RESUMO
BACKGROUND: At present, the need for vitamin C supplementation for pregnant smokers has not been fully studied. This study is aimed at investigating whether vitamin C supplementation for pregnant smoking women can improve the pulmonary function of their offspring. METHODS: Four databases were searched from inception to April 1, 2023 for studies on the effect of vitamin C supplementation to pregnant smokers on the pulmonary function of their offspring. Meanwhile, the reference lists of relevant studies were manually searched. The risk of bias in the included studies was assessed using the Cochrane Collaboration tool, and the data was analyzed using STATA/SE 17.0. RESULTS: Four randomized controlled trials (RCTs), all of high quality, were enrolled in this meta-analysis, including 787 pregnant women. The offspring of pregnant smokers who received vitamin C supplementation exhibited improved Forced Expiratory Flow between 25 and 75% (FEF25-75), FEF50, FEF75, and Forced Vital Capacity (FVC) compared to those who did not receive vitamin C supplementation. However, there was no statistically significant difference in Forced Expiratory Volume at 0.5 s (FEV0.5) and the ratio of FEV0.5 to FVC between the offspring of pregnant smokers who received vitamin C and the control group. CONCLUSION: Vitamin C supplementation for smoking pregnant women may enhance the pulmonary function of their offspring, particularly in FEF25-75, FEF50, FEF75, and FVC. Nevertheless, there are no significant differences in FEV0.5 and the FEV0.5/FVC ratio. These findings suggest that vitamin C supplementation has potential benefits for specific pulmonary function. Further studies are needed to comprehensively assess the effects of vitamin C on pulmonary function in the context of maternal smoking during pregnancy.
Assuntos
Fumantes , Vitaminas , Gravidez , Feminino , Humanos , Vitaminas/uso terapêutico , Pulmão , Ácido Ascórbico , Suplementos NutricionaisRESUMO
Selenium nanoparticles (SeNPs) can be biosynthesized by most Lactic acid bacteria thereby converting toxic sodium into SeNPs. However, few studies have reported the antimicrobial activity of biogenic SeNPs against Pseudomonas fluorescens which are the main species of psychrotrophic bacteria in raw milk. This study reported the synthesis and characterization of SeNPs from Lactobacillus casei ZK-AS 1.1482, and the antimicrobial mechanism against P. fluorescens ATCC 13525. The synthesized SeNPs were amorphous with sizes ranging from 52 to 103 nm. Fourier transform infrared spectroscopy (FT-IR) spectra showed the presence of proteins, polysaccharides, and lipids on the surface of particles, which evidently stabilized the SeNPs structure and morphology. Energy-dispersive X-ray (EDX) analysis revealed that the nanoparticles contained selenium. In addition, the minimal inhibitory concentration (MIC) of SeNPs against P. fluorescens ATCC 13525 was 0.1 mg ml-1 and the biofilm inhibition rate was 43.52 ± 0.26%. SeNPs decreased the number of living bacteria observed by confocal laser scanning microscopy (CLSM). Meanwhile, after SeNPs treatment, the intracellular adenosine triphosphate (ATP) concentration and antioxidant enzyme activity decreased, the content of reactive oxygen species (ROS) and the malondialdehyde (MDA) content increased, and lipid peroxidation intensified. Real-time fluorescence quantitative PCR (RT-qPCR) assay showed that the expression of flgA, luxR, lapD, MCP, cheA, c-di-GMP, phoB, and pstC gene were down-regulated after SeNPs treatment. The rfbC and DegT/DnrJ/EryC1/StrS gene were significantly up-regulated, indicating that SeNPs could destroy the integrity of cell membrane and thus play an antimicrobial role. Biogenic SeNPs are expected to be developed as an efficient and novel antimicrobial agent for application in the food industry.
