RESUMO
Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.
Assuntos
Alginatos , Microbioma Gastrointestinal , Oligossacarídeos , Alginatos/metabolismo , Oligossacarídeos/metabolismo , Camundongos , Animais , Humanos , Colite/microbiologia , Colite/induzido quimicamente , Camundongos Endogâmicos C57BL , Ácidos Graxos Voláteis/metabolismo , Inflamação/metabolismo , Sulfato de Dextrana , Fibras na Dieta/metabolismoRESUMO
AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.
Assuntos
Medicina Baseada em Evidências , Medicina Tradicional Chinesa , Medicina Tradicional Chinesa/métodos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Asthma is a common chronic respiratory diseases, and the relationship between pulmonary ventilation function and the prognosis of patients with suspected asthma is not well understood. This study aims to explore the impact of pulmonary ventilation functions on the prognosis of patients with suspected asthma. METHODS: This retrospective observational study included patients with suspected asthma who were diagnosed and treated at the Guangdong Provincial Hospital of Traditional Chinese Medicine between August 2015 and January 2020. The primary outcome of interest was improvement in asthma symptoms, as measured by bronchial provocation test (BPT) results within one year after diagnosis. The impact of pulmonary ventilation functions on prognosis was explored by multivariable logistic regression analysis. RESULTS: Seventy-two patients were included in the study. Patients with normal (OR = 0.123, p = .004) or generally normal (OR = 0.075, p = .039) pulmonary ventilation function were more likely to achieve improvement in asthma symptoms compared with patients with mild obstruction. There were no significant differences between the improvement and non-improvement groups in baseline characteristics. CONCLUSION: These results suggest that suspected asthma patients with normal or generally normal pulmonary ventilation function are more likely to achieve improvement in asthma symptoms within one year compared to patients with mild obstruction.
Assuntos
Asma , Humanos , Asma/diagnóstico , Asma/fisiopatologia , Asma/terapia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Prognóstico , Ventilação Pulmonar/fisiologia , Testes de Provocação Brônquica/métodos , Testes de Função Respiratória , IdosoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a prevalent female endocrine condition that significantly affects women of all age groups and is characterized by metabolic dysfunction. The efficacy of existing pharmaceutical interventions for the treatment of PCOS remains inadequate. With a rich history and cultural significance spanning thousands of years, Traditional Chinese Medicine (TCM) is extensively employed for treating a variety of ailments and can serve as a supplementary therapy for managing PCOS. Multiple clinical observations and laboratory tests have unequivocally demonstrated the substantial effectiveness and safety of TCM formulae in treating PCOS, and further investigations are currently in progress. AIM OF THE STUDY: To summarize the TCM formulae commonly employed in the clinical management of PCOS, examine their therapeutic benefits, investigate their mechanism of action, active constituents, and establish the correlation between efficacy, mechanism of action, and active constituents. MATERIALS AND METHODS: We conducted a comprehensive search on PubMed, Web of Science, and China national knowledge infrastructure (CNKI) using the following keywords: "Polycystic Ovary Syndrome", "Traditional Chinese Medicine Decoctions", "Traditional Chinese Medicine formulae", "Traditional Chinese Medicine", "Clinical Observation", "Mechanism", "Treatment", "Pharmacology", and various combinations of these terms. From January 1, 2006 until October 7, 2023, (inclusive). RESULTS: This paper summarized the clinical effectiveness, mechanism of action, and active components of 8 TCM formulae for the treatment of PCOS. Our research indicates that TCM formulae can potentially treat PCOS by enhancing the levels of hyperandrogenism and other endocrine hormones, decreasing insulin resistance and hyperinsulinemia, and controlling chronic low-grade inflammation, among other modes of action. In addition, we found an association between epigenetics and TCM formulae for the treatment of PCOS. CONCLUSION: TCM formulae have specific advantages in the treatment of Polycystic Ovary Syndrome (PCOS). They achieve therapeutic benefits by targeting several pathways and connections, attracting considerable interest and playing a vital role in the treatment of PCOS. TCM formulae can be used as an adjunctive therapy for the treatment of PCOS.
Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Medicina Tradicional Chinesa , Inflamação , ChinaRESUMO
Two actinomycete strains, designated MG62T and CRLD-Y-1, were isolated from rhizosphere soil of Koelreuteria paniculata and healthy leaves of Xanthium sibiricum, respectively, in Hunan province, PR China. They could produce abundant aerial mycelia that generated rod-shaped spores with spiny surfaces. Morphological features of the two strains are typical of the genus Streptomyces. Strains MG62T and CRLD-Y-1 exhibited 99.93â% 16S rRNA gene sequence similarity. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between them were 99.99 and 100â%, respectively, suggesting that they belonged to the same species. 16S rRNA gene sequences analysis revealed that the two strains belonged to the genus Streptomyces and showed highest similarities to Streptomyces violarus NBRC 13104T (99.07-99.29â%) and Streptomyces arenae ISP 5293T (99.21-99.35â%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains MG62T and CRLD-Y-1 were closely related to S. violarus NBRC 13104T and S. arenae ISP 5293T. However, the ANI, dDDH and multilocus sequence analysis evolutionary distance values between the two strains and their relatives provide a robust basis upon which to verify strains MG62T and CRLD-Y-1 as representing a novel species. Moreover, a comprehensive comparison of phenotypic and chemotaxonomic characteristics further confirmed that the two strains were distinct from their relatives. Based on all these data above, strains MG62T and CRLD-Y-1 should represent a novel Streptomyces species, for which the name Streptomyces koelreuteriae sp. nov. is proposed. The type strain is MG62T (=JCM 34747T=MCCC 1K06175T).
Assuntos
Streptomyces , Xanthium , Ácidos Graxos/química , Análise de Sequência de DNA , Filogenia , Rizosfera , RNA Ribossômico 16S/genética , Microbiologia do Solo , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Vitamina K 2RESUMO
Regulation of tumor vessels has become one of the most common strategies for clinical anti-tumor therapy. In recent years, studies have found that the anti-tumor effect of limotherapy, which routinely inhibits tumor angiogenesis, is not ideal and may even deteriorate the tumor microenvironment, causing tumor resistance and distal metastasis and increasing the risk of tumor metastasis and recurrence. However, the proper use of anti-angiogenic drugs can promote the normalization of tumor vessels, improve the structure and function of tumor vessels, increase the number of functional vessels in the tumor, and reduce the number of ineffective vessels. It is beneficial to promote the penetration of anti-tumor drugs into the tumor, improve the microenvironment of tumor hypoxia and immunosuppression, and enhance the anti-tumor effect. Traditional Chinese medicine(TCM) has a long history of understanding the etiology and pathogenesis of tumors and has accumulated rich experience in tumor treatment, with significant clinical advantages and broad application prospects. In this study, from the perspective of bidirectional "soothing" or "blockage" regulation of tumor vessels, the commonly used molecular targets were sorted out, and the research status of anti-tumor regulation of tumor vessels by monomer-single herb-compound(herb pair) of TCM in recent years was summarized. The research on the anti-tumor effects of TCM compounds and active ingredients by regulating tumor vessels combined with other therapies was analyzed and sorted out, so as to provide ideas for the clinical application of TCM in regulating functions and anti-tumor effects of tumor vessels.
