Anti-Ferroptosis: A Promising Therapeutic Method for Thyroid Cancer.

At present, many problems remain to be solved in studying the pathogenesis of thyroid cancer. Ferroptosis is a programmed cell death mode discovered in recent years, and many studies have found that ferroptosis plays a significant role in the prognosis and progression of thyroid cancer. The researchers showed that ferroptosis-related genes are essential in diagnosing thyroid cancer. Therefore, this paper summarizes some pathological and clinical characteristics of thyroid cancer and makes a series of combs on the relationship between ferroptosis and the basis and function of thyroid cancer, thus providing specific ideas for the diagnosis and treatment of thyroid cancer.

MiR-125a-3p alleviates hyperproliferation of keratinocytes and psoriasis-like inflammation by targeting TLR4/NF-κB pathway.

Introduction: Psoriasis is a chronic auto-inflammatory dermatosis characterized by hyperproliferation of keratinocytes. Emerging evidence has validated the dysregulated expression of microRNAs (miRNAs/miRs) in psoriasis patients. Aim: To probe into the role and precise mechanism of miR-125a-3p in HaCaT cells and imiquimod (IMQ)-stimulated psoriasis-like mice. Material and methods: In M5-treated HaCaT cells and IMQ-stimulated psoriasis-like mice, real-time quantitative polymerase chain reaction and western blot analysis were performed for detecting gene expression. Hematoxylin and eosin staining was used to evaluate pathological morphology of IMQ-induced psoriasis skin. The proliferation of keratinocytes was assessed using Cell Counting Kit-8 assay and Ki67 positive staining. The combination between miR-125a-3p and Toll-like receptor 4 (TLR4) was confirmed by luciferase reporter assay. Results: Our study showed reduced miR-125a-3p expression in psoriasis patients, psoriasis-like inflammatory cell models, and IMQ-generated psoriasis-like mouse models. MiR-125a-3p repressed the activity of keratinocytes in vitro by suppressing cell proliferation, inhibiting the production of psoriasis-related genes and inflammatory genes, and inactivating the NF-κB and interleukin (IL)-1ß pathways. Notably, the psoriasis-like inflammation was repressed by intradermal injection of agomiR-125a-3p in psoriatic mouse models in vivo. Mechanically, miR-125a-3p targeted and negatively regulated TLR4. Furthermore, the elevated expression of TLR4 reversed the influences of miR-125a-3p mimics on HaCaT cells. Conclusions: Upregulation of miR-125a-3p protects keratinocytes against hyperproliferation and inflammatory damage by inhibiting TLR4, suggesting that the miR-125a-3p/TLR4 axis might become a novel target for the prevention of psoriasis.

Involvement of miR-214-3p/FOXM1 Axis During the Progression of Psoriasis.

Psoriasis is a common, chronic, and relapsing skin disease characterized by hyperproliferation of keratinocytes and apoptosis delay. However, the molecular mechanisms underlying the progression of psoriasis remain elusive. MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs that play a crucial role in the development of psoriasis by promoting targeted mRNA degradation or translational inhibition. Here, we report that miR-214-3p, one of the downregulated miRNAs identified in the skin of psoriatic patients and imiquimod (IMQ)-induced mouse models, can negatively regulate the expression of forkhead box M1 (FOXM1). miR-214-3p inhibition leads to hyperproliferation and increased apoptosis of keratinocytes in vitro. Moreover, we show that miR-214-3p inhibition causes an arrest of the cell cycle at the S stage by elevating the expression of NEK2, KIF20A, CENP-A, CENP-F, and Cyclin B1 and by reducing the expression of Cyclin D1 in HaCaT cells. In vivo, the administration of miR-214-3p attenuates the psoriasis-like phenotype in IMQ-induced mice. Collectively, our results suggest that miR-214-3p/FOXM1 axis in keratinocytes could be a novel target in the treatment of psoriasis.

Our Choice: study protocol for a randomized controlled trial for optimal implementation of psoriasis treatment by the integration of Chinese and western medicine.

BACKGROUND: Plaque psoriasis is a refractory inflammatory skin disease. The common therapies used to treat plaque psoriasis in traditional Chinese medicine (TCM) and western medicine (WM) have distinct characteristics and advantages. Although a combination of TCM and WM therapies, adjusted to the clinical situation, is widely used, there are no systematic studies on the hierarchical selection of this treatment combination based on the severity of skin lesions. We therefore designed a randomized clinical trial to focus on the sequence of internal and external treatments of TCM in patients with mild-to-moderate plaque psoriasis and to optimize the integration of Chinese and western medicine for the treatment of patients with severe plaque psoriasis, thereby achieving high-level clinical evidence and establish treatment norms for the integrated use of Chinese and western medicines. METHODS: In this proposed multicenter, single-blinded, randomized controlled trial, 108 patients with mild-to-moderate plaque psoriasis will be randomly assigned to two groups in a 1:1 ratio to receive either internal or external TCM treatment, and 270 patients with severe plaque psoriasis will be randomly assigned to three groups in a 1:1:1 ratio to receive treatment with TCM or WM, or TCM + WM. All enrolled patients will receive 8 weeks of treatment. Follow-up assessments will be done 8 weeks after the treatment. The primary outcome of this study is the evaluation of efficacy and relapse rate, based on the Psoriasis Area and Severity Index, and the secondary outcome measures include determination of the affected body surface area, physician's global assessment, pruritus scores (determined using a visual analog scale), TCM symptom score, Dermatology Life Quality Index, patient-reported quality of life score and incidence of serious adverse events. DISCUSSION: This study will provide high-level clinical evidence for internal and external TCM treatment optimization and will contribute to establishing norms for the integration of Chinese and western Medicines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03941431. Registered on 8 May 2019.