DDIT4 is a mitochondrial and tumor-related protein involved in anti-tumor therapy resistance, proliferation, and invasion, etc. Its expression level increases under the stress such as chemotherapy, hypoxia, and DNA damage. A number of clinical studies have confirmed that DDIT4 can change the behavior of tumor cells and the prognosis of patients with cancer. However, the role of DDIT4 in promoting or suppressing cancer is still inconclusive. This article summarized the four characteristics of DDIT4 including a mitochondria-related protein, interactions with various protein molecules, immune and metabolic cell related proteins and participator in the oxygen sensing pathway, which may be related to the progress of cancer.

Stem cells have the ability of self‐replication and multidirectional differentiation, but the mechanism of how stem cells “maintain” this ability and how to “decide” to give up this state and differentiate into cells with specific functions is still unknown. The Nobel Prize in physiology and medicine in 2021 was awarded to “temperature and tactile receptor,” which made the pain receptor TRPV1‐calcitonin gene‐related peptide (CGRP) pathway active again. The activation and blocking technology of CGRP has been applied to many clinical diseases. CGRP gene has complex structure and transcription process, with multiple methylation and other modification sites. It has been considered as a research hotspot and difficulty since its discovery. Drug manipulation of TRPV1 and inhibition of CGRP might improve metabolism and prolong longevity. However, whether the TRPV1‐neuropeptide‐CGRP pathway is directly or indirectly involved in stem cell self‐replication and multidirectional differentiation is unclear. Recent studies have found that CGRP is closely related to the migration and differentiation of tumor stem cells, which may be realized by turning off or turning on the CGRP gene expression in stem cells and activating a variety of ways to regulate stem cell niches. In this study, we reviewed the advances in researches concentrated on the biological effects of CGRP as a new endogenous switching of cell stemness.

Calcitonin gene‐related peptide (CGRP) plays a diverse and intricate role in chronic low‐grade inflammation and is closely related to specific cancers. It includes two subtypes, CALCA (αCGRP) and CALCB (βCGRP), of which αCGRP expression accounts for more than 90%. Here, we show that methylation of CALCA and CALCB in pancreatic ductal adenocarcinoma was significantly higher than that in paracancer. Western blot and immunohistochemistry showed that CGRP, p‐AKT, and p‐CREB in the tumor tissues were lower than those in the paracarcinoma tissues. In vivo, the expressions of p‐AKT and p‐CREB in the pancreatic tissues of CALCA‐KO rats were also lower than those of wild type. Methylation of CALCA and CALCB is increased in pancreatic adenocarcinoma, and under that condition, p‐AKT and p‐CREB levels were decreased.

This study was aimed to explore the precise dose of corticosteroid therapy in critical COVID-19. A total of forty-five critical COVID-19 patients were enrolled. The process of critical COVID-19 was divided into alveolitis and fibrosis stages. Most nonsurvivors died in fibrosis phase. Nonsurvivors had more dyspnea symptoms, fewer days of hospitalization, shorter duration of alveolitis and fibrosis. High-dose daily corticosteroid therapy (≥150 mg/d) was associated with shorter survival time and lower lymphocyte count in fibrosis phase. Moreover, a high cumulative dose (≥604 mg) was tied to longer duration of virus shedding, lower oxygenation index (OI), higher incidence of tracheal intubation, fewer lymphocytes and higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). In alveolitis phase, the low-to-moderate-dose daily corticosteroid therapy and a small cumulative dose reduced lymphocytes. In conclusion, low-to-moderate dose corticosteroids may be beneficial in the fibrosis phase. High-dose corticosteroid therapy in the fibrosis phase aggravates the severity of critical COVID-19.

Trypsin is a protease-activated receptor-2 (PAR2) activator that upregulates the interleukin (IL)-17 receptor signal in the airway epithelial cells and amplifies the inflammatory response, but does not modify the growth kinetics of the metapneumovirus. How does the coronavirus spread from cell to cell is yet an enigma. The present study analyzed the possible role of trypsin in the activation of coronavirus in vitro and in vivo. We found that the overexpression of trypsin in A549 cells upregulated IL-17 and angiotensin-converting enzyme (ACE). In the humanized transgenic mice, trypsin activated M1 macrophages. Together, our results suggested that the upregulation of trypsin may support a new pathway for coronavirus transmission in patients.