Arsenic, a metal ubiquitously distributed in the environment, remains an important global health threat. Drinking arsenic-contaminated water is the major route of human exposure. Exposure to arsenic contributes to several malignancies, in the integumentary, respiratory, hepatobiliary, and urinary systems. Cutaneous lesions are important manifestations after long-term arsenic exposure. Arsenical skin cancers usually herald the development of other internal cancers, making the arsenic-induced skin carcinogenesis a good model to investigate the progression of chemical carcinogenesis. In fact, only a portion of arsenic-exposed humans eventually develop malignancies, likely attributed to the arsenic-impaired immunity in susceptible individuals. Currently, the exact pathophysiology of arsenic-induced carcinogenesis remains elusive, although increased reactive oxidative species, aberrant immune regulations, and chromosome abnormalities with uncontrolled cell growth might be involved. This review discusses how arsenic induces carcinogenesis, and how the dysregulated innate and adaptive immunities in systemic circulation and in the target organs contribute to arsenic carcinogenesis. These findings offer evidence for illustrating the mechanism of arsenic-related immune dysregulation in the progression of carcinogenesis, and this may help explain the nature of multiple and recurrent clinical lesions in arsenic-induced skin cancers.

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)–knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.

Extensive exposure to UVB (280–320 nm) is the major risk responsible for various skin injuries. Numerous reports have shown that natural products could demonstrate photochemopreventive efficacy against UVB damage. We investigated the preventive effects and associated molecular mechanisms of red raspberry extract upon UVB-caused damage in human epidermal keratinocytes and a nude mouse model. The protein profiles and immunohistological study on a nude mouse skin indicated that red raspberry extract could prevent UVB-caused cell death and protect the skin against UVB-exposed injury manifested by wrinkling, scaling, tanning, and water loss as well as epidermal thickening. In addition, red raspberry extract application effectively abolished oxidative damage in DNA and attenuated the carbonylation level of proteins, which attributed to the activation of SOD, Nrf2 and its target genes, and HO-1. Red raspberry extract also altered the cells’ apoptotic signaling pathways including caspase-3 as well as the inflammatory cascade such as c-jun and attenuated UVB-induced activation of NF-κB and COX-2. Red raspberry extract could alleviate direct photodamage to the skin caused by UVB exposure through the ROS scavenger and protection against inflammatory responses, which may allow the development of novel strategies in protecting the skin subjected to UVB radiation.