RESUMEN
Esophageal cancer (EC) is a malignancy causing lots of mortality worldwide. Long non-coding RNAs (lncRNAs) are involved in the progression of multiple cancer types. The present study aimed to explore the function and associated mechanisms of lncRNA metastasis-associated lung adenocarcinoma transcript1 (MALAT1) in EC development by focusing on its interaction with miR-1-3p. The levels of MALAT1 and miR-1-3p were investigated in clinical EC specimens. Then, the expression of MALAT1 was knocked down in EC cell lines, and the effects of MALAT1 inhibition on the viability, migration, and invasion, and miR-1-3p/Coronin-1C (CORO1C)/Tropomyosin3 (TPM3) axis in EC cells were detected. The interaction between MALAT1 and miR-1-3p in the progression of EC was further determined by suppressing the expression of miR-1-3p in MALAT1 inhibition cells. The results were further verified with EC xenograft mice model. MALAT1 level was downregulated, while miR-1-3p level was upregulated in EC specimens. The inhibition of MALAT1 suppressed the viability, migration, and invasion in EC cell lines. The changes in phenotypes of EC cells were associated with the upregulation of miR-1-3p level and inhibition of CORO1C/TPM3 activity. Furthermore, the results of dual-luciferase assay showed the direct binding of MALAT1 to the seed sequence of miR-1-3p. The suppressed level of miR-1-3p not only induced the activity of CORO1C/TPM3 signaling, but also upregulated MALAT1 expression, indicating the reciprocal regulation between the two factors. The inhibition of MALAT1 also inhibited tumor growth and epithelial-mesenchymal transition (EMT) in mice model, which was reversed by miR-1-3p inhibition. Collectively, MALAT1 was important to the survival and metastasis of EC cells by sponging miR-1-3p.
Asunto(s)
Neoplasias Esofágicas/genética , MicroARNs/genética , Proteínas de Microfilamentos/genética , ARN Largo no Codificante/genética , Tropomiosina/genética , Animales , Línea Celular Tumoral , Movimiento Celular , Supervivencia Celular , Transición Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos BALB C , Invasividad Neoplásica , Metástasis de la Neoplasia , Trasplante de NeoplasiasRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU). AIM: To investigate the contributions of H. pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases. METHODS: Patients with H. pylori infection and either GU or DU, and healthy individuals without H. pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed. RESULTS: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H. pylori-positive patients with GU was dominated by H. pylori, with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H. pylori-positive GU patients, were all derived from H. pylori, particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori-positive DU patients and healthy controls. CONCLUSION: H. pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU.
Asunto(s)
Úlcera Duodenal , Mucosa Gástrica , Microbioma Gastrointestinal , Infecciones por Helicobacter , Helicobacter pylori , Úlcera Gástrica , Humanos , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/genética , Úlcera Duodenal/microbiología , Úlcera Duodenal/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Úlcera Gástrica/microbiología , Adulto , Estudios de Casos y Controles , Anciano , Metagenómica/métodos , Duodeno/microbiología , Disbiosis/microbiologíaRESUMEN
Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells in situ constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells, dendritic cells, and megakaryocytes, evaluating their interaction with cytotoxic T lymphocytes and contribution to bone metastasis. As important components of skeletal tissue, osteoclasts and osteoblasts derived from bone marrow stromal cells, engaging in 'vicious cycle' accelerate osteolytic bone metastasis. We also explain the concept tumor dormancy and investigate underlying role of immune microenvironment on it. Additionally, a thorough review of emerging treatments for bone metastatic malignancy in clinical research, especially immunotherapy, is presented, indicating current challenges and opportunities in research and development of bone metastasis therapies.
Asunto(s)
Neoplasias Óseas , Microambiente Tumoral , Humanos , Recurrencia Local de Neoplasia , Huesos/patología , Neoplasias Óseas/patología , MacrófagosRESUMEN
OBJECTIVES: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. METHODS: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than -10%. RESULTS: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, -6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, -5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P <0.01). CONCLUSIONS: Our study proved that oral faropenem regimen can be used for the treatment of TB, with fewer adverse events. (Chinese Clinical Trial Registry, ChiCTR1800015959).
Asunto(s)
Antituberculosos , Tuberculosis Pulmonar , Humanos , Quimioterapia Combinada , Etambutol/uso terapéutico , Resultado del Tratamiento , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/diagnósticoRESUMEN
Background: Pulmonary infections remain a significant cause of morbidity and mortality in immunocompromised patients. The pathogens spectrum of pulmonary infection that can affect patients with human immunodeficiency virus (HIV) is wide such as bacterial, fungal, viral, parasitic organisms, and so on. The risk of multi-pathogenic pneumonia is higher in HIV-infected patients. However, the fast and accurate diagnosis of multi-pathogenic pneumonia is challenging because of the limitations of current conventional tests. Case Presentation: Here, we report a case of pneumonia due to Pneumocystis jirovecii and cytomegalovirus (CMV) in a 22-year-old male with newly diagnosed HIV infection. Blood tests revealed a low CD4 count, a chest computed tomography (CT) scan showed extensive ground-glass opacities in the bilateral lung with multiple cavity lesions in the left upper lung. Microscopic examination of stained sputum and bronchoalveolar lavage fluid (BALF) smear specimens did not find any pathogens. There was also no evidence of pathogens known to cause pneumonia in bacteria and fungi culture tests and virus antibodies such as EBV, CMV, and COVID-19. The nucleic acid of CMV in blood was reported by quantitative PCR. Next-generation sequencing (NGS) analysis of BALF specimens identified a large number of P. jirovecii and CMV reads, and confirmed the diagnosis of pneumonia due to P. jirovecii and CMV. Following the patient's treatment with anti-PCP and anti-CMV, the patient was cured and discharged. Conclusions: This case highlights the combined application of NGS in the clinical diagnosis of multi-pathogenic pneumonia in an HIV-infected patient. NGS is proposed as an important adjunctive diagnostic approach for identifying pathogens of multi-pathogenic pneumonia in HIV-infected patients.