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1.
BMC Musculoskelet Disord ; 22(1): 27, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407312

RESUMO

BACKGROUND: To investigate the imaging features of hemangiomas in long tabular bones for better diagnosis. METHODS: Twenty-four patients with long bone hemangiomas confirmed by pathology were enrolled. Nineteen patients had plain radiography, fourteen patients had computed tomography (CT) and eleven had magnetic resonance imaging (MRI). The hemangioma was divided into medullary [13], periosteal [6] and intracortical type [5]. RESULTS: Among 19 patients with plain radiography, eleven patients were medullary, three periosteal, and five intracortical. In the medullary type, the lesion was primarily osteolytic, including five cases with irregular and unclear rims and one lesion having osteosclerotic and unclear rims. In three patients with the periosteal type, the lesion had clear rims with involvement of the cortical bone in the form of bone defect, including two cases with local thickened bone periosteum and one case having expansile periosteum. Five intracortical hemangiomas had intracortical osteolytic lesions with clear margins. Among 14 patients with CT imaging, 8 cases were medullary, three periosteal, and three intracortical. Among 8 medullary hemangiomas, one had ground glass opacity, and seven had osteolytic, expansile lesions like soft tissue density with no calcification. In three periosteal cases, the lesion was osteolytic with thickened periosteum and narrowed medullary cavity. In three intracortical hemangiomas, the lesion was of even soft tissue density with no calcification. Among 11 patients with MRI imaging, seven were medullary, two periosteal, and two intracortical. Among 7 medullary lesions, six were of hypointense signal on T1WI and hyperintensesignal on T2 WI. In two periosteal cases, the periosteum was thickened, with one case being of equal signal, and the other having no signal. Two intracortical hemangiomas were both of slightly low signal on T1WI but hyperintense signal on T2WI. CONCLUSIONS: The long bone hemangiomas had characteristic cystic honeycomb-like presentations in plain radiograph. CT and MRI imagings are helpful for diagnosis of hemangiomas in long bone.

2.
Biochimie ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33485933

RESUMO

Lysine 2-hydroxyisobutyrylation (Khib) is a novel protein posttranslational modification conserved in eukaryotes and prokaryotes. However, the biological significance of Khib remains largely unknown. Here, through screening the proteome-wide Khib modification sites in bacteria using a bioinformatic method, we identified a potential Khib site (K201hib) targeted by de-2-hyroxyisobutyrylase CobB at the substrate-binding site of FabI, an enoyl-acyl carry protein reductase (EnvM or FabI) in fatty acid biosynthesis pathway. First, we confirmed that the previously identified de-2-hyroxyisobutyrylase CobB can remove Khib of FabI in an in vitro experiment. To investigate the biological effects of the Khib on FabI's activity, amino acid substitutes were introduced to the modification sites of the protein of E. coli origin to mimic modified/unmodified status. We found that the mutant mimicking K201hib reduced FabI activity with decreased Michaelis constant (Km) and catalytic turnover number (kcat), while the mutant mimicking the unmodified form and the recombinant wild-type protein treated with CobB exhibited increased activity. However, the dissociation constant (KD) between FabI and NADH was not affected by the mutation mimicking the modification, suggesting that K201hib didn't alter the binding between NADH and FabI. We also found that K201hib tended to increase the resistance of E. coli to triclosan (TCL), a widely-used antibiotics targeting FabI. Taken together, this study identified the regulatory role of Khib on FabI activity and pointed to a novel mechanism related to antibiotic resistance.

