on HCT116 cells apoptosis, whereas IL-18 in the presence of natural killer (NK) cells resulted in apoptosis and inhibition of cells proliferation in vitro. Profiling of miRNA expression following coculture with NK cells and treatment with IL-18 resulted in significant downregulation of miR-574-3p expression and upregulated expression of the target gene transforming growth factor beta 1 (TGF-ß1). miR-574-3p binds to TGF-ß1, and miR-574-3p overexpression increased the proliferation and decreased the apoptotic rate of HCT116 cells in NK cells coculture with IL-18 treatment; overexpression of TGF-ß1 restored the effect of miR-574-3p overexpression. The miRNA profile of HCT116 undergoes significant alteration before and after coculturing with NK cells and treatment with IL-18. IL-18 alone did not affect HCT116 cells apoptosis but did promote the antitumor ability of NK cells in coculture with HCT116 cells via the miR-574-3p/TGF-ß1 axis. Our study suggested that IL-18 can be a new potential target for cancer immunotherapy for CRC.

12.
Am Surg ; : 3134820981723, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33662220

RESUMO

BACKGROUND: To discuss the prevention and treatment of lymph or chyle leak following neck dissection in patients with thyroid carcinoma. METHODS: A total of 1724 patients with thyroid carcinoma received neck dissection in the Sun Yat-sen University Cancer Center between November 2009 and October 2014. The incidence and management of leak were analyzed. RESULTS: A total of 92 (5.34%) patients developed leak, 28 (1.62%) developed lymph leak, 59 (3.42%) developed chyle leak, and 5 (.29%) developed chylothorax. Medical management to stop postoperative lymph or chyle leak included pressure dressing, reoperation, fasting, or low-fat diet therapy. CONCLUSIONS: Lymph or chyle leak may occur in thyroid carcinoma patients who underwent neck dissection. Clinicians should alert to leak when there were IV + VI region lymph node metastasis and should become aware of chylothorax after pressure dressing. A careful identification and ligation of lymphatic duct may be an effective way to avoid lymph or chyle leak.

13.
Ann Surg Oncol ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33738720

RESUMO

BACKGROUND: Nodal-skip metastasis (NSM) is found in esophageal squamous cell carcinoma (ESCC), but its prognostic role is controversial. This study aimed to investigate the prognostic value of NSM for thoracic ESCC patients. METHODS: Categorization of NSM was according to the N groupings of Japan Esophagus Society (JES) staging system, which is dependent on tumor location. Using the Kaplan-Meier method and Cox-regression analysis, this study retrospectively analyzed the overall survival (OS) for 2325 ESCC patients after radical esophagectomy at three high-volume esophageal cancer centers. Predictive models also were constructed. RESULTS: The overall NSM rate was 20% (229/1141): 37.4% in the in upper, 12.9% in the middle, and 22.2% in the lower thoracic ESCC. The patients with NSM always had a better prognosis than those without NSM. Furthermore, NSM was an independent prognostic factor for thoracic ESCC patients (hazard ratio [HR], 0.633; 95% confidence interval [CI], 0.499-0.803; P < 0.001). By integrating the prognostic values of NSM and N stage, the authors proposed the new N staging system. The categories defined by the new N staging system were more homogeneous in terms of OS than those defined by the current N system. Moreover, the new N system was shown to be an independent prognostic factor also for thoracic ESCC patients (HR, 1.607; 95% CI, 1.520-1.700; P < 0.001). Overall, the new N system had slightly better homogeneity, discriminatory ability, and monotonicity of gradient than the current N system. CONCLUSIONS: This study emphasized the prognostic power of NSM and developed a modified node-staging system to improve the efficiency of the current International Union for Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) N staging system.

14.
Biochem Biophys Res Commun ; 551: 71-77, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33721833

RESUMO

Glyoxylate is an important chemical and is also an intermediate involved in metabolic pathways of living microorganisms. However, it cannot be rapidly utilized by many microbes. We observed a very long lag phase (up to 120 h) when E. coli is growing in a mineral medium supplemented with 50 mM glyoxylate. To better understand this strange growth pattern on glyoxylate and accelerate glyoxylate utilization, a random genomic library of E. coli was transformed into E. coli BW25113, and mutants that showed significantly shortened lag phase on glyoxylate were obtained. Interestingly, mutations in BtsT/BtsS, a two component system that is involved in pyruvate transport, were found to be a common feature in all mutants retrieved. We further demonstrated, through reverse engineering, that the mutations in BtsT/BtsS can indeed increase glyoxylate uptake. Growth experiments with different concentration of glyoxylate also showed the higher the concentration of glyoxylate, the shorter the lag phase. These new findings thus increased our understanding on microbial utilization of glyoxylate.

