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1.
J Med Chem ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34818014

RESUMO

The pandemic of acute respiratory disease in 2019 caused by highly pathogenic and infectious SARS-CoV-2 has seriously endangered human public safety. The 6-HB (HR1-HR2 complex) formation occurring in the process of spike protein-mediated membrane fusion could serve as a conserved and potential target for the design of fusion inhibitors. Based on the HR2 domain of 6-HB, we designed and synthesized 32 stapled peptides using an all-hydrocarbon peptide stapling strategy. Owing to the improved proteolytic stability and higher helical contents, the optimized stapled peptides termed SCH2-1-20 and SCH2-1-27 showed better inhibitory activities against pseudo and authentic SARS-CoV-2 compared to the linear counterpart. Of note, SCH2-1-20 and SCH2-1-27 were proved to interfere with S protein-mediated membrane fusion. Structural modeling indicated similar binding modes between SCH2-1-20 and the linear peptide. These optimized stapled peptides could serve as potent fusion inhibitors in treating and preventing SARS-CoV-2, and the corresponding SAR could facilitate further optimization.

2.
Biomed Chromatogr ; : e5235, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553391

RESUMO

Dingkun Dan (DKD), a reputable traditional Chinese medicine formula, has been used to treat gynecological diseases and showed significant clinical effects since ancient times. However, the application and development of DKD are seriously hampered by the unclear active substances. Structural characterization of compounds absorbed in vivo and their corresponding metabolites is significant for clarifying the pharmacodynamic material basis. In this study, an integrated strategy using ultra-performance liquid chromatography, coupled with quadrupole time-of-flight mass spectrometry and UNIFI™ software, was used to identify prototypes and metabolites after oral administration of DKD in rats. As a result, a total of 261 compounds, including 140 prototypes and 121 metabolites, were tentatively characterized in rat plasma, urine, and feces. The metabolic pathways of prototypes have been studied to clarify their possible transformation process in vivo. Moreover, an in vitro metabolism study was applied for verifying the metabolites under simulating the metabolic environment in vivo. This first systematic metabolic study of DKD is important for elucidating the metabolites and metabolic pathways and could provide a scientific basis for explaining the integrative mechanism in further pharmacology study.

3.
Int J Nanomedicine ; 16: 6297-6311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552326

RESUMO

Purpose: This study aimed to evaluate the pharmaceutical and pharmacokinetic effects of the natural nanoparticles (Nnps) isolated from Coptidis Rhizoma extract on berberine hydrochloride (BBR) and systematically explore the related mechanisms. Methods: Firstly, Nnps were isolated from Coptidis Rhizoma extract and then an Nnps-BBR complex was prepared. After qualitative and quantitative analysis in terms of size, Zeta potential, morphology, and composition of the Nnps and the Nnps-BBR complex, the effects of the Nnps on the crystallization of BBR were characterized. The effects of the Nnps on the solubility and dissolution of BBR were then evaluated. In addition, the effects of the Nnps on BBR in terms of cellular uptake, transmembrane transport, metabolic stability, and pharmacokinetics in mice were studied. Results: The Nnps had an average size of 166.6 ± 1.3 nm and Zeta potential of -12.5 ± 0.2 mV. The Nnps were formed by denaturation of co-existing plant proteins with molecular weight < 30 kDa. The Nnps adsorbed or dispersed BBR, thereby promoting BBR transformation from crystal to amorphous form and improving its solubility and dissolution. The Nnps carried and promoted BBR uptake by human colonic adenocarcinoma (Caco-2) cells via caveolae-mediated endocytosis, reducing P-gp-mediated efflux of BBR in mice gut sacs and Madin-Darby canine kidney cells stably expressing the transporter P-gp (MDCK-MDR1) cells. Moreover, the Nnps improved BBR metabolic stability in mouse intestinal S9, promoting BBR intestinal absorption in mice, as shown by increased peak BBR concentration (Cmax, 1182.3 vs 310.2 ng/mL) and exposure level (AUC0-12 h, 2842.8 vs 1447.0 ng·h/mL) in mouse portal vein. In addition, the Nnps increased BBR exposure level in mouse livers (95,443.2 vs 43,586.2 ng·h/g liver). Conclusion: The proteinaceous nanoparticles isolated from Coptidis Rhizoma extract can form a natural nano-drug delivery system with BBR, thereby significantly improving the pharmacokinetics of oral BBR.


