Improved Wound Healing and Skin Regeneration Ability of 3,2'-Dihydroxyflavone-Treated Mesenchymal Stem Cell-Derived Extracellular Vesicles.

Flavonoids enhance the self-renewal and differentiation potential of mesenchymal stem cells (MSCs) and have therapeutic activities, including regenerative, anti-oxidative, and anti-inflammatory effects. Recent studies have revealed that MSC-derived extracellular vesicles (MSC-EVs) have therapeutic effects on tissue regeneration and inflammation. To facilitate further research on the therapeutic potential of MSC-EVs derived from flavonoid-treated MSCs, we surveyed the production of EVs and their therapeutic applications in wound regeneration. MSCs treated with flavonoids enhanced EV production twofold compared with naïve MSCs. EVs produced by MSCs treated with flavonoids (Fla-EVs) displayed significant anti-inflammatory and wound-healing effects in vitro. The wound-healing capacity of EVs was mediated by the upregulation of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. Interestingly, the protein level of p-ERK under inhibition of MEK signals was maintained in Fla-EV-treated fibroblasts, suggesting that Fla-EVs have a higher therapeutic potential than naïve MSC-EVs (Cont-EVs) in wound healing. Moreover, the in vivo wound closure effect of the Fla-EVs showed significant improvement compared with that of the flavonoid-only treatment group and the Cont-EVs. This study provides a strategy for the efficient production of EVs with superior therapeutic potential using flavonoids.

Environmental survival of SARS-CoV-2 - A solid waste perspective.

The advent of COVID-19 has kept the whole world on their toes. Countries are maximizing their efforts to combat the virus and to minimize the infection. Since infectious microorganisms may be transmitted by variety of routes, respiratory and facial protection is required for those that are usually transmitted via droplets/aerosols. Therefore this pandemic has caused a sudden increase in the demand for personal protective equipment (PPE) such as gloves, masks, and many other important items since, the evidence of individual-to-individual transmission (through respiratory droplets/coughing) and secondary infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). But the disposal of these personal protective measures remains a huge question mark towards the environmental impact. Huge waste generation demands proper segregation according to waste types, collection, and recycling to minimize the risk of infection spread through aerosols and attempts to implement measures to monitor infections. Hence, this review focuses on the impact of environment due to improper disposal of these personal protective measures and to investigate the safe disposal methods for these protective measures by using the safe, secure and innovative biological methods such as the use of Artificial Intelligence (AI) and Ultraviolet (UV) lights for killing such deadly viruses.

Monitoring of Heavy Metals and Pesticide Residues of Herbal Decoctions in Traditional Korean Medicine Clinics in Korea.

In this study, we investigated whether the levels of heavy metal and pesticide residues in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for heavy metal content such as lead, arsenic, and cadmium using inductively coupled plasma optical emission spectrometry. For mercury, an automatic mercury analyzer based on the gold amalgamation process was used. For pesticide residues, gas chromatography with electron capture detection and gas chromatography with mass selective detection were used for the analyses. Based on the testing, heavy metals were identified in most of the decoctions (Cd: 0.000-0.003 ppm, Pb: 0.003-0.023 ppm, As: 0.000-0.016 ppm, Hg: 0.000-0.002 ppm). Pesticide residues (e.g., total DDT, total BHC, aldrin, endrin, dieldrin) were not detected at all. All of these were no more than the limit values in preceding studies. Therefore, this study confirms that the contents of heavy metals and pesticides in herbal decoctions are within safe levels based on a previous study and provides evidence for establishing safety management standards for herbal decoctions in Korea.

Modulation of Osteogenic Differentiation of Adipose-Derived Stromal Cells by Co-Treatment with 3, 4'-Dihydroxyflavone, U0126, and N-Acetyl Cysteine.

Background and Objectives: Flavonoids form the largest group of plant phenols and have various biological and pharmacological activities. In this study, we investigated the effect of a flavonoid, 3, 4'-dihydroxyflavone (3, 4'-DHF) on osteogenic differentiation of equine adipose-derived stromal cells (eADSCs). Methods and Results: Treatment of 3, 4'-DHF led to increased osteogenic differentiation of eADSCs by increasing phosphorylation of ERK and modulating Reactive Oxygen Species (ROS) generation. Although PD98059, an ERK inhibitor, suppressed osteogenic differentiation, another ERK inhibitor, U0126, apparently increased osteogenic differentiation of the 3, 4'-DHF-treated eADSCs, which may indicate that the effect of U0126 on bone morphogenetic protein signaling is involved in the regulation of 3, 4'-DHF in osteogenic differentiation of eADSCs. We revealed that 3, 4'-DHF could induce osteogenic differentiation of eADSCs by suppressing ROS generation and co-treatment of 3, 4'-DHF, U0126, and/or N-acetyl cysteine (NAC) resulted in the additive enhancement of osteogenic differentiation of eADSCs. Conclusions: Our results showed that co-treatment of 3, 4'-DHF, U0126, and/or NAC cumulatively regulated osteogenesis in eADSCs, suggesting that 3, 4'-DHF, a flavonoid, can provide a novel approach to the treatment of osteoporosis and can provide potential therapeutic applications in therapeutics and regenerative medicine for human and companion animals.

