RESUMEN
OBJECTIVE@#To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity.@*METHODS@#Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed.@*RESULTS@#The rats with TNBS- induced UC showed obvious weight loss (P < 0.01) and severe colon tissue injury with high pathological scores (P < 0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P < 0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P < 0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P < 0.05) ACE (P < 0.01)and Chao (P < 0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P < 0.01) and a lowered abundance of Burkholderiaceae (P < 0.05). Compared with the UC rats, the rats treated with E. faecium QH06 showed obvious body weight gain (P < 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P < 0.05), decreased protein expressions of IFN- γ, IL- 12, and TLR2 and mRNA expressions of IFN- γ and IL-12 (P < 0.01 or 0.05), and increased protein expressions of IL- 4 (P < 0.05). The Shannon index ACE (P < 0.05) and Chao (P < 0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P < 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae.@*CONCLUSION@#E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2.
Asunto(s)
Animales , Masculino , Ratas , Colitis Ulcerosa/tratamiento farmacológico , Colon/metabolismo , Interleucina-10 , Interleucina-12/uso terapéutico , ARN Mensajero/metabolismo , Ratas Wistar , Receptor Toll-Like 2/metabolismoRESUMEN
ABSTRACT: To explore the short-term effect of high-dose spironolactone (80âmg/d) on chronic congestive heart failure (CHF).The general clinical data of 211 patients with CHF from February 2016 to August 2019 were collected and analyzed. Patients were divided into Low-dose group (taking 40âmg/d spironolactone) and High-dose group (taking 80âmg/d spironolactone) according to the patient's previous dose of spironolactone. The changes of B-type brain natriuretic peptide (BNP), NT-pro BNP (N terminal pro B type natriuretic peptide), echocardiography, 6-minute walking test (6MWT), and comprehensive cardiac function assessment data were collected for analysis.Compared with before treatment, the blood potassium of the two groups increased significantly (Pâ<â.05), but the blood potassium did not exceed the normal range. Compared with before treatment, BNP, NT-pro BNP, LVEDD, LVEDV and NYHA grading were significantly decreased (Pâ<â.05), LVEF and 6-MWT were significantly increased (Pâ<â.05). Compared with the Low-dose group, the high-dose group BNP (117.49â±â50.32 vs 195.76â±â64.62, Pâ<â.05), NT-pro BNP (312.47â±â86.28 vs 578.47â±â76.73, Pâ<â.05), LVEDD (45.57â±â5.69 vs 51.96â±â5.41, Pâ<.05), LVEDV (141.63â±â51.14 vs 189.85â±â62.49, Pâ<â.05) and NYHA grading (1.29â±â0.41 vs 1.57â±â0.49, Pâ<â.05) were significantly reduced, but, 6-MWT (386.57â±â69.72 vs 341.73â±â78.62, Pâ<â.05), LVEF (41.62â±â2.76 vs 36.02â±â2.18, Pâ<â.05) and total effective rate (92.68% vs 81.39%, Pâ<â.05) increased significantly.Compared with 40âmg spironolactone, 80âmg spironolactone can rapidly reduce BNP and NT-pro BNP concentration, enhance exercise tolerance, improve clinical signs and cardiac function classification, and has better efficacy.
