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1.
Am J Chin Med ; 52(1): 35-55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38353635

RESUMO

Asian ginseng, the root of Panax ginseng C.A. Meyer, occupies a prominent position in the list of best-selling natural products in the world. There are two major types of ginseng roots: white ginseng and red ginseng, each with numerous preparations. White ginseng is prepared by air-drying fresh Asian ginseng roots after harvest. Red ginseng is prepared by steaming roots in controlled conditions using fresh or raw Asian ginseng. Red ginseng is commonly used in Asian countries due to its unique chemical profile, different therapeutic efficacy, and increased stability. Compared with the widespread research on white ginseng, the study of red ginseng is relatively limited. In this paper, after a botanical feature description, the structures of different types of constituents in red ginseng are systematically described, including naturally occurring compounds and those resulting from the steam processing. In red ginseng phytochemical studies, the number of published reports on ginsenosides is significantly higher than that for other constituents. Up to now, 57 ginsenosides have been isolated and characterized in red ginseng. The structural transformation pathways during steaming have been summarized. In comparison with white ginseng, red ginseng also contains other constituents, including polyacetylenes, Maillard reaction products, other types of glycosides, lignans, amino acids, fatty acids, and polysaccharides, which have also been presented. Appropriate analytical methods are necessary for differentiating between unprocessed white ginseng and processed red ginseng. Specific marker compounds and chemical profiles have been used to discriminate red ginseng from white ginseng and adulterated commercial products. Additionally, a brief phytochemical profile comparison has been made between white ginseng and black ginseng, and the latter is another type of processed ginseng prepared from white or red ginseng by steaming several times. In conclusion, to ensure the safe and effective use of red ginseng, phytochemical and analytical studies of its constituents are necessary and even crucial.


Assuntos
Terapias Complementares , Ginsenosídeos , Panax , Ginsenosídeos/uso terapêutico , Vapor , Panax/química , Compostos Fitoquímicos
2.
Cancer Chemother Pharmacol ; 93(5): 411-425, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38191768

RESUMO

BACKGROUND: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. METHODS: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. RESULTS: Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.


Assuntos
Apoptose , Artemisininas , Neoplasias do Colo , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Artemisininas/farmacologia , Artemisininas/química , Apoptose/efeitos dos fármacos , Neoplasias do Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Imunidade Adaptativa/efeitos dos fármacos , Rutênio/química , Rutênio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Células HCT116 , Células HT29 , Animais , Citocinas/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Camundongos
3.
BMJ ; 384: e076410, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38286487

RESUMO

OBJECTIVE: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. RESULTS: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A1c and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A1c concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. CONCLUSIONS: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A1c and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022342845.


Assuntos
Diabetes Mellitus Tipo 2 , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Adulto , Humanos , Glicemia , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hemoglobinas Glicadas , Controle Glicêmico/métodos , Hipoglicemiantes/efeitos adversos , Metanálise em Rede , Redução de Peso , Metabolismo dos Lipídeos/efeitos dos fármacos
4.
Front Immunol ; 14: 1264705, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954613

RESUMO

Background: Inflammatory bowel disease (IBD) has caused severe health concerns worldwide. Studies on gut microbiota have provided new targets for preventing and treating IBD. Therefore, it is essential to have a comprehensive understanding of the current status and evolution of gut microbiota and IBD studies. Methods: A bibliometric analysis was performed on documents during 2003-2022 retrieved from the Scopus database, including bibliographical profiles, citation patterns, and collaboration details. Software programs of VOSviewer, CiteSpace, and the Bibliometrix R package visually displayed the mass data presented in the scientific landscapes and networks. Results: 10479 publications were retrieved, showing a steadily growing tendency in interest. Xavier Ramnik J. group led the total number of publications (73 papers) and 19787 citations, whose productive work aroused widespread concern. Among the 1977 academic journals, the most prolific ones were Inflammatory Bowel Diseases, Frontiers in Immunology, and Nutrients. Research outputs from the United States (US, 9196 publications), China (5587), and Italy (2305) were highly ranked. Conclusion: Our bibliometric study revealed that the role of gut microbiota has become a hot topic of IBD research worldwide. These findings are expected to improve understanding of research characteristics and to guide future directions in this field.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Bibliometria , China , Bases de Dados Factuais
5.
Food Sci Biotechnol ; 32(10): 1361-1372, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37457401

