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The phenomenon of multidrug resistance (MDR) is called chemoresistance with respect to the treatment of cancer, and it continues to be a major challenge. The role of N-glycosylation in chemoresistance, however, remains poorly understood. Here, we established a traditional model for adriamycin resistance in K562 cells, which are also known as K562/adriamycin-resistant (ADR) cells. Lectin blot, mass spectrometry, and RT-PCR analysis showed that the expression levels of N-acetylglucosaminyltransferase III (GnT-III) mRNA and its products, bisected N-glycans, are significantly decreased in K562/ADR cells, compared with the levels in parent K562 cells. By contrast, the expression levels of both P-glycoprotein (P-gp) and its intracellular key regulator, NF-κB signaling, are significantly increased in K562/ADR cells. These upregulations were sufficiently suppressed by the overexpression of GnT-III in K562/ADR cells. We found that the expression of GnT-III consistently decreased chemoresistance for doxorubicin and dasatinib, as well as activation of the NF-κB pathway by tumor necrosis factor (TNF) α, which binds to two structurally distinct glycoproteins, TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), on the cell surface. Interestingly, our immunoprecipitation analysis revealed that only TNFR2, but not TNFR1, contains bisected N-glycans. The lack of GnT-III strongly induced TNFR2's autotrimerization without ligand stimulation, which was rescued by the overexpression of GnT-III in K562/ADR cells. Furthermore, the deficiency of TNFR2 suppressed P-gp expression while it increased GnT-III expression. Taken together, these results clearly show that GnT-III negatively regulates chemoresistance via the suppression of P-gp expression, which is regulated by the TNFR2-NF/κB signaling pathway.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP , NF-kappa B , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Resistencia a Medicamentos Antineoplásicos , Receptores Tipo II do Fator de Necrose Tumoral/genética , Transdução de Sinais , Doxorrubicina/farmacologia , Polissacarídeos/metabolismo , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismoRESUMO
Caffeine is one of the most popular consumed psychostimulants that mitigates several neurodegenerative diseases. Nevertheless, the roles and molecular mechanisms of caffeine in HIV-associated neurocognitive disorders (HAND) remain largely unclear. Transactivator of transcription (Tat) is a major contributor to the neuropathogenesis of HAND in the central nervous system. In the present study, we determined that caffeine (100 µM) treatment significantly ameliorated Tat-induced decreased astrocytic viability, oxidative stress, inflammatory response and excessive glutamate and ATP release, thereby protecting neurons from apoptosis. Subsequently, SIRT3 was demonstrated to display neuroprotective effects against Tat during caffeine treatment. In addition, Tat downregulated SIRT3 expression via activation of EGR1 signaling, which was reversed by caffeine treatment in astrocytes. Overexpression of EGR1 entirely abolished the neuroprotective effects of caffeine against Tat. Furthermore, counteracting Tat or caffeine-induced differential expression of SIRT3 abrogated the neuroprotection of caffeine against Tat-triggered astrocytic dysfunction and neuronal apoptosis. Taken together, our study establishes that caffeine ameliorates astrocytes-mediated Tat neurotoxicity by targeting EGR1/SIRT3 signaling pathway. Our findings highlight the beneficial effects of caffeine on Tat-induced astrocytic dysfunction and neuronal death and propose that caffeine might be a novel therapeutic drug for relief of HAND.
