Dong Jun Park

With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Significance: Release of extracellular vesicles (EVs) by various cell types has been shown to mediate the delivery of biologically active payloads from donor cells to recipient cells; however, it remains unclear what cell types these EVs come from. With a focus on fluorescent reporters to monitor the release of EVs, especially those under the control of cell type-specific promoters, we address the translational relevance of genetic tools in cultured cells, normal tissues, and in models of development, injury, cancer, and wound healing. Recent Advances: It is well established that EVs are released by many cell types in the body via fusion and release processes at the plasma membrane. Since there remains debate about what fraction of EVs are released through regulated endosomal trafficking pathways versus nonspecific mechanisms, the development and validation of novel molecular tools are important to address the cellular source of EVs. Critical Issues: There is a need to develop and characterize new cell type-specific reporter mouse models that build upon the examples detailed here to identify the cellular source of EVs with genetic approaches being useful in addressing these critical limitations. Future Directions: Advances in reporter systems will drive a better understanding of EV subsets to identify compartment-specific EV localization to guide the development of more translationally relevant models for the wound healing field.

Currently, ascorbic acid (AA) is widely used as a skin whitening material, but, AA, an unstable hydrophilic molecule, cannot penetrate the skin easily, due to the hydrophobic character of the stratum corneum. Therefore, we conjugated AA with hydrated zinc oxide—an inorganic matrix with positive surface charge, to improve the stability of AA. The metal-conjugated-ascorbic acid (ZnAA) was then combined with yeast vacuole through the vacuolar membrane proteins that relate to metal transportation to create an enhanced vacuole that contained ZnAA. The characteristics of vacuole with ZnAA (ZnAA_Vac) were next examined by various tests that included X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT–IR), Field emission scanning electron microscopy (FE–SEM), and energy-dispersive X-ray (EDX) analysis. Furthermore, the ability of ZnAA_Vac to degrade melanin was confirmed in both melanoma cell line B16F10, and the artificial human skin MelanoDerm. The results showed that ZnAA_Vac possessed a higher depigmenting effect than the wild-type vacuole or ascorbic acid by reducing 75% of melanin color. Interestingly, ZnAA_Vac was found to be harmless, and did not cause any cytotoxicity to the cells. Overall, ZnAA_Vac is expected to provide a robust, harmless, and effective whitening agent for the skin.

Chronic metabolic diseases such as diabetes are characterized by delayed wound healing and a dysregulation of the inflammatory phase of wound repair. Our study focuses on changes in the payload of extracellular vesicles (EVs) communicating between immune cells and stromal cells in the wound bed, which regulate the rate of wound closure. Adoptive transfer of EVs from genetically defined mouse models are used here to demonstrate a functional and molecular basis for differences in the pro-reparative biological activity of diabetic (db/db) vs. wildtype EVs in wound healing. We identify several members of the Serpin family of serine protease inhibitors that are absent in db/db EVs, then we overexpress Serpin A1, F2 and G1 in EVs to evaluate their effect on wound healing in db/db mice. Serpins have an important role in regulating levels of elastase, plasmin and complement factors that coordinate immune cell signaling in full thickness wounds in a diabetic model. Here, we establish a novel therapeutic approach by engineering the payload of EVs based on proteomic analysis. Serpin-loaded EVs were used to rescue the Serpin deficiency identified by proteomics and promote wound healing in db/db mice, as well as evaluated how EVs affected extracellular matrix remodeling and the resolution of tissue injury. Therefore, we propose that the identification of EV payloads that are downregulated in diabetic wounds can be systematically analyzed for their functional activity and potential as a therapeutic, based on whether their re-expression in engineered EVs restores normal kinetics of tissue repair in chronic wounds. Graphical Abstract

Recently, studies on the mechanism and clinical application of stem cell-derived exosomes have increased. Although the number of patients with hearing loss is increasing, there is no ideal therapy for the recovery of auditory cells of an independent organ in humans. In this review, we proposed the use of stem cell-derived exosomes for treating hearing loss and summarized the exosome research strategy platform for preclinical studies. It is necessary to select a research direction to assess direct or indirect effects on recipients based on the physiological mechanisms of exosomes that deliver useful molecules (called payloads) to recipient cells or tissues. To apply exosomes in the auditory field, researchers should select a model for assessing the toxicity to the auditory cells and analyzing their mechanisms in the recipient tissue. Such in vitro, ex vivo, and in vivo models have been designed and reported in previous studies. The analytical strategies in various models can evaluate the mechanism of exosomes based on exosome surface markers or the payload, thus helping the researchers in finding evidence regarding the efficacy of exosomes. Here, we propose three strategies for exosome application research in the auditory field.

In the field of tissue regeneration and tissue engineering, many years ago, various nano to macroscopic-sized materials have been used to reduce inflammation and restore damaged tissue. Whether it is safe to study the regeneration of all tissues based on the biological mechanisms of an organism composed of cells is still debated, and studies using extracellular vesicles derived from cells have become popular in the past decade. It has been reported that exosomes with a size of 100 nm or less, which plays an important role in cell–cell communication, contain various factors, such as proliferation, anti-inflammatory, and growth factors. In addition, the payload of exosomes varies depending on the parent cell and the recipient cell, and a technology to differentiate the selective payload must treat specific diseases. In this review, we examined the current trends in research using exosomes derived from cells or tissues and analyzed various research reports on factors that can affect tissue regeneration.

Background: The application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) requires customized materials to target disease or cell damage. We hypothesized that EVs exert different inflammatory effects on one recipient cell, although stem cells of different origins in humans have similar payloads. Results: Here, the payload of EVs released by crosstalk between MSCs and human middle ear epithelial cells (HMEECs) extracted from adipose tissue, bone marrow and tonsils significantly increased the level of anti-inflammatory factors. EVs derived from the co-culture medium decreased TNF-α, COX-2, IL-1β, and IL-6 levels to approximately zero within 3 h in HMEECs. Expression of miR-638 and amyloid-β A4 precursor protein-binding family A member 2 was analyzed using microarrays and gene ontology analysis, respectively. Conclusions: In conclusion, stem cells of different origins have different payloads through crosstalk with recipient-specific cells. Inducing specific factors in EVs by co-culture with MSCs could be valuable in regenerative medicine. Graphical