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ABSTRACT Introduction: Due to the high intensity and speed of cycling, a high technical and tactical level, physical quality, and psychological quality are required of athletes. Meniscal injuries are common in cyclists. In particular, chronic meniscal injuries are usually caused by an accumulation of fatigue or untimely and incomplete treatment of acute sports injuries. Objective: Analyze the protective factors and methods for meniscal injuries in cyclists. Methods: Volunteer male cyclists were selected for a questionnaire that investigated the athletes' meniscal injuries. The data collected were statistically analyzed. Results: There were 6 cases of right knee meniscus injury in athletes; these data accounted for 75% of the injuries. Left meniscus injuries accounted for 2 cases. There was one case of medial injury in both knees. The corresponding preventive measures are presented according to the cause of the injury. Conclusion: Causes of meniscal injuries in cyclists include insufficient knee strength, inadequate training methods, physical fatigue, and long-term localized effort. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução: Devido à alta intensidade e velocidade do ciclismo, é exigido um alto nível técnico e tático, qualidade física e qualidade psicológica dos atletas. Lesões meniscais são comuns em ciclistas. Em particular, as lesões meniscais crônicas são geralmente causadas por um acúmulo de fadiga ou tratamento inoportuno e incompleto de lesões esportivas agudas. Objetivo: Analisar os fatores e métodos de proteção para lesões meniscais em ciclistas. Métodos: Ciclistas do sexo masculino voluntários foram selecionados para um questionário que investigou as lesões meniscais dos atletas. Os dados coletados foram analisados estatisticamente. Resultados: Houve 6 casos de lesão meniscal do joelho direito em atleta, esses dados são responsáveis por 75% dos danos. Lesões no menisco esquerdo representaram 2 casos. Houve um caso de lesão medial em ambos os joelhos. As medidas preventivas correspondentes são apresentadas de acordo com a causa da lesão. Conclusão: As causas das lesões meniscais em ciclistas incluem força insuficiente no joelho, métodos de treinamento inadequados, fadiga física e esforço localizado a longo prazo. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción: Debido a la alta intensidad y velocidad del ciclismo, se exige a los deportistas un alto nivel técnico y táctico, calidad física y calidad psicológica. Las lesiones de menisco son comunes en los ciclistas. En particular, las lesiones crónicas de menisco suelen ser causadas por una acumulación de fatiga o por un tratamiento inoportuno e incompleto de las lesiones deportivas agudas. Objetivo: Analizar los factores y métodos de protección de las lesiones meniscales en ciclistas. Métodos: Se seleccionaron ciclistas masculinos voluntarios para un cuestionario que investigaba las lesiones meniscales de los atletas. Los datos recogidos se analizaron estadísticamente. Resultados: Hubo 6 casos de lesiones de menisco de la rodilla derecha en atletas, estos datos representaron el 75% de las lesiones. Las lesiones del menisco izquierdo representaron 2 casos. Hubo un caso de lesión medial en ambas rodillas. Las medidas preventivas correspondientes se presentan según la causa de la lesión. Conclusión: Las causas de las lesiones de menisco en los ciclistas incluyen una fuerza insuficiente de la rodilla, métodos de entrenamiento inadecuados, fatiga física y esfuerzos localizados a largo plazo. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
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ABSTRACT Introduction College students represent a large proportion of amateur athletes in China. In sports practices, some unavoidable situations lead to physical injuries that can seriously affect the daily life of these students. Formulating rehabilitation plans to avoid secondary complications and speed up the students' return to their daily activities is necessary. Objective To study the causes of sports injuries and the effect of sports rehabilitation on university physical training. Methods Through questionnaires and interviews, 720 students and 25 teachers with a history of sports injuries were selected to investigate the causes of students' sports injuries. Then, 20 volunteers were selected as research subjects. They received a rehabilitation training protocol three times a week for six weeks. EMG signals of the athletes' shoulder and neck muscles were measured. Results Sports injury is an inevitable problem during college physical training. Training joint flexibility and stability can effectively improve the surface EMG signals in the area adjacent to the joint to improve muscle strength and joint amplitude level. Conclusion Students should consciously undertake rehabilitation training under professional guidance and receive full instruction in sports rehabilitation procedures involving a combination of physical and psychological recovery. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução Estudantes universitários representam grande parte dos esportistas amadores na China. Nas práticas esportivas, algumas situações inevitáveis acarretam em lesões físicas que podem afetar seriamente o cotidiano desses alunos. Faz-se necessária a formulação de planos de reabilitação afim de evitar complicações secundárias e agilizar o retorno dos estudantes às suas atividades diárias. Objetivo Estudar as causas de lesões esportivas e o efeito da reabilitação esportiva no treinamento físico universitário. Métodos 720 alunos e 25 professores com histórico de lesão esportiva foram selecionados para investigar as causas de lesão esportiva dos alunos por meio de questionário e entrevista. Em seguida, foram selecionados 20 voluntários como objeto de pesquisa. Esses receberam um protocolo de treinamento em reabilitação três vezes por semana, durante 6 semanas. Foram mensurados os sinais EMG dos músculos do ombro e pescoço dos atletas. Resultados A lesão esportiva é um problema inevitável durante o treinamento físico universitário. Treinar a flexibilidade e estabilidade articular pode efetivamente melhorar os sinais EMG de superfície na área adjacente à articulação, de modo a melhorar a força muscular e o nível de amplitude articular. Conclusão Os alunos devem realizar conscientemente treinamento de reabilitação sob orientação profissional, além de receberem instrução plena sobre os procedimentos da reabilitação esportiva, envolvendo uma combinação de recuperação física e psicológica. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción Los estudiantes universitarios representan una gran parte de los deportistas aficionados en China. En las prácticas deportivas, algunas situaciones inevitables provocan lesiones físicas que pueden afectar gravemente a la vida cotidiana de estos alumnos. Es necesario formular planes de rehabilitación para evitar complicaciones secundarias y acelerar el regreso de los alumnos a sus actividades cotidianas. Objetivo Estudiar las causas de las lesiones deportivas y el efecto de la rehabilitación deportiva en el entrenamiento físico universitario. Métodos Se seleccionaron 720 estudiantes y 25 profesores con antecedentes de lesiones deportivas para investigar las causas de las lesiones deportivas de los estudiantes mediante un cuestionario y una entrevista. A continuación, se seleccionaron 20 voluntarios como sujetos de la investigación. Recibieron un protocolo de entrenamiento de rehabilitación tres veces por semana, durante 6 semanas. Se midieron las señales EMG de los músculos del hombro y del cuello de los atletas. Resultados Las lesiones deportivas son un problema inevitable durante el entrenamiento físico universitario. El entrenamiento de la flexibilidad y la estabilidad articulares pueden mejorar eficazmente las señales EMG superficiales en la zona adyacente a la articulación, de modo que se mejore la fuerza muscular y el nivel de amplitud articular. Conclusión Los estudiantes deben realizar conscientemente un entrenamiento de rehabilitación bajo la dirección de un profesional, y recibir una instrucción completa en los procedimientos de rehabilitación deportiva que impliquen una combinación de recuperación física y psicológica. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
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Aryl sulfides are in great demands in drugs and materials sciences. To avoid using nucleophilic and noxious thiols, many efforts have been focused on exploring novel sulfide resources. Herein, a reductive Pd-catalyzed, Ni-mediated method to synthesize aryl sulfides via a sulfide transfer reaction is developed. The utility and scope of this reaction is exemplified by various aryl electrophiles and aryl sulfides. Mechanistic studies reveal two competing catalytic cycles of sulfide transfer and aryl transfer in this reaction, where the former one is favored over the later one because of the large energy barrier difference during the transmetalation. Moreover, two important chemicals are late-stage functionalized by this method, exhibiting the potential applications in drugs and materials science.