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The involvement of Group 3 innate lymphoid cells (ILC3s) and dendritic cells (DCs) in chronic lung inflammation has been increasingly regarded as the key to understand the inflammatory mechanisms of smoke-related chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the engagement of both remains unclear. Our study aimed to explore NCR-ILC3 differentiation in the lungs of mice exposed to cigarette smoke (CS) and to further investigate whether DCs activated by CS exposure contribute to the differentiation of ILCs into NCR-ILC3s. The study involved both in vivo and in vitro experiments. In the former, the frequencies of lung NCR-ILC3s and NKp46-IL-17A+ ILCs and the expression of DCs, CD40, CD86, IL-23, and IL-1ß quantified by flow cytometry were compared between CS-exposed mice and air-exposed mice. In the latter, NKp46-IL-17A+ ILC frequencies quantified by flow cytometry were compared after two cocultures, one involving lung CD45+Lin-CD127+ ILCs sorted from air-exposed mice and DCs sifted by CD11c magnetic beads from CS-exposed mice and another including identical CD45+Lin-CD127+ ILCs and DCs from air-exposed mice. The results indicated significant increases in the frequencies of NCR-ILC3s and NKp46-IL-17A+ ILCs; in the expression of DCs, CD40, CD86, IL-23, and IL-1ß in CS-exposed mice; and in the frequency of NKp46-IL-17A+ ILCs after the coculture with DCs from CS-exposed mice. In conclusion, CS exposure increases the frequency of lung ILCs and NCR-ILC3s. CS-induced DC activation enhances the differentiation of ILCs into NCR-ILC3s, which likely acts as a mediating step in the involvement of NCR-ILC3s in chronic lung inflammation.
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Diferenciação Celular , Células Dendríticas , Interleucina-17 , Interleucina-1beta , Pulmão , Receptor 1 Desencadeador da Citotoxicidade Natural , Animais , Células Dendríticas/imunologia , Camundongos , Pulmão/imunologia , Pulmão/metabolismo , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Interleucina-23/metabolismo , Antígeno B7-2/metabolismo , Camundongos Endogâmicos C57BL , Fumaça/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/imunologia , Antígenos CD40/metabolismo , Fumar Cigarros/efeitos adversos , Imunidade Inata , Antígenos Ly/metabolismo , Técnicas de Cocultura , MasculinoRESUMO
Autoantibody (AAb) has a prominent role in prostate cancer (PCa), with few studies profiling the AAb landscape in Chinese patients. Therefore, the AAb landscape in Chinese patients was characterized using protein arrays. First, in the discovery phase, Huprot arrays outlined autoimmune profiles against ~ 21,888 proteins from 57 samples. In the verification phase, the PCa-focused arrays detected 25 AAbs selected from the discovery phase within 178 samples. Then, PCa was detected using a backpropagation artificial neural network (BPANN) model. In the validation phase, an enzyme-linked immunosorbent assay (ELISA) was used to validate four AAb biomarkers from 196 samples. Huprot arrays profiled distinct PCa, benign prostate diseases (BPD), and health AAb landscapes. PCa-focused array depicted that IFIT5 and CPOX AAbs could distinguish PCa from health with an area under curve (AUC) of 0.71 and 0.70, respectively. PAH and FCER2 AAbs had AUCs of 0.86 and 0.88 in discriminating PCa from BPD. Particularly, PAH AAb detected patients in the prostate-specific antigen (PSA) gray zone with an AUC of 0.86. Meanwhile, the BPANN model of 4-AAb (IFIT5, PAH, FCER2, CPOX) panel attained AUC of 0.83 among the two cohorts for detecting patients with gray-zone PSA. In the validation cohort, the IFIT5 AAb was upregulated in PCa compared to health (p < 0.001). Compared with BPD, PAH and FCER2 AAbs were significantly elevated in PCa (p = 0.012 and 0.039). We have demonstrated the first extensive profiling of autoantibodies in Chinese PCa patients, identifying novel diagnostic AAb biomarkers, especially for identification of gray-zone-PSA patients.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Autoanticorpos , Análise Serial de Proteínas , População do Leste Asiático , Biomarcadores Tumorais , Neoplasias da Próstata/diagnósticoRESUMO
Trophoblast cells are critical to placental angiogenesis in the first trimester of pregnancy. Dysfunction of trophoblast leads to defective vascular remodeling and impaired angiogenesis, which is believed as the major cause of placental insufficiency and pregnancy failure. Protein O-fucosyltransferase 1 (poFUT1) is mainly responsible for O-fucosylated glycan biosynthesis on glycoproteins, and poFUT1 deficiency causes embryonic lethality in mice. However, the expression and function of poFUT1 in trophoblast-mediated human placental vessel formation remain unclear. In the current study, we showed that fewer blood vessels were observed in the villi and decidua of miscarriage patients than in normal pregnancy women. The expression of poFUT1 was decreased in the trophoblast cells of miscarriage patients compared with normal pregnancy women. Employing HTR/SVneo cells and an in vivo chorioallantoic membrane assay, we demonstrated that poFUT1 promoted the proliferation, migration ability, and angiogenesis potential of trophoblast cells. The results also indicated that poFUT1 upregulated O-fucosylation on uPA, facilitated the binding of uPA and uPAR, activated the RhoA signaling pathway, and further enhanced the angiogenic capacity of trophoblast cells. Our study provides new evidence for a relationship between poFUT1/O-fucosylation and placental angiogenesis. These findings may provide potential diagnostic biomarkers and targeted therapies for miscarriage patients.
