SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/ß-catenin signaling.

Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with ß-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/ß-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the ß-catenin inhibitor XAV-939, ß-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/ß-catenin signaling pathway.

A population-based study of Helicobacter pylori: Does asymptomatic infection mean no gastroscopic lesions?

OBJECTIVES: We determined the common clinical characteristics of patients infected with Helicobacter pylori (H. pylori) and investigated the relationship between H. pylori infection, and clinical symptoms, and gastroscopic manifestations. Our focus was specifically on the clinical manifestations in asymptomatic patients. METHODS: We obtained the physical examination data of patients who underwent the 14C urea breath test between January 2018 and December 2020 at our Hospital. Basic demographic data, questionnaire data on clinical symptoms, and clinical examination data of the patients were also collected, and the correlation analysis was performed. RESULTS: A total of 2863 participants were included in the study. The overall H. pylori infection rate was 26.30%. The clinical symptoms between H. pylori-positive patients and H. pylori-negative patients did not differ significantly (P > .05). However, H. pylori-positive patients exhibited more severe gastroscopic manifestations (P < .001). The 14C urea breath test disintegrations per minute (DPM) values in H. pylori-positive patients correlated with their serum pepsinogen and gastrin-17 levels. With an increase in the DPM value, more combinations of clinical symptoms appeared in the patients. Among H. pylori-positive patients, DPM levels in asymptomatic patients were lower than those in symptomatic patients (P < .001). However, gastroscopic manifestations did not vary significantly between asymptomatic and symptomatic patients (P > .05). CONCLUSION: Patients infected with H. pylori showed no specific gastrointestinal symptoms. Patients with asymptomatic infection showed lower DPM levels, but their gastroscopic manifestations were similar to those of patients with symptomatic infection, and their lesions were more severe than H. pylori-negative people.

Effects of different water quality regulators on growth performance, immunologic function, and domestic water quality of GIFT tilapia.

Water quality regulation is widely recognized as a highly effective strategy for disease prevention in the field of aquaculture, and it holds significant potential for the development of sustainable aquaculture. Herein, four water quality regulators, including potassium monopersulfate (KMPS), tetrakis hydroxymethyl phosphonium sulfate (THPS), bacillus subtilis (BS), and chitosan (CS), were added to the culture water of Oreochromis niloticus (GIFT tilapia) every seven days. Subsequently, the effects of these four water quality regulators on GIFT tilapia were comprehensively evaluated by measuring the water quality index of daily growth-related performance and immune indexes of GIFT tilapia. The findings indicated that implementing the four water quality regulators resulted in a decrease in the content of ammonia nitrogen, active phosphate, nitrite, total organic carbon (TOC), and chemical oxygen demand (COD) in the water. Additionally, these regulators were found to maintain dissolved oxygen (DO) levels and pH of the water effectively. Furthermore, using these regulators demonstrated positive effects on various physiological parameters of GIFT tilapia, including improvements in final body weight, weight gain rate (WGR), specific growth rate (SGR), condition factor (CF), feed conversion ratio (FCR), spleen index (SI), hepato-somatic index (HSI), immune cell count, the activity of antioxidant-related enzymes (Nitric oxide, NO and Superoxide dismutase, SOD), and mRNA expression levels of immunity-related factors (Tumor Necrosis Factor-alpha, TNF-α and Interleukin-1 beta, IL-1ß) in the liver and spleen. Notably, the most significant improvements were observed in the groups treated with the BS and CS water quality regulators. Moreover, BS and CS groups exhibited significantly higher serum levels of albumin (ALB) and total protein (TP) (P < 0.05), whereas the other indicators showed no significant difference (P > 0.05) compared to the control group. However, the KMPS and THPS groups of GIFT tilapia exhibited significantly higher serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE) and blood urea nitrogen (BUN) (P < 0.05), whereas they exhibited significantly decreased HSI (P < 0.05). In addition, the partially pathological observations revealed the presence of cell vacuolation, nuclear shrinkage, and pyknosis within the liver. In conclusion, these four water quality regulators, mainly BS and CS, could improve the growth performance and immunity of GIFT tilapia to varying degrees by regulating the water quality and then further increasing the expression levels of immune-related factors or the activity of antioxidant-related enzymes of GIFT tilapia. On the contrary, the prolonged use of KMPS and THPS may gradually diminish their growth-enhancing properties and potentially hinder the growth of GIFT tilapia.

Tissue clearing to examine glioma complexity in 3 dimensions.

In recent years, tissue clearing has revolutionized the way we view biological materials. This has resulted in considerable advances in neuropathology and brain imaging. Its application to gliomas has the potential to increase understanding of tumor architecture, reveal mechanisms of tumor invasion, and provide valuable insights into diagnostics and treatments. This review outlines numerous tissue-clearing applications and recent developments in glioma research and delineates the limitations of existing technology and potential applications in experimental and clinical oncology.

