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A series of coal and gas outburst tests were conducted on coal seams in north China to determine the important order of gas pressure, in situ stress, and coal strength during coal and gas outbursts. And the typical phenomena of coal and gas outbursts were investigated. In addition, improved outburst energy equations were built to study the coal energy evolution process during coal and gas outbursts. The results show that the coal strength has the strongest influence on coal and gas outbursts, followed by the gas pressure and the in situ stress. The weights of pulverized coal with a particle size of less than 0.28 mm are consistent with the changing trend of the total weights of the pulverized coal particles in the corresponding outburst interval. Furthermore, the results suggest that the gas pressure monitored by the sensors close to the outburst hole begins to drop first and lasts for the longest time. The outburst coal presents obvious fracture and pulverization damage characteristics, and the pulverization damage features of the coal near the outburst hole are more obvious. In addition, the improved outburst energy equation was established, and the rationality of the improved outburst energy equation was verified by using the outburst orthogonal simulation experimental data and the on-site outburst accident cases. The results of this experiment have important guiding significance for preventing and controlling the occurrence of coal and gas outbursts and ensuring safe and efficient mining of coal mines.
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Background: Tumor local and distant relapse recurrence after radiotherapy (RT) is one of the critical factors leading to poor prognosis. The effective antitumor effects of RT are dependent upon the participation of innate and adaptive components of the immune system. C5a/C5aR1 signaling can regulate antitumor immune effect in the tumor microenvironment (TME). Thus, exploring the changes and mechanism in the TME induced by RT-mediated complement activation may provide a novel perspective for reversing radioresistance. Methods: First, fractionated radiation of 8 Gy ×3 fractions were targeted at Lewis lung carcinoma (LLC) tumor-bearing female mice to measure the infiltration of CD8+ T cell and analyze the RNA sequencing (RNA-seq) in RT-recruited CD8+ T cells. Second, tumor growth was measured in LLC tumor-bearing mice treated with RT either with or without C5aR1 inhibitor to clarify the antitumor effect of RT combined with C5aR1 inhibitor. Third, we detected the expression of C5a/C5aR1 and their signaling pathways on radiated tumor tissues. Furthermore, we investigated the expression of C5a in tumor cells at different time points after different doses of RT. Results: In our system, RT induced the increased infiltration of CD8+ T cells and local activation of complement C5a/C5aR. Concurrent administration of RT and blocking of C5aR improved radiosensitivity and tumor-specific immune response, which was reflected by high C5aR expression in CD8+ T cells. The AKT/NF-κB pathway was found to be an important signaling pathway in C5a/C5aR axis mediation by RT. Conclusions: RT promotes the release of C5a from tumor cells and leads to up-regulation of C5aR1 expression via the AKT/NF-κB pathway. Inhibition of the combination of complement C5a and C5aR could improve RT sensitivity. Our work provides evidence that the combination of RT and C5aR blockade opens a new window of opportunity to promote anti-tumor therapeutic effects in lung cancer.
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[This corrects the article DOI: 10.3389/fimmu.2023.1102778.].
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Lung cancer is responsible for the leading cause of cancer-related death worldwide, which lacks effective therapies. In recent years, accumulating evidence on the understanding of the antitumor activity of the immune system has demonstrated that immunotherapy is one of the powerful alternatives in lung cancer therapy. T cells are the core of cellular immunotherapy, which are critical for tumorigenesis and the treatment of lung cancer. Based on the different expressions of surface molecules and functional points, T cells can be subdivided into regulatory T cells, T helper cells, cytotoxic T lymphocytes, and other unconventional T cells, including γδ T cells, nature killer T cells and mucosal-associated invariant T cells. Advances in our understanding of T cells' functional mechanism will lead to a number of clinical trials on the discovery and development of new treatment strategies. Thus, we summarize the biological functions and regulations of T cells on tumorigenesis, progression, metastasis, and prognosis in lung cancer. Furthermore, we discuss the current advancements of technologies and potentials of T-cell-oriented therapeutic targets for lung cancer.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Linfócitos T Citotóxicos , Imunoterapia , Linfócitos T Reguladores , CarcinogêneseRESUMO
Liver cancer is the sixth most common cancer and the fourth most fatal cancer in the world. Immunotherapy has already achieved modest results in the treatment of liver cancer. Meanwhile, the novel and optimal combinatorial strategies need further research. The complement system, which consists of mediators, receptors, cofactors and regulators, acts as the connection between innate and adaptive immunity. Recent studies demonstrate that complement system can influence tumor progression by regulating the tumor microenvironment, tumor cells, and cancer stem cells in liver cancer. Our review concentrates on the potential role of the complement system in cancer treatment, which is a promising strategy for killing tumor cells by the activation of complement components. Conclusions: Our review demonstrates that complement components and regulators might function as biomarkers and therapeutic targets for liver cancer diagnosis and treatment.
