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.

Aromatase is a key enzyme in the transformation of androgen into estrogen. Its high expression will destroy the hormonal balance in the male body, and the excessive transformation of androgen into estrogen in the body will further damage the spermatogenic function of the testis, affect the normal development of the sperm, and cause spermatogenic disturbance. Adipose tissue has a high expression of aromatase and shows high enzymatic activity and ability to convert estrogen. Adipose tissue is the most estrogen‐producing nongonadal tissue in the body because of its large size, accounting for about 20% of the body mass in healthy adults. PPARγ is recognized as the key adipose differentiation in the transcriptional regulation of the transcription factor. In the process of adipocyte differentiation, PPARγ regulate the expression of aromatase. The increase of aromatase is associated with the inflammatory response in adipose tissue caused by obesity. After obesity, the increase of proinflammatory factors in adipocytes will lead to enhanced transcription of the CYP19 gene encoding aromatase in adipocytes, which in turn will lead to increased expression of aromatase in adipocytes. This article reviews the regulation of male sterility from the angle of the “obesity‐inflammation‐aromatase” axis.

The limited efficacy of current treatment methods and increased type 2 diabetes mellitus (T2DM) incidence constitute an incentive for investigating how metabolic homeostasis is maintained, to improve treatment efficacy and identify novel treatment methods. We analyzed a three-generation family of Chinese origin with the common feature of T2DM attacks and fatty pancreas (FP), alongside 19 unrelated patients with FP and 58 cases with T2DM for genetic variations in Enho, serum adropin, and relative T_reg amounts. Functional studies with adropin knockout (AdrKO) in C57BL/6J mice were also performed. It showed serum adropin levels were significantly lower in FP and T2DM patients than in healthy subjects; relative T_reg amounts were also significantly decreased in FP and T2DM patients, and positively associated with adropin (r=0.7220, P=0.0001). Sequencing revealed that the patients shared a Cys56Trp mutation in Enho. In vivo, adropin-deficiency was associated with increased severity of glucose homeostasis impairment and fat metabolism disorder. AdrKO mice exhibited reduced endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177), impaired glycosphingolipid biosynthesis, adipocytes infiltrating, and loss of T_reg, and developed FP and T2DM. Adropin-deficiency contributed to loss of T_reg and the development of FP disease and T2DM.

Adropin is a secretory protein encoded by the energy balance gene and is closely associated with regulation of energy metabolism and insulin resistance. The clinical findings demonstrated its decreased expression in various inflammatory diseases, its negative correlation with the expression levels of inflammatory cytokines, and its potential anti-inflammatory effects. We speculate that adropin plays a pivotal regulatory role in immune cells and inflammatory factors. In this study, we reviewed the advances in researches concentrated on immunological effects of adropin.

Ischemic stroke is the most common type of cerebrovascular disease with high disability and mortality rates, which severely burdens patients, their families, and society. At present, thrombolytic therapy is mainly used for the treatment of ischemic strokes. Even though it can achieve a good effect, thrombolytic recanalization can cause reperfusion injury. Calcitonin gene-related peptide (CGRP) is a neuropeptide that plays a neuroprotective role in the process of ischemia–reperfusion injury. By combining with its specific receptors, CGRP can induce vasodilation of local cerebral ischemia by directly activating the cAMP–PKA pathway in vascular smooth muscle cells and by indirectly activating the NO–cGMP pathway in an endothelial cell-dependent manner,thus rapidly increasing ischemic local blood flow together with reperfusion. CGRP, as a key effector molecule of neurogenic inflammation, can reduce the activation of microglia, downregulates Th1 classical inflammation, and reduce the production of TNF-α, IL-2, and IFN-γ and the innate immune response of macrophages, leading to the reduction of inflammatory factors. CGRP can reduce the overexpression of the aquaporin-4 (AQP-4) protein and its mRNA in the cerebral ischemic junction, and play a role in reducing cerebral edema. CGRP can protect endothelial cells from angiotensin II by reducing the production of oxidants and protecting antioxidant defense. Furthermore, CGRP-upregulated eNOS can further induce VEGF expression, which then promotes the survival and angiogenesis of vascular endothelial cells. CGRP can also reduce apoptosis by promoting the expression of Bcl-2 and inhibiting the expression of caspase-3. These effects suggest that CGRP can reduce brain injury and repair damaged nerve function. In this review, we focused on the role of CGRP in cerebral ischemia–reperfusion injury.

Background: Previous studies revealed somatic mutations of the cationic trypsinogen gene (PRSS1) in patients with chronic pancreatitis and pancreatic cancer. However, whether PRSS1 mutations trigger pancreatic cancer and/or promote malignant proliferation and metastasis in pancreatic cancer remains largely unclear, as well as the potential underlying mechanisms. Methods: In the present study, whole-exome sequencing was applied for screening, and the R116C mutation was validated by Sanger sequencing. Phosphorylation antibody array, RNA-Seq, and RT-qPCR were adopted to screen and validate that R116C mutation promoted pancreatic cancer progression via the JAK1-STAT5 pathway. Results: It showed that migration and invasion were significantly increased in R116C-bearing PANC-1 cells compared with wild type counterparts. In a transgenic mouse model of iZEG-PRSS1_R116C, primary pancreatic intraepithelial neoplasia (PanINs) was observed in the pancreatic duct. Conclusions: These findings suggested a novel pathway mediating pancreatic cancer development, with PRSS1 mutation and overexpression playing an “inside job” role in pancreatic carcinogenesis and tumor development.