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Introduction: Traditional surgical resection, radiotherapy, and chemotherapy have been the treatment options for patients with head and neck squamous cell carcinoma (HNSCC) over the past few decades. Nevertheless, the five-year survival rate for patients has remained essentially unchanged, and research into treatments has been relatively stagnant. The combined application of photothermal therapy (PTT) and immunotherapy for treating HNSCC has considerable potential. Methods: Live-dead cell staining and CCK-8 assays proved that Fe3O4 nanoparticles are biocompatible in vitro. In vitro, cellular experiments utilized flow cytometry and immunofluorescence staining to verify the effect of Fe3O4 nanoparticles on the polarisation of tumor-associated macrophages. In vivo, animal experiments were conducted to assess the inhibitory effect of Fe3O4 nanoparticles on tumor proliferation under the photothermal effect in conjunction with BMS-1. Tumour tissue sections were stained to observe the effects of apoptosis and the inhibition of tumor cell proliferation. The histological damage to animal organs was analyzed by hematoxylin and eosin (H&E) staining. Results: The stable photothermal properties of Fe3O4 nanoparticles were validated by in vitro cellular and in vivo animal experiments. Fe3O4 photothermal action not only directly triggered immunogenic cell death (ICD) and enhanced the immunogenicity of the tumor microenvironment but also regulated the expression of tumor-associated macrophages (TAMs), up-regulating CD86 and down-regulating CD206 to inhibit tumor growth. The PD-1/PD-L1 inhibitor promoted tumor suppression, and reduced tumor recurrence and metastasis. In vivo studies demonstrated that the photothermal action exhibited a synergistic effect when combined with immunotherapy, resulting in significant suppression of primary tumors and an extension of survival. Conclusion: In this study, we applied Fe3O4 photothermolysis in a biomedical context, combining photothermolysis with immunotherapy, exploring a novel pathway for treating HNSCC and providing a new strategy for effectively treating HNSCC.
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Neoplasias de Cabeza y Cuello , Inmunoterapia , Terapia Fototérmica , Carcinoma de Células Escamosas de Cabeza y Cuello , Macrófagos Asociados a Tumores , Animales , Terapia Fototérmica/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Ratones , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Inmunoterapia/métodos , Humanos , Línea Celular Tumoral , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/química , Terapia Combinada , Proliferación Celular/efectos de los fármacos , Antígeno B7-H1/antagonistas & inhibidores , Apoptosis/efectos de los fármacosRESUMEN
The intricate development of liquid-crystal lubricants necessitates the timely and accurate prediction of their tribological performance in different environments and an assessment of the importance of relevant parameters. In this study, a classification model using Gaussian noise extreme gradient boosting (GNBoost) to predict tribological performance is proposed. Three additives, polysorbate-85, polysorbate-80, and graphene oxide, were selected to fabricate liquid-crystal lubricants. The coefficients of friction of these lubricants were tested in the rotational mode using a universal mechanical tester. A model was designed to predict the coefficient of friction through data augmentation of the initial data. The model parameters were optimized using particle swarm optimization techniques. This study provides an effective example for lubricant performance evaluation and formulation optimization.
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There is no effective treatment for peripheral nerve injury-induced chronic neuropathic pain (NP), which profoundly impacts the quality of life of those affected. Transmembraneprotein100 (TMEM100) is considered to be a pain regulatory protein and is expressed in the dorsal root ganglion (DRG) of rats. However, the mechanism of pain regulation and the expression of TMEM100 following various peripheral nerve injuries are unclear. In this study, we constructed two pain models of peripheral nerve injury: tibial nerve injury (TNI) and chronic constriction injury (CCI). This study found that the Paw Withdrawal Mechanical Threshold (PWMT) and Paw Withdraw Thermal Latency (PWTL) of the rats in the two pain models decreased significantly, and the expression of TMEM100 in the DRG of two groups also decreased significantly. Furthermore, the decrease in the CCI group was more obvious than in the TNI group. There was no significant statistical significance (P > 0.05). We constructed an adeno-associated virus 6 (AAV6) vector expressing recombinant fluorescent TMEM100 protein and injected it into the sciatic nerve (SN) of two pain models: CCI and TNI. PWMT and PWTL were significantly increased in the two groups, along with the expression of TMEM100 in the spinal cord and DRG. It also significantly inhibited the activation of microglia, astrocytes, and several inflammatory mediators (TNF- α, IL-1 ß, and IL-6). In summary, the results of this study suggested that TMEM100 might be a promising molecular strategy for the treatment of NP, and its anti-inflammatory effects might play an important role in pain relief.