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Compuestos de Sulfhidrilo , Sulfuros , CatálisisRESUMEN
The Stille cross-coupling polymerization is one of the most efficient synthetic methods for donor-acceptor (D-A) type π-conjugated polymers (CPs). Nevertheless, thermal-activation Stille polymerization readily produced homocoupling defects, resulting in batch-to-batch variations in copolymers quality and deteriorating the device performance of electronics and optoelectronics. Here, a room-temperature Stille-type polymerization was developed, the utility and generality of which were demonstrated by synthesis of twelve D-A CPs with high molecular weights. Importantly, the resultant copolymers possessed no homocoupling (hc) structural defects, while hc reactions were observed in the thermal-activation Stille reactions. Thus, the organic field-effect transistors (OFETs) based on the former exhibited twofold higher charge transport mobility (2.10â cm2 â V-1 s-1 ), since it possessed stronger crystallinity and lower trap density of states (tDOS).
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PURPOSE: The aim of this study was to evaluate the therapeutic effect of Idelalisib, Apelisib and Copanlisib on 8-day-old cataract SD rat pups. MATERIALS AND METHODS: The rat model induced by sodium selenate (Na2SeO3) was used in this study. Experimental animals were randomly divided into five groups with eight animals in each group. They were control group, Na2SeO3 group, Idelalisib group, Apelisib group and Copanlisib group. On days 3, 5 and 7, all rats in Na2SeO3, Idelalisib, Apelisib and Copanlisib groups were given subcutaneous injection into the nape with Na2SeO3 and control group was given the same amount of saline. For days 1-14, Idelalisib, Apelisib and Copanlisib were given by intragastric administration, respectively, and the same amount of saline was given to the control group and Na2SeO3 group. On the 15th day of the experiment, we selected the Idelalisib group with the best effect from all groups, separated their lenses, and further analyzed the crystal proteins, oxidative damage and apoptosis indexes. RESULTS: The survival rate of rats in control and Idelalisib groups was 100%, the Na2SeO3 group was 37.5%, the Apelisib group was 25%, and the Copanlisib group was 0. According to the rat survival rate and lens score, we selected Idelalisib for further analysis of the crystallin, oxidative damage and apoptosis indexes. The results suggested that Na2SeO3 leads to cataract formation and crystallin precipitation. The levels of antioxidant enzymes GSH and SOD were decreased in the Na2SeO3 group, Nrf-2 and HO-1 were downregulated, Keap1 upregulated, and cleaved caspase-3 and Bax/Bcl-2 upregulated. Idelalisib significantly improved crystallin insolubility, reduced oxidative damage, and inhibited lens apoptosis. CONCLUSION: In summary, Idelalisib can significantly improve the progression of Na2SeO3-induced cataract in rats. In the future, it may be a potential effective drug candidate for the clinical treatment of cataract.
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Catarata , Cristalinas , Cristalino , Animales , Antioxidantes/uso terapéutico , Catarata/inducido químicamente , Catarata/tratamiento farmacológico , Catarata/prevención & control , Cristalinas/metabolismo , Glutatión/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Cristalino/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Purinas , Quinazolinonas , Ratas , Ratas Sprague-Dawley , Ácido Selenioso , Selenito de SodioRESUMEN
Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg-1 · d-1) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg-1 · d-1) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1ß, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.
