RESUMEN
OBJECTIVE: To evaluate the clinical efficacy and safety of combining omalizumab with budesonide formoterol to treat children with moderate and severe allergic asthma, and investigate the effect of this combination therapy on pulmonary and immune functions. METHODS: The data of 88 children with moderate and severe allergic asthma, who were admitted to our hospital between July 2021 and July 2022, were included in the study. The patients were randomly assigned either to control group (n = 44; received budesonide formoterol inhalation therapy) or experimental group (n = 44; received omalizumab subcutaneous injection + budesonide formoterol inhalation therapy) using computer-generated randomization. The clinical efficacy, asthma control (measured using childhood Asthma-Control Test [C-ACT] score), pulmonary function (forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow), immune function (cluster of differentiation 3 cells [CD3+ cells], cluster of differentiation 4 cells [CD4+ cells], immunoglobulin G, immunoglobulin A, and immunoglobulin E), and adverse reactions were observed and compared between both groups. RESULTS: After treatment, the experimental group had improved levels of pulmonary function and immune function indexes, higher C-ACT scores, and a higher overall response rate than the control group (P < 0.05). In addition, the incidence of adverse reactions was not significantly different between both groups (P > 0.05). CONCLUSION: The combination of omalizumab with budesonide formoterol for treating moderate and severe allergic asthma in children demonstrated promising clinical efficacy and improved their pulmonary and immune functions, leading to more rational asthma control. The combined regimen demonstrated satisfactory clinical safety and deserved clinical promotion.
Asunto(s)
Asma , Budesonida , Humanos , Niño , Budesonida/efectos adversos , Omalizumab/efectos adversos , Broncodilatadores/uso terapéutico , Fumarato de Formoterol/uso terapéutico , Etanolaminas/efectos adversos , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Administración por Inhalación , Volumen Espiratorio Forzado , Resultado del Tratamiento , Método Doble Ciego , InmunidadRESUMEN
OBJECTIVE: DNA vaccine has emerged as a promising approach with potential for Tuberculosis (TB) prevention in adults. However, the mechanism behind DNA vaccines is still largely unknown. MATERIALS AND METHODS: Utilizing the CRISPR/Cas9 technique, we engineered Ag85A mutated dendritic cells (Ag85A-M-DCs) in which the Ag85A mRNA derived from Mycobacterium tuberculosis was expressed but not the corresponding protein. Control cells (Ag85A-DCs) expressed both Ag85A mRNA and protein. To better understand the mechanism of antigen presentation following DNA vaccination, integrated transcriptomic and proteomic analysis of dendritic cells (DCs), Ag85A-DCs, and Ag85A-M-DCs were performed. RESULTS: A total of 723, 278, and 933 differentially expressed genes (DEGs), and 209, 134, and 509 differentially expressed proteins (DEPs) were identified between Ag85A-M-DCs and DCs, Ag85A-DCs and DCs, and Ag85A-M-DCs and Ag85A-DCs, respectively. Integration analysis detected 59, 15, and 64 associated DEGs/DEPs with the same expression trend between Ag85A-M-DCs and DCs, Ag85A-DCs and DCs, and Ag85A-M-DCs and Ag85A-DCs, respectively. KEGG pathway analysis showed that chemokine signaling pathway and MAPK signaling pathway were enriched in all three pairs of comparisons. The protein and protein interaction network revealed that ANXA1 was in the top 10 high-degree hub genes closely related to other genes in all three pairs of comparisons. CONCLUSION: The results indicated that Ag85A DNA vaccine might transmit immunogenicity information and induce immune responses by activating chemokine signaling pathway and MAPK signaling pathway. ANXA1 may serve as a key target molecule of the Ag85A vaccine with additional potential for TB prevention.