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Neuralgia , Traumatismos de los Nervios Periféricos , Ratas , Animales , Ratas Sprague-Dawley , Traumatismos de los Nervios Periféricos/metabolismo , Calidad de Vida , Médula Espinal/metabolismo , Neuralgia/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Hiperalgesia/metabolismoRESUMEN
Rheumatoid arthritis (RA) causes irreversible joint damage, but the pathogenesis is unknown. Therefore, it is crucial to identify diagnostic biomarkers of RA metabolism-related genes (MRGs). This study obtained transcriptome data from healthy individuals (HC) and RA patients from the GEO database. Weighted gene correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and random forest (RF) algorithms were adopted to identify the diagnostic feature biomarker for RA. In addition, biomarkers were verified by qRT-PCR and Western blot analysis. We established a mouse model of collagen-induced arthritis (CIA), which was confirmed by HE staining and bone structure micro-CT analysis, and then further verified the biomarkers by immunofluorescence. In vitro NMR analysis was used to analyze and identify possible metabolites. The correlation of diagnostic feature biomarkers and immune cells was performed using the Spearman-rank correlation algorithm. In this study, a total of 434 DE-MRGs were identified. GO and KEGG enrichment analysis indicated that the DE-MRGs were significantly enriched in small molecules, catabolic process, purine metabolism, carbon metabolism, and inositol phosphate metabolism. AKR1C3, MCEE, POLE4, and PFKM were identified through WGCNA, LASSO, and RF algorithms. The nomogram result should have a significant diagnostic capacity of four biomarkers in RA. Immune infiltration landscape analysis revealed a significant difference in immune cells between HC and RA groups. Our findings suggest that AKR1C3, MCEE, POLE4, and PFKM were identified as potential diagnostic feature biomarkers associated with RA's immune cell infiltrations, providing a new perspective for future research and clinical management of RA.
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Artritis Experimental , Artritis Reumatoide , Animales , Ratones , Mapeo Cromosómico , Aprendizaje Automático , Algoritmos , Artritis Experimental/genética , Artritis Reumatoide/genética , BiomarcadoresRESUMEN
Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to identify new potential therapeutic targets. For this study we used the carbon tetrachloride abdominal injection induced liver fibrosis animal model in mice. Primary hepatic stellate cell isolation was performed by a density-gradient separation method, and this was followed by immunofluorescence stain analyses. Signal pathway analysis was performed by dual-luciferase reporter assay and western blotting. Our results showed that RUNX1 was upregulated in cirrhotic liver tissues compared with normal liver tissues. Besides, overexpression of RUNX1 caused more severe liver fibrosis lesions than control group under CCl4 -induced conditions. Moreover, α-SMA expression in the RUNX1 overexpression group was significantly higher than in the control group. Interestingly, we found that RUNX1 could promote the activation of TGF-ß/Smads in a dual-luciferase reporter assay. Thus we demonstrated that RUNX1 could be considered as a new regulator of hepatic fibrosis by activating TGF-ß/Smads signalling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target in the treatment of liver fibrosis in the future. In addition, this study also provides a new insight about the aetiology of liver fibrosis.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal , Cirrosis Hepática , Animales , Ratones , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
With the development of implant applications, osseointegration has become a criterion for implant success. A good blood supply is essential for successful osseointegration. To improve the pro-angiogenic ability of the implants, in this experiment we introduced zinc into the titanium coating. The physical morphology, biocompatibility, pro-angiogenic ability, and osteogenic effect of the zinc-containing titanium coatings were investigated. The pro-angiogenic effect of zinc ions was determined, and the intrinsic link between angiogenesis and osteogenesis under the effect of zinc ions was investigated. Zinc-containing titanium coating was prepared using a micro-arc oxidation (MAO) technique. The physical properties of the coating materials were determined by analyzing the microstructure, roughness, hydrophilic properties, constituent elements, and ionic release of the coating. The biocompatibility of the coating materials was examined using apoptosis and proliferation assays of human umbilical vein endothelial cells (HUVECs). The pro-angiogenic function and osteogenic ability of the zinc-containing coating were investigated by CD31 immunofluorescence staining and quantitative polymerase chain reaction (q-PCR) assay. The optimal concentration of zinc ions for pro-angiogenesis was screened by ion assay. Conditioned media (CM) were prepared for the experiments. The intrinsic link between angiogenesis and osteogenesis was determined by q-PCR to detect the expression of genes related to HUVECs and BMSCs after culture in CM. The prepared Zn-containing micro-arc oxide coatings were shown to have good physical properties, stable Zn2+ release ability, and biocompatibility, as well as good angiogenic and osteogenic potential. In addition, ion experiments confirmed that 60 µM Zn2+ exhibited the best angiogenic effect; more importantly, a mutual promotion between angiogenesis and osteogenesis regeneration in the Zn2+ microenvironment was also found. The introduction of Zn2+ improved the implants' functionality and laid the foundation for the clinical application of Zn2+ pro-angiogenesis.
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Osteogénesis , Zinc , Humanos , Zinc/farmacología , Zinc/química , Titanio/farmacología , Titanio/química , Iones/farmacología , Células Endoteliales de la Vena Umbilical HumanaRESUMEN
Background: It is well established that discogenic low back pain (DLBP) is often caused by the inflammatory response during intervertebral disc degeneration (IDD). However, it remains unclear how inflammatory mediators such as Interleukin-6 (IL-6) are involved in discogenic pain caused by degeneration and intervertebral disc (IVD) metabolism. The purpose of this study is to study the relationship between IL-6 and Transmembrane protein 100 (TMEM100), and to analyze the different metabolites and metabolic pathways in various rat intervertebral discs by metabonomics. Methods: We established a rat model of IDD-DLBP by disc punctures and PBS infusion to examine the rat pain behaviors. Intervertebral disc tissues were harvested for molecular biology experiments to explore the relationship between IL-6 and TMEM100. High-resolution mass spectrometry (HRMS) was performed for untargeted metabolomics, and nuclear magnetic resonance spectroscopy metabolomics (MRS) for differential metabolites and metabolic pathways. Results: The results showed a significant decrease in vonFrey test, hot plate test and acetone test (P < 0.05). The expression of IL-6 and TMEM100 in DLBP model was significantly higher than that in sham control group and IDD discs without PBS infusion group (P < 0.05). There were 15 major contributing metabolites identified in the DLBP intervertebral discs through metabolomic studies, involving 6 major metabolic pathways. The main differential metabolites included nitric oxide (NO), ammonia, and lactic acid as the metabolic endpoints; and the differential metabolic pathways included the glycine-serine-threonine (Gly-Ser-Thr), which is gradually weakened with the progression of inflammation. Conclusion: The change of TMEM100 expression mediated by il-6 is related to the Gly-Ser-Thr metabolic axis and plays an important role in the relief of discogenic pain.
