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1.
Am J Respir Cell Mol Biol ; 70(5): 351-363, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38271683

RESUMEN

N6-methyladenosine (m6A) plays a role in various diseases, but it has rarely been reported in acute lung injury (ALI). The FTO (fat mass and obesity-associated) protein can regulate mRNA metabolism by removing m6A residues. The aim of this study was to examine the role and mechanism of the m6A demethylase FTO in LPS-induced ALI. Lung epithelial FTO-knockout mice and FTO-knockdown/overexpression human alveolar epithelial (A549) cell lines were constructed to evaluate the effects of FTO on ALI. Bioinformatics analysis and a series of in vivo and in vitro assays were used to examine the mechanism of FTO regulation. Rescue assays were conducted to examine whether the impact of FTO on ALI depended on the TXNIP/NLRP3 pathway. In LPS-induced ALI, RNA m6A modification amounts were upregulated, and FTO expression was downregulated. In vivo, lung epithelial FTO knockout alleviated alveolar structure disorder, tissue edema, and pulmonary inflammation and improved the survival of ALI mice. In vitro, FTO knockdown reduced A549 cell damage and death induced by LPS, whereas FTO overexpression exacerbated cell damage and death. Mechanistically, bioinformatics analysis revealed that TXNIP was a downstream target of FTO. FTO deficiency mitigated pyroptosis in LPS-induced ALI via the TXNIP/NLRP3 pathway. Rescue assays confirmed that the impact of FTO on the TXNIP/NLRP3 pathway was significantly reversed by the TXNIP inhibitor SRI-37330. Deficiency of FTO alleviates LPS-induced ALI via TXNIP/NLRP3 pathway-mediated alveolar epithelial cell pyroptosis, which might be a novel therapeutic strategy for combating ALI.


Asunto(s)
Lesión Pulmonar Aguda , Adenosina/análogos & derivados , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Células Epiteliales Alveolares , Proteínas Portadoras , Lipopolisacáridos , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/genética , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Humanos , Lipopolisacáridos/farmacología , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/patología , Piroptosis/efectos de los fármacos , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Ratones , Células A549 , Ratones Endogámicos C57BL , Tiorredoxinas/metabolismo , Tiorredoxinas/genética , Masculino , Transducción de Señal
2.
Chemphyschem ; 25(12): e202400039, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38526205

RESUMEN

In response to the global demand for sustainable energy solutions, the quest for stable and cost-effective hydrogen production has garnered significant attention in recent decades. Here, the emergence of layered metal phosphorus trichalcogenides (MPX3, M: transition metal, X: chalcogen) materials and their two-dimensional counterparts with customizable composition and electronic structure holds great promise for such purposes. In the present study, we successfully synthesized large-scale and high-quality FePS3, NiPS3, and an alloyed counterpart, Fe0.5Ni0.5PS3. Subsequent systematic investigations were conducted to probe their respective electronic structures and assess their hydrogen evolution reaction (HER) properties. Remarkably, our results unveiled the successful modulation of the bandgap for FexNiyPS3, ultimately bestowing it with the most favorable HER performance for Fe0.5Ni0.5PS3 when compared to the other two samples. Furthermore, our exploration into the evolution of the X-ray photoelectron spectroscopy (XPS) spectra demonstrated that the charge conversions of metal cations play a pivotal role in the HER reactions. This critical insight further enriches our understanding of the fundamental mechanisms governing the performance of the prepared layered MPX3-based electrocatalysts, thus facilitating a comprehensive and detailed analysis of the pre- and post-HER reactions. This work not only sheds light on the intricate interplay between composition, electronic structure, and catalytic performance in the realm of novel electrocatalysts, but also contributes to the broader scientific community's pursuit of sustainable and efficient hydrogen production.

