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1.
Am J Hematol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797941

RESUMO

Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had multiple lesions within a single system (SS-m), and 182 patients had multisystem disease (MS). The most common organ involved in MS patients was the bone (69.8%), followed by the pituitary (61.5%) and lung (61.0%). BRAFV600E , BRAF deletion, and MAP2K1 mutation were detected in 38.8%, 25.4%, and 19.4% patients, respectively. BRAF deletion was found more common in patients with MS LCH compared to single-system LCH (38.5% vs 7.1%, p = .004), also in patients with liver involvement (69.2% vs 14.3%, p < .001). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 94.4% and 54.7%, respectively, in SS-m and MS LCH. Multivariate Cox regression showed that involvement of the liver or spleen at baseline predicted poor EFS and receiving cytarabine-based therapy as a first-line treatment and age older than 30 years at diagnosis predicted favorable EFS. The involvement of risk organs and age older than 50 years predicted poor OS, and receiving cytarabine-based therapy predicted favorable OS. Therefore, BRAF deletion was correlated with MS LCH, particularly those with liver involvement. Liver or spleen involvement at baseline indicates a poor prognosis, and a cytarabine-based regimen could be considered as first-line treatment for adult LCH patients.

2.
Int J Biochem Cell Biol ; 142: 106123, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34826616

RESUMO

Hepatocellular carcinoma (HCC) has become the sixth highly diagnosed cancer and the fourth main reason of cancer deaths worldwide. HuaChanSu, an extract from dried toad skin, exhibits good anticancer effects and has been widely used in the treatment of liver cancer. The reprogramming of glucose metabolism is one remarkable feature of hepatocellular carcinoma, and the effects of HuaChanSu on the abnormal glucose metabolism of cancer cells have not been elucidated. In our study, we investigate the effects of HuaChanSu on glucose metabolism of hepatocellular carcinoma cells and tumor growth in vivo. The results show that HuaChanSu inhibits the tumor growth of hepatoma H22-bearing mice and prolongs the survival time of tumor-bearing mice, additionally, HuaChanSu has no obvious adverse effects in these mice. In vitro, HuaChanSu restrains the proliferation, induces apoptosis and cell cycle arrest of human hepatoma cells. HuaChanSu also promotes ROS production and causes mitochondrial damage. Furthermore, HuaChanSu inhibits glucose uptake and lactate release in human hepatoma cells. Mechanistically, we find that HuaChanSu downregulates Hexokinase-2 (HK2) expression, and using RNA interference, we confirm that HuaChanSu suppresses the growth of HepG2 cells by interfering with glucose metabolism through downregulation of Hexokinase-2. However, knockdown of Hexokinase-2 has no obvious effect on the proliferation of SK-HEP-1 cells, although glucose uptake and lactate release are reduced in siHK2-transfected SK-HEP-1 cells, subsequently, we illustrate that two human hepatoma cell lines exhibit glucose metabolism heterogeneity, which causes the different cell proliferation responses to the inhibition of Hexokinase-2. Taken together, our study indicates that HuaChanSu could inhibit tumor growth and interfere with glucose metabolism via suppression of Hexokinase-2, and these findings provide a new insight into the anti-hepatoma mechanisms of HuaChanSu and lay a theoretical foundation for the further clinical application of HuaChanSu.