Asunto(s)
Mycobacterium tuberculosis , Vacunas de ADN , Aciltransferasas/genética , Antígenos Bacterianos/genética , Mycobacterium tuberculosis/genética , Proteómica , ARN , Transcriptoma , Vacunas de ADN/genéticaRESUMEN
BACKGROUND/AIMS: Pioglitazone is a type of peroxisome proliferator-activated receptor x03B3; agonist and is capable of alleviating renal ischemia-reperfusion injury. METHODS: A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs. RESULTS: Subtotal nephrectomy caused severe damages to rat renal tissues, and administration of pioglitazone dramatically restored the structure and function of the kidney, which was evidenced by Periodic acid- Schiff staining and the reduced levels of urinary proteins, blood urea nitrogen, and creatinine. Furthermore, pioglitazone decreased the level of malondialdehyde and increased the level of superoxide dismutase in the injured renal tissues, suggesting that the antioxidative capacity in the injured kidney was augmented by pioglitazone. Additionally, pioglitazone inhibited HIF-1α-dependent angiogenesis by down-regulating the expression of a panel of angiogenic factors. CONCLUSION: The current study demonstrates that pioglitazone benefits renal failure through activation of the antioxidative system and inhibition of angiogenesis in the injured kidney. Our study provides preliminary evidences for the potential application of this agent in the treatment of CKDs.
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Antioxidantes/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , PPAR gamma/agonistas , Tiazolidinedionas/farmacología , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Riñón/irrigación sanguínea , Riñón/metabolismo , Malondialdehído/análisis , Nefrectomía , Óxido Nítrico/análisis , PPAR gamma/metabolismo , Pioglitazona , Ratas , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/etiología , Superóxido Dismutasa/análisis , Tiazolidinedionas/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.
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Colitis/inducido químicamente , Interleucina-33/farmacología , Células Th2/efectos de los fármacos , Enfermedad Aguda , Animales , Colitis/inmunología , Citocinas/biosíntesis , Sulfato de Dextran/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/farmacología , Células Th2/inmunología , Factores de Transcripción/biosíntesisRESUMEN
It is well accepted that vaccination by oral administration has many advantages over injected parenteral immunization. The present study focuses on whether oral vaccination with a DNA vaccine could induce protective immunity against respiratory challenge infection. The M1 gene of influenza A virus was used to construct DNA vaccine using pcDNA 3.1(+) plasmid, a eukaryotic expression vector. The cationic liposomes were used to deliver the constructed DNA vaccine. In vitro and in vivo expression of M1 gene was observed in the cell line and in the intestine of orally vaccinated C57BL/6 mice, respectively. It became clear that this type of oral DNA vaccination was capable of inducing both humoral and cellular immune responses, together with an augmentation of IFN-γ production. In addition, oral vaccination with liposome-encapsulated DNA vaccine could protect the mice against respiratory challenge infection. These results suggest that gastrointestinal tract, a constituent member of the common mucosal immune system, is a potent candidate applicable as a DNA vaccine route against virus respiratory diseases.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Liposomas/administración & dosificación , Infecciones por Orthomyxoviridae/prevención & control , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología , Administración Oral , Animales , Anticuerpos Antivirales/sangre , Modelos Animales de Enfermedad , Vacunas contra la Influenza/genética , Interferón gamma/metabolismo , Leucocitos Mononucleares/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Vacunas de ADN/genética , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/inmunologíaRESUMEN
The goal of this study was to examine the effects of oral administration of bovine milk from cows hyperimmunized with a proprietary bacterin (immune milk "Sustaina") on mucosal immunity in the intestine of adult mice. C57BL/6 mice were orally given immune or control milk for two weeks, and then lymphocyte population and the cytokine production in lamina propria of colon in normal mice and mice induced colitis by dextran sulphate sodium (DSS) were detected. We found that the levels of IFN-γ and IL-10 increased, but the levels of IL-17A and IL-4, decreased in lamina propria of colon in immune milk-fed mice as compared with those in control milk-fed mice. Interestingly, oral administration of immune milk partially improved the acute colitis induced by DSS. The levels of TNF-α and IFN-γ increased, but IL-6, IL-17A and IL-4 decreased in lamina propria (LP) of colon in immune milk-fed mice with DSS-induced colitis. Our results suggest that immune milk may stimulate CD4+ T cells to polarize towards a Th1 type response, but contrarily suppress Th17 and Th2 cells responses in large intestinal LP of mice. The results indicate that this kind of immune milk has is able to promote the maintainance of intestinal homeostasis and enhance protection against infection, and could alleviate the symptoms of acute colitis in mice.
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Vacunas Bacterianas/inmunología , Colitis/inmunología , Colitis/prevención & control , Leche/inmunología , Células TH1/inmunología , Administración Oral , Animales , Relación CD4-CD8 , Bovinos/inmunología , Colitis/inducido químicamente , Sulfato de Dextran , Inmunidad Mucosa , Interferón gamma/biosíntesis , Interleucina-10/biosíntesis , Interleucina-17/biosíntesis , Interleucina-4/biosíntesis , Interleucina-6/biosíntesis , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Células Th17/inmunología , Células Th2/inmunología , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
The aim of this study is to investigate macrophages polarization induced by methionine enkephalin (MENK) that promotes tumoricidal responses in vivo and in vitro. Both phenotypic and functional activities of macrophages were assessed by the quantitative analysis of key surface molecules on macrophages with flow cytometry, immunofluorescent staining, and the production of cytokines with enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Our results showed that MENK could down-regulate the expression of CD206 and the production of arginase-1 (the markers of alternatively activated (M2) macrophage) in tumor-associated macrophages in vivo, meanwhile it could significantly up-regulate the expression of CD64, MHC-II, and the production of induced nitric oxide synthase (the markers of classically activated (M1) macrophages). Furthermore, the studies on bone marrow-derived macrophages treated with MENK (10(-12) M) in vitro had demonstrated that MENK could markedly increase tumoricidal activity. MENK could also enhance the release of reactive oxidant species and the production of interleukin-12p40, tumor necrosis factor-α, while decrease the production of interleukin-10. In conclusion, MENK could effectively induce M2 macrophages polarizing to M1 macrophages, sequentially to modulate the Th1 responses of the host immune system. Our results suggest that MENK might have great potential as a new therapeutic agent for cancer.
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Polaridad Celular/efectos de los fármacos , Encefalina Metionina/uso terapéutico , Macrófagos/inmunología , Neoplasias/tratamiento farmacológico , Animales , Arginasa/biosíntesis , Línea Celular Tumoral , Citocinas/biosíntesis , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Antígenos de Histocompatibilidad Clase II/biosíntesis , Lectinas Tipo C/biosíntesis , Macrófagos/efectos de los fármacos , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/biosíntesis , Ratones , Ratones Endogámicos C57BL , Neoplasias/inmunología , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Especies Reactivas de Oxígeno/metabolismo , Receptores de Superficie Celular/biosíntesis , Receptores de IgG/biosíntesis , Regulación hacia ArribaRESUMEN
Methionine enkephalin (MENK), the endogenous neuropeptide, is known to exert direct effects on the neuroendocrine and the immune systems and participates in regulation of various functions of cells related to both the innate and adaptive immune systems. Dendritic cells (DCs) play important role in initiating and regulating T cell responses. The aim of this work is to investigate the effects of MENK on differentiation, maturation, and function of DCs derived from murine bone marrow progenitors (BM-derived DCs). Our result showed that MENK could induce BM-derived DCs to polarize predominantly to mDC subtype, rather than pDC both in vivo and in vitro, and this was in favor of Th1 response. BM-derived DCs, after treatment with MENK, up-regulated the expressions of MHC class II and key costimulatory molecules. Result by RT-PCR showed MENK could increase expressions of delta and kappa receptors on BM-derived DCs. Also MENK promoted BM-derived DCs to secret higher levels of proinflammatory cytokines of IL-12p70, TNF-α. Furthermore, differentiated BM-derived DCs treated with MENK displayed higher activity to induce allogeneic T cell proliferation and MENK also inhibited tumor growth in vivo and induced apoptosis of tumor cells in vitro. Thus, it is concluded that MENK could be an effective inducer of BM-derived DCs and might be a new therapeutic agent for cancer, as well as other immune handicapped disease. Also we may consider MENK as a potential adjuvant in vaccine preparation.
