The pancreatic duodenum homeobox-1 (PDX-1) is a transcription factor encoded by a Hox-like homeodomain gene that plays a crucial role in pancreatic development, β-cell differentiation, and the maintenance of mature β-cell functions. Research on the relationship between PDX-1 and diabetes has gained much attention because of the increasing prevalence of diabetes melitus (DM). Recent studies have shown that the overexpression of PDX-1 regulates pancreatic development and promotes β-cell differentiation and insulin secretion. It also plays a vital role in cell remodeling, gene editing, and drug development. Conversely, the absence of PDX-1 increases susceptibility to DM. Therefore, in this review, we summarized the role of PDX-1 in pancreatic development and the pathogenesis of DM. A better understanding of PDX-1 will deepen our knowledge of the pathophysiology of DM and provide a scientific basis for exploring PDX-1 as a potential target for treating diabetes.

The final outcome of diabetes is chronic complications, of which vascular complications are the most serious, which is the main cause of death for diabetic patients and the direct cause of the increase in the cost of diabetes. Type 1 and type 2 diabetes are the main types of diabetes, and their pathogenesis is completely different. Type 1 diabetes is caused by genetics and immunity to destroy a large number of β cells, and insulin secretion is absolutely insufficient, which is more prone to microvascular complications. Type 2 diabetes is dominated by insulin resistance, leading to atherosclerosis, which is more likely to progress to macrovascular complications. This article explores the pathogenesis of two types of diabetes, analyzes the pathogenesis of different vascular complications, and tries to explain the different trends in the progression of different types of diabetes to vascular complications, in order to better prevent diabetes and its vascular complications.

Berberine (BBR), extracted from the traditional medicinal plant Coptis chinensis Franch., has been widely used for the treatment of type 2 diabetes mellitus (T2DM) and its complications. To determine the potential pharmacological mechanisms underlying BBR therapeutic effect on T2DM and its complications by in silico network pharmacology and experimental in vivo validation. A predictive network depicting the relationship between BBR and T2DM was designed based on information collected from several databases, namely STITCH, CHEMBL, PharmMapper, TTD, Drugbank, and PharmGKB. Identified overlapping targets related to both BBR and T2DM were crossed with information on biological processes (BPs) and molecular/signaling pathways using the DAVID platform and Cytoscape software. Three candidate targets identified with the BBR-T2DM network (RXRA, KCNQ1 and NR3C1) were evaluated in the C57BL/6J mouse model of T2DM. The mice were treated with BBR or metformin for 10 weeks. Weight, fasting blood glucose (FBG), oral glucose tolerance, and expression levels of the three targets were evaluated. A total of 31 targets of BBR that were also related to T2DM were identified, of which 14 had already been reported in previous studies. Furthermore, these 31 overlapping targets were enriched in 21 related BPs and 18 pathways involved in T2DM treatment. The identified BP-target-pathway network revealed the underlying mechanisms of BBR antidiabetic activity were mediated by core targets such as RXRA, KCNQ1, and NR3C1. In vivo experiments further confirmed that treatment with BBR significantly reduced weight and FBG and alleviated insulin resistance in T2DM mice. Moreover, BBR treatment promoted RXRA expression, whereas it reduced KCNQ1 and NR3C1 expression in the liver. Using network pharmacology and a T2DM mouse model, this study revealed that BBR can effectively prevent T2DM symptoms through vital targets and multiple signaling pathways. Network pharmacology provides an efficient, time-saving approach for therapeutic research and the development of new drugs.

Background: Breast cancer is one of the most prevalent gynecologic malignancies worldwide. Despite the high sensitivity in response to chemotherapy, drug resistance occurred frequently in clinical treatment. Cryptotanshinone (CTS) is a herbal medicine and has been identified as an anti-inflammatory and anti-oxidative drug. Methods: In vitro assays, including the cell proliferation assay, colony formation assay, Western blot analysis, transwell migration/invasion assays, and cell scratch assay were used to explore the biological activities and working mechanism of CTS. Breast cancer cells were also transfected with PKM2 expressing vectors to define the molecular mechanisms involved in CTS-mediated anti-tumor activity. Results: We found that CTS shows anti-proliferative effects and decreases the clonogenic ability of breast cancer cells. We also found that CTS inhibited the migration and invasion activity of MCF-7 and MDA-MB-231 cells by different analyzed methods. CTS also downregulated the levels of glycolysis-related proteins, such as PKM2, LDHA, and HK2. In addition, overexpression of PKM2 recovered CTS-mediated suppression of cell proliferation, colony formation, and cell mobility of breast cancer cells. We also found PKM2 was significantly overexpressed in tumor tissues and invasive ductal breast carcinoma compared to normal tissues and patients with high PKM2 expression had worse overall survival and metastasis-free survival outcomes. Conclusion: CTS inhibited the proliferation, migration, and invasion of breast cancer cells. The involved mechanism may refer to the downregulation of the PKM2/β-catenin axis.