Assuntos
Anti-Infecciosos , Nanopartículas , Pseudomonas fluorescens , Selênio , Selênio/farmacologia , Selênio/química , Selênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Biofilmes , Nanopartículas/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antioxidantes/farmacologiaRESUMO
Background/Purpose: Mahuang decoction (MHD) is a classic famous traditional Chinese medicine and has various pharmacological effects, including anti-inflammation and anti-asthma. In this study, we aimed to investigate the potential protective effect of MHD against asthma and elucidated the underlying mechanism. Materials and Methods: A mouse model of asthma was induced by ovalbumin (OVA) treatment, and then treated with MHD to evaluate its effect on the asthma. Gain- or loss-of-function approaches were performed in SP1 and FGFR3 to study their roles in asthma via measurement of airway inflammation, airway remodeling and airway smooth muscle cell (ASMC) proliferation-related factors. Results: MHD reduced airway inflammation and remodeling. Additionally, MHD contributed to diminished expression of SP1, which was shown to repress airway inflammation and remodeling. Furthermore, SP1 bound to the FGFR3 promoter, resulting in the FGFR3 transcription promotion and ASMC proliferation. Conversely, FGFR3 knockdown abolished airway inflammation and remodeling, the mechanism of which was related to suppression of the PI3K/AKT signaling pathway. Meanwhile, MHD hindered airway inflammation and remodeling following asthma by suppressing the SP1/FGFR3/PI3K/AKT axis. Conclusion: Taken together, MHD may retard airway inflammation and remodeling by suppressing the SP1/FGFR3/PI3K/AKT axis, which contributes to an extensive understanding of asthma and may provide novel therapeutic options for this disease.
Assuntos
Asma , Proteínas Proto-Oncogênicas c-akt , Animais , Asma/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
OBJECT: Edible Brown Seaweed Sargassum fusiforme (Harvey) Setchell, 1931 abbreviated as Sargassum fusiforme was used for folk medical therapy in East Asia countries over five hundred years. Saringosterol acetate (SA) was isolated from S.â fusiforme in our previous study and indicated various effects. However, anti-obesity activity of SA and its mechanism still unknown. METHOD: The inhibitory effect of SA, isolated from S.â fusiforme, on adipogenesis in 3T3-L1 adipocytes was investigated inâ vitro and in zebrafish model. Cell toxicity, differentiation, signaling pathway, and lipid accumulation of SA treated 3T3-L1 adipocytes were determined. The body weight and triglyceride content of diet-induced obese (DIO) adult male zebrafish were measured from 12 to 17â weeks after fertilization. RESULT: SA attenuated the differentiation of cells and reduced lipid accumulation, and triglyceride content in the 3T3-L1 adipocytes. During the differentiation of adipocytes, SA suppressed fat accumulation and decreased the expression of signal factors responsible for adipogenesis. In SA-treated adipocytes, while fatty acid synthetase was downregulated, AMP-activated protein kinase (AMPK) was upregulated. Furthermore, SA suppressed body weight and triglyceride content in DIO zebrafish. CONCLUSION: SA is a potential therapeutic agent in the management of metabolic disorders, such as obesity.
Assuntos
Proteínas Quinases Ativadas por AMP , Peixe-Zebra , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Acetatos/farmacologia , Adipogenia , Animais , Peso Corporal , Dieta Hiperlipídica , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/farmacologia , Ácido Graxo Sintases/uso terapêutico , Masculino , Camundongos , Obesidade/tratamento farmacológico , Estigmasterol/análogos & derivados , Estigmasterol/farmacologia , Triglicerídeos/metabolismo , Peixe-Zebra/metabolismoRESUMO
Lactobacillus rhamnosus can metabolize selenite into organic selenium and Se0. In this paper, label-free quantitative proteomics was applied to explore the mechanism of salt stress promoting selenium enrichment of L.rhamnosus. 397 proteins were up-regulated and 147 proteins were down-regulated of selenium-enriched L.rhamnosus under salt stress. The differentially expressed proteins (DEPs) were mainly involved in metabolism, membrane transport and genetic information processing. The results of quantitative real-time PCR showed that gene opuA, metN, trxR and ldh of Se-enriched L.rhamnosus with salt stress were significantly up-regulated. However, the expression levels of gene luxS, groEL, dnaK and pgk were down-regulated. It was indicated that L.rhamnosus promoted part of amino acids combining with selenium into selenoamino acids with salt stress. Secondly, sodium chloride stimulated the expression of key enzymes involved in metabolism to provide energy for the process of Se-enrichment. In addition, NaCl induced the expression of enzymes and genes involved in the synthesis of selenoproteins. SIGNIFICANCE: It was indicated that L.rhamnosus promoted part of amino acids combining with selenium into selenoamino acids with salt stress. Secondly, sodium chloride stimulated the expression of key enzymes involved in metabolism to provide energy for the process of Se-enrichment. In addition, NaCl induced the expression of enzymes and genes involved in the synthesis of selenoproteins.
