Aging, cancer, and longevity have been linked to intracellular Ca2+ signaling and nociceptive transient receptor potential (TRP) channels. We found that TRP canonical 7 (TRPC7) is a nociceptive mechanoreceptor and that TRPC7 channels specifically mediate the initiation of ultraviolet B (UVB)‐induced skin aging and tumor development due to p53 gene family mutations. Within 30 min after UVB irradiation, TRPC7 mediated UVB‐induced Ca2+ influx and the subsequent production of reactive oxygen species in skin cells. Notably, this function was unique to TRPC7 and was not observed for other TRP channels. In TRPC7 knockout mice, we did not observe the significant UVB‐associated pathology seen in wild‐type mice, including epidermal thickening, abnormal keratinocyte differentiation, and DNA damage response activation. TRPC7 knockout mice also had significantly fewer UVB‐induced cancerous tumors than did wild‐type mice, and UVB‐induced p53 gene family mutations were prevented in TRPC7 knockout mice. These results indicate that TRPC7 activity is pivotal in the initiation of UVB‐induced skin aging and tumorigenesis and that the reduction in TRPC7 activity suppresses the UVB‐induced aging process and tumor development. Our findings support that TRPC7 is a potential tumor initiator gene and that it causes cell aging and genomic instability, followed by a change in the activity of proto‐oncogenes and tumor suppressor genes to promote tumorigenesis.

Transient receptor potential canonical 7 (TRPC7) has been reported to mediate aging-associated tumorigenesis, but the role of TRPC7 in cancer malignancy is still unclear. TRPC7 is associated with tumor size in patients with lung adenocarcinoma and the present study further evaluated the underlying mechanism of TRPC7 in the regulation of cancer progression. The clinicopathological role of TRPC7 was assessed using immunohistochemistry staining and the pathological mechanism of TRPC7 in lung adenocarcinoma cells was determined using cell cycle examination, invasion and calcium response assays, and immunoblot analysis. The results indicated that high TRPC7 expression was associated with a lower 5-year survival rate compared with low TRPC7 expression, which suggested that TRPC7 expression was inversely associated with overall survival in patients with lung adenocarcinoma. TRPC7 serves a pathological role by facilitating the enhancement of cell growth and migration with increased phosphorylation of Ca 2+ /calmodulin-dependent protein kinase II, AKT and ERK. TRPC7 knockdown in lung adenocarcinoma cells restrained cell cycle progression and cell migration by interrupting the TRPC7-mediated Ca 2+ signaling-dependent AKT and MAPK signaling pathways. These findings demonstrated for the first time a role of oncogenic TRPC7 in the regulation of cancer malignancy and could provide a novel therapeutic molecular target for patients with lung adenocarcinoma.

Vitiligo is an autoimmune skin disorder that occurs due to immunemediated loss of functional melanocytes, leading to patchy skin depigmentation. The triggering of an autoimmune phenomena in patients infected with coronavirus disease 2019 (COVID-19) and those receiving COVID-19 vaccinations has been increasingly reported, and these adverse events have also been seen in vitiligo. Cases of new-onset and exacerbation of vitiligo following COVID-19 vaccination have been reported in individuals of all ages, ethnicities, and with different vaccine types. While current guidelines and consensus recommend COVID-19 vaccination for most patients, including those with autoimmune diseases, 1,2 practitioners must assess the risk and potential for disease onset or flare-up. According to the Taiwan Centers for Disease Control, around 21.7 million people in our population have received at least one primary COVID-19 vaccine, with 94% of them having been vaccinated, while 88% have received at least two doses and 74% have received at least three doses. In light of the emergence of new Delta and Omicron variants, booster vaccination programs are now underway to enhance the humoral response. Some eligible groups can now receive the fourth vaccination booster and a fifth booster dose of Moderna's next-generation bivalent vaccine.Our study aims to report the incidence of vitiligo following primary and booster COVID-19 vaccines. We retrospectively reviewed electronic medical records of new-onset and exacerbations of vitiligo following COVID-19 vaccinations at our vitiligo clinic, which is located at a tertiary referral center. In addition, we conducted a systematic review to analyze the current evidence regarding COVID-19 vaccine-associated vitiligo. | MATERIAL S AND ME THODSWe conducted a retrospective study at our vitiligo clinic, which is located at a Taiwanese tertiary medical center (Chang Gung Memorial Hospital, Linkou, and Taipei branches). The study included patients with new-onset vitiligo or exacerbations of preexisting vitiligo that were diagnosed within a month of receiving COVID-19 vaccination between January 1, 2021, and September 30, 2022. We clinically diagnosed vitiligo based on the presence of acquired amelanotic macules and patches with well-defined margins and typical distribution. Wood's lamp examination was used to identify vitiligo lesions

induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes.