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1.
Cell ; 185(9): 1572-1587.e11, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35452622

RESUMO

The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1., and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lungs. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.


Assuntos
COVID-19 , SARS-CoV-2 , Vacina de mRNA-1273 contra 2019-nCoV , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Camundongos , SARS-CoV-2/genética , Vacinação , Vacinas Sintéticas , Vacinas de mRNA
2.
J Mol Evol ; 88(8-9): 641-652, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32864711

RESUMO

Maximum likelihood (ML) analysis of nucleotide or amino-acid alignments is widely used to infer evolutionary relationships among species. Computing the likelihood of a phylogenetic tree from such alignments is a complicated task because the evolutionary processes typically vary across sites. A number of studies have shown that partitioning alignments into sub-alignments of sites, where each sub-alignment is analyzed using a different model of evolution (e.g., GTR + I + G), is a sensible strategy. Current partitioning methods group sites into subsets based on the inferred rates of evolution at the sites. However, these do not provide sufficient information to adequately reflect the substitution processes of characters at the sites. Moreover, the site rate-based methods group all invariant sites into one subset, potentially resulting in wrong phylogenetic trees. In this study, we propose a partitioning method, called mPartition, that combines not only the evolutionary rates but also substitution models at sites to partition alignments. Analyses of different partitioning methods on both real and simulated datasets showed that mPartition was better than the other partitioning methods tested. Notably, mPartition overcame the pitfall of grouping all invariant sites into one subset. Using mPartition may lead to increased accuracy of ML-based phylogenetic inference, especially for multiple loci or whole genome datasets.


Assuntos
Evolução Molecular , Modelos Genéticos , Filogenia
3.
Life (Basel) ; 13(6)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37374064

RESUMO

Alzheimer's disease (AD) is the most common form of dementia, which is recorded as a global health issue. Natural acetylcholinesterase inhibitors (AChEIs) are considered a helpful therapy for the management of symptoms of patients with mild-to-moderate AD. This work aimed to investigate and characterize Euonymus laxiflorus Champ. (ELC) as a natural source of AChEIs compounds via in vitro and virtual studies. The screening parts used, including the leaves, heartwood, and trunk bark of ELC, revealed that the trunk bark extract possessed the highest activity, phenolics and flavonoid content. The in vitro anti-Alzheimer activity of ELC trunk bark was notably reclaimed for the first time with comparable effect (IC50 = 0.332 mg/mL) as that of a commercial AChEI, berberine chloride (IC50 = 0.314 mg/mL). Among various solvents, methanol was the most suitable to extract ELC trunk bark with the highest activity. Twenty-one secondary metabolites (1-21) were identified from ELC trunk bark extract, based on GCMS and UHPLC analyses. Of these, 10 volatile compounds were identified from this herbal extract for the first time. One phenolic (11) and seven flavonoid compounds (15-21) were also newly found in this herbal extract. Of the identified compounds, chlorogenic acid (11), epigallocatechin gallate (12), epicatechin (13), apigetrin (18), and quercetin (20) were major compounds with a significant content of 395.8-2481.5 µg/g of dried extract. According to docking-based simulation, compounds (11-19, and 21) demonstrated more effective inhibitory activity than berberine chloride, with good binding energy (DS values: -12.3 to -14.4 kcal/mol) and acceptable RMSD values (0.77-1.75 Å). In general, these identified compounds processed drug properties and were non-toxic for human use, based on Lipinski's rule of five and ADMET analyses.