3.
Nutrients ; 13(11)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34836115

RESUMO

Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure (ARF). Geumgwe-sinkihwan (GSH) was recorded in a traditional Chines medical book named "Bangyakhappyeon" in 1884. GSH has been used for treatment for patients with diabetes and glomerulonephritis caused by deficiency of kidney yang and insufficiency of kidney gi. Here we investigate the effects of GSH in mice model of ischemic acute kidney injury. The mice groups are as follows; sham group: C57BL6 male mice, I/R group: C57BL6 male mice with I/R surgery, GSH low group: I/R + 100 mg/kg/day GSH, and GSH high group: I/R + 300 mg/kg/day GSH. Ischemia was induced by clamping both renal arteries and reperfusion. Mice were orally given GSH (100 and 300 mg/kg/day) during 3 days after surgery. Treatment with GSH significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen levels. Treatment with GSH reduced neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), specific renal injury markers. GSH also reduced the periodic acid-Schiff and picro sirius red staining intensity in kidney of I/R group. Western blot and real-time RT-qPCR analysis demonstrated that GSH decreased protein and mRNA expression levels of the inflammatory cytokines in I/R-induced ARF mice. Moreover, GSH inhibited protein and mRNA expression of inflammasome-related protein including NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryoprin), ASC (Apoptosis-associated speck-like protein containing a CARD), and caspase-1. These findings provided evidence that GSH ameliorates renal injury including metabolic dysfunction and inflammation via the inhibition of NLRP3-dependent inflammasome in I/R-induced ARF mice.

4.
CNS Neurosci Ther ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837479

RESUMO

AIMS: To identify the metabolic pattern and prognostic predictors in anti-gamma-aminobutyric-acid B (GABAB) receptor encephalitis using 18 F-fluorodeoxy-glucose positron emission tomography (18 F-FDG-PET). METHODS: Twenty-one patients diagnosed anti-GABAB receptor encephalitis who underwent 18 F-FDG-PET at first hospitalization were retrospectively reviewed. 18 F-FDG-PET images were analyzed in comparison with controls. Further group comparisons of 18 F-FDG-PET data were carried out between prognostic subgroups. RESULTS: 18 F-FDG-PET was abnormal in 81% patients with anti-GABAB receptor encephalitis and was more sensitive than MRI (81% vs. 42.9%, p = 0.025). Alter limbic lobe glucose metabolism (mostly hypermetabolism) was observed in 14 patients (66.7%), of whom 10 (10/14, 71.4%) demonstrated hypermetabolism in the medial temporal lobe (MTL). Group analysis also confirmed MTL hypermetabolism in association with relative frontal and parietal hypometabolism was a general metabolic pattern. After a median follow-up of 33 months, the group comparisons revealed that patients with poor outcome demonstrated increased metabolism in the MTL compared to those with good outcome. CONCLUSION: 18 F-FDG-PET may be more sensitive than MRI in the early diagnosis of anti-GABAB receptor encephalitis. MTL hypermetabolism was associated with relative frontal or parietal hypometabolism and may serve as a prognostic biomarker in anti-GABAB receptor encephalitis.

5.
Nutrients ; 13(11)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34836432

RESUMO

Diabetic cardiovascular dysfunction is a representative complication of diabetes. Inflammation associated with the onset and exacerbation of type 2 diabetes mellitus (T2DM) is an essential factor in the pathogenesis of diabetic cardiovascular complications. Diabetes-induced myocardial dysfunction is characterized by myocardial fibrosis, which includes structural heart changes, myocardial cell death, and extracellular matrix protein accumulation. The mice groups in this study were divided as follows: Cont, control (db/m mice); T2DM, type 2 diabetes mellitus mice (db/db mice); Vil.G, db/db + vildagliptin 50 mg/kg/day, positive control, dipeptidyl peptidase-4 (DPP-4) inhibitor; Bla.C, db/db + blackcurrant 200 mg/kg/day. In this study, Bla.C treatment significantly improved the homeostatic model evaluation of glucose, insulin, and insulin resistance (HOMA-IR) indices and diabetic blood markers such as HbA1c in T2DM mice. In addition, Bla.C improved cardiac function markers and cardiac thickening through echocardiography. Bla.C reduced the expression of fibrosis biomarkers, elastin and type IV collagen, in the left ventricle of a diabetic cardiopathy model. Bla.C also inhibited TD2M-induced elevated levels of inflammatory cytokines in cardiac tissue (IL-6, IL-1ß, TNF-α, and TGF-ß). Thus, Bla.C significantly improved cardiac inflammation and cardiovascular fibrosis and dysfunction by blocking inflammatory cytokine activation signals. This showed that Bla.C treatment could ameliorate diabetes-induced cardiovascular complications in T2DM mice. These results provide evidence that Bla.C extract has a significant effect on the prevention of cardiovascular fibrosis, inflammation, and consequent diabetes-induced cardiovascular complications, directly or indirectly, by improving blood glucose profile.

