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1.
Clin Nutr ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-33008652

RESUMO

BACKGROUND & AIMS: Our previous study found that platelet counts were positively associated with body fat percentage in human. In the present study, we conducted a reverse translational study to explore the role of platelets in modulating pre-adipocyte proliferation in mice. METHODS: Mouse pre-adipocyte cell line (3T3-L1) and human pre-adipocytes harvested from female subcutaneous fat were used. Pre-adipocytes were co-cultured with platelets or platelet releasate, which were isolated from mice or humans. The cell viability and proliferative ability of the pre-adipocytes were examined by MTT and flow cytometry assays. Western blotting analysis was used to determine the phosphorylation levels of proteins in the mTOR pathway. RESULTS: The number of platelets in the adipose tissues from obese mice was significantly higher than that from lean mice. Platelets and collagen-activated platelet releasate stimulated the proliferation of human pre-adipocytes and 3T3-L1 cells in vitro. Besides, platelets from obese mice were more potent in stimulating pre-adipocyte proliferation than those from lean control mice. Mechanistically, platelets enhanced pre-adipocyte proliferation through the acceleration of cell cycle progression from G0/G1 to S phase cell cycle progression. At the molecular level, platelets promoted pre-adipocyte proliferation through mTOR pathway-mediated upregulation of cyclin D1 expression. CONCLUSION: In conclusion, platelets and platelet releasate play an important role in the proliferation of pre-adipocytes. Our study may provide new clues and the molecular mechanism of the causal pathways between platelets and body fat to explain the finding we observed in population study.

2.
J Org Chem ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058677

RESUMO

Stereoselective construction of α-sialyl linkages is one of the most significant challenges in carbohydrate chemistry. In this research, we developed a novel strategy for stereoselective synthesis of α-linked sialosides by protecting the 5-N,4-O-positions of a sialyl donor with an oxazolidinone group and its C-1 carboxylic functionality with a cyanoethyl ester to promote α-glycosylation. We also adopted the more electrophilic N-bromosuccinimide as a promoter to readily activate p-tolyl thiosialoside at -78 °C. The sialylation using this sialyl donor gave excellent yields and α-selectivity. The new synthetic method was used to successfully construct naturally occurring α-sialosides having sialic acid linked to the 6-O- or 3-O-position of galactoside, or 8-O-position of another sialic acid, respectively, as well as other α-linked sialosides.

3.
Clin Chim Acta ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058845

RESUMO

Chinese newborns have been screened for inborn errors of metabolism (IEM) for over 20 years. Although China features 56 different ethnic groups, there are no specific data describing the incidence of such genetic errors across difference ethnicities. To understand the ethnic preference distribution of the incidence and variants of IEM in the Ningxia Hui Autonomous Region of China, 189,354 newborns from 2016 to 2019 were screened by tandem mass spectrometry, including 87,482 from the Han ethnic population, 88,229 from the Hui population, 1,103 from other ethnicities, and 12,540 infants without ethnic registration. Suspected cases then underwent specific genetic profiling by targeted next generation sequencing. In total, 160 patients were diagnosed with 17 types of IEM, with a significant higher incidence in Hui infants (1/1,003) than in Han infants (1/1,232). Five diseases (eight patients) were specifically detected in Han infants, while three were exclusively diagnosed in six Hui infants. For shared diseases, the variants of keys genes also showed ethnic preference. Our findings enhance our understanding of the genetics underlying IEM, thus promoting the development of treatment plans for patients from different areas or ethnicities in China.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33059569