3.
AAPS PharmSciTech ; 22(2): 56, 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33486601

RESUMO

Compared with single micelle, the new PTX-HS15/T80 mixed micelle system (PTX-HS15/T80 MMs) had achieved better results in solubilization, stability, and sensitization before. Therefore, we intend to further verify the potential advantages of the mixed micelle delivery system through in vitro cytotoxicity test and animal test to understand the anticancer effect and in vivo pharmaceutical behavior of the system. In vitro cytotoxicity test showed that the new PTX-HS15/T80 MMs had a stronger ability to inhibit the proliferation of cancer cells. The results of in vivo pharmacokinetics showed that the micelle had shorter half-life, higher clearance rate, and lower blood concentration and had good blood clearance characteristics. The results of in vivo tissue distribution showed that, compared with the single micelle Taxol®, the new PTX-HS15/T80 MMs had good distribution characteristics in the lung (AUC (lung 0-4 H) increased about 26%) and low concentration in the heart (AUC (Heart 0-4 H) decreased about 10%). Paclitaxel was mainly metabolized through the liver and kidney. The above results suggested that the new PTX-HS15/T80 MMs may have a certain therapeutic potential against lung cancer and reduce the toxic and side effects. In general, the mixed micelle delivery system was not only simple and cheap to prepare but also had certain advantages in vitro and in vivo, indicating that the combination of surfactants provides a good choice for solving the problem of insoluble drug delivery.

4.
Chem Commun (Camb) ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33470263

RESUMO

An organocatalytic vinylogous Michael addition triggered triple-cascade reaction has been developed. 2-Hydroxycinnamaldehydes worked under iminium activation with either acyclic or cyclic ketone-derived α,α-dicyanoalkenes, yielding the benzofused oxabicyclo[3.3.1]nonanes bearing one quaternary stereocenter with excellent stereoselectivities.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33471146

RESUMO

BACKGROUND: Interest and activity are part of the positive mood domain. Evidence suggests the symptom domain of interest-activity at baseline as a clinical predictor for treatment response to traditional antidepressants. However, whether this domain is related to the response to a single low-dose ketamine infusion remains unclear. METHODS: Seventy-one patients with treatment-resistant depression were randomized to 3 treatment groups: a single 0.5 or 0.2 mg/kg ketamine or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale before infusions and at postinfusion period (at 40 min and up to 2 weeks). Low (mild) versus medium versus high (severe) interest-activity symptom domain groups were classified on the basis of the cutoff point of ± 0.4 standard deviation. The effect of baseline interest-activity symptoms on outcomes was tested using generalized estimating equation models. RESULTS: The interest-activity symptom domain as a continuous variable (ß = 8.413, p = .016) was related to the trajectory of depressive symptoms. Stratified by levels of the interest-activity symptom domain, in the low interest-activity, 0.2 mg/kg ketamine infusion (ß = 0.013) demonstrated the greatest antidepressant effect (p < .01) compared with 0.5 mg/kg ketamine (ß = 0.739) and placebo infusions; however, in the high interest-activity, 0.5 mg/kg ketamine infusion (ß = 0.001) demonstrated the best antidepressant effect (p < .01) compared with 0.2 mg/kg ketamine (ß = 1.372) and placebo infusions. DISCUSSION: The symptom domain of interest-activity was an independent predictor for the treatment response to a single low-dose ketamine infusion.