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Aborto Espontâneo , Fucosiltransferases , Placenta , Animais , Feminino , Humanos , Camundongos , Gravidez , Movimento Celular , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Placenta/metabolismo , Primeiro Trimestre da Gravidez , Transdução de Sinais , Trofoblastos/metabolismoRESUMO
N-Linked glycosylation and O-linked N-acetylglucosamine (O-GlcNAc) are important protein post-translational modifications that are orchestrated by a diverse set of gene products. Thus far, the relationship between these two types of glycosylation has remained elusive, and it is unclear whether one influences the other via UDP-GlcNAc, which is a common donor substrate. Theoretically, a decrease in O-GlcNAcylation may increase the products of GlcNAc-branched N-glycans. In this study, via examination by lectin blotting, HPLC, and mass spectrometry analysis, however, we found that the amounts of GlcNAc-branched tri-antennary N-glycans catalyzed by N-acetylglucosaminyltransferase IV (GnT-IV) and tetra-antennary N-glycans were significantly decreased in O-GlcNAc transferase knockdown cells (OGT-KD) compared with those in wild type cells. We examined this specific alteration by focusing on SLC35A3, which is the main UDP-GlcNAc transporter in mammals that is believed to modulate GnT-IV activation. It is interesting that a deficiency of SLC35A3 specifically leads to a decrease in the amounts of GlcNAc-branched tri- and tetra-antennary N-glycans. Furthermore, co-immunoprecipitation experiments have shown that SLC35A3 interacts with GnT-IV, but not with N-acetylglucosaminyltransferase V. Western blot and chemoenzymatic labeling assay have confirmed that OGT modifies SLC35A3 and that O-GlcNAcylation contributes to its stability. Furthermore, we found that SLC35A3-KO enhances cell spreading and suppresses both cell migration and cell proliferation, which is similar to the phenomena observed in the OGT-KD cells. Taken together, these data are the first to demonstrate that O-GlcNAcylation specifically governs the biosynthesis of tri- and tetra-antennary N-glycans via the OGT-SLC35A3-GnT-IV axis.
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Acetilglucosamina/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Polissacarídeos/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Glicosilação , Células HEK293 , Células HeLa , HumanosRESUMO
Rapid industrialization has inevitably led to serious air pollution problems, thus it is urgent to develop detection and treatment technologies for qualitative and quantitative analysis and efficient removal of harmful pollutants. Notably, the employment of functional nanomaterials, in sensing and photocatalytic technologies, is promising to achieve efficient in situ detection and removal of gaseous pollutants. Among them, carbon dots (CDs) have shown significant potential due to their superior properties, such as controllable structures, easy surface modification, adjustable energy band, and excellent electron-transfer capacities. Moreover, their environmentally friendly preparation and efficient capture of solar energy provide a green option for sustainably addressing environmental problems. Here, recent advances in the rational design of CDs-based sensors and photocatalysts are highlighted. An overview of their applications in air pollutants detection and photocatalytic removal is presented, especially the diverse sensing and photocatalytic mechanisms of CDs are discussed. Finally, the challenges and perspectives are also provided, emphasizing the importance of synthetic mechanism investigation and rational design of structures.
