Platelet-derived mitochondria transfer facilitates wound-closure by modulating ROS levels in dermal fibroblasts.

Platelets are known to improve the wound-repair capacity of mesenchymal stem cells (MSCs) by transferring mitochondria intercellularly. This study aimed to investigate whether direct transfer of mitochondria (pl-MT) isolated from platelets could enhance wound healing in vitro using a cell-based model. Wound repairs were assessed by 2D gap closure experiment in wound scratch assay using human dermal fibroblasts (hDFs). Results demonstrated that pl-MT were successfully internalized into hDFs. It increased cell proliferation and promoted the closure of wound gap. Importantly, pl-MT suppressed both intracellular and mitochondrial ROS production induced by hydrogen peroxide, cisplatin, and TGF-ß in hDFs. Taken together, these results suggest that pl-MT transfer might be used as a potential therapeutic strategy for wound repair.

What is the context? During the wound healing process, abnormal regulation of ROS and inflammation delays the healing process, resulting in chronic non-healing wounds.Mitochondria are key organelles responsible for the ROS generation. Mitochondrial dysfunction has been implicated in delayed wound repair.Mitochondria transfer, which utilizes intact mitochondria isolated from healthy cells to recover from disease, has been applied in various clinical studies, but additional evidence is needed to apply it to wound healing.What is new? In this study, we chose platelets as a cell source for mitochondrial transfer. We isolated the functional mitochondria from platelets and applied them to wound healing.What is the impact? This study provides evidence that platelet-derived mitochondria (pl-MT) improve the wound healing progress by increasing the viability of dermal fibroblasts and suppressing intracellular and mitochondrial ROS production.Platelets have also been demonstrated to be a suitable cell source for mitochondrial transfer.

Erratum to: Human umbilical cord mesenchymal stem cell-derived mitochondria (PN-101) attenuate LPS-induced inflammatory responses by inhibiting NFκB signaling pathway.

[Erratum to: BMB Reports 2022; 55(3): 136-141, PMID: 34488927, PMCID: PMC8972135] The BMB Reports would like to correct in BMB Rep. 55(3):136-141, titled "Human umbilical cord mesenchymal stem cell-derived mitochondria (PN-101) attenuate LPS-induced inflammatory responses by inhibiting NFκB signaling pathway". This research was supported by NRF-2016R1A2B4007640 grant (to C-H Kim). Since grant number is incorrect, this information has now been corrected as follows: We would like to thank various Paean Biotechnology Inc. members who participated in the project. This work was supported by NRF-2018M3A9B5023055 grant (to C-H Kim). The authors apologize for any inconvenience or confusion that may be caused by this error. The ACKNOWLEDGEMENTS of Original PDF version have been corrected.

Human umbilical cord mesenchymal stem cell-derived mitochondria (PN-101) attenuate LPS-induced inflammatory responses by inhibiting NFκB signaling pathway.

Inflammation is one of the body's natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases and multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases by inducing an abnormal inflammatory response. Therefore, treating inflammatory diseases by recovering mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation has been proven to be beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to PN-101. We found that PN-101 could significantly reduce LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated LPS-induced increase production of pro-inflammatory cytokines. Furthermore, the anti-inflammatory effect of PN-101 was mediated by blockade of phosphorylation, nuclear translocation, and trans-activity of NFκB. Taken together, our results demonstrate that PN-101 has therapeutic potential to attenuate pathological inflammatory responses. [BMB Reports 2022; 55(3): 136-141].

LIN28A enhances regenerative capacity of human somatic tissue stem cells via metabolic and mitochondrial reprogramming.

Developing methods to improve the regenerative capacity of somatic stem cells (SSCs) is a major challenge in regenerative medicine. Here, we propose the forced expression of LIN28A as a method to modulate cellular metabolism, which in turn enhances self-renewal, differentiation capacities, and engraftment after transplantation of various human SSCs. Mechanistically, in undifferentiated/proliferating SSCs, LIN28A induced metabolic reprogramming from oxidative phosphorylation (OxPhos) to glycolysis by activating PDK1-mediated glycolysis-TCA/OxPhos uncoupling. Mitochondria were also reprogrammed into healthy/fused mitochondria with improved functional capacity. The reprogramming allows SSCs to undergo cell proliferation more extensively with low levels of oxidative and mitochondrial stress. When the PDK1-mediated uncoupling was untethered upon differentiation, LIN28A-SSCs differentiated more efficiently with an increase of OxPhos by utilizing the reprogrammed mitochondria. This study provides mechanistic and practical approaches of utilizing LIN28A and metabolic reprogramming in order to improve SSCs utility in regenerative medicine.

Antimicrobial PEGtides: A Modular Poly(ethylene glycol)-Based Peptidomimetic Approach to Combat Bacteria.