Assuntos
Lacticaseibacillus rhamnosus , Selênio , Aminoácidos , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/metabolismo , Proteômica/métodos , Estresse Salino , Selênio/farmacologia , Selenoproteínas , Cloreto de SódioRESUMO
We identified the anti-Mullerian hormone (also known as Müllerian inhibiting substance or MIS) as an inhibitory hormone that induces long-term contraception in mammals. The type II receptor to this hormone, AMHR2 (also known as MISR2), represents a promising druggable target for the modulation of female reproduction with a mechanism of action distinct from steroidal contraceptives. We designed an in vitro platform to screen and validate small molecules that can activate MISR2 signaling and suppress ovarian folliculogenesis. Using a bone morphogenesis protein (BMP)response element luciferase reporter cellbased assay, we screened 5,440 compounds from a repurposed drug library. Positive hits in this screen were tested for specificity and potency in luciferase doseresponse assays, and biological activity was tested in ex vivo Mullerian duct regression bioassays. Selected candidates were further evaluated in ex vivo follicle/ovary culture assays and in vivo in mice and rats. Here, we report that SP600125, CYC-116, gandotinib, and ruxolitinib can specifically inhibit primordial follicle activation and repress folliculogenesis by stimulating the MISR2 pathway.
Assuntos
Anticoncepcionais , Reposicionamento de Medicamentos , Folículo Ovariano , Receptores de Peptídeos , Receptores de Fatores de Crescimento Transformadores beta , Bibliotecas de Moléculas Pequenas , Animais , Antracenos/química , Antracenos/farmacologia , Anticoncepcionais/química , Anticoncepcionais/farmacologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Camundongos , Nitrilas/química , Nitrilas/farmacologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Pirazóis/química , Pirazóis/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia , Ratos , Receptores de Peptídeos/agonistas , Receptores de Fatores de Crescimento Transformadores beta/agonistas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Tiazóis/química , Tiazóis/farmacologiaRESUMO
BACKGROUND: Recurrent respiratory tract infections (RRTIs) are common respiratory ailments in children. RRTIs are often difficult to control and thus generally have a long-term disease course. Children who receive ineffective treatments or those that experience poor treatment outcomes are prone to developing complications such as edema, cough and asthma. Such complications can seriously hinder a child's growth and development, while also adversely affecting the child's physical and mental health. Tuina massage, a traditional Chinese technique that has been practiced in China for >5000âyears, has recently been used to treat RRTIs, with good effect. However, no systematic review of research studies focusing on massage as a treatment for RRTIs can be found in the literature to date. The purpose of this study will be to evaluate the efficacy and safety of Tuina massage for the treatment of pediatric patients who experience RRTIs. METHODS: We will search the following databases using electronic methods: the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), Wanfang Data (WAN FANG), VIP Information (VIP), MEDLINE, PUBMED, EMBASE, and CINAHL. For each database search, the scope will include articles published between the date of database inception to September 2021. Revman5.4 software will be used to conduct this systematic review and meta-analysis. RESULTS: This meta-analysis will confirm whether Tuina massage is of clinical benefit to pediatric patients who experience RRTIs. CONCLUSION: The results of our systematic review and meta-analysis will be used to formulate conclusions as to whether massage therapy is an effective treatment for children suffering from RRTIs. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of tuina in the treatment of recurrent respiratory tract infections. Since all the data included were published, the systematic review did not require ethical approval. INPLASY REGISTRATION NUMBER: INPLASY202190107.