Assuntos
Berberina , Medicamentos de Ervas Chinesas , Animais , Células CACO-2 , Cães , Humanos , Absorção Intestinal , Camundongos
4.
Huan Jing Ke Xue ; 42(8): 3595-3603, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309246

RESUMO

In late August 2020, a period of O3 pollution occurred in the main urban area of Chongqing and lasted for approximately 2 weeks (till early September). Ambient air samples, collected using Summa Canisters and DNPH sampling columns at three observation sites in the main urban area, were used to study the composition, photochemical reaction activity, and source apportionment of volatile organic compounds (VOCs) during the period of O3 pollution. The results showed that the mean volume fraction of TVOCs in the main urban area of Chongqing during the observation period was 45.08×10-9, and the components were ranked by volume fraction in the following order:OVOCs, alkanes, halohydrocarbons, alkenes, aromatics, and alkynes. Formaldehyde, ethylene, and acetone made up the higher volume fraction of VOCs, together accounting for more than 30% of TVOCs. OVOCs and alkenes contributed more to · OH loss rate (Li·OH) and ozone formation potential (OFP) and were the key VOCs components for ozone generation. The main active species in the OVOCs component were formaldehyde, acetaldehyde, and acrolein; the main active species in the alkene component were isoprene, ethylene, and n-butene. The ratio of xylene to ethylbenzene in VOCs was low, and they showed a significant correlation, indicating that the VOCs air mass in the main urban area was highly aging and affected by long-distance transmission from other areas. The source apportionment results of the PMF model showed five main sources of VOCs, namely secondary generation (27.67%), vehicle exhaust (26.56%), industrial emission (17.86%), plant (14.51%), and fossil fuel combustion (13.4%).


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise
5.
J Med Chem ; 64(13): 8884-8915, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34170703

RESUMO

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates various biological processes, including proliferation, metastasis, angiogenesis, immune response, and chemoresistance. In normal cells, STAT3 is tightly regulated to maintain a transiently active state, while persistent STAT3 activation occurs frequently in cancers, associating with a poor prognosis and tumor progression. Targeting the STAT3 protein is a potentially promising therapeutic strategy for tumors. Although none of the STAT3 inhibitors has been marketed yet, a few of them have succeeded in entering clinical trials. This Review aims to systematically summarize the progress of the last 5 years in the discovery of directive STAT3 small-molecule inhibitors and degraders, focusing primarily on their structural features, design strategies, and bioactivities. We hope this Review will shed light on future drug design and inhibitor optimization to accelerate the discovery process of STAT3 inhibitors or degraders.


Assuntos
Antineoplásicos/farmacologia , Desenvolvimento de Medicamentos , Neoplasias/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Humanos , Estrutura Molecular , Neoplasias/metabolismo , Fosforilação/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química
6.
Biomed Pharmacother ; 141: 111833, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34175822

RESUMO

Natural products continue to be an unparalleled source of pharmacologically active lead compounds because of their unprecedented structures and unique biological activities. Natural product target discovery is a vital component of natural product-based medicine translation and development and is required to understand and potentially reduce mechanisms that may be associated with off-target side effects and toxicity. Omics-based techniques, including genomics, transcriptomics, proteomics, metabolomics, and bioinformatics, have become recognized as effective tools needed to construct innovative strategies to discover natural product targets. Although considerable progress has been made, the successful discovery of natural product targets remains a challenging time-consuming process that has come to increasingly rely on the effective integration of multi-omics-based technologies to create emerging panomics (a.k.a., integrative omics, pan-omics, multiomics)-based strategies. This review summarizes a series of successful studies regarding the application of integrative omics-based methods in natural product target discovery. The advantages and disadvantages of each technique are discussed, with a particular focus on the systematic integration of multi-omics strategies. Further, emerging micro-scale single-cell-based techniques are introduced, especially to deal with minute natural product samples.