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Colitis , Microbioma Gastrointestinal , Animales , Células CACO-2 , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colon/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Flavonoides/metabolismo , Flavonoides/farmacología , Flavonoides/uso terapéutico , Humanos , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo , Sirtuina 1/metabolismoRESUMEN
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. While many patients survive, a portion of PTC cases display high aggressiveness and even develop into refractory differentiated thyroid carcinoma. This may be alleviated by developing a novel model to predict the risk of recurrence. Ferroptosis is an iron-dependent form of regulated cell death (RCD) driven by lethal accumulation of lipid peroxides, is regulated by a set of genes and shows a variety of metabolic changes. To elucidate whether ferroptosis occurs in PTC, we analyse the gene expression profiles of the disease and established a new model for the correlation. METHODS: The thyroid carcinoma (THCA) datasets were downloaded from The Cancer Genome Atlas (TCGA), UCSC Xena and MisgDB, and included 502 tumour samples and 56 normal samples. A total of 60 ferroptosis related genes were summarised from MisgDB database. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) were used to analyse pathways potentially involving PTC subtypes. Single sample GSEA (ssGSEA) algorithm was used to analyse the proportion of 28 types of immune cells in the tumour immune infiltration microenvironment in THCA and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells. Spearman correlation analysis was performed on the ferroptosis gene expression and the correlation between immune infiltrating cells proportion. We established the WGCNA to identify genes modules that are highly correlated with the microenvironment of immune invasion. DEseq2 algorithm was further used for differential analysis of sequencing data to analyse the functions and pathways potentially involving hub genes. GO and KEGG enrichment analysis was performed using Clusterprofiler to explore the clinical efficacy of hub genes. Univariate Cox analysis was performed for hub genes combined with clinical prognostic data, and the results was included for lasso regression and constructed the risk regression model. ROC curve and survival curve were used for evaluating the model. Univariate Cox analysis and multivariate Cox analysis were performed in combination with the clinical data of THCA and the risk score value, the clinical efficacy of the model was further evaluated. RESULTS: We identify two subtypes in PTC based on the expression of ferroptosis related genes, with the proportion of cluster 1 significantly higher than cluster 2 in ferroptosis signature genes that are positively associated. The mutations of Braf and Nras are detected as the major mutations of cluster 1 and 2, respectively. Subsequent analyses of TME immune cells infiltration indicated cluster 1 is remarkably richer than cluster 2. The risk score of THCA is in good performance evaluated by ROC curve and survival curve, in conjunction with univariate Cox analysis and multivariate Cox analysis results based on the clinical data shows that the risk score of the proposed model could be used as an independent prognostic indicator to predict the prognosis of patients with papillary thyroid cancer. CONCLUSIONS: Our study finds seven crucial genes, including Ac008063.2, Apoe, Bcl3, Acap3, Alox5ap, Atxn2l and B2m, and regulation of apoptosis by parathyroid hormone-related proteins significantly associated with ferroptosis and immune cells in PTC, and we construct the risk score model which can be used as an independent prognostic index to predict the prognosis of patients with PTC.
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Carcinoma Papilar , Ferroptosis , Neoplasias de la Tiroides , Biomarcadores de Tumor , Carcinoma Papilar/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Recurrencia Local de Neoplasia , Pronóstico , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Microambiente TumoralRESUMEN
OBJECTIVE: The combination of two or more drugs with different mechanisms is a promising strategy for cancer treatment, and radioimmunotherapy (RIT) is a trending antitumor strategy. Radiotherapy (RT) can promote and activate antitumor immune effects, and immunotherapy can strengthen the effects of selective internal radiotherapy (SIRT); the RIT combination is synergistic and can overcome the adverse side effects of monotherapy. In this study, we developed a radioimmunoconjugate (RIC)-the iodine-131 (131I)-labeled caerin 1.1 peptide-to treat human anaplastic thyroid cancer (ATC). METHODS: Antitumor activity of caerin 1.1 peptide was determined by MTT assay, plate colony formation and cell wound scratch assays, and the mechanism of the inhibition of carein 1.1 peptide on the growth of CAL-62 cells was identified by cell cycle and western blot. Then, we investigated the efficacy of the caerin 1.1 peptide as a single drug and the 131I-labeled caerin 1.1 peptide for ATC. H&E and TUNEL staining was performed to detect dead cells in the tumor tissue sections. RESULTS: We found that caerin 1.1 arrested cells in the S phase to induce apoptosis and inhibited tumor growth to inhibit phosphorylation of Akt. In vivo, the iodine-131 (131I)-labeled caerin 1.1 peptide achieved better antitumor efficacy than radiotherapy alone and showed a good biosafety profile. CONCLUSIONS: Our study demonstrates for the first time that the iodine-131 (131I)-labeled caerin 1.1 peptide can inhibit CAL-62 tumor growth and migration. The iodine-131 (131I)-labeled caerin 1.1 peptide, which represents a radioimmunotherapy strategy based on the combination of SIRT with a peptide-drug conjugate, could provide a treatment means for the radical cure of ATC.
