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1.
Environ Pollut ; 267: 115542, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254676

RESUMO

Pyrrolizidine alkaloids (PAs) are common phytotoxins. We performed the first comprehensive investigation on PA contamination in Chinese honeys. LC-MS analysis revealed that 58% of 255 honey samples purchased from 17 regions across Mainland China and Taiwan contained PAs with total content ranging over 0.2-281.1 µg/kg. Monocrotaline (from Crotalaria spp), a PA never found in honey in other regions, together with echimidine (Echium plantagineum) and lycopsamine (from Senecio spp.), were three predominant PAs in PA-contaminated Chinese honeys. Further, PAs present in honeys were found to have geographically distinct pattern, indicating possible control of such contamination in future honey production. Moreover, we proposed a new risk estimation approach, which considered both content and toxic potency of individual PAs in honeys, and found that 12% of the PA-contaminated Chinese honeys tested might pose potential health risk. This study revealed a high prevalence and potential health risk of PA contamination in Chinese honeys.

2.
Redox Biol ; 38: 101795, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33232911

RESUMO

The formation of α-synuclein aggregates is a major pathological hallmark of Parkinson's disease. Copper promotes α-synuclein aggregation and toxicity in vitro. The level of copper and copper transporter 1, which is the only known high-affinity copper importer in the brain, decreases in the substantia nigra of Parkinson's disease patients. However, the relationship between copper, copper transporter 1 and α-synuclein pathology remains elusive. Here, we aim to decipher the molecular mechanisms of copper and copper transporter 1 underlying Parkinson's disease pathology. We employed yeast and mammalian cell models expressing human α-synuclein, where exogenous copper accelerated intracellular α-synuclein inclusions and silencing copper transporter 1 reduced α-synuclein aggregates in vitro, suggesting that copper transporter 1 might inhibit α-synuclein pathology. To study our hypothesis in vivo, we generated a new transgenic mouse model with copper transporter 1 conditional knocked-out specifically in dopaminergic neuron. Meanwhile, we unilaterally injected adeno-associated viral human-α-synuclein into the substantia nigra of these mice. Importantly, we found that copper transporter 1 deficiency significantly reduced S129-phosphorylation of α-synuclein, prevented dopaminergic neuronal loss, and alleviated motor dysfunction caused by α-synuclein overexpression in vivo. Overall, our data indicated that inhibition of copper transporter 1 alleviated α-synuclein mediated pathologies and provided a novel therapeutic strategy for Parkinson's disease and other synucleinopathies.

3.
BMC Complement Med Ther ; 20(1): 334, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167951

RESUMO

BACKGROUND: Recombinant insulin Lisargine is a new type of insulin. In this study, we aimed to compare its pharmacodynamic (PD) and pharmacokinetic (PK) with Lantus. METHODS: The PD test was performed by exploring the effect of single administration on blood glucose of normal rats and STZ-induced diabetic rats, and the effect of multiple administrations on blood glucose of STZ-induced diabetic rats. Further PD tests include receptor affinity test, receptor autophosphorylation test and adipocyte glucose uptake test. Four IU and 8 IU per dog Lisargine was used for PK test, insulin was measured and area under curve (AUC) was calculated. RESULTS: With single injection, Lisargine 1.5 IU/kg had significant hypoglycemic effects at 1 and 2 h, similar to that of Lantus. Lisargine 5 IU/kg and 10 IU/kg lowered the blood glucose of STZ-induced diabetic rats at 1, 2, 4 & 6 h significantly. With multiple injections, Lantus lowered blood glucose at 2, 4 & 6 h, Lisargine 2.5 IU/kg, 5 IU/kg, and 10 IU/kg lowered blood glucose at 2 & 4 h significantly, compared with vehicle. There was no difference for receptor affinity test, receptor autophosphorylation test and adipocyte glucose uptake test between Lisargine and Lantus. The PK of Lisargine and Lantus of healthy Beagle dogs was very similar. CONCLUSIONS: This animal study demonstrated that PK and PD of Lisargine and Lantus were similar, suggesting the bioequivalence of these products.

