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Wound healing in diabetic patients presents significant challenges in clinical wound care due to high oxidative stress, excessive inflammation, and a microenvironment prone to infection. In this study, we successfully developed a multifunctional tandem dynamic covalently cross-linked hydrogel dressing aimed at diabetic wound healing. This hydrogel was constructed using cyanoacetic acid functionalized dextran (Dex-CA), 2-formylbenzoylboric acid (2-FPBA) and natural oligomeric proanthocyanidins (OPC), catalyzed by histidine. The resulting Dex-CA/OPC/2-FPBA (DPOPC) hydrogel can be dissolved triggered by cysteine, thereby achieving "controllable and non-irritating" dressing change. Furthermore, the incorporation of OPC as a hydrogel building block endowed the hydrogel with antioxidant and anti-inflammatory properties. The cross-linked network of the DPOPC hydrogel circumvents the burst release of OPC, enhancing its biosafety. In vivo studies demonstrated that the DPOPC hydrogel significantly accelerated the wound healing process in diabetic mice compared to a commercial hydrogel, achieving an impressive wound closure rate of 98 % by day 14. The DPOPC hydrogel effectively balanced the disrupted inflammatory state during the healing process. This dynamic hydrogel based on natural polyphenols is expected to be an ideal candidate for dressings intended for chronic wounds.
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Diabetes Mellitus Experimental , Hidrogeles , Proantocianidinas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Proantocianidinas/química , Proantocianidinas/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Diabetes Mellitus Experimental/tratamiento farmacológico , Masculino , Reactivos de Enlaces Cruzados/química , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Dextranos/químicaRESUMEN
Androgenic alopecia (AGA) is a common disease that negatively affects patients' physical and mental health. AGA can be treated with drugs that improve the perifollicular microenvironment, such as 5α-reductase inhibitors (e.g., dutasteride [DUT]), androgen receptor blockers, and minoxidil. However, the efficacy of these treatments is limited. Therefore, this study aimed to show that nanoparticles are effective as stable carriers with high curative benefits and little adverse effects. The in vitro study showed that PLGA-DUT/siAR@DPCM NPs could deliver both DUT and siAR to dermal papilla cells. They could successfully suppress 5α-reductase and knock down androgen receptor, respectively, and thereby promote cell proliferation. In the in vivo study, PLGA-DUT/siAR@DPCM NPs showed a significant therapeutic effect in an AGA mouse model. They successfully penetrated the stratum corneum and showed a clear targeting effect on hair follicles and surrounding tissues. PLGA-DUT/siAR@DPCM NPs could enable the targeted delivery of DUT and siAR through percutaneous penetration, enhancing phagocytosis and decreasing adverse effects. Thus, they have great potential in the clinical treatment of AGA.
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Sonodynamic therapy (SDT) is garnering considerable attention in cancer treatment due to its non-invasive nature and the potential of spatiotemporal control. However, the high level of glutathione (GSH) in cancer cells can alleviate the SDT-mediated ROS-damages, resulting in a reduced SDT effect. Here, a two-in-one nano-prodrug for photoacoustic imaging-guided enhanced SDT against skin cancers is synthesized. A dual-prodrug molecule (DOA) of sulfide dioxide (SO2 ) and 5-aminolevulinic acid (ALA) is first synthesized and then co-assembled with methoxyl poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-PLL) to generate the two-in-one prodrug nanoparticles (P-DOA NPs). The P-DOA NPs simultaneously released ALA and SO2 in response to the overexpressed GSH in tumor cells. The released ALA is metabolically converted into protoporphyrin IX (PpIX) in tumor cells for SDT and photoacoustic imaging. Meanwhile, the released SO2 , together with the consumption of GSH based on the reaction of DOA in P-DOA NPs with intracellular GSH, can significantly increase the intracellular ROS content, leading to enhanced SDT. As a result, the P-DOA NPs significantly inhibited the growth of melanoma and squamous cell carcinoma xenografts in mouse models under the guidance of real-time photoacoustic imaging. Therefore, this novel two-in-one nano-prodrug is promising for effective SDT against skin cancers.