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Células de la Médula Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Dendríticas/efectos de los fármacos , Encefalina Metionina/farmacología , Neurotransmisores/farmacología , Células Madre/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Citocinas/metabolismo , Femenino , Genes MHC Clase II/efectos de los fármacos , Humanos , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Receptores Opioides delta/biosíntesis , Receptores Opioides kappa/biosíntesis , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Pathogenic mycobacteria possess two homologous chaperones encoded by cpn60.1 and cpn60.2. Cpn60.2 is essential for survival, providing the basic chaperone function, while Cpn60.1 is not. In the present study, we show that inactivation of the Mycobacterium bovis BCG cpn60.1 (Mb3451c) gene does not significantly affect bacterial growth in 7H9 broth, but that this knockout mutant (Δcpn60.1) forms smaller colonies on solid 7H11 medium than the parental and complemented strains. When growing on Sauton medium, the Δcpn60.1 mutant exhibits a thinner surface pellicle and is associated with higher culture filtrate protein content and, coincidentally, with less protein in its outermost cell envelope in comparison with the parental and complemented strains. Interestingly, in this culture condition, the Δcpn60.1 mutant is devoid of phthiocerol dimycocerosates, and its mycolates are two carbon atoms longer than those of the wild-type, a phenotype that is fully reversed by complementation. In addition, Δcpn60.1 bacteria are more sensitive to stress induced by H(2)O(2) but not by SDS, high temperature or acidic pH. Taken together, these data indicate that the cell wall of the Δcpn60.1 mutant is impaired. Analysis by 2D gel electrophoresis and MS reveals the upregulation of a few proteins such as FadA2 and isocitrate lyase in the cell extract of the mutant, whereas more profound differences are found in the composition of the mycobacterial culture filtrate, e.g. the well-known Hsp65 chaperonin Cpn60.2 is particularly abundant and increases about 200-fold in the filtrate of the Δcpn60.1 mutant. In mice, the Δcpn60.1 mutant is less persistent in lungs and, to a lesser extent, in spleen, but it induces a comparable mycobacteria-specific gamma interferon production and protection against Mycobacterium tuberculosis H37Rv challenge as do the parental and complemented BCG strains. Thus, by inactivating the cpn60.1 gene in M. bovis BCG we show that Cpn60.1 is necessary for the integrity of the bacterial cell wall, is involved in resistance to H(2)O(2)-induced stress but is not essential for its vaccine potential.
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Proteínas Bacterianas/inmunología , Proteínas Bacterianas/metabolismo , Técnicas de Inactivación de Genes , Chaperonas Moleculares/inmunología , Chaperonas Moleculares/metabolismo , Mycobacterium bovis/inmunología , Mycobacterium bovis/fisiología , Animales , Antibacterianos/toxicidad , Carga Bacteriana , Proteínas Bacterianas/análisis , Proteínas Bacterianas/genética , Pared Celular/química , Pared Celular/fisiología , Medios de Cultivo/química , Modelos Animales de Enfermedad , Electroforesis en Gel Bidimensional , Prueba de Complementación Genética , Peróxido de Hidrógeno/toxicidad , Lípidos/química , Pulmón/microbiología , Espectrometría de Masas , Ratones , Ratones Endogámicos BALB C , Chaperonas Moleculares/genética , Mycobacterium bovis/genética , Mycobacterium bovis/crecimiento & desarrollo , Ácidos Micólicos/química , Ácidos Micólicos/metabolismo , Estrés Oxidativo , Proteoma/análisis , Enfermedades de los Roedores/microbiología , Enfermedades de los Roedores/patología , Dodecil Sulfato de Sodio/toxicidad , Bazo/microbiología , Tuberculosis/microbiología , Tuberculosis/patologíaRESUMEN
BACKGROUND: Liver fibrosis progression is commonly found in patients with CHB. Liver biopsy is a gold standard for identifying the extent of liver fibrosis, but has many draw-backs. It is essential to construct a noninvasive model to predict the levels of risk for liver fibrosis. It would provide very useful information to help reduce the number of liver biopsies of CHB patients. METHODS: 339 chronic hepatitis B patients with HBsAg-positive were investigated retrospectively, and divided at random into 2 subsets with twice as many patients in the training set as in the validation set; 116 additional patients were consequently enrolled in the study as the testing set. A three-layer artificial neural network was developed using a Bayesian learning algorithm. Sensitivity and ROC analysis were performed to explain