Expression alteration and dysfunction of ion channels/transporters in the parietal cells induces gastric diffused mucosal injury.

Gastric mucosal injuries include focal and diffused injuries, which do and do not change the cell differentiation pattern. Parietal cells loss is related to the occurrence of gastric mucosal diffused injury, with two phenotypes of spasmolytic polypeptide-expressing metaplasia and neuroendocrine cell hyperplasia, which is the basis of gastric cancer and gastric neuroendocrine tumor respectively. Multiple ion channels and transporters are located and expressed in the parietal cells, which is not only regulate the gastric acid-base homeostasis, but also regulate the growth and development of parietal cells. Therefore, alteration and dysregulation of ion channels and transporters in the parietal cells impairs the morphology and physiological functions of stomach, resulted in gastric diffused mucosal damage. In this review, multiple ion channels and transporters in parietal cells, including K+ channels, aquaporins, Cl- channels, Na+/H+ transporters, and Cl-/HCO3- transporters are described, and their roles in gastric diffused mucosal injury are discussed. We hope to drive researcher's attention to focus on the role of ion channels/transporters loss in the parietal cells induced gastric diffused mucosal injury.

SPINKs in Tumors: Potential Therapeutic Targets.

The serine protease inhibitor Kazal type (SPINK) family includes SPINK1-14 and is the largest branch in the serine protease inhibitor family. SPINKs play an important role in pancreatic physiology and disease, sperm maturation and capacitation, Nager syndrome, inflammation and the skin barrier. Evidence shows that the unregulated expression of SPINK1, 2, 4, 5, 6, 7, and 13 is closely related to human tumors. Different SPINKs exhibit various regulatory modes in different tumors and can be used as tumor prognostic markers. This article reviews the role of SPINK1, 2, 4, 5, 6, 7, and 13 in different human cancer processes and helps to identify new cancer treatment targets.

Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases.

The incidence of gastrointestinal (GI) mucosal diseases, including various types of gastritis, ulcers, inflammatory bowel disease and GI cancer, is increasing. Therefore, it is necessary to identify new therapeutic targets. Ion channels/transporters are located on cell membranes, and tight junctions (TJs) affect acid-base balance, the mucus layer, permeability, the microbiota and mucosal blood flow, which are essential for maintaining GI mucosal integrity. As ion channel/transporter dysfunction results in various GI mucosal diseases, this review focuses on understanding the contribution of ion channels/transporters to protecting the GI mucosal barrier and the relationship between GI mucosal disease and ion channels/transporters, including Cl-/HCO3- exchangers, Cl- channels, aquaporins, Na+/H+ exchangers, and K+ channels. Here, we provide novel prospects for the treatment of GI mucosal diseases.

Alteration and dysfunction of ion channels/transporters in a hypoxic microenvironment results in the development and progression of gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant cancers in the world and has only few treatment options and, concomitantly, a poor prognosis. It is generally accepted now that the tumor microenvironment, particularly that under hypoxia, plays an important role in cancer development. Hypoxia can regulate the energy metabolism and malignancy of tumor cells by inducing or altering various important factors, such as oxidative stress, reactive oxygen species (ROS), hypoxia-inducible factors (HIFs), autophagy and acidosis. In addition, altered expression and/or dysfunction of ion channels/transporters (ICTs) have been encountered in a variety of human tumors, including GC, and to play an important role in the processes of tumor cell proliferation, migration, invasion and apoptosis. Increasing evidence indicates that ICTs are at least partly involved in interactions between cancer cells and their hypoxic microenvironment. Here, we provide an overview of the different ICTs that regulate or are regulated by hypoxia in GC. CONCLUSIONS AND PERSPECTIVES: Hypoxia is one of the major obstacles to cancer therapy. Regulating cellular responses and factors under hypoxia can inhibit GC. Similarly, altering the expression or activity of ICTs, such as the application of ion channel inhibitors, can slow down the growth and/or migration of GC cells. Since targeting the hypoxic microenvironment and/or ICTs may be a promising strategy for the treatment of GC, more attention should be paid to the interplay between ICTs and the development and progression of GC in such a microenvironment.

Physiological and pathophysiological role of ion channels and transporters in the colorectum and colorectal cancer.

The incidence of colorectal cancer has increased annually, and the pathogenesis of this disease requires further investigation. In normal colorectal tissues, ion channels and transporters maintain the water-electrolyte balance and acid/base homeostasis. However, dysfunction of these ion channels and transporters leads to the development and progression of colorectal cancer. Therefore, this review focuses on the progress in understanding the roles of ion channels and transporters in the colorectum and in colorectal cancer, including aquaporins (AQPs), Cl- channels, Cl- / HCO3- exchangers, Na+ / HCO3- transporters and Na+ /H+ exchangers. The goal of this review is to promote the identification of new targets for the treatment and prognosis of colorectal cancer.