RESUMO

Rice is an important grain as a major source of carbohydrates in Asia but contains more arsenic (As) than other grains. A total of 239 rice-based processed foods (rice, n = 30; rice cake, n = 30; porridge, n = 39; noodles, n = 33; bread, n = 20; snack, n = 59; powder, n = 28) were purchased in 2019 from domestic markets to measure total As (tAs) and As species. The average tAs and inorganic As (iAs) in each sample group ranged from 20 to 180 µg/kg (porridge for baby to noodle) and 4.4-85 µg/kg (porridge for baby to powder), respectively. The correlation between the iAs and tAs was affected by the variety of ingredients, such as the presence of seaweed (tAs) and the milling type of rice (iAs). Although rice cakes and baby rice-based powders are a source of concern for both adults and children, respectively, risk assessments indicate that most rice-based foods are generally safe to consume in South Korea. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01270-9.

6.
Am J Chin Med ; 51(6): 1577-1594, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465963

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer-related death in the United States, and chronic gut inflammation is a risk factor for CRC initiation and development. Curcuma longa L., or turmeric, has become one of the most studied herbal medicines in recent years due to its anticancer potentials. It is generally accepted that the major component in turmeric is curcuminoids, and the active constituent in curcuminoids is curcumin. However, unprocessed curcumin is characterized by poor water solubility, which means low bioavailability in humans. To increase the bioavailability of curcumin, in this study, we utilized a novel surfactant-formulated curcumin (CuminUP60[Formula: see text]) and evaluated its CRC chemopreventive activities. Compared with the chemo-sensitive CRC cell line HCT-116, the management of the CRC SW-480 cell line is a challenge, since the latter is chemo-resistant. In other words, these cancer cells resist the effects of the chemotherapy. Using the newly formulated CuminUP60[Formula: see text] water solution, this study demonstrated its strong antiproliferative effects on the SW-480 cells in a dose- and time-dependent manner. This new formulation induced early apoptosis and arrested the cell cycle in the G2/M phase via the upregulation of cyclin B1. We also observed that this new formulation possessed inhibitory effects on Th17 cell differentiation, which regulates the body's immune response against gut malignancies. In summary, our results exhibited a potential clinical utility of the surfactant-formulated curcumin in chemo-resistant colorectal cancer management.


Assuntos
Neoplasias Colorretais , Curcumina , Humanos , Curcumina/farmacologia , Diarileptanoides , Tensoativos , Curcuma , Neoplasias Colorretais/tratamento farmacológico , Água
7.
Food Chem ; 425: 136486, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37267785

RESUMO

An imbalance of l-tryptophan (l-Trp), a basic component of a healthy diet, is harmful to human health. Traditional methods for detecting l-Trp have many limitations. To correct a deficiency or excess of l-Trp in human diets, it is necessary to develop a novel method that is rapid, low-cost, and high-sensitivity. Herein, a molecularly imprinted polysaccharide electrochemical sensor termed MIP/CS/MWCNTs/GCE (molecularly imprinted polymer/chitosan/multiwalled carbon nanotubes/glassy carbon electrode) targeting l-Trp was first constructed on a glassy carbon electrode, which was modified with multiwalled carbon nanotubes and chitosan using bifunctional monomers. The MIP/CS/MWCNTs/GCE obtained a wide linear range (1-300 µM) for detecting l-Trp and accurately detected the proportion of l-Trp in mixtures of Trp enantiomers. In milk samples, the spiked recoveries of l-Trp were 86.50 to 99.65%. The MIP/CS/MWCNTs/GCE electrochemical sensor possessed good recognition and detection performance for l-Trp and has promising potential for practical application.


Assuntos
Quitosana , Impressão Molecular , Nanotubos de Carbono , Humanos , Impressão Molecular/métodos , Polímeros , Triptofano , Técnicas Eletroquímicas/métodos , Eletrodos , Dieta , Limite de Detecção
8.
Am J Chin Med ; 51(5): 1085-1104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37385964

