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This study sought to elucidate the mechanisms underlying the impact of the interferon signaling pathway on Ferroptosis in tumor cells and its correlation with CD8 + T cell exhaustion. Using mouse models and single-cell sequencing, the researchers studied the interaction between CD8 + T cells and the interferon signaling pathway. Differential gene analysis revealed key genes involved in CD8 + T cell exhaustion, and their downstream factors were explored using bioinformatics tools. The expression levels of interferon-related genes associated with Ferroptosis were analyzed using data from the TCGA database, and their relevance to tumor tissue Ferroptosis and patients' prognosis was determined. In vitro experiments were conducted to measure the levels of IFN-γ, MDA, and LPO, as well as tumor cell viability and apoptosis. In vivo validation using a mouse tumor model confirmed the results obtained from the in vitro experiments, highlighting the potential of silencing HSPA6 or DNAJB1 in enhancing the efficacy of PD-1 therapy and inhibiting tumor growth and migration.
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High-performance catalysts sufficient to significantly reduce the energy barrier of water activation are crucial in facilitating reactions that are restricted by water dissociation. Herein we present a Cu-Co double-atom catalyst (CuCo-DAC), which possesses a uniform and well-defined CuCoN6 (OH) structure, and works together to promote water activation in silane oxidation. The catalyst achieves superior catalytic performance far exceeding that of single-atom catalysts (SACs). Various functional silanes are converted into silanols with up to 98 % yield and 99 % selectivity. Kinetic studies show that the activation energy of silane oxidation by CuCo-DAC is significantly lower than that of Cu single-atom catalyst (Cu-SAC) and Co single-atom catalyst (Co-SAC). Theoretical calculations demonstrate two different reaction pathways where water splitting is the rate-determining step and it is accelerated by CuCo-DAC, whereas H2 formation is key for its single-atom counterpart.
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Intestinal epithelial cells (IECs) at the internal/external interface orchestrate the mucosal immune response, and IEC dysfunction has been linked to multiple inflammatory diseases, including inflammatory bowel disease. In this study, we found that a member of the TNF-α-induced protein 8 (TNFAIP8 or TIPE) family called TIPE1 is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. TIPE1-deficient mice, or chimeric mice that were deficient in TIPE1 in their nonhematopoietic cells, were more sensitive to dextran sulfate sodium-induced experimental colitis; however, TIPE1 deficiency had no impact on the development of inflammation-associated and sporadic colorectal cancers. Mechanistically, TIPE1 prevented experimental colitis through modulation of TNF-α-dependent inflammatory response in IECs. Importantly, genetic deletion of both TIPE1 and its related protein TNFAIP8 in mice led to the development of spontaneous chronic colitis, indicating that both of these two TIPE family members play crucial roles in maintaining intestinal homeostasis. Collectively, our findings highlight an important mechanism by which TIPE family proteins maintain intestinal homeostasis and prevent inflammatory disorders in the gut.
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Colitis , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Colitis/inducido químicamente , Colitis/genética , Sulfato de Dextran/toxicidad , Células Epiteliales/metabolismo , Inflamación/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti-inflammatory mechanisms of the gut-brain axis in PD models fed with KD.
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The transformation of plastic wastes into value-added carbon materials is a promising strategy for the recycling of plastics. Commonly used polyvinyl chloride (PVC) plastics are converted into microporous carbonaceous materials using KOH as an activator via simultaneous carbonization and activation for the first time. The optimized spongy microporous carbon material has a surface area of 2093 m2 g-1 and a total pore volume of 1.12 cm3 g-1, and aliphatic hydrocarbons and alcohols are yielded as the carbonization by-products. The PVC-derived carbon materials exhibit outstanding adsorption performance for removing tetracycline from water, and the maximum adsorption capacity reaches 1480 mg g-1. The kinetic and isotherm patterns for tetracycline adsorption follow the pseudo-second-order and Freundlich models, respectively. Adsorption mechanism investigation indicates that pore filling and hydrogen bond interaction are mainly responsible for the adsorption. This study provides a facile and environmentally friendly approach for valorizing PVC into adsorbents for wastewater treatment.