6.
Sci Rep ; 11(1): 1589, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452403

RESUMO

This study was performed to propose a method, the Feature Ambiguity Mitigate Operator (FAMO) model, to mitigate feature ambiguity in bone fracture detection on radiographs of various body parts. A total of 9040 radiographic studies were extracted. These images were classified into several body part types including 1651 hand, 1302 wrist, 406 elbow, 696 shoulder, 1580 pelvic, 948 knee, 1180 ankle, and 1277 foot images. Instance segmentation was annotated by radiologists. The ResNext-101+FPN was employed as the baseline network structure and the FAMO model for processing. The proposed FAMO model and other ablative models were tested on a test set of 20% total radiographs in a balanced body part distribution. To the per-fracture extent, an AP (average precision) analysis was performed. For per-image and per-case, the sensitivity, specificity, and AUC (area under the receiver operating characteristic curve) were analyzed. At the per-fracture level, the controlled experiment set the baseline AP to 76.8% (95% CI: 76.1%, 77.4%), and the major experiment using FAMO as a preprocessor improved the AP to 77.4% (95% CI: 76.6%, 78.2%). At the per-image level, the sensitivity, specificity, and AUC were 61.9% (95% CI: 58.7%, 65.0%), 91.5% (95% CI: 89.5%, 93.3%), and 74.9% (95% CI: 74.1%, 75.7%), respectively, for the controlled experiment, and 64.5% (95% CI: 61.3%, 67.5%), 92.9% (95% CI: 91.0%, 94.5%), and 77.5% (95% CI: 76.5%, 78.5%), respectively, for the experiment with FAMO. At the per-case level, the sensitivity, specificity, and AUC were 74.9% (95% CI: 70.6%, 78.7%), 91.7%% (95% CI: 88.8%, 93.9%), and 85.7% (95% CI: 84.8%, 86.5%), respectively, for the controlled experiment, and 77.5% (95% CI: 73.3%, 81.1%), 93.4% (95% CI: 90.7%, 95.4%), and 86.5% (95% CI: 85.6%, 87.4%), respectively, for the experiment with FAMO. In conclusion, in bone fracture detection, FAMO is an effective preprocessor to enhance model performance by mitigating feature ambiguity in the network.

7.
J Hum Hypertens ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462392

RESUMO

Numerous cohort studies have reported the association of long-term exposure to particulate matter <10 µm in diameter (PM10) and hypertension in American and European countries. However, these results have been inconsistent and subject to various confounding factors. The study aimed to explore the effect of long-term exposure to high-level concentrations of PM10 on incident hypertension in a large-scale cohort from northern China. A retrospective cohort study of 39,054 participants aged between 23 and 98 years old from four cities in northern China was followed from 1998 to 2009. Excluding those with hypertension, 37,386 non-hypertensive participants (overall population) were followed for self-reported hypertension. The individuals' exposure to PM10 was the mean concentration during the follow-up period, according to the data of local environmental monitoring centers. Hazard ratios (HRs) were calculated by Cox proportional hazards models. The adjusted potential confounding factors included sociodemographic information, lifestyle, and diet. There were 2619 (7.0%) incident cases of hypertension among the overall population. In multivariable models, the HR (95% CI) of incident hypertension was 1.537 (1.515, 1.560) for each 10 µg/m3 increase in PM10. Stratified analyses showed individuals (age <65) were prone to developing hypertension. Moreover, the effects of PM10 increased and produced an HR (95% CI) of 1.555 (1.527, 1.584) for the healthy population in the sensitivity analysis. We found that the association between long-term exposure to PM10 air pollution and incident hypertension was significantly positive.

8.
Epidemiol Infect ; 149: e4, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33397519

RESUMO

Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.


Assuntos
/complicações , Hipertensão/complicações , Adulto , Idoso , China , Comorbidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
9.
Nat Plants ; 7(1): 73-86, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33452487

RESUMO

Symbiosis between soybean (Glycine max) and rhizobia is essential for efficient nitrogen fixation. Rhizobial effectors secreted through the type-III secretion system are key for mediating the interactions between plants and rhizobia, but the molecular mechanism remains largely unknown. Here, our genome-wide association study for nodule number identified G. max Nodule Number Locus 1 (GmNNL1), which encodes a new R protein. GmNNL1 directly interacts with the nodulation outer protein P (NopP) effector from Bradyrhizobium USDA110 to trigger immunity and inhibit nodulation through root hair infection. The insertion of a 179 bp short interspersed nuclear element (SINE)-like transposon into GmNNL1 leads to the loss of function of GmNNL1, enabling bradyrhizobia to successfully nodulate soybeans through the root hair infection route and enhancing nitrogen fixation. Our findings provide important insights into the coevolution of soybean-bradyrhizobia compatibility and offer a way to design new legume-rhizobia interactions for efficient symbiotic nitrogen fixation.