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Carcinoma Anaplásico de Tiroides , Animales , Humanos , Radioisótopos de Yodo , Ratones , Radioinmunoterapia , Neoplasias de la TiroidesRESUMEN
Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. It takes some time from chronic gastritis to develop in GC. Early detection of GC will help patients obtain timely treatment. Understanding disease evolution is crucial for the prevention and treatment of GC. Here, we present a convolutional neural network (CNN)-based system to detect abnormalities in the gastric mucosa. We identified normal mucosa, chronic gastritis, and intestinal-type GC: this is the most common route of gastric carcinogenesis. We integrated digitalizing histopathology of whole-slide images (WSIs), stain normalization, a deep CNN, and a random forest classifier. The staining variability of WSIs was reduced significantly through stain normalization, and saved the cost and time of preparing new slides. Stain normalization improved the effect of the CNN model. The accuracy rate at the patch-level reached 98.4%, and 94.5% for discriminating normal â chronic gastritis â GC. The accuracy rate at the WSIs-level for discriminating normal tissue and cancerous tissue reached 96.0%, which is a state-of-the-art result. Survival analyses indicated that the features extracted from the CNN exerted a significant impact on predicting the survival of cancer patients. Our CNN model disclosed significant potential for adjuvant diagnosis of gastric diseases, especially GC, and usefulness for predicting the prognosis.
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Liver fibrosis is a disease caused by long-term damage that is related to a number of factors. The current research on the treatment of liver fibrosis mainly focuses on the activation of hepatic stellate cell, in addition to protecting liver cells. byakangelicin has certain anti-inflammatory ability, but its effect on liver fibrosis is unclear. This study aims to explore whether byakangelicin plays a role in the development of liver fibrosis and to explore its mechanism. We determined that byakangelicin has a certain ability to resist fibrosis and reduce liver cell damage in a model of carbon tetrachloride-induced liver fibrosis in mice. Thereafter, we performed further verification in vitro. The signalling pathways of two important pro-fibrotic cytokines, transforming growth factor-ß and platelet-derived growth factor, were studied. Results showed that byakangelicin can inhibit related pathways. According to the hepatoprotective effect of byakangelicin observed in animal experiments, we studied the effect of byakangelicin on 4-HNE-induced hepatocyte (HepG2) apoptosis and explored its related pathways. The results showed that byakangelicin could attenuate 4-HNE-induced hepatocyte apoptosis via inhibiting ASK-1/JNK signalling. In conclusion, byakangelicin could improve carbon tetrachloride-induced liver fibrosis and liver injury by inhibiting hepatic stellate cell proliferation and activation and suppressing hepatocyte apoptosis.
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Tetracloruro de Carbono/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Furocumarinas/farmacología , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Sustancias Protectoras/farmacología , Animales , Apoptosis/efectos de los fármacos , Biopsia , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Citocinas/metabolismo , Modelos Animales de Enfermedad , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/prevención & control , Masculino , Ratones , Transducción de Señal/efectos de los fármacos , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Interleukin 10 (IL-10) belongs to IL-10 family cytokines that are critical for maintaining the integrity of epithelial tissues, protecting pathogenic infection, and preventing excessive immune responses to damage self. Temporal IL-10 signaling blockade enhances vaccine-induced tumor regression by CD8 + T cells. IL-10, especially pegylated IL-10, mediates tumor regression by expanding tumor-infiltrating CD8 + T cells. Moreover, targeting IL-10 enhances immune checkpoint inhibitor mediated tumor regression. In the current paper, we will review recent advances in this area and discuss the complexity of IL-10 manipulation for cancer therapy.
