-
Journal of Neuroinflammation Sep 2020Ischemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for...
BACKGROUND
Ischemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Microglia and astrocyte activation-mediated inflammation play a pivotal role in ischemic stroke injury. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, although CSO is mostly used as a solvent for lipid-soluble drugs. However, the role of CSO in neuroprotection against stroke has not been previously reported.
METHODS
We treated adult male rats with CSO (1.3 ml/kg, subcutaneous injection, once every other day for 3 weeks) and then constructed a middle cerebral artery occlusion (MCAO) model followed by 24 h of reperfusion. Then, we measured the neurological scores, infarction volume, neuronal injury, and brain edema; we also measured the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), degree of microglial and astrocytic activation, protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), C3d and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes.
RESULTS
We found that CSO treatment significantly improved the neurological deficit, reduced infarction volume, and alleviated neuronal injuries, blood-brain barrier (BBB) disruption, and brain edema. Additionally, CSO treatment significantly reduced microglial and astrocytic activation, inhibited TLR4 and NF-κB protein expression, and reduced the release of IL-1β, IL-6, and TNF-α. Finally, CSO treatment significantly decreased the number of C3d/glial fibrillary acidic protein (GFAP)-positive cells and C3d protein expression, and increased the number of S100A10/GFAP-positive cells and S100A10 protein expression.
CONCLUSION
Our results first found that CSO treatment alleviated ischemic stroke injury by reducing microglial and astrocytic activation and inflammation, which was related to the inhibition of TLR4/NF-κB pathway and the reduction of A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.
Topics: Animals; Astrocytes; Cottonseed Oil; Cytokines; Inflammation; Ischemic Stroke; Male; Microglia; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Signal Transduction
PubMed: 32917229
DOI: 10.1186/s12974-020-01946-7 -
Stem Cell Research & Therapy Aug 2019Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived...
Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway.
BACKGROUND
Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating skin wounds. However, the exact effects of hAMSCs on the healing of thermal burn skin wounds and their potential mechanisms are not explored.
METHODS
hAMSCs were isolated from amniotic membrane and characterized by RT-PCR, flow cytometry, immunofluorescence, and tumorigenicity test. We assessed the effects of hAMSCs and hAMSC conditional medium (CM) on wound healing in a deep second-degree burn injury model of mice. We then investigated the biological effects of hAMSCs and hAMSC-CM on the apoptosis and proliferation of heat stress-injured human keratinocytes HaCAT and dermal fibroblasts (DFL) both in vivo and in vitro. Next, we explored the underlying mechanisms by assessing PI3K/AKT and GSK3β/β-catenin signaling pathways in heat injured HaCAT and DFL cells after hAMSCs and hAMSC-CM treatments using PI3K inhibitor LY294002 and β-catenin inhibitor ICG001. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may activate PI3K/AKT signaling pathway.
RESULTS
Our results showed that hAMSCs expressed various markers of embryonic stem cells and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAMSC and hAMSC-CM transplantation significantly promoted thermal burn wound healing by accelerating re-epithelialization with increased expression of CK19 and PCNA in vivo. hAMSCs and hAMSC-CM markedly inhibited heat stress-induced apoptosis in HaCAT and DFL cells in vitro through activation of PI3K/AKT signaling and promoted their proliferation by activating GSK3β/β-catenin signaling. Furthermore, we demonstrated that hAMSC-mediated activation of GSK3β/β-catenin signaling was dependent on PI3K/AKT signaling pathway. Antibody array assay showed that a panel of cytokines including PAI-1, C-GSF, periostin, and TIMP-1 delivered from hAMSCs may contribute to the improvement of the wound healing through activating PI3K/AKT signaling pathway.
CONCLUSION
Our results demonstrated that hAMSCs and hAMSC-CM efficiently cure heat stress-induced skin injury by inhibiting apoptosis of skin cells and promoting their proliferation through activating PI3K/AKT signaling pathway, suggesting that hAMSCs and hAMSC-CM may provide an alternative therapeutic approach for the treatment of skin injury.
Topics: Amnion; Animals; Apoptosis; Bridged Bicyclo Compounds, Heterocyclic; Burns; Cell Differentiation; Cell Proliferation; Chromones; Cytokines; Fibroblasts; Humans; Keratinocytes; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Morpholines; Paracrine Communication; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Pyrimidinones; Signal Transduction; Wound Healing; beta Catenin
PubMed: 31399039
DOI: 10.1186/s13287-019-1366-y -
Annals of Burns and Fire Disasters Dec 2021The recreational consumption of nitrous oxide has steadily increased in recent years. Before being inhaled, the nitrous oxide is contained in a gas cylinder held firmly...
The recreational consumption of nitrous oxide has steadily increased in recent years. Before being inhaled, the nitrous oxide is contained in a gas cylinder held firmly between the thighs and then the gas is transferred to a rubber balloon. During the deconditioning steps, the cylinder cools down and causes frostbite. We report the case of six third-degree burns on the inner side of the thighs. At first superficial, this burn will deepen and require surgical management.
PubMed: 35035324
DOI: No ID Found -
American Family Physician Apr 2020Most patients with burn injuries are treated as outpatients. Two key determinants of the need for referral to a burn center are burn depth and percentage of total body...
Most patients with burn injuries are treated as outpatients. Two key determinants of the need for referral to a burn center are burn depth and percentage of total body surface area involved. All burn injuries are considered trauma, prompting immediate evaluation for concomitant injuries. Initial treatment is directed at stopping the burn process. Superficial (first-degree) burns involve only the epidermal layer and require simple first-aid techniques with over-the-counter pain relievers. Partial-thickness (second-degree) burns are subdivided into two categories: superficial and deep. Superficial partial-thickness burns extend into the dermis, may take up to three weeks to heal, and require advanced dressings to protect the wound and promote a moist environment. Deep partial-thickness burns require immediate referral to a burn surgeon for possible early tangential excision. Full-thickness (third-degree) burns involve the entire dermal layer, and patients with these burns should automatically be referred to a burn center. Prophylactic antibiotics are not indicated for outpatient management and may increase bacterial resistance. People with diabetes mellitus are at increased risk of complications and infection, and early referral to a burn center should be considered. Pruritus, hypertrophic scarring, and permanent hyperpigmentation are long-term complications of partial-thickness burns. Burn injuries are more likely to occur in children and older people. Patient education during primary care visits may be an effective prevention strategy.
Topics: Aged; Ambulatory Care; Child; Humans; Outpatients; Skin; Wound Healing
PubMed: 32293848
DOI: No ID Found -
Advanced Science (Weinheim,... Jun 2022Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target...
Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target of high interest for therapeutic strategies. To gain insights into mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models. Leveraging Organ-on-Chip technology, a microphysiological in vitro model of human WAT is introduced: a tailored microfluidic platform featuring vasculature-like perfusion that integrates 3D tissues comprising all major WAT-associated cellular components (mature adipocytes, organotypic endothelial barriers, stromovascular cells including adipose tissue macrophages) in an autologous manner and recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. A precisely controllable bottom-up approach enables the generation of a multitude of replicates per donor circumventing inter-donor variability issues and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity via a flexible mix-and-match approach. This WAT-on-Chip system constitutes the first human-based, autologous, and immunocompetent in vitro adipose tissue model that recapitulates almost full tissue heterogeneity and can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.
Topics: Adipocytes, White; Adipose Tissue; Adipose Tissue, White; Animals; Humans; Microfluidics; Obesity
PubMed: 35466539
DOI: 10.1002/advs.202104451