4.
Trop Med Infect Dis ; 7(5)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35622703

RESUMO

Infections with the zoonotic liver flukes Fasciola gigantica and Fasciola hepatica may result in severe disease in humans. In Vietnam, an emergence of fascioliasis cases has been observed from the late 1990s onwards. Various diagnostic tools are used in the country, but the agreement between these tools has not been critically evaluated. We aimed to describe the clinical presentation and diagnostic outcomes in fascioliasis patients in Vietnam. A retrospective, cross-sectional study was conducted on the medical records of a group of 145 patients diagnosed with fascioliasis at a tertiary referral hospital in Hanoi. Based on the review, sociodemographic background and clinical presentation were recorded. These patients all received standard routine serologic tests, including internal antibody (Ab)-ELISA, an enzyme-linked immunosorbent assay (ELISA), and commercial coproantigen (cAg)-ELISA. The majority of cases were between 30 and 59 years old (68.3%), and about half of them were male (51.0%). Upper quadrant and epigastric pain were the most commonly reported symptoms (61.4% and 35.2%, respectively). All but one patient had liver lesions upon ultrasound examination (99.3%), and eosinophilia was present in most of the patients (89.7%). A high number of patients were positive in the in-house and the commercial Ab-ELISA (95.9% and 87.4%, respectively), yet only a slight agreement was observed between the two tests (kappa coefficient, 0.06). A further 47.4% of cases were positive for the commercial cAg-ELISA, whereas stool microscopy indicated the presence of Fasciola spp. eggs in 25.7% of patients. The current study emphasizes the challenges related to the diagnosis of human fascioliasis in Vietnam.

5.
bioRxiv ; 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35169795

RESUMO

The B.1.1.529 Omicron variant jeopardizes vaccines designed with early pandemic spike antigens. Here, we evaluated in mice the protective activity of the Moderna mRNA-1273 vaccine against B.1.1.529 before or after boosting with preclinical mRNA-1273 or mRNA-1273.529, an Omicron-matched vaccine. Whereas two doses of mRNA-1273 vaccine induced high levels of serum neutralizing antibodies against historical WA1/2020 strains, levels were lower against B.1.1.529 and associated with infection and inflammation in the lung. A primary vaccination series with mRNA-1273.529 potently neutralized B.1.1.529 but showed limited inhibition of historical or other SARS-CoV-2 variants. However, boosting with mRNA-1273 or mRNA-1273.529 vaccines increased serum neutralizing titers and protection against B.1.1.529 infection. Nonetheless, the levels of inhibitory antibodies were higher, and viral burden and cytokines in the lung were slightly lower in mice given the Omicron-matched mRNA booster. Thus, in mice, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against B.1.1.529 infection with limited differences in efficacy measured.

6.
Bioorg Med Chem Lett ; 21(2): 633-7, 2011 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21194938

RESUMO

By bioactive-guided fractionation of methanol extract of the Ficus microcarpa leaves, one new C-glucosylflavone, ficuflavoside (1), one new megastigmane glycoside, ficumegasoside (8), and twelve known compounds including flavonoids (2-6), phenylpropanoids (7), megastigmanes (9-11) and sterol derivatives (12-14) were isolated. Their chemical structures were elucidated by mass, 1D, and 2D NMR spectroscopies. The antioxidant activities of these compounds were measured using the oxygen radical absorbance capacity methods. Compounds 1-6 exhibited potent antioxidant activities of 6.6-9.5µM Trolox equivalents at the concentration of 2.0µM. The results indicated 2, 3, and 5 having meaningful reducing capacity of copper (I) ions concentration of 6.1-8.4µM.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Ficus/química , Flavonoides/química , Flavonoides/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/isolamento & purificação , Cromanos/farmacologia , Flavonoides/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química
7.
Polymers (Basel) ; 13(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946903