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Medicamentos de Ervas Chinesas , Neoplasias , Humanos , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Microambiente TumoralRESUMO
BACKGROUND: Upright positions, as a non-pharmacological, have been well documented in multiple studies to promote normal labor, facilitate favourable birth outcomes and positive childbirth experience. Yet, the application status of upright positions in China, and even globally, is unfavourable. Thus, we have developed the Program for Upright Positions in the Second Stage of Labor (UPSSL program) for the widespread application of upright positions. While there is limited research evidence on the areas of improvement and corresponding strategies for embedding the evidence into midwifery practice. OBJECTIVES: To explore perspectives of health care providers on improvement areas of upright positions in the second stage of labor, and to identify corresponding strategies in order to develop a management framework for successful implementation of upright positions. METHODS: A qualitative descriptive design with semi-structured interviews was conducted in the study. The participants involving 13 midwives, six obstetricians and six department managers were selected from three hospitals in Beijing, China. ATLAS.TI 8 software was utilized to manage, identify the transcript data, and the thematic analysis method guided the data analysis. RESULTS: A management framework of upright positions in the second stage of labor was developed based on our study, which included five improvement areas : (1) promoting the renewal of midwifery notions and the professional training;(2) strengthening maternal health education based on the "trinity" approach; (3) promoting multidisciplinary cooperation and refining the labor procedures in upright positions; (4) optimizing midwifery human resource allocation and formulating incentive policies; (5) encouraging partner involvement and improving the birth environment. CONCLUSIONS: The study findings could provide a comprehensive view to promote UPSSL Program to be utilized in practice. Our study also provided a way for midwives, obstetricians, and other healthcare providers to work together to facilitate high quality maternal care. IMPLICATIONS FOR PRACTICE: Our findings will be useful for nursing managers to carry out the UPSSL program through several strategies, such as strengthening the professional training for assisting labor in the upright positions, reallocating midwifery human resources, and developing the childbirth education on the upright positions.
Assuntos
Segunda Fase do Trabalho de Parto , Tocologia , Gravidez , Feminino , Humanos , Parto Obstétrico/métodos , Tocologia/métodos , Pesquisa Qualitativa , FamíliaRESUMO
BACKGROUND: Hypertension has seriously affected a large part of the adult and elderly population. The complications caused by hypertension are important risk factors for cardiovascular disease accidents. Capsaicin, a pungent component of chili pepper has been revealed to improve hypertension. However, its potential mechanism in improving hypertension remains to be explored. PURPOSE: In the present study, we aimed to investigate whether capsaicin could attenuate the SIRT1/NF-κB/MAPKs pathway in the paraventricular nucleus of hypothalamus (PVN). METHODS: We used spontaneous hypertensive rats (SHRs) as animal model rats. Micro osmotic pump was used to give capsaicin through PVN for 28 days, starting from age12-week-old. RESULTS: The results showed that capsaicin significantly reduced blood pressure from the 16th day of infusion onward. At the end of the experimental period, we measured cardiac hypertrophy index and the heart rate (HR), and the results showed that the cardiac hypertrophy and heart rate of rats was significantly improved upon capsaicin chronic infusion. Norepinephrine (NE) and epinephrine (EPI) in plasma of SHRs treated with capsaicin were also decreased. Additionally, capsaicin increased the protein expression and number of positive cells of SIRT1 and the 67-kDa isoform of glutamate decarboxylase (GAD67), decreased the production of reactive oxygen species (ROS), number of positive cells of NOX2, those of Angiotensin Converting Enzyme (ACE) and p-IKKß, tyrosine hydroxylase (TH), the gene expression levels of NOX4 and pro-inflammatory cytokines. Capsaicin also decreased the relative protein expressions of protein in MAPKs pathway. CONCLUSION: Current data indicated that capsaicin within the PVN improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the PVN of SHRs, supporting its potential as candidate drug for preventing and improving hypertension.