RESUMO

Ginseng is a very commonly used natural product in the world, and its two main species are Asian ginseng and American ginseng. Ginseng is an adaptogenic botanical that reportedly protects the body against stress, stabilizes physiological processes, and restores homeostasis. Previously, different animal models and contemporary research methodologies have been used to reveal ginseng's biomedical activities in different body systems and the linked mechanisms of actions. However, human clinical observation data on ginseng effects have attracted more attention from the general public and medical community. In this paper, after an introduction of the phytochemistry of ginseng species, we review positive ginseng clinical studies, mainly conducted in developed countries, performed over the past 20 years. The reported effects of ginseng are presented in several sections, and conditions impacted by ginseng include diabetes; cardiovascular disorders; cognition, memory, and mood; the common cold and flu; cancer fatigue and well-being; quality of life and social functioning, etc. Administration of ginseng demonstrated a good safety record in humans. Although encouraging beneficial effects obtained from clinical data, using the study treatment regimen, the reported ginseng effects in general only ranged from mild to moderate. Nonetheless, these beneficial effects of ginseng could be a valuable add-on therapy for patients receiving standard drug treatments. Additionally, as a dietary supplement, ginseng possesses an important role in maintaining and promoting human health. We believe that the quality of future ginseng trials should be improved, particularly by providing detailed herbal phytochemistry and quality control information. With solid effectiveness data obtained from a well-designed, carefully executed ginseng clinical trial, this meritoriously herbal medicine will be widely used by consumers and patients.


Assuntos
Medicamentos de Ervas Chinesas , Ginsenosídeos , Panax , Animais , Humanos , Fitoterapia , Qualidade de Vida , Ginsenosídeos/farmacologia
9.
Front Immunol ; 14: 1143548, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168869

RESUMO

Background: Probiotics play a vital role in treating immune and inflammatory diseases by improving intestinal barrier function; however, a comprehensive evaluation is missing. The present study aimed to explore the impact of probiotics on the intestinal barrier and related immune function, inflammation, and microbiota composition. A systematic review and meta-analyses were conducted. Methods: Four major databases (PubMed, Science Citation Index Expanded, CENTRAL, and Embase) were thoroughly searched. Weighted mean differences were calculated for continuous outcomes with corresponding 95% confidence intervals (CIs), heterogeneity among studies was evaluated utilizing I2 statistic (Chi-Square test), and data were pooled using random effects meta-analyses. Results: Meta-analysis of data from a total of 26 RCTs (n = 1891) indicated that probiotics significantly improved gut barrier function measured by levels of TER (MD, 5.27, 95% CI, 3.82 to 6.72, P < 0.00001), serum zonulin (SMD, -1.58, 95% CI, -2.49 to -0.66, P = 0.0007), endotoxin (SMD, -3.20, 95% CI, -5.41 to -0.98, P = 0.005), and LPS (SMD, -0.47, 95% CI, -0.85 to -0.09, P = 0.02). Furthermore, probiotic groups demonstrated better efficacy over control groups in reducing inflammatory factors, including CRP, TNF-α, and IL-6. Probiotics can also modulate the gut microbiota structure by boosting the enrichment of Bifidobacterium and Lactobacillus. Conclusion: The present work revealed that probiotics could improve intestinal barrier function, and alleviate inflammation and microbial dysbiosis. Further high-quality RCTs are warranted to achieve a more definitive conclusion. Clinical trial registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281822, identifier CRD42021281822.


Assuntos
Microbioma Gastrointestinal , Probióticos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Probióticos/uso terapêutico , Inflamação , Bifidobacterium
10.
Chem Eng J ; 451(Pt 2)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37033201

RESUMO

Inducing cell death while simultaneously enhancing antitumor immune responses is a promising therapeutic approach for multiple cancers. Celastrol (Cel) and 7-ethyl-10-hydroxycamptothecin (SN38) have contrasting physicochemical properties, but strong synergy in immunogenic cell death induction and anticancer activity. Herein, a hypoxia-sensitive nanosystem (CS@TAP) was designed to demonstrate effective immunotherapy for colorectal cancer by systemic delivery of an immunostimulatory chemotherapy combination. Furthermore, the combination of CS@TAP with anti-PD-L1 mAb (αPD-L1) exhibited a significant therapeutic benefit of delaying tumor growth and increased local doses of immunogenic signaling and T-cell infiltration, ultimately extending survival. We conclude that CS@TAP is an effective inducer of immunogenic cell death (ICD) in cancer immunotherapy. Therefore, this study provides an encouraging strategy to synergistically induce immunogenic cell death to enhance tumor cytotoxic T lymphocytes (CTLs) infiltration for anticancer immunotherapy.

