Exposure to atmospheric fine particulate matter has short-term and long-term adverse effects on pulmonary function, especially PM2.5; however, early lung function impairment is not easily detected in time. Notably, microRNAs (miRNAs) have been classified as novel biomarkers for diseases related to PM. Thus, the purpose of this study was to investigate whether miR-146 was related to the decline of lung function after exposure to air pollution. Thirty BALB/c mice were subjected to different concentrations of PM2.5 by noninvasive tracheal instillation for 56 days (two times one week), after which we detected the histopathological changes of mice lung, pulmonary functions, pro-inflammatory factors levels in bronchoalveolar lavage fluid (BALF) and lung tissue homogenate, and the relative expression of microRNA-146a and -146b. When BALB/c mice were exposed to 10 mg/kg PM2.5, severe changes such as widened alveolar interval and diffuse infiltration of macrophages with engulfed PM2.5 particles (dust cells) were found. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) were decreased significantly. Expiratory resistance (Re) and inspiratory resistance (Ri) were increased significantly in the 5 mg/kg and 10 mg/kg PM2.5 groups, meanwhile lung resistance increased and MVV (maximum minute ventilation) decreased from the general tendency; however, pro-inflammatory factors interleukin-6 (IL-6), interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were increased dramatically. MiR-146a and miR-146b were elevated remarkably in the PM2.5 groups compared to the NS group. We also found miR-146 had negative relationships with PIF and PEF, especially miR-146b. Thus, elevated miR-146a and miR-146b may have a relationship with pulmonary dysfunction after PM2.5 chronic exposure.

The double-stranded RNA-dependent protein kinase (PKR) is involved in inflammatory cytokine expression and disease pathogenesis in many conditions. The aim of this study was to explore the role of PKR in sepsis-induced renal tissue injury. Six-week-old C57BL/6J mice received PKR inhibitor (imoxin) and Endoplasmic reticulum (ER) inducer (tunicamycin) 2 hr prior to induction of inflammation via cecal ligation and puncture (CLP). Renal tissues were collected 24 hr after the CLP treatment and protein expression were assessed. The expression of creatinine (Cre) and blood urea nitrogen (BUN) in serum and inflammation factor in tissues was detected by ELISA, and the apoptosis of renal tissue was detected by TUNEL staining. PKR inhibitors reduce the expression of sepsis-induced ER stress in renal tissue, as well as the pathological changes and renal impairment in renal tissue. PKR inhibitors reduce the expression of sepsis-induced inflammatory response and sepsis-induced apoptosis in renal tissue by ER stress. In conclusion, PKR inhibitor alleviates ER stress and alleviates sepsis-induced renal injury.

The objective of this study was to investigate an appropriate observation period for an evaluation of tumorigenicity in NOD/Shi-scid IL-2 Rγ^null (NOG) mice. At SNBL, 19 male and 19 female NOG mice were observed the general condition from 7 weeks old up to 68 weeks old and at FBRI, 7 male and 16 female NOG mice were observed the general condition throughout the lifespan from 7 weeks old. The survival rate started to decline rapidly around 54 to 56 weeks of age in both facilities without a facility difference. Based on these survival data, it seems reasonable to terminate a tumorigenicity study at 52 weeks of age.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been reported worldwide and novel SARS-CoV-2 variants continue to emerge. A novel SARS-CoV-2 strain, the Delta variant (B.1.617.2), is spreading worldwide. The Delta variant has reportedly high infectivity and immune evasion potency. In June 2021, the World Health Organization categorized it as a variant of concern (VOC). Therefore, it is vital to develop tests that can exclusively identify the Delta variant. Here, we developed a rapid screening assay to detect characteristic mutations observed in the Delta variant using high-resolution melting (HRM) analysis. In this assay, we determined L452R and T478K, among which T478K is an identifier of the Delta variant since L452R is seen in other strains (Kappa and Epsilon variants). Additionally, nested PCR-based HRM analysis, which involved RT-PCR (1st PCR) and HRM analysis (2nd PCR), was developed to improve the specificity and sensitivity. Our method discriminated between the L452R mutant and wild-type L452. In addition, HRM analysis distinguished the T478K mutant from the wild-type T478. Seven clinical samples containing the Delta variant were successfully identified as L452R/T478K mutants. These results indicate that this HRM-based genotyping method can identify the Delta variant. This simple method should contribute to rapid identification of the Delta variant and the prevention of infection spread.

Objective: To investigate the protective effect of MZF1/RBM3 on rotenone-induced neuronal injury. Methods: Rotenone (1 μM) was used to treat SH-SY5Y cells for 24 hr to simulate the cellular model of Parkinson’s disease (PD), followed by detection of SH-SY5Y cell activities using MTT assay. MZF1 expression in rotenone-treated SH-SY5Y cells was detected by qRT-PCR and Western blot. MZF1 overexpression plasmid or MZF1 overexpression plasmid and RBM3 siRNA was transfected into SH-SY5Y cells, and then the expressions of MZF1 and RBM3 were detected. Oxidative stress (OS) in SH-SY5Y cells was detected using CMH2DCF-DA probes. Cell apoptosis rate was detected by flow cytometry. CHIP assay and dual-luciferase reporter assay were used to detect the binding between MZF1 and RBM3 promoter. Results: The expression of MZF1 was significantly lower in the rotenone-induced SH-SY5Y cells. Overexpression of MZF1 significantly reduced OS and apoptosis in rotenone-induced SH-SY5Y cells. MZF1 was a transcription factor of RBM3, which promoted the transcription of RBM3, and knockdown of RBM3 inhibited the protective effect of MZF1 overexpression on SH-SY5Y cells. Conclusion: MZF1 alleviates OS and apoptosis induced by rotenone in SH-SY5Y cells by promoting RBM3 transcription.

Cigarette smoke (CS) is the leading cause of chronic pulmonary diseases, including lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. In this study, we aimed to investigate the effects of repeated CS exposure on polyhexamethylene guanidine (PHMG)-induced pulmonary fibrosis in mice. A single intratracheal instillation of 0.6 mg/kg PHMG enhanced the immune response of mice by increasing the number of total and specific inflammatory cell types in the bronchoalveolar lavage fluid. It induced histopathological changes such as granulomatous inflammation/fibrosis and macrophage infiltration in the lungs. These responses were upregulated upon exposure to a combination of PHMG and CS. In contrast, a 4-hr/day exposure to 300 mg/m³ CS alone for 2 weeks by nose-only inhalation resulted in minimal inflammation in the mouse lung. Furthermore, PHMG administration increased the expression of fibrogenic mediators, especially in the pulmonary tissues of the PHMG + CS group compared with that in the PHMG alone group. However, there was no upregulation in the expression of inflammatory cytokines following exposure to a combination of PHMG and CS. Our results demonstrate that repeated exposure to CS may promote the development of PHMG-induced pulmonary fibrosis.