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1.
Molecules ; 27(9)2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35566072

RESUMO

The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2'-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein-ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.

2.
BMC Complement Med Ther ; 22(1): 123, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35509047

RESUMO

BACKGROUND: Bacteria-mediated cancer immunotherapy (BCI) robustly stimulates the immune system and represses angiogenesis, but tumor recurrence and metastasis commonly occur after BCI. The natural product Ilex kudingcha C. J Tseng enriched with ursolic acid has anti-cancer activity and could potentially augment the therapeutic effects of BCI. The objective of the present study was to determine potential additive effects of these modalities. METHODS: We investigated the anti-cancer activity of KDCE (Kudingcha extract) combined with S.t△ppGpp in the mice colon cancer models. RESULTS: In the present study, KDCE combined with S.t△ppGpp BCI improved antitumor therapeutic efficacy compared to S.t△ppGpp or KDCE alone. KDCE did not prolong bacterial tumor-colonizing time, but enhanced the antiangiogenic effect of S.t△ppGpp by downregulatingVEGFR2. We speculated that KDCE-induced VEGFR2 downregulation is associated with FAK/MMP9/STAT3 axis but not AKT or ERK. CONCLUSIONS: Ursolic acid-enriched KDCE enhances the antitumor activity of BCI, which could be mediated by VEGFR2 downregulation and subsequent suppression of angiogenesis. Therefore, combination therapy with S.t△ppGpp and KDCE is a potential cancer therapeutic strategy.


Assuntos
Ilex , Neoplasias , Animais , Bactérias , Modelos Animais de Doenças , Imunoterapia , Camundongos , Extratos Vegetais/farmacologia , Triterpenos
3.
Nat Commun ; 13(1): 2462, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513369

RESUMO

Magnetic droplets are non-topological magnetodynamical solitons displaying a wide range of complex dynamic phenomena with potential for microwave signal generation. Bubbles, on the other hand, are internally static cylindrical magnetic domains, stabilized by external fields and magnetostatic interactions. In its original theory, the droplet was described as an imminently collapsing bubble stabilized by spin transfer torque and, in its zero-frequency limit, as equivalent to a bubble. Without nanoscale lateral confinement, pinning, or an external applied field, such a nanobubble is unstable, and should collapse. Here, we show that we can freeze dynamic droplets into static nanobubbles by decreasing the magnetic field. While the bubble has virtually the same resistance as the droplet, all signs of low-frequency microwave noise disappear. The transition is fully reversible and the bubble can be thawed back into a droplet if the magnetic field is increased under current. Whereas the droplet collapses without a sustaining current, the bubble is highly stable and remains intact for days without external drive. Electrical measurements are complemented by direct observation using scanning transmission x-ray microscopy, which corroborates the analysis and confirms that the bubble is stabilized by pinning.

4.
World J Clin Cases ; 10(9): 2901-2907, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35434084

RESUMO

BACKGROUND: Nontraumatic myositis ossificans is a rare disease whose specific pathogenesis is unclear. Early diagnosis of this disease is very difficult in children because of difficulties in determining medical history and nonspecific early clinical manifestations, which may lead to the failure of timely and effective diagnosis and treatment in some patients. We report the diagnosis and treatment of a child with nontraumatic myositis ossificans and summarize the clinical characteristics and diagnosis and treatment of the disease. CASE SUMMARY: An 8-year-old girl first came to our hospital for more than a week with pain in the right lower limb. There was no history of trauma or strenuous activities. On physical examination, no mass on the right thigh was found, and the movement of the right lower extremity was limited. Ultrasonography showed synovitis of the hip, and bed rest was recommended. Three days later, the child's pain persisted and worsened, accompanied by fever and other discomforts. She came to our hospital again and a mass was found on the right thigh with redness and swelling on the surface. The images showed a soft tissue tumor on the right thigh with calcification. Routine blood tests revealed that the inflammation index was significantly increased. In case of infection, the patient was given antibiotics, and the pain was relieved soon after, without fever. However, the right thigh mass persisted and hardened. The patient underwent incision biopsy more than 1 mo later, and the postoperative pathology showed nontraumatic myositis ossificans. After approximately 9 mo of observation, the tumor still persisted, which affected the life of the child, and then resection was performed. Since follow-up, there has been no recurrence. CONCLUSION: Due to the difficulty in discerning a child's medical history and the diverse early manifestations, it is difficult to diagnose nonossifying muscle disease in children in its early stage. Measures such as timely follow-up and periodic image monitoring are conducive to early diagnosis of the disease. The disease has a certain degree of self-limitation, and it can be observed and treated first. If the tumor persists in the later stage or affects functioning, then surgery is considered.