Assuntos
Hipertensão , NF-kappa B , Idoso , Humanos , Ratos , Animais , NF-kappa B/metabolismo , Núcleo Hipotalâmico Paraventricular , Capsaicina/farmacologia , Sirtuína 1/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Ratos Endogâmicos SHRRESUMO
Cancer metastasis remains the most common cause of death in breast cancer patients. Tumor-associated macrophages (TAMs) are a novel therapeutic target for the treatment of metastatic breast cancer. Despite the good anti-cancer activity of garcinone E (GE), there are no reports on its therapeutic effects on breast cancer metastasis. The objective of this study was to examine the anti-cancer effects of GE on metastatic breast cancer. RAW 264.7 and THP-1 cells were polarized to M2 macrophages by IL-4/IL-13 in vitro. A 4T1 mouse breast cancer model and the tail vein breast cancer metastasis model were used to explore the effect of GE on breast cancer growth and metastasis in vivo. In vitro studies showed that GE dose-dependently suppressed IL-4 + IL-13-induced expression of CD206 in both RAW 264.7 cells and differentiated THP-1 macrophages. However, GE did not affect the LPS + IFN-γ-induced polarization to the M1-like macrophages in vitro. GE inhibited the expression of the M2 macrophage specific genes in RAW 264.7 cells, and simultaneously impaired M2 macrophage-induced breast cancer cell proliferation and migration, and angiogenesis. In animal studies, GE significantly suppressed tumor growth, angiogenesis, and lung metastasis in 4T1 tumor-bearing mice, without causing toxicity. In both tumor and lung tissues, the proportion of M2-like TAMs was significantly decreased while the proportion of M1-like TAMs was markedly increased by GE treatment. Mechanistically, GE inhibited phosphorylation of STAT6 in vitro and in vivo. Our results demonstrate for the first time that GE suppresses breast cancer growth and pulmonary metastasis by modulating M2-like macrophage polarization through the STAT6 signaling pathway.
Assuntos
Neoplasias da Mama , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/patologia , Macrófagos Associados a Tumor , Linhagem Celular Tumoral , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Interleucina-4/uso terapêutico , Interleucina-13/metabolismo , Interleucina-13/farmacologia , Interleucina-13/uso terapêutico , Transdução de Sinais , Fator de Transcrição STAT6/metabolismo , Fator de Transcrição STAT6/farmacologiaRESUMO
How to achieve stable co-delivery of multiple phytochemicals is a common problem. This study focuses on the development, optimization and characterization of Huanglian-HouPo extract nanoemulsion (HLHPEN), with multiple components co-delivery, to enhance the anti-ulcerative colitis (UC) effects. The formulation of HLHPEN was optimized by pseudo-ternary phase diagram combined with Box-Behnken design. The physicochemical properties of HLHPEN were characterized, and its anti-UC activity was evaluated in DSS-induced UC mice model. Based on preparation process optimization, the herbal nanoemulsion HLHPEN was obtained, with the droplet size, PDI value, encapsulation efficiency (EE) for 6 phytochemicals (berberine, epiberberine, coptisine, bamatine, magnolol and honokiol) of 65.21 ± 0.82 nm, 0.182 ± 0.016, and 90.71 ± 0.21%, respectively. The TEM morphology of HLHPEN shows the nearly spheroidal shape of particles. The optimized HLHPEN showed a brownish yellow milky single-phase and optimal physical stability at 25 °C for 90 days. HLHPEN exhibited the good particle stability and gradual release of phytochemicals in SGF and SIF, to resist the destruction of simulated stomach and small intestine environment. Importantly, the oral administration of HLHPEN significantly restored the shrunk colon tissue length and reduced body weight, ameliorated DAI value and colon histological pathology, decreased the levels of inflammatory factors in DSS-induced UC mice model. These results demonstrated that HLHPEN had a significant therapeutic effect on DSS-induced UC mice, as a potential alternative UC therapeutic agent.