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Técnicas Fotoacústicas , Profármacos , Neoplasias Cutáneas , Terapia por Ultrasonido , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Animales , Línea Celular Tumoral , Glutatión , Humanos , Ratones , Profármacos/farmacología , Profármacos/uso terapéutico , Especies Reactivas de Oxígeno , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/terapia , Terapia por Ultrasonido/métodosRESUMEN
Malignant melanoma is one of the most aggressive types of skin cancer. Thus, efficient diagnosis and treatment methods are crucial for advanced melanoma. Circular RNAs (circRNAs) have been regarded as a 'splicing noise' in the past decades. However, several circRNAs have been recently reported to be differentially expressed in melanoma, and the cell or tissue-specific expression makes these suitable candidate diagnostic or therapeutic biomarkers. In addition, emerging studies have confirmed that circular RNAs play pivotal roles in the proliferation, invasion, metastasis, and migration of malignant melanoma. However, specific pathogenic mechanisms between melanoma and circRNAs remain unclear. In the present study, it was summarized that circRNAs are associated with the pathogenesis of melanoma, including hsa_circ_0083444, hsa_circ_0005320, hsa_circ_0067531, hsa_circ_0084043, hsa_circ_0000082, hsa_circ_0016418, hsa_circ_0085533 and hsa_circ_0025039, hsa_circ_0001946, hsa_circ_0002770, hsa_circ_0079593, hsa_circ_0027247, hsa_circ_0017247, hsa_circ_0020710. These can provide potential diagnosis, treatment, and prognostication biomarkers for advanced melanoma in clinical applications.
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Melanoma , Neoplasias Cutáneas , Biomarcadores/metabolismo , Humanos , Melanoma/genética , ARN Circular/genética , Neoplasias Cutáneas/genética , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Keloid is a benign dermal tumor characterized by abnormal proliferation and invasion of fibroblasts. The establishment of biomarkers is essential for the diagnosis and treatment of keloids. METHODS: We systematically identified coexpression modules using the weighted gene coexpression network analysis method (WGCNA). Differential expressed genes (DEGs) in GSE145725 and genes in significant modules were integrated to identify overlapping key genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed, as well as protein-protein interaction (PPI) network construction for hub gene screening. RESULTS: Using the R package of WGCNA, 22 coexpression modules consisting of different genes were identified from the top 5,000 genes with maximum mean absolute deviation in 19 human fibroblast samples. Blue-green and yellow modules were identified as the most important modules, where genes overlapping with DEGs were identified as key genes. We identified the most critical functions and pathways as extracellular structure organization, vascular smooth muscle contraction, and the cGMP-PKG signaling pathway. Hub genes from key genes as BMP4, MSX1, HAND2, TBX2, SIX1, IRX1, EDN1, DLX5, MEF2C, and DLX2 were identified. CONCLUSION: The blue-green and yellow modules may play an important role in the pathogenesis of keloid. 10 hub genes were identified as potential biomarkers and therapeutic targets for keloid.