4.
Int J Pharm ; 591: 120002, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33141084

RESUMO

Human activities in the areas of high altitude have increased significantly recently. Brain is highly sensitive to changing of oxygen pressure due to high altitude, and this physiological response may lead to serious brain injury, such as learning and memory disabilities. Puerarin is a phytoestrogen with many pharmacological activities, such as treatment of neurological disorders. However, most of current drugs can not easily enter brain through the blood-brain barrier (BBB). The nose-to-brain route can bypass BBB for brain-targeting. Here, thermosensitive in situ hydrogels (TISGs) of puerarin were prepared with poloxamers 407, poloxamers 188 and propylene glycol to improve bioavailability and brain targeting. In vitro drug release in simulated nasal fluids, rheological properties and cilia toxicity of puerarin TISGs were explored. The pharmacodynamics and pharmacokinetics of puerarin by intranasal (i.n.) and oral (p.o.) administrations were also evaluated. The viscosity of puerarin TISGs tended to increase obviously with increased temperature. The puerarin release profile and transmucosal process of puerarin TISGs could be described with the first-order kinetics equation, depending on drug diffusion. The cilia toxicity of puerarin TISGs was not obvious. Rat models of hypobarism/hypoxia-induced brain injury were established with a hypobaric simulation chamber. Morris water maze and open filed tests indicated that puerarin TISGs improved the spatial memory and spontaneous exploratory behavior of the rats suffering from hypoxia-induced brain injury. Furthermore, puerarin TISGs decreased the level of oxidative stress cytokines (malondialdehyde (MDA) and glutathione (GSH)) in the peripheral circulation, alleviated the cerebral histological lesions, and relieved the expression of hypoxia-inducible factor-1α (HIF-1α). Intranasal puerarin TISGs were absorbed quickly with a shorter Tmax (10.0 ± 5.7 min) compared to that of oral puerarin (36 ± 13.4 min). In addition, the relative bioavailability of i.n. puerarin TISGs was high to 300% compared to oral administration of puerarin. The area under the curve (AUC) of brain after i.n. administration of puerarin TISGs was 954.5 ± 335.1 h.ng/mL, while no puerarin was detected in the brain after oral administration. Therefore, i.n. puerarin TISGs led to excellent brain targeting effect. Puerarin TISGs are an effective neuroprotector formulation for prevention of brain injury induced by acute high-altitude hypoxia.

6.
Arch Toxicol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33210216

RESUMO

Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins widely present in hundreds of plant species and also known to contaminate many foodstuffs, such as grain, honey, and tea. The formation of pyrrole-protein adducts via metabolic activation of PAs has been suggested as a primary trigger initiating hepatotoxicity. The present study for the first time tested the suitability of pyrrole-hemoglobin adducts as a novel and specific biomarker of PA exposure in humans. The level and elimination kinetics of pyrrole-hemoglobin adducts were systematically investigated in the blood samples of 43 PA-induced liver injury (PA-ILI) patients. The results revealed significantly higher concentrations (84.50 ± 78.38 nM) and longer persistence (~ 4 months) of pyrrole-hemoglobin adducts than that (concentration: 9.53 ± 10.72 nM; persistence: ~ 2 months) of pyrrole-plasma protein adducts, our previously developed PA exposure biomarker. Our findings confirmed that pyrrole-hemoglobin adducts with higher level and longer persistence should serve as a more applicable PA exposure biomarker for future clinical diagnosis of PA-ILI in drug/herb-induced liver injury patients.

