[Effects of biomechanics on colorectal organoid culture].

In recent years, organoids have become a crucial model for studying the physiopathological processes in tissues and organs. The emergence of organoids has promoted the research on the mechanisms of the occurrence and clinical translation of diseases. Among these organoid models, colorectal organoid models are increasingly mature. Colorectal cancer is a common gastrointestinal malignant tumor worldwide, posing a serious threat to human health. Colorectal organoids provide a new model for studying the pathophysiology, drug sensitivity, and precision medicine of colorectal cancer. The conventional culture systems of colorectal organoids focus more on the role of biochemical factors, neglecting the fact that the gut is also influenced by biophysical signals in vivo. Therefore, in this review, we discuss the theories related to colorectal organoids and biomechanics and expound the effects of biomechanics on colorectal organoid culture.

The Tumor Microenvironment: Signal Transduction.

In the challenging tumor microenvironment (TME), tumors coexist with diverse stromal cell types. During tumor progression and metastasis, a reciprocal interaction occurs between cancer cells and their environment. These interactions involve ongoing and evolving paracrine and proximal signaling. Intrinsic signal transduction in tumors drives processes such as malignant transformation, epithelial-mesenchymal transition, immune evasion, and tumor cell metastasis. In addition, cancer cells embedded in the tumor microenvironment undergo metabolic reprogramming. Their metabolites, serving as signaling molecules, engage in metabolic communication with diverse matrix components. These metabolites act as direct regulators of carcinogenic pathways, thereby activating signaling cascades that contribute to cancer progression. Hence, gaining insights into the intrinsic signal transduction of tumors and the signaling communication between tumor cells and various matrix components within the tumor microenvironment may reveal novel therapeutic targets. In this review, we initially examine the development of the tumor microenvironment. Subsequently, we delineate the oncogenic signaling pathways within tumor cells and elucidate the reciprocal communication between these pathways and the tumor microenvironment. Finally, we give an overview of the effect of signal transduction within the tumor microenvironment on tumor metabolism and tumor immunity.

The Role of the Hedgehog Pathway in Chemoresistance of Gastrointestinal Cancers.

The hedgehog pathway, which plays a significant role in embryonic development and stem cell regulation, is activated in gastrointestinal cancers. Chemotherapy is widely used in cancer treatment. However, chemoresistance becomes a substantial obstacle in cancer therapy. This review focuses on the recent advances in the hedgehog pathway's roles in drug resistance of gastrointestinal cancers and the novel drugs and strategies targeting hedgehog signaling.

MiR-9-3p augments apoptosis induced by H2O2 through down regulation of Herpud1 in glioma.

MicroRNAs are short, single-stranded non-coding RNA molecules that function as regulators of tumor progression in various cancers, including glioma. The present study sought to investigate the biological functions of miR-9-3p in glioma progression. The results of a microRNA microarray indicated that microRNA-9-3p (miR-9-3p, miR-9*) is down-regulated in high-grade (grades III and IV) gliomas compared with non-tumor tissues. These results were confirmed with real-time PCR. The miR-9-3p expression level was associated with age and tumor grade. Herpud1 was regulated by miR-9-3p in glioma cells and tissues and was identified as a miR-9-3p target with luciferase reporter assays. Glioma cells transfected with miR-9-3p mimics or HERPUD1-RNAi had more apoptotic cells than them in control after induced by H2O2. Our results indicated that low expression of miR-9-3p results in a high level of Herpud1, which may protect against apoptosis in glioma.

Porcine epidemic diarrhea virus N protein prolongs S-phase cell cycle, induces endoplasmic reticulum stress, and up-regulates interleukin-8 expression.

Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by porcine epidemic diarrhea virus (PEDV). The porcine intestinal epithelial cell is the PEDV target cell. In this study, we established a porcine intestinal epithelial cell (IEC) line which can stably express PEDV N protein. We also investigate the subcellular localization and function of PEDV N protein by examining its effects on cell growth, cycle progression, interleukin-8 (IL-8) expression, and survival. The results show that the PEDV N protein localizes in the endoplasmic reticulum (ER), inhibits the IEC growth and prolongs S-phase cell cycle. The S-phase is prolonged which is associated with a decrease of cyclin A transcription level and an increase of cyclin A degradation. The IEC expressing PEDV N protein can express higher levels of IL-8 than control cells. Further studies show that PEDV N protein induces ER stress and activates NF-κB, which is responsible for the up-regulation of IL-8 and Bcl-2 expression. This is the first report to demonstrate that PEDV N protein can induce cell cycle prolongation at the S-phase, ER stress and up-regulation interleukin-8 expression. These findings provide novel information on the function of the PEDV N protein and are likely to be very useful in understanding the molecular mechanisms responsible for PEDV pathogenesis.

Porcine epidemic diarrhea virus E protein causes endoplasmic reticulum stress and up-regulates interleukin-8 expression.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an important pathogen in swine and is responsible for substantial economic losses. Previous studies suggest that the PEDV E protein plays an important role in the viral assembly process. However, the subcellular localization and other functions of PEDV E protein still require more research. METHODS: The subcellular localization and function of PEDV E protein were investigated by examining its effects on cell growth, cell cycle progression, interleukin-8 (IL-8) expression and cell survival. RESULTS: The results show that plenty of PEDV E protein is localized in the ER, with small quantities localized in the nucleus. The PEDV E protein has no effect on the intestinal epithelial cells (IEC) growth, cell cycle and cyclin A expression. The cells expressing PEDV E protein express higher levels of IL-8 than control cells. Further studies show that PEDV E protein induced endoplasmic reticulum (ER) stress and activated NF-κB which is responsible for the up-regulation of IL-8 and Bcl-2 expression. CONCLUSIONS: This study shows that the PEDV E protein is localized in the ER and the nucleus and it can cause ER stress. The PEDV E protein had no effect on the IEC growth and cell cycle. In addition, the PEDV E protein is able to up-regulate IL-8 and Bcl-2 expression.