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Interleucina-10 , Neoplasias , Linfocitos T CD8-positivos , Citocinas , Humanos , Inmunoterapia , Interleucina-15 , Interleucina-2 , Neoplasias/terapiaRESUMEN
Genital warts, which are one of the most common sexually transmitted diseases (STDs), result from persistent infection with human papillomavirus (HPV), especially subtypes 6 or 11. Topical application of 5% imiquimod cream is currently recommended as a first-line treatment choice for genital warts, but the clearance and patient compliance rates remain less than sufficient. In the current study, we developed a temperature-sensitive gel that contains the host-defense peptides caerin 1.1 and 1.9, which were originally isolated from Australian tree frogs of the genus Litoria. Growth of HPV16 E6/E7-transformed TC-1 cells was inhibited in vitro and in vivo following injection of the tumor with the caerin gel in a TC-1 tumor mouse model. Furthermore, when the caerin gel was topically applied, the inhibitory effect remained, and T, NK cells were attracted to the tumor site. In addition, the gel maintained a similar level of bioactivity after incubation at room temperature for 30 days. Our results suggest that this caerin gel, following further optimization, may provide an alternative method for the management of genital warts.
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Carcinoma de Células Escamosas/patología , Papillomavirus Humano 16/genética , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/patología , Neoplasias de la Lengua/patología , Carcinoma de Células Escamosas/virología , China , ADN Viral/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/virología , Estudios Retrospectivos , Lengua/patología , Lengua/virología , Neoplasias de la Lengua/virologíaRESUMEN
Human papillomavirus (HPV) related tumours account for a significant proportion of head and neck squamous cell carcinomas (HNSCCs) in developed countries. They respond better to chemo- and radio-therapy, and have a better stage specific prognosis. To establish their prevalence in China, we assessed a series of histology confirmed HNSCCs collected in Zhejiang and Guangdong provinces by PCR for HPV DNA and by immunohistochemistry for p16 protein status. Among 303 HNSCCs, HPV DNA was detected in 26.4%, with HPV16 DNA in 71% of these. Of HNSCC located in the oropharynx, 38.55% (32/83) were HPV+ve. In this series, p16 status was a relatively poor predictor of HPV status as detected by PCR. The stage specific survival time of HPV+ HNSCCs was significantly longer than for HPV- HNSCC. HPV status should be assessed for oropharyngeal cancers in China to assist with appropriate management, and prophylaxis against HPV infection should be considered to reduce the incidence of this disease.
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Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Anciano , China/epidemiología , Susceptibilidad a Enfermedades , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Medición de Riesgo , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Análisis de SupervivenciaRESUMEN
BACKGROUND: Therapeutic vaccines against cervical cancer remain ineffective. Previously, we demonstrated that blocking the signalling of a cytokine, interleukin 10, at the time of immunisation elicited significantly higher numbers of antigen specific T cells and inhibited tumour growth in mice. RESULTS: In the current paper, we demonstrate, in a HPV16 E6/E7 transformed TC-1 tumour mouse model, that despite increased antigen specific T cell numbers, blocking IL-10 signalling at the time of immunisation does not increase the survival time of the TC-1 tumour bearing mice compared to mice receiving the same immunisation with no IL-10 signalling blockade. Moreover, the function of tumour infiltrating T cells isolated 3 weeks post TC-1 transplantation is more suppressed than those isolated 2 weeks after tumour inoculation. We demonstrate that synthesized caerin peptides, derived from amphibian skin secretions, 1) were able to inhibit TC-1 tumour growth both in vitro and in vivo; 2) are environmentally stable; and 3) promote the secretion of pro-inflammatory interlukine-6 by TC-1 cells. Notably caerin peptides were able to increase the survival time of TC-1 tumour bearing mice after therapeutic vaccination with a HPV16E7 peptide-based vaccine containing IL-10 inhibitor, via recruiting increased levels of T cells to the tumour site. CONCLUSION: Caerin peptides increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site.