3.
Funct Integr Genomics ; 23(3): 228, 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37423913

RESUMEN

Tumor-associated macrophages (TAMs) are pivotal components of tumor microenvironment (TME), and senescent TAMs contribute to the alternation of the profiles of TME. However, the potential biological mechanisms and the prognosis value of senescent macrophages are largely unknown, especially in bladder cancer (BLCA). Based on the single-cell RNA sequencing of a primary BLCA sample, 23 macrophage-related genes were identified. Genomic difference analysis, LASSO, and Cox regression were used to develop the risk model. TCGA-BLCA cohort (n = 406) was utilized as the training cohort, and then, three independent cohorts (n = 90, n = 221, n = 165) from Gene Expression Omnibus, clinical samples from the local hospital (n = 27), and in vitro cell experiments were used for external validation. Aldo-keto reductase family 1 member B (AKR1B1), inhibitor of DNA binding 1 (ID1), and transforming growth factor beta 1 (TGFB1I1) were determined and included in the predictive model. The model serves as a promising tool to evaluate the prognosis in BLCA (pooled hazard ratio = 2.51, 95% confidence interval = [1.43; 4.39]). The model was also effective for the prediction of immunotherapeutic sensitivity and chemotherapy treatment outcomes, which were further confirmed by IMvigor210 cohort (P < 0.01) and GDSC dataset, respectively. Twenty-seven BLCA samples from the local hospital proved that the risk model was associated with the malignant degree (P < 0.05). At last, the human macrophage THP-1 and U937 cells were treated with H2O2 to mimic the senescent process in macrophage, and the expressions of these molecules in the model were detected (all P < 0.05).Overall, a macrophage cell senescence-related gene signature was constructed to predict the prognosis, immunotherapeutic response, and chemotherapy sensitivity in BLCA, which provides novel insights to uncover the underlying mechanisms of macrophage senescence.


Asunto(s)
Peróxido de Hidrógeno , Neoplasias de la Vejiga Urinaria , Humanos , Macrófagos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Senescencia Celular , Inmunoterapia , Microambiente Tumoral/genética , Aldehído Reductasa
4.
Small ; 19(5): e2206127, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36440672

RESUMEN

The pursuit of single-assembled molecular cage reactors for complex tandem reactions is a long-standing target in biomimetic catalysis but still a grand challenge. Herein, nanozyme-like organic cages are reported by engineering air-stable radicals into the skeleton upon photoinduced electron transfer. The generation of radicals is accompanied by single-crystal structural transformation and exhibits superior stability over six months in air. Impressively, the radicals throughout the cage skeleton can mimic the peroxidase of natural enzymes to decompose H2 O2 into OH· and facilitate oxidation reactions. Furthermore, an integrated catalyst by encapsulating Au clusters (glucose oxidase mimics) into the cage has been developed, in which the dual active sites (Au cluster and radical) are spatially isolated and can work as cascade nanozymes to prominently promote the enzyme-like tandem reaction via a substrate channeling effect.

5.
Cytotherapy ; 25(11): 1176-1185, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37516947

RESUMEN

BACKGROUND AIMS: Extracellular vesicles and exosome-mimetic nanovesicles (NVs) derived from mesenchymal stromal cells (MSCs) have emerged as promising to promote hair growth. However, short local skin retention after subcutaneous administration hinders their clinical applications. METHODS: In this study, we prepared magnetic nanovesicles (MNVs) from iron oxide nanoparticle-incorporated MSCs. MNVs contained more therapeutic growth factors than NVs derived from naive MSCs, and their localization and internalization were manipulated by external magnetic field. RESULTS: Following the subcutaneous injection of MNVs into a mouse model of depilation-induced hair regeneration, the magnetic attraction increased their skin retention. Then, the cellular proliferation and ß-catenin signaling in hair follicles (HF) were markedly enhanced by MNV injection and magnetic field application. Furthermore, an acceleration of HF growth was revealed by histological analysis. CONCLUSIONS: The proposed strategy can enhance the therapeutic potential of MSC-derived NVs for hair regeneration and other dermatological diseases.