5.
Oxid Med Cell Longev ; 2022: 9731800, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464773

RESUMO

A healthy microenvironment of the intervertebral disc tissue is characterized by hypoxia owing to its sparse vascular distribution. Oxidative stress plays a pivotal role in the pathological development of intervertebral disc degeneration (IVDD). We found that the expression of prolyl endopeptidase (PREP) increased in degenerative nucleus pulposus (NP) tissues. The purpose of this study was to determine whether PREP is involved in oxidative-stress-induced IVDD. Tertbutyl hydroperoxide can inhibit the expression of PREP by activating the PI3K/AKT signaling pathway at low concentrations in NP cells. Knockdown of PREP protected NP cells from apoptosis induced by oxidative stress, whereas overexpression of PREP exacerbated the apoptosis of NP cells. We also investigated the connection between the PI3K/AKT signaling pathway and PREP and found that the activation of the PI3K/AKT signaling pathway downregulated the expression of PREP by inhibiting p53. As a crucial transcription factor, p53 binds to the PREP promoter region and promotes its transcription. Overexpression of PREP also impairs protein secretion in the extracellular matrix of NP cells. Furthermore, the in vivo knockout of PREP could attenuate puncture-induced IVDD. These findings suggested that the downregulation of PREP might maintain the viability of NP cells and attenuate IVDD under oxidative stress.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Apoptose/fisiologia , Humanos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/patologia , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Prolil Oligopeptidases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismo
6.
J Am Chem Soc ; 144(14): 6442-6452, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35363483

RESUMO

The enantioconvergent radical C(sp3)-C(sp2) cross-coupling of alkyl halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good functional group tolerance. The key to the success is the rational design of hemilabile N,N,N-ligands by mounting steric hindrance at the ortho position of one coordinating quinoline ring. Thus, the newly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliver enantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utility in the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.


Assuntos
Cobre , Ésteres , Alcenos , Catálise , Ligantes
7.
JAMA Netw Open ; 5(4): e226417, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35389497

RESUMO

Importance: Standard diabetic ketoacidosis care in the US includes intravenous insulin treatment in the intensive care unit. Subcutaneous (SQ) insulin could decrease intensive care unit need, but the data are limited. Objective: To assess outcomes after implementation of an SQ insulin protocol for treating diabetic ketoacidosis. Design, Setting, and Participants: This cohort study is a retrospective evaluation of a prospectively implemented SQ insulin protocol. The study was conducted at an integrated health care system in Northern California. Participants included hospitalized patients with diabetic ketoacidosis at 21 hospitals between January 1, 2010, and December 31, 2019. The preimplementation phase was 2010 to 2015, and the postimplementation phase was 2017 to 2019. Data analysis was performed from October 2020 to January 2022. Exposure: An SQ insulin treatment protocol for diabetic ketoacidosis. Main Outcomes and Measures: Difference-in-differences evaluation of the need for intensive care, mortality, readmission, and length of stay at a single intervention site using an SQ insulin protocol from 2017 onward compared with 20 control hospitals using standard care. Results: A total of 7989 hospitalizations for diabetic ketoacidosis occurred, with 4739 (59.3%) occurring before and 3250 (40.7%) occurring after implementation. The overall mean (SD) age was 42.3 (17.7) years, with 4137 hospitalizations (51.8%) occurring among female patients. Before implementation, SQ insulin was the first insulin used in 40 intervention (13.4%) and 651 control (14.7%) hospitalizations. After implementation, 98 hospitalizations (80.3%) received SQ insulin first at the intervention site compared with 402 hospitalizations (12.8%) at control sites. The adjusted rate ratio for intensive care unit admission was 0.43 (95% CI, 0.33-0.56) at the intervention sites, a 57% reduction compared with control sites, and was 0.50 (95% CI, 0.25-0.99) for 30-day hospital readmission, a 50% reduction. There were no significant changes in hospital length of stay and rates of death. Conclusions and Relevance: These findings suggest that a protocol based on SQ insulin for diabetic ketoacidosis treatment was associated with significant decreases in intensive care unit need and readmission, with no evidence of increases in adverse events.