RESUMO

This study consists of two parts. In the first, the woven polyester fabric, after washing to remove lubricant oils, was treated with the dielectric barrier discharge (DBD) plasma at the short plasma exposure time (from 15 to 90 s). The effect of the plasma exposure time on the activation of the polyester fabric was assessed by the wicking height of the samples. The results show that the wicking height in the warp direction of the plasma-treated samples improved but was virtually unchanged in the weft direction. Meanwhile, although the tensile strength in the warp direction of the fabric was virtually unaffected despite the plasma treatment time up to 90 s, in the weft direction it increased slightly with the plasma treatment time. Scanning Electron Microscope (SEM) images and the X-ray Photoelectron Spectroscopy (XPS) spectra of the samples before and after the plasma treatment were used to explain the nature of these phenomena. Based on the results of the first part, in the second part, two levels of the plasma treatment time (30 and 60 s) were selected to study their effect on the polyester fabric dyeability with disperse dyes. The color strength (K/S) values of the dyed samples were used to evaluate the dyeability of the fabric. The SEM images of the dyed samples also showed the difference in the dyeability between the plasma-treated and untreated samples. A new feature of this study is the DBD plasma treatment condition for polyester fabrics. The first is the use of DBD plasma in air (no addition of gas). Second is the very short plasma treatment time (only 15 to 90 s); this condition will be very favorable for the deployment on an industrial scale.

8.
AMA J Ethics ; 23(12): E926-930, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35072607

RESUMO

This commentary in response to a case considers how merit and features of medical school applicants' dossiers should be drawn upon in admissions processes to promote equity and inclusion in medicine. It is argued that medical schools should incentivize inclusion by redefining merit in their admissions goals and processes, promote meaningful inclusion, and show institutional leadership in addressing social justice.


Assuntos
Critérios de Admissão Escolar , Faculdades de Medicina , Humanos , Liderança , Justiça Social
9.
Sci Rep ; 11(1): 2032, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479433

RESUMO

A simple design of a broadband multifunctional polarization converter using an anisotropic metasurface for X-band application is proposed. The proposed polarization converter consists of a periodic array of the two-corner-cut square patch resonators based on the FR-4 substrate that achieves both cross-polarization and linear-to-circular polarization conversions. The simulated results show that the polarization converter displays the linear cross-polarization conversion in the frequency range from 8 to 12 GHz with the polarization conversion efficiency above 90%. The efficiency is kept higher than 80% with wide incident angle up to 45°. Moreover, the proposed design achieves the linear-to-circular polarization conversion at two frequency bands of 7.42-7.6 GHz and 13-13.56 GHz. A prototype of the proposed polarization converter is fabricated and measured, showing a good agreement between the measured and simulated results. The proposed polarization converter exhibits excellent performances such as simple structure, multifunctional property, and large cost-efficient bandwidth and wide incident angle insensitivity in the linear cross polarization conversion, which can be useful for X-band applications. Furthermore, this structure can be extended to design broadband polarization converters in other frequency bands.

10.
Nat Prod Res ; 35(23): 5502-5507, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32608263

RESUMO

A phytochemical investigation of Solanum torvum led to the isolation of eleven steroidal glycosides, including neochlorogenin 6-O-ß-D-quinovopyranoside (1), (22 R,23S,25R)-3ß-6α,23-trihydroxy-5α-spirostane 6-O-ß-D-xylopyranosyl-(1→3)-ß-D-quinovopyranoside (2), neochlorogenin 6-O-α-L-rhamnopyranosyl-(1→3)-ß-D-quinovopyranoside (3), solagenin 6-O-α-L-rhamnopyranosyl-(1→3)-ß-D-quinovopyranoside (4), paniculonin A (5), paniculonin B (6), 6α-O-[ß-D-xylopyranosyl-(1→3)ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (7), torvoside J (8), torvoside K (9), torvoside L (10) and solagenin 6-O-ß-D-quinovopyranoside (11). Their chemical structures were elucidated by 1D-NMR and 2D-NMR data as well as comparison with the data reported in the literature. Moreover, all isolated compounds were evaluated for their cytotoxic activities against SK-LU-1, HepG2, MCF-7 and T24 cancer cell lines. Among them, compounds 1, 3, 7 and 11 exhibited cytotoxicity against all four tested cell lines with IC50 values ranging from 7.89 ± 0.87 to 46.76 ± 3.88 µM.