Assuntos
Massagem , Medicina Tradicional Chinesa/métodos , Infecções Respiratórias/terapia , Criança , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
Retinoic acid (RA), the principal active metabolite of vitamin A, is known to be involved in stress-related disorders. However, its mechanism of action in this regard remains unclear. This study reports that, in mice, endogenous cellular RA binding protein 1 (Crabp1) is highly expressed in the hypothalamus and pituitary glands. Crabp1 knockout (CKO) mice exhibit reduced anxiety-like behaviors accompanied by a lowered stress induced-corticosterone level. Furthermore, CRH/DEX tests show an increased sensitivity (hypersensitivity) of their feedback inhibition in the hypothalamic-pituitary-adrenal (HPA) axis. Gene expression studies show reduced FKBP5 expression in CKO mice; this would decrease the suppression of glucocorticoid receptor (GR) signaling thereby enhancing their feedback inhibition, consistent with their dampened corticosterone level and anxiety-like behaviors upon stress induction. In AtT20, a pituitary gland adenoma cell line elevating or reducing Crabp1 level correspondingly increases or decreases FKBP5 expression, and its endogenous Crabp1 level is elevated by GR agonist dexamethasone or RA treatment. This study shows, for the first time, that Crabp1 regulates feedback inhibition of the the HPA axis by modulating FKBP5 expression. Furthermore, RA and stress can increase Crabp1 level, which would up-regulate FKBP5 thereby de-sensitizing feedback inhibition of HPA axis (by decreasing GR signaling) and increasing the risk of stress-related disorders.
Assuntos
Ansiedade/fisiopatologia , Homeostase/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Receptores do Ácido Retinoico/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Animais , Ansiedade/genética , Linhagem Celular Tumoral , Dexametasona/farmacologia , Retroalimentação Fisiológica/efeitos dos fármacos , Retroalimentação Fisiológica/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/genética , Hipotálamo/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/genética , Atividade Motora/fisiologia , Hipófise/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Receptores do Ácido Retinoico/genética , Proteínas de Ligação a Tacrolimo/genéticaRESUMO
BACKGROUND: Asthma is one of the most common chronic airway diseases and is characterized by wheezing, dyspnea, chest tightness, and coughing. These symptoms reduce the patient's quality of life and limit physical activity in daily life. However, there is no systematic review of the efficacy of cupping therapy in the treatment of asthma. To evaluate the efficacy and safety of cupping in the treatment of asthma, we conducted a systematic review and meta-analysis of published randomized clinical trials of cupping in the treatment of asthma. METHODS: We will search the following Chinese and English databases: China National Knowledge Infrastructure, China Science and Periodical Database, Wanfang Database, China Biomedical Literature Database, PubMed, Embase, Cochrane Library. All of the above electronic databases will be searched from inception to August 22, 2021. In addition, we will manually search for conference papers, ongoing experiments, and internal reports to supplement the studies retrieved via electronic search. We will use the Review Manager 5.4 provided by Cochrane Collaboration Network for statistical analysis. RESULTS: The study will prove the effectiveness and safety of cupping in the treatment of asthma. CONCLUSION: We plan to submit this systematic review to a peer-reviewed journal. INPLASY REGISTRATION NUMBER: INPLASY202180104.
Assuntos
Asma , Ventosaterapia , Feminino , Humanos , Masculino , Asma/epidemiologia , Asma/psicologia , Asma/terapia , China/epidemiologia , Ventosaterapia/efeitos adversos , Ventosaterapia/métodos , Qualidade de Vida/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Segurança , Resultado do Tratamento , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ma-xing-shi-gan-tang (MXSGT), which is documented in the Treatise on Febrile Diseases and is a therapeutic drug, is a well-known classic prescription in China and has been widely studied. Previous studies have shown that MXSGT has various pharmacological activities, including anti-influenza virus activity, and ameliorates microvascular hyperpermeability and inflammatory reactions. However, no study has reported the effect of MXSGT in the treatment of bacterial pneumonia. AIM OF THE STUDY: In this study, the potential inhibition of MXSGT against the virulence of S. pneumoniae by targeting PLY was investigated. MATERIALS AND METHODS: First, HPLC analysis was used to determine the main components of MXSGT. Then PLY protein was constructed and used for hemolysis assay and western blot to test the ability of MXSGT to inhibit PLY activity, production and widowed characteristics. The growth curve of S. pneumoniae was drawled with or without MXSGT treatment. In addition, the inhibition of MXSGT against PLY-mediated A549 cell death was examined by cytotoxicity assay. Finally, the mouse experiment was used to verify the effect of MXSGT on mouse lungs. RESULTS: This work has discovered that MXSGT, a TCM prescription, is an effective inhibitor of PLY, an important virulence factor that is essential for S. pneumoniae pathogenicity. MXSGT inhibits the oligomerization of PLY without affecting S. pneumoniae growth and PLY production. In addition, experimental MXSGT treatment was effective against S. pneumoniae infection both in vitro and in vivo. CONCLUSION: These findings directly demonstrate the potential mechanism of the Chinese herbal formula MXSGT in the treatment of pneumococcal disease and provide additional evidence for promotion of the wide use of MXSGT in the clinic.