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Currently, the construction of heterojunctions as a method to enhance photoelectrochemical (PEC) activity has shown prospective applications in the analytical field. Restricted by carrier separation at the interface, developing a heterojunction sensing platform with high sensitivity remains challenging. Here, a double-photoelectrode PEC sensing platform was fabricated based on an antenna-like strategy by integrating MIL-68(In)-NH2, a p-type metal-organic framework (MOF) photocatalyst, as a photocathode with the type-II heterojunction of CdSe/MgIn2S4 as a photoanode synchronously. According to the ligand-to-metal charge transition (LMCT), the photo-generated carriers of MIL-68(In)-NH2 transferred from the organic ligand to the metal cluster, which provides an efficient antenna-like transfer path for the charge at the heterojunction interface. In addition, the sufficient Fermi energy difference between the double photoelectrode provides the continuous internal driving force required for rapid carrier separation at the anode detection interface, significantly improving the photoelectric conversion efficiency. Hence, compared with the traditional heterojunction single electrode, the photocurrent response of the double-photoelectrode PEC sensing platform developed using the antenna-like strategy is 2.5 times stronger. Based on this strategy, we constructed a PEC biosensor for the detection of programed death-ligand 1 (PD-L1). The elaborated PD-L1 biosensor exhibited sensitive and precise detection capability with a detection range of 1 × 10-5 to 1 × 103 ng/mL and a lower detection limit of 3.26 × 10-6 ng/mL and demonstrated the feasibility of serum sample detection, providing a novel and viable approach for the unmet clinical need of PD-L1 quantification. More importantly, the charge separation mechanism at the heterojunction interface proposed in this study provides new creative inspiration for designing sensors with high-sensitivity PEC performance.
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Técnicas Biosensibles , Estructuras Metalorgánicas , Antígeno B7-H1 , Ligandos , Oro , Técnicas Biosensibles/métodos , Técnicas Electroquímicas , Límite de DetecciónRESUMEN
Background: Natural killer (NK) cells are involved in monitoring and eliminating cancers. The purpose of this study was to develop a NK cell-related genes (NKGs) in pancreatic cancer (PC) and establish a novel prognostic signature for PC patients. Methods: Omic data were downloaded from The Cancer Genome Atlas Program (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), and used to generate NKG-based molecular subtypes and construct a prognostic signature of PC. NKGs were downloaded from the ImmPort database. The differences in prognosis, immunotherapy response, and drug sensitivity among subtypes were compared. 12 programmed cell death (PCD) patterns were acquired from previous study. A decision tree and nomogram model were constructed for the prognostic prediction of PC. Results: Thirty-two prognostic NKGs were identified in PC patients, and were used to generate three clusters with distinct characteristics. PCD patterns were more likely to occur at C1 or C3. Four prognostic DEGs, including MET, EMP1, MYEOV, and NGFR, were found among the clusters and applied to construct a risk signature in TCGA dataset, which was successfully validated in PACA-CA and GSE57495 cohorts. The four gene expressions were negatively correlated with methylation level. PC patients were divided into high and low risk groups, which exerts significantly different prognosis, clinicopathological features, immune infiltration, immunotherapy response and drug sensitivity. Age, N stage, and the risk signature were identified as independent factors of PC prognosis. Low group was more easily to happened on PCD. A decision tree and nomogram model were successfully built for the prognosis prediction of PC patients. ROC curves and DCA curves demonstrated the favorable and robust predictive capability of the nomogram model. Conclusion: We characterized NKGs-derived molecular subtypes of PC patients, and established favorable prognostic models for the prediction of PC prognosis, which may serve as a potential tool for prognosis prediction and making personalized treatment in PC.
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Drug resistance is a great obstacle to the clinical application of paclitaxel (PTX) in breast cancer treatment. Chemoresistance can be either primary or acquired. Multifarious factors are related to drug resistance. Among these factors, drug-induced autophagy has been shown to contribute to acquired chemoresistance in cancer cells. Additionally, cancer stem cells (CSCs) drive primary chemoresistance. Recent advances regarding TIPE2 demonstrate that TIPE2 enhances osteosarcoma and non-small cell lung cancer cell sensitivity to cisplatin. However, the role of TIPE2 in PTX resistance in breast cancer cells has not been elucidated. Here, the in vitro and in vivo study demonstrated that TIPE2 sensitized breast cancer cells to PTX by suppressing drug-induced autophagy and CSC properties. Mechanistically, we found that TIPE2 activated the AKT/mTOR signalling pathway and inhibited the TAK1/MAPK signalling pathway to suppress drug-induced autophagy. Moreover, TIPE2 inhibited TAK1/NF-κB activation to reduce breast CSC properties. Collectively, our results first elucidated the inhibitory role of TIPE2 in breast cancer chemoresistance. Thus, TIPE2 may be a new target for breast cancer chemotherapy.
