Long-term intake of sulforaphene alleviates D-galactose-induced skin senescence by activating AMPK-Sirt 1 pathway.

D-Galactose (D-gal) accumulation triggers the generation of oxygen free radicals, resulting in skin aging. Sulforaphene (SFE), an isothiocyanate compound derived from radish seeds, possesses diverse biological activities, including protective effects against inflammation and oxidative damage. This investigation delves into the antioxidant impact of SFE on age-related skin injury. In vivo experiments demonstrate that SFE treatment significantly improves the macro- and micro-morphology of dorsal skin. It effectively diminishes the elevation of oxidative stress biomarkers in mice skin tissue treated with D-gal, concurrently enhancing the activity of antioxidant enzymes. Additionally, SFE mitigates collagen mRNA degradation, lowers pro-inflammatory cytokine levels, and downregulates MAPK-related protein expression in the skin. Moreover, SFE supplementation reduces lipid metabolite levels and elevates amino acid metabolites, such as L-cysteine and L-histidine. These findings suggest that SFE holds promise as a natural remedy to mitigate aging induced by oxidative stress.

New Insight into the Potential Protective Function of Sulforaphene against ROS-Mediated Oxidative Stress Damage In Vitro and In Vivo.

Sulforaphene (SFE) is a kind of isothiocyanate isolated from radish seeds that can prevent free-radical-induced diseases. In this study, we investigated the protective effect of SFE on oxidative-stress-induced damage and its molecular mechanism in vitro and in vivo. The results of cell experiments show that SFE can alleviate D-gal-induced cytotoxicity, promote cell cycle transformation by inhibiting the production of reactive oxygen species (ROS) and cell apoptosis, and show a protective effect on cells with H2O2-induced oxidative damage. Furthermore, the results of mice experiments show that SFE can alleviate D-galactose-induced kidney damage by inhibiting ROS, malondialdehyde (MDA), and 4-hydroxyalkenals (4-HNE) production; protect the kidney against oxidative stress-induced damage by increasing antioxidant enzyme activity and upregulating the Nrf2 signaling pathway; and inhibit the activity of pro-inflammatory factors by downregulating the expression of Toll-like receptor 4 (TLR4)-mediated inflammatory response. In conclusion, this research shows that SFE has antioxidant effects, providing a new perspective for studying the anti-aging properties of natural compounds.

Stem Cells from Human Exfoliated Deciduous Teeth Attenuate Atopic Dermatitis Symptoms in Mice through Modulating Immune Balance and Skin Barrier Function.

Atopic dermatitis (AD) is a chronic skin inflammatory disease associated with immune abnormalities and disrupted skin barrier function. Mesenchymal stem cells (MSCs) have been suggested as an alternative therapeutic option in AD. Stem cells from human exfoliated deciduous teeth (SHEDs) are a unique postnatal stem cell population with high immunomodulatory properties. The aim of this study was to explore the effects of SHEDs on AD in the BALB/c mouse model induced by 2,4-dinitrochlorobenzene (DNCB). SHEDs were administrated intravenously or subcutaneously, and clinical severity, histopathological findings, skin barrier function, and organ indexes were evaluated. Skin tissue cytokine mRNA levels and serum cytokine protein levels were further analysed. SHED administration significantly alleviated AD clinical severity, including dermatitis scores, ear thickness, scratching behaviour, and infiltration of mast cells. In addition, disrupted skin barrier function and enlarged spleens were restored by SHED administration. Further, SHED treatment reduced the levels of IgE, IgG1, and thymic stromal lymphopoietin (TSLP) in the serum and the modulated expression of Th1-, Th2-, and Th17-associated cytokines in skin lesions. In conclusion, SHEDs attenuated AD-like skin lesions in mice by modulating the immune balance and skin barrier function. SHEDs could be a potential new treatment agent for AD.

Application Values of 2D and 3D Radiomics Models Based on CT Plain Scan in Differentiating Benign from Malignant Ovarian Tumors.

BACKGROUND: Accurate identification of ovarian tumors as benign or malignant is highly crucial. Radiomics is a new branch of imaging that has emerged in recent years to replace the traditional naked eye qualitative diagnosis. OBJECTIVE: This study is aimed at exploring the difference in the application potential of two- (2D) and three-dimensional (3D) radiomics models based on CT plain scan in differentiating benign from malignant ovarian tumors. METHOD: A retrospective analysis was performed on 140 patients with ovarian tumors confirmed by surgery and pathology in our hospital from July 2017 to August 2020. These 140 patients were divided into benign group and malignant group according to the pathological results. The ITK-SNAP software was used to outline the regions-of-interest (ROI) of 2D or 3D tumors on the CT plain scan image of each patient; the texture features were extracted through analysis kit (AK), and the cases were randomly divided into training groups (n = 99) and validation group (n = 41) in a ratio of 7 : 3. The least absolute shrinkage and selection operator (LASSO) algorithm was used to perform dimensionality reduction, followed by the construction of the radiomics nomogram model using the logistic regression method. The receiver operating characteristic (ROC) curve was drawn, and the calibration curve and decision curve analysis (DCA) were used to evaluate and verify the results of the radiomics nomogram and compare the differences between 2D and 3D diagnostic performance. RESULTS: There were 396 quantitative radiomics feature parameters extracted from 2D group and the 3D group, respectively. The area under the curve (AUC) of the radiomics nomogram of the 2D training group and the validation group were 0.96 and 0.97, respectively. The accuracy, specificity, and sensitivity of the training set were 92.9%, 88.9%, and 96.3%, respectively, and those of the validation set were 90.2%, 82.6%, and 100.0%, respectively. The AUCs of the radiomics nomogram of the 3D training group and validation group were 0.96% and 0.99%, respectively. The accuracy, sensitivity, and specificity of the training set were 92.9%, 96.3%, and 88.9%, respectively, and those of the validation set were 97.6%, 95.7%, and 100.0%, respectively. DeLong's test indicated that there was no statistical significance between the two sets (P > 0.05). CONCLUSIONS: For the differential diagnosis of benign and malignant ovarian tumors, the 2D and 3D radiomics nomogram models exhibited comparable diagnostic performance. Considering that the 2D model was cost-effective and time-efficient, it was more recommended to use 2D features in future research.