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BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs which function as novel regulators in human cancers. In this study, we aimed to investigate the functional roles and related molecular mechanisms of circ_0006282 in gastric cancer (GC) progression. METHODS: Fifty-five GC patients were enrolled in this study. GC cells (AGS and HGC-27) and normal cells (GES-1) were cultured in RPMI1640 added with 10% FBS and 1% penicillin-streptomycin. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the expression levels of circ_0006282, transcription elongation factor B subunit 1 (TCEB1) mRNA, miR-144-5p and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein ß (YWHAB; also known as 14-3-3ß). RNase R assay was used to determine the characteristic of circ_0006282. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were employed for cell proliferation. Transwell assay was conducted for cell migration and invasion. Western blot assay was carried out to measure the protein levels of Cyclin D1, matrix metalloprotein 9 (MMP9) and YWHAB. Dual-luciferase reporter assay, RNA pull-down assay and RIP assay were adopted to analyze the interaction between miR-144-5p and circ_0006282 or YWHAB. Murine xenograft model assay was performed to explore the function of circ_0006282 in vivo. RESULTS: Circ_0006282 level was increased in GC tissues and cells compared to normal tissues and cells. Silencing of circ_0006282 restrained GC cell proliferation, migration and invasion. For mechanism analysis, circ_0006282 was identified to function as the sponge for miR-144-5p to positively regulate YWHAB expression in GC cells. Moreover, miR-144-5p inhibition or YWHAB overexpression effectively reversed the impacts of circ_0006282 knockdown on GC cell growth and motility. Additionally, circ_0006282 knockdown blocked tumor growth of GC in vivo. CONCLUSION: Circ_0006282 facilitated the malignant behaviors of GC cells through circ_0006282/miR-144-5p/YWHAB axis.
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Wnt5a has been found recently to be involved in inflammation regulation through a mechanism that remains unclear. Immunohistochemical staining of infected human dental pulp and tissue from experimental dental pulpitis in rats showed that Wnt5a levels were increased. In vitro, Wnt5a was increased 8-fold in human dental pulp cells (HDPCs) after TNF-α stimulation compared with control cells. We then investigated the role of Wnt5a in HDPCs. In the presence of TNF-α, Wnt5a further increased the production of cytokines/chemokines, whereas Wnt5a knockdown markedly reduced cytokine/ chemokine production induced by TNF-α. In addition, in HDPCs, Wnt5a efficiently induced cytokine/chemokine expression and, in particular, expression of IL-8 (14.5-fold) and CCL2 (25.5-fold), as assessed by a Luminex assay. The cytokine subsets regulated by Wnt5a overlap partially with those induced by TNF-α. However, no TNF-α and IL-1ß was detected after Wnt5a treatment. We then found that Wnt5a alone and the supernatants of Wnt5a-treated HDPCs significantly increased macrophage migration, which supports a role for Wnt5a in macrophage recruitment and as an inflammatory mediator in human dental pulp inflammation. Finally, Wnt5a participates in dental pulp inflammation in a MAPK-dependent (p38-, JNK-, and ERK-dependent) and NF-κB-dependent manner. Our data suggest that Wnt5a, as an inflammatory mediator that drives the integration of cytokines and chemokines, acts downstream of TNF-α.