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Neoplasias Óseas , Neoplasias de la Mama , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Femenino , Paclitaxel/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Línea Celular Tumoral , Autofagia/genética , Células Madre Neoplásicas , Resistencia a Antineoplásicos/genéticaRESUMEN
Osteosarcoma (OS), the most common primary malignancy of the bone, has a poor prognosis due to its high mortality rate and high potential for metastasis. Thus, it is urgently necessary to explore functional molecular targets of therapeutic strategies for osteosarcoma. Here, we reported that TIPE1 expression was decreased in osteosarcoma tissues compared to normal and adjacent nontumor tissues, and its expression was negatively related to tumor stage and tumor size. Functional assays showed that TIPE1 inhibited osteosarcoma carcinogenesis and metastatic potential both in vivo and in vitro. Furthermore, we investigated that the STAT3 signaling pathway was significantly downregulated after TIPE1 overexpression. Mechanistically, TIPE1 bind to the catalytic domain of PRMT1, which deposits an asymmetric dimethylarginine (ADMA) mark on histone/non-histone proteins, and thus inhibited PRMT1 mediated STAT3 methylation at arginine (R) residue 688. This abolished modification decreased STAT3 transactivation and expression, by which subsequently suppressed osteosarcoma malignancy. Taken together, these data showed that TIPE1 inhibits the malignant transformation of osteosarcoma through PRMT1-mediated STAT3 arginine methylation and ultimately decreases the development and metastasis of osteosarcoma. TIPE1 might be a potential molecular therapeutic target and an early biomarker for osteosarcoma diagnosis.
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Neoplasias Óseas , Péptidos y Proteínas de Señalización Intracelular , Osteosarcoma , Proteína-Arginina N-Metiltransferasas , Factor de Transcripción STAT3 , Arginina/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Transformación Celular Neoplásica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Metilación , Osteosarcoma/genética , Osteosarcoma/patología , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Represoras/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
Although increasing evidence links the gut microbiota with the development of colorectal cancer, the molecular mechanisms for microbiota regulation of tumorigenesis are not fully understood. Here, we found that a member of the TNFα-induced protein 8 (TNFAIP8) family called TIPE2 (TNFAIP8-like 2) was significantly upregulated in murine intestinal tumors and in human colorectal cancer, and colorectal cancer with high expression of Tipe2 mRNA associated with reduced survival time of patients. Consistent with these findings, TIPE2 deficiency significantly inhibited the development of colorectal cancer in mice treated with azoxymethane/dextran sodium sulfate and in Apcmin/+ mice. TIPE2 deficiency attenuated the severity of colitis by successfully resolving and restricting colonic inflammation and protected colonic myeloid cells from death during colitis. Transplantation of TIPE2-deficient bone marrow into wild-type mice successfully dampened the latter's tumorigenic phenotype, indicating a hematopoietic-specific role for TIPE2. Mechanistically, restricting the expansion of Enterobacteriaceae/Escherichia coli (E. coli) decreased intestinal inflammation and reduced the incidence of colonic tumors. Collectively, these data suggest that hematopoietic TIPE2 regulates intestinal antitumor immunity by regulation of gut microbiota. TIPE2 may represent a new therapeutic target for treating colorectal cancer.
