Homeostasis Regulation by Potassium Channel Subfamily K Member 3 (KCNK3) in Various Fishes

Potassium channels are important for K+ transport and cell volume regulation, which play important roles in many biological processes such as hormone secretion, ion homeostasis, excitability, and cell development. In mammals, a total of 15 potassium channels were identified and they were divided into six subfamilies, including TALK (TALK1, TALK2, TASK2), TASK (TASK1, TASK3, TASK5), TREK (TREK1, TREK2, TRAAK), TWIK (TWIK1, TWIK2, KCNK7), THIK (THIK1, THIK2) and TRESK. TASK1, also known as potassium channel subfamily k member 3 (KCNK3), is the first member identified in the TASK subfamily. This K2P channel has potential applications in fish breeding and aquaculture industry due to its important roles in various physiological processes. Despite its functional role has been well studied in mammals; however, it is less known in fishes. In this review, we systematically summarize recent research advances of this critical potassium channel in representative fishes, such as gene number variation, tissue distribution, phylogeny, and potential homeostasis regulation role. This paper provides novel insights into the functional properties of these fish kcnk3 genes (including osmoregulation, energy homeostasis maintenance and fatty acids metabolism regulation), and also expands our knowledge about their variations among diverse fishes.

Particition of Sodium-potassium Adenosine Triphosphatases in Homeostasis Regulation

A literature review presented an analysis of data regarding the mechanisms of the Na pump in nephron and hormonal regulators of enzyme activity, including enzymatic catalysts. Investigating the regulatory mechanisms of metabolic processes can facilitate the development of new strategies to repair various pathological conditions. Among these functional proteins, Na+/K+ATPase is responsible for the regulation of hydroionic homeostasis and signaling. Ion transport in different parts of the nephron is mediated via sodium transporters, which are characterized by a clear topographical expression. In the oligomeric Na+/K+ATPase molecule, the α-subunit comprises 10 transmembrane domains and performs a catalytic function. The signal function of Na+/K+ATPase and its interaction with the molecular environment in lipid microdomains involve rafts and caveolae. Analysis of the literature data demonstrated an important function of Na+/K+ATPase, along with its interaction with caveolin-1, in the regulation of intracellular cholesterol traffic. Moreover, reciprocal interactions of enzymes and cholesterol have been indicated. The status of Na+/K+ATPase activity is affected by hypoxia, reactive oxygen species, lipid peroxidation (LPO), increased cholesterol concentrations, and the viscosity of the cytoplasmic membrane. Ecological pollutants, including heavy metals, have significant effects on enzyme activity in nephron, hepatocytes and cardiomyocytes. Thus, available literature data indicate an important role of Na+/K+ATPase in the regulation of metabolic processes.

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are closely related to a variety of biological and functional aspects of human health. When the exosomal ncRNAs undergo tissue-specific changes due to diverse internal or external disorders, they can cause tissue dysfunction, aging, and diseases. In this review, we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases. In addition, we explore the current knowledge on the roles of exosomal miRNAs, lncRNAs, and circRNAs in human health and diseases, including cancers, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and infectious diseases, to determine their potential implication in biomarker identification and therapeutic exploration.

Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation

Nanomaterials with enzyme-like activity (nanozymes) have found applications in various fields of medicine, industry, and environmental protection. This review discusses the use of nanozymes in the regulation of cellular homeostasis. We also review the latest biomedical applications of nanozymes related to their use in cellular redox status modification and detection. We present how nanozymes enable biomedical advances and demonstrate basic design strategies to improve diagnostic and therapeutic efficacy in various diseases. Finally, we discuss the current challenges and future directions for developing nanozymes for applications in the regulation of the redox-dependent cellular processes and detection in the cellular redox state changes.

Prostate Cancer—Focus on Cholesterol

Prostate cancer (PC) is the most common malignancy in men. Common characteristic involved in PC pathogenesis are disturbed lipid metabolism and abnormal cholesterol accumulation. Cholesterol can be further utilized for membrane or hormone synthesis while cholesterol biosynthesis intermediates are important for oncogene membrane anchoring, nucleotide synthesis and mitochondrial electron transport. Since cholesterol and its biosynthesis intermediates influence numerous cellular processes, in this review we have described cholesterol homeostasis in a normal cell. Additionally, we have illustrated how commonly deregulated signaling pathways in PC (PI3K/AKT/MTOR, MAPK, AR and p53) are linked with cholesterol homeostasis regulation.

The multiple mechanisms of MCL1 in the regulation of cell fate

MCL1 (myeloid cell leukemia-1) is a widely recognized pro-survival member of the Bcl-2 (B-cell lymphoma protein 2) family and a promising target for cancer therapy. While the role MCL1 plays in apoptosis is well defined, its participation in emerging non-apoptotic signaling pathways is only beginning to be appreciated. Here, we synthesize studies characterizing MCL1s influence on cell proliferation, DNA damage response, autophagy, calcium handling, and mitochondrial quality control to highlight the broader scope that MCL1 plays in cellular homeostasis regulation. Throughout this review, we discuss which pathways are likely to be impacted by emerging MCL1 inhibitors, as well as highlight non-cancerous disease states that could deploy Bcl-2 homology 3 (BH3)-mimetics in the future.