6.
Food Chem X ; 12: 100132, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34761199

RESUMO

Plant-derived protein hydrolysates (PH) offer many promising benefits and applications. In this paper, PH was prepared from soy-based processing waste via enzymatic-digestion method and supplemented into hydroponic grow medium solution. The hydroponic-planted lettuces were then harvested and assessed for their selected phytochemical contents, biochemical parameters, antioxidative enzymes and mineral contents. Additionally, the lettuce's physical properties were assessed. Based on our results, increases in three phytochemical contents were observed, in a PH concentration-dependent manner (0-0.01 mg/mL). Similar trends were also observed for chlorophyll and carotenoid contents. Harvested lettuce length and fresh weight peaked at 0.01 mg/mL PH treatment group, but not in a PH concentration-dependent manner. Whereas, for other physical properties (lettuce leaf surface area, root length, root weight), no significant difference was detected. Through this study, we are hoping to contribute toward the potential PH application as agricultural nutrient supplement for hydroponic plants, with accompanied improvements in harvest yields and nutritional contents.

7.
Oxid Med Cell Longev ; 2021: 7301373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777693

RESUMO

Accumulating evidence suggests that developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved GTP-binding protein, plays an important role in regulating cell growth, inflammation, and mitochondria dynamics. However, the effect of DRG2 in aging remains unclear. In this study, we found that endogenous DRG2 protein expression is upregulated in oxidative stress-induced premature senescence models and tissues of aged mice. Ectopic expression of DRG2 significantly promoted senescence-associated ß-galactosidase (SA-ß-gal) activity and inhibited cell growth, concomitant with increase in levels of acetyl (ac)-p53 (Lys382), ac-nuclear factor-kB (NF-κB) p65 (Lys310), p21 Waf1/Cip1 , and p16 Ink4a and a decrease in cyclin D1. In this process, reactive oxygen species (ROS) and phosphorylation of H2A histone family member X (H2A.X), forming γ-H2A.X, were enhanced. Mechanistically, ectopic expression of DRG2 downregulated Sirtuin-1 (SIRT1), resulting in augmented acetylation of p53 and NF-κB p65. Additionally, DRG2 knockdown significantly abolished oxidative stress-induced premature senescence. Our results provide a possible molecular mechanism for investigation of cellular senescence and aging regulated by DRG2.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34667620

RESUMO

Background: Tuberculous pleural effusion (TPE) is paucibacillary, making its diagnosis difficult based on laboratory investigations alone. We present a case of a patient with a TPE who was initially misdiagnosed to have azathioprine-induced lung injury. The diagnosis of TPE was arrived at with the help of clinical assessment, laboratory and radiological investigations. Case presentation: A 25-year-old chronic smoker with sympathetic ophthalmia on long-term immunosuppression, latent tuberculosis infection and a significant family history of tuberculosis presented with a three-week history of productive cough, low-grade fever, night sweats and weight loss. Examination of the lungs showed reduced breath sounds at the right lower zone. Chest x-ray showed minimal right pleural effusion with a small area of right upper lobe consolidation. The pleural fluid was exudative with predominant mononuclear leukocytes. Direct smears of sputum and pleural fluid; polymerase chain reaction of pleural fluid; and sputum, pleural fluid and blood cultures were negative for M. tuberculosis (MTB) and other organisms. As he did not respond to a course of broad-spectrum antibiotics, he was then treated as a case of azathioprine-induced lung injury. However, his condition did not improve despite the cessation of azathioprine. A contrast-enhanced computed tomography of the thorax showed right upper lobe consolidation with tree-in-bud changes, bilateral lung atelectasis, subpleural nodule, mild right pleural effusion and mediastinal lymphadenopathy. Bronchoalveolar lavage was negative for malignant cells and microorganisms including, MTB. However, no pleural biopsy was done. He was empirically treated with anti-tubercular therapy for 9 months duration and showed complete recovery. Conclusion: A high index of suspicion for TPE is required in individuals with immunosuppression living in regions endemic to tuberculosis. Targeted investigations and sound clinical judgement allow early diagnosis and prompt treatment initiation to prevent morbidity and mortality.