7.
ACS Appl Mater Interfaces ; 12(47): 52402-52414, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33169982

RESUMO

Tumor-associated macrophages (TAMs), a major player in the tumor microenvironment, were recently recognized as a potential therapeutic target. To date, very few anticancer drugs or drug-delivery systems were designed to target the TAMs. Inspired by the "eat me" signal, phosphatidylserine (PS), mediated phagocytic clearance of apoptotic bodies, in this study, the matrix metalloproteinase 2 (MMP2)-sensitive PS-modified nanoparticles were developed. In the design, the PS is externalized to the nanoparticles' surface only when the nanoparticles reach the MMP2-overexpressing tumor site, allowing for the TAM-specific phagocytosis. The nanoparticles' excellent macrophage/TAM selectivity was observed in various biological models, including various cell lines, coculture cells, coculture cell spheroids, zebrafish, and tumor-bearing mice. The nanoparticles' TAM specificity remarkably enhanced the TAM depletion capability of the loaded model drug, dasatinib, resulting in the improved anticancer activity. The MMP2-sensitive apoptotic body-mimicking nanoparticles might be a promising delivery tool for TAM-centered cancer diagnoses and treatments.

8.
J Clin Epidemiol ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33227445

RESUMO

OBJECTIVES: To assess the methods used, and potential for bias, in post-trial studies of cardiovascular disease (CVD) where legacy effects may be estimated. STUDY DESIGN AND SETTING: We undertook a methods review of post-trial studies after randomized controlled trials of interventions to prevent CVD. For each included article, we extracted information on important aspects of the design and analysis of the study, and on the reporting of legacy effects. RESULTS: Of 2622 retrieved articles, 46 were included in the review: 13 on blood glucose control, 13 on blood pressure control and 20 on blood lipids control. The median duration for the RCT and post-trial follow-up studies were 5.0 and 5.8 years respectively. At least 80% of initial RCT participants were enrolled in the post-trial study in 32 of the reports. Most reports used both linkage to routine administrative data sources and active data collection for the post-trial study. Of the 46 included articles, the authors assessed and reported post-trial covariate balance in 29, and made statistical adjustments in the analysis for potential confounding in 25. Post-trial results were reported separately to overall results (from time of randomization) in 21 articles. Legacy effects were claimed in 19 reports, of which 16 could be justified on the basis of the post-trial results. CONCLUSION: Post-trial studies may provide valuable information for investigating legacy effects, but better reporting of results is needed to realize their full potential. Robust methods of data collection and analysis may address the risk of selection and confounding biases in post-trial studies.

9.
Opt Lett ; 45(22): 6338-6341, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186984

RESUMO

In this Letter, we have demonstrated wavelength beam combining (WBC) through hybrid integration of photonic integrated circuits (PICs) to significantly reduce the size, weight, and operation power of the laser combining system. The hybrid integration WBC includes III/V semiconductor optical amplifiers (SOAs), which provide gain, and the silicon nitride PICs, which perform as the external cavity. We first show that the arrayed waveguide grating (AWG) -based hybrid laser defines the lasing wavelength through the AWG passband. We then demonstrate that the AWG successfully forms multiple channel lasers by combining SOAs in the hybrid platform.

10.
J Phys Chem Lett ; : 10348-10353, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232157

RESUMO

Efficient and stable deep-blue emission from perovskite light-emitting diodes (LEDs) is required for their application in lighting and displays. However, this is difficult to achieve due to the phase segregation issue of mixed halide perovskites and the challenge of synthesizing high-quality single-halide deep-blue perovskite nanocrystals through a traditional method. Here, we show that an antisolvent treatment can facilitate the in situ formation of perovskite nanocrystals using a facile spin-coating method. We find that the dropping time of the antisolvent can significantly affect the constitution of nanocrystal perovskite films. With a delay in the start time of the antisolvent treatment, small single-halide perovskite nanocrystals can be achieved, exhibiting efficient deep-blue emission. The LED device shows a stable electroluminescence (EL) peak at 465 nm, with a peak external quantum efficiency and a peak current efficiency of 2.4% and 2.5 cd A-1, respectively. This work provides a facile approach to changing the size of perovskite nanocrystals, thus effectively tuning their EL emission spectra.

