RESUMEN
Traditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.
Asunto(s)
Estreñimiento , Morus , Hojas de la Planta , Sesamum , Morus/química , Estreñimiento/tratamiento farmacológico , Hojas de la Planta/química , Sesamum/química , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Microbioma Gastrointestinal/efectos de los fármacos , Metabolómica/métodos , Masculino , Motilidad Gastrointestinal/efectos de los fármacos , Tránsito Gastrointestinal/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Perfilación de la Expresión Génica , Modelos Animales de Enfermedad , MultiómicaRESUMEN
BACKGROUND: Breast cancer (BC) is a heterogeneous tumor with a variety of etiology and clinical features. Antibody-dependent cell phagocytosis (ADCP) is the last step of immune checkpoint inhibition (ICI), and macrophages detect and recognize tumor cells, then destroy and engulf tumor cells. Despite the large number, negative regulators that inhibit phagocytic activity are still a key obstacle to the full efficacy of ICI. PATIENTS AND METHODS: An ADCP-related risk score prognostic model for risk stratification as well as prognosis prediction was established in the Cancer Genome Atlas (TCGA) cohort. The predictive value of ADCP risk score in prognosis and immunotherapy was also further validated in the TCGA along with International Cancer Genome Consortium cohorts. To promote the clinical application of the risk score, a nomogram was established, with its effectiveness verified by different methods. RESULTS: In this study, the genes collected from previous studies were defined as ADCP-related genes. In BC patients, two ADCP-related subtypes were identified. The immune characteristics and prognostic stratification were significant different between them. CONCLUSIONS: We identified two subtypes associated with ADCP gene expression in breast cancer. They have significant differences in immune cells, molecular functions, HLA family genes, immune scores, stromal scores, and inflammatory gene expression, which have important guiding significance for the selection of clinical treatment methods. At the same time, we constructed a risk model based on ADCP, and the risk score can be used as a good indicator of prognosis, providing potential therapeutic advantages for chemotherapy and immunotherapy, thus helping the clinical decision-making of BC patients.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Citofagocitosis , Pronóstico , Anticuerpos , Nomogramas , Microambiente TumoralRESUMEN
Due to the widespread abuse of antibiotics, drug resistance in Enterococcus has been increasing. However, the speed of antibiotic discovery cannot keep pace with the acquisition of bacterial resistance. Thus, drug repurposing is a proposed strategy to solve the crises. Lusutrombopag (LP) has been approved as a thrombopoietin receptor agonist by the Food and Drug Administration. This study demonstrated that LP exhibited significant antimicrobial activities against vancomycin-resistant Enterococcus in vitro with rare resistance occurrence. Further, LP combined with tobramycin exhibited synergistic antimicrobial effects in vitro and in vivo against Enterococcus. No in vitro or in vivo detectable toxicity was observed when using LP. Mechanism studies indicated that the disrupted proton motive force may account for LP's antimicrobial activity. In summary, these results demonstrate that LP has the previously undocumented potential to serve as an antibacterial agent against refractory infections caused by Enterococcus.
Asunto(s)
Aminoglicósidos , Cinamatos , Tiazoles , Enterococos Resistentes a la Vancomicina , Estados Unidos , Aminoglicósidos/farmacología , Vancomicina/farmacología , Preparaciones Farmacéuticas , Reposicionamiento de Medicamentos , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVE: This systematic review of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of moxibustion as a complementary or alternative treatment for asthma. METHODS: Seven databases were searched up to June 23, 2024, to identify RCTs assessing moxibustion for bronchial asthma. The outcomes of interest included response to treatment, asthma control, quality of life, lung function, immunological indicators, and incidence of adverse events (AEs). The treatment effects were measured by proportional odds ratios or mean differences with 95% confidence intervals. RESULTS: Thirty-seven RCTs (n = 2,879) were included. Moderate- to very low-quality evidence showed that compared with anti-asthmatic drugs alone, moxibustion plus anti-asthmatic drugs led to a significantly better response and greater increases in lung function, asthma control, and IgE levels. However, the combination therapy had no effect on children's quality of life. In the active comparisons, moxibustion resulted in a superior response to treatment and a greater improvement in asthma control and had comparable effects on lung function, quality of life, and IgE levels compared with anti-asthmatic drugs. The effects of moxibustion on the proportions of CD4 + and CD8 + T cells and the eosinophil count were inconsistent between the add-on and active comparisons. All reported AEs related to moxibustion were mild. CONCLUSIONS: Moxibustion, as an adjunctive treatment or used alone, may improve the response to treatment, lung function, asthma control, and IgE levels in patients with asthma with good safety. Its effects on children's quality of life and immune cell levels remain uncertain.
Asunto(s)
Asma , Moxibustión , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Moxibustión/efectos adversos , Moxibustión/métodos , Humanos , Asma/terapia , Asma/inmunología , Resultado del Tratamiento , Antiasmáticos/uso terapéutico , Terapias Complementarias/métodos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Terapia CombinadaRESUMEN
BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.