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There is a lack of effective programmed cell death protein 1 (PD-1)-targeted immunotherapy with good tolerability in patients with advanced hepatocellular carcinoma (HCC) and severely compromised liver function. We assessed patient outcomes after combined camrelizumab and molecular targeted therapy in a multicenter cohort study in China. The study included 99 patients with advanced HCC (58 Child-Pugh A and 41 Child-Pugh B), 84 of them received camrelizumab combined with molecular targeted therapy from January 10, 2019, to March 31, 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed. The median follow-up was 12.1 months. For patients with Child-Pugh B, the OS probability at 12-months, ORR and DCR were 49.7%, 31.7% and 65.9%, respectively, and the median PFS was 5.1 months [95% confidence interval (CI) 3.0-7.1], which were comparable with Child-Pugh A patients, although median OS was shorter in Child-Pugh B patients (20.5 vs.13.4 months, P = 0.12). In multivariate analysis, macrovascular infiltration (MVI), but not sex, age, hepatitis B virus etiology, extrahepatic metastasis, Child-Pugh B, or AFP > 400 ng/ml, was associated with 12-months OS [hazard ratio (HR) 2.970, 95% CI 1.276-6.917, P = 0.012] and ORR (HR 2.906, 95% CI 1.18-7.16, P = 0.020). Grade 3/4 immune-related AEs occurred in 26.8% of Child-Pugh B patients, including one potentially treatment-related death. In both groups, the most common AEs were immune thrombocytopenia and hepatotoxicity. Camrelizumab combined with targeted therapy showed favorable effectiveness and tolerability with manageable toxicities in Chinese HCC patients, regardless of Child-Pugh A/B liver function. MVI was associated with suboptimal immunotherapy response and poor prognosis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Terapia Molecular Dirigida , Estudios de CohortesRESUMEN
Radiotherapy (RT) is one of the main clinical therapeutic strategies against cancer. Currently, multiple radiosensitizers aimed at enhancing X-ray absorption in cancer tissues have been developed, while limitations still exist for their further applications, such as poor cellular uptake, hypoxia-induced radioresistance, and unavoidable damage to adjacent normal body tissues. In order to address these problems, a cell-penetrating TAT peptide (YGRKKRRQRRRC)-modified nanohybrid was constructed by doping high-Z element Au in hollow semiconductor Cu2-xSe nanoparticles for combined RT and photothermal therapy (PTT) against breast cancer. The obtained Cu2-xSe nanoparticles possessed excellent radiosensitizing properties based on their particular band structures, and high photothermal conversion efficiency beneficial for tumor ablation and promoting RT efficacy. Further doping high-Z element Au deposited more high-energy radiation for better radiosensitizing performance. Conjugation of TAT peptides outside the constructed Cu2-xSe/Au nanoparticles facilitated their cellular uptake, thus reducing overdosage-induced side effects. This prepared multifunctional nanohybrid showed powerful suppression effects towards breast cancer, both in vitro and in vivo via integrating enhanced cell penetration and uptake, and combined RT/PTT strategies.
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Neoplasias de la Mama , Péptidos de Penetración Celular , Nanopartículas del Metal , Neoplasias , Humanos , Femenino , Terapia Fototérmica , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/química , Oro/farmacología , Oro/química , Neoplasias de la Mama/terapia , Línea Celular TumoralRESUMEN
The objective of this research was to develop a solution for the deterioration effect on the high-temperature rutting performance and water stability of SMC. This research proposed a method for designing an SMC normal temperature modified asphalt mixture based on the existing findings, experimental research and the performance balance. First, the power function curve model of the aggregate gradation was put forward. The 0.075 mm, 4.75 mm and nominal maximum particle size were the key points of the aggregate gradation, and their passing rate was about 6%, 30%, and 95% respectively. Then, on the basis of the quadratic curve model, a method for determination of the optimum asphalt aggregate ratio of SMC normal temperature modified asphalt mixture was put forward, considering the skeleton-density structure. Last, rutting tests, small beam bending tests, freeze-thaw split tests, permeability coefficient tests, texture depth tests and pavement roughness tests were conducted, and the test results all met the performance requirements of the specifications for the construction of highway asphalt pavement in China perfectly, especially the high-temperature and water stability properties, which indicated that the design method for SMC normal temperature modified asphalt mixtures based on performance balance presented in this paper was reasonable and practical.
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Wound healing is a critical challenge in diabetic patients, mainly due to long-term dysglycemia and its related pathological complications. Subcutaneous insulin injection represents a typical clinical solution, while the low controllability of insulin administration commonly leads to a result far from the optimal therapeutic effect. In this work, we developed a glucose-responsive insulin-releasing hydrogel for microneedle dressing fabrication and then investigated its effects on diabetic wound healing. The hydrogel system was composed of biocompatible gelatin methacrylate (GelMa), glucose-responsive monomer 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA) and gluconic insulin (G-insulin), and the Gel-AFPBA-ins hydrogel-based microneedle dressing was developed by replicating PDMS molds. The resultant hydrogel microneedle dressing exhibited adequate mechanical properties, high biocompatibility, glucose-responsive insulin release behavior upon exposure to different glucose solutions, and potent adhesion to the skin compared to hydrogels without microstructures. The microneedle dressing could accelerate the diabetic wound healing process with decreased inflammatory reaction, enhanced collagen deposition on the regenerated tissue sites, and improved blood glucose control in animals. Therefore, the glucose-responsive insulin-releasing hydrogel microneedle dressing is effective in diabetic wound management and has potential for treatment of other chronic skin injuries.
