BTB and CNC homology 1 inhibition ameliorates fibrosis and inflammation via blocking ERK pathway in pulmonary fibrosis.

OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) are still suffering from unfavorable survival. BTB and CNC homology1 (Bach1) is a regulator of oxidative stress and participates in the pathogenesis of multiple lung diseases. Thus, this study aimed to determine the effect of Bach1 knockdown on fibrosis and inflammation in pulmonary fibrosis (PF) mice and cell models. METHODS: Bleomycin induced PF mice were constructed and treated with Bach1 siRNA adenovirus (BLM + Bach1 siRNA group), control siRNA adenovirus (BLM + Control siRNA group) or normal saline (BLM group), then lung tissues were collected for Bach1 expression detection, H&E staining and Masson's trichrome staining. Afterwards, collagen type I alpha 1 chain (COL1A1) and interleukin-6 (IL-6) expressions in serum and bronchoalveolar lavage fluid (BALF) were examined. Subsequently, mouse lung fibroblasts (MLFs) were collected from PF mice and treated with TGF-ß1 to construct PF cell model, which was treated with Bach1 siRNA adenovirus (TGF-ß1 + Bach1 siRNA group) and MAP kinase (ERK) inhibitor U0126 alone (TGF-ß1 + U0126 group) or in combination (TGF-ß1 + U0126 + Bach1 siRNA group), then alpha-smooth muscle actin (α-SMA), fibronectin 1 (Fn1), COL1A1, IL-6 expressions and cell viability were detected. RESULTS: Lung tissue Bach1 mRNA and protein expressions were upregulated in PF mice compared to control mice. Bach1 knockdown reduced lung fibrosis (displayed by Masson's trichrome staining) and inflammation (displayed by H&E staining), then downregulated serum and BALF expressions of COL1A1 and IL-6 in PF mice. Subsequently, in PF cell model, Bach1 knockdown blocked ERK pathway, but did not affect Smads, c-Jun N-terminal kinase (JNK) or thymoma viral proto-oncogene 1 (Akt) pathways. Further experiments revealed that Bach1 knockdown repressed cell viability, α-SMA, Fn1, IL-6 and COL1A1 expressions in PF cell model, then ERK inhibition by U0126 enhanced these effects. CONCLUSIONS: Bach1 is involved in the PF pathogenesis via modulating ERK signaling pathway.

A review on histotechnology practices in COVID-19 pathology investigations.

COVID-19 disease in humans, caused by the novel SARS-CoV-2 virus, was first reported in the city of Wuhan, China in December 2019. This disease has quickly developed into a global pandemic, resulting in over 350,000 deaths worldwide and over 5 million confirmed infections in a matter of 6 months. Although the genome of this novel viral RNA was sequenced quickly and testing kits were manufactured to assist in combatting COVID-19, the diagnosis and treatment will remain relatively unsuccessful until the pathology of this disease is fully understood. Histotechnology plays an important role in understanding the pathology of many diseases, including COVID-19. The first postmortem biopsy of a COVID-19 patient was collected on 27 January 2020, and the pathology finding was published in mid-February 2020. Since then, more studies have been published in scientific literatures as the global outbreak continues. This mini-review summarizes the published articles in which histotechnology aspects were utilized with the intent to understand the pathology of COVID-19. In addition, it is anticipated there will be more molecular and immunohistochemical studies to further understand the mechanism of the disease in the near future.