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Insuficiencia Cardíaca/tratamiento farmacológico , Espironolactona/uso terapéutico , Anciano , Relación Dosis-Respuesta a Droga , Ecocardiografía , Femenino , Pruebas de Función Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Potasio/sangre , Estudios Retrospectivos , Espironolactona/administración & dosificación , Prueba de PasoRESUMEN
Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, are two of the deadliest pathogenic bacteria that have been used as biological warfare agents. Although Biothrax is a licensed vaccine against anthrax, no Food and Drug Administration-approved vaccine exists for plague. Here, we report the development of a dual anthrax-plague nanoparticle vaccine employing bacteriophage (phage) T4 as a platform. Using an in vitro assembly system, the 120- by 86-nm heads (capsids) of phage T4 were arrayed with anthrax and plague antigens fused to the small outer capsid protein Soc (9 kDa). The antigens included the anthrax protective antigen (PA) (83 kDa) and the mutated (mut) capsular antigen F1 and the low-calcium-response V antigen of the type 3 secretion system from Y. pestis (F1mutV) (56 kDa). These viral nanoparticles elicited robust anthrax- and plague-specific immune responses and provided complete protection against inhalational anthrax and/or pneumonic plague in three animal challenge models, namely, mice, rats, and rabbits. Protection was demonstrated even when the animals were simultaneously challenged with lethal doses of both anthrax lethal toxin and Y. pestis CO92 bacteria. Unlike the traditional subunit vaccines, the phage T4 vaccine uses a highly stable nanoparticle scaffold, provides multivalency, requires no adjuvant, and elicits broad T-helper 1 and 2 immune responses that are essential for complete clearance of bacteria during infection. Therefore, phage T4 is a unique nanoparticle platform to formulate multivalent vaccines against high-risk pathogens for national preparedness against potential bioterror attacks and emerging infections.IMPORTANCE Following the deadly anthrax attacks of 2001, the Centers for Disease Control and Prevention (CDC) determined that Bacillus anthracis and Yersinia pestis that cause anthrax and plague, respectively, are two Tier 1 select agents that pose the greatest threat to the national security of the United States. Both cause rapid death, in 3 to 6 days, of exposed individuals. We engineered a virus nanoparticle vaccine using bacteriophage T4 by incorporating key antigens of both B. anthracis and Y. pestis into one formulation. Two doses of this vaccine provided complete protection against both inhalational anthrax and pneumonic plague in animal models. This dual anthrax-plague vaccine is a strong candidate for stockpiling against a potential bioterror attack involving either one or both of these biothreat agents. Further, our results establish the T4 nanoparticle as a novel platform to develop multivalent vaccines against pathogens of high public health significance.
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Vacunas contra el Carbunco/inmunología , Carbunco/prevención & control , Antígenos Bacterianos/inmunología , Bacteriófago T4 , Vacuna contra la Peste/inmunología , Peste/prevención & control , Infecciones del Sistema Respiratorio/prevención & control , Animales , Anticuerpos Antibacterianos/sangre , Bacillus anthracis , Proteínas Bacterianas/inmunología , Toxinas Bacterianas/inmunología , Proteínas de la Cápside/inmunología , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Nanopartículas , Proteínas Citotóxicas Formadoras de Poros/inmunología , Conejos , Ratas , Células TH1/inmunología , Células Th2/inmunología , Yersinia pestisRESUMEN
In the present study, three compounds were isolated from Argyreia acuta, among them, compounds 1 and 2 were new and Compounds 1 and 3 were isomers. They were separated by several types of columns, such as normal phase, RP, size exclusion and preparative HPLC, and their structures were elucidated by several spectroscopic methods, such as 1D- and 2D-NMR and HR-TOF-MS.
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Convolvulaceae , Química , Medicamentos Herbarios Chinos , Química , Glicósidos , Química , Isomerismo , Espectrometría de Masas , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Componentes Aéreos de las Plantas , Química , Resinas de Plantas , Química , EspectrofotometríaRESUMEN
In the present study, three compounds were isolated from Argyreia acuta, among them, compounds 1 and 2 were new and Compounds 1 and 3 were isomers. They were separated by several types of columns, such as normal phase, RP, size exclusion and preparative HPLC, and their structures were elucidated by several spectroscopic methods, such as 1D- and 2D-NMR and HR-TOF-MS.
Asunto(s)
Convolvulaceae , Química , Medicamentos Herbarios Chinos , Química , Glicósidos , Química , Isomerismo , Espectrometría de Masas , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Componentes Aéreos de las Plantas , Química , Resinas de Plantas , Química , EspectrofotometríaRESUMEN
PURPOSE: We surveyed the benefit of dietary supplements to treat tinnitus and reported adverse effects. METHOD: A website was created for people with tinnitus to complete a variety of questions. RESULTS: The 1,788 subjects who responded to questionnaires came from 53 different countries; 413 (23.1%) reported taking supplements. No effect on tinnitus was reported in 70.7%, improvement in 19.0%, and worsening in 10.3%. Adverse effects were reported in 6% (n = 36), including bleeding, diarrhea, headache, and others. Supplements were reported to be helpful for sleep: melatonin (effect size, d = 1.228) and lipoflavonoid (d = 0.5244); emotional reactions: melatonin (d = 0.6138) and lipoflavonoid (d = 0.457); hearing: Ginkgo biloba (d = 0.3758); and concentration Ginkgo biloba (d = 0.3611). The positive, subjective reports should be interpreted cautiously; many might have reported a positive effect because they were committed to treatment and expected a benefit. Users of supplements were more likely to have loudness hyperacusis and to have a louder tinnitus. CONCLUSIONS: The use of dietary supplements to treat tinnitus is common, particularly with Ginkgo biloba, lipoflavonoids, magnesium, melatonin, vitamin B12, and zinc. It is likely that some supplements will help with sleep for some patients. However, they are generally not effective, and many produced adverse effects. We concluded that dietary supplements should not be recommended to treat tinnitus but could have a positive outcome on tinnitus reactions in some people.