11.
J Med Internet Res ; 22(11): e21672, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33152684

RESUMO

BACKGROUND: COVID-19 has posed a global threat due to substantial morbidity and mortality, and health education strategies need to be adjusted accordingly to prevent a possible epidemic rebound. OBJECTIVE: This study aimed to evaluate the perceptions of COVID-19 among individuals coming to, returning to, or living in Jiangsu Province, China, and determine the impact of the pandemic on the perceptions of the public. METHODS: In this study, an online questionnaire was distributed to participants between February 15 and April 21, 2020. The questionnaire comprised items on personal information (eg, sex, age, educational level, and occupation); protection knowledge, skills, and behaviors related to COVID-19; access to COVID-19-related information; and current information needs. Factors influencing the knowledge score, skill score, behavior score, and total score for COVID-19 were evaluated using univariate and multivariate analyses. The time-varying reproduction number (Rt) and its 95% credible interval were calculated and compared with the daily participation number and protection scores. RESULTS: In total, 52,066 participants were included in the study; their average knowledge score, skill score, behavior score, and total score were 25.58 (SD 4.22), 24.05 (SD 4.02), 31.51 (SD 2.84), and 90.02 (SD 8.87), respectively, and 65.91% (34,315/52,066) had a total protection score above 90 points. For the knowledge and skill sections, correct rates of answers to questions on medical observation days, infectiousness of asymptomatic individuals, cough or sneeze treatment, and precautions were higher than 95%, while those of questions on initial symptoms (32,286/52,066, 62.01%), transmission routes (37,134/52,066, 71.32%), selection of disinfection products (37,390/52,066, 71.81%), and measures of home quarantine (40,037/52,066, 76.90%) were relatively low. For the actual behavior section, 97.93% (50,989/52,066) of participants could wear masks properly when going out. However, 19.76% (10,290/52,066) could not disinfect their homes each week, and 18.42% (9589/52,066) could not distinguish differences in initial symptoms between the common cold and COVID-19. The regression analyses showed that the knowledge score, skill score, behavior score, and total score were influenced by sex, age, educational level, occupation, and place of residence at different degrees (P<.001). The government, television shows, and news outlets were the main sources of protection knowledge, and the information released by the government and authoritative medical experts was considered the most reliable. The current information needs included the latest epidemic developments, disease treatment progress, and daily protection knowledge. The Rt in the Jiangsu Province and mainland China dropped below 1, while the global Rt remained at around 1. The maximal information coefficients ranged from 0.76 to 1.00, which indicated that the public's perceptions were significantly associated with the epidemic. CONCLUSIONS: A high proportion of the participants had sufficient COVID-19 protection knowledge and skills and were able to avoid risky behaviors. Thus, it is necessary to apply different health education measures tailored to work and study resumption for specific populations to improve their self-protection and, ultimately, to prevent a possible rebound of COVID-19.

12.
Tissue Eng Regen Med ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33165769

RESUMO

BACKGROUND: Due to adipose-derived stem cells (ASCs) being easy to obtain, their rapid proliferation rate, and their multidirectional differentiation capabilities, they have been widely used in the field of regenerative medicine. With the progress of decellularized adipose tissue (DAT) and adipose tissue engineering research, the role of DAT in promoting angiogenesis has gradually been emphasized. METHODS: We examined the biological characteristics and biosafety of DAT and evaluated the stem cell maintenance ability and promotion of growth factor secretion through conducting in vitro and in vivo studies. RESULTS: The tested ASCs showed high rat:es of proliferation and adhered well to DAT. The expression levels of essential genes for cell stem maintenance, including OCT4, SOX2, and Nanog were low at 2-24 h and much higher at 48 and 96 h. The Adipogenic expression level of markers for ASCs proliferation including PPARγ, C/EPBα, and LPL increased from 2 to 96 h. Co-culture of ASCs and DAT increased the secretion of local growth factors, such as VEGF, PDGF-bb, bFGF, HGF, EGF, and FDGF-bb, and secretion gradually increased from 0 to 48 h. A model of full-thickness skin defects on the back of nude mice was established, and the co-culture of ASCs and DAT showed the best in vivo treatment effect. CONCLUSION: The application of DAT promotes wound healing, and DAT combined with ASCs may be a promising material in adipose tissue engineering and regenerative medicine.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33146824