Assuntos
Antibacterianos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Streptococcus pneumoniae/efeitos dos fármacos , Estreptolisinas/antagonistas & inibidores , Células A549 , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Hemólise/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Medicina Tradicional Chinesa , Camundongos Endogâmicos BALB C , Ovinos , Streptococcus pneumoniae/patogenicidade , Estreptolisinas/metabolismo , Virulência/efeitos dos fármacosRESUMO
OBJECTIVE: Mycoplasma pneumoniae (MP) is the only pathogen in the Mycoplasma family that can cause respiratory symptoms, including acute upper respiratory tract infection and bronchitis, which are often attributed to Mycoplasma pneumoniae pneumonia (MPP). MPP is one of the diseases that commonly affects the pediatric respiratory system, but its pathogenesis is unclear. This study investigated the therapeutic effects and mechanisms of Qingxuan Tongluo formula and its main component, curcumin, on MPP. METHODS: A mouse model of MPP was obtained by nasal drip of the MP strain. The effects of Qingxuan Tongluo formula and curcumin on the treatment of MPP were studied. The proteomic profiles of the alveolar lavage fluid of mice in the model group, Qingxuan Tongluo formula group and curcumin group were evaluated by LC-MS/MS. ELISA and immunohistochemistry were used to verify the possible presence of MP infection biomarkers and drug target proteins. RESULTS: Compared with the mice in the model group, the MPP mice in the Qingxuan Tongluo formula group had significantly reduced fever and cough and prolonged the cough incubation period. Moreover, the pulmonary pathology of the MPP mice was significantly improved, and the lung histopathological score was decreased. After treatment with Qingxuan Tongluo formula and curcumin, the functional and pathway abnormalities caused by MP were mainly inhibited. Levels of HSP90AA1, GRP94, ENO1 and PLG expression were verified by ELISA and immunohistochemistry. CONCLUSION: Qingxuan Tongluo formula significantly reduced fevers and cough and prolonged the cough incubation period of MPP mice. Qingxuan Tongluo formula and curcumin significantly improved the pathological changes in lung tissue caused by MP infection. Proteomics analyses indicated that Qingxuan Tongluo formula and curcumin may have therapeutic effects on MPP by regulating energy metabolism, relieving oxidative stress and activating the fibrinolytic system. ENO1 and PLG were found to be potential drug targets.
Assuntos
Curcumina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Pulmão/efeitos dos fármacos , Mycoplasma pneumoniae/patogenicidade , Pneumonia por Mycoplasma/tratamento farmacológico , Proteômica , Animais , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP90/metabolismo , Interações Hospedeiro-Patógeno , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos BALB C , Fosfopiruvato Hidratase/metabolismo , Plasminogênio/metabolismo , Pneumonia por Mycoplasma/metabolismo , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/patologia , Mapas de Interação de ProteínasRESUMO
BACKGROUND: Pneumonia is the second leading cause of death in children worldwide after preterm birth and certification. Bacteria, viruses, mycoplasma, and other microorganisms are known to be the main causes of pneumonia, of which bacterial pathogenic factors account for 12.5% of cases. The invention and application of antibiotics have improved the prognosis of children with community-acquired bacterial pneumonia (CABP) to a certain extent, but with the emergence of antibiotic resistance worldwide, the mortality of children with CABP is still high. "Maxing Shigan Decoction" and "Qingfei Decoction" have significant efficacy in the treatment of CABP in children, but there is no standardized randomized controlled trial to systematically evaluate the outcomes. METHODS: This study is a randomized, double-blind, placebo-controlled, multicenter clinical trial that will randomize 240 patients with CABP to group of Oral Maxing Shigan Decoction, group of Qingfei Decoction or group of placebos administered 3 times a day for 7 days. This study will observe a wide range of clinically relevant endpoints that have been used in clinical trials of pneumonia, including but not limited to clinical cure rate, antibiotic application days, complete antipyretic rate, complete antipyretic days, disease efficacy, traditional Chinese medicine syndrome effect, and antibiotic upgrade treatment rates. Safety will be assessed by monitoring for the incidence of adverse events during the study. DISCUSSION: This clinical trial is the first to evaluate the efficacy and safety of "Maxing Shigan Decoction" and "Qingfei Decoction" in the treatment of children with CABP. The research results will provide a reference for future research design. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025354. Registered on 14th October 2019-Retrospectively registered, http://www.chictr.org.cn/.