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Poluentes Atmosféricos , Poluentes Ambientais , Nanoestruturas , Carbono , GasesRESUMO
BACKGROUND: Inflammation is a necessary component of chronic kidney disease (CKD) that can be attributed to an accumulation of toxins and a reduced clearance of proinflammatory cytokines. Procalcitonin (PCT) is a widely applied biomarker in the diagnosis of infection, and considering the presence of pre-existing inflammation in CKD patients, the PCT level could be high in such a population; however, no reference value for PCT in CKD patients has been available to date. METHODS: During the present study period, 361 CKD patients and 119 healthy controls were included. The PCT level and other biochemistry parameters were assayed by using a COBAS system. Statistical analysis was conducted to compare the differences in PCT levels and other biochemistry parameters between the two groups, and linear regression was used to assess the correlation between two variables. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of PCT and the optimal cutoff value to differentiate between CKD patients and healthy controls. RESULTS: The PCT level in CKD patients was significantly higher than that in healthy controls, and among the CKD patients, the PCT level was increased with advanced clinical stage. Moreover, PCT was moderately correlated with CysC. The optimal off-value was 0.075 with a sensitivity of 94.7% and specificity of 90.8%. CONCLUSION: The PCT level was significantly higher in CKD patients than in healthy controls, and the reference value for CKD patients should be adjusted to avoid unnecessary antibiotic treatments which may pose a negative impact on residual renal function.
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Biomarcadores/sangue , Pró-Calcitonina/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Infecções/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Curva ROC , Insuficiência Renal Crônica/terapiaRESUMO
The proliferation and adhesion abilities of placental trophoblasts are critical for embryo implantation and successful pregnancy. Protein O-fucosyltransferase 1 (poFUT1) and the transcription factor c-Fos/c-Jun have been found to promote trophoblastic cell invade into the endometrium. Progesterone is critical to the regulation of embryonic implantation. However, the exact role of poFUT1 in embryo proliferation and adhesion to the endometrium, and the relationship between progesterone, c-Fos/c-Jun, and poFUT1 has not been studied in detail. In the current study, we found that the serum levels of poFUT1 and progesterone significantly was decreased in miscarriage patients compared with those in normal pregnancy women, and there is a positive correlation between the changes in progesterone and poFUT1. Employing a human embryo trophoblastic cell line (JAR), we showed that progesterone facilitated the activation of c-Fos/c-Jun. Using an electrophoretic mobility shift assay and chromatin immunoprecipitation, we confirmed that the specific transcription factor c-Fos/c-Jun regulated the poFUT1 promoter, which could enhance poFUT1 transcriptional activity, thus further increasing trophoblast cell proliferation and adhesion potential. Taking these findings together, progesterone upregulates poFUT1 expression via the specific transcription factor c-Fos/c-Jun, and then increase trophoblast cell proliferation and adhesion potential. poFUT1 and progesterone may be used together as potential markers of miscarriage, and they may be diagnostic and therapeutic targets for miscarriage.
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Implantação do Embrião/efeitos dos fármacos , Fucosiltransferases/genética , Progesterona/farmacologia , Aborto Espontâneo/sangue , Aborto Espontâneo/genética , Aborto Espontâneo/patologia , Adulto , Células Cultivadas , Implantação do Embrião/fisiologia , Feminino , Fucosiltransferases/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Gravidez , Progesterona/sangue , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Ativação Transcricional/efeitos dos fármacos , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Trofoblastos/patologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
Background: Gestational Diabetes Mellitus (GDM) significantly increases the risk of adverse pregnancy outcomes, including elective pre-labor cesarean deliveries. Postoperative surgical site infections (SSIs) pose a significant concern, underscoring the need for a detailed investigation into their causes and preventative measures. The aim of this study is to systematically identify and analyze the microbial etiology and antimicrobial resistance profiles of pathogens responsible for SSIs in GDM patients undergoing elective pre-labor cesarean deliveries. Additionally, this research aims to elucidate the risk factors contributing to SSIs, with a specific focus on operation duration, amniotic fluid contamination, and genital tract inflammation, and their correlation with the incidence of SSIs. Methods: A retrospective analysis was conducted at our Hospital between September 2018 and July 2023, involving 150 GDM patients who underwent elective pre-labor cesarean deliveries. Patients were categorized into infected and uninfected groups based on postoperative SSIs. Clinical data were meticulously collected and analyzed using SPSS software (version 27.0). Independent sample t-tests and chi-square tests were employed for statistical analysis. Results: Microbial profiling revealed that Gram-negative bacteria, primarily E. coli, constituted approximately 59.46% of the isolated strains, exhibiting significant resistance to commonly used antibiotics such as ampicillin and cefotaxime. Elevated levels of biomarkers, including Procalcitonin (PCT) and Hemoglobin A1c (HbA1c), were significantly associated with SSIs. Multivariate logistic regression analysis identified operation time ≥1-hour, amniotic fluid contamination, and genital tract inflammation as significant risk factors. Conclusion: This study highlights the microbial etiology, resistance patterns, and risk factors for SSIs in GDM cesarean patients, emphasizing the need for tailored preoperative evaluations.