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Queloide , Algoritmos , Biomarcadores/metabolismo , Fibroblastos/metabolismo , Perfilación de la Expresión Génica/métodos , Proteínas de Homeodominio/genética , Humanos , Queloide/genéticaRESUMEN
OBJECTIVE: This meta-analysis was performed to identify the prognostic value of SLNCR1 in multiple cancer types. METHODS: Electronic databases, including PubMed, EMBASE, and Web of Science, Cochrane Library, Medline, BioMed Central, Springer, Science Direct, and China National Knowledge Internet (CNKI), were searched for relevant studies up to August 2021, and the hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated to assess the relationship between SLNCR1 expression and overall survival (OS). RESULTS: 12 studies with a total of 1155 patients with 9 different types of cancers were included in this meta-analysis. The pooled HR indicates that high SLNCR1 expression represented poorer prognosis of cancer (HR = 2.11, 95% CI: 1.59-2.80, I 2 = 0%, P < 0.00001). Additionally, high SLNCR1 expression was correlated with TNM stage (odds ratio (OR): 1.72, 95% CI: 1.08-2.74, I 2 = 62%, P=0.02), lymph node metastasis (LNM) (OR:2.42, 95% CI: 1.61-3.64, I 2 = 55%, P < 0.0001), and distant metastases (DM) (OR: 2.30, 95% CI: 1.50-3.55, I 2 = 27%, P=0.0002). However, no evidence was found for a relationship between SLNCR1 expression and clinical features such as tumor size (OR: 1.71, 95% CI: 0.93-3.14, I 2 = 71%, P=0.09), age (OR: 0.86, 95% CI: 0.68-1.08, I 2 = 0%, P=0.19), or gender (OR: 1.07, 95% CI: 0.64-1.81, I 2 = 55%, P=0.79). CONCLUSION: Our findings found that high SLNCR1 expression was associated with poor OS, advanced tumor stage, tumor size, LNM, and DM in multiple cancers, indicating that SLNCR1 may serve as a potential prognostic biomarker for cancer patients in China.
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Background: Neuropilin 1 (NRP1) is a pleiotropic receptor that interacts with multiple ligands and their receptors and plays a critical role in the process of tumor metastasis and radiation resistance in endothelial cells and tumor cells. In this study, we sought to investigate the mechanistic role of NRP1 in the radiation resistance of non-small cell lung cancer (NSCLC) cells and the role of EG00229 (an inhibitor of NRP1) on reversing radiation resistance. Materials and Methods: A549 and H1299 NSCLC cells were used to construct radiation resistance models. Western blot, ELISA, and qRT-PCR were used to detect protein and mRNA levels of NRP1, epithelial-mesenchymal transition (EMT) markers, and molecules in signaling pathways. Immunofluorescence was used to measure changes in co-expression of NRP1 and VEGF-165 in radiation-resistant model cells. An immunoprecipitation assay was used to detect the binding capacity of NRP1 and VEGF-165. Results: We successfully created two radiation resistant models (A549RR and H1299-RR). The expression levels of NRP1, EMT-related proteins, and proteins in metastasis-related pathways were increased in NSCLC cells with radiation resistance. After adding EG00229, the expression levels and binding capacity of NRP1 and VEGF-165 proteins were significantly reduced. The expression of EMT-related proteins and proteins in metastasis-related pathways were reduced in NSCLC cells with radiation resistance. Conclusion: Our data provide an insight into the molecular mechanisms of radiation resistance and suggest that EG00229 may contribute to reversing the radiation resistance of NSCLC cells by inhibiting the binding of NRP1 and VEGF-165. Our findings could provide a novel theoretical and experimental foundation for improving the efficacy of lung cancer radiotherapy.
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BACKGROUND: To explore the suppressive effect of Apoptin-loaded oncolytic adenovirus (Ad-VT) on luciferase-labeled human melanoma cells in vitro and in vivo. METHODS: The stable luciferase-expressing human melanoma cells A375-luc or M14-luc were obtained by transfecting the plasmid pGL4.51 and selection with G418, followed by luciferase activity, genetic stability and bioluminescence intensity assays. In vitro, the inhibitory effects of Ad-VT on A375-luc or M14-luc were evaluated using the MTS cell proliferation, FITC-Annexin V apoptosis detection, transwell migration, Matrigel invasion and scratch assays. The inhibition pathway in Ad-VT-infected A375-luc and M14-luc cells were analyzed by JC-1 staining and Western-blot detection of mitochondrial apoptosis-related proteins. In vivo, the suppressive effects of Ad-VT on A375-luc or M14-luc were assessed by living imaging technology, tumor volume, bioluminescence intensity, survival curves and immunohistochemical analysis of the tumors from the xenograft tumor model BALB/c nude mice. RESULTS: The growth and migration of A375-luc and M14-luc were significantly inhibited by Ad-VT in vitro. The evaluations of A375-luc and M14-luc tumor models in BALB/c nude mice were successfully performed using living imaging technology. Ad-VT had an anti-tumor effect by reducing tumor growth and increasing survival in vivo. Ad-VT significantly changed the mitochondrial membrane potential by triggering the the mitochondrial release of apoptosis-related proteins, AIF (apoptosis inducing factor), ARTS (Apoptosis-Related Proteins), and Cyto-c (cytochrome c) from the mitochondria. CONCLUSION: Ad-VT reduced the mitochondrial membrane potential in A375-luc or M14-luc cells and induced the mitochondrial release of AIF, ARTS and Cyto-C. Ad-VT induced apoptosis in A375-luc or M14-luc cells via the mitochondrial apoptotic pathway.