Asunto(s)
Folículo Piloso , Células Madre Mesenquimatosas , Ratones , Animales , Folículo Piloso/metabolismo , Piel , Células Madre Mesenquimatosas/metabolismo , Proliferación Celular , Fenómenos Magnéticos
6.
J Biochem Mol Toxicol ; 37(4): e23301, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36644941

RESUMEN

This study investigates the therapeutic effect and the underlying mechanisms of ergothioneine (EGT) on the testicular damage caused by varicocele (VC) in vivo, in vitro, and in silico. This preclinical study combines a series of biological experiments and network pharmacology analyses. A total of 18 Sprague Dawley (SD) male rats were randomly and averagely divided into three groups: the sham-operated, VC model, and VC model with EGT treatment (VC + EGT) groups. The left renal vein of the VC model and the VC + EGT groups were half-ligated for 4 weeks. Meanwhile, the VC + EGT group was intragastrically administrated with EGT (10 mg/kg). GC1 and GC2 cells were exposed to H2 O2 with or without EGT treatment to re-verify the conclusion. The structure disorder of seminiferous tubules ameliorated the apoptosis decrease in the VC rats receiving EGT. EGT can also increase the sperm quality of the VC model rats (p < 0.05). The exposure to H2 O2 decreased proliferation and increased apoptosis of GC1 and GC2 cells, which was revisable by adding EGT to the plates (p < 0.05). The network pharmacology and molecular docking were conducted to explore the potential targets of EGT in VC, and HSP90AA1 was identified as the pivotal gene, which was validated by western blot, immunohistochemistry, and RT-qPCR both in vivo and in vitro (p < 0.05). Overall, EGT attenuates the testicular injury in the VC model both in vivo and in vitro by potentially potentiating the expression of HSP90AA1.


Asunto(s)
Ergotioneína , Varicocele , Humanos , Ratas , Masculino , Animales , Ergotioneína/farmacología , Ratas Sprague-Dawley , Varicocele/tratamiento farmacológico , Varicocele/metabolismo , Simulación del Acoplamiento Molecular , Semen/metabolismo , Testículo/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/uso terapéutico
7.
Angew Chem Int Ed Engl ; 62(12): e202215591, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36691958

RESUMEN

Multiple charge separation has been successfully realized by a proton-coupled electron transfer reaction in an organic cocrystal. Benefiting from the adjustable electronic energy level of the electron donor and acceptor through thermal-induced proton migration, distinct optical absorption behaviors combined with color changes to blue or green are observed in these charge-separated states. It is of interest to note that such charge-separated states exhibit a longer lifetime of over a month as a result of the excellent coplanarity and π-π interaction of the electron acceptors. Moreover, the enhanced absorption toward longer wavelengths endows the charge-separated state with near-infrared (808 nm) photothermal conversion for imaging and bacterial inhibition, whereby the conversion performance can be controlled by the degree of proton migration.

8.
Fish Shellfish Immunol ; 130: 332-341, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36115605

RESUMEN

Grass carp (Ctenopharyngodon idella) is the largest economic fish in freshwater culture in China, which is predisposed to infectious diseases under high temperature. Under the background of global warming, the industrialization of the Pearl River Delta region has led to aggravated thermal pollution, which has increasingly serious impacts on the aquatic ecological environment. This will result in more frequent exposure of grass carp to overheated water temperatures. Previous studies have only identified the regulatory genes of fish that respond to pathogens or temperature stress, but the transcriptional response to both is unknown. In this study, the histopathological analysis showed heat stress exacerbated spleen damage induced by Aeromonas hydrophila. The transcriptional responses of the spleens from A. hydrophila lipopolysaccharide (LPS) -injected grass carp undergoing heat stress and at normal temperatures for 6, 24, and 72 h were investigated by mRNA and microRNA sequencing. We identified 28, 20, and 141 differentially expressed (DE) miRNAs and 126, 383, and 4841 DE mRNAs between the two groups after 6, 24, and 72 h, respectively. There were 67 DE genes mainly involved in the cytochrome P450 pathway, antioxidant defense, inflammatory response, pathogen recognition pathway, antigen processing and presentation, and the ubiquitin-proteasome system. There were 5 DE miRNAs involved in regulating apoptosis and inflammation. We further verified 17 DE mRNAs and 5 DE miRNAs using quantitative real-time PCR. Based on miRNAs and mRNAs analysis, continuous heat stress will affect the antibacterial responses of grass carp spleens, resulting in aggravation of spleen injury. Together, these results provide data for further understanding of the decreased tolerance of fish to pathogen infection in persistent high-temperature environments.