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BACKGROUND: Perinatal exposure to maternal obesity predisposes offspring to develop obesity later in life. Immune dysregulation in the hypothalamus, the brain center governing energy homeostasis, is pivotal in obesity development. This study aimed to identify key candidate genes associated with the risk of offspring obesity in maternal obesity. METHODS: We obtained obesity-related datasets from the Gene Expression Omnibus (GEO) database. GSE135830 comprises gene expression data from the hypothalamus of mouse offspring in a maternal obesity model induced by a high-fat diet model (maternal high-fat diet (mHFD) group and maternal chow (mChow) group), while GSE127056 consists of hypothalamus microarray data from young adult mice with obesity (high-fat diet (HFD) and Chow groups). We identified differentially expressed genes (DEGs) and module genes using Limma and weighted gene co-expression network analysis (WGCNA), conducted functional enrichment analysis, and employed a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to pinpoint candidate hub genes for diagnosing obesity-associated risk in offspring of maternal obesity. We constructed a nomogram receiver operating characteristic (ROC) curve to evaluate the diagnostic value. Additionally, we analyzed immune cell infiltration to investigate immune cell dysregulation in maternal obesity. Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro. RESULTS: The GSE135830 dataset revealed 2868 DEGs between the mHFD offspring and the mChow group and 2627 WGCNA module genes related to maternal obesity. The overlap of DEGs and module genes in the offspring with maternal obesity in GSE135830 primarily enriched in neurodevelopment and immune regulation. In the GSE127056 dataset, 133 DEGs were identified in the hypothalamus of HFD-induced adult obese individuals. A total of 13 genes intersected between the GSE127056 adult obesity DEGs and the GSE135830 maternal obesity module genes that were primarily enriched in neurodevelopment and the immune response. Following machine learning, two candidate hub genes were chosen for nomogram construction. Diagnostic value evaluation by ROC analysis determined Sytl4 and Kncn2 as hub genes for maternal obesity in the offspring. A gene regulatory network with transcription factor-miRNA interactions was established. Dysregulated immune cells were observed in the hypothalamus of offspring with maternal obesity. Expression of Sytl4 and Kncn2 was validated in a mouse model of hypothalamic inflammation and a palmitic acid-stimulated microglial inflammation model. CONCLUSION: Two candidate hub genes (Sytl4 and Kcnc2) were identified and a nomogram was developed to predict obesity risk in offspring with maternal obesity. These findings offer potential diagnostic candidate genes for identifying obesity-associated risks in the offspring of obese mothers.
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MicroRNAs , Obesidade Materna , Humanos , Gravidez , Adulto Jovem , Feminino , Animais , Camundongos , Obesidade/genética , Biologia Computacional , InflamaçãoRESUMO
Venetoclax is a potent inhibitor that specifically targets B-cell lymphoma-2 (BCL-2), which has been demonstrated to be effective in preclinical studies utilizing acute myeloid leukemia (AML) cell lines and xenograft models. Significant antileukemic activity was also observed in clinical trials, both as a monotherapy and in combination with other drugs. This novel therapeutic approach has revolutionized the treatment prospects for AML patients with unfavorable prognoses and those who are unable to tolerate intensive chemotherapy. Nevertheless, further investigations are required to establish the optimal dosing, sequencing, and combinational strategies of venetoclax for AML treatments. Additionally, identifying biomarkers is crucial for predicting response and resistance to this targeted intervention. In this review, we provide an overview of venetoclax-based therapy for AML and explore potential avenues for future research.