Assuntos
Colite Ulcerativa , Colite , Medicamentos de Ervas Chinesas , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Colo , Compostos Fitoquímicos/efeitos adversos , Administração Oral , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colite/tratamento farmacológicoRESUMO
Background: Influenza virus causes significant morbidity and mortality with pandemic threat. Oleaceae Fructus Forsythiae is a medicinal herb. This study aimed to investigate antiviral effect of Phillyrin, a purified bioactive compound from this herb, and its reformulated preparation FS21 against influenza and its mechanism. Methods: Madin-Darby Canine Kidney (MDCK) cells were infected by one of six influenza viruses: five influenza A viruses (IAVs: three H1N1 and two H3N2) and one influenza B virus (IBV). Virus-induced cytopathic effects were observed and recorded under microscope. Viral replication and mRNA transcription were evaluated by quantitative polymerase chain reaction (qPCR) and protein expression by Western blot. Infectious virus production was assessed using TCID50 assay, and IC50 was calculated accordingly. Pretreatment and time-of-addition experiments with Phillyrin or FS21 added 1 h before or in early (0-3 h), mid (3-6 h), or late (6-9 h) stages of viral infection were performed to assess their antiviral effects. Mechanistic studies included hemagglutination and neuraminidase inhibition, viral binding and entry, endosomal acidification, and plasmid-based influenza RNA polymerase activity. Results: Phillyrin and FS21 had potent antiviral effects against all six IAV and IBV in a dose-dependent manner. Mechanistic studies showed that both suppressed influenza viral RNA polymerase with no effect on virus-mediated hemagglutination inhibition, viral binding or entry, endosomal acidification, or neuraminidase activity. Conclusions: Phillyrin and FS21 have broad and potent antiviral effects against influenza viruses with inhibition of viral RNA polymerase as the distinct antiviral mechanism.
Assuntos
Antivirais , Glucosídeos , Infecções por Orthomyxoviridae , Animais , Cães , Humanos , Antivirais/farmacologia , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Neuraminidase , Proteínas do Complexo da Replicase Viral , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/tratamento farmacológico , Glucosídeos/farmacologiaRESUMO
In the present study, a novel and green temperature-responsive deep eutectic solvent (TRDES) system was developed and applied for the simultaneous extraction and separation of different polar active phytochemicals from Schisandra chinensis (Turcz.) Baill. The TRDES, consisting of amino alcohols and phenolic compounds, was chosen as the switching medium, and an upper critical solution temperature (UCST) type switchable solvent was obtained by adding an inorganic salt solution. The switchable phase diagram was plotted based on the relationship between the phase change temperature, the concentration and the amount of sodium chloride solution. Under optimal parameters, the yields with TRDES for different polar active phytochemicals (lignanoids and polysaccharides) from the dried fruit of Schisandra chinensis (DFSC) were 1.62 â¼ 1.17-fold and 1.39-fold to those with conventional solvents. Also, the TRDES system was still effective on extraction of DFSC lignanoids and polysaccharides after four cycles of extraction. The separated polysaccharides and lignanoids both had strong antioxidant activities with IC50 values of 1.92 mg/ mL and 0.10 mg/ mL against 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), respectively. The extraction mechanism of TRDES was postulated by Density functional theory (DFT) calculations the hydrogen bonding in TRDES was the main factor to the higher extraction yield. This temperature-responsive deep eutectic solvent could be widely used for the efficient extraction and separation of multi-polar components. As a green and recyclable solvents, TRDES has great potential for the lower cost production from plants.
Assuntos
Solventes Eutéticos Profundos , Schisandra , Temperatura , Compostos Fitoquímicos , Solventes , Extratos VegetaisRESUMO
Background: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated. Methods: A pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg-1·day-1) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice. Results: Our results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis. Conclusion: These results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials.
