The pathogenesis of psoriasis, a chronic inflammatory autoimmune skin disease with a high global prevalence, remains unclear. We performed a high-resolution single-cell RNA sequencing analysis of 94,759 cells from 13 samples, including those from psoriasis model mice and wild-type mice. We presented a single-cell atlas of the skin of imiquimod-induced mice with psoriasis and WT mice, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial–mesenchymal transition and validated the results with drug verification. Moreover, we conducted a tentative exploration of the potential pathways involved and revealed that the IL-17 signalling pathway may be the most relevant pathway. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

Psoriasis is an inflammatory autoimmune skin condition that is clinically marked by chronic erythema and scaling. The traditional Chinese herb Tripterygium wilfordii Hook. F. (TwHF) is commonly used in the treatment of immune-related skin illnesses, such as psoriasis. In clinical studies, PASI (Psoriasis Area and Severity Index) were dramatically decreased by TwHF and its extracts. Their benefits for psoriasis also include relief from psoriasis symptoms such as itching, dryness, overall lesion scores and quality of life. And the pathological mechanisms include anti-inflammation, immunomodulation and potentially signaling pathway modulations, which are achieved by modulating type-3 inflammatory cytokines including IL-22, IL-23, and IL-17 as well as immune cells like Th17 lymphocytes, γδT cells, and interfering with IFN-SOCS1, NF-κB and IL- 36α signaling pathways. TwHF and its extracts may cause various adverse drug reactions, such as gastrointestinal responses, aberrant hepatocytes, reproductive issues, and liver function impairment, but at adequate doses, they are regarded as an alternative therapy for the treatment of psoriasis. In this review, the effectiveness and mechanisms of TwHF and its extracts in psoriasis treatment are elucidated.

The regulatory network of competing endogenous RNAs (ceRNA) exists widely in tumors and affects the expression of cancer-related genes, thus playing an important role in the development and prognosis of human tumors. In this research, we explored the role and mechanism of LINC00665 as a ceRNA in breast cancer. We analyzed the expression and targets of LINC00665 in breast cancer using bioinformatics, and detected their effects on breast cancer cells by CCK8, transwell, colony formation and flow cytometry assays. From our results, LINC00665 knockdown suppressed the proliferation, migration and invasion and induced the apoptosis through inactivating the AKT/mTOR signaling pathway in MCF7 and MDA-MB-231 cells. LINC00665 had five potential downstream target miRNAs (miR-542-3p, miR-624-5p, miR-641, miR-425-5p, and miR-30-3p). In dual-luciferase report gene assay, the fluorescence activity of cells transfected with miR-641 mimics decreased, and the expression of miR-641 decreased significantly after knocking down LINC00665. miR-641 mimics significantly inhibited cell proliferation and invasion in MCF7 and MDA-MB-231 cells. We detected five potential direct targets of miR-641 using qPCR (SRCAP, SIKE1, NADK, KHDC4, and HSPG2). SRCAP expression decreased significantly in miR-641 overexpression cells and the binding of SRCAP’s 3ʹUTR and miR-641 was further confirmed by dual-luciferase report gene assay. SRCAP blocked the proliferation and invasion inhibition induced by miR-641 or si-LINC00665 in MCF7 and MDA-MB-231 cells. In conclusion, LINC00665 could promote the survival and metastasis of breast cancer cells through sponging miR-641 and targeting SRCAP. This research provided new potential targets for targeted therapy in human breast cancer.

The Atg8-family proteins, including LC3B (microtubule-associated protein 1 light chain 3 beta), are pivotal for key steps in the autophagy process. Proper regulation of LC3B homeostasis is essential for its function. Although LC3B is modulated by various posttranslational modifications (PTMs), the impact of these modifications on LC3B protein homeostasis remains unclear. Neddylation, a recently identified ubiquitin-like modification, plays diverse biological roles. Here, we identify LC3B as a specific target for neddylation. This modification weakens LC3B’s interaction with the ubiquitin E3 ligases VHL and BIRC6, thereby reducing LC3B ubiquitination. Depletion of ubiquitin-conjugating enzyme E2M (UBE2M), the primary E2 enzyme in the neddylation pathway, destabilizes LC3B and suppresses autophagy activity. Heterozygous Ube2m knockout ( Ube2m ^+/− ) mice exhibit pronounced aging-like phenotypes, with reduced LC3B expression and impaired autophagy in skin tissues. Our findings demonstrate that LC3B neddylation is vital for maintaining its stability and regulating autophagy flux, offering a potential therapeutic avenue to mitigate aging-related processes.