Psoriasis is one of several chronic inflammatory skin diseases with a high rate of recurrence, and its pathogenesis remains unclear. Nicotinamide mononucleotide (NMN), as an important precursor of nicotinamide adenine dinucleotide (NAD+), has been reported to be a promising agent in treating various diseases, its positive effects including those induced via its anti-inflammatory and antioxidant properties. For this reason, we have aimed to explore the possible role of NMN in the treatment of psoriasis. Psoriasis models were constructed with imiquimod (IMQ) stimulation for 5 days in vivo and with M5 treatment in keratinocyte cell lines in vitro. NMN treatment during the IMQ application period markedly attenuated excess epidermal proliferation, splenomegaly, and inflammatory responses. According to GEO databases, Sirtuin1 (SIRT1) levels significantly decreased in psoriasis patients’ lesion tissues; this was also the case in the IMQ-treated mice, while NMN treatment reversed the SIRT1 decline in the mouse model. Moreover, NMN supplementation also improved the prognoses of the mice after IMQ stimulation, compared to the untreated group with elevated SIRT1 levels. In HEKa and HaCaT cells, the co-culturing of NMN and M5 significantly decreased the expression levels of proinflammation factors, the phosphorylation of NF-κB, stimulator of interferon genes (STING) levels, and reactive oxygen species levels. NMN treatment also recovered the decrease in mitochondrial membrane potential and respiration ability and reduced mtDNA in the cytoplasm, leading to the inhibition of autoimmune inflammation. The knockdown of SIRT1 in vitro eliminated the protective and therapeutic effects of NMN against M5. To conclude, our results indicate that NMN protects against IMQ-induced psoriatic inflammation, oxidative stress, and mitochondrial dysfunction by activating the SIRT1 pathway.

Numerous therapeutic anti-tumor strategies have been developed in recent decades. However, their therapeutic efficacy is reduced by the intrinsic protective autophagy of tumors. Autophagy plays a key role in tumorigenesis and tumor treatment, in which the overproduction of reactive oxygen species (ROS) is recognized as the direct cause of protective autophagy. Only a few molecules have been employed as autophagy inhibitors in tumor therapy to reduce protective autophagy. Among them, hydroxychloroquine is the most commonly used autophagy inhibitor in clinics, but it is severely limited by its high therapeutic dose, significant toxicity, poor reversal efficacy, and nonspecific action. Herein, we demonstrate a reductive-damage strategy to enable tumor therapy by the inhibition of protective autophagy via the catalytic scavenging of ROS using porous nanorods of ceria (PN-CeO₂) nanozymes as autophagy inhibitor. The antineoplastic effects of PN-CeO₂ were mediated by its high reductive activity for intratumoral ROS degradation, thereby inhibiting protective autophagy and activating apoptosis by suppressing the activities of phosphatidylinositide 3-kinase/protein kinase B and p38 mitogen-activated protein kinase pathways in human cutaneous squamous cell carcinoma. Further investigation highlighted PN-CeO₂ as a safe and efficient anti-tumor autophagy inhibitor. Overall, this study presents a reductive-damage strategy as a promising anti-tumor approach that catalytically inhibits autophagy and activates the intrinsic antioxidant pathways of tumor cells and also shows its potential for the therapy of other autophagy-related diseases.

Psoriasis, a chronic immune‐mediated dermatological disease with high recurrence rates and limited therapeutic efficacy, requires novel treatment strategies. Dictamni Cortex (BXP), a traditional Chinese medicine (TCM), has demonstrated potential in alleviating psoriasis; however, its clinical application is hampered by poor water solubility and low bioavailability. It is developed infinite coordination polymer nanoparticles (BXP‐Fe (III) ICPs, NB), which enhance the aqueous solubility by 95‐fold and bioavailability of BXP, exerting therapeutic effect through efficient transdermal delivery. NB significantly suppresses keratinocyte hyperproliferation, inflammation, and oxidative stress in both M5 (a cocktail of cytokines)‐treated human epidermal keratinocytes (HEKa) cells and imiquimod (IMQ)‐induced psoriatic mice. Nascent proteomics identified heat shock protein 90 alpha family class B member 1 (HSP90AB1) as a key target downregulated by NB. It is further revealed that NB suppresses HSP90AB1 transcription by inhibiting its activator, CCCTC‐binding factor (CTCF), and disrupts the HSP90AB1‐CDC37 (cell division cycle 37, the co‐chaperone) chaperone complex, thereby inactivating the pivotal client proteins STAT3 and Akt. Notably, NB demonstrated superior therapeutic efficacy over the canonical HSP90 inhibitor AUY922. This study highlights NB as a promising topical nanotherapy for psoriasis, integrating TCM with modern nanotechnology to overcome pharmacological limitations. The underlying molecular mechanisms of NB are elucidated through the CTCF‐HSP90AB1‐STAT3 axis.

Background Transcription Enhanced Association Domain (TEAD) transcription factors family involves in many signal transduction pathways, and is necessary for cell proliferation, apoptosis and other vital activities. TEAD1-4 is abnormally expressed in many tumors, and is related to tumor progression, drug resistance, poor prognosis, etc. In this study, we assessed the effect of the TEAD family on pan-cancer. Methods We downloaded transcriptome and clinical data from 33 types of TCGA tumor samples and adjacent tissues. Then, the expression characteristics of TEAD family members TEAD1, TEAD2, TEAD3 and TEAD4 in pan-cancer were analyzed. R packet and Cox regression were used to analyze the clinical correlation. In addition, the transcription level of TEAD and immune subtypes, stem cells, immune tumor microenvironment and drug sensitivity were analyzed by multidimensional correlation. Results We found the expression of TEAD1-4 was significantly different in various tumors. The survival time of patients with high and low TEAD1-4 gene expression was significantly different. TEAD1-4 was significantly associated with immune-infiltrating subtypes of tumor microenvironment (TME), and was positively correlated with interstitial cell infiltration and tumor cell dryness. The transcriptional expression level of TEAD1-4 was also related to drug response. TEAD may play a role in the sensitivity or resistance of tumor cells to drug therapy, and may serve as a therapeutic target to overcome drug-induced resistance. Conclusions Our systematic analysis reveals TEAD gene expression and its relationship with immune invasion, TME, tumor stem cells, drug sensitivity, and prognosis in cancer patients, and it is necessary to study the role of each TEAD family member in specific cancer type. Although further laboratory validation is needed, our study confirms that TEAD family genes are promising therapeutic targets and potential prognostic indicators in cancers.