7.
Front Oncol ; 11: 687120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34109132

RESUMO

Despite the dramatic advances in cancer research in the past few years, effective therapeutic strategies are urgently needed. Endothelial cell-specific molecule 1 (ESM-1), a soluble dermatan sulfate proteoglycan, also known as endocan, serves as a diagnostic and prognostic indicator due to its aberrant expression under pathological conditions, including cancer, sepsis, kidney diseases, and cardiovascular disease. Significantly, ESM-1 can promote cancer progression and metastasis through the regulation of tumor cell proliferation, migration, invasion, and drug resistant. In addition, ESM-1 is involved in the tumor microenvironment, containing inflammation, angiogenesis, and lymph angiogenesis. This article reviews the molecular and biological characteristics of ESM-1 in cancer, the underlying mechanisms, the currently clinical and pre-clinical applications, and potential therapeutic strategies. Herein, we propose that ESM-1 is a new therapeutic target for cancer therapy.

8.
J Inflamm Res ; 14: 2389-2401, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163207

RESUMO

Background: Zc3h12d is a negative regulator which plays a crucial role in immune modulation. However, the role of zc3h12d in lung adenocarcinoma (LUAD) remains unclear. We aim to explore the prognostic of zc3h12d and investigate the relationship between zc3h12d expression and immune infiltration in LUAD. Methods: TIMER site was used to analyze the expression of zc3h12d in LUAD. The zc3h12d protein levels in patient tissue samples were detected by immunohistochemistry staining assays. Meanwhile, based on UALCAN database and samples' data from our cohort, we explored the relationship of clinicopathological features and zc3h12d expression to determine the clinical effect of zc3h12d in LUAD. Several databases including GEPIA, Kaplan-Meier plotter and our samples' data were used to explore the prognostic value of zc3h12d in LUAD. Cox regression analysis was established to further evaluate the prognostic value of zc3h12d in LUAD. In addition, zc3h12d promoter methylation was analyzed by UALCAN database. Genetic alteration analysis was observed in the cBioPortal web. GO and KEGG analyses were conducted to elucidate the underlying mechanisms. Finally, the correlation between zc3h12d and tumor-infiltrating immune cells in LUAD was investigated by TIMER database. The B cells level was investigated by flow cytometry analysis of peripheral blood from our LUAD cohort. Results: Zc3h12d expression was significantly higher in LUAD, compared with adjacent normal tissues. The clinical data from the UALCAN database demonstrated that zc3h12d expression was closely related with cancer stage and nodal metastasis. However, patient sample detection revealed that zc3h12d expression was closely related to pathological N (p = 0.0431) and grade (p = 0.004). Moreover, low zc3h12d expression was associated with poorer overall survival in LUAD. We analyzed the methylation level of zc3h12d in LUAD and found that the methylation levels of zc3h12d promoter in LUAD were significantly reduced. In addition, zc3h12d genetic alterations, including deep deletion, could be found in LUAD. GO and KEGG pathway analysis results indicated that zc3h12d has a certain value in immune infiltration. We investigated the expression of zc3h12d in tumor-immune interactions. It was found that zc3h12d might be associated with the immune infiltration and markers of infiltrating immune cells of LUAD. The results of patient sample detection confirmed that B cells level was significantly lower in the patients with low zc3h12d expression than those in the patients with high zc3h12d expression. Conclusion: zc3h12d might be considered as a potential biomarker for determining prognosis and immune-related therapeutic target in LUAD.