15.
Org Lett ; 23(7): 2807-2810, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33755492

RESUMO

Fortuneicyclidins A (1) and B (2), a pair of epimeric pyrrolizidine alkaloids containing an unprecedented 7-azatetracyclo[5.4.3.0.02,8]tridecane core, were isolated from the seeds of Cephalotaxus fortunei, along with two biogenetically relative known analogues, 3 and 4. The structures were determined by multiple spectral techniques and chemical derivatization methods. Compound 1 showed inhibitory activity against α-glucosidase.

16.
Transl Oncol ; 14(6): 101075, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33773404

RESUMO

BACKGROUND: Cisplatin (DDP) remains the backbone of chemotherapy for non-small cell lung cancer (NSCLC), yet its clinical efficacy is limited by DDP resistance. We aim to investigate the role of the SET and MYND domain-containing protein 3 (SMYD3) in DDP resistance of NSCLC. METHODS: Expression pattern of SMYD3 was determined in NSCLC tissues using qRT-PCR, which also validated its correlation with NSCLC clinicopathological stages. Impacts of SMYD3 on DDP resistance were evaluated by knocking down SMYD3 in DDP-resistant cells and overexpressing it in DDP-sensitive cells, and assessed for several phenotypes: IC50 by MTT, long-term proliferation by colony formation, apoptosis and cell-cycle distribution by flow cytometry. The interaction between Ankyrin Repeat and KH Domain Containing 1 (ANKHD1) and SMYD3 was examined by co-immunoprecipitation and immunofluorescence. The transcriptional regulation of SMYD3 on cyclin-dependent kinase 2 (CDK2) promoter regions was confirmed using chromatin-immunoprecipitation. The in vivo experiments using DDP-resistant cells with altered SMYD3 and ANKHD1 expression were further performed to verify the SMYD3/ANKHD1 axis. RESULTS: Highly expressed SMYD3 was observed in NSCLC tissues or cells, acted as a sensitive indicator for NSCLC, correlated with higher TNM stages or resistant to DDP treatment, and shorter overall survival. The promotion of SMYD3 on DDP resistance requires co-regulator, ANKHD1. CDK2 was identified as a downstream effector. In vivo, SMYD3 knockdown inhibited the growth of DDP-resistant NSCLC cells, which was abolished by ANKHD1 overexpression. CONCLUSIONS: SMYD3 confers NSCLC cells chemoresistance to DDP in an ANKHD1-dependent manner, providing novel therapeutic targets to overcome DDP resistance in NSCLC .

17.
Mol Biol Rep ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629201

RESUMO

High-throughput sequencing of the Phoebe bournei transcriptome was performed, and novel SSR markers were identified. A total of 73,518 nonredundant unigenes were assembled and annotated by sequence similarity searching in diverse public databases. A total of 40,853 SSRs were identified from 73,518 unigenes. Twenty-three pairs of polymorphic EST-SSR markers were selected from 98 markers and used for genetic analyses in 75 individuals from three P. bournei populations. The 23 pairs of markers could detect abundant genetic information from the samples (PIC = 0.769), and cross-species amplification was successfully performed in other related species. Three populations had high level of genetic diversity (He = 0.658 in average), of which the population YS from Jiangxi province had the most abundant genetic diversity (He = 0.722). The results of genetic structure analyses showed that the population YS from Jiangxi province had obvious genetic differences from the other two populations, and the genetic information of the population SX from Fujian province was related to that of the population LC from Guangdong province and the population YS. The transcriptomic resources and EST-SSR markers are valuable tools not only for the ecological conservation of P. bournei but also for phylogenetic studies.