Asunto(s)
Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , MicroARNs , Aeromonas hydrophila/fisiología , Animales , Antibacterianos , Antioxidantes , Carpas/genética , Carpas/metabolismo , Proteínas de Peces , Respuesta al Choque Térmico , Inmunidad Innata/genética , Lipopolisacáridos/farmacología , MicroARNs/genética , Complejo de la Endopetidasa Proteasomal , ARN Mensajero/metabolismo , Ubiquitinas , Agua
9.
Cancer Cell Int ; 21(1): 660, 2021 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-34895217

RESUMEN

BACKGROUND: In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear. METHODS: Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses. RESULTS: ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/ß-catenin pathway. CONCLUSIONS: This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.

10.
Jpn J Clin Oncol ; 50(4): 456-464, 2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-31894237

RESUMEN

BACKGROUND: Cadherin-11 (CDH11) is a type II cadherin and reported to function as an oncogene in various cancers. Our present study aims to investigate the role of CDH11 in bladder cancer (BCA). METHODS: Bioinformatics analysis was performed in four independent microarray data including 56 non-muscle-invasive bladder cancer (NMIBC) and 132 muscle-invasive bladder cancer (MIBC) tissues from Gene Expression Omnibus to screen out differentially expressed genes. Next, we detected CDH11 expression in BCA specimens and cell lines by qPCR and western blotting assays. Immunohistochemical analyses were performed in 209 paraffin-embedded BCA samples and 30 adjacent normal bladder tissues. RESULTS: Bioinformatics analysis revealed that CDH11 had a higher expression level in MIBC tissues than in NMIBC, which was consistent with our clinical BCA specimens and cell lines at both mRNA and protein levels. Immunohistochemical analysis demonstrated that over-expression of CDH11 was closely related to the histological grade, pT status, tumour size and poor outcomes of BCA patients. What's more, CDH11 (area under curve (AUC) = 0.673 and 0.735) had a better predictive value than E-cadherin (AUC = 0.629 and 0.629) and a similar discrimination with the European Organization for Research and Treatment of Cancer (EORTC) score system (AUC = 0.719 and 0.667) in evaluating potential recurrence and progression of NMIBC. Moreover, combination of CDH11 and EORTC score system was the best predictive model in predicting recurrence of NMIBC (AUC = 0.779) among the three models. CONCLUSIONS: CDH11 was a reliable therapeutic target in BCA and a useful index to predict the possibilities of recurrence and progression in NMIBC patients.


Asunto(s)
Cadherinas/metabolismo , Músculos/patología , Recurrencia Local de Neoplasia/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Anciano , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/genética , Valor Predictivo de las Pruebas , Pronóstico , Regulación hacia Arriba/genética , Neoplasias de la Vejiga Urinaria/genética
11.
Urol Int ; 104(3-4): 230-238, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31770767

RESUMEN

OBJECTIVE: To investigate the optimal age for the baseline serum prostate-specific antigen (PSA) test and for repeat screening and its economic burden in a single center in China. MATERIALS AND METHODS: 35,533 men with PSA screening were retrospectively enrolled in this study. Follow-ups were conducted in 1,586 men with PSA >4 ng/mL, and receiver-operating characteristic (ROC) curves were employed to investigate the optimal cutoffs. RESULTS: ROC analysis indicated that the optimal age for initial PSA screening was 57.5 years (AUC = 0.84), 62.5 years (AUC = 0.902), 60.5 years (AUC = 0.909), and 61.5 years (AUC = 0.890) for individuals with PSA >4 and >10 ng/mL, a diagnosis of prostate cancer (PCa), and clinically significant PCa defined as the focus events, respectively. For Chinese men aged 50-59, 60-69, and >70 years, the initial PSA levels of 1.305 ng/mL (AUC = 0.699), 1.975 ng/mL (AUC = 0.711), and 2.740 ng/mL (AUC = 0.720) might have a PSA velocity >0.75 ng/mL per year during the follow-up. In addition, the total cost amounts to CNY 13,609,260 in these cases, but only 60 of the 35,533 (0.17%) men gained benefit from PSA screening. CONCLUSION: In our opinion, the optimal starting age for initial PSA testing was 57.5 years. The necessity for repeat screening should be based on the first PSA level depending on age. A cost--benefit analysis should be included in population-based screening.