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Suplementos Dietéticos , Hiperacusia/tratamiento farmacológico , Acúfeno/tratamiento farmacológico , Depresores del Sistema Nervioso Central/uso terapéutico , Estudios Transversales , Femenino , Flavonoides/uso terapéutico , Ginkgo biloba , Humanos , Hiperacusia/etiología , Magnesio/uso terapéutico , Masculino , Melatonina/uso terapéutico , Persona de Mediana Edad , Extractos Vegetales/uso terapéutico , Encuestas y Cuestionarios , Acúfeno/complicaciones , Oligoelementos/uso terapéutico , Vitamina B 12/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Zinc/uso terapéuticoRESUMEN
In the present study, two new compounds from Ipomoea cairica were identified and demonstrated to have α-glucosidase inhibitory activity. They were isolated by column chromatography on silica gel and sephadex LH-20 and finally purified by prep-HPLC, with their structures being elucidated by spectroscopic methods, such as 1D- and 2D-NMR and HR-TOF-MS, and chemical methods. Compounds 1 and 2, named cairicoside A and cairicoside B, were evaluated for α-glucosidase inhibitory activity by the MTT method, with the IC50 values being 25.3 ± 1.6 and 28.5 ± 3.3 μmol·L(-1), respectively.
Asunto(s)
Inhibidores de Glicósido Hidrolasas , Farmacología , Ipomoea , Química , Estructura Molecular , Extractos Vegetales , Farmacología , Resinas de Plantas , Farmacología , Análisis Espectral , alfa-GlucosidasasRESUMEN
Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague. The NH2-terminal ß-strand of F1 was transplanted to the COOH-terminus and the sequence flanking the ß-strand was duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence factor that forms the tip of the type three secretion system (T3SS). The F1mut-V protein showed a dramatic switch in solubility, producing a completely soluble monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses in mice. Inclusion of an oligomerization-deficient YscF, another component of the T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion of the putative immunomodulatory sequence of the V antigen did not improve the vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel) and T4 decorated F1mut-V (no adjuvant) provided 100% protection to mice and rats against pneumonic plague evoked by high doses of Y. pestis CO92. These novel platforms might lead to efficacious and easily manufacturable next generation plague vaccines.
Asunto(s)
Antígenos Bacterianos/metabolismo , Antígenos Virales/metabolismo , Bacteriófago T4/inmunología , Cápside/inmunología , Peste/inmunología , Vacunas de Partículas Similares a Virus/inmunología , Yersinia pestis/virología , Animales , Antígenos Bacterianos/química , Antígenos Bacterianos/genética , Antígenos Virales/química , Antígenos Virales/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Bacteriófago T4/química , Bacteriófago T4/metabolismo , Cápside/química , Cápside/metabolismo , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Femenino , Ratones , Ratones Endogámicos BALB C , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Tamaño de la Partícula , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Peste/microbiología , Peste/prevención & control , Peste/virología , Vacuna contra la Peste/química , Vacuna contra la Peste/inmunología , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Dominios y Motivos de Interacción de Proteínas , Distribución Aleatoria , Ratas , Ratas Endogámicas BN , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Vacunas de Partículas Similares a Virus/química , Yersinia pestis/inmunologíaRESUMEN
It is very necessary to apply case-teaching method to Emergency Medicine in Universities of TCM. To establish the case-teaching system,we ourselves have written teaching materials,trained teachers, and designed all sorts of the medical records. Moreover, we have deployed other methods and principles to put this teaching into practice, used clinical skill practising as a essential supplement of teaching effect. Comparing with the traditional teaching method, it is clear that case-teaching method could make students' learning initiative and positivity improved significantly, their test scores promoted obviously. Thus, carrying out case-teaching method in Emergency Medicine could advance students capability of acquisition of knowledge and their clinical thinking .