10.
Food Funct ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410435

RESUMO

Duck egg white (DEW) is considered as an abandoned protein resource. For a higher-value utilization, preparation of immunomodulatory peptides from the extracted ovalbumin in DEW was explored. Among the hydrolysates catalyzed by five proteases, papain hydrolysate (PH) shows the highest degree of hydrolysis and the strongest immunomodulatory activity. PH could significantly enhance the phagocytic capacity and promote the NO, TNF-α, and IL-6 secretion of RAW 264.7 cells, involving toll-like receptor 2 and 4. After purification, nine identified peptides were synthesized to confirm the immunomodulatory effect, and five of them exhibit a strong activity. The peptide, TQIDKVVHFDKLPGF, presents the highest immunomodulatory activity. Moreover, the results of molecular docking indicate that nine peptides interacted with toll-like receptor 2 and 4 and all show good affinity. Furthermore, three peptides with high affinity and strong immune activity were selected for interaction site map analysis. Three peptides could form hydrogen bonds with the receptor and bind stably, which contributes to the immunomodulatory activity of the peptide. Results suggest that DEW can be a promising source of immunomodulatory peptides.

11.
Cellulose (Lond) ; : 1-14, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33424143

RESUMO

Hydrogels are attractive due to their various applications in the fields of biomedical materials, cosmetics, and biosensors. To enhance UV protection and prevent skin penetration behaviors, inspired by the mussel adhesive proteins, the functional polydopamine (PDA) is employed herein to fabricate polydopamine/carboxymethyl cellulose/polyacrylic acid (PDA/CMC/PAA) adhesive hydrogels. To disperse PDA nanoparticles well in the PAA matrix, dopamine was self-polymerized in CMC solution to form PDA/CMC complex. Acrylic acid was polymerized in PDA/CMC complex solution and cross-linked to construct UV-resistant PDA/CMC/PAA hydrogel. The morphology, rheological behavior, mechanical properties and adhesion strength of PDA/CMC/PAA hydrogels were studied by scanning electron microscopy, rotational rheometer, universal test machine. Owing to the hydrogen bonding interaction between the PDA/CMC complex and PAA, the PDA/CMC/PAA hydrogels showed high resilience and compressive strength to withstand large deformation. The hydrogels exhibited strong adhesion to various substrate surfaces, such as stainless steel, aluminum, glass and porcine skin. The biocompatibility and UV-shielding properties were investigated through culture of cells and UV irradiation test. The adhesiveness of PDA promoted cell adhesion and provided the PDA/CMC/PAA hydrogels good biocompatibility with 96% of relative cell viability. The hydrogels possessed excellent UV-shielding ability to prevent collagen fibers from being destroyed during UV irradiation, which has promising potential in the practical applications for UV filtration membrane and skin care products.

12.
Virol Sin ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400089

RESUMO

Ticks are well known as vectors of many viruses which usually do great harm to human and animal health. Yunnan Province, widely covered by flourishing vegetation and mainly relying on farming husbandry, is abundant with Rhipicephalus microplus ticks. Therefore, it is of great significance to characterize the viral profile present in R. microplus parasitizing on cattle in Yunnan Province. In this study, a total of 7387 R. microplus ticks were collected from cattle and buffalo in the northwest and southeast areas of Yunnan Province from 2015 to 2017. We investigated the virome of R. microplus using next-generation sequencing (NGS) and the prevalence of important identified viruses among tick groups by RT-PCR. It revealed the presence of diverse virus concerning chu-, rhabdo-, phlebo-, flavi- and parvo- viruses in Yunnan. These viruses consist of single-stranded, circular and segmented sense RNAs, showing a greatly diversity in genomic organization. Furthermore, continuous epidemiological survey among ticks reveals broad prevalence of three viruses (Yunnan mivirus 1, Wuhan tick vrius 1 and YN tick-associated phlebovirus 1) and two possible prevalent viruses including a flavivirus-like segmented virus (Jingmen tick virus) and a bovine hokovirus 2 in Yunnan. Serological investigation among cattle indicates that these identified viruses may be infectious to cattle and can elicit corresponding antibody. Our findings on R. microplus-associated viral community will contribute to the prevention of viral disease and tracking the viral evolution. Further analysis is needed to better elucidate the pathogenicity and natural circulation of these viruses.