9.
Front Pharmacol ; 12: 675368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163360

RESUMO

Primary plant metabolites can be used for artificial preparation of natural deep eutectic solvents (NADESs), which have strong dissolving capacity, good biocompatibility, and biodegradability. In this study, for the first time, we verified that NADESs were present in Coptidis Rhizoma extract and systematically investigated its effects and mechanisms on the pharmacokinetics of oral berberine hydrochloride (BBR), a co-existing bioactive constituent. First, three LC-MS/MS based methods were established and fully validated to determine the levels of 11 primary metabolites in Coptidis Rhizoma extract. According to the weight ratio of four major primary metabolites in the Coptidis Rhizoma extract, a stable "endogenous" NADES was prepared using the heating method by the addition of 350 µl of water to 1,307.8 mg of the mixture of malic acid (490.5 mg), glucose (280.6 mg), sucrose (517.7 mg), and choline chloride (19.0 mg). The prepared NADES showed significant acute toxicity in mice and cytotoxicity in MDCK-MDR1 cells. However, after being diluted 10 times or 100 times, the NADES had no significant acute toxicity or cytotoxicity, respectively. The dilutions of the NADES significantly increased the water solubility of BBR, reduced its efflux in gut sacs and MDCK-MDR1 cell monolayer, and improved its metabolic stability in intestinal S9. In addition, the NADES dilutions reversibly opened the tight junctions between the enterocytes in the gut sacs. Moreover, the NADES dilutions significantly improved the exposure levels of BBR in the portal vein and livers of mice that were administered oral BBR. Malic acid was identified as a major component in the NADES in terms of solubility, acute toxicity, cytotoxicity, and pharmacokinetic-improving effects on oral BBR. In conclusion, the primary metabolites of Coptidis Rhizoma extract could form "endogenous" NADES, and its dilutions improve the pharmacokinetics of oral BBR. This study demonstrates the synergistic interaction of the constituents of Coptidis Rhizoma extract and the potential use of the NADES dilutions in oral BBR delivery.

10.
Acta Pharmacol Sin ; 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183756

RESUMO

Jingyin granules, a marketed antiviral herbal medicine, have been recommended for treating H1N1 influenza A virus infection and Coronavirus disease 2019 (COVID-19) in China. To fight viral diseases in a more efficient way, Jingyin granules are frequently co-administered in clinical settings with a variety of therapeutic agents, including antiviral drugs, anti-inflammatory drugs, and other Western medicines. However, it is unclear whether Jingyin granules modulate the pharmacokinetics of Western drugs or trigger clinically significant herb-drug interactions. This study aims to assess the inhibitory potency of the herbal extract of Jingyin granules (HEJG) against human drug-metabolizing enzymes and to clarify whether HEJG can modulate the pharmacokinetic profiles of Western drug(s) in vivo. The results clearly demonstrated that HEJG dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1; this herbal medicine also time- and NADPH-dependently inhibited human CYP2C19 and CYP3A. In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir (a CYP3A-substrate drug) by 2.43-fold and strongly prolonged its half-life by 1.91-fold when HEJG (3 g/kg) was co-administered with lopinavir to rats. Further investigation revealed licochalcone A, licochalcone B, licochalcone C and echinatin in Radix Glycyrrhizae, as well as quercetin and kaempferol in Folium Llicis Purpureae, to be time-dependent CYP3A inhibitors. Collectively, our findings reveal that HEJG modulates the pharmacokinetics of CYP substrate-drug(s) by inactivating CYP3A, providing key information for both clinicians and patients to use herb-drug combinations for antiviral therapy in a scientific and reasonable way.

11.
Front Pharmacol ; 12: 692574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025443

RESUMO

Proteolysis targeting chimeric (PROTAC) technology is an effective endogenous protein degradation tool developed in recent years that can ubiquitinate the target proteins through the ubiquitin-proteasome system (UPS) to achieve an effect on tumor growth. A number of literature studies on PROTAC technology have proved an insight into the feasibility of PROTAC technology to degrade target proteins. Additionally, the first oral PROTACs (ARV-110 and ARV-471) have shown encouraging results in clinical trials for prostate and breast cancer treatment, which inspires a greater enthusiasm for PROTAC research. Here we focus on the structures and mechanisms of PROTACs and describe several classes of effective PROTAC degraders based on E3 ligases.