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Adenoviridae/patogenicidad , Melanoma/microbiología , Animales , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Desnudos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Melanoma, as the most aggressive and treatment-resistant skin malignancy, is responsible for about 80% of all skin cancer mortalities. Prone to invade into the dermis and form distant metastases significantly reduce the patient survival rate. Therefore, early treatment of the melanoma in situ or timely blocking the deterioration of metastases is critical. In this study, a sulfur dioxide (SO2) polymer prodrug was designed as both an intracellular glutathione (GSH)-responsive SO2 generator and a carrier of doxorubicin (DOX), and used for the treatment of subcutaneous and metastatic melanoma. Firstly, chemical conjugation of 4-N-(2,4-dinitrobenzenesulfonyl)-imino-1-butyric acid (DIBA) onto the side chains of methoxy poly (ethylene glycol) grafted dextran (mPEG-g-Dex) resulted in the synthesis of the amphiphilic polymer prodrug of SO2, mPEG-g-Dex (DIBA). The obtained mPEG-g-Dex (DIBA) could self-assemble into stable micellar nanoparticles and exhibited a glutathione-responsive SO2 release behavior. Subsequently, DOX was encapsulated into the core of mPEG-g-Dex (DIBA) micelles to form DOX-loaded nanoparticles (PDDN-DOX). The formed PDDN-DOX could be internalized by B16F10 cells and synchronously release DOX and SO2 into the tumor cells. As a result, PDDN-DOX exerted synergistic anti-tumor effects in B16F10 melanoma cells because of the oxidative damage properties of SO2 and toxic effects of DOX. Furthermore, in vivo experiments verified that PDDN-DOX had great potential for the treatment of subcutaneous and metastasis melanoma. Collectively, our present work demonstrates that the combination of SO2-based gas therapy and chemotherapeutics offers a new avenue for inhibiting melanoma progression and metastases.
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BACKGROUND: Topical isotretinoin is commonly used to treat acne. However, topical isotretinoin has side effects and can hardly permeate through the stratum corneum, the most important skin barrier. Therefore, this study aimed to demonstrate the efficacy of nanoparticles as stable carriers with great curative effects, low side effects, and strong transdermal ability. RESULTS: In a rabbit model of hyperkeratinization, STCM-ATRA-NPs showed significant therapeutic efficacy. By contrast, negative therapeutic efficacy was observed in a golden hamster model of hyper sebum production. Scanning electron microscopy and Fourier transform infrared spectral analyses showed that nanoparticles could penetrate the stratum corneum. Western blotting demonstrated that the nanoparticles could enhance the transdermal efficacy of isotretinoin by reducing the effect of keratin and tight junction proteins. Further, nanoparticles enhanced endocytosis, thereby promoting drug penetration and absorption into the skin. CONCLUSION: STCM-ATRA-NPs were demonstrated to control isotretinoin release, reducing its side effects, and efficiently permeating through the skin by reducing the effect of keratin and tight junction proteins and enhancing endocytosis.