RESUMO

Diseases, trauma, and injuries are highly prevalent conditions that lead to many critical tissue defects. Tissue engineering has great potentials to develop functional scaffolds that mimic natural tissue structures to improve or replace biological functions. In many kinds of technologies, electrospinning has received widespread attention for its outstanding functions, which is capable of producing nanofibre structures similar to the natural extracellular matrix. Amongst, the electrospinning of available biopolymers, poly (caprolactone) (PCL), has shown favorable outcomes for tissue regeneration applications. According to the characteristics of different tissues, PCL can be modified by altering the functional groups or combining with other materials such as synthetic polymers, natural polymers, and metal materials to improve its physicochemical, mechanical, and biological properties, making the electrospun scaffolds meet the requirements of different tissue engineering and regenerative medicine. Moreover, efforts have been made to modify nanofibres with several bioactive substances to provide cells with the necessary chemical cues and a more in vivo like environment. In this review, some recent developments in both the design and utility of electrospun PCL-based scaffolds in the fields of bone, cartilage, skin, tendon, ligament and nerve are highlighted, along with their potential impact on future research and clinical applications.

5.
Nature ; 586(7829): 434-439, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33029007

RESUMO

Cysteine palmitoylation (S-palmitoylation) is a reversible post-translational modification that is installed by the DHHC family of palmitoyltransferases and is reversed by several acyl protein thioesterases1,2. Although thousands of human proteins are known to undergo S-palmitoylation, how this modification is regulated to modulate specific biological functions is poorly understood. Here we report that the key T helper 17 (TH17) cell differentiation stimulator, STAT33,4, is subject to reversible S-palmitoylation on cysteine 108. DHHC7 palmitoylates STAT3 and promotes its membrane recruitment and phosphorylation. Acyl protein thioesterase 2 (APT2, also known as LYPLA2) depalmitoylates phosphorylated STAT3 (p-STAT3) and enables it to translocate to the nucleus. This palmitoylation-depalmitoylation cycle enhances STAT3 activation and promotes TH17 cell differentiation; perturbation of either palmitoylation or depalmitoylation negatively affects TH17 cell differentiation. Overactivation of TH17 cells is associated with several inflammatory diseases, including inflammatory bowel disease (IBD). In a mouse model, pharmacological inhibition of APT2 or knockout of Zdhhc7-which encodes DHHC7-relieves the symptoms of IBD. Our study reveals not only a potential therapeutic strategy for the treatment of IBD but also a model through which S-palmitoylation regulates cell signalling, which might be broadly applicable for understanding the signalling functions of numerous S-palmitoylation events.

6.
Nat Commun ; 11(1): 4968, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009413

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.


Assuntos
Infecções por Coronavirus/diagnóstico , Progressão da Doença , Pneumonia Viral/diagnóstico , Pneumonia , Tomografia Computadorizada por Raios X/métodos , Adulto , Betacoronavirus , China , Técnicas de Laboratório Clínico , Coinfecção , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Feminino , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
7.
Am J Emerg Med ; 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-33041109

RESUMO

During the pandemic of 2019-nCoV, large public hospitals are facing great challenges. Multi-hospital development will be the main mode of hospital administrative management in China in the future. West China Hospital of Sichuan University implemented multi-hospital integrated management, in which the branch district established the administrative multi-department collaboration mode. As an important part of the operation of branch district, how to effectively organize transportation of staffs and patients and to prevent and control the pandemic of 2019-nCoV simultaneously between different hospitals have been the key and difficult points, which should be solved urgently in the management of the branch district.