the importance of input variables and the performance of the neural network. RESULTS: There were 329 patients without significant fibrosis and 126 with significant fibrosis in the study. All markers except gender, HB, ALP and TP were found to be statistically significant factors associated with significant fibrosis. The sensitivity analysis showed that the most important factors in the predictive model were age, AST, platelet, and GGT, and the influence on the output variable among coal miners were 22.3-24.6%. The AUROC in 3 sets was 0.883, 0.884, and 0.920. In the testing set, for a decision threshold of 0.33, sensitivity and negative predictive values were 100% and all CHB patients with significant fibrosis would be identified. CONCLUSIONS: The artificial neural network model based on routine and serum markers would predict the risk for liver fibrosis with a high accuracy. 47.4% of CHB patients at a decision threshold of 0.33 would be free of liver biopsy and wouldn't be missed.
Asunto(s)
Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/patología , Cirrosis Hepática/diagnóstico , Redes Neurales de la Computación , Medición de Riesgo , Adolescente , Adulto , Anciano , Biomarcadores , Femenino , Humanos , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Distribución Aleatoria , Adulto JovenRESUMEN
Bacillus CalmetteGuérin (BCG) has become a significant treatment for bladder cancer, and neutrophils are reported to be associated with the antitumor effect of BCG. The aim of the present study was to clarify the antitumor function of neutrophils stimulated by BCG. Initially, the killing effect and cytotoxic activity of neutrophils treated with BCG was detected. Subsequently, the effectiveness of BCGtreated neutrophils extracted from tumorbearing mice was analyzed. The results revealed that the cytotoxic effect of neutrophils was stronger in the BCGtreated group compared with that in the normal saline (NS)treated and control groups (P<0.05). A significantly higher concentration of cytokines tumor necrosis factor (TNF)α, interleukin (IL)1ß, IL6 and TNFrelated apoptosisinducing ligand occurred in the BCGtreated neutrophil group compared with the NS and control groups (P<0.01), which was also associated with the BCG dose (P<0.01). The gross tumor volume percentage in BCGtreated neutrophils from tumorbearing mice (BCGT group) was significantly lower in comparison with that in the NStreated neutrophils from tumorbearing mice (NST group; P<0.05). In addition, the survival rate of tumorbearing mice was higher in the BCGT group compared with the NST group (P<0.05), while more BCGtreated neutrophils from tumorbearing mice were infiltrated in the MethA tumor (P<0.01). In conclusion, BCGtreated neutrophils were observed to enhance the antitumor efficacy and extend the life span of mice.
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Antineoplásicos/farmacología , Vacuna BCG/inmunología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Animales , Línea Celular Tumoral , Citocinas/metabolismo , Citotoxicidad Inmunológica , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Neutrófilos/metabolismo , Tasa de Supervivencia , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Dendritic cells (DCs) are able to trigger T-cell activation and thus have been considered important for vaccine production against cancers. Vaccines containing DCs have been reported to be effective for developing immunity against cancer cells. The interactions between DCs and auxiliary agents are critical in the development of second-generation vaccines. In the present study, it was evaluated whether Ag85A-mixed DCs could enhance anti-tumor immunity in laboratory mice with colorectal carcinoma. Functional and phenotypic analyses of the effects of Ag85A-mixed DCs were conducted via flow cytometry and measurement of T-cell proliferation. In addition, interferon (IFN)-γ production was assessed. The therapeutic efficacy of DC vaccination for colorectal carcinoma treatment in mice was investigated. It was identified that Ag85A-mixed DCs exhibited strong upregulation of CD80, CD86 and major histocompatibility complex class II. Cytotoxic T-lymphocytes with CT26-primed Ag85A-DCs were indicated to induce stronger responses against CT26 tumor cells and trigger IFN-γ production. Furthermore, the Ag85A-mixed DC vaccine exerted a considerable inhibitory effect on tumor progression in mice as compared with the control group. Therefore, DCs in combination with the Ag85A gene may reinforce anti-colorectal carcinoma immunity. The current study provides a novel potential strategy for cancer treatment by enhancing immunity via Ag85A-mixed DC vaccination.