18.
EBioMedicine ; 64: 103227, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33530002

RESUMO

BACKGROUND: Urolithin A (URA) is an intestinal microbiota metabolic product from ellagitannin-containing foods with multiple biological activities. However, its role in autoimmune diseases is largely unknown. Here, for first time, we demonstrate the therapeutic effect of URA in an experimental autoimmune encephalomyelitis (EAE) animal model. METHODS: Therapeutic effect was evaluated via an active and passive EAE animal model in vivo. The function of URA on bone marrow-derived dendritic cells (BM-DCs), T cells, and microglia were tested in vitro. FINDINGS: Oral URA (25 mg/kg/d) suppressed disease progression at prevention, induction, and effector phases of preclinical EAE. Histological evaluation showed that significantly fewer inflammatory cells, decreased demyelination, lower numbers of M1-type microglia and activated DCs, as well as reduced infiltrating Th1/Th17 cells were present in the central nervous system (CNS) of the URA-treated group. URA treatment at 25 µM inhibited the activation of BM-DCs in vitro, restrained Th17 cell differentiation in T cell polarization conditions, and in a DC-CD4+ T cell co-culture system. Moreover, we confirmed URA inhibited pathogenicity of Th17 cells in adoptive EAE. Mechanism of URA action was directly targeting Aryl Hydrocarbon Receptor (AhR) and modulating the signaling pathways. INTERPRETATION: Collectively, our study offers new evidence that URA, as a human microbial metabolite, is valuable to use as a prospective therapeutic candidate for autoimmune diseases.

19.
Biochem Soc Trans ; 49(1): 519-529, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33544148

RESUMO

The ubiquitin proteasome system (UPS) serves as the major posttranslational modification system for the maintenance of protein homeostasis. The ubiquitin ligases (E3s) are responsible for the recognition and recruitment of specific substrate proteins for polyubiquitination. Really interesting new gene (RING) finger E3s account for the majority of E3s. The human genome encodes more than 600 RING E3s, which are divided into three subclasses: single polypeptide E3s, cullin-RING ligases (CRLs) and other multisubunit E3s. The abnormal regulation of RING E3s has been reported to disrupt normal biological processes and induce the occurrence of many human malignancies. Glioma is the most common type of malignant primary brain tumor. In the last few decades, patient prognosis has improved as novel targeted therapeutic agents have developed. In this review, we will summarize the current knowledge about the dysregulation of RING E3s and the altered stability of their substrates in glioma. We will further introduce and discuss the current status and future perspectives of the application of small inhibitors and proteolysis-targeting chimeric molecules (PROTACs) interfering with RING E3s as potential anticancer agents for glioma.

20.
CMAJ ; 193(8): E270-E277, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619067

RESUMO

BACKGROUND: New case-mix tools from the Canadian Institute for Health Information offer a novel way of exploring the prevalence of chronic disease and multimorbidity using diagnostic data. We took a comprehensive approach to determine whether the prevalence of chronic disease and multimorbidity has been rising in Ontario, Canada. METHODS: In this observational study, we applied case-mix methodology to a population-based cohort. We used 10 years of patient-level data (fiscal years 2008/09 to 2017/18) from multiple care settings to compute the rolling 5-year prevalence of 85 chronic diseases and multimorbidity (i.e., the co-occurrence of 2 or more diagnoses). Diseases were further classified based on type and severity. We report both crude and age- and sex-standardized trends. RESULTS: The number of patients with chronic disease increased by 11.0% over the 10-year study period to 9.8 million in 2017/18, and the number with multimorbidity increased 12.2% to 6.5 million. Overall increases from 2008/09 to 2017/18 in the crude prevalence of chronic conditions and multimorbidity were driven by population aging. After adjustments for age and sex, the prevalence of patients with ≥ 1 chronic conditions decreased from 70.2% to 69.1%, and the prevalence of multimorbidity decreased from 47.1% to 45.6%. This downward trend was concentrated in minor and moderate diseases, whereas the prevalence of many major chronic diseases rose, along with instances of extreme multimorbidity (≥ 8 conditions). Age- and sex-standardized resource intensity weights, which reflect relative expected costs associated with patient diagnostic profiles, increased 4.6%. INTERPRETATION: Evidence of an upward trend in the prevalence of chronic disease was mixed. However, the change in case mix toward more serious conditions, along with increasing patient resource intensity weights overall, may portend a future need for population health management and increased health system spending above that predicted by population aging.

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