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Diabetes Mellitus , Hidrogeles , Animales , Vendajes , Diabetes Mellitus/tratamiento farmacológico , Glucosa , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Insulina/farmacología , Insulina/uso terapéutico , Cicatrización de HeridasRESUMEN
Objective: Through the follow-up analysis of cervical spine fracture cases with ankylosing spondylitis (AS), a treatment-oriented fracture classification method is introduced to evaluate the clinical efficacy guided by this classification method. Method: A retrospective analysis was performed on 128 AS patients who underwent comprehensive treatment in the Spine Surgery Department of Qingdao University Hospital from January 2009 to May 2018. Statistics of patient demographic data, distribution of different fractures corresponding to surgical methods, 3-year follow-up outcomes, and summary of objective fracture classification methods were analyzed. A prospective 5-year follow-up study of 90 patients with AS cervical spine fractures from June 2015 to August 2020 was also included. Statistical differences on the distribution of factors such as case information, cervical spine sagittal sequence parameters, and fracture classification were assessed. Correlations between surgical information, American Spinal Injuries Association grade (ASIA), modified Japanese Orthopaedic Association scores (mJOA), and other factors were analyzed to establish a nomogram predictive model for curative effect outcomes. Overall, three major types and the four subtypes of AS cervical spine fractures were evaluated based on the clinical efficacy of the classification and the selection of surgical treatment methods. Result: The most common type of fracture was type II (30 cases, 33.33%), most of the subtypes were A (37 cases), followed by B (36 cases) and C (17 cases). Twenty-four of 28 patients with type I underwent anterior surgery, and 47 of 62 patients with type II and III underwent posterior surgery. The average follow-up time was 25.76 ± 11.80 months. The results of predicting clinical variables are different but include factors such as fracture type and subtype, type of operation, and age. The predictor variables include the above-mentioned similar variables, but survival is more affected by the fracture type of the patient. Conclusion: This predictive model based on follow-up information delineation points out the impact of ankylosing spondylitis cervical spine fracture classification on surgical selection and clinical efficacy.
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Fracturas de la Columna Vertebral , Espondilitis Anquilosante , Vértebras Cervicales/cirugía , Estudios de Seguimiento , Humanos , Nomogramas , Estudios Prospectivos , Estudios Retrospectivos , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/cirugía , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/cirugía , Resultado del TratamientoRESUMEN
The epidemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has increasingly attracted worldwide concern. Liver damage or dysfunction occurred in patients with COVID-19 (mainly characterized by moderately elevated serum aspartate aminotransferase levels). However, it is not yet clear whether the COVID-19-related liver injury is mainly caused by the virus infection, potentially hepatotoxic drugs, or other coexisting conditions. Progression of pre-existing chronic liver disease (CLD) may be the underlying mechanism of liver injury. Although COVID-19 patients with CLD, such as nonalcoholic fatty liver disease, liver cirrhosis, and liver cancer, have been deemed at increased risk for serious illness in many studies, little is known about the impact of CLD on the natural history and outcome of COVID-19 patients. Thereby, based on the latest evidence from case reports and case series, this paper discusses the clinical manifestations, treatment, prognosis, and management of the COVID-19 patients with different CLD. This article also reviews the effect of COVID-19 on liver transplantation patients (LT), hoping to work for future prevention, management, and control measures of COVID-19. However, due to the lack of relevant research, most of them are still limited to the theoretical stage, further study of COVID-19 and CLD needs to be improved in the future.