13.
Biol Open ; 10(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419776

RESUMO

Acoustic signals play a key role in animal communication. Animals usually use alarm signals to warn mates or offspring of the presence of threats or to intimidate or distract predators. Birds commonly use acoustic signals as a means of communication. Alarm calls in passerines at different breeding stages can reflect their nest defense intensity. However, little is known about the characteristics, plasticity, and impact factors of alarm calls during the reproductive period in raptors. Here, from March to July in 2019, the alarm calls of eight pairs of common kestrels (Falco tinnunculus) during the breeding period were recorded using a portable recorder with a strongly directed microphone in the Zuojia Nature Reserve, Jilin province, China. The differences in acoustic parameters of parental alarm calls in different breeding stages were analyzed. The results showed that the alarm calls of common kestrels were composed of multi-harmonic arched frequency modulation with the maximum energy distribution in the second harmonic. The duration and rate of the alarm calls increased significantly as the breeding season progressed, showing that parents spent increasing amounts of time on nest defense. Additionally, the acoustic parameters of alarm calls in common kestrels were significantly different depending on offspring numbers, suggesting that offspring numbers influenced parental nest defense. These results showed that differences in alarm calls during different breeding stages may reflect a trade-off between defense costs and reproductive benefits.

14.
Pediatr Neurol ; 115: 10-20, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33310532

RESUMO

BACKGROUND: Central nervous system infections cause substantial morbidity and mortality in pediatric patients. However, in approximately half of the clinical cases, the etiology is unidentified. As an unbiased molecular diagnostic technology, next-generation sequencing is gradually being applied to investigate central nervous system infections. This review summarizes and critiques the literature on this new technology for etiologic identification of unexplained central nervous system infections in pediatric patients and discusses the future prospects for development of this technology in pediatrics. METHODS: A comprehensive PubMed search was conducted of articles published from January 1, 2008, to June 26, 2020 in order to retrieve all available studies on this topic. Other relevant articles were identified from recent reviews and the bibliographies of the retrieved full-text articles. RESULTS: Among the 441 studies retrieved, 26 pediatric studies, comprising 15 case reports and 11 case series, used next-generation sequencing as a diagnostic tool. In these 26 studies, next-generation sequencing was performed on cerebrospinal fluid samples from 529 pediatric patients, and potential causal pathogens were identified in 22.1% of the cases. CONCLUSION: There is increasing evidence that next-generation sequencing can play a role in identifying the causes of unexplained encephalitis, meningoencephalitis, and meningitis in pediatric patients, although the diagnostic value of next-generation sequencing is difficult to quantify. There is an increasing need for close collaboration between laboratory scientists and clinicians. We believe that further clinical studies should be performed to evaluate the performance of next-generation sequencing for individual targets and in high-risk populations.

15.
Mol Med Rep ; 23(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33236158

RESUMO

Resveratrol confers neuroprotective effects in cerebral ischemia; however, the involvement of mitophagy in the neuroprotective function of resveratrol remains unclear. The aim of the present study was to investigate whether resveratrol exerts neuroprotective effects on primary cortical neurons subjected to oxygen/glucose deprivation/reoxygenation (OGD/R) via modulating mitophagy. The data demonstrated that resveratrol at 1­10 µM during reoxygenation improved cell viability and suppressed apoptosis following OGD/R in a concentration­dependent manner. Moreover, resveratrol alleviated OGD/R­induced loss of mitochondrial membrane potential and excessive oxidative stress. Confocal imaging of LC3 and TOM20 antibody­labeled mitochondria, as well as western blot analysis, demonstrated that mitophagy was further enhanced following resveratrol treatment. In addition, resveratrol was revealed to stimulate the phosphatase and tensin homolog­induced kinase 1/Parkin pathway. Mitophagy inhibition then inhibited the protective effects of resveratrol. These results indicated that resveratrol exerts its protective effects against OGD/R damage, at least in part, by promoting mitophagy.