RESUMEN
Objective: To evaluate the clinical efficacy and safety of combining omalizumab with budesonide formoterol to treat children with moderate and severe allergic asthma, and investigate the effect of this combination therapy on pulmonary and immune functions. Methods: The data of 88 children with moderate and severe allergic asthma, who were admitted to our hospital between July 2021 and July 2022, were included in the study. The patients were randomly assigned either to control group (n = 44; received budesonide formoterol inhalation therapy) or experimental group (n = 44; received omalizumab subcutaneous injection + budesonide formoterol inhalation therapy) using computer-generated randomization. The clinical efficacy, asthma control (measured using childhood Asthma-Control Test [C-ACT] score), pulmonary function (forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow), immune function (cluster of differentiation 3 cells [CD3+ cells], cluster of differentiation 4 cells [CD4+ cells], immunoglobulin G, immunoglobulin A, and immunoglobulin E), and adverse reactions were observed and compared between both groups. Results: After treatment, the experimental group had improved levels of pulmonary function and immune function indexes, higher C-ACT scores, and a higher overall response rate than the control group (P < 0.05). In addition, the incidence of adverse reactions was not significantly different between both groups (P > 0.05). Conclusion: The combination of omalizumab with budesonide formoterol for treating moderate and severe allergic asthma in children demonstrated promising clinical efficacy and improved their pulmonary and immune functions, leading to more rational asthma control. The combined regimen demonstrated satisfactory clinical safety and deserved clinical promotion (AU)
Asunto(s)
Humanos , Masculino , Femenino , Niño , Omalizumab/administración & dosificación , Antiasmáticos/administración & dosificación , Budesonida/administración & dosificación , Broncodilatadores/administración & dosificación , Asma/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Quimioterapia CombinadaRESUMEN
BACKGROUND: Ganoderma lucidum polysaccharides (GLP) has anti-inflammatory and immunomodulatory effects. Dysregulated immune responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The aim of this study was to assess the therapeutic potential of GLP to alleviate DSS-induced colitis. METHODS: The mice were administered with GLP by intragastric gavage daily for two weeks prior to the DSS treatment. Mice were orally administered with 2.5% DSS dissolved in drinking water with GLP or water treatment for 6 days. The mice were killed on day 7 after induction of colitis. Survival rates, body weight loss, colon lengths, histological changes, and disease activity index scores (DAI) were evaluated. RESULTS: GLP significantly improved survival rates, colon length shortening, body weight loss, histopathological score, and DAI scores in mice with DSS-induced colitis. GLP markedly suppressed the secretions of TNF-α, IL-1ß, IL-6, IL-17A, and IL-4 and significantly affected populations of Th17 cells, B cells, NK cells, and NKT cells in the lamina propria lymphocytes. CONCLUSIONS: GLP prevented inflammation, maintained intestinal homeostasis, and regulated the intestinal immunological barrier functions in mice with DSS-induced colitis.