Warfarin-induced Stevens-Johnson syndrome with severe liver injury.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening mucocutaneous disease that is predominantly drug-induced. Warfarin is the most commonly used drug for long-term anti-coagulant therapy; however, warfarin-induced SJS/TEN is seldom reported. In this study, we presented the case of a 61-year-old man who developed SJS after receiving multiple-drug therapy following aortic valve replacement surgery. The patient was diagnosed with drug-induced liver injury (DILI) based on significantly abnormal liver function test results. Warfarin was identified as the culprit drug using the algorithm of drug causality for epidermal necrolysis (ALDEN) score, enzyme-linked immunospot (ELISPOT) assay, and Roussel Uclaf Causality Assessment Method (RUCAM). After warfarin discontinuation and corticosteroid therapy, the lesions and liver function test findings improved. Human leukocyte antigen typing was conducted to detect the risk allele. To our knowledge, this is the first reported case of warfarin-induced SJS/TEN with DILI. This case suggests that commonly used and safe pharmaceutical agents such as warfarin can potentially cause serious adverse events, including SJS/TEN and DILI. The application of ALDEN, the ELISPOT assay, and RUCAM could be useful in identifying culprit drugs.

Downregulation of lncRNA TSLNC8 promotes melanoma resistance to BRAF inhibitor PLX4720 through binding with PP1α to re-activate MAPK signaling.

PURPOSE: Approximately 60% of patients with melanoma harbor BRAF mutation and targeting BRAF offers enormous advance in the treatment of those patients. Unfortunately, the efficacy of the BRAF inhibitors is usually restricted by the onset of drug resistance. Therefore, better understanding of the adaptive drug resistance mechanisms is essential for the development of alternative therapeutic strategies, and offers more promising measures to promote the short duration of response to BRAF inhibitors. METHODS: The levels of tumor suppressive long noncoding RNA on chromosome 8p12 (TSLNC8) were evaluated by qPCR. The MTT assay, colony formation assay, apoptosis assay, and in vivo xenograft tumor model were performed to assess the functions of TSLNC8 on drug resistance. Western blotting, RNA pull-down, and RNA immunoprecipitation (RIP) assays were applied to investigate the mechanisms of TSLNC8 in melanoma. RESULTS: Herein, our findings demonstrate that TSLNC8 is significantly downregulated in BRAF inhibitor-resistant melanoma tissues and cells. Moreover, downregulation of TSLNC8 in BRAF inhibitor sensitive cells reduces the toxicity response to BRAF inhibitor PLX4720, and inhibits apoptosis of melanoma cells-treated with PLX4720. Further assay elucidates that TSLNC8 can bind with the catalytic subunit of protein phosphatase 1α (PP1α) to regulate its distribution, and Downregulation of TSLNC8 results in PP1α cytoplasmic accumulation, thus re-activating the MAPK signaling. Eventually, the overexpression of TSLNC8 in BRAF inhibitor PLX4720-resistant melanoma cells restores the sensitive to BRAF inhibitor. CONCLUSION: Collectively, our research provides a compelling rationale for resistance to BRAF inhibitor in melanoma, and the patient might benefit from the combinatorial therapy of BRAF inhibitors and lncRNA TSLNC8.

[Targeting microRNA-mediated suppression of vascular endothelial growth factor gene expression and proliferation in malignant melanoma cells in vitro].

OBJECTIVE: To explore the inhibitory effect of targeting miRNA on the expression of vascular endothelial growth factor (VEGF) and cell proliferation in malignant melanoma (MM) SKmel-28 cells. METHODS: Recombination miRNA plasmid vectors targeting VEGF gene were transfected into SKmel-28 cells via Lipofectamine 2000. The integrity of the inserted fragments was detected using colony PCR and sequence analysis. The expression of VEGF mRNA and protein in SKmel-28 cells was detected by RT-PCR and Western blotting, respectively. MTS assay was used to determine the inhibitory effect of a selected targeting miRNA on SKmel-28 cell proliferation, and the apoptosis of SKmel-28 cells was detected using flow cytometry. RESULTS: Transfection with the targeting miRNAs significantly down-regulated the expressions of VEGF mRNA and protein in SKmel-28 cells (P<0.01), and the miRNA construct X-26-2n-1 showed the highest inhibitory effect. The miRNA X-26-2n-1 significantly suppressed SKmel-28 cell proliferation in a time-dependent manner (P<0.01) and increased the early, late and overall apoptosis rates of the cells (P<0.01). CONCLUSION: The targeting miRNA we constructed can effectively suppress the cell proliferation and induce apoptosis of SKmel-28 cells by down-regulating the expressions of VEGF gene.