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BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) remains an unmet medical challenge. Metabolic reprogramming is a hallmark of diverse cancers, including HNSCC. METHODS: We investigated the metabolic profile in HNSCC by using The Cancer Genome Atlas (TCGA) (n = 481) and Gene Expression Omnibus (GEO) (n = 97) databases. The metabolic stratification of HNSCC samples was identified by using unsupervised k-means clustering. We analyzed the correlations of the metabolic subtypes in HNSCC with featured genomic alterations and known HNSCC subtypes. We further validated the metabolism-related subtypes based on features of ENO1, PFKFB3, NSDHL and SQLE expression in HNSCC by Immunohistochemistry. In addition, genomic characteristics of tumor metabolism that varied among different cancer types were confirmed. RESULTS: Based on the median expression of coexpressed cholesterogenic and glycolytic genes, HNSCC subtypes were identified, including glycolytic, cholesterogenic, quiescent and mixed subtypes. The quiescent subtype was associated with the longest survival and was distributed in stage I and G1 HNSCC. Mutation analysis of HNSCC genes indicated that TP53 has the highest mutation frequency. The CDKN2A mutation frequency has the most significant differences amongst these four subtypes. There is good overlap between our metabolic subtypes and the HNSCC subtype. CONCLUSION: The four metabolic subtypes were successfully determined in HNSCC. Compared to the quiescent subtype, glycolytic, cholesterogenic and mixed subtypes had significantly worse outcome, which might offer guidelines for developing a novel treatment strategy for HNSCC.

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Background: Head and neck squamous cell carcinoma's tumor immune microenvironment (TIME) plays an important role in tumorigenesis and progression, but its clinical significance remains unclear. Therefore, the TIME needs to be better understood in order to improve the response of diagnosis and therapy. Methods: The gene expression and clinical data of 569 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Immune-related genes (IRGs) from the ImmPort database were used for immunotyping of HNSCC patients, and independent GEO datasets were used for subtype verification and comprehensive molecular identification. Results: The patients were divided into three subtypes (C1, C2, and C3) related to different gene expression profiles. The three subtypes showed widely different patterns in tumor genetic distortion, immune cell composition, cytokine profile, and so on, verifying that the immune-enhanced C2 subtype was associated with better prognosis. In addition, the stroma-deficient C1 subtype may be more efficient for the immune response than the C3 subtype. Furthermore, using WGCNA on the IRGs of those three subtypes, we found two C2-positive gene modules closely related to infection- and immune-associated pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, and the two modules had 22 common pathways. Conclusion: This study improves the power for prognosis prediction and develops new therapeutic strategies to stratify HNSCC patients into clinically significant groups through TIME-related prognostic signature.

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In the last decade, numerous circRNAs were discovered by virtue of the RNA-Seq technique. With the deepening of experimental research, circRNAs have brought to light the key biological functions and progression of human diseases. CircRNA ITCH has been demonstrated to be a tumor suppressor in numerous cancers, and recently it was found to play an important role in bone diseases, diabetes mellitus, and cardiovascular diseases. However, the functions of circ-ITCH have not been completely understood. In this review, we comprehensively provide a conceptual framework to elucidate circ-ITCH biological functions of cell proliferation, apoptosis and differentiation, and the pathological mechanisms of inflammation, drug resistance/toxicity, and tumorigenesis. Finally, we summarize its clinical applications in various diseases. This research aimed at clarifying the role of circ-ITCH, which could be a promising therapeutic target.

Asunto(s)

MicroARNs , ARN Circular , Apoptosis/genética , Proliferación Celular/genética , Genes Supresores de Tumor , Humanos , MicroARNs/genética , ARN/genética , ARN Circular/genética

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Electrochromic (EC)/electrofluorochromic (EFC) bifunctional materials are receiving great attention because of their promising applications in optoelectronic devices. However, the development of ideal EC/EFC bifunctional materials is still a great challenge because of the poor integration of EC/EFC performances (optical contrast, response speed, and switching stability). Herein, we reported two novel diphenylamine-based mixed valence (MV) polyamides (S-HPA and P-HPA) with spirobifluorene (2,7-positions) and pyrene (1,6-positions) as bridged fluorescence units, respectively, showing impressive cyclability and fluorescence contrast with rapid switching. Through the formation of an effective electronic coupling between the two nitrogen centers using spirobifluorene/pyrene bridges, we demonstrated that different bridges have significant effects on the thermal and electrooptical characteristics of polyamides. In addition to lower fluorescence quantum yield and glass transition temperature, the S-HPA exhibited superior cyclability (contrast change <3.4%/14% over 500/300 cycles for EC/EFC switching), higher color/fluorescence contrast (64%/304%), and faster switching time (<2.6 s), mainly owing to the shorter conjugated length and more twisted configuration of the spirobifluorene bridge. The design principle of MV polymers with fluorophore bridges proposed here will be a promising way to realize high-performance EC/EFC devices and will also provide new insights into their future development and applications.

