The bicarbonate ion has a fundamental role in vital systems. Impaired bicarbonate transport leads to various diseases, including immune disorders, cystic fibrosis, tumorigenesis, kidney diseases, brain dysfunction, tooth fracture, ischemic reperfusion injury, hypertension, impaired reproductive system, and systemic acidosis. Carbonic anhydrases are involved in the mechanism of bicarbonate movement and consist of complex of bicarbonate transport systems including bicarbonate transporters. This review focused on the convergent regulation of ion homeostasis through various ion transporters including bicarbonate transporters, their regulatory enzymes, such as carbonic anhydrases, pH regulatory role, and the expression pattern of ion transporters in non-secretory systems throughout the body. Understanding the correlation between these systems will be helpful in order to obtain new insights and design potential therapeutic strategies for the treatment of pH-related disorders. In this review, we have discussed the broad prospects and challenges that remain in elucidation of bicarbonate-transport-related biological and developmental systems.

Applications of nanoparticles in various fields have been addressed. Nanomaterials serve as carriers for transporting conventional drugs or proteins through lysosomes to various cellular targets. The basic function of lysosomes is to trigger degradation of proteins and lipids. Understanding of lysosomal functions is essential for enhancing the efficacy of nanoparticles-mediated therapy and reducing the malfunctions of cellular metabolism. The lysosomal function is modulated by the movement of ions through various ion channels. Thus, in this review, we have focused on the recruited ion channels for lysosomal function, to understand the lysosomal modulation through the nanoparticles and its applications. In the future, lysosomal channels-based targets will expand the therapeutic application of nanoparticles-associated drugs.

PyK2 is a member of the proline-rich tyrosine kinase and focal adhesion kinase families and is ubiquitously expressed. PyK2 is mainly activated by stimuli, such as activated Src kinases and intracellular acidic pH. The mechanism of PyK2 activation in cancer cells has been addressed extensively. The up-regulation of PyK2 through overexpression and enhanced phosphorylation is a key feature of tumorigenesis and cancer migration. In this review, we summarized the cancer milieu, including acidification and cancer-associated molecules, such as chemical reagents, interactive proteins, chemokine-related molecules, calcium channels/transporters, and oxidative molecules that affect the fate of PyK2. The inhibition of PyK2 leads to a beneficial strategy to attenuate cancer cell development, including metastasis. Thus, we highlighted the effect of PyK2 on various cancer cell types and the distribution of molecules that affect PyK2 activation. In particular, we underlined the relationship between PyK2 and cancer metastasis and its potential to treat cancer cells.

The ubiquitin–proteasome system (UPS) is the main proteolytic pathway by which damaged target proteins are degraded after ubiquitination and the recruit of ubiquitinated proteins, thus regulating diverse physiological functions and the maintenance in various tissues and cells. Ca²⁺ signaling is raised by oxidative or ER stress. Although the basic function of the UPS has been extensively elucidated and has been continued to define its mechanism, the precise relationship between the UPS and Ca²⁺ signaling remains unclear. In the present review, we describe the relationship between the UPS and Ca²⁺ signaling, including Ca²⁺-associated proteins, to understand the end point of oxidative stress. The UPS modulates Ca²⁺ signaling via the degradation of Ca²⁺-related proteins, including Ca²⁺ channels and transporters. Conversely, the modulation of UPS is driven by increases in the intracellular Ca²⁺ concentration. The multifaceted relationship between the UPS and Ca²⁺ plays critical roles in different tissue systems. Thus, we highlight the potential crosstalk between the UPS and Ca²⁺ signaling by providing an overview of the UPS in different organ systems and illuminating the relationship between the UPS and autophagy.

Cholesterol trafficking is initiated by the endocytic pathway and transported from endo/lysosomes to other intracellular organelles. Deficiencies in cholesterol-sensing and binding proteins NPC1 and NPC2 induce accumulation in lysosomes and the malfunction of trafficking to other organelles. Each organelle possesses regulatory factors to induce cholesterol trafficking. The mutation of NPC1 and NPC2 genes induces Niemann-Pick disease type C (NPDC), which is a hereditary disease and causes progressive neurodegeneration, developmental disability, hypotonia, and ataxia. Oxidative stress induces damage in NPDC-related intracellular organelles. Although studies on the relationship between NPDC and oxidation are relatively rare, several studies have reported the therapeutic potential of antioxidants in treating NPDC. Investigating antioxidant drugs to relieve oxidative stress and cholesterol accumulation is suggested to be a powerful tool for developing treatments for NPDC. Understanding NPDC provides challenging issues in understanding the oxidative stress–lysosome metabolism of the lipid axis. Thus, we elucidated the relationship between complexes of intracellular organelles and NPDC to develop our knowledge and suggested potential antioxidant reagents for NPDC therapy.

Poly L-lactic acid (PLLA) fillers stimulate collagen synthesis by activating various immune cells and fibroblasts. Piezo1, an ion channel, responds to mechanical stimuli, including changes in extracellular matrix stiffness, by mediating Ca²⁺ influx. Given that elevated intracellular Ca²⁺ levels trigger signaling pathways associated with fibroblast proliferation, Piezo1 is a pivotal regulator of collagen synthesis and tissue fibrosis. The aim of the present study was to investigate the impact of PLLA on dermal collagen synthesis by activating Piezo1 in both an H₂O₂-induced cellular senescence model in vitro and aged animal skin in vivo. PLLA elevated intracellular Ca²⁺ levels in senescent fibroblasts, which was attenuated by the Piezo1 inhibitor GsMTx4. Furthermore, PLLA treatment increased the expression of phosphorylated ERK1/2 to total ERK1/2 (pERK1/2/ERK1/2) and phosphorylated AKT to total AKT (pAKT/AKT), indicating enhanced pathway activation. This was accompanied by upregulation of cell cycle-regulating proteins (CDK4 and cyclin D1), promoting the proliferation of senescent fibroblasts. Additionally, PLLA promoted the expression of phosphorylated mTOR/S6K1/4EBP1, TGF-β, and Collagen I/III in senescent fibroblasts, with GsMTx4 treatment mitigating these effects. In aged skin, PLLA treatment similarly upregulated the expression of pERK1/2/ERK1/2, pAKT/AKT, CDK4, cyclin D1, mTOR/S6K1/4EBP1, TGF-β, and Collagen I/III. In summary, our findings suggest Piezo1′s involvement in PLLA-induced collagen synthesis, mediated by heightened activation of cell proliferation signaling pathways such as pERK1/2/ERK1/2, pAKT/AKT, and phosphorylated mTOR/S6K1/4EBP1, underscoring the therapeutic potential of PLLA in tissue regeneration.