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Leucemia Mieloide Aguda , Proteínas Proto-Oncogênicas c-bcl-2 , Humanos , Adulto , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêuticoRESUMO
Active oxygen species (AOS) play an essential role in modulating the activity of activated coke (AC) based samples. In this paper, AC was endowed with abundant AOS by modifying with (NH4)2S2O8 and MnOx-FeOx for Hg0 removal. (NH4)2S2O8 treatment induced abundant micropores and oxygen-containing functional groups, and thus provided more anchoring sites for the dispersion of MnOx-FeOx. The synergy of MnOx-FeOx and interaction between MnOx-FeOx and NAC support contributed to a larger surface area, highly-dispersed active components, stronger reducibility, and more metal ions with high valence of MnFe/NAC. The optimal MnFe/NAC exhibited superior Hg0 removal efficiency above 90% at 120â¼180 â, as well as excellent performance for simultaneous removal of Hg0 and NO, and 600 ppm SO2 and 8 vol.% H2O addition led to a slight deterioration. XPS and Hg-TPD revealed that mercury adsorbed on MnFe/NAC included phy-Hg, C=O-Hg, COO-Hg, and OL-HgO. Besides, the priority of AOS for Hg0 chemisorption was C=O > COO- > OL, and Hg2+ was also detected in the outlet. Moreover, the SO2-poisoning effect was ascribed to the sulfation of MnOx and the occupation of COO- and C=O, and FeOx incorporation enhanced the SO2-resistance through weakening SO2 adsorption on C=O and COO-. The motivation of O2 mainly contributed to the regeneration of AOS, especially OL. The excellent regeneration performance and stability further affirmed the application potential of MnFe/NAC for Hg0 capture from coal-fired flue gas.
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Coque , Mercúrio , Sulfato de Amônio , Dióxido de Carbono , Catálise , Compostos Férricos , Ferro , Manganês , Óxidos/química , Oxigênio , Espécies Reativas de Oxigênio , Compostos de Enxofre/química , Dióxido de EnxofreRESUMO
Transition metal oxides have high photothermal conversion capacity and excellent thermal catalytic activity, and their photothermal catalytic ability can be further improved by reasonably inducing the photoelectric effect of semiconductors. Herein, Mn3O4/Co3O4 composites with S-scheme heterojunctions were fabricated for photothermal catalytic degradation of toluene under ultraviolet-visible (UV-Vis) light irradiation. The distinct hetero-interface of Mn3O4/Co3O4 effectively increases the specific surface area and promotes the formation of oxygen vacancies, thus facilitating the generation of reactive oxygen species and migration of surface lattice oxygen. Theoretical calculations and photoelectrochemical characterization demonstrate the existence of a built-in electric field and energy band bending at the interface of Mn3O4/Co3O4, which optimizes the photogenerated carriers' transfer path and retains a higher redox potential. Under UV-Vis light irradiation, the rapid transfer of electrons between interfaces promotes the generation of more reactive radicals, and the Mn3O4/Co3O4 shows a substantial improvement in the removal efficiency of toluene (74.7%) compared to single metal oxides (53.3% and 47.5%). Moreover, the possible photothermal catalytic reaction pathways of toluene over Mn3O4/Co3O4 were also investigated by in situ DRIFTS. The present work offers valuable guidance toward the design and fabrication of efficient narrow-band semiconductor heterojunction photothermal catalysts and provides deeper insights into the mechanism of photothermal catalytic degradation of toluene.
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ABSTRACTThrombocytopenia is one of the most common hematological adverse reactions in chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKI) therapy, causing life-threatening bleeding cases. However, there are fewer therapeutic drugs for TKI-induced thrombocytopenia. Eltrombopag is a non-peptide thrombopoietin receptor agonist used for the treatment of immune thrombocytopeniaï¼ aplastic anemia, and hepatitis C-associated thrombocytopenia. Nevertheless, studies of eltrombopag for TKI-induced thrombocytopenia are still lacking. This study retrospectively analyzed the clinical and test data of 21 CML patients with TKI-related thrombocytopenia. The results demonstrated that the median baseline value of thrombocytopenia in the 21 CML patients was 15.57 × 109/L [2-28 × 109/L]. Following treatment with eltrombopag, 16 patients had a significant increase in their platelet levels. The peak median for platelet increase in effective responders was 145.12 × 109/L (51-460 × 109/L). However, 5 patients failed to respond to eltrombopag. Moreover, 4 of the 21 patients enrolled had adverse reactions, including reversible liver function impairment, palpitation, headache, insomnia, and loss of appetite. Nonetheless, no cases of disease progression, thrombotic events, or myelofibrosis were observed. Hence, eltrombopag may be a useful adjunctive therapy for relieving TKI-related thrombocytopenia in patients with CML.