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Polpa Dentária/metabolismo , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Wnt/metabolismo , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Polpa Dentária/patologia , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , NF-kappa B/genética , Proteínas Proto-Oncogênicas/genética , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Wnt/genética , Proteína Wnt-5aRESUMO
OBJECTIVE: To investigate qualitatively and quantitatively the diagnostic performance of 320-slice CT for detection of coronary artery disease with respect to different atherosclerotic plaque characteristics. METHODS: A retrospective search was performed for inpatients underwent both coronary CT and further coronary angiography (CAG) from December 1, 2008 to December 31, 2012. The diagnostic performance of 320-slice CTA for detecting significant stenosis ( ≥ 50% diameter) with respect to atherosclerotic plaque characteristics were analyzed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, kappa index (κ), and area under the receiver operating characteristic curve (AUC). Chi-square test was used to evaluate whether there were significant differences of the true-case frequency (true positive + true negative) and false-case frequency (false positive + false negative) among groups. Bland-Altman analysis was used to determine limits of agreement between CTA and CAG. RESULTS: A total of 454 patients and 6 779 segments were analyzed. Diagnostic accuracy was higher in non-calcified segments; whereas they decreased in the presence of both mild-moderately and heavily calcified plaques. Excellent agreement (κ = 0.810) between CT and CAG was observed for non-calcified segments, while good agreement was observed for both mild-moderately (κ = 0.701) and heavily calcified segments (κ = 0.750). Both mild-moderate (P = 0.000) and heavy (P = 0.000) calcification decreased the true-case frequency and increased the false-case frequency when compared to non-calcification. There were no significant underestimation or overestimation for non-calcified (P = 0.087) and mild-moderately calcified (P = 0.704) segments, while there was significant overestimation for heavily calcified segments (P = 0.001). CONCLUSIONS: Great qualitative and quantitative diagnostic performances of 320-slice CT were observed in non-calcified coronary segments. However, qualitative diagnostic performance decreased in both mild-moderately and heavily calcified segments, and quantitative overestimation were observed in heavily calcified segments.
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Doença da Artéria Coronariana , Placa Aterosclerótica , Calcinose , Angiografia Coronária , Humanos , Curva ROC , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Heroin dependence is a multifactor disorder. We investigated the association of genetic factors and heroin-dependent temperaments to determine whether a temperament-gene interaction is involved in the pathogenesis of heroin dependence. METHODS: Three hundred seventy participants (259 heroin-dependent patients and 111 healthy controls) were recruited and finished the Tridimensional Personality Questionnaire to assess personality traits (temperament). The genotypes of the aldehyde dehydrogenase 2 (ALDH2) gene and the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS: Multiple logistic regression analysis showed significant main effects for novelty seeking (P ≤ 0.001) and harm-avoidance (P = 0.001) scores, and a significant interaction effect between novelty seeking and ALDH2 genotypes (P = 0.016) in heroin-dependent patients compared with controls. When stratified by the ALDH2 genotypes, only heroin-dependent patients with the *1*2 and *2*2 genotypes at ALDH2 had higher novelty-seeking scores than did controls (heroin dependence = 15.94, controls = 12.46; P ≤ 0.001). CONCLUSIONS: Our results provide initial evidence that the ALDH2 gene interacted with novelty seeking in heroin-dependent Han Chinese patients in Taiwan.
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Aldeído Desidrogenase/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Comportamento Exploratório , Dependência de Heroína/genética , Adulto , Aldeído-Desidrogenase Mitocondrial , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Inquéritos e Questionários , TaiwanRESUMO
Understanding the influences of genes involved in dopamine and serotonin metabolism, such as the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) genes, is critical for understanding addictive behavior. In addition, dopamine D2 receptor (DRD2) gene may also interact with the dopamine metabolizing genes and link to addiction. Therefore, we investigated the association between the ALDH2, ADH1B and DRD2 polymorphisms and heroin dependence. Heroin-dependent Han Chinese patients (n=304) and healthy controls (n=335) were recruited. Genotypes of ALDH2, ADH1B and DRD2 polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. The frequency of the ALDH2*1/*1 genotype was significantly lower in heroin-dependent patients than in controls, but the frequency of ADH1B and DRD2 genotypes was not significantly different. Further stratification of the ALDH2 gene with the ADH1B gene showed that the protective effect of ALDH2*1/*1 existed only in patients who also carried the ADH1B*1/*1 and ADH1B*1/*2 genotype. Logistic regression analysis showed a significant interaction between ALDH2 and ADH1B (P=0.022) and DRD2, ALDH2 and ADH1B in patients (P=0.037). The ALDH2*1/*1, ADH1B*1/*1, and ADH1B*1/*2 genotypes may interact and protect their carriers against heroin dependence and the protective effect may be varied by the DRD2 gene polymorphism. We conclude that the protective effect of the ALDH2 polymorphism against heroin dependence may be modified by the ADH1B and DRD2 polymorphism.
