M1 macrophage-derived exosomal microRNA-29c-3p suppresses aggressiveness of melanoma cells via ENPP2.

In the tumor microenvironment, macrophages play crucial roles resulting in tumor suppression and progression, depending on M1 and M2 macrophages, respectively. In particular, macrophage-derived exosomes modulate the gene expression of cancer cells by delivering miRNAs which downregulate specific genes. The communication between macrophages and cancer cells is especially important in immunogenic tumors such as melanoma, where the cancer pogression is significantly influenced by the surrounding immune cells.

Alginate Hydrogel Integrated with a Human Fibroblast-Derived Extracellular Matrix Supports Corneal Endothelial Cell Functionality and Suppresses Endothelial-Mesenchymal Transition.

Human corneal transplantation is still the only option to restore the function of corneal endothelial cells (CECs). Therefore, there is an urgent need for hCEC delivery systems to replace the human donor cornea. Here, we propose an alginate hydrogel (AH)-based delivery system, where a human fibroblast-derived, decellularized extracellular matrix (ECM) was physically integrated with AH.

Calcium homeostasis modulator 2 (Calhm2) as slowly activating membrane current channel in mouse B cells.

In mouse B lymphocytes, an unidentified slow-activating voltage-dependent current resembling the characteristics of the Calhm family ion channel (I) was investigated. RT-PCR analysis revealed the presence of Calhm2 and 6 transcripts, with subsequent whole-cell patch-clamp studies indicating that the I is augmented by heat, alkaline pH, and low extracellular [Ca]. Overexpression of Calhm2, but not Calhm6, in N2A cells recapitulated I.

Mesenchymal stem cell-derived secretomes-enriched alginate/ extracellular matrix hydrogel patch accelerates skin wound healing.

Background: The secretomes of mesenchymal stem cells (MSCs) have great therapeutic potential and thereby their efficient delivery into the target site is of particular interest. Here, we propose a new strategy of hMSCs-derived secretomes delivery for advanced wound healing upon harnessing the working principle of extracellular matrix (ECM)-growth factors interaction in vivo.

Methods: We prepared an alginate hydrogel based wound patch, where it contains both human MSC-derived secretomes and ECM.

The novel K7 channel activator URO-K10 exerts enhanced pulmonary vascular effects independent of the KCNE4 regulatory subunit.

K7 channels exert a pivotal role regulating vascular tone in several vascular beds. In this context, K7 channel agonists represent an attractive strategy for the treatment of pulmonary arterial hypertension (PAH). Therefore, in this study, we have explored the pulmonary vascular effects of the novel K7 channel agonist URO-K10.

Bidirectional sensitivity of CALHM1 channel to protons from both sides of plasma membrane.

Calcium homeostasis modulator 1 (CALHM1), a newly discovered voltage-dependent nonselective ion channel, has drawn attention for its role in neuronal activity and taste sensation. Its sluggish voltage-dependent activation is facilitated by lowering extracellular Ca concentration ([Ca]). Here, we investigated the effects of extracellular and intracellular pH (pH and pH) on human CALHM1.

Discovery and characterization of a potent activator of the BK channel that relives overactive bladder syndrome in rats.

The large-conductance Ca-activated K channel (BK channel) is involved in repolarizing the membrane potential and has a variety of cellular functions. The BK channel is highly expressed in bladder smooth muscle and mediates muscle relaxation. Compounds that activate the BK channel have therapeutic potential against pathological symptoms associated with the overactivity of bladder smooth muscle.

Lower troponin expression in the right ventricle of rats explains interventricular differences in E-C coupling.

Despite distinctive functional and anatomic differences, a precise understanding of the cardiac interventricular differences in excitation-contraction (E-C) coupling mechanisms is still lacking. Here, we directly compared rat right and left cardiomyocytes (RVCM and LVCM). Whole-cell patch clamp, the IonOptix system, and fura-2 fluorimetry were used to measure electrical properties (action potential and ionic currents), single-cell contractility, and cytosolic Ca2+ ([Ca2+]i), respectively.

M2 Macrophage-Derived Concentrated Conditioned Media Significantly Improves Skin Wound Healing.

Background: Macrophages, with many different phenotypes play a major role during wound healing process, secreting the cytokines crucial to angiogenesis, cell recruitment and ECM remodeling. Therefore, macrophage-derived cytokines may be attractive therapeutic resource for wound healing.

Methods: To obtain a conditioned media (CM) from macrophages, human monocyte THP-1 cells were seeded on TCP or human fibroblast-derived matrix (hFDM) and they were differentiated into M1 or M2 phenotype using distinct protocols.

Intramolecular Disulfide Bonds for Biogenesis of CALHM1 Ion Channel Are Dispensable for Voltage-Dependent Activation.

Calcium homeostasis modulator 1 (CALHM1) is a membrane protein with four transmembrane helices that form an octameric ion channel with voltage-dependent activation. There are four conserved cysteine (Cys) residues in the extracellular domain that form two intramolecular disulfide bonds. We investigated the roles of C42-C127 and C44-C161 in human CALHM1 channel biogenesis and the ionic current ().

Thermosensitivity of the voltage-dependent activation of calcium homeostasis modulator 1 (calhm1) ion channel.

Calcium homeostasis modulator 1 (calhm1) proteins form an outwardly rectifying nonselective ion channel having exceedingly slow kinetics and low sensitivity to voltage that is shifted by lowering extracellular Ca ([Ca]). Here we found that physiological temperature dramatically facilitates the voltage-dependent activation of the calhm1 current (I); increased amplitude (Q, 7-15) and fastened speed of activation. Also, the leftward shift of the half-activation voltage (V) was similary observed in the normal and lower [Ca].

Characterization of an antibiotic produced by Bacillus subtilis JW-1 that suppresses Ralstonia solanacearum.

Bacillus subtilis JW-1 was isolated from rhizosphere soil as a potential biocontrol agent of bacterial wilt caused by Ralstonia solanacearum. Seed treatment followed by a soil drench application with this strain resulted in >80% reduction in bacterial wilt disease compared with that in the untreated control under greenhouse conditions. The antibacterial compound produced by strain JW-1 was purified by bioactivity-guided fractionation.