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Acné Vulgar , Membrana Celular , Fármacos Dermatológicos , Isotretinoína , Células Madre/citología , Administración Cutánea , Animales , Membrana Celular/química , Membrana Celular/metabolismo , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/química , Fármacos Dermatológicos/farmacocinética , Fármacos Dermatológicos/farmacología , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Isotretinoína/administración & dosificación , Isotretinoína/química , Isotretinoína/farmacocinética , Isotretinoína/farmacología , Masculino , Mesocricetus , Nanopartículas , Conejos , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Absorción CutáneaRESUMEN
The polydopamine coating on Au-Ag nanoparticles (Au-Ag-PDA) possess excellent photothermal conversion efficiency after absorbing near-infrared laser light. After the stem cell membrane (STCM) encapsulates Au-Ag-PDA (Au-Ag-PDA@STCM), the nanoparticles (NPs) exhibit less cytotoxicity, and further optimizing their efficiency in photothermal therapy. The photothermal activity of Au-Ag-PDA@STCM has not yet been reported. Therefore, in this study, the sebaceous gland cell line SZ95 and the golden hamsters were used to observe the photothermal effects of the Au-Ag-PDA@STCM. SZ95 cells were treated with various concen-trations of Au-Ag-PDA@STCM NPs. The photothermal effect on cell proliferation was analyzed after irradiating the cells with a 808â¯nm laser. After laser treatment of golden hamsters, the flank organs were observed at 4 different time points. Histological analysis was performed to observe tissue damage. The results suggest that Au-Ag-PDA@STCM NPs significantly inhibited the proliferation of sebaceous gland cells in vitro, and reduced the size of sebaceous glands and sebum secretion in vivo. Therefore, NPs can be used to treat acne by thermally injuring sebaceous gland cells.
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Cutaneous squamous cell carcinoma (SCC) is a common cancer that significantly decreases the quality of life. It is known that external stimulus such as ultraviolet (UV) radiation induces cutaneous SCC via provoking oxidative stress. NAD(P)H dehydrogenase 1 (NQO1) is a ubiquitous flavoenzyme that functions as a guardian against oxidative stress. However, the effect of NQO1 on cutaneous SCC is not clearly elucidated. In this study, we investigated the effect of NQO1 on cutaneous SCC cells using the recombinant adenoviruses that can upregulate and/or downregulate NQO1 expression. Overexpression of NQO1 resulted in significant decrease of cell proliferation and colony forming activity of SCC lines (SCC12 and SCC13 cells). By contrast, knockdown of NQO1 increased the cell proliferation and colony forming activity. Accordingly, the levels of proliferation-related regulators, such as Cyclin D1, Cyclin E, PCNA, SOX2, and p63, were decreased by the overexpression of NQO1, while those were increased by knockdown of NQO1. In addition, NQO1 affected the invasion and migration of SCC cells in a very similar way, with the regulation of epithelial-mesenchymal transition- (EMT-) related molecules, including E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Finally, the overexpression of NQO1 decreased the level of phosphorylated AKT, JNK, and p38 MAPK, while the knockdown of NQO1 increased the level of phosphorylated signaling molecules. Based on these data, NQO1 has tumor suppressive function in cutaneous SCC cells.
