Quyu Shengji Formula Facilitates Diabetic Wound Healing via Inhibiting the Expression of Prostaglandin Transporter

Background. Quyu Shengji Formula (QSF), a Chinese medicine formula widely used in the clinic, has proven therapeutic effects on diabetic ulcers. Nevertheless, the potential mechanism of how QSF cures diabetic ulcer remains elusive. Objective. To assess the mechanism of QSF against wound healing defects in diabetes. Methods. Db/db mice were adopted to determine the therapeutic potential of QSF. Further histology analysis was performed by hematoxylin and eosin (H&E) staining. Moreover, the expression patterns of prostaglandin transporter (PGT), prostaglandin E2 (PGE2), and angiogenesis factor vascular endothelial growth factor (VEGF) were evaluated by immunostaining (IHC) analysis, ELISA assay, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot analysis in vivo. Human dermal microvascular endothelial cells (HDMECs) and the shRNA interference technique were used to explore the effects of QSF on cell migration, PGT, PGE2, and angiogenesis factor VEGF in vitro. Results. Applied QSF on the wound of db/db mice significantly accelerated wound closure. Reductions of PGT and elevations of PGE2 and increased angiogenesis factor VEGF levels were shown after QSF treatment in vivo and in vitro. Furthermore, QSF promoted HDMEC migration. Inhibition of the expression of PGT by shRNA reversed phenotypes of QSF treatment in vitro. Conclusion. Taken together, our findings reveal that QSF ameliorates diabetes-associated wound healing defects by abolishing the expression of PGT.

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Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

International Journal of Molecular Sciences ◽

10.3390/ijms20153679 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3679 ◽

Cited By ~ 3

Author(s):

Lin Chen ◽

Alyne Simões ◽

Zujian Chen ◽

Yan Zhao ◽

Xinming Wu ◽

...

Keyword(s):

Wound Healing ◽

Oral Mucosa ◽

Wound Closure ◽

Expression Patterns ◽

Skin Wound ◽

Skin Wound Healing ◽

Specific Expression ◽

Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

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Therapeutic effects of EGF-modified curcumin/chitosan nano-spray on wound healing

Regenerative Biomaterials ◽

10.1093/rb/rbab009 ◽

2021 ◽

Vol 8 (2) ◽

Author(s):

Yue Li ◽

QingQing Leng ◽

XianLun Pang ◽

Huan Shi ◽

YanLin Liu ◽

...

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Chitosan Nanoparticles ◽

Skin Lesions ◽

In Vitro Assays ◽

Therapeutic Effects ◽

Skin Defects ◽

Post Operation

Abstract Dermal injury, including trauma, surgical incisions, and burns, remain the most prevalent socio-economical health care issue in the clinic. Nanomedicine represents a reliable administration strategy that can promote the healing of skin lesions, but the lack of effective drug delivery methods can limit its effectiveness. In this study, we developed a novel nano-drug delivery system to treat skin defects through spraying. We prepared curcumin-loaded chitosan nanoparticles modified with epidermal growth factor (EGF) to develop an aqueous EGF-modified spray (EGF@CCN) for the treatment of dermal wounds. In vitro assays showed that the EGF@CCN displayed low cytotoxicity, and that curcumin was continuously and slowly released from the EGF@CCN. In vivo efficacy on wound healing was then evaluated using full-thickness dermal defect models in Wistar rats, showing that the EGF@CCN had significant advantages in promoting wound healing. On day 12 post-operation, skin defects in the rats of the EGF@CCN group were almost completely restored. These effects were related to the activity of curcumin and EGF on skin healing, and the high compatibility of the nano formulation. We therefore conclude that the prepared nano-scaled EGF@CCN spray represents a promising strategy for the treatment of dermal wounds.

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Strong Antimicrobial and Healing Effects of Beta-Acids from Hops in Methicillin-Resistant Staphylococcus aureus-Infected External Wounds In Vivo

Antibiotics ◽

10.3390/antibiotics10060708 ◽

2021 ◽

Vol 10 (6) ◽

pp. 708

Author(s):

Radek Sleha ◽

Vera Radochova ◽

Jiri Malis ◽

Alexander Mikyska ◽

Milan Houska ◽

...