12.
Acta Pharmacol Sin ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875797

RESUMO

The excess deposition of underlying extracellular matrix (ECM) in adipose tissue is defined as adipose tissue fibrosis that is a major contributor to metabolic disorder such as obesity and type 2 diabetes. Anti-fibrosis therapy has received much attention in the treatment of metabolic disorders. Orosomucoid (ORM) is an acute-phase protein mainly produced by liver, which is also an adipokine. In this study, we investigated the effects of ORM on adipose tissue fibrosis and the potential mechanisms. We showed that ORM1-deficient mice exhibited an obese phenotype, manifested by excessive collagen deposition in adipose tissues and elevated expression of ECM regulators such as metalloproteinases (MMP-2, MMP-13, MMP-14) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3). Administration of exogenous ORM (50 mg· kg-1· d-1, ip) for 7 consecutive days in high-fat diet (HFD)-fed mice and leptin receptor (LepR)-deficient db/db mice attenuated these abnormal expressions. Meanwhile, ORM administration stimulated AMP-activated protein kinase (AMPK) phosphorylation and decreased transforming growth factor-ß1 (TGF-ß1) level in adipose tissues of the mice. In TGF-ß1-treated 3T3-L1 fibroblasts, ORM (10 µg/mL) improved the impaired expression profiles of fibrosis-related genes, whereas a selective AMPK inhibitor dorsomorphin (1 µmol/mL) abolished these effects. Together, our results suggest that ORM exerts a direct anti-fibrosis effect in adipose tissue via AMPK activation. ORM is expected to become a novel target for the treatment of adipose tissue fibrosis.

13.
Chin J Nat Med ; 19(4): 305-320, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33875170

RESUMO

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Administração Oral , Alcaloides/análise , Animais , COVID-19 , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Camundongos , SARS-CoV-2 , Saponinas/análise , Triterpenos/análise
14.
Autoimmunity ; 54(2): 104-113, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33719773

RESUMO

BACKGROUND: Bronchopneumonia is a disease of the respiratory tract. It leads to other complications and endangers life and health. Long non-coding RNA (lncRNA) participates in the occurrence and development of bronchopneumonia. Nuclear paraspeckle assembly transcript 1 (NEAT1) plays a key role in inflammatory diseases, but the function of NEAT1 in bronchopneumonia remains unclear. METHODS: RT-qPCR and Western blotting were performed to determine genes and proteins expressions. MTT was applied to test cell viability. Cell apoptosis was detected by flow cytometry. RIP was used to investigate the correlation between NEAT1 and miR-155-5p. The interaction between miR-155-5p and NEAT1 or MyD88 was evaluated by the dual-luciferase reporter gene. RESULTS: NEAT1 and MyD88 were upregulated in BEAS-2B cells by LPS, while miR-155-5p was downregulated. Knockdown of NEAT1 inhibited LPS-induced BEAS-2B cells growth inhibition by inhibiting the apoptosis. In addition, NEAT1 silencing suppressed LPS-induced inflammatory responses in BEAS-2B cells via suppression of TNF-α, IL-1ß, IL-6, and IL-18. Meanwhile, NEAT1 is directly bound to miR-155-5p to regulate MyD88/NF-κB axis, and overexpression of miR-155-5p increased cell proliferation and suppressed inflammatory factors expression levels and cell apoptosis. Furthermore, sh-NEAT1-induced inhibition of BEAS-2B cells injury was partially reversed by miR-155-5p inhibitor or MyD88 overexpression. CONCLUSION: NEAT1 silencing suppressed LPS-induced BEAS-2B cells injury and inflammation by the mediation of miR-155-5p/MyD88/NF-κB axis. Thus, our study might shed new light on exploring the new strategies for the treatment of bronchopneumonia.

