scholarly journals Loss of Diacylglycerol Kinase α Enhances Macrophage Responsiveness

2021 ◽  
Vol 12 ◽  
Author(s):  
Laryssa C. Manigat ◽  
Mitchell E. Granade ◽  
Suchet Taori ◽  
Charlotte Anne Miller ◽  
Luke R. Vass ◽  
...  

The diacylglycerol kinases (DGKs) are a family of enzymes responsible for the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). In addition to their primary function in lipid metabolism, DGKs have recently been identified as potential therapeutic targets in multiple cancers, including glioblastoma (GBM) and melanoma. Aside from its tumorigenic properties, DGKα is also a known promoter of T-cell anergy, supporting a role as a recently-recognized T cell checkpoint. In fact, the only significant phenotype previously observed in Dgka knockout (KO) mice is the enhancement of T-cell activity. Herein we reveal a novel, macrophage-specific, immune-regulatory function of DGKα. In bone marrow-derived macrophages (BMDMs) cultured from wild-type (WT) and KO mice, we observed increased responsiveness of KO macrophages to diverse stimuli that yield different phenotypes, including LPS, IL-4, and the chemoattractant MCP-1. Knockdown (KD) of Dgka in a murine macrophage cell line resulted in similar increased responsiveness. Demonstrating in vivo relevance, we observed significantly smaller wounds in Dgka-/- mice with full-thickness cutaneous burns, a complex wound healing process in which macrophages play a key role. The burned area also demonstrated increased numbers of macrophages. In a cortical stab wound model, Dgka-/- brains show increased Iba1+ cell numbers at the needle track versus that in WT brains. Taken together, these findings identify a novel immune-regulatory checkpoint function of DGKα in macrophages with potential implications for wound healing, cancer therapy, and other settings.

2018 ◽  
Vol 9 (4) ◽  
pp. 2374-2385 ◽  
Author(s):  
Chenggui Wang ◽  
Zengjie Zhang ◽  
Tianzhen Xu ◽  
Yiting Lou ◽  
Qingqing Wang ◽  
...  

LN promoted the angiogenesis of endothelial cells by activating the mTOR/ERK pathway, and efficiently enhanced the wound-healing processin vivo.


Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 191
Author(s):  
Atiqah Salleh ◽  
Mh Busra Fauzi

Wound is defined as primarily damaged or disruption of skin contributed to the loss of its microstructure stability and which undergoes complex wound healing process. However, there are tons of factors that could affect the wound healing process such as infection and slow angiogenesis. Involvement of nanotechnologies therapies in wound care research aims to facilitates this healing process. Quantum dots (QDs) are an advanced nanomaterial technology found to be useful in clinical and biomedical applications. This review has been carried out to provide a summary of the application of QDs in acute or chronic wound healing. A thorough searching was done via Web of Science and SCOPUS database to obtain relevant articles including the in vivo, in vitro and in ovo studies. The results demonstrated a similar effect of different types of QDs, or an improvement of QDs in wound healing, antibacterial and angiogenesis properties. This review demonstrated the effectiveness of QDs for the wound healing process mainly by their antibacterial activity. Uniquely, the antibacterial effect unraveled an increasing trend over time influenced by the various concentration of QDs. In conclusion, the application of QDs support the wound healing phases and proven to be effective in vivo, in vitro and in ovo. However, the future QDs work should focus on the molecular level for the details of cellular interactions and pathways.


2021 ◽  
Vol 22 (8) ◽  
pp. 4087
Author(s):  
Maria Quitério ◽  
Sandra Simões ◽  
Andreia Ascenso ◽  
Manuela Carvalheiro ◽  
Ana Paula Leandro ◽  
...  

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.


2017 ◽  
Vol 751 ◽  
pp. 581-585 ◽  
Author(s):  
Piyaporn Kampeerapappun ◽  
Pornpen Siridamrong

The objective of this study was to investigate sericin-polyurethane nanofiber cover (SUC) for wound dressing materials in a rat skin. Sericin-polyurethane blended nanofibers were fabricated by using electrospinning. The composition of 3%w/v polyurethane in ethanol and 19% w/v sericin were blended and electrospun at 15 kV, 20 cm from tip to collector with a feed rate of 6.2 ml/hr. The mats, approximately 1.5 mm thick, were sterile by gamma irradiation with a radiation dose of 15 kGy. The samples of in vitro and in vivo testing were separated into three groups; gauze, polyurethane nanofiber cover (UC), and SUC. In vitro cultured L929 cell lines were investigated with inverted microscope. It was found that cells migrated to SCU. For in vivo tests, the remaining wound in rats was measured on day 2-14 after excision. Compared to original size of wound samples, the size of the wound remained 24% for SUC, 33% for gauze, and 34% for UC at day 8. The sericin, an active agent, contained in SUC mats was about 5 µl at 1.5 ×1.5 cm. It can be concluded that sericin is non-toxic to cells and can promote wound healing process in rats.