16.
Food Chem ; 334: 127475, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32688176

RESUMO

Although numerous types of organisms have been used to enrich selenium, a low-cost and efficient organism is yet to be identified. This study aimed to develop a new means of selenium enrichment using Tenebrio molitor larvae. Our results indicated that the total selenium content in larvae was increased 83-fold to 54.21 ± 1.25 µg/g, and of this content, organic selenium accounted for over 97% after feeding the larvae with 20 µg/g of sodium selenite. Selenium was distributed unequally in the protein fraction with following order: alkali-soluble protein-bound selenium (36.32%) > salt-soluble protein-bound selenium (19.41%) > water-soluble protein-bound selenium (17.03%) > alcohol-soluble protein-bound selenium (3.21%). Additionally, 81% of the selenium within the soluble proteins was distributed in subunits possessing molecular weights of <40 kDa. After hydrolysis by alcalase, the protein hydrolysate of selenium-enriched larvae possessing 75% selenium recovery exhibited stronger antioxidant and immunoregulatory activities than those of regular larvae.


Assuntos
Antioxidantes/farmacologia , Fatores Imunológicos/farmacologia , Proteínas de Insetos/metabolismo , Hidrolisados de Proteína/farmacologia , Selênio/farmacocinética , Tenebrio/metabolismo , Adulto , Aminoácidos/análise , Aminoácidos/metabolismo , Animais , Antioxidantes/metabolismo , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Hidrólise , Fatores Imunológicos/metabolismo , Proteínas de Insetos/farmacologia , Larva/efeitos dos fármacos , Larva/metabolismo , Camundongos , Hidrolisados de Proteína/metabolismo , Células RAW 264.7 , Selênio/análise , Subtilisinas/química , Subtilisinas/metabolismo , Tenebrio/efeitos dos fármacos
17.
Phytomedicine ; 80: 153385, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33091854

RESUMO

BACKGROUND: Microglia-mediated neuroinflammation is one of the most prominent characteristics of multiple sclerosis (MS), a chronic demyelination disease. As one of the main active ingredients in Astragali radix, total flavonoids of Astragalus (TFA) has multiple pharmacological effects such as immunomodulation, anti-inflammation and and anti-tumor. However, little is known about whether TFA could inhibit microglia-mediated neuroinflammation in MS. PURPOSE: This study was aimed to elucidate whether TFA could inhibit microglia-mediated neuroinflammation in MS. STUDY DESIGN: In the present study, we explored the protective effect of TFA on experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in mice for the first time, and discussed its mechanism from the aspect of anti-microglia-mediated neuroinflammation. METHODS: The mice received oral administration of TFA (25 and 50 mg/kg) daily from two days before immunization and continued until day 21 post-immunization. The effect of TFA on EAE in mice and its mechanism were investigated by ELISA, Western blot, real-time PCR, luciferase reporter assay, histopathology and immunohistochemistry. RESULTS: TFA were shown to alleviate the severity of EAE in mice. It inhibited the excessive activation of microglia both in spinal cords of EAE mice and in LPS-stimulated BV-2 cells, evidenced by weakening the production of inflammatory mediators such as NO, TNF-α, IL-6, and IL-1ß markedly at either protein or mRNA level. Further study demonstrated that TFA repressed the phosphorylation, nuclear translocation and transcriptional activity of NFκB, and inhibited the activation of AKT and JNK signaling in BV-2 cells induced by LPS. The agonists of AKT and JNK, anisomycin and SC79, could partly abolish the inhibitory effect of TFA on the production of inflammatory mediators in BV-2 cells induced by LPS. CONCLUSIONS: Taken together, our results clarified that TFA inhibited microglia-mediated inflammation in EAE mice probably through deactivating JNK/AKT/NFκB signaling pathways. The novel findings may lay a theoretical foundation for the clinical application of TFA in the treatment of MS.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Astrágalo (Planta)/química , Encefalomielite Autoimune Experimental/tratamento farmacológico , Flavonoides/farmacologia , Microglia/efeitos dos fármacos , Animais , Linhagem Celular , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Flavonoides/química , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia
18.
Pharmazie ; 75(12): 651-655, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303059