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Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica/genética , NAD(P)H Deshidrogenasa (Quinona) , Neoplasias Cutáneas/genética , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Humanos , NAD(P)H Deshidrogenasa (Quinona)/genética , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Neoplasias Cutáneas/metabolismoRESUMEN
Objective: The study aimed to synthesize superparamagnetic NaYF4:Yb,Er@PE3@Fe3O4 upconversion nanoprobes and to study their photothermal effects for the treatment of malignant melanoma. Methods: Morphological characteristics of the synthesized nanoprobes were examined by scanning electron microscopy. Their biocompatibility and biodistribution profiles were assessed through blood routine/biochemistry tests and the inductively coupled plasma/optical emission spectrometry-based analysis of tissue metal elements. Their photothermal conversion efficiency and their potential as contrast agents for upconversion luminescence (UCL)/magnetic resonance imaging (MRI) dual-modal imaging were tested. Efficacy in photothermal therapy, which was achieved by combining nanoprobes with near-infrared (NIR) irradiation, was evaluated in both A375 cell line and BALB/c mice models. The underlying mechanisms were interrogated by molecular approaches including the MTT assay, flow cytometry, semiquantitative PCR, western blot, and immunohistochemistry. Results: 1) Our synthesized NaYF4:Yb,Er@PE3@Fe3O4 nanoprobes exhibited a uniform cubic morphology with a diameter of ~50 nm. Subcutaneous administration led to no severe, long-lasting adverse effects in mice, possibly due to complete removal of these nanomaterials within one month. 2) Our nanoprobes possessed superior photothermal conversion efficiency and strong contrasting effects during UCL/MRI dual-modal imaging, corroborating their applications in imaging-guided photothermal therapy. 3) Combinatorial treatment of these nanoprobes with NIR irradiation induced profound apoptosis/necrosis in A375 cells. Similarly, the same treatment modality led to strong therapeutic effects in BALB/c mice implanted with A375 tumor xenografts. Mechanistic studies suggested an involvement of heat shock protein 70 in mediating the observed antitumor effects of our nanoprobes. Conclusion: Our study describes a convenient method to synthesize a new type of superparamagnetic upconversion nanoprobes, which possess high biocompatibility and can be used in imaging-guided photothermal therapy for the treatment of malignant melanoma. Importantly, our findings will promote clinical applications of NaYF4:Yb,Er@PE3@Fe3O4 as novel theranostic agents in treating melanoma and many other tumors.
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Erbio/química , Fluoruros/química , Hipertermia Inducida , Nanopartículas de Magnetita/uso terapéutico , Melanoma/terapia , Fototerapia , Itrio/química , Animales , Línea Celular Tumoral , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Rayos Infrarrojos , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/ultraestructura , Melanoma/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Distribución Tisular , Carga TumoralRESUMEN
Mitochondria are the primary sites for ATP synthesis and free radical generation in organisms. Abnormal mitochondrial metabolism contributes to many diseases, including obesity, diabetes and cancer. UCP2 is an ion/anion transporter located in mitochondrial inner membrane, and has a crucial role in regulating oxidative stress, cellular metabolism, cell proliferation and cell death. Polymorphisms of the UCP2 gene have been associated with diabetes and obesity because UCP2 is involved in energy expenditure and insulin secretion. Moreover, UCP2 gene expression is often amplified in cancers, and increased UCP2 expression contributes to cancer growth, cancer metabolism, anti-apoptosis and drug resistance. The present review summarizes the latest findings of UCP2 with respect to obesity, diabetes and cancer.
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Diabetes Mellitus/genética , Neoplasias/genética , Obesidad/genética , Polimorfismo Genético , Proteína Desacopladora 2/genética , Resistencia a Antineoplásicos/genética , HumanosRESUMEN
Drug repurposing and/or repositioning is an alternative method to develop new treatment for certain diseases. Albendazole was originally developed as an anthelmintic medication, and it has been used to treat a variety of parasitic infestations. In this study, we investigated the antitumor effect of albendazole and putative action mechanism. Results showed that albendazole dramatically decreased the cell viability of SCC cell lines (SCC12 and SCC13 cells). Albendazole increased apoptosis-related signals, including cleaved caspase-3 and PARP-1 in a dose-dependent fashion. The mechanistic study showed that albendazole induced endoplasmic reticulum (ER) stress, evidenced by increase of CHOP, ATF-4, caspase-4, and caspase-12. Pretreatment with ER stress inhibitor 4-PBA attenuated albendazole-induced apoptosis of SCC cells. In addition, albendazole decreased the colony-forming ability of SCC cells, together with inhibition of Wnt/ß-catenin signaling. These results indicate that albendazole shows an antitumor effect via regulation of ER stress and cancer stemness, suggesting that albendazole could be repositioned for cutaneous SCC treatment.