11.
12.
Front Immunol ; 12: 672846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616389

RESUMO

Purpose: Brain 18F-fluorodeoxyglucose positron emission tomography (FDG PET) is a sensitive technique for assisting in the diagnosis of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis. However, the common pattern of this disorder assessed by FDG PET remains unknown. The present study aimed to explore the glucose metabolic patterns of this disorder based on PET voxel analysis. Methods: This retrospective study enrolled 25 patients with anti-LGI1 encephalitis, who were admitted in Beijing Tiantan Hospital between September 2014 and July 2019. The glucose metabolic pattern was compared between the included patients and 44 age- and gender-matched healthy controls using Statistical Parametric Mapping. Then, the correlation between the metabolic pattern and scaled activities of daily living (ADLs) of the patients was assessed. Results: The median time from symptom onset to PET scans was 9 w (range:2-53w). The groupwise analysis revealed that patients with anti-LGI1 encephalitis had left hippocampal hypermetabolism and hypometabolism in almost all neocortical regions. The individual-level results showed most patients presented a decreased metabolism in neocortical regions, as well as an increase in metabolism in the hippocampus and basal ganglia. Furthermore, the metabolic gradient between hippocampus and neocortical regions was positively associated with the ADLs (frontal lobe, r=0.529, P=0.008; parietal lobe, r=0.474, P=0.019; occipital lobe, r=0.413, P=0.045; temporal lobe, r=0.490, P=0.015), respectively. In addition, the patients with facio-brachial dystonic seizures (FBDS) presented bilateral putamen hypermetabolism, when compared to patients without FBDS and healthy controls. Conclusion: Subcortical hypermetabolism associated with cortical hypometabolism presented with a common metabolic pattern in patients with anti-LGI1 encephalitis in the present study. The resolution of the metabolic gradient of the hippocampal hypermetabolism and neocortical hypometabolism may bring about improved clinical neurologic disability.


Assuntos
Encéfalo/diagnóstico por imagem , Encefalite/diagnóstico por imagem , Doença de Hashimoto/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Atividades Cotidianas , Adolescente , Adulto , Idoso , Autoanticorpos/imunologia , Encéfalo/imunologia , Encéfalo/metabolismo , Encefalite/imunologia , Encefalite/metabolismo , Feminino , Fluordesoxiglucose F18 , Doença de Hashimoto/imunologia , Doença de Hashimoto/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Adulto Jovem
13.
Trop Dis Travel Med Vaccines ; 7(1): 27, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34649627

RESUMO

BACKGROUND: Tuberculous pleural effusion (TPE) is paucibacillary, making its diagnosis difficult based on laboratory investigations alone. We present a case of a patient with a TPE who was initially misdiagnosed to have azathioprine-induced lung injury. The diagnosis of TPE was arrived at with the help of clinical assessment, laboratory and radiological investigations. CASE PRESENTATION: A 25-year-old chronic smoker with sympathetic ophthalmia on long-term immunosuppression, latent tuberculosis infection and a significant family history of tuberculosis presented with a three-week history of productive cough, low-grade fever, night sweats and weight loss. Examination of the lungs showed reduced breath sounds at the right lower zone. Chest x-ray showed minimal right pleural effusion with a small area of right upper lobe consolidation. The pleural fluid was exudative with predominant mononuclear leukocytes. Direct smears of sputum and pleural fluid; polymerase chain reaction of pleural fluid; and sputum, pleural fluid and blood cultures were negative for M. tuberculosis (MTB) and other organisms. As he did not respond to a course of broad-spectrum antibiotics, he was then treated as a case of azathioprine-induced lung injury. However, his condition did not improve despite the cessation of azathioprine. A contrast-enhanced computed tomography of the thorax showed right upper lobe consolidation with tree-in-bud changes, bilateral lung atelectasis, subpleural nodule, mild right pleural effusion and mediastinal lymphadenopathy. Bronchoalveolar lavage was negative for malignant cells and microorganisms including, MTB. However, no pleural biopsy was done. He was empirically treated with anti-tubercular therapy for 9 months duration and showed complete recovery. CONCLUSION: A high index of suspicion for TPE is required in individuals with immunosuppression living in regions endemic to tuberculosis. Targeted investigations and sound clinical judgement allow early diagnosis and prompt treatment initiation to prevent morbidity and mortality.