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Colitis , Neoplasias del Colon , Microbioma Gastrointestinal , Animales , Carcinogénesis/genética , Colitis/inducido químicamente , Escherichia coli/metabolismo , Humanos , Inflamación/complicaciones , Péptidos y Proteínas de Señalización Intracelular/genética , Ratones , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Advanced oxidation processes (AOPs) are important technologies for aqueous organics removal. Despite organic pollutants can be degraded via AOPs generally, high mineralization of them is hard to achieve. Herein, we synthesized a manganese oxide nanomaterial (H2-OMS-2) with abundant Brønsted-acid sites via ion-exchange of cryptomelane-type MnO2 (OMS-2), and tested its catalytic performance for the degradation of phthalate esters via peroxymonosulfate (PMS) activation. About 99% of dimethyl phthalate (DMP) at a concentration of 20 mg/L could be degraded within 90 min and 82% of it could be mineralized within 180 min over 0.6 g/L of catalyst and 1.8 g/L of PMS. The catalyst could activate PMS to generate SO4-Ë and ·OH as the dominant reactive oxygen species to reach complete degradation of DMP. Especially, the higher TOC removal rate was obtained due to the rich Brønsted-acid sites and surface oxygen vacancies on the catalyst. Kinetics and mechanism study showed that MnII/MnIII might work as the active sites during the catalytic process with a lower reaction energy barrier of 55.61 kJ/mol. Furthermore, the catalyst could be reused for many times through the regeneration of the catalytic ability. The degradation and TOC removal efficiencies were still above 98% and 65% after seven consecutive cycles, respectively. Finally, H2-OMS-2-catalyzed AOPs significantly reduced the organismal developmental toxicity of the DMP wastewater through the investigation of zebrafish model system. The present work, for the first time, provides an idea for promoting the oxidative degradation and mineralization efficiencies of aqueous organic pollutants by surface acid-modification on the catalysts.
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Compuestos de Manganeso , Óxidos , Animales , Ésteres , Óxidos/toxicidad , Peróxidos , Ácidos Ftálicos , Pez CebraRESUMEN
Controlling the reaction selectivity of organic transformations without losing high conversion is always a challenge in catalytic processes. In this work, a H3PO4·12WO3/OMS-2 nanocomposite catalyst ([PW]-OMS-2) was prepared through the oxidation of a Mn(ii) salt with sodium phosphotungstate by KMnO4. Comprehensive characterization indicates that different Mn2+ precursors significantly affected the crystalline phase and morphology of the as-synthesized catalysts and only MnSO4·H2O as the precursor could lead to a cryptomelane phase. Moreover, [PW]-OMS-2 demonstrated excellent catalytic activity toward aerobic oxidative dehydrogenation of tetrahydro-ß-carbolines due to mixed crystalline phases, enhanced surface areas, rich surface oxygen vacancies and labile lattice oxygen species. In particular, ß-carbolines and 3,4-dihydro-ß-carbolines could be obtained from tetrahydro-ß-carbolines with very high selectivity (up to 99%) over [PW]-OMS-2 via tuning the reaction solvent and temperature. Under the present catalytic system, scalable synthesis of a ß-carboline was achieved and the composite catalyst showed good stability and recyclability. This work not only clarified the structure-activity relationship of the catalyst, but also provided a practical pathway to achieve flexible, controllable synthesis of functional N-heterocycles.
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The content of cardiac troponin I (CTnI) in human blood is the key factor in judging acute myocardial infarction (AMI). In order to detect the content of CTnI, we constructed a sandwich-type electrochemical immunosensor based on hydrogen peroxide (H2O2) as a signal source. Dendritic platinum-copper alloy nanoparticles (DPCN) loaded on molybdenum disulfide (MoS2) nanosheets (DPCN/MoS2) as secondary antibodies (Ab2) label provided signal amplification. The hollow three-dimensional (3D) pyramid-shaped structure of DPCN exposed abundant active sites and exhibited excellent catalytic properties. MoS2 nanosheets with flower-like structure and a larger specific surface area can effectively load more DPCN. The combination of MoS2 and DPCN enhanced the catalytic performance of DPCN/MoS2 towards H2O2 reduction and realized signal amplification. For the substrate material, the two-dimensional (2D) metal-organic framework (Co-BDC, 1,4-benzenedicarboxylate is abbreviated as BDC) was hybridized with MoS2 nanosheets to load gold nanoparticles (Au NPs). The obtained Au/Co-BDC/MoS2 had low catalytic activity and excellent electrical conductivity, which was used to load primary antibodies (Ab1) to effectively enhance the sensitivity. Under the best conditions, we constructed the immunosensor with the detection range of 10 fg/mL to 100 ng/mL and the limit of detection (LOD) of 3.02 fg/mL. At the same time, the content of CTnI in human serum was tested with satisfactory results. Therefore, the constructed immunosensor has important significance in the sensitive and accurate detection of CTnI and early diagnosis of AMI.