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Electrofluorochromism has attracted great attention due to the intelligence optoelectronic and sensing applications. The intrinsically switchable fluorophores with high solid-state fluorescence are regarded as key for ideal electrofluorochromic materials. Here, we reported an AIE-active polyamide with diphenylamine and tetraphenylethylene units, showing high fluorescence quantum yield up to 69.1% for the solid polymer film and stable electrochemical cycling stability. The polyamide exhibited reversible color and emission switching even in hundreds of cycles, and the fluorescence on/off contrast ratio was determined up to 417, which is the highest value to our knowledge. Furthermore, as the response time is vital for the real-life applications, to speed up the response of electrofluorochromism, a porous polymer film was readily prepared through a facile method, notably exhibiting high fluorescence contrast, long-term stability and obviously improved response, due to the sharply increased surface area. Therefore, the AIE-functionalization combining the porous structure strategy will synergistically and dramatically improve the electrofluorochromic performance, which will also promote their practical applications in the near future.

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BACKGROUND: Hypoxia is a well-known factor in the promotion of apoptosis, which contributes to the development of numerous cardiac diseases, such as heart failure and myocardial infarction. Inhibiting apoptosis is an important therapeutic strategy for the treatment of related heart diseases caused by ischemia/hypoxic injury. Previous studies have demonstrated that BAG3 plays an important role in cardiomyocyte apoptosis and survival. However, the role of BAG3 in hypoxia-induced cardiomyocyte apoptosis remains to be clarified. Here, we demonstrate that BAG3 is induced by hypoxia stimuli in cultured cardiomyocytes. METHODS: BAG3 expression level was measured in H9c2 cells treated with hypoxia for 48 h. Cell proliferation and apoptosis were tested using MTT assay and Annexin V FITC-PI staining assay, respectively. The mRNA or protein expression level of BAG3, LC3-I, LC3-II, Atg5, NF-x03BA;B p65 and phosphorylated NF-x03BA;B p65 were assessed by qRT-PCR and western blot assay, respectively. Resluts: Overexpression of BAG3 inhibited cell apoptosis and promoted proliferation in hypoxia-injured H9c2 cells. Furthermore, autophagy and NF-x03BA;B were activated by BAG3 overexpression, and the NF-x03BA;B inhibitor PDTC could inhibit the activation of autophagy induced by BAG3 overexpression. In addition, the autophagy inhibitor 3-MA partly impeded the inhibitory effect of BAG3 on hypoxia-induced cardiomyocyte apoptosis. CONCLUSION: these results suggested that overexpression of BAG3 promoted cell proliferation and inhibited apoptosis by activating autophagy though the NF-x03BA;B signaling pathway in hypoxia-injured cardiomyocytes.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Apoptosis/genética , Autofagia/genética , Miocitos Cardíacos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Antioxidantes/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismo , Western Blotting , Hipoxia de la Célula , Línea Celular , Supervivencia Celular/genética , Expresión Génica , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Miocitos Cardíacos/citología , Prolina/análogos & derivados , Prolina/farmacología , Interferencia de ARN , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tiocarbamatos/farmacología , Factor de Transcripción ReIA/antagonistas & inhibidores , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Regulación hacia Arriba

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In order to examine how implanted bone marrow stromal cells (BMSCs) encourage peripheral nerve regeneration, the present study investigated the interaction of BMSCs and Schwann cells (SCs) using an indirect in vitro co­culture model. SCs and BMSCs were obtained from adult Sprague­Dawley rats. The passaged BMSCs were CD29­ and CD44­positive but CD45­negative and were co­cultured with the primary SCs using a Millicell system, which allows BMSCs and SCs to grow in the same culture medium but without direct contact. Expression of the typical SC markers S­100 and glial fibrillary acidic protein (GFAP) of the treated BMSCs as well as the proliferation capacity of the co­cultured SCs was evaluated by immunocytochemical staining on the 3rd and 5th day of co­culture. Immunocytochemical staining showed that >75% of the BMSCs in the indirect co­culture model were GFAP­ and S­100­positive on the 3rd and 5th day after co­culture, as opposed to <5% of the BMSCs in the control group. On the 3rd day after co­culture, only a few co­cultured BMSCs showed the typical SC­like morphology, while most BMSCs still kept their native appearance. By contrast, on the 5th day after co­culture, almost all of the co­cultured BMSCs appeared with the typical SC­like morphology. Furthermore, 70.71% of the SCs in the indirect co­culture model were S­100­positive on the 5th day of co­culture, as opposed to >30.43% of the SCs in the control group. These results indicated that BMSCs may interact synergistically with SCs with regard to promoting peripheral nerve regeneration.

Asunto(s)

Técnicas de Cocultivo/métodos , Células Madre Mesenquimatosas/citología , Células de Schwann/citología , Animales , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Regulación de la Expresión Génica , Marcadores Genéticos , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Regeneración Nerviosa , Nervios Periféricos/citología , Ratas , Ratas Sprague-Dawley , Proteínas S100/genética , Proteínas S100/metabolismo