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1.
J Ethnopharmacol ; 330: 118102, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38561057

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoqinglong Decotion (XQLD) is a commonly used Chinese herbal formula in clinical practice, especially for allergic diseases such as asthma. However, its intrinsic mechanism for the treatment of neutrophilic asthma (NA) remains unclear. AIM OF THE STUDY: The aim of this study was to evaluate the efficacy and potential mechanisms of XQLD on NA using network pharmacology and in vivo experiments. MATERIALS AND METHODS: First, the active compounds, potential targets and mechanisms of XQLD against NA were initially elucidated by network pharmacology. Then, OVA/CFA-induced NA mice were treated with XQLD to assess its efficacy. Proteins were then analyzed and quantified using a Tandem Mass Tags approach for differentially expressed proteins (DEPs) to further reveal the mechanisms of NA treatment by XQLD. Finally, the hub genes, critical DEPs and potential pathways were validated. RESULTS: 176 active compounds and 180 targets against NA were identified in XQLD. Protein-protein interaction (PPI) network revealed CXCL10, CX3CR1, TLR7, NCF1 and FABP4 as hub genes. In vivo experiments showed that XQLD attenuated inflammatory infiltrates, airway mucus secretion and remodeling in the lungs of NA mice. Moreover, XQLD significantly alleviated airway neutrophil inflammation in NA mice by decreasing the expression of IL-8, MPO and NE. XQLD also reduced the levels of CXCL10, CX3CR1, TLR7, NCF1 and FABP4, which are closely associated with neutrophil inflammation. Proteomics analysis identified 28 overlapping DEPs in the control, NA and XQLD groups, and we found that XQLD inhibited ferroptosis signal pathway (elevated GPX4 and decreased ASCL3) as well as the expression of ARG1, MMP12 and SPP1, while activating the Rap1 signaling pathway. CONCLUSION: This study revealed that inhibition of ARG1, MMP12 and SPP1 expression as well as ferroptosis pathways, and activation of the Rap1 signaling pathway contribute to the therapeutic effect of XQLD on NA.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Farmacologia em Rede , Proteômica , Animais , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Mapas de Interação de Proteínas , Feminino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Camundongos Endogâmicos BALB C , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Antiasmáticos/farmacologia , Modelos Animais de Doenças , Ovalbumina , Masculino
2.
Front Immunol ; 15: 1299484, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380329

RESUMO

Introduction: Peanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models. Methods: Compounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200µg or 400µg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE + B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP. Results: XPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p <0.01), and plasma histamine levels and protected the mice against peanut-allergic reactions in both early and late treatment experiments (p < 0.05, n=9). XPP showed a strong protective effect even 5 weeks after discontinuing the treatment. XPP significantly reduced the IL-4 level without affecting IgG or IgA and IFN-γ production. Flow cytometry data showed that XPP reduced peripheral and bone marrow IgE + B cells compared to the untreated group. XPP increased IL-4 promoter methylation. RNA-Seq and RT-PCR experiments revealed that XPP regulated the gene expression of CCND1, DUSP4, SDC1, ETS1, PTPRC, and IL6R, which are related to plasma cell IgE production. All safety testing results were in the normal range. Conclusions: XPP successfully protected peanut-allergic mice against peanut anaphylaxis by suppressing IgE production. XPP suppresses murine IgE-producing B cell numbers and inhibits IgE production and associated genes in human plasma cells. XPP may be a potential therapy for IgE-mediated food allergy.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Hipersensibilidade a Amendoim , Camundongos , Humanos , Animais , Hipersensibilidade a Amendoim/terapia , Anafilaxia/prevenção & controle , Histamina , Interleucina-4 , Medula Óssea , Camundongos Endogâmicos C3H , Imunoglobulina E , Água
3.
Age Ageing ; 53(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38251736