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Técnicas Biosensibles , Grafito , Nanopartículas del Metal , Aleaciones , Cobre , Técnicas Electroquímicas , Oro , Humanos , Peróxido de Hidrógeno , Inmunoensayo , Límite de Detección , Molibdeno , Platino (Metal) , Troponina IRESUMEN
Brassinosteroids (BRs) play critical roles in plant growth and development, as well as in responses to abiotic stresses. The BRASSINAZOLE RESISTANT 1 (BZR1) and BRI1-EMS-SUPPRESSOR 1 (BES1) families of transcription factors have been elucidated largely in Arabidopsis and rice but not in other plant species. Here, we studied the functional characterization of a tomato (Solanum lycopersicum) BZR homolog gene, SlBZR1, in BR-regulated plant growth and tolerance to salt stress. SlBZR1 was highly expressed in the flowers and developing fruits of tomato. Both SlBZR1 and SlBZR1D (proline to leucine mutation at the 239th amino acid of SlBZR1) were transcriptional repressors and localized in the nucleus. SlBZR1 or SlBZR1D could interact with SlMYB30, SlMYBL2, SlPIF4, SlHAT1, SlIWS1 and SlREF6 in tomato. Overexpression of SlBZR1D enhanced the BR response and improved tolerance to salt stress in Arabidopsis, consistent with the phenotype of the Arabidopsis bes1-D mutant. Moreover, SlBZR1D-overexpressing tomato lines showed a short plant height, smaller and curly leaves, and delayed flowering. Additionally, SlBZR1D positively regulated salt tolerance in tomato and upregulated the expression of multiple stress-related genes. Our study provides new insights for understanding the function and mechanism of BZR transcription factors in BR-regulated plant growth and abiotic stress responses.
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Brasinoesteroides/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/fisiología , Solanum lycopersicum/fisiología , Factores de Transcripción/fisiología , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Reguladores del Crecimiento de las Plantas/fisiología , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Reacción en Cadena en Tiempo Real de la Polimerasa , Estrés Salino , Factores de Transcripción/metabolismoRESUMEN
Circular RNAs (circRNAs) are regarded as pivotal regulators in bone metabolism. However, the role of circRNAs in osteoblast mineralization remains largely unknown. Herein, we explored the expression profiles of circRNAs in 4 groups of osteoblasts with varying mineralization processes. Hsa_circ_0008500 (circ8500), which is upregulated in the RNA-seq data, is sifted through 194 candidate circRNAs in osteoblasts during mineralization. We characterize the features of novel circRNAs and find that the elevated expression of circ8500 promotes osteoblast mineralization. Mechanistically, circ8500 contains a critical binding site for miR-1301-3p. We further show that circ8500 competitively binds miR-1301-3p to abolish its suppressive effect on peptidyl arginine deiminase 4 (PADI4). PADI4 works as a binding partner of RUNX2 and stabilizes its protein expression levels by inhibiting the ubiquitin-proteasome pathway. This work provides new insights on the circRNA patterns in osteoblasts and the role of PADI4 in matrix mineralization.
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Electrochemical immunoassays are often used in the detection of biomarkers, and their sensitivity depends on the nature of the substrate and the catalytic activity of the signal amplification platform. In this work, a novel sandwich-type signal amplification strategy with a "gold-plated" organometallic frame (Au/IRMOF-3) as the substrate and the sea cucumber-like Pd@PtRh trimetallic nanomaterial (Pd@PtRh SNRs) as label was fabricated. For the substrate, gold nanoparticles (Au NPs) are stably connected to the free amino groups on the surface of organometallic frame (IRMOF-3), which not only prevent the agglomeration of Au NPs, but also greatly enhance the conductivity of the nanocomposites. The synergy between the two nanomaterials further shows a stronger affinity for the fixation of capture antibodies (Ab1). For the label, the effective high catalytic activity comes from the Pd@PtRh SNRs with a sea cucumber-like morphology. The nano-scale spherical PtRh crystals epitaxially grown on smooth Pd nanorods (Pd NRs) have more catalytically active sites because of the abundant edge and corner atoms, resulting in high catalytic activity and durability towards H2O2 reduction. Choosing calcitonin (PCT) as the target, differential pulse voltammetry (DPV) and amperometric i-t dual-mode detection was used to demonstrate the feasibility of the immunosensor. The results confirmed that the immunosensor exhibits excellent analytical capabilities and is satisfied in the analysis of human serum samples. Therefore, this strategy has great potential in the clinical application of electrochemical immunosensors.