Assuntos
Diabetes Mellitus , Cetoacidose Diabética , Adulto , Estudos de Coortes , Cetoacidose Diabética/tratamento farmacológico , Cetoacidose Diabética/epidemiologia , Feminino , Hospitais , Humanos , Insulina/uso terapêutico , Insulina Regular Humana , Tempo de Internação , Estudos Retrospectivos
8.
ACS Med Chem Lett ; 13(4): 586-592, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35450381

RESUMO

Several antibodies targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) have been approved by the U.S. Food and Drug Administration (FDA) for cancer therapy. Although many small-molecule inhibitors of the PD-1/PD-L1 pathway have been reported, no small-molecule inhibitors have been approved for cancer treatment. In this work, a series of novel benzamide derivatives were designed, synthesized, and evaluated to find effective inhibitors of the PD-1/PD-L1 interaction. The most potent compound D2 exhibited better activity than that of BMS202, with an IC50 of 16.17 nM. D2 could activate the antitumor immunity of T cells efficiently in PBMCs. The proposed binding mode of compound D2 was investigated by docking analysis. These results indicate that compound D2 is a promising lead compound that can be used for further development.

9.
Int J Surg ; 100: 106598, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35288339

RESUMO

BACKGROUND: Postoperative pain has become one of the major obstacles to postoperative recovery and can lead to increasing demand for opioids. So far, a wide variety of drugs is used for regional block anesthesia, but which one is the best remains unclear. Thus, this study aims to obtain the best drug for thyroid surgery regional block based on their efficacy and side effects through Bayesian network meta-analysis. METHODS: Systemically searched MEDLINE, CENTRAL, Embase, and web of science on July 3, 2021 to obtain randomized controlled trials (RCTs) focusing on adults who underwent open thyroidectomy and regional blocks, and took opioids requirement, and the postoperative pain level as outcomes. The "Gemtc" package of R-4.1.1 was used for Bayesian network meta-analysis based on extracted data. RESULTS: We retrieved 398 articles, and finally included 31 RCTs, which included a total of 2221 patients. Patients received levobupivacaine had the lowest requirement rate for opioids and lowest pain score at T6 and T12. Non-steroidal anti-inflammatory drugs show significant superiority neither in the opioids requirement nor the pain score. Clonidine has a better potential to act as a qualified anesthetic adjuvant compared to adrenaline. The ranking results of the subgroup analysis were consistent with the integrated analysis. CONCLUSION: Levobupivacaine has a relatively greater advantage in reducing opioids requirement and decreasing the pain score of patients, and bilateral superficial cervical plexus blockade and pre thyroidectomy intervention have more advantages than local wound infiltration and post thyroidectomy intervention in alleviating patients' pain.


Assuntos
Analgesia , Tireoidectomia , Adulto , Analgesia/métodos , Analgésicos Opioides/uso terapêutico , Humanos , Levobupivacaína/uso terapêutico , Metanálise em Rede , Dor Pós-Operatória/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tireoidectomia/efeitos adversos
10.
Phytomedicine ; 100: 154059, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35338992