Assuntos
Saponinas , Solanum , Glicosídeos/farmacologia , Componentes Aéreos da Planta , Vietnã
12.
Chem Pharm Bull (Tokyo) ; 58(10): 1408-10, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20930414

RESUMO

One new monoterpenoid glycoside, myresculoside (1), and eleven known compounds, were isolated from methanol extract of Myrica esculenta leaves by repeated column chromatography. The effects of these compounds on angiotensin I-converting enzyme (ACE) inhibition were investigated. Compounds 3 and 4 showed the most potent ACE inhibition with rates of 29.97% and 25.63% at concentration of 100 µM, respectively. Compounds 5, 6, and 11 showed weak activity with inhibitory rates of 0.07-1.41% at concentration of 100 µM.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Glicosídeos/química , Monoterpenos/química , Myrica/química , Peptidil Dipeptidase A/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Conformação Molecular , Monoterpenos/isolamento & purificação , Peptidil Dipeptidase A/metabolismo , Folhas de Planta/química
13.
Chemosphere ; 232: 164-170, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31154176

RESUMO

The influence of an ionic functional group on the fate of chemicals in the environment, especially the formation of non-extractable residues (NER), has not been systematically investigated. Using 4-n-dodecylphenol[phenylring-14C(U)], 4-n-dodecylbenzenesulfonicacid[phenylring-14C(U)] sodiumsalt (14C-DS-) and 4-n-dodecylbenzyltrimethylammoniumchloride[phenylring-14C(U)] (14C-DA+) all with a high structural similarity, the formation, classification and identification of NER of negatively (14C-DS-), positively (14C-DA+) and uncharged (14C-DP) chemicals were investigated in a sterilized and non-sterilized soil. After 84 days of incubation in non-sterile soil, 40.6%, 21.7% and 33.5% of the applied radioactivity (AR) of 14C-DP, 14C-DS- and 14C-DA+, respectively, were converted to NER. In contrast, in sterile soil NER formation was markedly lower. The NER were further investigated with respect to sequestered, covalently bound and biogenic residues (i.e. NER types I, II, and III). Silylation of 14C-DP, 14C-DS- and 14C-DA+ derived NER released 3.0-23.2% AR, indicating that these were sequestered, whereas the residual NER (12.9-33.1% AR) was covalently bound to the soil. Analysis of extracts derived by silylation showed that 14C-DP, but neither 14C-DS- nor 14C-DA+, were released by silylation, suggesting that DP might be part of the sequestered NER. Acid hydrolysis of the NER containing soil and subsequent analysis of soil extracts for 14C-aminoacids indicated that 2.5-23.8% AR were biogenic residues. Most DP and DS- derived NER were biogenically or covalently bound, whereas DA+ predominantly forms sequestered NER in soil. From these results we propose that chemicals forming high amounts of NER should be investigated regarding types I-III NER because sequestered parent compounds should be considered in persistence assessments.


Assuntos
Monitoramento Ambiental/métodos , Poluentes do Solo/análise , Isótopos de Carbono/análise , Íons , Solo/química , Microbiologia do Solo
14.
Artigo em Inglês | MEDLINE | ID: mdl-33581010

RESUMO

The present study investigated the phytochemicals and antidiabetic effect of the aqueous extract of the fruit of Punica granatum Linn. in streptozotocin (STZ)-induced diabetic mice. The fruit of P. granatum was extracted with water. The phytochemicals of the water extract were investigated by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The water extract of P. granatum at doses of 150 and 300 mg/kg body weight (bw) was administered to mice for 21 days, and blood glucose level, triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein-cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme were estimated. Analyzed phytochemicals showed the fruit of P. granatum Linn has a high amount of phenolic and flavonoid compounds, which provide beneficial effect for this plant. The oral administration of the fruit extract of P. granatum at doses of 150 and 300 mg/kg bw for 21 days significantly reduced blood glucose level, triglycerides, serum cholesterol, LDL-cholesterol, AST and ALT enzyme. Our results suggested that the fruit extract of P. granatum has strong antidiabetic effect in STZ-induced diabetic mice. The fruit of this plant might be a potential source of drug for treatment of diabetes.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31778363