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Técnicas Biosensibles , Grafito , Nanopartículas del Metal , Pepinos de Mar , Animales , Anticuerpos Inmovilizados , Técnicas Electroquímicas , Oro , Humanos , Peróxido de Hidrógeno , Inmunoensayo , Límite de Detección , Compuestos OrganometálicosRESUMEN
OBJECTIVE: A prospective, randomized, controlled clinical study was conducted with surgery performed by the same surgeon. The aim was to present a new technique for preserving the ligament flavum during lumbar microdiscectomy, and to evaluate whether this helps prevent postoperative fibrosis and improve outcome. METHODS: From January to December 2017, 251 patients with indication for microdiscectomy were randomly divided into test group using ligament flavum preservation technique and control group using conventional procedures. Visual analogue scale (VAS) scores and Oswestry Disability Index (ODI) were assessed before the surgery, and 3 days, 1 month, 6 months, 1 year and 2 years after the operation respectively. The grade of epidural fibrosis on MRI after 6 months was evaluated by two radiologists independently and double-blindly. RESULTS: Both groups' VAS and ODI were significantly improved after surgery, but there was no significant difference between two groups at 3d and 1 month after operation. The grade of epidural fibrosis in test group was significantly lower than that in control group at 6 months postoperative. The VAS and ODI were significantly lower in test group than that in control group at 6 months,1 year and 2 years after operation. CONCLUSION: Preservation of more ligament flavum is practicable during the procedure of microdiscectomy. It can prevent postoperative epidural fibrosis, and is helpful to achieve a better clinical outcome.
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Discectomía/métodos , Desplazamiento del Disco Intervertebral/cirugía , Ligamento Amarillo/cirugía , Vértebras Lumbares/cirugía , Microcirugia/métodos , Complicaciones Posoperatorias/prevención & control , Adulto , Discectomía/tendencias , Espacio Epidural/diagnóstico por imagen , Femenino , Fibrosis , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Ligamento Amarillo/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/tendencias , Masculino , Microcirugia/tendencias , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Recent studies have shown that tumour necrosis factor-α-induced protein 8 like-1(TIPE1) plays distinct roles in different cancers. TIPE1 inhibits tumour proliferation and metastasis in a variety of tumours but acts as an oncogene in cervical cancer. The role of TIPE1 in nasopharyngeal carcinoma (NPC) remains unknown. Interestingly, TIPE1 expression was remarkably increased in NPC tissue samples compared to adjacent normal nasopharyngeal epithelial tissue samples in our study. TIPE1 expression was positively correlated with that of the proliferation marker Ki67 and negatively correlated with patient lifespan. In vitro, TIPE1 inhibited autophagy and induced cell proliferation in TIPE1-overexpressing CNE-1 and CNE-2Z cells. In addition, knocking down TIPE1 expression promoted autophagy and decreased proliferation, whereas overexpressing TIPE1 increased the levels of pmTOR, pS6 and P62 and decreased the level of pAMPK and the LC3B. Furthermore, the decrease in autophagy was remarkably rescued in TIPE1-overexpressing CNE-1 and CNE-2Z cells treated with the AMPK activator AICAR. In addition, TIPE1 promoted tumour growth in BALB/c nude mice. Taken together, results indicate that TIPE1 promotes NPC progression by inhibiting autophagy and inducing cell proliferation via the AMPK/mTOR signalling pathway. Thus, TIPE1 could potentially be used as a valuable diagnostic and prognostic biomarker for NPC.
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Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/fisiología , Proliferación Celular/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Previous studies have revealed that TIPE1 serves as a tumor suppressor gene in several tumor types. However, we demonstrated that TIPE1 can promote cervical cancer proliferation by suppressing p53 activity. Here, we showed that TIPE1 inhibits cervical cancer cell apoptosis both in vivo and in vitro. Mechanistically, we revealed that TIPE1 facilitates chemoresistance in a wild-type p53-dependent manner. The results indicated that TIPE1 is responsible for the transition from chemosensitivity to chemoresistance, and that it can serve as a promising target in cervical cancer chemotherapy.