RESUMO

BACKGROUND: The synergic action of compound prescriptions is an important feature and core advantage of traditional medicine. Ginseng-Fuzi decoction is a classic compatible phytomedicine in China, of which Ginseng can effectively reduce the toxicity of Fuzi in clinical, but the detoxification chemical mechanism is still unclear. PURPOSE: Develop a novel method for real-time tracking and monitoring of complex substances in the decoction system of traditional Chinese medicine to uncover the detoxification effect Ginseng on Fuzi and explore the possible chemical reaction mechanism of Ginseng-Fuzi co-decoction. METHODS: A novel real-time monitoring system, online filtration electrospray ionization mass spectrometry, was developed for extremely complex substances analysis in the decoction of traditional medicine compounds to uncover the directionally detoxification effect and the mechanism of compatibility interaction. RESULTS: Nine key alkaloids and 7 ginsenosides in Ginseng-Fuzi decoction were simultaneously in-situ monitoring in positive ion mode or negative ion mode respectively. Both types of targeted analytes had satisfactory MS signal response for real-time qualitative and quantitative analysis with high precision (RSD < 14.04%) and low LLODs (0.002 ng/ml-10 ng/ml). Through long-term tracking analysis, the exact detoxification and synergistic effect of Ginseng-Fuzi decoction were confirmed as the concentration of main toxic alkaloids decreased (e.g. the content of mesaconitine has been reduced by about 38%) and the main active monoester alkaloids increased obviously. More importantly, the possible molecular mechanism of the detoxification effect of Ginseng compatibility was revealed for the first time, which was the nucleophilic substitution reaction of diester alkaloids catalyzed by fatty acids. CONCLUSION: This study revealed the exact effect of co-decoction of Ginseng and Fuzi at the molecular level and the chemical reaction mechanism of fatty acid-catalyzed degradation of toxic diester-type alkaloids. The comprehensive multi-component real-time monitoring strategy for complex traditional medicine compounds developed and implemented here has important demonstration significance for revealing the scientific connotation of the compatibility of compound traditional medicine.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Panax , Aconitum/química , Alcaloides/química , Cromatografia Líquida de Alta Pressão/métodos , Diterpenos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas por Ionização por Electrospray/métodos
11.
Respir Physiol Neurobiol ; 300: 103883, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35247623

RESUMO

Lung diseases such as acute respiratory distress syndrome affect the patient's lung compliance, which in turn affects the ability of gas exchange. Changes in alveolar diameter relate to local lung compliance. How alveolar diameter affects gas exchange, particularly oxygen concentrations in alveolar capillaries, is a topic of concern for researchers, and can be studied using mathematical models. The level of small-scale mathematical models of the pulmonary circulatory system was the alveolar capillaries, but existing models do not consider the gas-exchange function and fail to reflect the influence of alveolar diameter. Therefore, we proposed a pulmonary acinar capillary model with gas exchange function, and most importantly, introduced alveolar diameter into the model, to analyze the effect of alveolar diameter on the gas exchange function of the pulmonary acini. The model was tested by three respiratory function simulation experiments. According to the simulation results of changing diameter, we found that the alveolar diameter mainly affects the alveolar gas exchange function of lung acinar inlets and the middle section compared with the peripheral section.


Assuntos
Troca Gasosa Pulmonar , Síndrome do Desconforto Respiratório , Capilares , Humanos , Pulmão , Complacência Pulmonar , Alvéolos Pulmonares
12.
J Phys Chem Lett ; 13(11): 2555-2562, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35285656

RESUMO

Perovskite-related materials with various dimensionalities have attracted sustained attention owing to their extraordinary electronic and optoelectronic properties, but it is still challenging in the synthesis of compounds with desired compositions and structures. Herein, a two-dimensional (2D) CsPb2I5 perovskite has been synthesized by the conversion of CsPbI3 at high-pressure and high-temperature (high P-T) conditions, which is quenchable at ambient conditions. In situ synchrotron X-ray diffraction shows that high-pressure monoclinic CsPbI3 converts into tetragonal CsPb2I5 and cubic CsI at 8.7 GPa upon heating from 644 to 666 K. Keeping the tetragonal structure stable, CsPb2I5 exhibits tunable optical properties with the bandgap changing from ∼2.4 eV at ambient pressure to ∼1.4 eV at 36.9 GPa. Further experiments demonstrate similar structural evolution in the typical three-dimensional CsPbBr3 perovskite into 2D CsPb2Br5 at high P-T conditions, indicating that the conversion of CsPbX3 (X = Br and I) into CsPb2X5 is ubiquitous.

14.
J Med Chem ; 65(5): 3879-3893, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35188766

RESUMO

Several monoclonal antibodies targeting the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway have been used successfully in anticancer immunotherapy. Inherent limitations of antibody-based therapies remain, however, and alternative small-molecule inhibitors that can block the PD-1/PD-L1 axis are urgent needed. Herein, we report the discovery of compound 17 as a bifunctional inhibitor of PD-1/PD-L1 interactions. 17 inhibits PD-1/PD-L1 interactions and promotes dimerization, internalization, and degradation of PD-L1. 17 promotes cell-surface PD-L1 internalized into the cytosol and induces the degradation of PD-L1 in tumor cells through a lysosome-dependent pathway. Furthermore, 17 suppresses tumor growth in vivo by activating antitumor immunity. These results demonstrate that 17 targets the PD-1/PD-L1 axis and induces PD-L1 degradation.


Assuntos
Antígeno B7-H1 , Neoplasias , Antígeno B7-H1/metabolismo , Humanos , Imunoterapia , Neoplasias/metabolismo , Receptor de Morte Celular Programada 1/metabolismo
15.
Radiat Res ; 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35172004

RESUMO

Radiation-induced esophageal injury (RIEL) is a major dose-limiting complication of radiotherapy, especially for esophageal and thoracic cancers. RIEL is a multi-factorial and multi-step process, which is regulated by a complex network of DNA, RNA, protein and metabolite. However, it is unclear which esophageal metabolites are altered by ionizing radiation and how these changes affect RIEL progression. In this work, we established a rat model of RIEL with 0-40 Gy X-ray irradiation. Esophageal irradiation using ≥25 Gy induced significant changes to rats, such as body weight, food intake, water intake and esophageal structure. The metabolic changes and related pathways of rat esophageal metabolites were investigated by liquid chromatography-mass spectrometry (LC-MS). One hundred eighty metabolites showed an up-regulation in a dose-dependent manner (35 Gy ≥ 25 Gy > controls), and 199 metabolites were downregulated with increasing radiation dose (35 Gy ≤ 25 Gy < controls). The KEGG analysis showed that ionizing radiation seriously disrupted multiple metabolic pathways, and arachidonic acid metabolism was the most significantly enriched pathway. 20 metabolites were dysregulated in arachidonic acid metabolism, including up-regulation of five prostaglandins (PGA2, PGJ2, PGD2, PGH2, and PGI2) in 25 or 35 Gy groups. Cyclooxygenase-2 (COX-2), the key enzyme in catalyzing the biosynthesis of prostaglandins from arachidonic acid, was highly expressed in the esophagus of irradiated rats. Additionally, receiver operating characteristic (ROC) curve analysis revealed that PGJ2 may serve as a promising tissue biomarker for RIEL diagnosis. Taken together, these findings indicate that ionizing radiation induces esophageal metabolic alterations, which advance our understanding of the pathophysiology of RIEL from the perspective of metabolism.

16.
Front Pharmacol ; 13: 818159, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185572

RESUMO

The harm of nonalcoholic fatty liver disease to human health is increasing, which calls for urgent prevention and treatment of the disease. Isoorientin is an effective ingredient of Chinese herbal medicine with anti-inflammatory and antioxidant effects. However, the effect of isoorientin in nonalcoholic fatty liver disease is still unclear. In this study, combined in vivo and in vitro experiments, through pathological observation, flow cytometry, immunofluorescence and western blot analysis to explore the role of isoorientin in steatosis and reveal its molecular mechanism. The results demonstrated that oleic acid treatment significantly increased the content of ROS and lipid droplets in rat hepatocytes, and promoted the expression of γH2AX, HO-1, PPARγ, SREBP-1c, FAS. The ROS content in the cells of co-treated with isoorientin and oleic acid was significantly reduced compared to the oleic acid group, and the expression of γH2AX, HO-1, PPARγ, SREBP-1c, FAS, and the nuclear translocation of NF-κB p65 were also significantly inhibited. Our data showed that oleic acid induce oxidative damage and steatosis in hepatocytes both in vitro and in vivo, and activate the PPARγ/NF-κB p65 signal pathway. Moreover, isoorientin can significantly reduce oleic acid -induced oxidative damage and steatosis by regulating the PPARγ/NF-kB p65 signal pathway.