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Leucemia Mielogênica Crônica BCR-ABL Positiva , Trombocitopenia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Estudos Retrospectivos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
A 26-year-old man who had inhaled a dried pepper 7 years previously was admitted to our hospital for repeated coughing with yellow sputum and occasional hemoptysis. A thoracic high-resolution computed tomography scan revealed a foreign body at the proximal end of the right lower bronchus. We attempted to remove the foreign body by flexible bronchoscopy, but this was unsuccessful because the foreign body fell deeper into the bronchus. After a multidisciplinary team meeting, the foreign body was successfully extracted by bronchoscope suction and forceps under conscious sedation with spontaneous respiration. We avoided rigid bronchoscopy and traumatic surgery, thus decreasing the patient's risk and cost. We herein share our successful experience with this case.
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Sedação Consciente , Corpos Estranhos , Adulto , Brônquios/diagnóstico por imagem , Brônquios/cirurgia , Broncoscopia , Sedação Consciente/efeitos adversos , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Humanos , Masculino , RespiraçãoRESUMO
BACKGROUND: Pancreatic carcinoma is one of the deadliest malignant diseases, in which the increased expression of α1,6-fucosyltransferase (FUT8), a sole enzyme responsible for catalyzing core fucosylation, has been reported. However, its pathological roles and regulatory mechanisms remain largely unknown. Here, we use two pancreatic adenocarcinoma cell lines, MIA PaCa-2 and PANC-1 cells, as cell models, to explore the relationship of FUT8 with the malignant transformation of PDAC. METHODS: FUT8 knockout (FUT8-KO) cells were established by the CRISPR/Cas9 system. Cell migration was analyzed by transwell and wound-healing assays. Cell proliferation was examined by MTT and colony-formation assays. Cancer stemness markers and spheroid formations were used to analyzed cancer stemness features. RESULTS: Deficiency of FUT8 inhibited cell migration and proliferation in both MIA PaCa-2 and PANC-1 cells compared with wild-type cells. Moreover, the expression levels of cancer stemness markers such as EpCAM, CXCR4, c-Met, and CD133 were decreased in the FUT8-KO cells compared with wild-type cells. Also, the spheroid formations in the KO cells were loose and unstable, which could be reversed by restoration with FUT8 gene in the KO cells. Additionally, FUT8-KO increased the chemosensitivity to gemcitabine, which is the first-line therapy for advanced pancreatic cancer. CONCLUSIONS: FUT8-KO reduced the cell proliferation and migration. Our results are the first to suggest that the expression of FUT8 is involved in regulating the stemness features of pancreatic cancer cells. GENERAL SIGNIFICANCE: FUT8 could provide novel insights for the treatment of pancreatic carcinoma.
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Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Movimento Celular , Fucosiltransferases/metabolismo , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Feminino , Fucosiltransferases/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. However, its genetic characteristics in the Chinese population have not been extensively profiled. Here we screened 27 Chinese patients and preformed whole-genome sequencing to dissect their genomic patterns. We found that 18.5% (5/27) tumors harbored non-protein coding mutations on FOXA1. Besides, novel focal amplifications/deletions involving ZBTB7B, SLC4A4, TBX18, CYSLTR2 and EFNA5 were frequently present in tumors. Notably, group specificity of base substitution signature B displayed a strong link to hotspot mutations on SPOP gene. Furthermore, based on six rearrangement signatures, tumors were assigned to five subgroups that revealed different biological mechanisms. Of which, tandem duplicator subgroup harbored all CDK12 mutations, small deletor subgroup owned 75% TP53 changes, and large deletor subgroup had 66.7% SPOP mutations. Taken together, we provide a comprehensive view of genomic patterns which affect the critical cell regulators of PCa in the Chinese population. Our findings may provide valuable insights for designing specific treatments for Chinese patients with PCa.