8.
JAMA Dermatol ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052382

RESUMO

Importance: Demonstrating the value of therapies from a patient's perspective is increasingly important for patient-centered care. Objective: To compare patient-reported outcomes (PROs) with risankizumab vs ustekinumab and placebo in psoriasis symptoms, health-related quality of life (HRQL), and mental health among patients with moderate to severe psoriasis. Design, Setting, and Participants: The UltIMMa-1 and UltIMMa-2 studies were replicate 52-week phase 3, randomized, multisite, double-blind, placebo-controlled and active comparator-controlled trials conducted in 139 sites (including hospitals, academic medical centers, clinical research units, and private practices) globally in Asia-Pacific, Japan, Europe, and North America. Adults (≥18 years) with moderate to severe chronic plaque psoriasis with body surface area (BSA) involvement of 10% or more, Psoriasis Area Severity Index (PASI) scores of 12 or higher, and static Physician's Global Assessment (sPGA) scores of 3 or higher were included. Interventions: In each trial, patients were randomly assigned (3:1:1) to 150 mg of risankizumab, 45 mg or 90 mg of ustekinumab (weight-based per label) for 52 weeks, or matching placebo for 16 weeks followed by risankizumab. Main Outcomes and Measures: Integrated data from 2 trials were used to compare Psoriasis Symptom Scale (PSS) (total score and item scores for pain, redness, itchiness, and burning), Dermatology Life Quality Index (DLQI), 5-level EuroQoL-5D (EQ-5D-5L), and Hospital Anxiety and Depression Scale (HADS), at baseline, week 16, and week 52. Results: A total of 997 patients with moderate to severe chronic plaque psoriasis were analyzed. Across all arms, the mean age was 47.2 to 47.8 years and 68.3% (136/199 for ustekinumab) to 73.0% (146/200 for placebo) were men. Patients' characteristics and PROs were comparable across all treatment arms at baseline (n = 598, 199, 200 for risankizumab, ustekinumab, and placebo, respectively). At week 16, a significantly greater proportion of patients treated with risankizumab than those treated with ustekinumab or placebo achieved PSS = 0, indicating no psoriasis symptoms (30.3% [181/598], 15.1% [30/199], 1.0% [2/200], both P < .001), and DLQI = 0 or 1 indicating no impact on skin-related HRQL (66.2%, 44.7%, 6.0%, P < .001). Significantly greater proportions of patients treated with risankizumab achieved minimally clinically important difference (MCID) than ustekinumab or placebo for DLQI (94.5% [516/546], 85.1% [149/175], 35.6% [64/180]; both P < .001), EQ-5D-5L (41.7% [249/597] vs 31.5% [62/197], P = .01; vs 19.0% [38/200], P < .001), and HADS (anxiety: 69.1% [381/551] vs 57.1% [104/182], P = .004; vs 35.9% [66/184], P < .001; depression: 71.1% [354/598] vs 60.4% [96/159], P = .01; vs 37.1% [59/159], P < .001). At week 52, improvements in patients treated with risankizumab compared with those treated with ustekinumab were sustained for PSS, DLQI, and EQ-5D-5L. Conclusions and Relevance: Risankizumab significantly improved symptoms of moderate to severe psoriasis, improved HRQL, and reduced psychological distress compared with ustekinumab or placebo. Trial Registration: ClinicalTrials.gov Identifiers: NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2).

9.
Front Immunol ; 11: 2133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013900

RESUMO

The small GTPase Rab5 is one of the master regulators of vesicular trafficking that participates in early stages of the endocytic pathway, such as endocytosis and endosome maturation. Three Rab5 isoforms (a, b, and c) share high sequence identity, and exhibit complex functions. However, the role of Rab5c in virus infection and cellular immune responses remains poorly understood. In this study, based on the established virus-cell infection model, Singapore grouper iridovirus (SGIV)-infected grouper spleen (GS) cells, we investigated the role of Rab5c in virus infection and host immune responses. Rab5c was cloned from the orange-spotted grouper, Epinephelus coioides, and termed EcRab5c. EcRab5c encoded a 220-amino-acid polypeptide, showing 99% and 91% identity to Anabas testudineus, and Homo sapiens, respectively. Confocal imaging showed that EcRab5c localized as punctate structures in the cytoplasm. However, a constitutively active (CA) EcRab5c mutant led to enlarged vesicles, while a dominant negative (DN) EcRab5c mutant reduced vesicle structures. EcRab5c expression levels were significantly increased after SGIV infection. EcRab5c knockdown, or CA/DN EcRab5c overexpression significantly inhibited SGIV infection. Using single-particle imaging analysis, we further observed that EcRab5c disruption impaired crucial events at the early stage of SGIV infection, including virus binding, entry, and transport from early to late endosomes, at the single virus level. Furthermore, it is the first time to investigate that EcRab5c is required in autophagy. Equally, EcRab5c positively regulated interferon-related factors and pro-inflammatory cytokines. In summary, these data showed that EcRab5c exerted a bi-functional role on iridovirus infection and host immunity in fish, which furthers our understanding of virus and host immune interactions.