17.
Zhongguo Zhong Yao Za Zhi ; 47(1): 95-102, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35178915

RESUMO

In this experiment, Panax notoginseng saponins chitosan nanoparticles(PNS-NPs) were prepared by self-assembly and their appearance, particle size, encapsulation efficiency, drug loading, polydispersity index(PDI), Zeta potential, and microstructure were characterized. The prepared PNS-NPs were intact in structure, with an average particle size of(209±0.258) nm, encapsulation efficiency of 42.34%±0.28%, a drug loading of 37.63%±0.85%, and a Zeta potential of(39.8±3.122) mV. The intestinal absorption of PNS-NPs in rats was further studied. The established HPLC method of PNS was employed to investigate the effects of pH, perfusion rate, and different drugs(PNS raw materials, Xuesaitong Capsules, and PNS-NPs). The absorption rate constant(K_a) and apparent permeability coefficient(P_(app)) in the duodenum, jejunum, ileum, and colon were calculated and analyzed. As illustrated by the results, the intestinal absorption of PNS-NPs was increased in the perfusion solution at pH 6.8(P<0.05), and perfusion rate had no significant effect on the K_a and P_(app) of PNS-NPs. The intestinal absorption of PNS-NPs was significantly different from that of PNS raw materials and Xuesaitong Capsules(P<0.05), and the intestinal absorption of PNS-NPs was significantly improved.


Assuntos
Quitosana , Nanopartículas , Panax notoginseng , Saponinas , Animais , Quitosana/farmacologia , Absorção Intestinal , Panax notoginseng/química , Ratos , Saponinas/farmacologia
18.
Zhongguo Zhong Yao Za Zhi ; 47(1): 279-284, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35178935

RESUMO

Quality is the guarantee for the clinical safety and effectiveness of Chinese medicine. Accurate quality evaluation is the key to the standardization and modernization of Chinese medicine. Efforts have been made in improving Chinese medicine quality and strengthening the quality and safety supervision in China, but rapid and accurate quality evaluation of complex Chinese medicine samples is still a challenge. On the basis of the development of ambient mass spectrometry and the application in quality evaluation of complex Chinese medicine systems in recent years, the authors developed the multi-scenario Chinese medicine quality evaluation strategies. A systematic methodology was proposed in specific areas such as real-time monitoring of the quality of complex Chinese medicine decoction system, rapid toxicity grading of compound Chinese patent medicine, and evaluation of bulk medicinals of Chinese patent medicine. Allowing multi-scenario analysis of Chinese medicine, it is expected to provide universal research ideas and technical methods for rapid and accurate quality evaluation of Chinese medicine and boost the high-quality development of Chinese medicine industry.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , China , Espectrometria de Massas , Medicamentos sem Prescrição , Padrões de Referência
19.
Emerg Microbes Infect ; 11(1): 730-740, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35171086

RESUMO

ABSTRACTThe COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development, and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus-neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. This study predicted several potential T cell epitopes with web-based analytic tools and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants and compatible with a presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Vacinas contra COVID-19 , Epitopos de Linfócito T/genética , Humanos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
20.
Virulence ; 13(1): 297-309, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35068319

RESUMO

Feline viral diseases, such as feline panleukopenia, feline infectious peritonitis, and feline coronaviral enteritis, seriously endanger the health of cats, and restrict the development of pet industry. Meanwhile, there is a current lack of effective vaccines to protect against feline viral diseases. Thus, effective therapeutic agents are highly desirable. Interferons (IFNs) are important mediators of the antiviral host defense in animals, particularly type I IFNs. In this study, a novel feline IFN omega (feIFN-ω) gene was extracted from the cat stimulated with feline parvovirus (FPV) combined with poly(I:C), and following codon optimization encoding the feIFN-ω, the desired gene (feIFN-ω') fragment was inserted into plasmid pPICZαA, and transformed into Pichia pastoris GS115, generating a recombinant P. pastoris GS115 strain expressing the feIFN-ω'. After induction, we found that the expression level of the feIFN-ω' was two times more than that of feIFN-ω (p < 0.01). Subsequently, the feIFN-ω' was purified and modified with polyethylene glycol, and its antiviral efficacy was evaluated in vitro and in vivo, using vesicular stomatitis virus (VSV) and FPV as model virus. Our results clearly demonstrated that the feIFN-ω' had significant antiviral activities on both homologous and heterologous animal cells in vitro. Importantly, the feIFN-ω' can effectively promote the expression of antiviral proteins IFIT3, ISG15, Mx1, and ISG56, and further enhance host defense to eliminate FPV infection in vivo, suggesting a potential candidate for the development of therapeutic agent against feline viral diseases.


Assuntos
Antivirais , Interferon Tipo I , Animais , Antivirais/farmacologia , Gatos , Clonagem Molecular , Códon , Interferon Tipo I/genética , Polietilenoglicóis , Saccharomycetales
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