Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.

Locally advanced breast cancer patients should be cautious about the immediate breast reconstruction after mastectomy: a pooling analysis of safety and efficacy.

BACKGROUND: The purpose of this study was to compare safety and efficacy outcomes between immediate breast reconstruction (IBR) and mastectomy alone in locally advanced breast cancer patients. METHODS: We conducted a comprehensive literature search of PUBMED, EMBASE, and Cochrane databases. The primary outcomes evaluated were overall survival, disease-free survival, and local recurrence. The secondary outcome was the incidence of surgical complications. All data were analyzed using Review Manager 5.3. RESULTS: Sixteen studies, involving 15,364 participants were included in this meta-analysis. Pooled data demonstrated that patients underwent IBR were more likely to experience surgical complications than those underwent mastectomy alone (HR: 3.96, 95%CI [1.07,14.67], p = 0.04). No significant difference was found in overall survival (HR: 0.94, 95%CI [0.73,1.20], p = 0.62), disease-free survival (HR: 1.03, 95%CI [0.83,1.27], p = 0.81), or breast cancer specific survival (HR: 0.93, 95%CI [0.71,1.21], p = 0.57) between IBR group and Non-IBR group. CONCLUSIONS: Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of locally advanced breast cancer patients. However, IBR brings with it a nonnegligible higher risk of complications and needs to be fully evaluated and carefully decided.

Comparing the Mechanical Properties of Rice Cells and Protoplasts under PEG6000 Drought Stress Using Double Resonator Piezoelectric Cytometry.

Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cells' mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. In this study, we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the surface stress (ΔS) generated and viscoelasticity (storage modulus G' and loss modulus G″) of protoplasts and suspension cells of rice under a drought stress of 5-25% PEG6000. The findings demonstrate that rice suspension cells and protoplasts react mechanically differently to 5-15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress; they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

Stemness subtypes in lower-grade glioma with prognostic biomarkers, tumor microenvironment, and treatment response.

Our research endeavors are directed towards unraveling the stem cell characteristics of lower-grade glioma patients, with the ultimate goal of formulating personalized treatment strategies. We computed enrichment stemness scores and performed consensus clustering to categorize phenotypes. Subsequently, we constructed a prognostic risk model using weighted gene correlation network analysis (WGCNA), random survival forest regression analysis as well as full subset regression analysis. To validate the expression differences of key genes, we employed experimental methods such as quantitative Polymerase Chain Reaction (qPCR) and assessed cell line proliferation, migration, and invasion. Three subtypes were assigned to patients diagnosed with LGG. Notably, Cluster 2 (C2), exhibiting the poorest survival outcomes, manifested characteristics indicative of the subtype characterized by immunosuppression. This was marked by elevated levels of M1 macrophages, activated mast cells, along with higher immune and stromal scores. Four hub genes-CDCA8, ORC1, DLGAP5, and SMC4-were identified and validated through cell experiments and qPCR. Subsequently, these validated genes were utilized to construct a stemness risk signature. Which revealed that Lower-Grade Glioma (LGG) patients with lower scores were more inclined to demonstrate favorable responses to immune therapy. Our study illuminates the stemness characteristics of gliomas, which lays the foundation for developing therapeutic approaches targeting CSCs and enhancing the efficacy of current immunotherapies. By identifying the stemness subtype and its correlation with prognosis and TME patterns in glioma patients, we aim to advance the development of personalized treatments, enhancing the ability to predict and improve overall patient prognosis.

Minimally Invasive Chevron Akin (MICA) Osteotomy Corrects Radiographic Parameters but Not Central Metatarsal Loading in Moderate to Severe Hallux Valgus without Metatarsalgia.

BACKGROUND: Central metatarsal pressure is increased in patients with hallux valgus, but the pedographic outcomes after hallux valgus (HV) correction are inconclusive. No known literature has reported the pedographic outcomes after HV correction with Minimally Invasive Chevron and Akin Osteotomy (MICA). METHODS: A prospective cohort of 31 feet from 25 patients with moderate-to-severe symptomatic HV but without metatarsalgia underwent MICA and was evaluated using radiographic parameters and pedographic measurements (Footscan®, RSscan International, Olen, Belgium). Data were collected preoperatively and 3 months after surgery. RESULTS: The radiographic parameters of the hallux valgus angle, intermetatarsal angle, distal metatarsal articular angle, first metatarsal head lateral shape, and lateral sesamoid grade significantly improved after MICA. The corrected first metatarsal length was significantly shortened by 2.3 mm, with consistent second metatarsal protrusion distance, lateral Meary's angle, and calcaneal pitch angle. Max force, max pressure, cumulative force, and cumulative pressure on the central metatarsals did not show significant changes between pre- and post-operative measurements, while these parameters significantly decreased in the hallux and first metatarsal area. CONCLUSION: MICA effectively corrects radiographic parameters but does not reduce central metatarsal loading in patients with moderate-to-severe HV without metatarsalgia.

Nuclear receptors for epidermal lipid barrier: Advances in mechanisms and applications.

The skin plays an essential role in preventing the entry of external environmental threats and the loss of internal substances, depending on the epidermal permeability barrier. Nuclear receptors (NRs), present in various tissues and organs including full-thickness skin, have been demonstrated to exert significant effects on the epidermal lipid barrier. Formation of the lipid lamellar membrane and the normal proliferation and differentiation of keratinocytes (KCs) are crucial for the development of the epidermal permeability barrier and is regulated by specific NRs such as PPAR, LXR, VDR, RAR/RXR, AHR, PXR and FXR. These receptors play a key role in regulating KC differentiation and the entire process of epidermal lipid synthesis, processing and secretion. Lipids derived from sebaceous glands are influenced by NRs as well and participate in regulation of the epidermal lipid barrier. Furthermore, intricate interplay exists between these receptors. Disturbance of barrier function leads to a range of diseases, including psoriasis, atopic dermatitis and acne. Targeting these NRs with agonists or antagonists modulate pathways involved in lipid synthesis and cell differentiation, suggesting potential therapeutic approaches for dermatosis associated with barrier damage. This review focuses on the regulatory role of NRs in the maintenance and processing of the epidermal lipid barrier through their effects on skin lipid synthesis and KC differentiation, providing novel insights for drug targets to facilitate precision medicine strategies.

Historic dog furs unravel the origin and artificial selection of modern Nordic Lapphund and Elkhound dog breeds.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100-200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored. Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression. Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy. Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.

Occurrence and spatiotemporal distribution of arsenic biotransformation genes in urban dust.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

Effects of aluminum (Al) stress on the isoprenoid metabolism of two Citrus species differing in Al-tolerance.

Isoprenoid metabolism and its derivatives took part in photosynthesis, growth regulation, signal transduction, and plant defense to biotic and abiotic stresses. However, how aluminum (Al) stress affects the isoprenoid metabolism and whether isoprenoid metabolism plays a vital role in the Citrus plants in coping with Al stress remain unclear. In this study, we reported that Al-treatment-induced alternation in the volatilization rate of monoterpenes (α-pinene, ß-pinene, limonene, α-terpinene, γ-terpinene and 3-carene) and isoprene were different between Citrus sinensis (Al-tolerant) and C. grandis (Al-sensitive) leaves. The Al-induced decrease of CO2 assimilation, maximum quantum yield of primary PSII photochemistry (Fv/Fm), the lower contents of glucose and starch, and the lowered activities of enzymes involved in the mevalonic acid (MVA) pathway and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway might account for the different volatilization rate of isoprenoids. Furthermore, the altered transcript levels of genes related to isoprenoid precursors and/or derivatives metabolism, such as geranyl diphosphate (GPP) synthase (GPPS) in GPP biosynthesis, geranylgeranyl diphosphate synthase (GGPPS), chlorophyll synthase (CHS) and GGPP reductase (GGPPR) in chlorophyll biosynthesis, limonene synthase (LS) and α-pinene synthase (APS) in limonene and α-pinene synthesis, respectively, might be responsible for the different contents of corresponding products in C. grandis and C. sinensis. Our data suggested that isoprenoid metabolism was involved in Al tolerance response in Citrus, and the alternation of some branches of isoprenoid metabolism could confer different Al-tolerance to Citrus species.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Effectiveness of instant versus text messaging intervention on antiretroviral therapy adherence among men who have sex with men living with HIV.

Objective: This study aimed to compare the effectiveness of instant versus text messaging intervention (TMI) on antiretroviral therapy (ART) adherence among men who have sex with men (MSM) living with HIV. Methods: This study was conducted in an infectious disease hospital of Jinan, China from October 2020 to June 2021, using non-randomized concurrent controlled design to compare the effectiveness of instant messaging intervention (IMI) versus TMI. The intervention strategies (health messaging, medication reminder, and peer education) and contents were consistent between the two groups, and the difference was service delivery method and type of information. The primary outcome was the proportion of achieving optimal ART adherence, defined as never missing any doses and delayed any doses more than 1 hour. Results: A total of 217 participants (including 72 in TMI group and 145 in IMI group) were included in the study. The proportion of achieving optimal adherence was higher in IMI group than TMI group at the first follow-up (90.2% versus 77.6%, p = 0.021) and second follow-up (86.5% versus 76.6%, p = 0.083). The effect of IMI versus TMI on improving ART adherence was found not to be statistically significant (risk ratio (RR) = 1.93, 95% confidence interval (CI): 0.95-3.94) in complete-case analysis. However, when excluding participants who did not adhere to the interventions, a significant improvement was observed (RR = 2.77, 95%CI: 1.21-6.38). More participants in IMI group expressed highly rated satisfaction to the intervention services than those in TMI group (67.3% versus 50.0%). Conclusions: The IMI demonstrated superior efficacy over TMI in improving ART adherence and satisfaction with intervention services. It is suggested that future digital health interventions targeting ART adherence should prioritize instant messaging with multimedia information in areas with Internet access. Trial registration: The study was registered at the Chinese Clinical Trial Register (ChiCTR), with number [ChiCTR2000041282].

Inhibiting mitochondrial citrate shuttling induces hepatic triglyceride deposition in Nile tilapia (Oreochromis niloticus) through lipid anabolic remodeling.

The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for six weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for seven days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis.

Removal of V(V) from a Mixed Solution Containing Vanadium and Chromium Using a Micropocrous Resin in a Column: Migration Regularity of the Mass Transfer Zone and Analysis of Dynamic Properties.

In China, both vanadium(V) and chromium(VI) are present in wastewater resulting from vanadate precipitation (AVP wastewater) and from leaching vanadium-chromium reduction slag. Addressing environmental preservation and the comprehensive utilization of metal resources necessitates the extraction and separation of V(V) and Cr(VI) from these mixed solutions. However, their separation is complicated by very similar physicochemical properties. This study establishes a method for the dynamic selective adsorption of V(V) from such mixtures. It evaluates the impact of various operating conditions in columns on dynamic adsorption behavior. This study examines the migration patterns of the mass transfer zone (MTZ) and forecasts its effective adsorption capacity through multivariate polynomial regression and a neural network (NN) model. The NN model's outcomes are notably more precise. Its analysis reveals that C 0 is the most critical factor, with Q and H following in importance. Furthermore, the dynamic properties were analyzed using two established models, Thomas and Klinkenberg, revealing that both intraparticle and liquid film diffusion influence the rates of exchange adsorption, with intraparticle diffusion being the more significant factor. Using 3 wt % sodium hydroxide as the eluent to elute V(V)-loaded resin at a flow rate of 4 mL/min resulted in a chromium concentration of less than 3 mg/L in the V(V) eluate, indicating high vanadium-chromium separation efficiency in this method. These findings offer theoretical insights and economic analysis data that are crucial for optimizing column operation processes.

Identification of lipid-modifying drug targets for autoimmune diseases: insights from drug target mendelian randomization.

BACKGROUNDS: A growing body of evidence has highlighted the interactions of lipids metabolism and immune regulation. Nevertheless, there is still a lack of evidence regarding the causality between lipids and autoimmune diseases (ADs), as well as their possibility as drug targets for ADs. OBJECTIVES: This study was conducted to comprehensively understand the casual associations between lipid traits and ADs, and evaluate the therapeutic possibility of lipid-lowering drug targets on ADs. METHODS: Genetic variants for lipid traits and variants encoding targets of various lipid-lowering drugs were derived from Global Lipid Genetics Consortium (GLGC) and verified in Drug Bank. Summary data of ADs were obtained from MRC Integrative Epidemiology Unit (MER-IEU) database and FinnGen consortium, respectively. The causal inferences between lipid traits/genetic agents of lipid-lowering targets and ADs were evaluated by Mendelian randomization (MR), summary data-based MR (SMR), and multivariable MR (MVMR) analyses. Enrichment analysis and protein interaction network were employed to reveal the functional characteristics and biological relevance of potential therapeutic lipid-lowering targets. RESULTS: There was no evidence of causal effects regarding 5 lipid traits and 9 lipid-lowering drug targets on ADs. Genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with a reduced risk of rheumatoid arthritis (RA) in both discovery (OR [odds ratio] = 0.45, 95%CI: 0.32, 0.63, P = 6.79 × 10- 06) and replicate datasets (OR = 0.37, 95%CI: 0.23, 0.61, P = 7.81 × 10- 05). SMR analyses supported that genetically proxied HMGCR inhibition had causal effects on RA in whole blood (OR = 0.48, 95%CI: 0.29, 0.82, P = 6.86 × 10- 03) and skeletal muscle sites (OR = 0.75, 95%CI: 0.56, 0.99, P = 4.48 × 10- 02). After controlling for blood pressure, body mass index (BMI), smoking and drinking alchohol, HMGCR suppression showed a direct causal effect on a lower risk of RA (OR = 0.33, 95%CI: 0.40, 0.96, P = 0.042). CONCLUSIONS: Our study reveals causal links of genetically proxied HMGCR inhibition (lipid-lowering drug targets) and HMGCR expression inhibition with a decreased risk of RA, suggesting that HMGCR may serve as candidate drug targets for the treatment and prevention of RA.

Echinatin suppresses cutaneous squamous cell carcinoma by targeting GSTM3-mediated ferroptosis.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers for which effective drugs are urgently needed. Echinatin, a natural compound extracted from Glycyrrhiza plants, has shown promising antitumour effects. However, the efficacy and the direct target of echinatin in cSCC remain unclear. PURPOSE: This study conducted a systematic investigation of the antitumour effects of echinatin on cSCC and the underlying mechanisms involved. STUDY DESIGN AND METHODS: Three cSCC cell lines, a xenograft model, and a UV-induced cSCC mouse model were used to investigate the potential protective effects of echinatin. The interactions between echinatin and glutathione S-transferase mu3 (GSTM3) and between echinatin and peroxiredoxin-2 (PRDX2) were evaluated by a proteome microarray assay, pull-down LC‒MS/MS analysis, surface plasmon resonance, and molecular docking. The potential mechanisms of GSTM3-mediated echinatin activity were analysed by using western blotting, lentivirus infection and small interfering RNA (siRNA) transfection. RESULTS: In this study, we found that echinatin inhibited the proliferation and migration of cSCC cells but had no cytotoxic effect on primary human keratinocytes. Furthermore, echinatin significantly inhibited tumour growth in vivo. Mechanistically, our data showed that echinatin could directly bind to GSTM3 and PRDX2. Notably, echinatin inhibited GSTM3 and PRDX2 levels by promoting their proteasomal degradation, which led to the disruption of ROS production. We then revealed that echinatin increased mitochondrial ROS production by inhibiting GSTM3. Moreover, echinatin triggered ferroptosis by inhibiting GSTM3-mediated ferroptosis negative regulation (FNR) proteins. In addition, echinatin regulated GSTM3-mediated ROS/MAPK signalling. CONCLUSION: Echinatin has good antitumour effects both in vitro and in vivo. Moreover, our findings indicate that GSTM3 and PRDX2 could function as viable targets of echinatin in cSCC. Consequently, echinatin represents a novel treatment for cSCC through the targeting of GSTM3-mediated ferroptosis.