Asunto(s)
Detección Precoz del Cáncer/economía , Detección Precoz del Cáncer/estadística & datos numéricos , Antígeno Prostático Específico/sangre , Antígeno Prostático Específico/economía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo
12.
Angew Chem Int Ed Engl ; 59(49): 22109-22116, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32748542

RESUMEN

The capability to significantly shorten the synthetic period of a broad spectrum of open organic materials presents an enticing prospect for materials processing and applications. Herein we discovered 1,2,4-triazolium poly(ionic liquid)s (PILs) could serve as a universal additive to accelerate by at least one order of magnitude the growth rate of representative imine-linked crystalline open organics, including organic cages, covalent organic frameworks (COFs), and macrocycles. This phenomenon results from the active C5-protons in poly(1,2,4-triazolium)s that catalyze the formation of imine bonds, and the simultaneous salting-out effect (induced precipitation by decreasing solubility) that PILs exert on these crystallizing species.

13.
J Cell Mol Med ; 23(3): 1852-1864, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30515972

RESUMEN

Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumours, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of their specific association with NSCLC have not been fully elucidated. Here, we report that a cytoplasmic lncRNA, DUXAP9-206 is overexpressed in NSCLC cells and closely related to NSCLC clinical features and poor patient survival. We reveal that DUXAP9-206 induced NSCLC cell proliferation and metastasis by directly interacting with Cbl-b, an E3 ubiquitin ligase, and reducing the degradation of epidermal growth factor receptor (EGFR) and thereby augmenting EGFR signaling in NSCLC. Notably, correlations between DUXAP9-206 and activated EGFR signaling were also validated in NSCLC patient specimens. Collectively, our findings reveal the novel molecular mechanisms of DUXAP9-206 in mediating the progression of NSCLC and DUXAP9-206 may serve as a potential target for NSCLC therapy.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/secundario , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas c-cbl/metabolismo , ARN Largo no Codificante/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Movimiento Celular , Proliferación Celular , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Pronóstico , Proteínas Proto-Oncogénicas c-cbl/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Angew Chem Int Ed Engl ; 58(40): 14197-14201, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31385423

RESUMEN

Bimetal-S-O composites have been rarely researched in electrochemical reduction of CO2 . Now, an amorphous Ag-Bi-S-O decorated Bi0 catalyst derived from Ag0.95 BiS0.75 O3.1 nanorods by electrochemical pre-treatment was used for catalyzing eCO2 RR, which exhibited a formate FE of 94.3 % with a formate partial current density of 12.52 mA cm-2 at an overpotential of only 450 mV. This superior performance was attributed to the attached amorphous Ag-Bi-S-O substance. S could be retained in the amorphous region after electrochemical pre-treatment only in samples derived from metal-S-O composites, and it would greatly enhance the formate selectivity by accelerating the dissociation of H2 O. The existence of Ag would increase the current density, resulting in a higher local pH, which made the role of S in activating H2 O more significantly and suppressed H2 evolution more effectively, thus endowing the catalyst with a higher formate FE at low overpotentials.

