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Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.
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The NLRP3 inflammasome represents a cytoplasmic multiprotein complex with the capability to recognize a wide range of pathogen-derived, environmental, and endogenous stress-related factors. Dysregulated activation of the NLRP3 inflammasome has been implicated in the development of various inflammasome-associated disorders, highlighting its significance as a pivotal target for the treatment of inflammatory diseases. Nonetheless, despite its clinical importance, there is currently a lack of specific drugs available for directly targeting the NLRP3 inflammasome. Several strategies have been explored to target different facets of the NLRP3 inflammasome, with interventions aimed at directly inhibiting NLRP3 demonstrating the most promising efficacy and safety profiles. In this review, we provide a summary of direct inhibitors targeting NLRP3, elucidating their inhibitory mechanisms, clinical trial phases, and potential applications. Through this discussion, we aim to shed light on the implications of NLRP3 inhibition for the treatment of inflammatory diseases.
Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLRRESUMO
The oncogene MYC is dysregulated in a host of human cancers, and as an important point of convergence in multitudinous oncogenic signaling pathways, it plays a crucial role in tumor immune regulation in the tumor immune microenvironment (TIME). Specifically, MYC promotes the expression of immunosuppressive factors and inhibits the expression of immune activation regulators. Undoubtedly, a therapeutic strategy that targets MYC can initiate a new era of cancer treatment. In this review, we summarize the essential role of the MYC signaling pathway in tumor immunity and the development status of MYC-related therapies, including therapeutic strategies targeting MYC and combined MYC-based immunotherapy. These studies have reported extraordinary insights into the translational application of MYC in cancer treatment and are conducive to the emergence of more effective immunotherapies for cancer.
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OBJECTIVE: To report the clinical result of the improved island skin flap with distally-based sural nerve nutrient vessels in repairing skin defect in the heel, ankle or foot. METHODS: From August 2004 to April 2005, 15 patients with skin defect in the heel, ankle or foot at distal part were treated by the improved island skin flap with distally-based of sural nerve nutrient vessels. Of 15 flaps, 12 were simplex flaps and 3 were complex flaps. These flap area ranged from 7 cm x 6 cm to 11 x 8 cm. The donor sites were sutured directly and covered with free flap. RESULTS: All flaps survived without flap swelling and disturbance of blood circulation. The wounds of donor and recipient sites healed by first intention. The follow-up period ranged from 3 to 6 months. The texture of flap was soft and the color of flap was similar to that of normal skin. The foot function was excellent. CONCLUSION: The improved island skin flap with distally-based sural nerve nutrient vessels is an ideal skin flap for repairing skin defect in the heel, ankle or foot distal part in clinical. The operation is simple and need not to anastomose blood vessel.