DAMP-modulating nanoparticle for successful pancreatic islet and stem cell transplantation.

Cell therapy is targeted at many organs, but locally or systemically delivered cells are shortly able to survive resulting from the immune/inflammation reactions and irregular cell targeting. Here we explore the multimodal nanoparticle having anti-inflammation and magnetic guidance for successful cell transplantation. We design magnetic resonance (MR)-active glycyrrhizin-chitosan coated superparamagnetic iron oxide nanoparticle (SPIO@Chitosan-GL) to inhibit release of inflammatory damage-associated molecular pattern (DAMP) protein and to offer noninvasive monitoring after intrahepatic transplantation of pancreatic islets and mesenchymal stem cell (MSC) spheroids. Intracellular delivered SPIO@Chitosan-GL is not cytotoxic to pancreatic islets and MSC spheroids and attenuate DAMP release from them. Also, therapeutic cells labeled with SPIO@Chitosan-GL are magnetically localized to the intended lobe of liver during transplantation procedure. If necessary, partial hepatectomy can be performed to remove the localized therapeutic cells for protection of the remaining liver lobes from systemic inflammation. Therapeutically, the cells selectively localized in the liver can treat blood glucose in diabetic mice to normal levels with DAMP modulation, and are visualized using in vivo MR imaging for over 4 weeks. Collectively, DAMP-modulating SPIO@Chitosan-GL can be used in multimodal nanomedince for attenuating the inflammation reaction by transplanted cells and for noninvasively long-term monitoring of transplanted cells.

Superior therapeutic activity of TGF-ß-induced extracellular vesicles against interstitial cystitis.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by incapacitating pelvic pain. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are considered key mediators of the paracrine action of MSCs and show better biological activities than the parent MSCs, especially in the bladder tissue, which may be unfavorable for MSC survival. Here, we produced MSC-EVs using advanced three-dimensional (a3D) culture with exogenous transforming growth factor-ß3 (TGF-ß3) (T-a3D-EVs). Treatment with T-a3D-EVs led to significantly enhanced wound healing and anti-inflammatory capacities. Moreover, submucosal layer injection of T-a3D-EVs in chronic IC/BPS animal model resulted in restoration of bladder function, superior anti-inflammatory activity, and recovery of damaged urothelium compared to MSCs. Interestingly, we detected increased TGF-ß1 level in T-a3D-EVs, which might be involved in the anti-inflammatory activity of these EVs. Taken together, we demonstrate the excellent immune-modulatory and regenerative abilities of T-a3D-EVs as observed by recovery from urothelial denudation and dysfunction, which could be a promising therapeutic strategy for IC/BPS.

Bioinformatics Approach for Identifying Novel Biomarkers and Their Signaling Pathways Involved in Interstitial Cystitis/Bladder Pain Syndrome with Hunner Lesion.

The complexity of interstitial cystitis/bladder pain syndrome (IC/BPS) has led to considerable uncertainty in terms of diagnosis and prevalence of the condition. Here, we try to identify the IC/BPS-associated genes through an integrated analysis of Gene Expression Omnibus (GEO) datasets and confirm experimentally to predict the pathologic diagnosis of IC/BPS. Data mining analysis of GEO datasets (GSE621, GSE11783, GSE28242, and GSE57560) revealed a total of 53 (51 upregulated and two downregulated) common differentially expressed genes (DEGs) in IC/BPS. A protein-protein interaction (PPI) network was then constructed with the 53 common DEGs using Cytoscape v3.7.2, and subsequently, six hub genes (CD5, CD38, ITGAL, IL7R, KLRB1, and IL7R) were identified using cytoHubba v0.1 that were upregulated in IC/BPS. Enrichment analysis of common DEGs revealed that hematopoietic cell lineage, immune system, and T-cell receptor (TCR) signaling in naïve CD4+ T cell signaling pathways were prominently involved with the common 51 upregulated DEGs. The two common downregulated DEGs may enrich linoleic acid metabolism and synthesis of epoxy (EET) and dihydroxyeicosatrienoic acid (DHET) signaling pathways in IC/BPS. Moreover, our RT-PCR data confirmed that the expression of the five hub genes (CD38, ITGAL, IL7R, KLRB1, and IL7R) was significantly augmented in IC/BPS patients' samples when compared with their normal counterparts. In this study, we systematically predict the significant biomarkers and possible signaling pathways involved in IC/BPS, confirming the differential expression of the hub genes in tissue samples from patients with IC/BPS. Thus, the hub genes might be used as potential diagnostic biomarkers of IC/BPS.