15.
Surg Laparosc Endosc Percutan Tech ; 31(5): 550-553, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33734209

RESUMO

BACKGROUND: Endoscopic thyroidectomy via areola approach (ETA) has been widely used in thyroidectomy for many years as it can effectively avoid a scar in the neck. Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is newly applied and has gained popularity quickly. This study is to compare the safety and effectiveness of TOETVA and ETA. MATERIALS AND METHODS: A total of 95 patients who underwent TOETVA or ETA with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2020. The basic information (such as gender, age), intraoperative hemorrhage, postoperative drainage volume, hospital durations, intraoperative and postoperative complications, operative time, central lymph node dissection time, total number of central lymph nodes, and number of metastatic central lymph nodes were compared. RESULTS: The operative time of the TOETVA group was significantly longer than the ETA group (148.11±19.78 vs. 135.90±12.77 min, P<0.05). However, the result was opposite when central lymph node dissection time was compared (10.31±2.93 vs. 12.48±3.55, P<0.05). TOETVA had an advantage on total number of central lymph nodes over ETA (7.82±3.35 vs. 5.26±2.45, P<0.05). No differences were found between the 2 groups on other data. CONCLUSION: TOETVA and ETA have the similarity on surgical safety and effectiveness. TOETVA has its advantage on central lymph node dissection and might be a reasonable alternative for ETA and open surgery in the future.


Assuntos
Neoplasias da Glândula Tireoide , Tireoidectomia , Endoscopia , Humanos , Mamilos , Estudos Retrospectivos , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia
16.
Nat Prod Bioprospect ; 11(1): 119-126, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33389669

RESUMO

Four new 3,4-secocycloartane triterpenoids, pseudolactones A-D (1-4), were isolated from the ethanol extract of the cones of Pseudol arixamabilis. Their structures were established by extensive 1D- and 2D-NMR experiments. The cones of P. arixamabilis are enriched in the ring-expanded or cleaved cycloartane triterpenoids. This work provides new insight into cycloartane triterpenoids from the cones of P. arixamabilis.

17.
Medicine (Baltimore) ; 100(1): e23879, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429749

RESUMO

BACKGROUND: Despite the availability of pharmacological intervention, patients with burn injuries experience pain during the treatment of wounds. Supplementary rehabilitation nursing intervention are required to enhance the wellbeing of patients sustaining injuries from burns. The present study aims to conduct a systematic exploration of the impact of rehabilitation nursing intervention on the wellbeing in patients sustaining burn injuries. METHODS: The electronic databases listed below will be searched systematically: PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure, and WanFang database. All the databases will be searched from their inauguration to November 2020. There will be no language constraints. Independent undertaking by 2 authors will select studies, extract data from selected studies, and assess the quality of the included studies. All disagreements will be resolved through discussion, or by consulting a third independent author. This study will make use of RevMan 5.3 software to perform statistical analysis. RESULTS: The present protocol summarizes high-quality evidence to assess the impact of rehabilitation nursing intervention on the wellbeing of patients sustaining burn injuries. CONCLUSION: The results of the present protocol has the potential to present evidence to assess whether rehabilitation nursing intervention can enhance the wellbeing of patients sustaining burn injuries. REGISTRATION NUMBER: November 17, 2020.osf.io/t6b8c/. (https://osf.io/t6b8c/).


Assuntos
Queimaduras/enfermagem , Protocolos Clínicos , Qualidade de Vida/psicologia , Enfermagem em Reabilitação/normas , Queimaduras/psicologia , Humanos , Metanálise como Assunto , Enfermagem em Reabilitação/métodos , Revisões Sistemáticas como Assunto
18.
Food Chem Toxicol ; 149: 111998, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33476691