RESUMO

The conservation and management of rain and water in a city environment are a crucial aspect of sustainability. Sponge cities are a solution for the remediation of excessive water consumption, high pollution, and rainstorm waterlogging in urban areas. Perennial ryegrass (Lolium perenne L.) is a common species and promising bioremediation plant for the construction of sponge cities. It could be useful to purify high nitrogen and phosphorus content in wastewater runoff, but its response to high total nitrogen (TN) and total phosphorus (TP) levels has not been studied. The present study aimed to evaluate the effects of high TN + TP level on seed germination, plant growth, antioxidant response, and assimilation rate of N and P in perennial ryegrass. Compared with the control, treatments with 20 mg/L N + 4 mg/L P (20N4P) significantly decreased germination potential at day 3, but the germination rate at day 10 was similar between all treatments and the control, suggesting that a high TN + TP concentration might delay germination, but not prevent it. Treatment with 20N4P also induced significant withering and decreased shoot length, root length, and dry shoot weight of ryegrass seedlings, compared with the control. Treatments with 80N16P significantly decreased levels of chlorophyll a (Chl-a) and chlorophyll b (Chl-b), demonstrating inhibition of photosynthesis. Compared with the control, treatment with 40N8P increased the carotenoid (Car), malondialdehyde (MDA), and glutathione (GSH) content, which might alleviate oxidative stress induced by high TN + TP concentration. Moreover, high levels of TN + TP (160N32P and 320N64P) significantly reduced the removal capacity of N and P by plants. Overall, the present results provide a theoretical foundation for the development of ryegrass for bioremediation of wastewater during construction of sponge cities.

14.
Sci Total Environ ; : 143210, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33158538

RESUMO

Due to energy dissipation, turbulent energy reaching bed sediment greatly differs in lakes with different depths, which potentially affects sediment denitrification and thereby nitrogen loss. In this study, we explored the impacts of turbulent energy reaching sediment on sediment nitrification rate using turbulence simulation experiments, and analyzed its role in determining sediment nitrogen loss in global lakes by investigating the relationship between denitrification rate with lake depth. Results demonstrated that sediment denitrification rate is affected by water depth in lakes with a depth of <~10 m, in which the rate was negatively correlated with lake depth, and maintained stably at low levels of <2.4 mg N m-2 day-1 in lakes with a depth of >~10 m. In shallow lakes, stronger turbulence reaching on sediment yielded higher nitrogen loss rate. Compare with the control, cumulated nitrogen loss from sediment increased by 10% at the turbulent velocity of 4.33 cm s-1 upon sediment. It is possibly because turbulence promoted faster transport of oxygen to surface sediment and enhanced the mineralization of buried organic matters to feed nitrification, which subsequently accelerated denitrification and thereby nitrogen loss. This study can add to our understanding of the role of lake morphology in nitrogen biogeochemical cycles.