10.
Plant Dis ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021908

RESUMO

Gleditsia Sinensis Lam is a kind of legume perennial woody plant, which is a traditional Chinese medicine with high economic and ecological value. Its planting area is about 0.1 million ha. In July 2018, symptoms of stem blight were observed on G. sinensis in An shun (26.072311°N, 106.097433°E), Guizhou province (southwestern China). Symptoms included stem canker and dieback, twig blight and extensive vascular discoloration, with incidence rate of 45 to 70%. Samples from plants with symptoms were washed with running tap water, surface sterilized with 2% sodium hypochlorite and then 75% ethanol, rinsed in sterile distilled water, plated on potato dextrose agar (PDA) and incubated at 28°C. Fungal isolates developed copious white aerial mycelium that became dark grey after four to five days, and formed black pycnidia after 23 days. Single hyphal tip cultures of putative 27 isolates were stored in the culture collection (CMW) of the Urban Modern Agriculture Engineering Research Center at the Kunming University. Conidia forming on pycnidia were one-celled, hyaline, aseptate, and fusiform, with dimensions of 20.3-25.9 µm x 4.2-6.5 µm (average 22.5 x 5.5 µm) (sixty conidia were measured). DNA sequence analysis of the ribosomal internal transcribed spacer regions ITS1-5.8S-ITS4, ß-tubulin, and the translation elongation factor 1-alpha (EF1-α) were performed. BLAST searches at GenBank showed the highest nucleotide sequence identity with Botryosphaeria dothidea reference sequence (ITS: >99.82%, KR708996; EF1-α: 99.62%, KP183214; ß-tubulin: > 99.67%, KU306116). Representative sequences of isolates from these regions were deposited in GenBank (ITS: Accession No. MT449017; EF1-α: Accession No. MT454342; ß-tubulin: Accession No. MT454343). Morphological and molecular results confirmed this species as B. dothidea (Aguirre et al. 2018). Pathogenicity tests were conducted by stem inoculation of two-year-old G. sinensis seedlings. Mycelial plugs (2-3 mm in diameter) from actively growing colonies of B. dothidea (PDA) were applied to same-size bark wounds on the middle point of the stems. Inoculated wounds were wrapped with Parafilm. Control seedlings received sterile PDA plugs. Inoculated and control seedlings (9 each), and kept in the greenhouse (28℃, 80% humidity); After 10 days, all of the inoculated plants showed dark vascular stem tissue, and the controls remained healthy. After 30 days, all of the inoculated but none of the control G. sinensis seedlings showed leaf wilting and tissue discoloration. B. dothidea was re-isolated from symptomatic tissues, thus fulfilling Koch's postulates. No symptoms were visible in the control seedlings, and no B. dothidea was re-isolated from the control seedlings tissues. B. dothidea is a member of Botryosphaeriaceae, commonly associated with cankers and dieback of woody plants. B. dothidea has been reported as a pathogen causing stem dieback and branch canker on Malosma laurina (Aguirre et al. 2018), Helwingia chinensis (Yu et al. 2012), and blueberry (Choi 2011; Yu et al. 2012). To our knowledge, this is the first report of B. dothidea on G. sinensis in China.