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COVID-19/terapia , Hepatopatías/epidemiología , Trasplante de Hígado , SARS-CoV-2 , Receptores de Trasplantes , COVID-19/epidemiología , Enfermedad Crónica , Comorbilidad , Humanos , Hepatopatías/cirugía , Pandemias , PronósticoRESUMEN
OBJECTIVE: The current study aimed to explore the efficacy of Zero profile intervertebral fusion system (Zero-P) and traditional anterior plate cage system (PC) in the treatment of cervical spondylotic myelopathy (CSM). Further, the present study evaluated effects of the treatments on medical security, height of intervertebral disc, adjacent-level ossification development (ALOD), and adjacent segmentation disease (ASD) through a systematic retrospective analysis. METHODS: Studies on Zero-P system and traditional anterior plate cage system for ACDF in the treatment of CSM were searched in PubMed, Web of Science, Ovid, Embase, and Cochrane Library databases. Two independent researchers screened articles, extracted data, and evaluated the quality of the articles based on the inclusion and exclusion criteria of the current study. RevMan5.3 software was used for meta-analysis following the guidelines of Cochrane collaboration network. Cervical curvature, interbody fusion rate, preoperative and postoperative disc height index (DHI), fusion cage sinking rate, postoperative dysphagia, ASD, ALOD, and loosening of screw were compared between the two groups. RESULTS: A total of 17 literatures were included in the present study, including 6 randomized controlled trials and 11 observational studies. The studies comprised a total of 1204 patients with CSM, including 605 patients in the Zero-P system group (Zero-P group) and 599 patients in the traditional animal plate cage group (PC group). Results of this meta-analysis showed that postoperative dysphagia [OR = 0.40, CI (0.28, 95% 0.58), P < 0.00001], ALOD [OR = 0.09, CI (0.02, 95% 0.39), P = 0.001], ASD [OR = 0.42, CI (0.20, 95% 0.86), P = 0.02], and screw loosening [OR = 0.20, CI (0.08, 95% 0.52), P = 0.0009] of the Zero-P group were significantly lower compared with the PC group. On the other hand, preoperative cervical curvature [WMD = -0.23, CI (-1.38, 95% 0.92), P = 0.69], postoperative cervical curvature [WMD = -0.38, CI (-1.77, 95% 1.01), P = 0.59], cage sinking rate [OR = 1.41, CI [0.52, 95% 3.82], P = 0.50], intervertebral fusion rate [OR = 0.76, CI (0.27, 95% 2.48), P = 0.38], preoperative DHI [WMD = -0.04, CI (-0.14, 95% 0.22), P = 0.65], and postoperative DHI [WMD = 0.06, CI (-0.22, 95% 0.34), P = 0.675] were not significantly different between the two groups. CONCLUSION: It was evident that the Zero-P system used in ACDF is superior compared with the traditional anterior plate cage system in postoperative dysphagia, avoiding ALOD, ASD, and screw loosening.
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Fusión Vertebral , Espondilosis , Vértebras Cervicales/cirugía , Discectomía , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Espondilosis/cirugía , Resultado del TratamientoRESUMEN
Increasing studies have demonstrated that dysfunction of long noncoding RNAs (lncRNAs) plays critical roles in the development of human cancers. THAP9-AS1 has been reported to be dysregulated and associated with tumor progression in some cancers. However, the function and mechanism of THAP9-AS1 in osteosarcoma (OS) remain unclear. In the present study, we found that the expression of THAP9-AS1 was significantly upregulated in OS tissues and associated with the advanced stage of tumors and poor prognosis of patients. Blast comparison results showed that the SOCS3 promoter region and THAP9-AS1 had base complementary pairing binding sites. The interactions between THAP9-AS1, DNA methyltransferases (DNMTs), and SOCS3 were assessed by RIP and ChIP assays. The results of methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) validated that THAP9-AS1 enhanced the methylation level of the SOCS3 promoter. The mRNA levels of SOCS3 in OS cells could be reversed by the demethylation agent 5-aza-2'-deoxycytidine. The mRNA expression of SOCS3 was downregulated in OS tissues and negatively correlated with THAP9-AS1 expression in tumors. Moreover, the western blot and immunofluorescence (IF) assay data showed that THAP9-AS1 activated the JAK2/STAT3 signaling pathway by upregulating p-JAK2 and p-STAT3 and the nuclear translocation of p-STAT3. Functionally, ectopic expression of THAP9-AS1 promoted cell proliferation, migration, and invasion and inhibited apoptosis, and this phenomenon could be reversed by SOCS3. Introduction of the JAK/STAT inhibitor AG490 partially abolished the stimulative effect of THAP9-AS1 on cellular processes. In addition, THAP9-AS1 decreased oxidative stress by reducing reactive oxygen species (ROS) and enhancing the mitochondrial membrane potential of OS cells via the SOCS3/JAK2/STAT3 pathway. Stable overexpression of THAP9-AS1 contributed to tumor growth and metastasis in vivo. In total, our findings suggested that upregulation of THAP9-AS1 might recruit DNMTs to epigenetically inhibit SOCS3, thereby activating the JAK2/STAT3 signaling pathway and oncogenesis of OS. These results provide novel insights for the understanding of OS progression.