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Albendazol/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Albendazol/química , Albendazol/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/patología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Tunicamicina/farmacologíaRESUMEN
Antifungal therapy is used to treat sporotrichosis. However, there are several limitations in this therapy, such as development of drug resistance and potential health risks including liver injury. The purpose of our study was to evaluate the antifungal efficacy of antibody against the hybrid phage nanofibers displaying KPVQHALLTPLGLDR (phage-KR) in a fungal-infected mouse model. In this study, we extracte an antibody against hybrid phage nanofibers (phage-KR) from immunized mice and passively inoculate Sporothrix globosa (S. globosa) infected mice. The study shows that the antibody exhibits efficient inhibition efficacy of the S. globosa infection, including reduction of the progressive fungi colonizing, increase of animal survival rate and relief of organ inflammation in the mice. The results indicate that antibody against phage-KR may act as a potential strategy for safe and efficient treatment of S. globosa infections.
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BACKGROUND: Skin keratinocytes participate actively in inducing immune responses when external pathogens are introduced, thereby contributing to elimination of pathogens. However, in condition where the excessive inflammation is occurred, chronic skin disease such as psoriasis can be provoked. OBJECTIVE: We tried to screen the putative therapeutics for inflammatory skin disease, and found that salvianolic acid A (SAA) has an inhibitory effect on keratinocyte inflammatory reaction. The aim of this study is to demonstrate the effects of SAA in poly(I:C)-induced inflammatory reaction in skin keratinocytes. METHODS: We pre-treated keratinocytes with SAA then stimulated with poly(I:C). Inflammatory reaction of keratinocytes was verified using real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot. RESULTS: When skin keratinocytes were pre-treated with SAA, it significantly inhibited poly (I:C)-induced expression of inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, and CCL20. SAA inhibited poly(I:C)-induced activation of nuclear factor-κB signaling. And SAA also inhibited inflammasome activation, evidenced by decrease of IL-1ß secretion. Finally, SAA markedly inhibited poly(I:C)-induced NLRP3 expression. CONCLUSION: These results demonstrate that SAA has an inhibitory effect on poly(I:C)-induced inflammatory reaction of keratinocytes, suggesting that SAA can be developed for the treatment of inflammatory skin diseases such as psoriasis.
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BACKGROUND: Sebocytes are the major cells of sebaceous gland. The essential role of sebocytes is the production of sebum, a specific lipid mixture, that covers the body surface and provides the barrier function. At puberty, sebum production increases under the effects of various stimuli including androgens and insulin-like growth factor-1 (IGF-1). Excessive sebum production changes the microenvironment surrounding hair follicle, often leading to the onset of acne. OBJECTIVE: We previously performed screening test using cultured human sebocytes, and found that bilobetin had a potential for inhibiting lipid production. The aim of this study is to demonstrate the effects of bilobetin on IGF-1-induced lipogenesis in sebocytes. METHODS: We pretreated simian virus 40 T (SV40T)-transformed sebocytes with bilobetin then stimulated with IGF-1. Effects of bilobetin on lipogenesis of sebocytes were examined by thin layer chromatography and Western blot. RESULTS: Bilobetin markedly inhibited IGF-1-induced lipid production in sebocytes, especially in terms of production of squalene and wax ester. Supporting these results, bilobetin showed significant inhibitory effect on squalene synthase promoter activity. In addition, bilobetin significantly down-regulated lipogenic transcription factors such as sterol response element binding protein (SREBP)-1 and SREBP-2. To delineate the possible action mechanism, we investigated the effect of bilobetin on intracellular signaling. As a result, bilobetin inhibited IGF-1-induced phosphorylation of AKT. CONCLUSION: Together, these results suggest that bilobetin has an inhibitory potential on sebum production in sebocytes, being applicable for acne treatment.