Polymers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 3116
Author(s):  
Thien Do ◽  
Tien Nguyen ◽  
Minh Ho ◽  
Nghi Nguyen ◽  
Thai Do ◽  
...  

(1) Background: Wounds with damages to the subcutaneous are difficult to regenerate because of the tissue damages and complications such as bacterial infection. (2) Methods: In this study, we created burn wounds on pigs and investigated the efficacy of three biomaterials: polycaprolactone-gelatin-silver membrane (PCLGelAg) and two commercial burn dressings, Aquacel® Ag and UrgoTulTM silver sulfadiazine. In vitro long-term antibacterial property and in vivo wound healing performance were investigated. Agar diffusion assays were employed to evaluate bacterial inhibition at different time intervals. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assays were used to compare antibacterial strength among samples. Second-degree burn wounds in the pig model were designed to evaluate the efficiency of all dressings in supporting the wound healing process. (3) Results: The results showed that PCLGelAg membrane was the most effective in killing both Gram-positive and Gram-negative bacteria bacteria with the lowest MBC value. All three dressings (PCLGelAg, Aquacel, and UrgoTul) exhibited bactericidal effect during the first 24 h, supported wound healing as well as prevented infection and inflammation. (4) Conclusions: The results suggest that the PCLGelAg membrane is a practical solution for the treatment of severe burn injury and other infection-related skin complications.


2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.


2020 ◽  
Vol 8 (39) ◽  
pp. 9035-9042
Author(s):  
Ming-Yu Wu ◽  
Li Liu ◽  
Qian Zou ◽  
Jong-Kai Leung ◽  
Jia-Li Wang ◽  
...  

An isoquinolinium-based photosensitizer was developed for mitochondrial and bacterial imaging, and used in photodynamic anticancer and antibacterial therapy in a wound healing process in vivo.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Richard Komakech ◽  
Motlalepula Gilbert Matsabisa ◽  
Youngmin Kang

Wounds remain one of the major causes of death worldwide. Over the years medicinal plants and natural compounds have played an integral role in wound treatment. Aspilia africana (Pers.) C. D. Adams which is classified among substances with low toxicity has been used for generations in African traditional medicine to treat wounds, including stopping bleeding even from severed arteries. This review examined the potential of the extracts and phytochemicals from A. africana, a common herbaceous flowering plant which is native to Africa in wound healing. In vitro and in vivo studies have provided strong pharmacological evidences for wound healing effects of A. africana-derived extracts and phytochemicals. Singly or in synergy, the different bioactive phytochemicals including alkaloids, saponins, tannins, flavonoids, phenols, terpenoids, β-caryophyllene, germacrene D, α-pinene, carene, phytol, and linolenic acid in A. africana have been observed to exhibit a very strong anti-inflammatory, antimicrobial, and antioxidant activities which are important processes in wound healing. Indeed, A. africana wound healing ability is furthermore due to the fact that it can effectively reduce wound bleeding, hasten wound contraction, increase the concentration of basic fibroblast growth factor (BFGF) and platelet derived growth factor, and stimulate the haematological parameters, including white and red blood cells, all of which are vital components for the wound healing process. Therefore, these facts may justify why A. africana is used to treat wounds in ethnomedicine.


2012 ◽  
Vol 57 (No. 2) ◽  
pp. 77-82 ◽  
Author(s):  
F. Sabol ◽  
L. Dancakova ◽  
P. Gal ◽  
T. Vasilenko ◽  
M. Novotny ◽  
...  

The complexity of the wound healing process, which is still poorly understood, prompted us to perform an immunohistochemical investigation using rat skin as an in vivo model. Fifteen Sprague-Dawley rats were included in the experiment. Two round full thickness wounds, 4 mm in diameter, were made on the backs of all rats. Haematoxylin and eosin basic staining as well as antibodies against wide spectrum keratin, keratin 10, keratin 14, α-smooth muscle actin, vimentin, fibronectin, collagens Type 1 and 3, and the transcription factor Sox-2 were applied to paraffin and frozen sections of skin wound specimens two, six and fourteen days after surgery, respectively. New hair follicles with Sox-2-positive cells were present after fourteen days; keratin/vimentin positivity was restricted to specimens of day two. Collagen-3 expression prevailed over collagen-1 expression at all evaluated time intervals, except in the uninjured part of the dermis. In conclusion, rat skin wound healing is a dynamic process which can serve as a model for studying phenomena such as cell-cell interactions and transitions in vivo.


Author(s):  
Claire Robertson ◽  
Joe Jing ◽  
Emerald Chun ◽  
Kenji Ikemura ◽  
Anna Aledia ◽  
...  

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