Recombinant Klotho Protein Ameliorates Myocardial Ischemia/Reperfusion Injury by Attenuating Sterile Inflammation.

Currently, no effective therapy and potential target have been elucidated for preventing myocardial ischemia and reperfusion injury (I/R). We hypothesized that the administration of recombinant klotho (rKL) protein could attenuate the sterile inflammation in peri-infarct regions by inhibiting the extracellular release of high mobility group box-1 (HMGB1). This hypothesis was examined using a rat coronary artery ligation model. Rats were divided into sham, sham+ rKL, I/R, and I/R+ rKL groups (n = 5/group). Administration of rKL protein reduced infarct volume and attenuated extracellular release of HMGB1 from peri-infarct tissue after myocardial I/R injury. The administration of rKL protein inhibited the expression of pro-inflammatory cytokines in the peri-infarct regions and significantly attenuated apoptosis and production of intracellular reactive oxygen species by myocardial I/R injury. Klotho treatment significantly reduced the increase in the levels of circulating HMGB1 in blood at 4 h after myocardial ischemia. rKL regulated the levels of inflammation-related proteins. This is the first study to suggest that exogenous administration of rKL exerts myocardial protection effects after I/R injury and provides new mechanistic insights into rKL that can provide the theoretical basis for clinical application of new adjunctive modality for critical care of acute myocardial infarction.

Rapid preparation of a noncultured skin cell suspension that promotes wound healing.

Autologous skin cell suspensions have been used for wound healing in patients with burns and against normal pigmentation in vitiligo. To separate cells and the extracellular matrix from skin tissue, most researchers use enzymatic digestion. Therefore, this process is difficult to perform during a routine surgical procedure. We aimed to prepare a suspension of noncultured autologous skin cells (NCSCs) using a tissue homogenizer as a new method instead of harsh biochemical reagents. The potential clinical applicability of NCSCs was analyzed using a nude-rat model of burn healing. After optimization of the homogenizer settings, cell viability ranged from 52 to 89%. Scanning electron microscopy showed evidence of keratinocyte-like cell morphology, and several growth factors, including epidermal growth factor and basic fibroblast growth factor, were present in the NCSCs. The rat model revealed that NCSCs accelerated skin regeneration. NCSCs could be generated using a tissue homogenizer for enhancement of wound healing in vivo. In the NCSC group of wounds, on day 7 of epithelialization, granulation was observed, whereas on day 14, there was a significant increase in skin adnexa regeneration as compared to the control group (PBS treatment; p < 0.05). This study suggests that the proposed process is rapid and does not require the use of biochemical agents. Thus, we recommend a combination of surgical treatment with the new therapy for a burn as an effective method.