Estrogen is an important sex steroid hormone which serves an important role in the regulation of a number of biological functions, including regulating bone density, brain function, cholesterol mobilization, electrolyte balance, skin physiology, the cardiovascular system, the central nervous system and female reproductive organs. Estrogen exhibits various functions through binding to its specific receptors, estrogen receptor α, estrogen receptor β and G protein-coupled estrogen receptor 1. In recent years, researchers have demonstrated that estrogen and its receptors serve an important role in the gastrointestinal (GI) tract and contribute to the progression of a number of GI diseases, including gastroesophageal reflux, esophageal cancer, peptic ulcers, gastric cancer, inflammatory bowel disease, irritable bowel syndrome and colon cancer. The aim of this review is to provide an overview of estrogen and its receptors in GI disease, and highlight potential avenues for the prevention and treatment of GI diseases.

Transient receptor potential vanilloid subtype 1 (TRPV1), a member of the transient receptor potential vanilloid (TRPV) channel family, is a nonselective cation channel that is widely expressed in sensory nerve fibers and nonneuronal cells, including certain vascular endothelial cells and smooth muscle cells. The activation of TRPV1 may be involved in the regulation of various physiological functions, such as the release of inflammatory mediators in the body, gastrointestinal motility function, and temperature regulation. In recent years, a large number of studies have revealed that TRPV1 plays an important role in the physiological and pathological conditions of the digestive system, cardiovascular system, and respiratory system, but there is no systematic report on TRPV1. The objective of this review is to explain the function and effects of TRPV1 on specific diseases, such as irritable bowel syndrome, hypertension, and asthma, and to further investigate the intrinsic relationship between the expression and function of TRPV1 in those diseases to find new therapeutic targets for the cure of related diseases.

The gut-brain axis is a bidirectional information interaction system between the central nervous system (CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut- liver-brain axis.

Estrogen-dependent breast cancer (EDBC) is a kind of common malignant tumor in postmenopausal women with growing tendency in recent years. Aromatase (AR) is the key enzyme responsible for estrogen biosynthesis and has been considered as an important target for designing inhibitors as potent therapeutic agents for EDBC. AR inhibitors (AIs) are divided into steroidal and nonsteroidal compounds, and the latter shows high inhibitory potency against AR. This review summarizes recent advancement in nonsteroidal AIs.

The Na+/Ca2+ exchanger (NCX) protein family is a part of the cation/Ca2+ exchanger superfamily and participates in the regulation of cellular Ca2+ homeostasis. NCX1, the most important subtype in the NCX family, is expressed widely in various organs and tissues in mammals and plays an especially important role in the physiological and pathological processes of nerves and the cardiovascular system. In the past few years, the function of NCX1 in the digestive system has received increasing attention; NCX1 not only participates in the healing process of gastric ulcer and gastric mucosal injury but also mediates the development of digestive cancer, acute pancreatitis, and intestinal absorption. This review aims to explore the roles of NCX1 in digestive system physiology and pathophysiology in order to guide clinical treatments.

Neurotransmitters are special molecules that serve as messengers in chemical synapses between neurons, cells, or receptors, including catecholamines, serotonin, dopamine, and other neurotransmitters, which play an important role in both human physiology and pathology. Compelling evidence has indicated that neurotransmitters have an important physiological role in various digestive diseases. They act as ligands in combination with central or peripheral receptors, and transmits signals through chemical synapses, which are involved in regulating the physiological and pathological processes of the digestive tract organs. For instance, neurotransmitters regulate blood circulation and affect intestinal movement, nutrient absorption, the gastrointestinal innate immune system, and the microbiome. In this review, we will focus on the role of neurotransmitters in the pathogenesis of digestive tract diseases to provide novel therapeutic targets for new drug development in digestive diseases.

Cancer stem cells (CSCs) are immortal cells in tumor tissues that have been proposed as the driving force of tumorigenesis and tumor invasion. Previously, ion channels were revealed to contribute to cancer cell proliferation, migration and apoptosis. Recent studies have demonstrated that ion channels are present in various CSCs; however, the functions of ion channels and their mechanisms in CSCs remain unknown. The present review aimed to focus on the roles of ion channels in the regulation of CSC behavior and the CSC-like properties of cancer cells. Evaluation of the relationship between ion channels and CSCs is critically important for understanding malignancy.

Tumors pose a major threat to human health and present with difficulties that modern medicine has yet to overcome. It has been demonstrated that the acid-base balance of the tumor microenvironment is closely associated with the dynamic balance in the human body and that it regulates several processes, such as cell proliferation and differentiation, intracellular enzyme activity, and cytoskeletal assembly and depolymerization. It has been well established that the regulation of intra-and extracellular pH depends on a series of functional ion transporters and hydrogen ion channels, such as the Na + /H + exchanger (NHE) protein and thee Cl/HCO 3-exchange protein, among which the NHE1 member of the NHE family has been attracting increasing attention in recent years, particularly in studies on the correlation between pH regulation and tumors. NHE1 is a housekeeping gene encoding a protein that is widely expressed on the surface of all plasma membranes. Due to its functional domain, which determines the pHi at its N-terminus and C-terminus, NHE1 is involved in the regulation of the cellular pH microenvironment. It has been reported in the literature that NHE1 can regulate cell volume, participate in the transmembrane transport of intracellular and extracellular ions, affect cell proliferation and apoptosis, and regulate cell behavior and cell cycle progression; however, research on the role of NHE1 in tumorigenesis and tumor development in various systems is at its early stages. The aim of the present study was to review the current research on the correlation between the NHE family proteins and various systemic tumors, in order to indicate a new direction for antitumor drug development with the pH microenvironment as the target.