Assuntos
Antibacterianos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Pore-forming toxins produced by bacteria are some of the most important molecular weapons for bacterial virulence. Pneumolysin (PLY) is a pore-forming toxin secreted by Streptococcus pneumoniae (S. pneumoniae) and plays a vital role in the spread, colonization, and invasion of this bacterium in the host, indicating that PLY is a promising target for developing treatments against S. pneumoniae infection. In this study, Cortex Cercis chinensis granules (CCCGs), a prescription drug on the market, were shown to inhibit the pore-forming activity of PLY and protect against PLY-mediated cell hemolysis and A549 cell death without antibacterial activity or inhibition of PLY production. In addition, CCCG treatment inhibited the oligomerization of PLY. Animal experiments showed that CCCGs can reduce the death of mice infected with S. pneumoniae, the degree of pathological damage to the lungs, and the levels of TNF-α and IL-6 in the lungs. In summary, our results demonstrated that CCCGs, a marketed Chinese medicine, inhibit PLY activity and subsequently attenuate S. pneumoniae virulence, which would offer a novel strategy for fighting S. pneumoniae infection and a new use for CCCGs.
RESUMO
Streptococcus pneumoniae (S. pneumoniae) is an opportunistic pathogen that causes pneumonia, meningitis and bacteremia in humans and animals. Pneumolysin (PLY), a major pore-forming toxin that is important for S. pneumoniae pathogenicity, is a promising target for the development of anti-infective agents. Ephedra sinica granules (ESG) is one of the oldest medical preparation with multiple biological activities (such as a divergent wind and cold effect); however, the detailed mechanism remains unknown. In this study, we found that ESG treatment significantly inhibited the oligomerization of PLY and then reduced the activity of PLY without affecting S. pneumoniae growth and PLY production. In a PLY and A549 cell co-incubation system, the addition of ESG resulted in significant protection against PLY-mediated cell injury. Furthermore, S. pneumoniae-infected mice showed decreased mortality, and alleviated tissue damage and inflammatory reactions following treatment with ESG. Our results indicate that ESG is a potential candidate treatment for S. pneumoniae infection that targets PLY. This finding partially elucidates the mechanism of the Chinese herbal formula ESG in the treatment of pneumococcal disease.
Assuntos
Antibacterianos/uso terapêutico , Ephedra sinica , Preparações de Plantas/uso terapêutico , Infecções Pneumocócicas/tratamento farmacológico , Estreptolisinas/antagonistas & inibidores , Células A549 , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Líquido da Lavagem Broncoalveolar/imunologia , Feminino , Humanos , Interleucina-6/imunologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Medicina Tradicional Chinesa , Camundongos Endogâmicos BALB C , Preparações de Plantas/farmacologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/patologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/crescimento & desenvolvimento , Estreptolisinas/metabolismo , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: Adequate thickness of the endometrium has been well recognized as a critical factor for embryo implantation. This was a prospective cohort study to investigate the benefits of platelet-rich plasma (PRP) for women with thin endometrium who received frozen embryo transfer (FET) program in a larger number of patients and explore the underlying mechanism. METHODS: In this study, we investigated the effects of PRP in women with thin endometrium in FET program. 64 patients with thin endometrium (<7âmm) were recruited. PRP intrauterine infusion was given in PRP group during hormone replacement therapy (HRT) cycle in FET cycles. RESULTS: After PRP infusion, the endometrium thickness in PRP group was 7.65â±â0.22âmm, which was significantly thicker than that in control group (6.52â±â0.31âmm) (Pâ<.05). Furthermore, PRP group had lower cycle cancellation rate when compared to control group (19.05% vs. 41.18%, Pâ<.01). The implantation rate and clinical pregnancy rate in PRP group were significantly higher than those in control group (27.94% vs 11.67%, Pâ<.05; 44.12% vs 20%, Pâ<.05, respectively). PRP blood contained 4 folds higher platelets and significantly greater amounts of growth factors including platelet-derived growth factor (PDGF)-AB, PDGF-BB, and transforming growth factor (TGF)-ß than peripheral blood (Pâ<.01). CONCLUSIONS: PRP plays a positive role in promoting endometrium proliferation, improving embryo implantation rate and clinical pregnancy rate for women with thin endometrium in FET cycles.
Assuntos
Transferência Embrionária/métodos , Endométrio/patologia , Transfusão de Plaquetas/métodos , Plasma Rico em Plaquetas , Doenças Uterinas/terapia , Adulto , Transfusão de Sangue Autóloga/métodos , Criopreservação , Feminino , Humanos , Infusões Intravenosas , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Resultado do Tratamento , Doenças Uterinas/patologiaRESUMO
OBJECTIVE: To observe effects of acupuncture on quality of life of patients with chronic fatigue syndrome (CFS). METHODS: Randomized, controlled and single-blinded study method was used, 70 cases were divided into an observation group and a control group, 35 cases in each group. The observation group was treated with acupuncture at Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), Hegu (LI 4), Zusanli (ST 36), etc.; the control group was treated with acupuncture at non-meridian points (2 cm to the acupoints), thrice a week. The treatment was given for 14 times. The World Health Organization Quality of Life (WHOQOL-BREF) scale was used to evaluate the patients' quality of life before and after treatment. RESULTS: The physiological field, individuals own perception of his health condition and total score were significantly improved after treatment in the observation group (all P<0.05); there were no obvious changes in the psychology, social relationships, environment and subjective feelings about the quality of life (all P>0.05). The score of the environmental field in the control group was significantly decreased compared to that before treatment (P<0.05), and there were no significant changes in the other scores. There were no adverse effects in patients. CONCLUSION: Acupuncture can improve the quality of life of CFS patients, especially in physiological field and the individual perception to his well being. Acupuncture has high safety, and the acupoints has high specific degree than non-meridian points.
Assuntos
Terapia por Acupuntura , Síndrome de Fadiga Crônica/terapia , Qualidade de Vida , Pontos de Acupuntura , Adulto , Síndrome de Fadiga Crônica/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To observe the effect of acupuncture on the fatigue degree in patients with chronic fatigue syndrome (CFS). METHODS: Seventy CFS patients were equally randomized into control and treatment groups according to randomized block design. Acupuncture was applied to Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), etc., for patients in treatment group, and to non-acupoints (2 cm respectively to the abovementioned acupoints) for those in control group. The treatment was given once every other day, 14 times altogether. The fatigue degree and the therapeutic effect were assessed by Chalder's fatigue scale (FS). RESULTS: A total of 64 cases (32/group) were finished in this study. After the treatment, the physical FS (5.0 +/- 2.4 vs 6.8 +/- 1.5), mental FS (1.8 +/-1.8 vs 3.1 +/- 1.5) and the total FS (6.8 +/- 3.8 vs 9.9 +/- 2.5) in treatment group, physical FS (5.0 +/- 2.5 vs 6.4 +/- 1.5) and the total FS (7.5 +/- 3.4 vs 9.6 +/- 2.8) in control group decreased significantly compared with pre-treatment (P < 0.01, P < 0.05). There was no marked change in mental FS (2.5 +/- 11.6 vs 3.2 +/- 11.6) in control group after the treatment (P > 0.05). Comparison between two groups showed no significant differences in the 3 indexes (P > 0.05). CONCLUSION: Acupuncture can relieve CFS patients' physical and mental fatigue and the therapeutic effect of acupuncture of acupoints is relatively better than that of non-acupoints in reducing mental fatigue.