RESUMO

Alzheimer's disease (AD), which relates to nervous degeneration, is the most popular form of memory loss. The pathogenesis of AD is not fully understood, and there are no therapies for this disorder. Some drugs have been used in clinical applications for preventing and treating AD, but they have significant adverse reactions. Therefore, there is a need to develop treatment for AD. Traditional medicine has used many medicinal plants to alleviate the symptoms of AD. Medicinal plants may reduce neurodegenerative disorders with fewer side effects than chemical drugs, and they are promising drug candidates for AD therapy. This review is the summary of the pathogenesis and treatments of AD and includes information about the chemistry and bioactivities of some medicinal plants from the Huperzia species, such as Huperzia saururus, Huperzia selago, Huperzia phlegmaria, Huperzia fargesii, Huperzia serrata, Huperzia reflexa and Huperzia quadrifariata, that are used for the treatment of AD. We searched literature, including Medline, Embase, Google Scholar and PubMed database, and did a bibliographic review of relevant articles. Key words included Huperzia species, huperzine, huperin, Huperzia and Alzheimer's disease. We found that the main bioactive compounds of the Huperzia species are alkaloids, which have shown significant effects on preventing the development of AD. They are new promising compounds against AD due to their antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities in the neural system. Our conclusion from this review is that the Huperzia species are potential source containing various pharmaceutical compounds for the treatment of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Huperzia/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos
16.
Mil Med ; 172(6): 666-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17615855

RESUMO

An active duty male presented to the emergency room with dyspnea for 2 days after undergoing liposuction surgery. Upon presentation, the patient was afebrile, tachycardic, tachypneic, and hypoxemic. The initial chest radiograph demonstrated bilateral patchy opacities and the PaO2/FiO2 ratio was <200. The patient was admitted to the medical intensive care unit for supportive care. He was treated empirically for pneumonia. Blood and sputum cultures were negative. A computed tomography angiogram of the chest was negative for pulmonary embolism but did reveal a bilateral, perihilar air space process. The patient's oxygen requirement improved and the abnormal chest radiographic findings resolved over the next 48 hours. Given his clinical presentation, negative workup, and rapid recovery, the patient was given a presumptive diagnosis of pulmonary fat embolism. Fat embolism occurs when adipocytes and small blood vessels are damaged during the liposuction procedure. Patients may present with low-grade fever, tachycardia, tachypnea, hypoxemia, and hypocapnia. The differential diagnosis includes venous thromboembolism, aspiration pneumonitis, and pneumonia. The mainstay of treatment for pulmonary fat embolism is supportive care. The risk of mortality is 5 to 15%.


Assuntos
Dispneia/etiologia , Embolia Gordurosa/diagnóstico , Lipectomia/efeitos adversos , Medicina Militar , Militares , Embolia Pulmonar/diagnóstico , Doença Aguda , Adulto , Dispneia/diagnóstico , Embolia Gordurosa/etiologia , Humanos , Masculino , Embolia Pulmonar/etiologia , Fatores de Risco , Estados Unidos
17.
Zootaxa ; 4179(2): 279-287, 2016 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-27811675

RESUMO

A new species of semi-terrestrial crab of the family Potamidae, Rathbunamon chumomrayense sp. nov. is described from Chu Mom Ray National Park, the Central Highlands of Vietnam. The new species can be distinguished from R. lacunifer (Rathbun, 1904), the only other species in the genus, by a suite of characters, including the slightly more rugose anterolateral regions, confluent epigastric and postorbital cristae that are sinuous, less convex anterolateral margins, relatively shorter fingers of the chelipeds, and the terminal segment of the male first gonopod being slightly curved outwards, with narrower dorsal flap.


Assuntos
Braquiúros/anatomia & histologia , Braquiúros/classificação , Animais , Ecossistema , Masculino , Especificidade da Espécie , Vietnã
18.
Acad Med ; 95(9S A Snapshot of Medical Student Education in the United States and Canada: Reports From 145 Schools): S74-S78, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33626650
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