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

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8849935 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Yi Lu ◽

Xiaojie Ding ◽

Fei Qi ◽

Yi Ru ◽

Le Kuai ◽

...

Keyword(s):

Wound Healing ◽

Therapeutic Potential ◽

Quantitative Polymerase Chain Reaction ◽

Expression Patterns ◽

Therapeutic Effects ◽

Diabetic Ulcer ◽

Angiogenesis Factor ◽

Endothelial Growth Factor

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

10.21203/rs.2.18433/v1 ◽

2019 ◽

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 ◽

Chronic Wound ◽

Therapeutic Effects ◽

And Migration ◽

Proliferation And Migration

Abstract Background: Chronic diabetic wounds are a disturbing and rapidly growing clinical problem. Parathyroid hormone related peptide (PTHrP-2) was assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in chronic 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 was determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 was 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 was 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 hub role in PTHrP-2 indirect effects in wound healing. Conclusion: The findings of this study indicate that PTHrP-2, a multifunctional factor, can promote chronic wound healing via synergistic multicellular stimulating and exosomal activities.

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Quinine Enhances Photo-Inactivation of Gram-Negative Bacteria

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz487 ◽

2019 ◽

Vol 221 (4) ◽

pp. 618-626 ◽

Cited By ~ 3

Author(s):

Leon G Leanse ◽

Pu-Ting Dong ◽

Xueping S Goh ◽

Min Lu ◽

Ji-Xin Cheng ◽

...

Keyword(s):

Mouse Skin ◽

Multidrug Resistant ◽

Infection Model ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Antimicrobial Effects ◽

Therapeutic Modalities ◽

Novel Approach

Abstract Background Antimicrobial resistance is a significant concern to public health, and there is a pressing need to develop novel antimicrobial therapeutic modalities. Methods In this study, we investigated the capacity for quinine hydrochloride (Q-HCL) to enhance the antimicrobial effects of antimicrobial blue light ([aBL] 405 nm wavelength) against multidrug-resistant (MDR) Gram-negative bacteria in vitro and in vivo. Results Our findings demonstrated the significant improvement in the inactivation of MDR Pseudomonas aeruginosa and Acinetobacter baumannii (planktonic cells and biofilms) when aBL was illuminated during Q-HCL exposure. Furthermore, the addition of Q-HCL significantly potentiated the antimicrobial effects of aBL in a mouse skin abrasion infection model. In addition, combined exposure of aBL and Q-HCL did not result in any significant apoptosis when exposed to uninfected mouse skin. Conclusions In conclusion, aBL in combination with Q-HCL may offer a novel approach for the treatment of infections caused by MDR bacteria.

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

10.21203/rs.2.18433/v2 ◽

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 ◽

Chronic Wound ◽

Therapeutic Effects ◽

And Migration ◽

Proliferation And Migration

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Autologous Exosome Transfer: A New Personalised Treatment Concept to Prevent Colitis in a Murine Model

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz184 ◽

2019 ◽

Vol 14 (6) ◽

pp. 841-855 ◽

Cited By ~ 6

Author(s):

Chunhua Yang ◽

Mingzhen Zhang ◽

Junsik Sung ◽

Lixin Wang ◽

Yunjin Jung ◽

...

Keyword(s):

Ulcerative Colitis ◽

Wound Healing ◽

Intestinal Inflammation ◽

Personalised Medicine ◽

Hydrodynamic Diameter ◽

Therapeutic Effects ◽

Healing Phase ◽

Anti Inflammatory

Abstract Background and Aims Epigenetic information delivered by intestinal exosomes can be useful for diagnosing intestinal diseases, such as ulcerative colitis, but the therapeutic effects of intestinal exosomes have not been fully exploited. We herein developed an autologous exosome therapy that could treat intestinal disease without any risk of inducing a systemic immunological reaction. Methods Intestinal exosomes were isolated and purified from faeces by our newly developed multi-step sucrose gradient ultracentrifugation method. Lipopolysaccharide [LPS]-activated macrophages were employed to test the in vitro anti-inflammatory ability of intestinal exosomes. To evaluate the in vivo anti-inflammatory activity of our system, we gavaged dextran sulphate sodium [DSS]-induced colitic mice with their own healing phase intestinal exosomes. Results Mouse intestinal exosomes are round extracellular vesicles with a hydrodynamic diameter of ~140 [±20] nm and a surface charge of ~-12 [±3] mV. Among the exosomes obtained at four different stages of DSS-induced ulcerative colitis [1, before treatment; 2, DSS-treated; 3, healing phase; and 4, back to normal], the healing phase exosomes showed the best in vitro anti-inflammatory effects and promotion of wound healing. Moreover, oral co-administration of autologous healing phase exosomes with DSS was found to significantly reduce the risk of a second round of DSS-induced ulcerative colitis in mice. Conclusions Intestinal exosomes obtained during the healing phase that follows induced intestinal inflammation could strongly promote wound healing in the host. Oral administration of autologous exosomes from the healing phase could be a safe and effective approach for treating the ulcerative colitis of a given patient in the context of personalised medicine.

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Novel antimicrobial ointment for infected wound healing in an in vitro and in vivo porcine model

Wound Repair and Regeneration ◽

10.1111/wrr.12922 ◽

2021 ◽

Author(s):

Ray Hachem ◽

Umang M. Parikh ◽

Ruth Reitzel ◽

Joel Rosenblatt ◽

Aditya Kaul ◽

...

Keyword(s):

Wound Healing ◽

Porcine Model ◽

Infected Wound

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Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647910 ◽

1976 ◽

Vol 35 (01) ◽

pp. 049-056 ◽

Cited By ~ 4

Author(s):

Christian R Klimt ◽

P. H Doub ◽

Nancy H Doub

Keyword(s):

Myocardial Infarction ◽

Secondary Prevention ◽

Case Control ◽

Therapeutic Effects ◽

Case Control Studies ◽

Definitive Answer ◽

Inhibition Of Platelet Aggregation ◽

Prospective Trials

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

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