11.
Am J Chin Med ; 51(3): 677-699, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36883990

RESUMO

Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights the necessity and urgency to explore novel therapies. Sijunzi Decoction (SJZD), a classical Chinese herbal formula, has been comprehensively applied and clinically proven effective in treating UC; however, the pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis and intestinal barrier integrity in DSS-induced colitis. SJZD significantly alleviated the colonic tissue damage and improved the goblet cell count, MUC2 secretion, and tight junction protein expressions, which indicated enhanced intestinal barrier integrity. SJZD remarkedly suppressed the abundance of phylum Proteobacteria and genus Escherichia-Shigella, which are typical features of microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight and colon length, and positively correlated with disease activity index and IL-1[Formula: see text]. Furthermore, through gut microbiota depletion, we confirmed that SJZD exerted anti-inflammatory activities in a gut microbiota-dependent manner, and fecal microbiota transplantation (FMT) validated the mediating role of gut microbiota in the SJZD treatment of UC. Through gut microbiota, SJZD modulates the biosynthesis of bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), which has been identified as the signature BA during SJZD treatment. Cumulatively, our findings disclose that SJZD attenuates UC via orchestrating gut homeostasis in microbial modulation and intestinal barrier integrity, thus offering a promising alternative approach to the clinical management of UC.


Assuntos
Colite Ulcerativa , Colite , Medicamentos de Ervas Chinesas , Panax , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Homeostase , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Colo , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
12.
Mikrochim Acta ; 190(4): 118, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36884097

RESUMO

A novel molecular-imprinted polymer (MIP)-based enzyme-free biosensor was created for the selective detection of glycoprotein transferrin (Trf). For this purpose, MIP-based biosensor for Trf was prepared by electrochemical co-polymerization of novel hybrid monomers 3-aminophenylboronic acid (M-APBA) and pyrrole on a glassy carbon electrode (GCE) modified with carboxylated multi-walled carbon nanotubes (cMWCNTs). Hybrid epitopes of Trf (C-terminal fragment and glycan) have been selected as templates. The produced sensor exhibited great selective recognition ability toward Trf under optimal preparation conditions, offering good analytical range (0.125-1.25 µM) with a detection limit of 0.024 µM. The proposed hybrid epitope in combination with hybrid monomer-mediated imprinting strategy was successfully applied to detect Trf in spiked human serum samples, with recoveries and relative standard deviations ranging from 94.7 to 106.0% and 2.64 to 5.32%, respectively. This study provided a reliable protocol for preparing hybrid epitopes and monomers-mediated MIP for the synergistic and effective determination of glycoprotein in complicated biological samples.


Assuntos
Técnicas Biossensoriais , Impressão Molecular , Nanotubos de Carbono , Humanos , Polímeros , Epitopos , Impressão Molecular/métodos , Transferrina , Glicoproteínas , Técnicas Biossensoriais/métodos
13.
Cell Host Microbe ; 31(1): 33-44.e5, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36495868

RESUMO

Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that increases gut motility. While anecdotal evidence suggests that the gut microbiota contributes to serotonin biosynthesis, mechanistic insights are limited. We determined that the bacterium Ruminococcus gnavus plays a pathogenic role in IBS-D. Monocolonization of germ-free mice with R. gnavus induced IBS-D-like symptoms, including increased GI transit and colonic secretion, by stimulating the production of peripheral serotonin. R. gnavus-mediated catabolism of dietary phenylalanine and tryptophan generated phenethylamine and tryptamine that directly stimulated serotonin biosynthesis in intestinal enterochromaffin cells via a mechanism involving activation of trace amine-associated receptor 1 (TAAR1). This R. gnavus-driven increase in serotonin levels elevated GI transit and colonic secretion but was abrogated upon TAAR1 inhibition. Collectively, our study provides molecular and pathogenetic insights into how gut microbial metabolites derived from dietary essential amino acids affect serotonin-dependent control of gut motility.


Assuntos
Síndrome do Intestino Irritável , Animais , Camundongos , Serotonina/metabolismo , Diarreia/metabolismo
14.
Int Immunopharmacol ; 114: 109562, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36508914