14.
Toxicol Appl Pharmacol ; 431: 115739, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34619160

RESUMO

Hepatocellular carcinoma (HCC) is one of the deadliest cancers with high mortality and poor prognosis, and the investigation on new approaches and effective drugs for HCC therapy is of great significance. In our study, we demonstrate that treatment with cinobufagin, a natural compound isolated from traditional chinese medicine Chansu, reduces proliferation and the colony formation capacity of the human hepatoma cells in vitro, in addition, cinobufagin induces mitotic arrest in human hepatoma cells. The results of a network pharmacology-based analysis show that EGFR, MAPK1, PTK2, CDK2, MAPK3, ESR1, CDK1, PRKCA, AR, and CSNK2A1 are the key targets involved in the anti-tumor activities of cinobufagin, additionally, several signaling pathways such as proteoglycans in cancer, pathways in cancer, HIF-1 signaling pathway, VEGF signaling pathway, ErbB signaling pathway, and PI3K-AKT signaling pathway are identified as the potential pathways involved in the inhibitory effects of cinobufagin against HCC. Furthermore, at the molecular level, we find that cinobufagin decreases EGFR expression and CDK2 activity in human hepatoma cells. Inhibition of EGFR or CDK2 expression could not only suppress the growth of tumor cells but also enhance the inhibitory effects of cinobufagin on the proliferative potential of human hepatoma cells. We also demonstrate that EGFR positively regulates CDK2 expression. Furthermore, EGFR inhibitor gefitinib or CDK2 inhibitor CVT-313 synergistically enhances anticancer effects of cinobufagin in human hepatoma cells. Taken together, these findings indicate that cinobufagin may exert antitumor effects by suppressing EGFR-CDK2 signaling, and our study suggests that cinobufagin may be a novel, promising anticancer agent for the treatment of HCC.

15.
Chemosphere ; 288(Pt 2): 132541, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34648782

RESUMO

The spatiotemporal presence of overall disinfection by-products (DBPs) in two full-scale drinking water supply systems (DWSSs) were investigated using quantification of total organic halogen (TOX). The relationships of TOX with water quality parameters (especially the most regulated DBPs, trihalomethanes (THMs)) were also evaluated. The TOX levels ranged between 2.6 and 70.3 µg Cl/L and between 46.6 and 205.9 µg Cl/L in raw water and distribution water, respectively. The TOX concentration in water increased by an average of nine times after water treatment and varied slightly during distribution, suggesting that TOX in drinking water was mainly formed during chlorination disinfection rather than distribution. No clear seasonality in TOX level was observed. Positive correlations were found between raw water dissolved organic carbon (DOC) with an increase in TOX in treated water and between DOC level with TOX content in distributed water, emphasizing a key role of organics in TOX formation. Chloroform (TCM) was the dominant THM, followed by bromodichloromethane (BDCM) in the drinking water, and the levels of the other two measured THMs (dibromochloromethane and bromoform) were negligible. THM2 (sum of TCM and BDCM) made up average of 18% of the TOX, and was weakly correlated with TOX content (rs = 0.321; P < 0.05), implying that THM is not a suitable surrogate measure for TOX in drinking water. This study provides basic data on the occurrence and variation of TOX within conventional DWSSs and highlights the importance of using TOX measurements to obtain more accurate information about DBP occurrence, for exposure assessment and regulatory determination.

