Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: GSTK1 suppresses HCC aggravation via L-carnitine metabolism by PGAM5/DRP1 complex-mediated mitochondrial quality control

doi: 10.1186/s13046-025-03580-8

Figure Lengend Snippet: GSTK1 is regulated by PPARα/RXRα and Bexarotene could inhibit the proliferation and migration of tumor cells, enhanced by GSTK1 overexpression or weaken by GSTK1 knockdown ( A-C ) RT-qPCR analysis of GSTK1 mRNA levels in HepG2 cells treated with LG100064 ( A ), GW6471 ( B ), Pirinixic acid ( C ). ( D ) The luciferase reporter gene assay of RXRα and GSTK1. ( E-H ) Cell proliferation ability detection of HepG2 cells overexpress GSTK1 or HCC-LM3 cells knockdown GSTK1 treated with Bexarotene (40 µM), detected by CCK8 ( E-F ), Colony formation ( G-H ). ( I-J ) Cell migration ability detection of HepG2 cells overexpress GSTK1 or HCC-LM3 cells knockdown GSTK1 treated with Bexarotene (40 µM), detected by Transwell (Bar = 100 μm). ( K-L ) The apoptosis ratio of HepG2 cells overexpress GSTK1 or HCC-LM3 cells knockdown GSTK1 treated with Bexarotene (40 µM), detected by flow cytometry using the Annexin V-FITC/PI staining kit. ( M ) Immunoblotting analysis of Bcl-xL, Bcl-2, and β-Actin in HepG2 cells overexpressing GSTK1 or HCC-LM3 cells with GSTK1 knockdown following treatment with Bexarotene (40 µM). ( N-O ) Hep3B cells with GSTK1 overexpression were transplanted on BALB/c-Nude mice, then treated or not treated with Bexarotene, and tumor volumes and tumor weights were recorded ( n = 6). Schematic diagram of Bexarotene treated model ( N ). ( Q ) Immunohistochemistry staining of Ki67 (Bar = 100 μm). Data are presented as mean ± SD. n.s, no significance, * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001

Article Snippet: To explore the upstream promoter mechanism of GSTK1, RXRa agonist LG100064 (MedChenExpress, HY-104070) was used at 200, 400, 600, 800, 1000 nM for 24 h; PPARa inhibitor GW6471 (MedChenExpress, HY-15372) was used at 0, 5, 10 μM for 48 h; PPARa agonist Pirinixic acid (MedChenExpress, HY-16995) was used at 0, 10, 20, 40, 60, 100 μM for 24 h.

Techniques: Migration, Over Expression, Knockdown, Quantitative RT-PCR, Luciferase, Reporter Gene Assay, Flow Cytometry, Staining, Western Blot, Immunohistochemistry

Journal: Advanced Science

Article Title: Reprogramming of Fatty Acid Metabolism via PPARα‐Orchestrated FADS2 in Keratinocytes Modulates Skin Inflammation in Psoriasis

doi: 10.1002/advs.202417049

Figure Lengend Snippet: PPARα acts as an upstream positive regulator of FADS2 in psoriatic keratinocytes. A) RT‐qPCR analysis of PPARA expression in normal skin from healthy controls (NN, n = 4) and lesional skin tissue from psoriasis patients (PS, n = 5). B) Representative immunofluorescence images of PPARα and K14 co‐staining in normal skin from healthy controls and lesional skin tissue from psoriasis patients. C) RT‐qPCR analysis of PPARA in psoriatic lesional skin before and 10 weeks after infliximab treatment (n = 5). D) Representative images of PPARα immunofluorescence staining in lesional skin from psoriasis patients at baseline and week 10 following infliximab treatment. E) Representative immunofluorescence images of PPARα staining in healthy skin from control mice and skin lesions from IMQ‐induced psoriasis mouse model. F,G) RT‐qPCR analysis of PPARA (F) and FADS2 (G) expression in HaCaT cells stimulated with M5 for 12 h (n = 3). H) Immunoblotting of PPARα and FADS2 in HaCaT cells stimulated with M5 cytokines for the indicated time. I) RT‐qPCR analysis of PPARA , FADS2 , and indicated genes in HaCaT cells transfected with PPARA siRNA (si PPARA ) and control siRNA (siNC) for 24 h, followed by PBS or M5 stimulation for 12 h (n = 3). J) RT‐qPCR analysis of FADS2 and indicated genes in HaCaT cells pretreated with WY14643 or DMSO for 21 h, followed by PBS or M5 stimulation for 3 h (n = 3). K) ELISA quantification of CXCL1, CXCL8, and CSF3 protein levels in cell lysates and supernatants from HaCaT cells treated as in (J) (n = 3). L) RT‐qPCR analysis of the indicated genes in HaCaT cells transfected with si FADS2 and siNC for 24 h, followed by M5 stimulation for 3 h before WY14643 or DMSO pretreatment (n = 3). Scale bar, 50 µm. Data are presented as mean ± SD. Statistical significance was determined by unpaired two‐tailed Student's t test (A,F,G,K), paired two‐tailed Student's t test (C), or one‐way ANOVA (I,J,L). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001; ns, not significant.