Keyword(s):

Wound Healing ◽

Porcine Model ◽

Therapeutic Effects ◽

Methicillin Resistant ◽

Antimicrobial Effects ◽

Therapeutic Modalities ◽

Positive Effects ◽

Inflammatory Parameters

Staphylococcus (S.) aureus is an important causative agent of wound infections with increasing incidence in the past decades. Specifically, the emergence of methicillin-resistant S. aureus (MRSA) causes serious problems, especially in nosocomial infections. Therefore, there is an urgent need to develop of alternative or supportive antimicrobial therapeutic modalities to meet these challenges. Purified compounds from hops have previously shown promising antimicrobial effects against MRSA isolates in vitro. In this study, purified beta-acids from hops were tested for their potential antimicrobial and healing properties using a porcine model of wounds infected by MRSA. The results show highly significant antimicrobial effects of the active substance in both the powder and Ambiderman-based application forms compared to both no-treatment control and treatment with Framycoin. Moreover, the macroscopic evaluation of the wounds during the treatment using the standardized Wound Healing Continuum indicated positive effects of the beta-acids on the overall wound healing. This is further supported by the microscopic data, which showed a clear improvement of the inflammatory parameters in the wounds treated by beta-acids. Thus, using the porcine model, we demonstrate significant therapeutic effects of hops compounds in the management of wounds infected by MRSA. Beta-acids from hops, therefore, represent a suitable candidate for the treatment of non-responsive nosocomial tissue infections by MRSA.

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Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.687033 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiyuan Yan ◽

Yingchi Zhang ◽

Gaohong Sheng ◽

Bowei Ni ◽

Yifan Xiao ◽

...

Keyword(s):

Therapeutic Potential ◽

Cartilage Damage ◽

Cartilage Degradation ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Therapeutic Effects ◽

Exact Role

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

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P13.08 Novel Thioridazine derivates: Antiproliferative and apoptosis-inducing activity on glioblastoma cells in vitro

Neuro-Oncology ◽

10.1093/neuonc/noab180.116 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii34-ii34

Author(s):

S G Schwab ◽

K Sarnow ◽

E Alme ◽

R Goldbrunner ◽

H Bjørsvik ◽

...

Keyword(s):

Imaging System ◽

Therapeutic Potential ◽

Flow Cytometric Analysis ◽

Annexin V ◽

Therapeutic Effects ◽

Cell Viability Assay ◽

Selective Cytotoxicity ◽

Viability Assay

Abstract BACKGROUND Although withdrawn from the market due to cardiotoxicity, we have shown that the antipsychotic drug Thioridazine shows chemosensitizing effects in combination with Temozolomide (TMZ) for the treatment of glioblastoma multiforme (GBM). Based on our prior observations, the aim of the presented project was through medicinal chemistry, to design and synthesize new compounds based on Thioridazines tricyclic structure, and to determine their therapeutic potential. MATERIAL AND METHODS Fourteen compounds were synthesized where variations were made within the tricyclic side chains. The newly synthesized compounds were screened for therapeutic efficacy with or without TMZ using a WST-1 cell viability assay as well as a real-time imaging system (IncuCyte). Tests were performed on both monolayer cell cultures, as well as on glioma stem cell spheroids (GSC). The therapeutic effects were also studied on human astrocytes (NHA) as well as on rat brain organoids (BO). Annexin V/propidium iodide (PI) double staining followed by flow cytometric analysis was performed after 48 hours of treatment. RESULTS Following an extensive screening, we identified two novel compounds (EA01 and EA02) that at concentrations of 4 and 9.5 µM showed a strong cytotoxicity on GBM cell lines (U-87 MG p<0,0001, U251 p<0,0001, LN18 p=0,0004) as well as on glioma stem cells (GSC) (P3 p<0,0001) compared to NHA and BOs respectively. Also, when BOs were confronted with GSC spheres in an invasion assay, a selective cytotoxicity was observed in the GSCs. Mechanistically, we show that both compounds induce apoptosis in the GBM cells. Moreover, intravenous delivery of increasing concentrations of EA01 and EA02 revealed no toxicity in animals at concentrations up to 21 mg/kg. CONCLUSION We have developed two new tricyclic therapeutic compounds that show a strong selective cytotoxicity in GBM cells with limited systemic toxicity in animals. Ongoing studies are investigating the therapeutic potential of EA01 and EA02 in orthotopic xenografts in vivo.

