Topical JAK inhibition ameliorates EGFR inhibitor-induced rash in rodents and humans.

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition.

Higher percentage of CD34+ stem cells and elevated efficacy in androgenetic alopecia treatment observed in CGF prepared from 640 nm laser-pretreated blood: A preliminary study.

BACKGROUND: Concentrated growth factor (CGF) injection has proven effective in treating androgenetic alopecia (AGA). The primary mechanism of CGF in treating AGA is thought to be the CD34+ stem cells and platelets-associated growth factors being injected into the scalp. CGF efficacy in treating AGA may rely on the activation level of these stem cells and platelets. The 640 nm laser is a United States Food and Drug Administration approved AGA treatment that activates follicle stem cells. Therefore, we hypothesize that pretreating CGF with a 640 nm laser may further activate CD34+ stem cells and platelets, thereby improving the efficacy of CGF in treating AGA. OBJECTIVE: This study aims to investigate whether 640 nm laser pretreated CGF (640CGF) has a greater effect in treating AGA than 640 nm laser non-pretreated CGF (N640CGF) and evaluate whether 640 nm laser pretreatment changed CD34+ cell percentage. METHODS: This study enrolled 10 patients (8 male, 2 female) with AGA aged 18-60 years who received CGF injections. The 640CGF group was pretreated with a 640 nm laser at an energy density of 4 J/cm2, with a 30 cm irradiation distance for 30 min. Half of the scalp was treated with 640CGF, whereas the other half was treated with N640CGF. The injection was prepared by a doctor who did not know which blood tube had been pretreated. The treatment efficacy was evaluated using a trichoscope 1 month after injection. RESULTS: All 10 (100%) patients participated in the follow-up visit, and a higher quantity of new hairs was observed on the side injected with 640CGF than N640CGF (p = 0.019). Additionally, fewer malnourished hairs were observed on the 640CGF pretreated side (p = 0.015). No serious adverse events were reported. CONCLUSIONS: A higher percentage of CD34+ stem cells and improved efficacy in AGA treatment could be observed with CGF prepared from 640 nm laser-pretreated blood.

Molybdenum nanoparticles as a potential topical medication for alopecia treatment through antioxidant pathways that differ from minoxidil.

BACKGROUND: Hair loss is a common dermatological condition including various types such as alopecia areata, androgenetic alopecia, etc. Minoxidil is a topical medication used for treating hair loss, which is effective for various types of alopecia. However, minoxidil has limitations in treating hair loss, such as slow onset of action and low efficacy, and it cannot effectively inhibit one of the major pathogenic factors of hair loss - excessive oxidative stress. METHODS: Transition metal elements with rapid electron transfer, such as molybdenum, have been extensively studied and applied for inhibiting oxidative stress. We established a mouse model for hair growth and intervened with nano-sized molybdenum, minoxidil, and a combination of both. The physicochemical properties of nano-sized molybdenum enabled it to mediate oxidative stress more quickly. RESULTS: The results showed that nano-sized molybdenum can accelerate hair growth, increase the number of local hair follicles, and reduce the expression of oxidative stress-related molecules such as iNOS, COX2, and androgen receptors. The combination of nano-sized molybdenum and minoxidil showed an additive effect in promoting hair growth. CONCLUSION: Our findings suggest that nano-sized molybdenum might be a potential topical medication for treating hair loss by inhibiting the oxidative stress pathway. Nano-sized molybdenum, alone or in combination with minoxidil, could be a promising therapeutic approach for patients with hair loss, particularly those who do not respond well to current treatments. Further clinical studies are warranted to confirm the efficacy and safety of this novel treatment.