Article Snippet: To activate PPARα in dorsal skin, 60μl of 10 m m PPARα agonist WY14643 (HY‐16995, Medchemexpress) dissolved in a 7:3 (v/v) mixture of propylene glycol and ethanol (vehicle) was applied topically once daily starting one day before IMQ treatment, and 4 h after IMQ treatment, for 6 consecutive days.

Techniques: Quantitative RT-PCR, Expressing, Immunofluorescence, Staining, Control, Western Blot, Transfection, Enzyme-linked Immunosorbent Assay, Two Tailed Test

Journal: Advanced Science

Article Title: Reprogramming of Fatty Acid Metabolism via PPARα‐Orchestrated FADS2 in Keratinocytes Modulates Skin Inflammation in Psoriasis

doi: 10.1002/advs.202417049

Figure Lengend Snippet: PPARα agonist WY14643 alleviates IMQ‐induced psoriasis‐like skin inflammation. A) Schematic diagram of experimental design involving topical application of WY14643 or vehicle in combination with IMQ or Vaseline treatment. B) Representative immunofluorescence images of PPARα staining in dorsal skin from mice treated with WY14643 or vehicle after IMQ or Vaseline treatment. C) Representative phenotypic images and H&E staining image of mouse dorsal skin treated with WY14643 or vehicle following IMQ or Vaseline treatment for 6 days. D–F) Quantification of PASI scores (D), epidermal thickness (E), and dermal cell infiltration (F) of mouse dorsal skin treated with WY14643 or vehicle after IMQ treatment for 6 days (n = 5). G,H) Representative immunofluorescence staining of Ki67 (G) and quantitation of Ki67 + epidermal cells (H) in IMQ‐induced skin lesions treated with WY14643 or vehicle in the indicated locations (n = 5). I) RT‐qPCR analysis of Fads2 in IMQ‐induced skin lesions treated with WY14643 or vehicle (n = 5). J) Representative immunofluorescence images of FADS2 staining in mouse dorsal skin treated with WY14643 or vehicle after IMQ or Vaseline treatment for 6 days. K) RT‐qPCR analysis of the indicated genes in IMQ‐induced skin lesions treated with WY14643 or vehicle (n = 5‐6). L) ELISA quantification of IL‐1β and CXCL1 protein levels in IMQ‐induced skin lesions treated with WY14643 or vehicle (n = 4). M,N) Representative flow cytometry plot (M) and quantification (N) of neutrophils in IMQ‐induced skin lesions treated with WY14643 or vehicle (n = 5). O) Representative immunofluorescence images of pNF‐κB staining in IMQ‐induced skin lesions treated with WY14643 or vehicle. Scale bar, 50 µm. Data are presented as mean ± SD. Statistical significance was determined by unpaired two‐tailed Student's t test. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001; ns, not significant.

Article Snippet: To activate PPARα in dorsal skin, 60μl of 10 m m PPARα agonist WY14643 (HY‐16995, Medchemexpress) dissolved in a 7:3 (v/v) mixture of propylene glycol and ethanol (vehicle) was applied topically once daily starting one day before IMQ treatment, and 4 h after IMQ treatment, for 6 consecutive days.

Techniques: Immunofluorescence, Staining, Quantitation Assay, Quantitative RT-PCR, Enzyme-linked Immunosorbent Assay, Flow Cytometry, Two Tailed Test

Journal: Advanced Science

Article Title: Reprogramming of Fatty Acid Metabolism via PPARα‐Orchestrated FADS2 in Keratinocytes Modulates Skin Inflammation in Psoriasis

doi: 10.1002/advs.202417049

Figure Lengend Snippet: Fads2 knockdown abrogates the anti‐inflammatory effects of the PPARα agonist WY14643 in IMQ‐induced psoriasis‐like inflammation. A) Schematic diagram of experimental design involving topical administration of WY14643 or vehicle followed by IMQ treatment, prior to si Fads2 or siNC application on mouse ear for 11 days. B,C) Representative phenotypic images and H&E staining images (B), ear thickness of the indicated time points (C) of ear skin lesion treated as (A). D,E) Quantification of PASI scores (D) (n = 5), epidermal thickness (E) (n = 6) of ear skin lesions treated as (A). F) Representative immunofluorescence images of Ki67 staining in IMQ‐induced skin lesion treated as (A). G) RT‐qPCR analysis of the indicated genes in IMQ‐induced skin lesion treated as (A) (n = 5). Scale bar, 50 µm. Data are presented as mean ± SD. Statistical significance was determined by two‐way ANOVA (C), one‐way ANOVA (D,E), or unpaired two‐tailed Student's t ‐test (G). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001; ns, not significant.

Article Snippet: To activate PPARα in dorsal skin, 60μl of 10 m m PPARα agonist WY14643 (HY‐16995, Medchemexpress) dissolved in a 7:3 (v/v) mixture of propylene glycol and ethanol (vehicle) was applied topically once daily starting one day before IMQ treatment, and 4 h after IMQ treatment, for 6 consecutive days.

Techniques: Knockdown, Staining, Immunofluorescence, Quantitative RT-PCR, Two Tailed Test