RESUMO

BACKGROUND: Fragmentation of services increases health and social care burden as people live longer with higher prevalence of diseases, frailty and dependency. Local evidence for implementing person-centred integrated care is urgently needed to advance practice and policies to achieve healthy ageing. OBJECTIVE: To test the feasibility and impact of World Health Organization's (WHO) Integrated Care for Older People (ICOPE) approach in China. DESIGN: A randomised controlled trial examining the feasibility of implementing ICOPE approach, evaluating its impact on health outcomes and health resource utilisation. SETTING: Primary care setting in urban and suburban communities of Chaoyang District, Beijing, China. SUBJECTS: Community-dwelling older adults screened as at-risk of functional declines and randomised into intervention (537) and control (1611) groups between September 2020 and February 2021. METHODS: A 6-month intervention program following WHO's ICOPE care pathways implemented by integrated care managers compared to standard available care. RESULTS: After 1 to 1 propensity score matching, participants in intervention and control groups (totally 938) had comparable baseline characteristics, demonstrated feasibility of implementing ICOPE with satisfaction by participants (97-99%) and providers (92-93%). All outcomes showed improvements after a 6-month intervention, while statistically significant least-squares mean differences (control-intervention) in vitality (Mini-Nutritional Assessment Short Form to measure vitality, -0.21, 95% CI, -0.40-0.02), mobility (Short Physical Performance Battery to measure mobility, -0.29, 95% CI, -0.44-0.14) and psychological health (Geriatric Depression Scale five items to measure psychological health, 0.09, 95% CI, 0.03-0.14) were observed (P < 0.05). CONCLUSIONS: It is feasible to localise and implement WHO's ICOPE approach in regions with fragmented resources such as China. Preliminary evidence supports its acceptance among key stakeholders and impact on health outcomes.


Assuntos
Sobrecarga do Cuidador , Prestação Integrada de Cuidados de Saúde , Humanos , Idoso , China/epidemiologia , Organização Mundial da Saúde , Procedimentos Clínicos
4.
Fish Shellfish Immunol ; 144: 109243, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37995892

RESUMO

Large yellow croaker (Larimichthys crocea) farm industry in China suffered from huge economic loss caused by Pseudomonas plecoglossicida infection. Due to multi-antibiotic resistance, efficient vaccines are urgent to be developed to combat this pathogen. In this study, an inactivated vaccine was developed with an aluminium adjuvant (Alum) plus ginseng stem and leaf saponins (GSLS). As a result, the relative percentage survival (RPS) against P. plecoglossicida was up to 67.8 %. Comparatively, RPS of groups that vaccinated with only inactivated vaccine and vaccine containing Alum or Montanide™ 763A as adjuvant were 21.8 %, 32.2 % and 62.1 %, respectively. Assays for total serum protein and serum lysozyme activity in group vaccinated with inactivated vaccine plus Alum + GSLS adjuvant were significantly higher than that in control group. Moreover, specific antibody in serum elicited a rapid and persistent level. According to the expression of some immune related genes, inactivated vaccine plus Alum + GSLS adjuvant induced a stronger cellular immune response which was vital to defend against P. plecoglossicida. In conclusion, our study demonstrated that the compound Alum and GSLS adjuvant is a potential adjuvant system to develop LYC vaccine.


Assuntos
Panax , Perciformes , Infecções por Pseudomonas , Saponinas , Animais , Alumínio , Vacinas de Produtos Inativados , Saponinas/farmacologia , Adjuvantes Imunológicos/farmacologia , Infecções por Pseudomonas/prevenção & controle , Infecções por Pseudomonas/veterinária , Folhas de Planta
5.
BMC Geriatr ; 23(1): 509, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612657

RESUMO

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of an individual's positive attributes. The World Health Organization (WHO) recommends a two-step approach to assess IC decline among older people. The first step involves the used of the integrated care for older people (ICOPE) screening tool to identify potential issues, and the second step involves using detailed assessments for confirmation. This study aimed to assess the diagnostic performance of the ICOPE screening tool as a simple preliminary screening to identify IC decline among community-dwelling older people, which has been rarely reported in China. METHODS: This cross-sectional study included 228 community-dwelling older individuals aged ≥ 75 (mean age, 84.0 ± 4.4 years; 131 [57.5%] females) who completed the IC evaluation according to the WHO IC assessment pathway. The diagnostic performance of the ICOPE screening tool was calculated using a 2 × 2 table and a receiver operating characteristic curve. RESULTS: The proportion of possible IC decline identified by the ICOPE screening tool was 79.4%, whereas the actual IC decline assessed by the detailed assessment was 73.2%, mainly in locomotion. The ICOPE screening tool showed sensitivity and specificity of 94.6% and 62.3%, respectively, with an overall diagnostic accuracy of 86.0%. The diagnostic effectiveness of the ICOPE screening tool was 0.91 (95% confidence interval: 0.87-0.95, p = 0.020). Except for the sensory dimension, the sensitivity of the ICOPE screening tool for diagnosing impairments in each dimension of the IC was the highest in the cognition domain (100%) and the lowest in the vitality domain (51.3%), whereas the specificity was the highest in vitality (94.7%) and the lowest in cognition (55.6%). CONCLUSIONS: The ICOPE screening tool exhibits high sensitivity and can be used as an IC screening tool in community-dwelling older people. However, further improvements are needed in the vitality dimension of the ICOPE screening tool to enhance its sensitivity in identifying individuals at risk of malnutrition.


Assuntos
Cognição , Prestação Integrada de Cuidados de Saúde , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Transversais , China/epidemiologia , Vida Independente
6.
China CDC Wkly ; 5(23): 505-510, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37404292

RESUMO

What is already known about this topic?: Inconsistent results have been reported on the association between periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and the risk of gestational diabetes mellitus (GDM) in previous research. What is added by this report?: In a prospective cohort study conducted among pregnant women in Haidian District, Beijing Municipality, it was observed that those who took MMFA demonstrated a higher likelihood of developing GDM in comparison to those who consumed FAO periconceptionally. Interestingly, the increased risk for GDM in pregnant women supplemented with MMFA compared to FAO was primarily due to changes in fasting plasma glucose. What are the implications for public health practice?: It is highly recommended that women prioritize the use of FAO in order to yield potential benefits in the prevention of GDM.

7.
Thorax ; 78(1): 69-75, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35483892

RESUMO

PURPOSE: To evaluate whether traditional mind-body movement therapy (TMBM) can be used as a complementary or alternative therapy for exercise-based cardiopulmonary rehabilitation (EBCR) on chronic cardiopulmonary dyspnoea. METHODS: PubMed, Embase, Scopus, Web of Science and China National Knowledge Infrastructure were searched from their inception to 2 July 2021. Randomised clinical trials evaluating the effectiveness of TMBM versus EBCR, and TMBM +EBCR versus TMBM in the treatment of chronic cardiopulmonary dyspnoea were selected. The outcomes were exercise capacity (6 min walk distance, 6MWD) and quality of life (QoL). RESULTS: Thirty-four randomised clinical trials with 2456 patients were included. For TMBM vs EBCR alone, statistically significant improvements in the 6MWD favoured the TMBM for chronic obstructive pulmonary disease (COPD) (mean difference(MD)=12.22 m; 95% CI 5.94 to 18.50; I2=56%) and heart failure (HF) patients (MD=43.65 m; 95% CI 7.91 to 79.38; I2=0%). Statistically significant improvements in QoL also favoured TMBM over EBCR for patients with HF(MD=-9.19; 95% CI -11.05 to -7.32; I2=0%) but non-significant trend for COPD (standardised mean difference (SMD)=-0.31; 95% CI -0.62 to 0.01; I2=78%). Comparisons of TMBM +EBCR versus EBCR alone revealed significant improvements in the QoL for COPD (SMD=-0.52; 95% CI -0.94 to -0.10; I2=86%) and patients with HF (MD=-2.82; 95% CI -4.99 to -0.64; I2=0%). The 6MWD results favoured the TMBM +EBCR for patients with COPD (MD=16.76 m; 95% CI 10.24 to 23.29; I2=0%), but only showed a slight trend towards additional benefits of TMBM +EBCR in the HF studies (MD=13.77 m; 95% CI -1.01 to 28.54; I2=65%) . CONCLUSIONS: TMBM has positive effects on patients' 6MWD and QoL, with similar or even better effects than EBCR. It may be beneficial to use TMBM as a supplementary or alternative strategy for EBCR in treatment plans. PROSPERO REGISTRATION NUMBER: CRD42021241181.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Terapia por Exercício/métodos , Doença Pulmonar Obstrutiva Crônica/reabilitação , Dispneia/etiologia , Dispneia/terapia , Exercício Físico , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Nat Commun ; 13(1): 7228, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434014