Despite their high potency, the widespread implementation of natural antimicrobial peptides is still challenging due to their low scalability and high hemolytic activities. Herein, we address these issues by employing a modular approach to mimic the key amino acid residues present in antimicrobial peptides, such as lysine, leucine, and serine, but on the highly biocompatible poly(ethylene glycol) (PEG) backbone. A series of these PEG-based peptides (PEGtides) were developed using functional epoxide monomers, corresponding to each key amino acid, with several possessing highly potent bactericidal activities and controlled selectivities, with respect to their hemolytic behavior. The critical role of the composition and the structure of the PEGtides in their selectivities was further supported by coarse-grained molecular dynamic simulations. This modular approach is anticipated to provide the design principles necessary for the future development of antimicrobial polymers.

Identification of candidate medicinal herbs for skincare via data mining of the classic Donguibogam text on Korean medicine.

BACKGROUND: Korean cosmetics are widely exported throughout Asia. Cosmetics exploiting traditional Korean medicine lead this trend; thus, the traditional medicinal literature has been invaluable in terms of cosmetic development. We sought candidate medicinal herbs for skincare. METHODS: We used data mining to investigate associations between medicinal herbs and skin-related keywords (SRKs) in a classical text. We selected 26 SRKs used in the Donguibogam text; these referred to 626 medicinal herbs. Using a term frequency-inverse document frequency approach, we extracted data on herbal characteristics by assessing the co-occurrence frequencies of 52 medicinal herbs and the 26 SRKs. RESULTS: We extracted the characteristics of the 52 herbs, each of which exhibited a distinct skin-related action profile. For example Ginseng Radix was associated at a high-level with tonification and anti-aging, but Rehmanniae Radix exhibited a stronger association with anti-aging. Of the 52 herbs, 46 had been subjected to at least one modern study on skincare-related efficacy. CONCLUSIONS: We made a comprehensive list of candidate medicinal herbs for skincare via data mining a classical medical text. This enhances our understanding of such herbs and will help with discovering new candidate herbs.

Chromobacterium violaceum delivers violacein, a hydrophobic antibiotic, to other microbes in membrane vesicles.

This study describes Chromobacterium violaceum's use of extracellular membrane vesicles (MVs) to both solubilize and transport violacein to other microorganisms. Violacein is a hydrophobic bisindole with known antibiotic activities against other microorganisms. Characterization of the MVs found they carried more violacein than protein (1.37 ± 0.19-fold), suggesting they may act as a reservoir for this compound. However, MVs are not produced in response to violacein - a ΔvioA isogenic mutant, which is incapable of making violacein, actually produced significantly more MVs (3.2-fold) than the wild-type strain. Although violacein is insoluble in water (Log Poctanol:water = 3.34), 79.5% remained in the aqueous phase when it was present within the C. violaceum MVs, an increase in solubility of 1740-fold. Moreover, tests with a strain of Staphylococcus aureus showed MV-associated violacein is bactericidal, with 3.1 mg/l killing 90% of S. aureus in 6 h. Tests with the ΔvioA MVs found no loss in the S. aureus viability, even when its MVs were added at much higher concentrations, demonstrating violacein is the active component within the wild-type MVs. In conclusion, our study clearly demonstrates C. violaceum produces MVs and uses them as vehicles to solubilize violacein and transport this hydrophobic antibiotic to other microbes.

Viscosity has dichotomous effects on Bdellovibrio bacteriovorus HD100 predation.

Bdellovibrio bacteriovorus HD100 is a highly motile predatory bacterium that consumes other Gram-negative bacteria for its sustenance. Here, we describe the impacts the media viscosity has both on the motility of predator and its attack rates. Experiments performed in polyethylene glycol (PEG) solutions, a linear polymer, found a viscosity of 10 mPa s (5% PEG) negatively impacted predation over a 24-h period. When the viscosity was increased to 27 mPa s (10% PEG), predation was nearly abolished. Tests with three other B. bacteriovorus strains, i.e., 109J and two natural isolates, found identical results. Short-term (2-h) experiments, however, found attack rates were improved in 1% PEG, which had a viscosity of 5.4 mPa s, using bioluminescent prey and their viabilities. In contrast, when experiments were performed in dextran, a branched polymer, no increase in predation was seen even though the viscosity was a comparable 5.1 mPa s. The enhanced attack rates in this solution coincided with a 31% increase in B. bacteriovorus HD100 swimming speeds (62 µm s-1 in 1% PEG vs. 47.5 µm s-1 in HEPES-salt).

Sensitivity of predatory bacteria to different surfactants and their application to check bacterial predation.