15.
Zhonghua Nan Ke Xue ; 22(11): 963-967, 2016 Nov.
Artículo en Zh | MEDLINE | ID: mdl-29281201

RESUMEN

OBJECTIVE: To investigate the changes in the percentage of myeloid-derived suppressor cells (MDSCs) in the peripheral blood of prostate cancer (PCa) patients and explore the correlation of MDSCs and their subsets with the prognosis of PCa. METHODS: Using flow cytometry, we determined the percentage of MDSCs and the levels of Arg-1, iNOS and PD-L1 in the peripheral blood of 32 PCa patients and 25 healthy controls, detected the distribution of CD14+ Mo-MDSC and CD15+ PMN-MDSC subsets, and analyzed the correlation between the obtained parameters and the prognosis of PCa. RESULTS: Compared with the healthy controls, the PCa patients showed significant increases in the percentage of MDSCs (P<0.01) and levels of Arg-1, iNOS and PD-L1 in the peripheral blood. Statistically significant differences were observed in the distribution of the CD14+ Mo-MDSC and CD15+ PMN-MDSC subsets between the two groups(60.4% vs 72.2%, 29.5% vs 18.8%) (P<0.05). The percentages of MDSCs and Mo-MDSCs were remarkably correlated with the total survival rate of the PCa patients (P=0.025 and 0.017). CONCLUSIONS: The percentages of MDSCs and CD14+ Mo-MDSCs in the peripheral blood were correlated with the prognosis of PCa, which may provide a target or some evidence for the clinical treatment of PCa.


Asunto(s)
Células Supresoras de Origen Mieloide/citología , Neoplasias de la Próstata/fisiopatología , Arginasa/sangre , Antígeno B7-H1/sangre , Estudios de Casos y Controles , Citometría de Flujo , Humanos , Masculino , Óxido Nítrico Sintasa de Tipo II/sangre , Pronóstico , Neoplasias de la Próstata/sangre
16.
Biol Reprod ; 92(1): 28, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25505194

RESUMEN

Cysteine-rich secretory protein 2 (CRISP2) is an important sperm protein and plays roles in spermatogenesis, modulation of flagellar motility, acrosome reaction, and gamete fusion. Clinical evidence shows a reduced CRISP2 expression in spermatozoa from asthenozoospermic patients, but the molecular mechanism underlying its reduction remains unknown. Herein, we carried out a study focusing on the CRISP2 reduction and its roles in asthenozoospermia. Initially, through analyzing CRISP2 expression and methylation on CRISP2 promoter activity in sperm, we observed a decreased expression of CRISP2 protein rather than its mRNA in the ejaculated spermatozoa from asthenozoospermic patients and no methylation in the CRISP2 promoter, suggesting CRISP2 expression may be regulated in the sperm at the posttranscriptional level. Subsequently, we found that microRNA 27b (miR-27b), predicted as a candidate regulator of CRISP2 using bioinformatics, was highly expressed in the ejaculated spermatozoa from asthenozoospermic patients. Luciferase reporter assay and transfection experiments disclosed that this microRNA could target CRISP2 by specifically binding its 3' untranslated region, suppressing CRISP2 expression. Extended clinical observation further confirmed a highly expressed miR-27b and its obviously negative correlation with CRISP2 protein expression in ejaculated spermatozoa samples from asthenozoospermic patients. Finally, we conducted a retrospective follow-up study to support that either high miR-27b expression or low CRISP2 protein expression was significantly associated with low sperm progressive motility, abnormal morphology, and infertility. Thus, this study provides the first preliminary insight into the mechanism leading to the reduced CRISP2 expression in asthenozoospermia, offering a potential therapeutic target for treating male infertility or for male contraception.


Asunto(s)
Astenozoospermia/genética , Glicoproteínas/genética , MicroARNs/genética , Espermatozoides/metabolismo , Adulto , Astenozoospermia/metabolismo , Secuencia de Bases , Estudios de Casos y Controles , Moléculas de Adhesión Celular , Células Cultivadas , Metilación de ADN , Regulación de la Expresión Génica , Glicoproteínas/metabolismo , Humanos , Masculino , MicroARNs/metabolismo , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Estudios Retrospectivos , Adulto Joven
17.
Nat Commun ; 15(1): 2478, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509092

RESUMEN

Biological cell membrane featuring smart mass-transport channels and sub-10 nm thickness was viewed as the benchmark inspiring the design of separation membranes; however, constructing highly connective and adaptive pore channels over large-area membranes less than 10 nm in thickness is still a huge challenge. Here, we report the design and fabrication of sub-8 nm networked cage nanofilms that comprise of tunable, responsive organic cage-based water channels via a free-interface-confined self-assembly and crosslinking strategy. These cage-bearing composite membranes display outstanding water permeability at the 10-5 cm2 s-1 scale, which is 1-2 orders of magnitude higher than that of traditional polymeric membranes. Furthermore, the channel microenvironments including hydrophilicity and steric hindrance can be manipulated by a simple anion exchange strategy. In particular, through ionically associating light-responsive anions to cage windows, such 'smart' membrane can even perform graded molecular sieving. The emergence of these networked cage-nanofilms provides an avenue for developing bio-inspired ultrathin membranes toward smart separation.