11.
Biomolecules ; 10(10)2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33027960

RESUMO

Corilagin (CLG), a major component of several medicinal plants, can exhibit diverse pharmacological properties including those of anti-cancer, anti-inflammatory, and hepatoprotective qualities. However, there are no prior studies on its potential impact on the epithelial-to-mesenchymal transition (EMT) process. EMT can lead to dissemination of tumor cells into other organs and promote cancer progression. Hence, we aimed to investigate the effect of CLG on EMT and its mechanism(s) of action in tumor cells. We noted that CLG reduced the expression of various epithelial markers and up-regulated the expression of Occludin and E-cadherin in both basal and TGFß-stimulated tumor cells. CLG treatment also abrogated cellular invasion and migration in colon and prostate carcinoma cells. In addition, CLG effectively attenuated the Wnt/ß-catenin signaling cascade in TGFß-stimulated cells. Overall, our study suggests that CLG may function as and effective modulator of EMT and metastasis in neoplastic cells.

13.
Nanoscale ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006354

RESUMO

There are only a handful of reports on indium sulfide (In2S3) in the electrochemical energy storage field without a clear electrochemical reaction mechanism. In this work, a simple electrospinning method has been used to synthesize In2S3/C nanofibers for the first time. In lithium-ion batteries (LIBs), the In2S3/C nanofiber electrode can not only deliver a high initial reversible specific capacity of 696.4 mA h g-1 at 50 mA g-1, but also shows ultra-long cycle life with a capacity retention of 80.5% after 600 cycles at 1000 mA g-1. In sodium-ion batteries (SIBs), the In2S3/C nanofibers electrode can exhibit a high initial reversible specific capacity (393.7 mA h g-1 at 50 mA g-1) and excellent cycling performance with a high capacity retention of 97.3% after 300 cycles at 1000 mA g-1. The excellent electrochemical properties mainly benefited from In2S3 being encapsulated by a carbon matrix, which buffers the volume expansion and significantly improves the conductivity of the composite. Furthermore, the structural evolution of In2S3 during the first lithiation/delithiation and sodiation/desodiation processes has been illustrated by ex situ XRD. The results confirm that the reaction mechanism of In2S3 in both LIBs and SIBs can be summarized as conversion reactions and alloying reactions, which provide theoretical support for the development of In2S3 in the field of electrochemistry.

14.
Int Immunopharmacol ; 89(Pt B): 107072, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33059198

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy is a breakthrough in cancer treatment. With the widespread use of this therapy, increasing evidence is available that CAR-T cell therapy is associated with acute kidney injury (AKI). Nephrologists need to understand the potential nephrotoxicity arising from CAR-T cell therapy. Determining the cause of AKI is a key factor of clinical management. This review focuses on the clinical use of CAR-T cell therapy and the cause and outcomes of nephrotoxicity with its use. We also provide clinical suggestions for clinicians towards both better diagnosis and management of AKI in those receiving CAR-T cell therapy.

15.
Biomed Pharmacother ; 132: 110745, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068938

RESUMO

The present work was aimed to evaluate the effect of valproic acid(VPA), simvastatin (SIM)+VPA on Ti(titanium) rods osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. The MC3T3-E1 cells were co-cultured with VPA, SIM + VPA and induced to osteogenesis, and the cell viability, mineralization ability were observed by MTT and ALP staining, Alizarin Red staining and Western blotting. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: group OVX and VPA, SIM + VPA, and all the rats received Ti implants and animals belong to group VPA, SIM + VPA received valproic acid(300 mg/kg/day), valproic acid(300 mg/kg/day) plus SIM (25 mg/kg/day), respectively, treatment until death at 12 weeks. Micro-CT, histology, biomechanical testing, bone metabolism index and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism. Results shown that VPA decreased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed combined application of systemic VPA showed harmful effects than OVX group on bone formation in osteopenic rats, with the worse effects on CTX-1, P1NP and microarchitecture as well as biomechanical parameters by down-regulated gene expression of Runx2, OCN, Smad1, BMP-2 and OPG, while up-regulated RANKL. However, after SIM treatment, the above indicators were significantly improved. The present study suggests that systemic use of VPA may bring harm to the stability of titanium implants in osteoporosis, SIM can reverse the negative effect of VPA on the osseointegration of titanium rods in ovariectomized rats.