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Carcinogénesis/metabolismo , Metilación de ADN/genética , Osteosarcoma/genética , Factor de Transcripción STAT3/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Transposasas/metabolismo , Adulto , Femenino , Humanos , Masculino , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Adulto JovenRESUMEN
Although intervertebral disc degeneration (IDD) can be described as different stages of change through biological methods, this long and complex process cannot be defined in stages by single or simple combination of biological techniques. Under the background of the development of nuclear magnetic resonance (NMR) technology and the emerging metabonomics, we based on animal models and expanded to the study of clinical human degeneration models. The characteristics of different stages of IDD were analyzed by omics. Omics imaging combined with histology, cytology, and proteomics was used for screening of the intervertebral disc (IVD) of research subjects. Furthermore, mass spectrometry nontargeted metabolomics was used to explore profile of metabolites at different stages of the IDD process, to determine differential metabolic pathways and metabolites. NMR spectroscopy was used to qualitatively and quantitatively identify markers of degeneration. NMR was combined with mass spectrometry metabolomics to explore metabolic pathways. Metabolic pathways were determined through protein molecular biology and histocytology of the different groups. Distinguishing advantages of magnetic resonance spectroscopy (MRS) for analysis of metabolites and effective reflection of structural integrity and water molecule metabolism through diffusion tensor imaging (DTI) were further used to verify the macrometabolism profile during degeneration. A corresponding model of in vitro metabolomics and in vivo omics imaging was established. The findings of this study show that a series of metabolic pathways associated with the glycine-serine-threonine (Gly-Ser-Thr) metabolic axis affects carbohydrate patterns and energy utilization efficiency and ultimately delays disc degeneration through antioxidant effects.
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Antioxidantes/uso terapéutico , Imagen de Difusión Tensora/métodos , Glicina/uso terapéutico , Degeneración del Disco Intervertebral/tratamiento farmacológico , Metabolómica/métodos , Serina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Humanos , Persona de Mediana Edad , Ratas , Ratas Sprague-Dawley , Adulto JovenRESUMEN
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with high bacterial infection (BI) and short-term mortality. However, many ACLF prognostic predictive modelsare complicated. The aim of this study is to develop prognostic models for ACLF patients to predict BI and mortality. We retrospective recruited 263 patients with ACLF from Shandong Provincial Hospital and Taizhou Enze Medical Center (Group) Enze Hospital. ACLF was defined according to the Asian Pacific Association for the Study of the Liver (APASL) criteria. Multivariable logistic regression was used to derive prediction models for occurring BI and 28-day mortality in ACLF patients. Ninety seven of 263 patients (37%) occurred BI and 41 of 155 (26%) died within 28 days of admission. C-reactive protein (CRP), glucose, and albumin were the independent predictors for occurring BI during the hospital stay. We also found that hepatic encephalopathy (HE), prothrombin time, activated partial thromboplastin time (APRI), and glucose were the independent predictors of 28-day mortality of ACLF patients. Using logistic regression model, we generated a new modified MELD model (M-MELD) by incorporating HE, APRI, and glucose. AUC of M-MELD model was 0.871, which were significantly higher than MELD score (AUC:0.734), MELD-Na score (AUC:0.742), and integrated MELD score (iMELD) (AUC:0.761). HE, MELD score, APRI, and blood glucose were independent risk factors for 28-day mortality of ACLF patients. The modified MELD model (M-MELD) by incorporating HE, APRI, and glucose has better discriminative performances compared with MELD in predicting 28-day mortality.