RESUMO

Corona Virus Disease 2019 (COVID-19) has spread all over the world and brings significantly negative effects on human health. To fight against COVID-19 in a more efficient way, drug-drug or drug-herb combinations are frequently used in clinical settings. The concomitant use of multiple medications may trigger clinically relevant drug/herb-drug interactions. This study aims to assay the inhibitory potentials of Qingfei Paidu decoction (QPD, a Chinese medicine compound formula recommended for combating COVID-19 in China) against human drug-metabolizing enzymes and to assess the pharmacokinetic interactions in vivo. The results demonstrated that QPD dose-dependently inhibited CYPs1A, 2A6, 2C8, 2C9, 2C19, 2D6 and 2E1 but inhibited CYP3A in a time- and NADPH-dependent manner. In vivo test showed that QPD prolonged the half-life of lopinavir (a CYP3A substrate-drug) by 1.40-fold and increased the AUC of lopinavir by 2.04-fold, when QPD (6 g/kg) was co-administrated with lopinavir (160 mg/kg) to rats. Further investigation revealed that Fructus Aurantii Immaturus (Zhishi) in QPD caused significant loss of CYP3A activity in NADPH-generating system. Collectively, our findings revealed that QPD potently inactivated CYP3A and significantly modulated the pharmacokinetics of CYP3A substrate-drugs, which would be very helpful for the patients and clinicians to avoid potential drug-interaction risks in COVID-19 treatment.


Assuntos
COVID-19/tratamento farmacológico , Citocromo P-450 CYP3A/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Interações Ervas-Drogas , Animais , Área Sob a Curva , China , Medicamentos de Ervas Chinesas/uso terapêutico , Lopinavir/farmacocinética , Masculino , Microssomos Hepáticos , NADP/metabolismo , Fitoterapia , Ratos Sprague-Dawley , SARS-CoV-2
19.
Nat Prod Rep ; 38(1): 7-17, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32776055

RESUMO

Covering: up to 2020Treatment resistance and drug-induced refractory malignancies pose significant challenges for current chemotherapy drugs. There have been increasing research efforts aimed at developing novel chemotherapeutics, especially from natural products and related derivatives. Natural cytotoxic peptides, an emerging source of chemotherapeutics, have exhibited the advantage of overcoming drug resistance and displayed broad-spectrum antitumor activities in the clinic. This highlight examines the increasingly popular cytotoxic peptides from isolated natural products. In-depth review of several peptides provides examples for how this novel strategy can lead to the improved anti-tumor effects. The mechanisms and current application of representative natural cytotoxic peptides (NCPs) have also been discussed, with a particular focus on future directions for interdisciplinary research.

20.
Acta Pharmacol Sin ; 42(9): 1461-1471, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33268823

RESUMO

Endoplasmic reticulum (ER) homeostasis is regulated by ER-resident E3 ubiquitin ligase Hrd1, which has been implicated in inflammatory bowel disease (IBD). Ginsenoside Rb1 (GRb1) is the major ginsenoside in ginseng with multiple pharmacological activities. In this study we investigated the role of Hrd1 in IBD and its regulation by GRb1. Two mouse colitis models were established to mimic human IBD: drinking water containing dextran sodium sulfate (DSS) as well as intra-colonic infusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Colitis mice were treated with GRb1 (20, 40 mg·kg-1·d-1, ig) or a positive control drug sulfasalazine (500 mg·kg-1·d-1, ig) for 7 days. The model mice showed typical colitis symptoms and pathological changes in colon tissue. In addition to significant inflammatory responses and cell apoptosis in colon tissue, colon epithelial expression of Hrd1 was significantly decreased, the expression of ER stress markers GRP78, PERK, CHOP, and caspase 12 was increased, and the expression of Fas was increased (Fas was removed by Hrd1-induced ubiquitination). These changes were partially, or completely, reversed by GRb1 administration, whereas injection of Hrd1 inhibitor LS102 (50 mg·kg-1· d-1, ip, for 6 days) exacerbated colitis symptoms in colitis mice. GRb1 administration not only normalized Hrd1 expression at both the mRNA and protein levels, but also alleviated the ER stress response, Fas-related apoptosis, and other colitis symptoms. In intestinal cell line IEC-6, the expression of Hrd1 was significantly decreased by LPS treatment, but was normalized by GRb1 (200 µM). GRb1 alleviated LPS-induced ER stress and cell apoptosis in IEC-6 cells, and GRb1 action was inhibited by knockdown of Hrd1 using small interfering RNA. In summary, these results reveal a pathological role of Hrd1 in colitis, and provide a novel insight into alternative treatment of colitis using GRb1 activating Hrd1 signaling pathway.

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