Asunto(s)
Antiinflamatorios/farmacología , Colitis/etiología , Colitis/metabolismo , Polisacáridos Fúngicos/farmacología , Inmunomodulación/efectos de los fármacos , Células Th17/inmunología , Animales , Basidiomycota/inmunología , Biomarcadores , Colitis/tratamiento farmacológico , Colitis/patología , Citocinas/genética , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Expresión Génica , Inmunofenotipificación , Leucocitos/inmunología , Leucocitos/metabolismo , Masculino , Ratones , Células Th17/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Low immunogenicity is one of the major problems limiting the clinical use for DNA vaccines, which makes it impossible to obtain a strong protective immune response after vaccination. In order to explore whether Ag85A DNA vaccine could mount more efficiently protective immune response through new RNA sensor and its signal transduction pathway of antigen presentation we designed and synthesized Ag85A gene fragment containing multiple points mutations and transfected the gene fragment into the dendritic cell line (DC2.4) by CRISPR/Cas9. Subsequently, we focused on the changes of RNA sensors RIG-I, Mda-5, and the downstream adaptors MAVS, IRF3, IRF7 and IFN-ß. The results indicated the significant increases in the mRNA and protein expression of RNA sensors RIG-I, Mda-5 and related adaptors MAVS, IRF3, IRF7, and IFN-ß in the mutant DC 2.4 cells. The flow cytometry results demonstrated that the expression of MHC II on the surface of DC 2.4 significantly increased when compared with that in control. Therefore, it is suggested that Ag85A mutant DNA could release immunogenic message through RNA sensors and related adaptors via non protein pathway. There is at least one RNA signal transduction pathway of Ag85A DNA in DC2.4 cell. The work provides a new mode of action for nucleic acid vaccine to improve immunogenicity and meaningful data for the better understanding of the mechanisms of DNA vaccine.
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Aciltransferasas/genética , Antígenos Bacterianos/genética , ARN , Vacunas de ADN , Animales , Sistemas CRISPR-Cas , Línea Celular , Células Dendríticas , Femenino , Interferón beta/metabolismo , Ratones Endogámicos C57BL , Transducción de SeñalRESUMEN
BACKGROUND: Previously, we have reported that IL-33 functioned as a protective modulator in dextran sulfate sodium- (DSS-) induced chronic colitis by suppressing Th17 cell response in colon lamina propria and IL-33 induced both regulatory B cells (Bregs) and regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) of mice with DSS-induced acute colitis. Moreover, we speculated that IL-33 would promote the Treg or Breg responses leading to the attenuation of DSS-induced chronic colitis. So, we investigated the role of IL-33 on Bregs and Tregs in the MLN of DSS-induced chronic colitis mice. METHODS: IL-33 was administered by intraperitoneal injection to mice with DSS-induced chronic colitis. Clinical symptoms, colon length, and histological changes were determined. The production of cytokines was measured by ELISA. The T and B cell subsets were measured by flow cytometry. The expression of mRNA of transcription factors was measured by quantitative real-time PCR. RESULTS: We show that IL-33 treatment increases both Breg and Treg responses in the MLN of mice with DSS-induced chronic colitis. Moreover, IL-33 treatment also decreases Th17 cell response in the MLN of mice with DSS-induced chronic colitis. CONCLUSION: Our data provide clear evidence that IL-33 plays a protective role in DSS-induced chronic colitis, which is closely related to increasing Breg and Treg responses in the MLN of mice as well as suppressing Th17 cell responses.
Asunto(s)
Linfocitos B Reguladores/inmunología , Colitis/inmunología , Interleucina-33/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Animales , Enfermedad Crónica , Sulfato de Dextran , Modelos Animales de Enfermedad , Humanos , Tolerancia Inmunológica , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Ras-related protein Rab-5A (Rab5a) has been identified to be overexpressed in several types of human cancer. However, its clinical significance and biological roles in oral cancer remain unclear. In the present study, the protein expression of Rab5a was examined in 79 cases of oral squamous cell carcinoma samples using immunohistochemistry. It was demonstrated that Rab5a protein was upregulated in 49.3% (39/79) of cancer samples. Small interfering RNA knockdown was performed on Detroit 562 cells with high endogenous expression. Rab5a transfection was performed in FaDu cells with low endogenous levels. Rab5a depletion was revealed to inhibit cell growth, invasion and colony formation while its overexpression facilitated cell growth, invasion, and colony formation. In addition, Rab5a facilitated cell cycle progression and cell migration. It was also demonstrated that Rab5a depletion downregulated and its overexpression upregulated the expression levels of various cell cycleassociated proteins, and matrix metalloproteinase2 (MMP2). Furthermore, Rab5a positively regulated the extracellular signalregulated kinase (ERK) signaling pathway and promoted epithelialmesenchymal transition (EMT). ERK inhibitor PD98059 partially inhibited the role of Rab5a on MMP2, cyclin D1, cell proliferation and invasion. The results of the present study suggest that Rab5a is overexpressed in oral cancer tissue samples and promotes the malignant phenotype through EMT and the ERK/MMP2 signaling pathway.
Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Expresión Génica , Metaloproteinasas de la Matriz/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Transducción de Señal , Proteínas de Unión al GTP rab5/genética , Adulto , Anciano , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Transición Epitelial-Mesenquimal/genética , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias de la Boca/patología , Clasificación del Tumor , Estadificación de NeoplasiasRESUMEN
BACKGROUND: The role of the Th17/Treg balance in the development of experimental colitis remains poorly understood. METHODS: We exploited the differential response of BALB/c mice and C57BL/6 mice towards drinking water mediated by dextran sulfate sodium (DSS) challenge. RESULTS: DSS-resistant BALB/c mice were characterized by low levels of IFN-γ and TNF-α but high levels of IL-4, IL-6, IL-10, IL-17A, IL-17F, and colon lamina propria and mesenteric lymph node (MLN) CD4+CD25+FoxP3+ T cells when compared to C57BL/6 mice. Collectively, these data indicate the propensity of BALB/c mice towards a Th2/Th17/Treg-polarized immunity protecting these animals against DSS challenge, whereas Th1-polarization of C57BL/6 mice confers sensitivity to DSS-induced colitis. CONCLUSIONS: The intrinsic congenital capacity of mouse strains with respect to T cell proliferation determines sensitivity to experimental colitis.
Asunto(s)
Colitis Ulcerosa/inmunología , Linfocitos T Reguladores/inmunología , Balance Th1 - Th2 , Células Th17/inmunología , Animales , Proliferación Celular , Colitis Ulcerosa/inducido químicamente , Colon/inmunología , Citocinas/genética , Citocinas/inmunología , Sulfato de Dextran , Agua Potable , Predisposición Genética a la Enfermedad , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Mucosa Intestinal/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T Reguladores/fisiología , Células Th17/fisiología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ) agonist and has been demonstrated to be effective in chronic kidney diseases (CKD) treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx) rats and TGF-ß1-exposed HK-2 cells. Pioglitazone attenuated renal injury and improved renal function, as examined by 24 h urinary protein, blood urea nitrogen and plasma creatinine in Nx rats. Renal fibrosis and enhanced expressions of profibrotic proteins TGF-ß1, fibronectin and collagen I caused by Nx were significantly alleviated by pioglitazone. In addition, pioglitazone protected mitochondrial functions by stabilizing the mitochondrial membrane potential, inhibiting ROS generation, maintaining ATP production and the activities of complexes I and III, and preventing cytochrome C leakage from mitochondria. Pioglitazone also upregulated the expression levels of ATP synthase ß, COX I and NDUFB8, which were downregulated in the kidney of Nx rats and TGF-ß1-exposed HK-2 cells. Furthermore, pioglitazone increased fusion proteins Opa-1 and Mfn2 expressions and decreased fission protein Drp1 expression. The results imply that pioglitazone may exert the renoprotective effects through modulating mitochondrial electron transport chain and mitochondrial dynamics in CKD. Finally, these recoveries were completely or partly inhibited by GW9662, which suggests that these effects at least partly PPARγ dependent. This study provides evidence for the pharmacological mechanism of pioglitazone in the treatment of CKD.
RESUMEN
AIM: To assess the effect of sodium selenite on the severity of dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. METHODS: Mice were randomly divided into four groups (n = 10/group): normal group, selenium (Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes (LPL) of the colon, the expression of mRNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured. RESULTS: Se significantly ameliorated the symptoms of colitis and histological injury (P < 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells (P < 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL (P < 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17A, IL-21, T-bet, and RORγt (P < 0.05 each), but enhanced the expression of IL-10 and Foxp3 (P < 0.05 each). CONCLUSION: These results suggest that Se protects against DSS-induced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells.