Prevalence of Nontuberculous Mycobacterial Disease in the Changchun District of China.

Rates of nontuberculous mycobacterial (NTM) disease are rapidly increasing throughout the globe. NTM disease, as an emerging infectious disease, it is very important to summarize and analyze the prevalence and main pathogenic bacteria. However, there is no relevant report in Changchun district. In the present report, 8765 clinical samples were collected between January 2017 and December 2019, we reviewed patient electronic medical records and thereby summarized the causative species associated with NTM disease in the Changchun district of China. Of 8765 clinical samples, 1987 samples yielded positive cultures. Of these cultures, 1868 (94.01%) were Mycobacterium tuberculosis, 37 (1.86%) were Mycobacterium bovis, and 82 (4.13%) were NTM. A total of 84 NTM strains were isolated from these 82 cultures, with Mycobacterium intracellulare being the most prevalent isolate therein (44.05%). NTM infection status was associated with location of residence [OR (95% CI) 3.92 (1.20-12.8)]. No apparent correlations were observed between cultured NTM species and patient clinical symptoms. Bronchiectasis was the most prevalent radiographic finding associated with NTM cases [OR (95% CI) 9.00 (1.27-63.89)]. In summary, NTM disease is a growing threat to global public health, and researchers and clinicians should thus focus on the appropriate identification of NTM species and the differentiation between NTM infections and tuberculosis.

Mycobacterium intracellulare mediates macrophage pyroptosis by activating AIM2 and NLRP3 inflammasomes.

Clinically, the incidence of nontuberculous mycobacteria (NTM) lung disease is on the rise, and Mycobacterium intracellulare (M. intracellulare) has attracted much attention as a common opportunistic pathogen in clinical practice. So it is very important to study its immunopathogenic mechanism. In this study, the mechanism of M. intracellulare induced pyroptosis of macrophage was investigated. As shown in Fig. 1, the secretion of IL-1ß and IL-18 in J774A.1 cells increased with time after M. intracellulare infection and was affected by caspase-1 activation and K + efflux, while caspase-1 was significantly expressed in infected cells. Further from Fig. 2, NLRP3,AIM2,ASC proteins were significantly expressed in J774A.1 cells after infection, indicating that the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasome were involved in the infection process. In addition, when caspase-1 activity and K + efflux were inhibited, the expression of related proteins was significantly reduced. It indicates that the activation of NLRP3 and AIM2 is regulated by caspase-1 and K+. Figure 3, the percentage of dead cells with cell membrane damage increases after infection and cleavage of GSDMD proteins occurs. In summary, infection of J774A.1 cells with M. intracellulare induces pyroptosis, and this process is mediated by caspase-1. Our study provides information for further understanding of the molecular mechanism of M. intracellulare infection.

Double strand RNA-guided endogeneous E-cadherin up-regulation induces the apoptosis and inhibits proliferation of breast carcinoma cells in vitro and in vivo.

E-cadherin plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Down-regulation of E-cadherin expression correlates with a strong invasive potential, resulting in poor prognosis in many human carcinomas, including breast cancer. Restoration of E-cadherin can inhibit cell invasion and metastasis in many types of tumors. It has been demonstrated that promoter hypermethylation causes transcriptional down-regulation of E-cadherin. Here, using an RNAa technique specifically activating the expression of E-cadherin through transcriptional regulation, we assessed the phenotype changes of a breast carcinoma cell line with transfection of small-activating RNAs (saRNAs). We observed cell apoptosis, proliferation inhibition and reduction in human breast cancer migration in vitro. Animal experiment results showed that saRNA could inhibit tumor growth in vivo compared with scramble double-small RNA (dsRNA).This study provides a new potential strategy for breast cancer therapy, and also demonstrates the potential for saRNA as a therapeutic option for enhancing tumor suppressor gene expression in breast cancer. (Cancer Sci 2010).

Downregulation of stathmin expression is mediated directly by Egr1 and associated with p53 activity in lung cancer cell line A549.

Stathmin is overexpressed in a variety of assessed human malignancies and is correlated with tumor progression and poor prognosis. Downregulation of its expression will contribute to optimize therapeutic outcomes in the treatment of various malignancies. However, the mechanisms of stathmin gene overexpression are not completely elucidated at present. Early growth response 1 (Egr1) is a transcription factor that triggers transcription of downstream genes mediating cell growth and angiogenesis upon various stimulations. Following the previous computational identification of a site that was thought to be an Egr1 consensus binding sequence at -85 to -94 region in stathmin gene promoter, we analyzed the role of Egr1 in the regulation of stathmin gene expression in lung cancer cell line A549. The results showed that Egr1 transcription factor bound to the sequence 5'-GCGGGGGCG-3' within human stathmin gene promoter; and in reporter gene assays and overexpression experiments, both stathmin gene promoter activity and stathmin gene expression level were downregulated following endogenous or exogenous expression of Egr1. Using wild type Egr1 and knockout Egr1 cell lines, we demonstrated that p53 negatively regulates stathmin expression through Egr1 pathway. In summary, Egr1 is a novel regulator of stathmin expression and p53 mediates the transcriptional repression of stathmin by Egr1 in human lung cancer cells.