RESUMO

CXC chemokine receptor6 (CXCR6)-based immunotherapy plays a significant role in autoimmune diseases, however, little is known about possible small compounds that inhibit pathogenic CXCR6+ T cells for treating multiple sclerosis (MS). Baicalein, a flavonoid isolated from Scutellarin baicalensis (Huang Qin), was shown to exert therapeutic effects on MS, but the underlying mechanisms are largely unknown. In the current study, we found that baicalein inhibited Th1 and Th17 differentiation in vitro. Oral administration of baicalein (25 mg/kg) significantly reduced the disease severity and the infiltration process, decreased the extent of demyelination in EAE, and selectively blocked IL-17A production and specific antibodies (IgG and IgG3) in MOG35-55-induced specific immune responses. In addition, the expression of CD4 cell effectors (CD44hiCD62Llow) and pathogenic Th17 cells was decreased by baicalein treatment. Furthermore, baicalein treatment largely decreased CXCR6+ CD4 and CD8 cells and prominently inhibited CXCR6+ Th17 cells in EAE. Taken together, the findings of this study suggest for the first time that baicalein may ameliorate EAE by suppressing pathogenetic CXCR6+ CD4 cells.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Camundongos , Quimiocinas CXC/metabolismo , Células Th1 , Diferenciação Celular , Imunoglobulina G/uso terapêutico , Células Th17 , Camundongos Endogâmicos C57BL , Receptores CXCR6/metabolismo
15.
Acta Pharmaceutica Sinica ; (12): 867-874, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978756

RESUMO

Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.

16.
Biochim Biophys Acta Mol Basis Dis ; 1868(12): 166539, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36100155

RESUMO

Muscone is the main active compound of Moschus. In this paper, the cardioprotective effect of Muscone on acute myocardial ischemia (AMI) rats and its potential mechanisms were investigated. AMI rat models were established to evaluate the protective effect and antioxidative function of Muscone on the hearts. Moreover, Western blot analysis was conducted to quantify the phosphorylated PI3K and AKT levels in PI3K/Akt pathway for further investigating the mechanism of Muscone. Results showed that Muscone could markedly lessen the infarct size and myocardial injury, improve cardiac function, inhibit cardiomyocyte apoptosis and down-regulate serum reactive oxygen species level as indicated by the decreased MDA, BNP and c-TnI activities and the increased SOD, GSH-px, CAT activities and the expression of Bax protein. In addition, it was revealed that Muscone notably promoted the phosphorylation of PI3K and AKT. These findings denote that Muscone exerts a protective effect in heart via inhibition of oxidative stress and apoptosis, offering new insights into the treatment of CHD and the clinical application of Muscone.


Assuntos
Cicloparafinas , Isquemia Miocárdica , Transdução de Sinais , Animais , Cicloparafinas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
17.
Pharmacol Res ; 182: 106355, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35842183

RESUMO

Obesity-prone (OP) individuals have a significant predisposition to obesity and diabetes. Previously, we have found that OP individuals, despite being normal in weight and BMI, have already exhibited diabetes-related DNA methylation signatures. However, the underlying mechanisms remain obscure. Here we determined the effects of gut microbiota on DNA methylation and investigated the underlying mechanism from microbial-derived short-chain fatty acids (SCFAs). Diabetes-related DNA methylation loci were screened and validated in a new OP cohort. Moreover, the OP group was revealed to have distinct gut microbiota compositions, and fecal microbiota transplantation (FMT) demonstrated the role of gut microbiota in inducing diabetes-related DNA methylations and glucolipid disorders. UPLC-ESI-MS/MS analysis indicated a significantly lower level of total fecal SCFAs in the OP group. The gut microbiota from OP subjects yielded markedly decreased total SCFAs, while notably enriched propionate. Additionally, propionate was also identified by variable importance in projection (VIP) score as the most symbolic SCFAs of the OP group. Further cellular experiments verified that propionate could induce hypermethylation at locus cg26345888 and subsequently inhibit the expression of the target gene DAB1, which was crucially associated with clinical vitamin D deficiency and thus may affect the development and progression of diabetes. In conclusion, our study revealed that gut microbiota-derived propionate induces specific DNA methylation, thus predisposing OP individuals to diabetes. The findings partially illuminate the mechanisms of diabetes susceptibility in OP populations, implying gut microbiota and SCFAs may serve as promising targets both for clinical treatment and medication development of diabetes.


Assuntos
Diabetes Mellitus , Microbioma Gastrointestinal , Metilação de DNA , Ácidos Graxos Voláteis/metabolismo , Humanos , Obesidade/genética , Obesidade/metabolismo , Propionatos/farmacologia , Espectrometria de Massas em Tandem
18.
Cancer Epidemiol Biomarkers Prev ; 31(5): 1036-1042, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506245