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Recapitulation of Transcriptomic Characteristics of Primary Breast Tumours in Patient-Derived 3D Cultures in Vitro

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/prolas-2021-0004 ◽

2021 ◽

Vol 75 (1) ◽

pp. 20-24

Author(s):

Dina Nitiša ◽

Nityanand Jain ◽

Arvīds Irmejs ◽

Valdis Pirsko ◽

Inese Čakstiņa

Keyword(s):

Gene Expression ◽

Quantitative Polymerase Chain Reaction ◽

Expression Patterns ◽

3D Cell Culture ◽

Model System ◽

Gene Expression Patterns ◽

3D Cultures ◽

Culture Development

AbstractBreast cancer (BC) is the most common cause of cancer-related deaths among women in Europe and worldwide. Adherent (2D) cell cultures have been the routine in vitro model system employed in preclinical BC research for the last half-century. Over the past decade, new protocols have been developed allowing patient-derived three-dimensional organoid (3D) cell culture development from a range of solid tumours, including BC. These 3D models offer a promise of closer resemblance to the native tumour than the 2D cultures. To test the assumption that an in vitro 3D BC model system provides increased faithfulness to the molecular processes happening in vivo, as compared to 2D BC cultures, post-operational material from three BC patients was used to simultaneously develop 2D and 3D cultures in vitro. When analysed by quantitative polymerase chain reaction (PCR), the gene expression patterns of the cells from 3D cultures resembled the original tissues, while the gene expression patterns of the conventional 2D cultures were more distant.

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PTH Derivative Promotes Wound Healing via Synergistic Multicellular Stimulating and Exosomal Activities

10.21203/rs.2.18433/v3 ◽

2020 ◽

Author(s):

Yi-Fan Shen ◽

Jing-Huan Huang ◽

Kai-Yang Wang ◽

Jin Zheng ◽

Lin Cai ◽

...

Keyword(s):

Wound Healing ◽

Epithelial Cells ◽

Intercellular Communication ◽

Indirect Effects ◽

Clinical Problem ◽

Therapeutic Effects ◽

And Migration ◽

Proliferation And Migration

Abstract Background: Diabetic wounds are a disturbing and rapidly growing clinical problem. A novel peptide, parathyroid hormone related peptide (PTHrP-2), is assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 were determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 were determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos were added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played a hub role in PTHrP-2 indirect effects in wound healing. Conclusion: These findings of this study indicated that PTHrP-2, a multifunctional factor, could promote wound healing via synergistic multicellular stimulating and exosomal activities. Key words PTH, multifunctional factor, diabetic wound, exosomes, synergistic effect

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Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Inflammatory Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms23010126 ◽

2021 ◽

Vol 23 (1) ◽

pp. 126

Author(s):

Alasdair G. Kay ◽

Kane Treadwell ◽

Paul Roach ◽

Rebecca Morgan ◽

Rhys Lodge ◽

...

Keyword(s):

T Cell ◽

Extracellular Vesicles ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Histopathological Analysis ◽

Therapeutic Effects ◽

Synovial Joint ◽

Paracrine Signalling

Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA). EVs isolated from MSCs cultured normoxically (21% O2, 5% CO2), hypoxically (2% O2, 5% CO2) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA. All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Regulatory T cell (Treg):Th17 homeostatic balance. Normoxic EVs present the optimal strategy for broad therapeutic benefit. EVs present an effective novel technology with the potential for cell-free therapeutic translation.