Assuntos
Mutação , Neoplasias da Próstata/genética , Sequenciamento Completo do Genoma , Humanos , MasculinoRESUMO
Uterine angiogenesis and vascular remodeling play critical roles in determing the normal menstrual cycle and successful pregnancy. Poor uterine angiogenesis usually results in pregnancy failure. Protein O-fucosyltransferase 1 (poFUT1) is the key enzyme responsible for O-fucosylated glycan biosynthesis on glycoproteins. However, the dynamic expression and regulation of poFUT1 on the uterine angiogenesis and vascular remodeling remain unknown. Here, we showed that the enlargement of the vascular lumen in the secretory phase was greater than that in the proliferative phase of the uterine endometrium during menstrual cycle; whereas there was a narrower vessel lumen and fewer blood vessels in the decidua from miscarriage patients than in that from healthy pregnancy women. Additionally, the expression of poFUT1 was increased in the uterine endometrium during the secretory phase compared with that in the proliferation phase, and its expression was decreased in the uterus of miscarriage patients compared with that of the healthy pregnancy women. Using hESCs and a mouse model, we demonstrated that poFUT1 increased the O-fucosylation on uPA, and activated of the RhoA signaling pathway, thus facilitating uterine angiogenesis and vascular remodeling. We also provide evidence that poFUT1 promotes hESCs angiogenesis by the decreased stemness of hESCs. These findings reveal a new insight into the uterine angiogenesis and vascular remodeling. The study suggests that poFUT1 could be seen as a novel potential diagnostic and therapeutic target for miscarriage.
Assuntos
Aborto Espontâneo/enzimologia , Endométrio/irrigação sanguínea , Endométrio/enzimologia , Glucosiltransferases/metabolismo , Neovascularização Patológica/enzimologia , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Aborto Espontâneo/metabolismo , Animais , Endométrio/citologia , Endométrio/metabolismo , Feminino , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Glucosiltransferases/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica/genética , Gravidez , Transdução de Sinais/fisiologia , Células Estromais/enzimologia , Células Estromais/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/química , Remodelação Vascular/genética , Remodelação Vascular/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
OBJECTIVE: To detect the levels of Treg, Th17, Th9 cells and expression of transforming growth factor-ß (TGF-ß), interleukin-17 (IL-17) and interleukin-9 (IL-9) in peripheral blood of patients with immune thrombocytopenia (ITP) and to explore its role in the pathogenesis of ITP. METHODS: Fifty-four patients with ITP (ITP group) and 40 healthy volunteers (control group) were selected in our hospital. The of Treg, Th17 and Th9 cells in peripheral blood of 2 groups were measured by flow cytometry, and the expression of cytokines, such as TGF-ß, IL-17 and IL-9 in the peripheral blood of 2 groups were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: The level of Treg cells in the peripheral blood of the ITP group was significantly decreased in comparison with the control group, while the levels of Th17 and Th9 cells significantly increased in comparison with the control group (all P<0.01). The expression of cytokine such as TGF-ß in the peripheral blood of the case group significantly decreased in comparison with the control group, while the expression levels of IL-17 and IL-9 significantly increased in comparison with the control group (P<0.01). The results of Pearson correlation analysis showed that there was a positive correlation between the level of Treg cells and platelet count (PLT) in peripheral blood of the ITP group (r=0.35, P<0.05), and there were negative correlation between the level rate of Th17, Th9 cells and Plt count (r=-0.37, -0.43, P<0.05); there was a positive correlation between the expression of the TGF-ß in the ITP group and Plt count (r=0.46, P<0.05), while the expression of IL-17 and IL-9 showed negative correlation with PLT (r=-0.48, -0.54, P<0.05). CONCLUSION: The percentage of Treg, Th17 and Th9 cells in the peripheral blood of patients with ITP is abnormal, and the expression of TGF-ß, IL-17 and IL-9 also is abnormal, which may play an important role in the pathogenesis of ITP.