RESUMO

Sulfur bonds, especially trisulfide bond, have been found to ameliorate the self-assembly stability of homodimeric prodrug nanoassemblies and could trigger the sensitive reduction-responsive release of active drugs. However, the antitumor efficacy of homodimeric prodrug nanoassemblies with single reduction-responsivity may be restricted due to the heterogeneous tumor redox microenvironment. Herein, we replace the middle sulfur atom of trisulfide bond with an oxidizing tellurium atom or selenium atom to construct redox dual-responsive sulfur-tellurium-sulfur and sulfur-selenium-sulfur hybrid chalcogen bonds. The hybrid chalcogen bonds, especially the sulfur-tellurium-sulfur bond, exhibit ultrahigh dual-responsivity to both oxidation and reduction conditions, which could effectively address the heterogeneous tumor microenvironment. Moreover, the hybrid sulfur-tellurium-sulfur bond promotes the self-assembly of homodimeric prodrugs by providing strong intermolecular forces and sufficient steric hindrance. The above advantages of sulfur-tellurium-sulfur bridged homodimeric prodrug nanoassemblies result in the improved antitumor efficacy of docetaxel with satisfactory safety. The exploration of hybrid chalcogen bonds in drug delivery deepened insight into the development of prodrug-based chemotherapy to address tumor redox heterogeneity, thus enriching the design theory of prodrug-based nanomedicines.


Assuntos
Neoplasias , Pró-Fármacos , Selênio , Humanos , Pró-Fármacos/química , Microambiente Tumoral , Liberação Controlada de Fármacos , Telúrio , Oxirredução , Neoplasias/tratamento farmacológico , Enxofre
9.
Langmuir ; 38(40): 12307-12315, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36154182

RESUMO

Chemodynamic therapy (CDT) is a promising hydroxyl radical (•OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrrolidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of •OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved •OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Cobre/farmacologia , Glutationa , Humanos , Peróxido de Hidrogênio , Radical Hidroxila , Peróxidos Lipídicos/farmacologia , Neoplasias/tratamento farmacológico , Oxirredução , Peróxidos/farmacologia , Peróxidos/uso terapêutico , Povidona , Sorafenibe/farmacologia , Microambiente Tumoral
10.
Fish Shellfish Immunol ; 128: 60-66, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35843529

RESUMO

Furunculosis caused by Aeromonas salmonicida in turbot farming is increasingly leading to huge economic losses. In this study, an inactivated vaccine containing a compound adjuvant of ginseng stem leaf saponins and aluminum hydroxide gel (GSLS/Alum) was developed against A. salmonicida and evaluated on turbot. As a result, serum antibody titer in vaccinated group was significantly higher than that in control group and the relative percentage survival (RPS) was up to 75.7%. Comparatively, the RPS of groups that vaccinated with only inactivated vaccine and vaccine containing Alum adjuvant or an oil emulsion Montanide™ ISA 763A were 32.4%, 48.6% and 64.9%, respectively. Although the vaccine containing oil adjuvant elicited comparable IgM level as that containing the compound GSLS/Alum adjuvant, the latter had no obvious side effects. Moreover, the inactivated vaccine containing the compound adjuvant was more likely to induce a higher cellular immune response according to the expressions of some immune related genes. Most importantly, an excellent protection of the vaccine containing GSLS/Alum adjuvant was obtained when turbots were naturally infected under clinical condition. In summary, our study demonstrated that the formulation of GSLS and Alum is a potential compound adjuvant in turbot vaccine development.


Assuntos
Aeromonas salmonicida , Linguados , Panax , Saponinas , Adjuvantes Imunológicos/farmacologia , Compostos de Alúmen , Alumínio , Hidróxido de Alumínio , Animais , Emulsões , Imunoglobulina M , Folhas de Planta , Saponinas/farmacologia , Vacinas de Produtos Inativados
11.
Int J Nanomedicine ; 17: 617-633, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173433

RESUMO

BACKGROUND: Breast cancer is a common malignancy in women. Conventional clinical therapies for breast cancer all display moderate clinical efficacies and limitations. It is urgent to explore the novel and combined therapeutic strategies for breast cancer to meet clinical demand. METHODS: An iRGD tumor-penetrating peptide-modified nano-delivery system (denoted as iRGD-PSS@PBAE@JQ1/ORI nanoparticles) based on a marine sulfated polysaccharide was developed by codelivery of JQ1 (BET inhibitor) and oridonin (ORI, bioactive diterpenoid derived from traditional Chinese medicine herb). The iRGD-PSS@PBAE@JQ1/ORI NPs, surface modified with iRGD peptide conjugated propylene glycol alginate sodium sulfate (iRGD-PSS). The antitumor efficacy was evaluated both in vitro and in vivo. RESULTS: The prepared iRGD-PSS@PBAE@JQ1/ORI NPs effectively enhanced the tumor targeting and cellular internalization of JQ1 and ORI. Thus, JQ1 exerted the reversal effect on immune tolerance by decreasing the expression of PD-L1, while ORI displayed multiple antitumor effects, such as antiproliferation, inhibition of intracellular ROS production and inhibition of lactic acid secretion. CONCLUSION: Our data revealed that iRGD peptide could significantly improve the cellular internalization and tumor penetration of the nano-delivery system. The combination of JQ1 and ORI could exert synergistic antitumor activities. Taken together, this study provides a multifunctional nanotherapeutic system to enhance the anti-tumor efficiency against breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Sistemas de Liberação de Fármacos por Nanopartículas , Oligopeptídeos/uso terapêutico , Polissacarídeos , Sulfatos
12.
J Investig Med ; 70(4): 907-913, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35074856

RESUMO

Calcific aortic valve disease (CAVD) is an active pathological process mediated by abnormal activation and transdifferentiation of valvular interstitial cells (VICs). The present study aims to investigate the function and underlying mechanism of the basic fibroblast growth factor (BFGF) on osteogenic differentiation of VICs. Porcine VICs cultured with osteogenic induction medium are supplemented with or without BFGF. Morphology of VICs is identified by fluorescein isothiocyanate-labeled phalloidin, the cell viability is assessed by the cell counting kit-8 method, and protein and mRNA expression level of osteogenic differentiation markers, including Runx2, osteopontin, and Sp7, are verified by western blot analysis and quantitative real-time PCR, respectively. RNA sequencing is used to identify changes in gene profiles. Alizarin Red S staining is used to measure calcium deposition. The results demonstrate that the content of calcium deposition and the expression level of osteogenic markers are downregulated by supplementing BFGF. Notch1 signaling pathway is extracted as a candidate target after bioinformatics analysis by RNA sequencing. The transfection of si-Notch1 abolishes the calcification inhibitory effect of BFGF. Taken together, our findings shed the light on the mechanism and potential therapeutics of BFGF for CAVD.


Assuntos
Estenose da Valva Aórtica , Calcinose , Animais , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Calcinose/genética , Calcinose/metabolismo , Calcinose/patologia , Cálcio/metabolismo , Células Cultivadas , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Osteogênese/genética , Receptor Notch1/metabolismo , Suínos
13.
Front Microbiol ; 13: 1095068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36817101

RESUMO

Background: Base mutations increase the contagiousness and transmissibility of the Delta and Lambda strains and lead to the severity of the COVID-19 pandemic. Molecular docking and molecular dynamics (MD) simulations are frequently used for drug discovery and relocation. Small molecular compounds from Chinese herbs have an inhibitory effect on the virus. Therefore, this study used computational simulations to investigate the effects of small molecular compounds on the spike (S) protein and the binding between them and angiotensin-converting enzyme 2 (ACE2) receptors. Methods: In this study, molecular docking, MD simulation, and protein-protein analysis were used to explore the medicinal target inhibition of Chinese herbal medicinal plant chemicals on SARS-CoV-2. 12,978 phytochemicals were screened against S proteins of SARS-CoV-2 Lambda and Delta mutants. Results: Molecular docking showed that 65.61% and 65.28% of the compounds had the relatively stable binding ability to the S protein of Lambda and Delta mutants (docking score ≤ -6). The top five compounds with binding energy with Lambda and Delta mutants were clematichinenoside AR2 (-9.7), atratoglaucoside,b (-9.5), physalin b (-9.5), atratoglaucoside, a (-9.4), Ochnaflavone (-9.3) and neo-przewaquinone a (-10), Wikstrosin (-9.7), xilingsaponin A (-9.6), ardisianoside G (-9.6), and 23-epi-26-deoxyactein (-9.6), respectively. Four compounds (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) could interact with S protein mutation sites of Lambda and Delta mutants, respectively, and MD simulation results showed that four plant chemicals and spike protein have good energy stable complex formation ability. In addition, protein-protein docking was carried out to evaluate the changes in ACE2 binding ability caused by the formation of four plant chemicals and S protein complexes. The analysis showed that the binding of four plant chemicals to the S protein could reduce the stability of the binding to ACE2, thereby reducing the replication ability of the virus. Conclusion: To sum up, the study concluded that four phytochemicals (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) had significant effects on the binding sites of the SARS-CoV-2 S protein. This study needs further in vitro and in vivo experimental validation of these major phytochemicals to assess their potential anti-SARS-CoV-2. Graphical abstract.

14.
Anat Rec (Hoboken) ; 305(7): 1672-1681, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34708578

RESUMO

Effective therapeutics are not available for acute lung injury (ALI) and acute respiratory distress syndrome. Modified Xiaoqinglong decoction (M-XQL) is reported to effectively treat pneumonia, but the underlying mechanisms are unclear. In this study, the therapeutic effect and mechanism of M-XQL were examined using a lipopolysaccharide (LPS)-induced ALI mouse model. The effects of M-XQL on lung injury, inflammatory responses, and cell apoptosis were analyzed. Additionally, high-throughput sequencing was performed to evaluate the therapeutic mechanism of M-XQL. Pretreatment with M-XQL significantly and dose-dependently mitigated the pathological changes and upregulation of pulmonary, nitric oxide content and cell apoptosis and serum tumor necrosis factor-alpha contents in the LPS-induced ALI mouse model. RNA sequencing analysis revealed that the expression of several arachidonic acid metabolism-associated genes in the LPS + high-dose M-XQL group differed from that in the LPS group. In particular, the Cbr2, Cyp4f18, and Cyp2e1 levels were upregulated, whereas the Alox12, Ptges, and Ptges2 levels were downregulated in the LPS + high-dose M-XQL group. These results suggest that M-XQL exerts therapeutic effects in ALI mice by regulating arachidonic acid metabolism and exerting anti-apoptotic and anti-inflammatory effects. Thus, M-XQL is a potential agent for the clinical treatment of ALI.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Araquidônico/metabolismo , Ácido Araquidônico/farmacologia , Ácido Araquidônico/uso terapêutico , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Camundongos
15.
Curr Drug Metab ; 22(13): 1017-1034, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34825869

RESUMO

The N-3 polyunsaturated fatty acids (PUFAs) have a wide range of health benefits, including antiinflammatory effects, improvements in lipids metabolism and promoting insulin secretion, as well as reduction of cancer risk. Numerous studies support that N-3 PUFAs have the potentials to improve many metabolic diseases, such as diabetes, nonalcoholic fatty liver disease and obesity, which are attributable to N-3 PUFAs mediated enhancement of insulin secretion by pancreatic ß-cells and improvements in insulin sensitivity and metabolic disorders in peripheral insulin-sensitive tissues such as liver, muscles, and adipose tissue. In this review, we summarized the up-to-date clinical and basic studies on the regulatory effects and molecular mechanisms of N-3 PUFAs mediated benefits on pancreatic ß-cells, adipose tissue, liver, and muscles in the context of glucose and/or lipid metabolic disorders. We also discussed the potential factors involved in the inconsistent results from different clinical researches of N-3 PUFAs.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Células Secretoras de Insulina , Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas , Animais , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Humanos , Insulina/biossíntese , Insulina/metabolismo , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Doenças Metabólicas/classificação , Doenças Metabólicas/metabolismo , Doenças Metabólicas/prevenção & controle
16.
China CDC Wkly ; 3(37): 783-787, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34594990

RESUMO

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Neural tube defects can be effectively prevented by folic acid supplementation. However, compliance with the recommendations for supplementation is still low in China. WHAT IS ADDED BY THIS REPORT?: This study investigated the rate of correct use of folic acid supplementation and its risk factors among pregnant women in Beijing. Women who took folic acid correctly only comprised less than 50% of the total, possibly due to unexpected pregnancy. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Given the low rate in Beijing, an area with high health literacy, the rate may also be low in other areas in China. Regulations for mandatory fortification of food with folic acid are recommended in China.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34589129

RESUMO

OBJECTIVE: Colon cancer (CC) shows a gradual increasing incidence in recent years, and chemotherapy is a frequently adopted treatment for patients with middle or advanced colon cancer (ACC), but it lacks prognostic markers after CC. METHODS: The changes of lncRNA CASC9 in 58 patients with CC were determined using a real-time quantitative PCR (qRT-PCR) assay before and after chemotherapy, and the correlation of serum lncRNA CASC9 with efficacy of FOLFOX4 regimen (oxaliplatin + calcium folinate + fluorouracil) was analyzed. The patients were followed up to understand the association of lncRNA CASC9 with overall survival (OS) and progression-free survival (PFS). RESULTS: Patients with CC showed notably higher lncRNA CASC9 expression than controls, and lncRNA CASC9 presented an association with the clinical stage of the patients. In addition, lncRNA CASC9 demonstrated a clinical value in predicting efficacy on patients and acted as one independent prognostic factor for PFS in patients with ACC. CONCLUSIONS: With increased expression of serum lncRNA CASC9, patients with ACC suffered an unfavorable chemotherapy effect. In addition, serum lncRNA CASC9 is a promising sensitive indicator for prediction of ACC and is related to the clinical efficacy and prognosis of patients.

18.
Cell Metab ; 33(7): 1433-1448.e5, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34129812

RESUMO

Knowledge of how leptin receptor (LepR) neurons of the mediobasal hypothalamus (MBH) access circulating leptin is still rudimentary. Employing intravital microscopy, we found that almost half of the blood-vessel-enwrapping pericytes in the MBH express LepR. Selective disruption of pericytic LepR led to increased food intake, increased fat mass, and loss of leptin-dependent signaling in nearby LepR neurons. When delivered intravenously, fluorescently tagged leptin accumulated at hypothalamic LepR pericytes, which was attenuated upon pericyte-specific LepR loss. Because a paracellular tracer was also preferentially retained at LepR pericytes, we pharmacologically targeted regulators of inter-endothelial junction tightness and found that they affect LepR neuronal signaling and food intake. Optical imaging in MBH slices revealed a long-lasting, tonic calcium increase in LepR pericytes in response to leptin, suggesting pericytic contraction and vessel constriction. Together, our data indicate that LepR pericytes facilitate localized, paracellular blood-brain barrier leaks, enabling MBH LepR neurons to access circulating leptin.