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Heparin-Modified Amniotic Membrane Combined With Growth Factors for Promoting Corneal Wound Healing After Alkali Burn

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.599800 ◽

2020 ◽

Vol 8 ◽

Author(s):

Xuan Zhao ◽

Xin Zuo ◽

Jing Zhong ◽

Bowen Wang ◽

Saiqun Li ◽

...

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Sustained Release ◽

Corneal Epithelial Cell ◽

Control Group ◽

Therapeutic Effects ◽

Cell Growth And Migration ◽

Corneal Epithelial

Ocular chemical burns are potentially blinding ocular injuries and require urgent management. Amniotic membrane (AM) transplantation is an effective surgical treatment, one of the reasons is because AM is a rich source of growth factors that can promote epithelialization and wound healing. However, growth factors will be gradually lost and insufficient after preparation process and long-time storage, leading to unsatisfactory therapeutic effects. Herein, we present a modified AM (AM-HEP) for the supplement and sustained release of growth factor by surface grafting heparin for treatment of ocular chemical burns. Heparin grafting rate and stability, microstructure, physical property, and sustained release of epithelial growth factor (EGF) of AM-HEP were characterized. Biocompatibility and ability to promote corneal epithelial cell growth and migration were evaluated and compared with a biological amnion, which is available on the market in vitro. The therapeutic effects of AM-HEP combined with EGF (AM-HEP@EGF) in vivo had been evaluated in a model of mouse corneal alkali burn. The results indicated that heparin was introduced into AM and maintain stability over 3 weeks at 37°C. The modification process of AM-HEP did not affect microstructure and physical property after comparing with non-modified AM. EGF could be combined quickly and effectively with AM-HEP; the sustained release could last for more than 14 days. AM-HEP@EGF could significantly promote corneal epithelial cell growth and migration, compared with non-modified AM and control group. Faster corneal epithelialization was observed with the transplantation of AM-HEP@EGF in vivo, compared with the untreated control group. The corneas in the AM-HEP@EGF group have less inflammation and were more transparent than those in the control group. The results from in vitro and in vivo experiments demonstrated that AM-HEP@EGF could significantly enhance the therapeutic effects. Taken together, AM-HEP@EGF is exhibited to be a potent clinical application in corneal alkali burns through accelerating corneal epithelial wound healing.

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Cordycepin in Anticancer Research: Molecular Mechanism of Therapeutic Effects

Current Medicinal Chemistry ◽

10.2174/0929867325666181001105749 ◽

2020 ◽

Vol 27 (6) ◽

pp. 983-996 ◽

Cited By ~ 1

Author(s):

Md. Asaduzzaman Khan ◽

Mousumi Tania

Keyword(s):

Anticancer Activity ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Cancer Drug ◽

Therapeutic Effects ◽

Anticancer Activities ◽

Cancer Cell Growth ◽

Ongoing Research

Background: Cordycepin is a nucleotide analogue from Cordyceps mushrooms, which occupies a notable place in traditional medicine. Objective: In this review article, we have discussed the recent findings on the molecular aspects of cordycepin interactions with its recognized cellular targets, and possible mechanisms of its anticancer activity. Methods: We have explored databases like pubmed, google scholar, scopus and web of science for the update information on cordycepin and mechanisms of its anticancer activity, and reviewed in this study. Results: Cordycepin has been widely recognized for its therapeutic potential against many types of cancers by various mechanisms. More specifically, cordycepin can induce apoptosis, resist cell cycle and cause DNA damage in cancer cells, and thus kill or control cancer cell growth. Also cordycepin can induce autophagy and modulate immune system. Furthermore, cordycepin also inhibits tumor metastasis. Although many success stories of cordycepin in anticancer research in vitro and in animal model, and there is no successful clinical trial yet. Conclusion: Ongoing research studies have reported highly potential anticancer activities of cordycepin with numerous molecular mechanisms. The in vitro and in vivo success of cordycepin in anticancer research might influence the clinical trials of cordycepin, and this molecule might be used for development of future cancer drug.

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