18.
BMC Med Genomics ; 17(1): 153, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38840097

RESUMEN

BACKGROUND: Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown. METHODS: Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration. RESULTS: It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments. CONCLUSIONS: Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.


Asunto(s)
Anoicis , Biomarcadores de Tumor , Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Pronóstico , Anoicis/genética , Biomarcadores de Tumor/genética , MicroARNs/genética , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/metabolismo , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino , Estimación de Kaplan-Meier
19.
Small Methods ; : e2301468, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38295090

RESUMEN

The exploration of a facile approach to create structurally versatile substances carrying air-stable radicals is highly desired, but still a huge challenge in chemistry and materials science. Herein, a non-contact method to generate air-stable radicals by exposing pyridine/imidazole ring-bearing substances to volatile cyanuric chloride vapor, harnessed as a chemical fuel is reported. This remarkable feat is accomplished through a nucleophilic substitution reaction, wherein an intrinsic electron transfer event transpires spontaneously, originating from the chloride anion (Cl- ) to the cationic nitrogen (N+ ) atom, ultimately giving rise to pyridinium/imidazolium radicals. Impressively, the generated radicals exhibit noteworthy stability in the air over one month owing to the delocalization of the unpaired electron through the extended and highly fused π-conjugated pyridinium/imidazolium-triazine unit. Such an approach is universal to diverse substances, including organic molecules, metal-organic complexes, hydrogels, polymers, and organic cage materials. Capitalizing on this versatile technique, surface radical functionalization can be readily achieved across diverse substrates. Moreover, the generated radical species showcase a myriad of high-performance applications, including mimicking natural peroxidase to accelerate oxidation reactions and achieving high-efficiency near-infrared photothermal conversion and photothermal bacterial inhibition.

20.
Artículo en Inglés | MEDLINE | ID: mdl-38363328

RESUMEN

PURPOSE: This meta-analysis aimed to evaluate the performance of the Injury Severity Score (ISS), Trauma and Injury Severity Score (TRISS), and the Geriatric Trauma Outcome Score (GTOS) in predicting mortality in geriatric trauma patients. METHODS: The MEDLINE, Web of Science, and EMBASE databases were searched for studies published from January 2008 to October 2023. Studies assessing the performance of the ISS, TRISS, or GTOS in predicting mortality in geriatric trauma patients (over 60 years old) and reporting data for the analysis of the pooled area under the receiver operating characteristic curve (AUROC) and the hierarchical summary receiver operating characteristic curve (HSROC) were included. Studies that were not conducted in a group of geriatric patients, did not consider mortality as the outcome variable, or had incomplete data were excluded. The Critical Appraisal Skills Programme (CASP) Clinical Prediction Rule Checklist was utilized to assess the risk of bias in included studies. STATA 16.0. was used for the AUROC analysis and HSROC analysis. RESULTS: Nineteen studies involving 118,761 geriatric trauma patients were included. The pooled AUROC of the TRISS (AUC = 0.82, 95% CI: 0.77-0.87) was higher than ISS (AUC = 0.74, 95% CI: 0.71-0.79) and GTOS (AUC = 0.80, 95%CI: 0.77-0.83). The diagnostic odds ratio (DOR) calculated from HSROC curves also suggested that the TRISS (DOR = 21.5) had a better performance in predicting mortality in geriatric trauma patients than the ISS (DOR = 6.27) and GTOS (DOR = 4.76). CONCLUSION: This meta-analysis suggested that the TRISS showed better accuracy and performance in predicting mortality in geriatric trauma patients than the ISS and GTOS.

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