16.
Front Genet ; 12: 728960, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539756

RESUMO

Despite that several therapeutic agents have exhibited promising prevention or treatment on Coronavirus disease-2019 (COVID-19), there is no specific drug discovered for this pandemic. Targeting virus-host interactome provides a more effective strategy for antivirus drug discovery compared with targeting virus proteins. In this study, we developed a network-based infrastructure to prioritize promising drug candidates from natural products and approved drugs via targeting host proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We firstly measured the network distances between drug targets and COVID-19 disease module utilizing the network proximity approach, and identified 229 approved drugs as well as 432 natural products had significant associations with SARS-CoV-2. After searching for previous literature evidence, we found that 60.7% (139/229) of approved drugs and 39.6% (171/432) of natural products were confirmed with antivirus or anti-inflammation. We further integrated our network-based predictions and validated anti-SARS-CoV-2 activities of some compounds. Four drug candidates, including hesperidin, isorhapontigenin, salmeterol, and gallocatechin-7-gallate, have exhibited activity on SARS-COV-2 virus-infected Vero cells. Finally, we showcased the mechanism of actions of isorhapontigenin and salmeterol via network analysis. Overall, this study offers forceful approaches for in silico identification of drug candidates on COVID-19, which may facilitate the discovery of antiviral drug therapies.

17.
Am J Prev Med ; 61(4): 606-617, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34544560

RESUMO

INTRODUCTION: Suboptimal and differential participant engagement in randomized trials-including retention at primary outcome assessments and attendance at intervention sessions-undermines rigor, internal validity, and trial conclusions. METHODS: First, this study describes Methods-Motivational Interviewing approach and strategies for implementation. This approach engages potential participants before randomization through interactive, prerequisite orientation sessions that illustrate the scientific rationale behind trial methods in accessible language and use motivational interviewing to diffuse ambivalence about participation. Then, this study examines the potential improvements in retention (proportion of participants assessed at follow-up visits) and attendance (e.g., mean percentage of intervention sessions attended, percentage of participants who attended 0 sessions) in 3 randomized weight-management trials that quickly added prerequisite orientations to their protocols following early signs of suboptimal or differential participant engagement (Supporting Health by Integrating Nutrition and Exercise [2009-2013, n=194]; Get Social [2016-2020, n=217]; GestationaL Weight Gain and Optimal Wellness [2014-2018, n=389]). Using a pre-post analytical design, adjusted estimates from regression models controlling for condition and assessment timepoint (analyses from 2020) are reported. RESULTS: After adding prerequisite orientations, all 3 trials attained higher participant engagement. Retention at assessments was 11.4% and 17.3% higher (Get Social and Supporting Health by Integrating Nutrition and Exercise, respectively). Mean percentage of attendance at intervention sessions was 8.8% higher (GestationaL Weight Gain and Optimal Wellness), and 10.1% fewer participants attended 0 intervention sessions (Get Social). Descriptively, all the remaining retention and attendance outcomes were consistently higher but were nonsignificant. Across the trials, adding prerequisite orientations did not impact the proportion of eligible participants enrolled or the baseline demographics. CONCLUSIONS: The Methods-Motivational Interviewing approach shows promise for increasing the rigor of randomized trials and is readily adaptable to in-person, webinar, and conference call formats. TRIAL REGISTRATION: All 3 trials are registered at www.clinicaltrials.gov (Supporting Health by Integrating Nutrition and Exercise: NCT00960414; Get Social: NCT02646618; and GestationaL Weight Gain and Optimal Wellness: NCT02130232).