Assuntos
Terapia por Acupuntura , Síndrome de Fadiga Crônica/terapia , Pontos de Acupuntura , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To assess the effectiveness of acupuncture treatment of chronic fatigue syndrome (CFS). METHODS: According to the requirement of evidence-based medicine, CFS, fatigue syndrome, acupuncture and moxibustion, acupuncture, electroacupuncture, auricular acupuncture, auricular pellet pressure, plum-blossom needle, intradermal needle, moxibustion, three edged needle, cupping, cup-moving, acupoint injection, etc. were selected as the subject words for retrieving the related papers form domestic and foreign medical databases. The RCT was used as the enrolled criteria, and the clinical cure rate, markedly effective rate, total effective rate, and the scores of the Fatigue Assessment Instrument Questionnaire (FAI) and fatigue scale (FS) were used as the assessment indexes. The statistical package (RevMan 4.2) was used to review management and analysis of 13 papers. RESULTS: A total of 28 papers were enrolled. Logistic regression analysis showed that the total odds ratio (OR) was 4.56, with 95% confidence interval (CI) [2.84, 7.33] for the total effective rate in 10 studies, the total OR was 2.07 with 95% CI [1.49, 2.88] for the markedly effective rate in 8 studies, and the total OR was 2.51 with 95% CI [1.64, 3.85] for the clinical cure rate in 8 studies. The weighted mean difference (WMD) was -29.52 with 95% CI [-36.17, -22.88] for the FAI score in 3 studies, and the WMD -1.22 with 95% CI [-1.77, -0.67] for the FS score in 4 studies. The therapeutic effect in the treatment group of CFS was superior to that in the control group (P<0.01). CONCLUSION: Acupuncture therapy is effective for CFS, but still needs being confirmed by more high-quality studies.
Assuntos
Terapia por Acupuntura , Síndrome de Fadiga Crônica/terapia , Eletroacupuntura , Humanos , Moxibustão , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, is an important cofactor in amino acid metabolism, and supplementary vitamin B6 has protective effects in many disorders. Other than serving as a cofactor, it can also modulate the activities of steroid hormone receptors and transcription factors. However, the molecular basis of this modulation is unclear. Here, we report that mouse nuclear receptor interacting protein 140 (RIP140) can be modified by PLP conjugation. We mapped the modification site to Lys613 by LC-ESI-MS/MS analysis. This modification enhanced its transcriptional corepressive activity and its physiological function in adipocyte differentiation. We attribute this effect to increased interaction of RIP140 with histone deacetylases and nuclear retention of RIP140. This study uncovers a new physiological role of vitamin B6 in gene regulation by PLP conjugation to a transcriptional coregulator, which represents a new function of an old form of protein post-translational modification that has important biological consequences.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Nucleares/química , Vitamina B 6/química , Células 3T3-L1 , Proteínas Adaptadoras de Transdução de Sinal/genética , Adipócitos/fisiologia , Alitretinoína , Animais , Células Cultivadas , Mapeamento Cromossômico , Histona Desacetilases/metabolismo , Metabolismo dos Lipídeos/fisiologia , Camundongos , Microscopia de Fluorescência , Proteínas Nucleares/genética , Proteína 1 de Interação com Receptor Nuclear , Plasmídeos/genética , Processamento de Proteína Pós-Traducional , Receptores de Esteroides/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massas por Ionização por Electrospray , Transcrição Gênica , Transfecção , Tretinoína/químicaRESUMO
Retinoic acid (RA) constitutes the major active ingredient of vitamin A and is required for various biological processes. The tissue RA level is maintained through a cascade of metabolic reactions where retinal dehydrogenases (RALDHs) catalyze the terminal reaction of RA biosynthesis from retinal, a rate-limiting step. We showed that dietary supplement of cholesterol enhanced the expression of RALDH1 and 2 genes and the cellular RA content in vital organs such as brain, kidney, liver and heart. Consistently, the cholesterol-lowering agent (pravastatin sodium) downregulated the expression of RALDH1 and 2 genes in several organs especially the liver and in cultured liver cells. Further, cholesterol metabolites, predominantly the oxysterols, the natural ligands for liver X receptor (LXR), induced these genes via upregulation of sterol regulatory element binding protein-1c (SREBP-1c) that bound to the regulatory regions of these genes. Knockdown of LXRalpha/beta or SREBP-1c downregulated the expression of RALDH genes, which could be rescued by re-expressing SREBP-1c, suggesting SREBP-1c as a direct positive regulator for these genes. This study uncovered a novel crosstalk between cholesterol and RA biosynthesis.