Assuntos
Microbioma Gastrointestinal , Síndrome do Ovário Policístico , Camundongos , Feminino , Humanos , Animais , Síndrome do Ovário Policístico/metabolismo , Microbioma Gastrointestinal/fisiologia , Disbiose/microbiologia , RNA Ribossômico 16SRESUMO
To further study the aminoalcohol-diterpenoid alkaloids (ADAs) in Fuzi (Aconiti Lateralis Radix Praeparata), a simple and sensitive UFLC-MS/MS method was established and validated for the determination of five ADAs, aconine, mesaconine, hypaconine, deoxyaconine and fuziline, in rat plasma to compare the pharmacokinetic characteristics of pure ADAs and Fuzi decoction. After precipitating protein with methanol, plasma samples were isolated at 0.5 mL/min flow rate on Waters Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm). The mobile phase was composed of 0.1% formic acid-water and methanol with gradient elution. Mass spectrometric inspection was conducted on a 5500 UFLC-MS/MS system with an electrospray ionization source in patterns of positive ion and multiple reaction-monitoring (MRM). All calibration curves were proved to have acceptable linearity (r2 > 0.99) in linear ranges. Intra-day and inter-day precision and the accuracy met the requirements. The matrix effects of all analytes were between 85% and 115% of three concentration levels. This method has been under verification for comparative pharmacokinetic research after oral administration between aqueous extract of Fuzi and single pure ADAs. The results demonstrated that there are evident pharmacokinetic discrepancies between them, and administration in the extract form instead of pure form may contribute to higher absorption.
Assuntos
Aconitum , Alcaloides , Diterpenos , Medicamentos de Ervas Chinesas , Ratos , Animais , Espectrometria de Massas em Tandem/métodos , Metanol , Cromatografia Líquida de Alta Pressão/métodos , Alcaloides/química , Medicamentos de Ervas Chinesas/química , Aconitum/química , Administração Oral , Água , Amino Álcoois , Reprodutibilidade dos TestesRESUMO
Periodontitis is an inflammatory disease caused by bacterial infection. Excessive immune response and high levels of reactive oxygen species (ROS) further lead to the irreversible destruction of surrounding tissues. Developing new antimicrobial materials that regulate the immune system to resist inflammation can effectively treat periodontal inflammation. A nanoplatform integrating Ag+, photothermal therapy (PTT), and procyanidins (PC) for precision antibacterial and synergistic immunotherapy for periodontitis was proposed. This work loaded PC into AuAg nanoparticles, and the resulting nanocomposite was named AuAg-PC. PTT can effectively remove pathogenic bacteria, but high temperatures can cause tissue damage. Ag+ contributes to the preparation of a nanoparticle branched structure that improves the photothermal efficiency and helps PTT achieve an excellent antibacterial effect and avoid periodontal tissue damage. PC regulates host immunity by eliminating intracellular ROS, inhibiting inflammatory factors, and regulating macrophage polarisation in periodontal disease sites. It enhances the host's resistance to bacterial inflammation. AuAg-PC exerted an excellent anti-inflammatory effect and promoted tissue repair in animal periodontal inflammation models. Hence, AuAg-PC significantly combats periodontal pathogens and shows great application potential in the photothermal-assisted immunotherapy of periodontitis. This design provided a new controllable and efficient treatment platform for controlling persistent inflammation infection and regulating immunity.
Assuntos
Nanopartículas Metálicas , Nanopartículas , Proantocianidinas , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Inflamatórios , Bactérias , Imunoterapia , Inflamação , Nanopartículas Metálicas/química , Nanopartículas/química , Fototerapia/métodos , Proantocianidinas/farmacologia , Espécies Reativas de Oxigênio , Prata/farmacologia , OuroRESUMO
Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20[Formula: see text]mg/kg) doses were injected intraperitoneally 1[Formula: see text]h before and 23[Formula: see text]h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4[Formula: see text]h before CCl4 administration to explore the mechanism. The blood and liver were collected 24[Formula: see text]h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI.
Assuntos
Isquemia Encefálica , Doença Hepática Induzida por Substâncias e Drogas , Ferroptose , Acidente Vascular Cerebral , Camundongos , Animais , Isquemia Encefálica/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/farmacologia , Tetracloreto de Carbono/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismoRESUMO
Coronavirus disease (COVID-19) caused by SARS-COV-2 infection has been widely prevalent in many countries and has become a common challenge facing mankind. Traditional Chinese medicine (TCM) has played a prominent role in this pandemic, and especially TCM with the function of "heat-clearing and detoxifying" has shown an excellent role in anti-virus. Fufang Shuanghua oral liquid (FFSH) has been used to treat the corresponding symptoms of influenza such as fever, nasal congestion, runny nose, sore throat, and upper respiratory tract infections in clinic, which are typical symptoms of COVID-19. The content of chlorogenic acid, andrographolide and dehydrated andrographolide as the quality control components of FFSH is not less than 1.0 mg/mL, 60 µg/mL and 60 µg/mL respectively. In this study, UPLC-Q-TOF-MS/MS was employed to describe the chemical profile of FFSH. Virtual screening and fluorescence resonance energy transfer (FRET) were used to screen the effective components of FFSH acting on SARS-CoV-2 main protease (Mpro). As a result, 214 compounds in FFSH were identified or preliminarily characterized by UPLC-Q-TOF-MS/MS, and 61 active ingredients with potential inhibitory effects on Mpro were selected through receptor-based and ligand-based virtual screening. In particular, quercetin, forsythoside A, and linoleic acid showed a good inhibitory effect on Mpro in FRET evaluation with IC50 values of 26.15 µM, 22.26 µM and 47.09 µM respectively, and had a strong binding affinity with the receptor Mpro (6LU7) in molecular docking. CYS145 and HIS41 were the main amino acid residues affected by small molecules in the protein binding domain. In brief, we characterized, for the first time, 214 chemical components in FFSH, and three of them, including quercetin, forsythoside A and linoleic acid, were screened out to exert beneficial anti-COVID-19 effects through CYS145 and HIS41 sites, which may provide a new research strategy for TCM to develop new therapeutic drugs against COVID-19.
Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Humanos , Simulação de Acoplamento Molecular , Peptídeo Hidrolases , Quercetina/farmacologia , Espectrometria de Massas em Tandem , Ácido Linoleico , Proteínas não Estruturais Virais , Inibidores de Proteases/farmacologiaRESUMO
A novel actinobacterium, designated strain CRSS-Y-16T, was isolated from the healthy leaves of Xanthium sibiricum, in China and characterized by a polyphasic approach. This strain produced abundant aerial mycelia that generated rod-shaped spores with spiny surfaces. The cell wall contained LL-diaminopimelic acid. The major cellular fatty acids (>10.0%) were C16:0, iso-C16:0, and C18:1 ω9c. The predominant menaquinones were MK-9(H2) and MK-9(H4). The detected polar lipids were diphosphatidylglycerol, hydroxyl phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositolmannoside, phospholipids of unknown structure containing glucosamine and unidentified phospholipids. The genomic G+C content was 70.7%. The full-length 16S rRNA gene sequence analysis indicated that strain CRSS-Y-16T belonged to the genus Streptomyces and shared <98.7% sequence similarities with all recognized type species of the genus. Phylogenetic analysis based on 16S rRNA gene sequences showed that this strain formed a distinct branch. Phylogenomic analysis demonstrated that it was closely related to Streptomyces panaciradicis 1MR-8T. However, the clustering patterns resulting from phylogenomic tree verified that strain CRSS-Y-16T represented a novel Streptomyces species. This result was further confirmed by low average nucleotide identity and digital DNA-DNA hybridization values (87.54% and 30.1%) between them. Based on all these data, it is concluded that strain CRSS-Y-16T represents a novel Streptomyces species, for which the name Streptomyces spinosirectus sp. nov. is proposed. The type strain is CRSS-Y-16T (=MCCC 1K06950T=JCM 35007T).
Assuntos
Plantas Medicinais , Streptomyces , Xanthium , Filogenia , RNA Ribossômico 16S/genética , Streptomyces/genética , DNARESUMO
Ischemic heart disease (IHD) is a high-risk disease in the middle-aged and elderly population. The ischemic heart may be further damaged after reperfusion therapy with percutaneous coronary intervention (PCI) and other methods, namely, myocardial ischemia-reperfusion injury (MIRI), which further affects revascularization and hinders patient rehabilitation. Therefore, the investigation of new therapies against MIRI has drawn great global attention. Within the long history of the prevention and treatment of MIRI, traditional Chinese medicine (TCM) has increasingly been recognized by the scientific community for its multi-component and multi-target effects. These multi-target effects provide a conspicuous advantage to the anti-MIRI of TCM to overcome the shortcomings of single-component drugs, thereby pointing toward a novel avenue for the treatment of MIRI. However, very few reviews have summarized the currently available anti-MIRI of TCM. Therefore, a systematic data mining of TCM for protecting against MIRI will certainly accelerate the processes of drug discovery and help to identify safe candidates with synergistic formulations. The present review aims to describe TCM-based research in MIRI treatment through electronic retrieval of articles, patents, and ethnopharmacology documents. This review reported the progress of research on the active ingredients, efficacy, and underlying mechanism of anti-MIRI in TCM and TCM formulas, provided scientific support to the clinical use of TCM in the treatment of MIRI, and revealed the corresponding clinical significance and development prospects of TCM in treating MIRI.
RESUMO
To illustrate the effects of long-term straw returning on the fungal community, soil enzyme activity, and crop yield in a fluvo-aquic soil area typical of the Huang-Huai-Hai Plain, a 10-year field experiment (established in 2010) located in Dezhou City, Shandong province, was performed, including three fertilization regimes (NF, no fertilization control; NPK, fertilization with chemical N, P, and K fertilizers; NPKS, straw returning combined with chemical N, P, and K fertilizers). This study aimed to explore the regulation mechanisms of fungal communities on soil fertility, enzyme activities, and crop yield by employing co-occurrence network and structural equation model analyses. Our results showed that long-term straw returning significantly improved soil nutrients, enzyme activity, and wheat yield. Compared with the NPK and NF treatments, soil organic matter (SOM) increased by 9.20% and 34.75%, alkali-hydrolyzed nitrogen (AN) increased by 12.03% and 39.17%, dehydrogenase (DHA) increased by 37.21% and 50.91%, ß-glucosidase (ß-GC) increased by 17.29% and 73.48%, and wheat production increased by 16.22% and 125.53%, respectively. Different long-term fertilization regimes did not significantly change soil fungal α-diversity but resulted in significant differences in ß-diversity. Available phosphorus (AP), SOM, and AN were the main driving factors of fungal community differentiation based on redundancy analysis and hierarchical partitioning analysis. Different abundance analyses revealed significantly different fungal community compositions among fertilization regimes. The long-term NF treatment resulted in a significant enrichment of phosphate/potassium-solubilizing species (i.e., Mortierella, Aspergillus, Ceriporia, and Acremonium) and symbiotic species (i.e., Leohumicola and Hyalodendriella). The relative abundance of pathogenic fungi, namely Sarocladium, Fusarium, and Fusicolla, increased significantly in the NPK treatment. Long-term straw returning in the NPKS treatment significantly stimulated the growth of plant growth-promoting species (i.e., Pseudogymnoascus and Schizothecium) and straw-degrading species (i.e., Trichocladium and Lobulomyces). Co-occurrence network analysis showed that the fungal network was composed of four main modules; the cumulative relative abundance of module 2 was significantly increased under the NPKS treatment and showed a positive linear correlation with DHA and ß-GC. The structural equation model further indicated that the wheat yield was mainly regulated by SOM, whereas species of module 2 could indirectly affect SOM and wheat yield by positively regulating DHA and ß-GC. Taken together, long-term straw returning to the fluvo-aquic soil area of the Huang-Huai-Hai Plain could regulate fungal interspecific interactions, stimulate the growth of specific species groups, inhibit the activity of pathogens, increase the activity of soil enzymes, promote the accumulation of SOM, and achieve high crop yield.