Search

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. [ABSTRACT FROM AUTHOR]

Lysosomes are responsible for protein degradation and clearance in cellular recycling centers. It has been known that the lysosomal chloride level is enriched and involved in the intrinsic lysosomal function. However, the mechanism by which chloride levels can be sensed and that of the chloride-mediated lysosomal function is unknown. In this study, we verified that reduced chloride levels acutely induced lysosomal calcium release through TRPML1 and lysosomal repositioning toward the juxtanuclear region. Functionally, low chloride-induced lysosomal calcium release attenuated cellular migration. In addition, spontaneous exposure to low chloride levels dysregulated lysosomal biogenesis and subsequently induced delayed migration and promoted apoptosis. Two chloride-sensing GXXXP motifs in the TRPML1 were identified. Mutations in the GXXXP motif of TRPML1 did not affect chloride levels, and there were no changes in migratory ability. In this study, we demonstrated that the depletion of chloride induces reformation of the lysosomal calcium pool and subsequently dysregulated cancer progression, which will assist in improving therapeutic strategies for lysosomal accumulation-associated diseases or cancer cell apoptosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Twisted string actuation is an actuation concept which uses the twisting motion of strings to convert the rotational motion of a motor into a linear motion. By replacing the heavy, high friction, and high-cost gearheads with light, silent, compliant, and low-cost strings, twisted string actuators (TSAs) can provide powerful tendon-based transmission, making it a unique solution for human–robot interactive tasks. Despite such advantages, TSAs exhibit highly nonlinear force/displacement characteristics when compared to conventional geared motors, thus limiting their performance in bidirectional joints. In order to implement TSAs in a bidirectional joint, two motors had to be used to compensate for the nonlinearities, which eventually increased the control complexity, weight, and overall cost of the robotic system. In addition, TSAs show poor durability, which also limits its applicability. To address these issues, a high-performance bidirectional joint has been proposed by implementing optimized TSAs with lubrication, and a variable radius pulley (VRP). By implementation of specially designed TSAs, we achieved 1) extended service time of the strings. Furthermore, by replacing the conventional circular pulley with a VRP, we achieved 2) improved range of motion; 3) increased payload; and 4) better tracking performance, even with a single motor. [ABSTRACT FROM AUTHOR]

Simple Summary: Intracellular Ca2+ signaling is a critical factor in breast cancer metastasis. In the proliferation stage, increases in intracellular Ca2+ concentration through voltage-dependent Ca2+ channels, P2Y2 channels, transient receptor potential (TRP) channels, store-operated Ca2+ channels (SOCCs), and IP3 receptors and a decrease in intracellular Ca2+ concentration through plasma membrane Ca2+ ATPases and secretory pathway Ca2+ ATPases (SPCA) activate breast cancer cell proliferation. TRPM7, SOCC, inositol trisphosphate receptor (IP3R), ryanodine receptor (RyR), and sarco-/endo-plasmic reticulum Ca2+-ATPase (SERCA) increase the expression of epithelial-to-mesenchymal transition (EMT)-related proteins; meanwhile, SPCA and the Na+/Ca2+ exchanger (NCX) control the activation of EMT-related proteins. Increased Ca2+ through TRPC1, TRPM7/8, P2X7, and SOCC enhances breast cancer cell migration. The stromal interaction molecule (STIM)-Orai complex, P2X7, and Ca2+ sensing receptors are involved in invadopodia. Various pharmacological agents for Ca2+ channels have been proposed against breast cancer and have provided potential strategies for treating metastatic processes. Metastatic features of breast cancer in the brain are considered a common pathology in female patients with late-stage breast cancer. Ca2+ signaling and the overexpression pattern of Ca2+ channels have been regarded as oncogenic markers of breast cancer. In other words, breast tumor development can be mediated by inhibiting Ca2+ channels. Although the therapeutic potential of inhibiting Ca2+ channels against breast cancer has been demonstrated, the relationship between breast cancer metastasis and Ca2+ channels is not yet understood. Thus, we focused on the metastatic features of breast cancer and summarized the basic mechanisms of Ca2+-related proteins and channels during the stages of metastatic breast cancer by evaluating Ca2+ signaling. In particular, we highlighted the metastasis of breast tumors to the brain. Thus, modulating Ca2+ channels with Ca2+ channel inhibitors and combined applications will advance treatment strategies for breast cancer metastasis to the brain. [ABSTRACT FROM AUTHOR]

Highlights: [•] Carbon coated TiO2-Li4Ti5O12 hierarchical spheres are fabricated by a simplistic hydrothermal procedures. [•] TiO2-Li4Ti5O12@C spheres were investigated as anode materials for Li-ion batteries. [•] These unique mosoporous composite spheres demonstrated improvements to the anode capacity and cycle life while providing inherent advantages in terms of safety. [ABSTRACT FROM AUTHOR]