RESUMO

BACKGROUND: Modifiable lifestyle-related factors heighten the risk and severity of coronavirus disease 2019 (COVID-19) in patients with cancer. Whether exercise lowers susceptibility or severity is not known. METHODS: We identified 944 cancer patients from Memorial Sloan Kettering Cancer Center (mean age: 64; 85% female; 78% White) completing an exercise survey before receiving a confirmed positive or negative SARS-CoV-2 test. Exercise was defined as reporting moderate-intensity ≥5 days per week, ≥30 minutes/session or strenuous-intensity ≥3 days per week, ≥20 minutes/session. Multivariable logistic regression was used to determine the relationship between exercise and COVID-19 susceptibility and severity (i.e., composite of hospital admission or death events) with adjustment for clinical-epidemiologic covariates. RESULTS: Twenty-four percent (230/944) of the overall cohort were diagnosed with COVID-19 and 35% (333/944) were exercisers. During a median follow-up of 10 months, 26% (156/611) of nonexercising patients were diagnosed with COVID-19 compared with 22% (74/333) of exercising patients. The adjusted OR for risk of COVID-19 was 0.65 [95% confidence interval (CI), 0.44-0.96, P = 0.03] for exercisers compared with nonexercisers. A total of 20% (47/230) of COVID-19 positive patients were hospitalized or died. No difference in the risk of severe COVID-19 as a function of exercise status was observed (P > 0.9). CONCLUSIONS: Exercise may reduce the risk of COVID-19 infection in patients with a history of cancer, but not its severity. IMPACT: This study provides the first data showing that exercise might lower the risk of COVID-19 in cancer patients, but further research is required.


Assuntos
COVID-19 , Neoplasias , COVID-19/epidemiologia , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Inquéritos e Questionários
19.
Am J Chin Med ; 50(3): 723-732, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35331086

RESUMO

Constipation is a very common medical condition worldwide, negatively affecting patients' quality of life and healthcare system. Rhubarb, senna leaf, and aloe are three frequently used herbal medications for achieving regular bowel movement. Rhubarb is also a key ingredient in MaZiRenWan, a Chinese medicine formula used every so often for constipation in oriental countries. We reviewed and summarized the major chemical components from these three botanicals, including dianthrones, anthraquinone glycosides, free anthraquinones, and other polyphenols. The purgative actions of these constituents have been compared. Anthraquinone, especially its dianthrone compounds such as sennoside A and sennoside B, as natural stimulant laxatives, possesses significant effects to promote gastrointestinal motility and relieve functional constipation. Furthermore, the safety, reported side effects, and other benefits of anthraquinone compounds are presented. To date, many anti-constipation natural products are being used but their research is relatively limited, and thus, more investigations in this field are indeed needed.


Assuntos
Plantas Medicinais , Rheum , Antraquinonas/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Qualidade de Vida , Rheum/química , Senosídeos
20.
Artigo em Inglês | MEDLINE | ID: mdl-35245842

RESUMO

A new method involving gut microbiota biotransformation, spectrum-effect relationship analysis and metabolomics analysis was developed to study the antitussive and expectorant microbial metabolites of platycosides fraction (MPFs) of Platycodonis Radix. Furthermore, their possible metabolic mechanisms were studied for the first time. The findings showed that the antitussive and expectorant effects of the platycosides fraction (PF) were significantly enhanced by the gut microbiota biotransformation. 11 active antitussive microbial metabolites and 12 active expectorant microbial metabolites, which shared 8 components, were successfully screened out via spectrum-effect relationship analysis. The prototypes of the active microbial metabolites could be reversely traced according to the gut microbiota biotransformation pathways. It was found out that one platycoside could produce several active microbial metabolites and several different platycosides could produce the same active microbial metabolite. In addition, the metabolomics analysis showed that both the PF and its active microbial metabolites could regulate the same metabolomic pathways of Linoleic acid metabolism, Arachidonic acid metabolism and Glycerophospholipid metabolism to exert antitussive activity, and regulate the same metabolomic pathway of Arachidonic acid metabolism to exert expectorant activity. These findings suggested the microbial metabolites may be the active forms of the platycosides. Overall, the proposed approach was useful in screening the active microbial metabolites; this work explained the in vivo antitussive and expectorant metabolic mechanisms of multi-constituents, multi-targets and synergistic effects of PF of Platycodonis Radix.


Assuntos
Antitussígenos , Expectorantes , Metaboloma/efeitos dos fármacos , Extratos Vegetais , Platycodon , Animais , Antitussígenos/química , Antitussígenos/farmacologia , Cromatografia Líquida , Expectorantes/química , Expectorantes/farmacologia , Microbioma Gastrointestinal , Metabolômica , Camundongos , Ácido Oleanólico/análogos & derivados , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Platycodon/química , Saponinas
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