16.
Eur J Clin Nutr ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082534

RESUMO

BACKGROUND: Some studies have suggested that daytime napping may increase the risk of type 2 diabetes. However, limited data have revealed the association between nap duration and other metabolic diseases. Data from the baseline survey of Lanxi Cohort Study, a population-based study of natural residents in Zhejiang Province, China, were used to investigate the relationship between nap duration and metabolic abnormalities. METHODS: A total of 3236 participants underwent a physical examination, laboratory tests, and face to face interview. They were categorized into four groups according to nap duration. Logistic regression models were used to examine the odds ratios (ORs) of napping duration with four metabolism-related diseases. Stratified analysis was further used to explore the interaction effects of gender and age on results. RESULTS: Compared to the no daytime napping group, people who napped during the daytime for more than 1 h were independently associated with a greater prevalence of diabetes (OR 1.56). Those who napped during the daytime within a half hour showed a lower prevalence of fatty liver, dyslipidemia, and central obesity. To be more specific, those who habitually napped during the daytime for more than 1 h exhibited an increasing prevalence of diabetes among female older than 50 years old. Those who habitually napped during the daytime within a half hour exhibited a decreasing prevalence of fatty liver and dyslipidemia among male <50 years old, and that of central obesity among female <50 years old. CONCLUSIONS: Short daytime napping duration is associate with reduced rate of metabolism-related diseases and may protects people from negative health conditions, whereas long daytime napping duration is associate with higher prevalence of diabetes, which then can be harmful for health.

17.
Nat Prod Bioprospect ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33083968

RESUMO

A phytochemical investigation of the EtOH extract of the flowers of Lagerstroemia indica L. led to the isolation and characterization of a new pyrrole alkaloid, named lagerindicine (1), along with four known compounds (2-5). Their structures were elucidated by the detailed spectroscopic analysis and comparison with literature data, whereas the structure, in particularly, the absolute configuration (AC) of 1, was firmly determined by total synthesis. All the isolates were evaluated for their cytotoxic effects against human colon cancer cell (HCT-116), and compound 3 exhibited weak cytotoxicity with IC50 value of 28.4 µM.

18.
Nutrition ; 79-80: 110963, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33011471

RESUMO

OBJECTIVES: Objective nutritional indexes have been shown to predict prognosis in some clinical settings. We aimed to explore the predictive values of these indexes in patients undergoing peritoneal dialysis (PD). METHODS: This is a single-center retrospective observational study in patients undergoing PD. The controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) were calculated at baseline. The primary outcome was all-cause mortality. The secondary outcome was new-onset cardiocerebrovascular disease (CVD) events. Univariate and multivariate Cox regressions were performed to investigate the association between confounding factors and outcomes. The optimal cutoff values were determined using a receiver operating characteristic curve analysis. We used the Kaplan-Meier curve to compare the outcomes according to the cutoff values. The area under the curve (AUC) was used to test discriminative power of these objective nutritional indexes. RESULTS: We analyzed 252 patients undergoing PD at our institution. On the Cox hazard analysis, the CONUT score, PNI, and GNRI were independently associated with all-cause mortality (CONUT: hazard ratio [HR]: 1.496; 95% confidence interval (CI), 1.241-1.804; P < 0.001; PNI: HR: 0.878; 95% CI, 0.815-0.946; P = 0.001; and GNRI: HR: 0.930; 95% CI, 0.885-0.978; P = 0.040) and CVD incidence (CONUT: HR: 1.385; 95% CI, 1.177-1.630; P < 0.001; PNI: HR: 0.885; 95% CI, 0.826-0.949; P = 0.001; and GNRI: HR: 0.936; 95% CI, 0.893-0.981; P = 0.005). In the Kaplan-Meier analysis, patients with a higher CONUT score and lower PNI had significantly higher incidence of all-cause mortality (17.7% versus 3.0%; P = 0.022; 24.3% versus 5.7%, P = 0.003, respectively). As for new-onset CVD, patients with a higher CONUT score, lower PNI, and lower GNRI had higher occurrence rates (19.4% versus 3.0%; P = 0.006; 28.7% versus 7.9%; P = 0.001; 24.4% versus 9.9%; P = 0.035, respectively). The largest AUC to predict all-cause mortality was the CONUT score (AUC: 0.733; 95% CI, 0.674-0.787). For CVD prevalence, the largest AUC was the PNI (AUC: 0.718; 95% CI, 0.658-0.773). CONCLUSIONS: Objective nutritional indexes were independently associated with all-cause mortality and CVD events in patients undergoing PD. Moreover, assessments of the CONUT score and PNI may provide more useful predictive values than GNRI.

