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Psoriasis, a chronic and easily recurring inflammatory skin disease, causes a great economic burden to the patient's family because the etiology and mechanism are still unclear and the treatment cycle is long. In this study, the function and related mechanisms of Momordin Ic in psoriasis were investigated. The IMQ-induced mouse psoriasis model was constructed. The protective effects of different doses of Momordin Ic on psoriasis skin damage in mice were detected by PASI score, HE staining and Ki-67 staining. A psoriasis-like keratinocyte model was established at the cellular level using M5 (IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α) triggered HaCaT. The effects of Momordin Ic upon HaCaT cell biological behavior were examined using MTT and CCK-8 assays. In terms of mechanism, the expression level of each inflammatory factor was assessed using IHC staining and/or ELISA, qRT-PCR, the expression of oxidative stress-related indicators was detected biochemically, and western blot was performed to detect the levels of key proteins of the Wnt signaling and VEGF. As the results shown, at the in vivo level, Momordin Ic significantly alleviated skin damage, reduced PASI score and inhibited hyperproliferation of keratinized cells in psoriasis mice. At the cellular level, Momordin Ic also significantly reversed M5-induced hyperproliferation of HaCaT keratinocytes. In terms of mechanism, Momordin Ic significantly inhibited the IL-23/IL-17 axis, dramatically elevated the levels of intracellular antioxidants including SOD, GSH-Px, and CAT, and significantly down-regulated the levels of the indicator of oxidative damage, malondialdehyde (MDA). In addition, Momordin Ic also significantly inhibited the level of ß-catenin, a pivotal protein of the Wnt signaling, C-Myc, a target gene of the Wnt signaling, and VEGF, a critical protein of angiogenesis. In conclusion, Momordin Ic can be involved in the skin-protective effects of psoriasis by multiple mechanisms, including inhibition of the Wnt signaling pathway and the IL-23/IL-17 axis, and suppression of oxidative damageand VEGF expression. Momordin Ic has been proven to be an underlying therapeutic drug for the treatment of psoriasis.
Assuntos
Modelos Animais de Doenças , Interleucina-17 , Interleucina-23 , Queratinócitos , Psoríase , Pele , Via de Sinalização Wnt , Animais , Humanos , Camundongos , Proliferação de Células/efeitos dos fármacos , Células HaCaT , Imiquimode , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Psoríase/tratamento farmacológico , Psoríase/patologia , Psoríase/induzido quimicamente , Psoríase/imunologia , Pele/patologia , Pele/efeitos dos fármacos , Pele/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Uncontrolled hemorrhage results in various complications and is currently the leading cause of death in the general population. Traditional hemostatic methods have drawbacks that may lead to ineffective hemostasis and even the risk of secondary injury. Therefore, there is an urgent need for more effective hemostatic techniques. Polymeric hemostatic materials, particularly hydrogels, are ideal due to their biocompatibility, flexibility, absorption, and versatility. Functional hemostatic hydrogels can enhance hemostasis by creating physical circumstances conducive to hemostasis or by directly interfering with the physiological processes of hemostasis. The procoagulant principles include increasing the concentration of localized hemostatic substances or establishing a physical barrier at the physical level and intervention in blood cells or the coagulation cascade at the physiological level. Moreover, synergistic hemostasis can combine these functions. However, some hydrogels are ineffective in promoting hemostasis or have a limited application scope. These defects have impeded the advancement of hemostatic hydrogels. To provide inspiration and resources for new designs, this review provides an overview of the procoagulant principles of hemostatic hydrogels. We also discuss the challenges in developing effective hemostatic hydrogels and provide viewpoints.
Assuntos
Hemostáticos , Humanos , Hemostáticos/farmacologia , Hidrogéis/farmacologia , Hemostasia , Coagulação Sanguínea , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controleRESUMO
Although the past decade has witnessed unprecedented medical advances, achieving rapid and effective hemostasis remains challenging. Uncontrolled bleeding and wound infections continue to plague healthcare providers, increasing the risk of death. Various types of hemostatic materials are nowadays used during clinical practice but have many limitations, including poor biocompatibility, toxicity and biodegradability. Recently, there has been a burgeoning interest in organisms that stick to objects or produce sticky substances. Indeed, applying biological adhesion properties to hemostatic materials remains an interesting approach. This paper reviews the biological behavior, bionics, and mechanisms related to hemostasis. Furthermore, this paper covers the benefits, challenges and prospects of biomimetic hemostatic materials.
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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and an adaptor protein that primarily regulates adhesion signaling and cell migration. FAK promotes cell survival in response to stress. Increasing evidence has shown that at the pathological level, FAK is highly expressed in multiple tumors in several systems (including lung, liver, gastric, and colorectal cancers) and correlates with tumor aggressiveness and patient prognosis. At the molecular level, FAK promotes tumor progression mainly by altering survival signals, invasive capacity, epithelial-mesenchymal transition, the tumor microenvironment, the Warburg effect, and stemness of tumor cells. Many effective drugs have been developed based on the comprehensive role of FAK in tumor cells. In addition, its potential as a tumor marker cannot be ignored. Here, we discuss the pathological and pre-clinical evidence of the role of FAK in cancer development; we hope that these findings will assist in FAK-based clinical studies.
RESUMO
Clostridial gas gangrene is an unusual but fast-spreading necrotic infection of soft tissue relevant to high mortality rates. We report a case of postoperative gas gangrene of the pelvic wall, scrotum, and perineal site, with very acute onset and rapid progression of symptoms after laparoscopic radical resection for rectal cancer. Although potentially treatable with appropriate antibiotic cover and urgent thorough surgical debridement, this case still developed irreversibly into fulminant and fatal sepsis. The possible etiologic factors, better measures of diagnosis, and treatment are discussed, and the relevant literature is reviewed.