Assuntos
Regulação do Apetite/genética , Hipotálamo/metabolismo , Leptina/farmacologia , Pericitos/fisiologia , Receptores para Leptina/fisiologia , Animais , Comportamento Alimentar/fisiologia , Feminino , Hipotálamo/citologia , Hipotálamo/efeitos dos fármacos , Leptina/sangue , Leptina/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
19.
Altern Ther Health Med ; 27(5): 58-60, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34144528

RESUMO

OBJECTIVE: The aim of this study was to explore the relationship between psychological distress and disordered eating attitudes. METHODS: The study design was cross-sectional study. The 12-item General Health Questionnaire (ghq-12) and Eating Attitude Test-26 (eat-26) were used to measure psychological distress and disordered eating attitudes, respectively. The data were analyzed using spss version 20.0 Software (spss Inc, ii, Chicago, il, usa). Description statistics were used for height, weight, bmi), age, eat-26 scores and ghq-12 scores. Pearson's correlation analysis was performed to explore the relationship between the eat-26 scores and the ghq-12 scores. RESULTS: The overall prevalence of disordered eating attitudes was 4.6%. The mean ghq-12 score in subjects with disordered eating attitude was higher than that of the control group (P < .05) in both the male and female groups. CONCLUSION: Our study suggested that psychological distress is associated with disordered eating attitudes. Bmi and gender turned out to not be correlated with disordered eating attitude. The findings of this study revealed that university students who have psychological distress also have a tendency toward disordered eating attitudes.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Angústia Psicológica , Atitude , Estudos Transversais , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Masculino , Estudantes , Inquéritos e Questionários , Universidades
20.
Sci Rep ; 11(1): 11270, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34050206

RESUMO

Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association between dietary calcium, magnesium, phosphorus, and stroke incidence in Chinese adults, we collected data from the China Health and Nutrition Survey (CHNS) from 2004 to 2011, including 6411 participants aged 45-79 years and free of stroke at baseline. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. The stroke incident was identified based on the validated self-report. Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For 32,024 person-years of follow-up, 179 stroke cases were documented. After adjustment for major lifestyle and dietary risk factors, calcium intake was positively associated with reduced stroke risk, and the HR of stroke comparing extreme quartiles was 0.53 (95% CI 0.29-0.96, Ptrend = 0.03). In further stratified analyses, significant heterogeneity across sex strata was found (Pinteraction = 0.03). Dietary calcium intake among men was more inversely related to stroke, with HRs being 0.33 (95% CI 0.15-0.76, P trend = 0.02), compared to 1.24 (95% CI 0.46-3.35, Ptrend = 0.89) among women. However, no significant association between stroke and magnesium or phosphorus was revealed. Our findings suggest that higher dietary calcium intake was associated with a lower risk of stroke in Chinese adults, particularly in men.


Assuntos
Cálcio da Dieta/metabolismo , Fósforo na Dieta/metabolismo , Acidente Vascular Cerebral/metabolismo , Idoso , Povo Asiático/genética , Cálcio/metabolismo , Cálcio/farmacologia , China/epidemiologia , Dieta/estatística & dados numéricos , Suplementos Nutricionais , Feminino , Humanos , Incidência , Magnésio/metabolismo , Magnésio/farmacologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estado Nutricional , Fósforo/metabolismo , Fósforo/farmacologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Inquéritos e Questionários
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