Assuntos
Entrevista Motivacional , Exercício Físico , Humanos , Avaliação de Resultados em Cuidados de Saúde
18.
J Am Chem Soc ; 143(40): 16813-16823, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34582185

RESUMO

Despite the degradability and biocompatibility of poly(α-hydroxy acids), their utility remains limited because their thermal and mechanical properties are inferior to those of commodity polyolefins, which can be attributed to the lack of side-chain functionality on the polyester backbone. Attempts to synthesize high-molecular-weight functionalized poly(α-hydroxy acids) from O-carboxyanhydrides have been hampered by scalability problems arising from the need for an external energy source such as light or electricity. Herein, we report an operationally simple, scalable method for the synthesis of stereoregular, high-molecular-weight (>200 kDa) functionalized poly(α-hydroxy acids) by means of controlled ring-opening polymerization of O-carboxyanhydrides mediated by a highly redox reactive manganese complex and a zinc-alkoxide. Mechanistic studies indicated that the ring-opening process likely proceeded via the Mn-mediated decarboxylation with alkoxy radical formation. Gradient copolymers produced directly by this method from mixtures of two O-carboxyanhydrides exhibited better ductility and toughness than their corresponding homopolymers and block copolymers, therefore highlighting the potential feasibility of functionalized poly(α-hydroxy acids) as ductile and resilient polymeric materials.

19.
Nat Commun ; 12(1): 5138, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446702

RESUMO

Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient-response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, we develop an implantable miniaturized device using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks. The combination of local immune checkpoint blockade antibodies delivery via this device with photodynamic therapy elicits a sustained anti-tumor immunity in multiple tumor models. Our device uses tumor impedance measurement for timely presentation of treatment outcomes, and allows modifications to the delivered drugs and their concentrations, rendering this device potentially useful for on-demand delivery of potent immunotherapeutics without exacerbating toxicities.


Assuntos
Anticorpos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Inibidores de Checkpoint Imunológico/administração & dosagem , Imunoterapia/métodos , Neoplasias/química , Neoplasias/tratamento farmacológico , Animais , Terapia Combinada , Sistemas de Liberação de Medicamentos/instrumentação , Impedância Elétrica , Feminino , Humanos , Imunoterapia/instrumentação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fibras Ópticas , Fotoquimioterapia , Próteses e Implantes
20.
Vector Borne Zoonotic Dis ; 21(10): 777-784, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34375121

RESUMO

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, which has caused unprecedented damage to human health and life. The present study aimed to carry out and discover asymptomatic infected individuals in Shenzhen, China. The data will provide the control measures to stop COVID-19 prevalence. Methods: The study was a retrospective review of medical records from 462 confirmed patients with COVID-19 and 45 asymptomatic infected individuals in Shenzhen from January 19 to April 30, 2020; this is a retrospective, observational multicenter study. Results: A total of 462 confirmed cases were diagnosed in Shenzhen from January 19 to April 30, 2020. The cohort included 423 domestic cases (91.56%, 95% confidence interval [CI]: 88.67-93.76) and 39 (8.44%, 95% CI: 6.24-11.33) imported cases from other countries. Moreover, a total of 45 asymptomatic infections were found, encompassing 31 (68.89%, 95% CI: 54.34-80.47) local infections and 14 (31.11%, 95% CI: 19.53-45.66) individuals imported from other countries. The proportion of asymptomatic infected persons in Shenzhen is continuously increasing (Z = 13.19, p < 0.0001). The total number of local asymptomatic infections was more than that in other provinces (χ2 = 118.83, p < 0.0001). The proportion of asymptomatic infected individuals among cases imported from other countries was higher than the domestic cases (χ2 = 22.51, p < 0.0001, odds ratio = 4.90, 95% CI: 2.40-9.98). Conclusions: The proportion of asymptomatic infection is increasing. Hence, development and application of the diagnosis method with high sensitivity and specificity play a critical role in reducing COVID-19 global epidemics.


Assuntos
Infecções Assintomáticas/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , China/epidemiologia , Estudos de Coortes , Humanos , Prevalência , Estudos Retrospectivos , Fatores de Tempo
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