We evaluated the toxicity of surfactants against different predatory bacteria. Tests with Bdellovibrio bacteriovorus HD100 and SDS, an anionic surfactant, showed the predator was very sensitive; 0.02% SDS completely killed the predatory population (7-log loss; < 10 PFU/ml remaining) both when free-swimming or within the bdelloplast, i.e., intraperiplasmic. Similar results were also observed with B. bacteriovorus 109J and Peredibacter starrii. In contrast, none of the prey (E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, or Pseudomonas sp. DSM 50906) viabilities were negatively affected by SDS. Triton X-100, a nonionic surfactant, was slightly less toxic towards B. bacteriovorus HD100 (viability loss of only 4-log), while two cationic surfactants, i.e., benzalkonium chloride (BZC) and cetyltrimethylammonium bromide (CTAB), were toxic towards both the predator and prey. Based on the above findings, we tested the potential use of SDS as a means to control predation. Addition of 0.02% SDS immediately halted predation based upon the prey bioluminescence, which leveled off and remained steady. This was confirmed using the predator viabilities; no predators were found in any of the samples where SDS was added. Consequently, low concentrations of SDS can be used as a simple means to control B. bacteriovorus HD100 activities.

Effect of Curing Mode on Shear Bond Strength of Self-Adhesive Cement to Composite Blocks.

To overcome the disadvantages of computer-aided design/computer-aided manufacturing (CAD/CAM) processed indirect restorations using glass-ceramics and other ceramics, resin nano ceramic, which has high strength and wear resistance with improved polish retention and optical properties, was introduced. The purpose of this study was to evaluate the shear bond strength and fracture pattern of indirect CAD/CAM composite blocks cemented with two self-etch adhesive cements with different curing modes. Sand-blasted CAD/CAM composite blocks were cemented using conventional resin cement, Rely X Ultimate Clicker (RXC, 3M ESPE, St. Paul, MN, USA) with Single Bond Universal (SB, 3M ESPE, St. Paul, MN, USA) for the control group or two self-adhesive resin cements: Rely X U200 (RXU, 3M ESPE, St. Paul, MN, USA) and G-CEM Cerasmart (GC, GC corporation, Tokyo, Japan). RXU and GC groups included different curing modes (light-curing (L) and auto-curing (A)). Shear bond strength (SBS) analyses were performed on all the specimens. The RXC group revealed the highest SBS and the GC A group revealed the lowest SBS. According to Tukey's post hoc test, the RXC group showed a significant difference compared to the GC A group (p < 0.05). For the curing mode, RXU A and RXU L did not show any significant difference between groups and GC A and GC L did not show any significant difference either. Most of the groups except RXC and RXU L revealed adhesive failure patterns predominantly. The RXC group showed a predominant cohesive failure pattern in their CAD/CAM composite, LavaTM Ultimate (LU, 3M ESPE, St. Paul, MN, USA). Within the limitations of this study, no significant difference was found regarding curing modes but more mixed fracture patterns were showed when using the light-curing mode than when using the self-curing mode.

Age-related changes in skin bio-mechanical properties: the neck skin compared with the cheek and forearm skin in Korean females.

BACKGROUND: There are many reports on regional variations in skin bio-mechanical properties, but few studies have been performed on the neck. The neck is sun-exposed and continues to move so the neck skin can be more apt to aging. METHODS: The skin properties of the neck, cheek, and ventral forearm of 58 Korean female volunteers in good health (25-64 years old, 42.3 ± 11.7) were assessed non-invasively with skin measuring devices, and the correlation with age and wrinkles was analyzed. RESULTS: Neck skin was more extensible, elastic and visco-elastic than the cheek. The dermal layer for the neck skin was thinner and more intense than the cheek, but the results were opposite when compared with the skin of the forearm. We could observe that the subcutaneous layer was divided by the fascia with regard to the neck skin, and this thickness increased BMI-dependently. The neck skin had the correlation between R0, R3, and dermal thickness. The correlation coefficient of elasticity on the neck with ages was -0.550 and the elasticity on the neck skin was highly negatively correlated with age than any other sites. Therefore, this bio-mechanical property was important for determining the aging. TEWL was correlated with ages for only neck skin(R = 0.368). We found that the wrinkles on the neck were correlated with age, the elasticity, skin color (L*), TEWL. CONCLUSION: The biomechanical properties of the neck skin were highly correlated with age than skin parameters of other sites. These results were influenced by constant movement and sun-exposure, and therefore, the neck wrinkles were apt to form.

The current acceptance, accessibility and recognition of Chinese and Ayurvedic medicine in the United States in the public, governmental, and industrial sectors.

To assess the current level of acceptance in the United States of complementary and alternative medicine, recent research into the prevalence, acceptance, accessibility, and recognition of complementary and alternative therapies were reviewed. Several signs point to an increasing acceptance of complementary and alternative medicine in the United States; the use of complementary and alternative medicine is significantly increasing, many aspects of Chinese medicine and Ayurveda are becoming mainstream, practitioners in the United States are beginning to be licensed, and insurance companies are beginning to cover some complementary and alternative therapies. Remaining challenges to true acceptance include the restrictive Western mindset, the absence of published studies, a lack of consistent manufacturing processes and quality standards, and a fear of adulteration. Although the field still faces many challenges, alternative and complementary medicine, including Chinese medicine and Ayurvedic medicine, is becoming more accepted and accessible in the United States.