RESUMO

Objective: To compare the efficacy and safety of genotype-guided antiplatelet strategy and standard treatment in patient with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Methods: Relevant studies published in Medline, Embase, CoChrane Library were searched for randomized controlled trials (RCTs) until August 2020. Studies were screened by selection criteria, quality assessed using the Cochrane Collaboration's tool. Data were extracted from the included studies and statistically analyzed by RevMan 5.3 software. Results: Four RCTs involving 4,604 patients were included in this meta-analysis. Compared with the standard treatment group, the pooled results showed that genotype-guided group associated with lower risk of major adverse cardiovascular events (MACE, OR=0.52, 95%CI:0.35-0.78, P =0.001), any bleeding (OR=0.77, 95%CI: 0.62-0.95, P =0.02) and myocardial infarction (MI, OR=0.48, 95%CI:0.33-0.68, P <0.0001). There was no significant difference in death of any cause (OR=0.53, 95%CI: 0.18-1.54, P =0.25), cardiovascular death (OR=0.74, 95%CI:0.48-1.14, P =0.17), target vessel revascularization (OR=0.66, 95%CI:0.39-1.12, P =0.12) and major bleeding events (OR=0.86, 95%CI: 0.58-1.28, P =0.47). Conclusion: Genotype guided antiplatelet therapy could reduce the risk of MACE, MI and any bleeding events in patients with CAD undergone PCI, compared with standard treatment. Therefore, the findings support that implementation of genotype testing to tailor antiplatelet therapy after PCI.

19.
Food Chem ; : 128667, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33288349

RESUMO

Flammulina velutipes is one of the most popular edible mushrooms worldwide. A selenium-biofortification method for its fruiting body was developed using selenite. This study investigated the selenium content, distribution, speciation and the effect of selenium on mushroom growth, nutritive value, and mineral accumulation. Results showed that F. velutipes accumulated nearly 108 µg/g of organic selenium under treatment with 20 µg/g selenite, which accounts for over 97% of total selenium. Most (60-74%) of selenium combined with the protein fraction, whereas 15-21% combined with the polysaccharide fraction. Selenomethionine (56.8%), selenocysteine (22.8%), and methylselenocysteine (17.3%) were the main organic selenium compounds in the fruiting body. Selenium biofortification increased the biomass yield of fruiting body and elevated the content of polysaccharides, proteins, total amino acids, essential amino acids, and several minerals, including iron, calcium, and copper. F. velutipes might become a suitable selenium supplement.

20.
J Org Chem ; 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33378188

RESUMO

In the presence of the chiral Pd(0)/ligand complex, vinyl benzoxazinanones underwent the [4+2] cycloaddition with alkylidene pyrazolones smoothly and delivered spiropyrazolones in reasonable yields, diastereoselectivities, and eneantioselectivities (up to >99% yield, >99:1 dr and 99% ee). The absolute configuration of the obtained spiropyrazolones was unambiguously characterized with the use of X-ray single-crystal structure analysis. Moreover, the reaction mechanism was assumed to interpret the formation of the target compounds.

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