19.
Life Sci ; 263: 118594, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33075375

RESUMO

Estrogen receptor alpha (ERα) is a vital molecular target in ER-positive breast cancer. Genistin (GS) is one of isoflavones that can exert diverse pharmacological effects including that of anti-proliferation, anti-tumor angiogenesis, induce cell cycle arrest and apoptosis. Here, we examined the efficacy of GS as an anti-cancer agent against breast cancer cells. We observed that GS exhibited more cytotoxic activity against MCF-7 cells than MDA-MB-231cells. We found that GS caused negative regulation of ERα. It also effectively down-modulated ER nuclear translocation as well DNA binding activity in breast cancer cells. Moreover, GS effectively induced apoptosis and suppressed levels of oncogenic markers in MCF-7 cells. Interestingly, in ERα knocked-down MCF-7 cells, cell viability was found to be increased and the levels of cleaved PARP was abolished. We found completely contrasting results in ERα overexpressed MDA-MB-231 cells, where cell viability was decreased and expression level of apoptotic markers was enhanced. Our results demonstrate that GS can suppress ERα signaling and can be useful for prevention and therapy of ER-positive breast cancer.

20.
J Parkinsons Dis ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33104041

RESUMO

BACKGROUND: Although the dopaminergic system is interconnected with the hypothalamic-pituitary-thyroid axis, few studies have explained the causal relationship between thyroid disease and Parkinson's disease (PD). OBJECTIVE: The goal of this study was to investigate the association between thyroid diseases and PD in Korean residents. METHODS: The Korean National Health Insurance Service-National Sample Cohort, which includes individuals aged ≥40 years, was assessed from 2002 to 2015. A total of 5,586 PD patients were matched by age, sex, income, and the region of residence with 22,344 control participants at a ratio of 1:4. In the PD and control groups, previous histories of levothyroxine treatment, goiter, hypothyroidism, thyroiditis, and hyperthyroidism were investigated. RESULTS: The rates of levothyroxine treatment for more than 3 months, hypothyroidism, and hyperthyroidism were higher in the PD group than the control group (3.2%, 3.8%, and 2.8% vs. 2.5%, 2.9%, and 1.9%, respectively, p <  0.05). The adjusted odds ratios (ORs) in model 2, which was adjusted for all potential confounders, for hypothyroidism and hyperthyroidism in the PD group were 1.25 (95% confidence interval (CI) 1.01-1.55, p = 0.044) and 1.37 (95% CI 1.13-1.67, p = 0.002), respectively. In subgroup analyses, the association between hypothyroidism and PD was maintained in men older than 70 years and the association between hyperthyroidism and PD was maintained in women younger than 70 years. CONCLUSION: Both hyperthyroidism and hypothyroidism were associated with higher risk of PD, particularly for women younger than 70 years and men older than 70 years, respectively.

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