15.
Acta Pharmacol Sin ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154553

RESUMO

Herbs and dietary supplement-induced liver injury (HILI) is the leading cause of drug-induced liver injury in China. Among different hepatotoxic herbs, the pyrrolizidine alkaloid (PA)-producing herb Gynura japonica contributes significantly to HILI by inducing hepatic sinusoidal obstruction syndrome (HSOS), a liver disorder characterized by hepatomegaly, hyperbilirubinemia, and ascites. In China, G. japonica has been used as one of the plant species for Tu-San-Qi and is often misused with non-PA-producing Tu-San-Qi (Sedum aizoon) or even San-Qi (Panax notoginseng) for self-medication. It has been reported that over 50% of HSOS cases are caused by the intake of PA-producing G. japonica. In this review, we provide comprehensive information to distinguish these Tu-San-Qi-related herbal plant species in terms of plant/medicinal part morphologies, medicinal indications, and chemical profiles. Approximately 2156 Tu-San-Qi-associated HSOS cases reported in China from 1980 to 2019 are systematically reviewed in terms of their clinical manifestation, diagnostic workups, therapeutic interventions, and outcomes. In addition, based on the application of our developed mechanism-based biomarker of PA exposure, our clinical findings on the definitive diagnosis of 58 PA-producing Tu-San-Qi-induced HSOS patients are also elaborated. Therefore, this review article provides the first comprehensive report on 2214 PA-producing Tu-San-Qi (G. japonica)-induced HSOS cases in China, and the information presented will improve public awareness of the significant incidence of PA-producing Tu-San-Qi (G. japonica)-induced HSOS and facilitate future prevention and better clinical management of this severe HILI.

16.
Int J Mol Sci ; 21(19)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003317

RESUMO

Gibberellins (GAs), a class of phytohormones, act as an essential natural regulator of plant growth and development. Many studies have shown that GA is related to rhizobial infection and nodule organogenesis in legume species. However, thus far, GA metabolism and signaling components are largely unknown in the model legume Medicago truncatula. In this study, a genome-wide analysis of GA metabolism and signaling genes was carried out. In total 29 components, including 8 MtGA20ox genes, 2 MtGA3ox genes, 13 MtGA2ox genes, 3 MtGID1 genes, and 3 MtDELLA genes were identified in M. truncatula genome. Expression profiles revealed that most members of MtGAox, MtGID1, and MtDELLA showed tissue-specific expression patterns. In addition, the GA biosynthesis and deactivation genes displayed a feedback regulation on GA treatment, respectively. Yeast two-hybrid assays showed that all the three MtGID1s interacted with MtDELLA1 and MtDELLA2, suggesting that the MtGID1s are functional GA receptors. More importantly, M. truncatula exhibited increased plant height and biomass by ectopic expression of the MtGA20ox1, suggesting that enhanced GA response has the potential for forage improvement.

17.
Medicine (Baltimore) ; 99(42): e22719, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080728

RESUMO

BACKGROUND: To compare perioperative outcomes and surgeon physical and mental stress when performing lobectomy through uniportal and multiportal video-assisted thoracoscopic surgery (VATS) on patients with non-small-cell lung cancer (NSCLC). METHODS: Patients aged 41 to 73 years with resectable NSCLC were randomly assigned via a computer-generated randomisation sequence to receive either uniportal VATS (UVATS) or multiportal VATS (MVATS) lobectomy and lymphadenectomy between December 2015 and October 2016. Overall, we randomly assigned 35 patients to the UVATS and 34 to the MVATS group. Patients and the investigators undertaking interventions, assessing short-term outcomes, performing ergonomic evaluations, and analyzing data were not masked to group assignment. RESULTS: Patient demographics of the 2 groups were comparable. The ergonomic evaluation considered eye blink rate and the NASA Task Load Index (NASA-TLX), better results were observed in UVATS than in MVATS. The operative time, number of lymph nodes harvested, chest tube duration, length of hospital stay, and lung function were not significantly different between the groups. Compared with MVATS lobectomy, UVATS lobectomy was associated with less intraoperative blood loss and less volume of total drainage in the 24 hours. No conversion, no reoperation, and no in-hospital mortality occurred in either group. CONCLUSIONS: UVATS lobectomy is a safe and programmable technique with some better perioperative outcomes and ergonomic results than MVATS. Further studies based on large numbers of patients and with long-term follow-up are required to confirm its benefits towards patients. TRIAL REGISTRATION: ClinicalTrials.gov ID:NCT02462356. Registered May 27, 2015.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/instrumentação , Cirurgia Torácica Vídeoassistida/instrumentação , Adulto , Idoso , Ergonomia , Feminino , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
18.
Hepatol Int ; 14(5): 723-732, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33026573

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. METHODS: A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury. RESULTS: Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)]. CONCLUSION: Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.