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Insuficiencia Hepática Crónica Agudizada , Encefalopatía Hepática , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Humanos , Modelos Logísticos , Pronóstico , Estudios RetrospectivosRESUMEN
Gastric cancer is a commonly diagnosed, often fatal malignancy and requires novel anticancer therapies and preventative approaches. This study described the involvement of MAFG-AS1, a lncRNA with important functions in cancer biology, in gastric adenocarcinoma (GA). Thirty-six male and forty-two female GA patients with an average age of 51.9 ± 5.7 years in the range of 35 to 68 years were enrolled. Paired gastric cancer (GC) and non-tumor tissues were collected from each patient. MAFG-AS1 expression was determined. RNA interaction prediction, dual luciferase reporter assay, RT-qPCR assay, Western blot, and CCK-8 assay were conducted. The results indicated that MAFG-AS1 was highly expressed in GA and closely correlated with poor survival. MAFG-AS1 interacted with miR-505, but MAFG-AS1 and miR-505 overexpression showed no significant effects on each other's expression. In addition, MAFG-AS1 increased the expression of PLK1, a miR-505 target. MAFG-AS1 and PLK1 overexpression increased GC cell proliferation rate. MiR-505 overexpression reduced the effects of MAFG-AS1 and PLK1 overexpression on cell proliferation. Therefore, MAFG-AS1 might upregulate PLK1 by sponging miR-505 to promote GA cell proliferation.
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Proteínas de Ciclo Celular/metabolismo , Factor de Transcripción MafG/metabolismo , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , ARN Largo no Codificante/metabolismo , Proteínas Represoras/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Anciano , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Factor de Transcripción MafG/genética , Masculino , Persona de Mediana Edad , ARN Largo no Codificante/genética , Proteínas Represoras/genética , Neoplasias Gástricas/genética , Quinasa Tipo Polo 1RESUMEN
Triple-negative breast cancer (TNBC) is an aggressive subset of breast cancer and currently lacks effective therapeutic targets. As two main phototherapeutic methods, photothermal therapy (PTT) and photodynamic therapy (PDT) show many advantages in TNBC treatment, and their combination with chemotherapy can achieve synergistic therapeutic effects. In the present study, a biomimetic nanoplatform was developed based on leukocyte/platelet hybrid membrane (LPHM) and dendritic large pore mesoporous silicon nanoparticles (DLMSNs). A near infrared (NIR) fluorescent dye IR780 and a chemotherapeutic drug doxorubicin (DOX) were co-loaded into the large pores of DLMSNs to prepare DLMSN@DOX/IR780 (DDI) nanoparticles (NPs), followed by camouflage with LPHM to obtain LPHM@DDI NPs. Through the mediation of LPHM, LPHM@DDI NPs showed an excellent TNBC-targeting ability and very high PTT/PDT performances in vitro and in vivo. Upon NIR laser irradiation, LPHM@DDI NPs exhibited synergistic cytotoxicity and apoptosis-inducing activity in TNBC cells, and effectively suppressed tumor growth and recurrence in TNBC mice through tumor ablation and anti-angiogenesis. These synergistic effects were sourced from the combination of PTT/PDT and chemotherapy. Altogether, this study offers a promising biomimetic nanoplatform for efficient co-loading and targeted delivery of photo/chemotherapeutic agents for TNBC combination treatment.
RESUMEN
This study shows that people are likely to consider themselves special after experiencing lucky events, which increases the motivation for self-enhancement, consequently prompting them to deviate from majority-endorsed options and express a need for uniqueness. Prior luck-related research has primarily explored the effects of perceived luck on superstition or the illusion of control. The present study explored whether incidental luck affects consumers' motivation to conform or stand out, specifically people's tendency to diverge from others by choosing minority-endorsed options. The results from three experiments supported the proposed hypotheses in this study. Experiment 1 revealed that a lucky event arouses people's need for uniqueness. Experiment 2 demonstrated that when people experience a lucky event and perceive that luck favors them after making a downward comparison, they consider themselves special and prefer minority-endorsed options. Experiment 3 revealed that self-enhancement is a mediator in the effect of lucky events on the need for uniqueness-seeking behavior. The findings of this research not only provide additional insight into the behavioral consequences of lucky events but also extend the understanding of uniqueness-seeking behavior.