Polarization of macrophage cellular center during endometrioid cyst evolution

Introduction. Macrophages are the center of homeostasis regulation in endometrioid heterotopia tissue. Being one of the most important elements in understanding the pathogenesis of endometriosis, macrophages control the changes in the cooperation of cellular elements.Aim. The aim of the study was to assess the location, nature, and strength of correlation relationships between the macrophages/ siderophages and other cell populations in the endometrioid cysts wall at various stages of their formation.Material and Methods. The study comprised 57 patients with a histologically verified diagnosis of endometrioid ovarian cyst. All the studied endometrioid cysts were divided into “young”, “mature”, and “old” based on the morphological features. The macrophages/siderophages, lymphocytes, neutrophils, and eosinophils were counted in 10 visual fields in the cyst wall after staining with hematoxylin and eosin at ×400 magnification at the different layers of cyst wall.Results. The dynamics of changes in the location, direction, and strength of correlations showed that the functional destruction of macrophage cell center occurred during maturation and aging of the ovarian endometrioid cyst. This process was caused by an insufficient vascularization of endometrioid heterotopia, increasing pressure inside the cyst, and the gradual compaction of underlying fibrous layer, which lead to the atrophy of endometrioid lining and inability of macrophage cell center to maintain homeostasis. These changes caused a complete depletion of macrophage cell center due to macrophage polarization and subsequent formation of siderophages.Conclusion. In the absence of endometrium-associated macrophage pool renewal, endometrioid heterotopia eventually subside due to the destruction of macrophage cell center that controls its homeostasis.

Can Homeostasis Be Static?

Особое понимание гомеостаза и гомеостатичного регулирования в целом появилось за последние 20 лет в связи с доказательством гипотезы W. Weaver о биосистемах третьего типа и открытием эффекта Еськова–Зинченко. Однако имеется ряд работ, в которых высказывалось мнение о нестатичности в гомеостатичном регулировании внутренней среды организма человека. Более того, в рамках этого эффекта сейчас говорят об отсутствии статичных состояний любых функций организма человека. Это существенно расширяет наши представления о теории функциональных систем организма человека, которую разрабатывал П. К. Анохин в середине XX века. Сейчас мы вправе говорить о новом понимании кибернетики, которая лежит в основе описания различных физиологических функций человека. Возникает новая биологическая и медицинская кибернетика, в которой нет статичного гомеостаза и нет статики в параметрах функций организма человека. In 20 years the new understanding of homeostasis and special homeostatic regulation emerged associated with the W. Weaver hypothesis on biosystems of the third type and the discovery of the Eskov-Zinchenko effect. There are some papers about the unstable behavior of the homeostasis regulation in the human body. Now we can speak about the absence of any stable states of any human body function. This significantly expands our understanding of the theory of human functional systems developed by P. K. Anokhin in the middle of the 20th century. Now we can speak of a new understanding of cybernetics as a basis for the definition of various human physiological functions. A new biological and medical cybernetics is emerging; it denies static homeostasis and static parameters of the human body functions.

Targeting the Copper Transport System to Improve Treatment Efficacies of Platinum-Containing Drugs in Cancer Chemotherapy

The platinum (Pt)-containing antitumor drugs including cisplatin (cis-diamminedichloroplatinum II, cDDP), carboplatin, and oxaliplatin, have been the mainstay of cancer chemotherapy. These drugs are effective in treating many human malignancies. The major cell-killing target of Pt drugs is DNA. Recent findings underscored the important roles of Pt drug transport system in cancer therapy. While many mechanisms have been proposed for Pt-drug transport, the high-affinity copper transporter (hCtr1), Cu chaperone (Atox1), and Cu exporters (ATP7A and ATP7B) are also involved in cDDP transport, highlighting Cu homeostasis regulation in Pt-based cancer therapy. It was demonstrated that by reducing cellular Cu bioavailable levels by Cu chelators, hCtr1 is transcriptionally upregulated by transcription factor Sp1, which binds the promoters of Sp1 and hCtr1. In contrast, elevated Cu poisons Sp1, resulting in suppression of hCtr1 and Sp1, constituting the Cu-Sp1-hCtr1 mutually regulatory loop. Clinical investigations using copper chelator (trientine) in carboplatin treatment have been conducted for overcoming Pt drug resistance due in part to defective transport. While results are encouraging, future development may include targeting multiple steps in Cu transport system for improving the efficacies of Pt-based cancer chemotherapy. The focus of this review is to delineate the mechanistic interrelationships between Cu homeostasis regulation and antitumor efficacy of Pt drugs.