Assuntos
Infecções por Coronavirus , Citocinas/sangue , Insuficiência Hepática , Contagem de Leucócitos/métodos , Testes de Função Hepática , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Estado Terminal/epidemiologia , Estado Terminal/terapia , Feminino , Insuficiência Hepática/sangue , Insuficiência Hepática/epidemiologia , Insuficiência Hepática/virologia , Humanos , Incidência , Testes de Função Hepática/métodos , Testes de Função Hepática/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
19.
Front Immunol ; 11: 569530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101289

RESUMO

Matrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens, suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10. In an effort to find the upstream pathway(s) of the mechanism underlying these effects, we have tested certain upregulated immunomodulatory molecules. Among them, we found increased levels of IL-27 and IFN-ß, one of the first-line MS therapies. Indeed, while low levels of IFN-ß production in sera and type I interferon receptor (IFNAR1) expression in spinal cord of saline-treated control EAE mice were detected, they were significantly increased after MAT treatment. Increased numbers of CD11b+IFN-ß+ microglia/infiltrating macrophages were observed in the CNS of MAT-treated mice. The key role of IFN-ß induction in the suppressive effect of MAT on EAE was further verified by administration of anti-IFN-ß neutralizing antibody, which largely reversed the therapeutic effect of MAT. Further, we found that, while MAT treatment induced production of IL-27 and IL-10 by CNS microglia/macrophages, this effect was significantly reduced by IFN-ß neutralizing antibody. Finally, the role of IFN-ß in MAT-induced IL-27 and IL-10 production was further confirmed in human monocytes in vitro. Together, our study demonstrates that MAT exerts its therapeutic effect in EAE through an IFN-ß/IL-27/IL-10 pathway, and is likely a novel, safe, low-cost, and effective therapy as an alternative to exogenous IFN-ß for MS.

20.
Mol Pharm ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33108189

RESUMO

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and therefore is an attractive target for prostate cancer diagnosis and radionuclide therapy. Recently, published results from clinical studies using a new PSMA-targeting PET imaging agent, [68Ga]Ga-PSMA-093 ([68Ga]Ga-HBED-CC-O-carboxymethyl-Tyr-CO-NH-Glu), support the development of this agent for the diagnosis of prostate cancer. In this study, the HBED-CC chelating group in PSMA-093 was replaced by stereoselective (R)- or (S)-DOTAGA. This chelating group serves not only for chelating 68Ga but is also amendable for complexing other radioactive metals for radionuclide therapy. The corresponding optically pure (R)- and (S)-[68Ga/177Lu]-DOTAGA derivatives, (R)-[68Ga/177Lu]-13 and (S)-[68Ga/177Lu]-13, were successfully prepared. Comparison of radiolabeling, binding affinity, cell uptake, and biodistribution between the two isomers was performed. Radiolabeling of (R)-[177Lu]Lu-13 and (S)-[177Lu]Lu-13 at 50 °C suggested that rates of complex formation were time-dependent and the formation of (S)-[177Lu]Lu-13 was distinctly faster. The rates of complex formation for the corresponding 68Ga agents were comparable between structural isomers. The natGa and natLu equivalents showed high binding PSMA affinity (IC50 = 24-111 nM), comparable to that of the parent agent, [natGa]Ga-PSMA-093 (IC50 = 34.0 nM). Results of cell uptake and biodistribution studies in PSMA-expressing PC3-PIP tumor-bearing mice appeared to show no difference between the labeled (R)- and (S)-isomers. This is the first time that a pair of [68Ga/177Lu]-(R)- and (S)-DOTAGA isomers of PSMA agents were evaluated. Results of biological studies between the isomers showed no noticeable difference; however, the distinctions on the rate of Lu complex formation should be considered in the development of new 177Lu-DOTAGA-based radionuclide therapy agents in the future.

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