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Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Dependência de Heroína/genética , Polimorfismo Genético/genética , Receptores de Dopamina D2/genética , Adulto , Aldeído-Desidrogenase Mitocondrial , Alelos , Interpretação Estatística de Dados , Feminino , Frequência do Gene , Genótipo , Dependência de Heroína/epidemiologia , Humanos , Modelos Logísticos , Masculino , Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND: Determining the influences of genes involved in metabolizing dopamine and encoding dopamine receptors, such as the aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) genes, is critical for understanding addictive behavior. Therefore, we investigated the association between the ALDH2 and DRD2/ANKK1 Taq IA polymorphisms and heroin dependence. METHODS: Heroin-dependent Han Chinese patients (250) and healthy controls (312) were recruited. ALDH2 and DRD2/ANKK1 Taq IA polymorphisms were genotyped. RESULTS: The frequency of ALDH2*1/*2 and *2/*2 genotypes was significantly higher in heroin-dependent patients than in controls, but the frequency of DRD2 Taq IA genotypes was not significantly different. Logistic regression analysis showed no significant interaction between ALDH2 and DRD2 Taq IA genotypes in patients. CONCLUSIONS: The ALDH2 polymorphism, but not the DRD2, was associated with heroin dependence.
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Aldeído Desidrogenase/genética , Dependência de Heroína/genética , Adulto , Aldeído-Desidrogenase Mitocondrial , Alelos , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Modelos Logísticos , Masculino , Polimorfismo Genético/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de Dopamina D2/genéticaRESUMO
Complicated thumb loss of the hand still remains a great challenge to hand and microsurgeons. In this article, we report our technique and outcomes in 10 cases using one-stage microsurgical procedures. In each case, three tissue transplants in combination with a sequential vascular anastomoses was performed, i.e. the second toe for the thumb, the extensor digitorum brevis for thenar opponent muscle, and the anterolateral thigh flap for the first web space, and adjacent soft tissue defects. All the transplants survived eventually. After an average of 6 years follow-up, the results were very inspiring. Combined tissue transfer can hasten patient recovery and improve functional outcomes. However, this method needs meticulous technique and great experience in microsurgery.
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Músculo Esquelético/transplante , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele , Polegar/lesões , Polegar/cirurgia , Dedos do Pé/transplante , Acidentes de Trabalho , Adolescente , Adulto , Anastomose Cirúrgica , Feminino , Humanos , Masculino , Microcirurgia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To observe the clinical outcome of primary repair of the tissue defects of the Achilles tendon and skin by thigh anterolateral free flap and free iliotibial tract. METHODS: From January 2000 to January 2005, the thigh anterolateral free flap and the iliotibial tract were used to primarily repair the defects of the Achilles tendon and skin in 11 patients (7 males and 4 females, aged 6-45 years). The defects of the skin and Achilles tendon were found in 6 patients, and the defects of the Achilles tendon and skin accompanied by the fracture of the calcaneus were found in 5 patients. The defect of the Achilles skin was 6 cm X 5 cm-14 cm X 8 cm in area. The defect of the Achilles tendon was 5-11 cm in length. The skin flap was 11 cm X 6 cm-17 cm X 11 cm in area. The iliotibial tract was 7-13 cm in length and 3-5 cm in width. The medial and lateral borders were sutured to from double layers for Achilles tendon reconstruction. The wound on the donor site could be sutured directly in 5 patients, and the others could be repaired with skin grafting. RESULTS: After operation, all the flaps survived and the wound healed by first intention. The follow-up of the 11 patients for 6 mouths-4 years (average, 30 months) revealed that according to Yin Qingshui's scale, the result was excellent in 6 patients, good in 4, and fair in 1. The excellent and good rate was 99%. The results showed a significant improvement in the "heel test" and the Thompson sign, and both were negative. No complications of ulceration on the heel and re-rupture of the Achilles tendon occurred. CONCLUSION: The primary repair of the tissue defects of the Achilles tendon and skin by free grafting of the anterolateral femoral skin flap and the iliotibial tract is an effective surgical method.