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1.
Biochem Biophys Res Commun ; 712-713: 149941, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38643718

RESUMEN

While diosgenin has been demonstrated effective in various cardiovascular diseases, its specific impact on treating heart attacks remains unclear. Our research revealed that diosgenin significantly improved cardiac function in a myocardial infarction (MI) mouse model, reducing cardiac fibrosis and cell apoptosis while promoting angiogenesis. Mechanistically, diosgenin upregulated the Hand2 expression, promoting the proliferation and migration of endothelial cells under hypoxic conditions. Acting as a transcription factor, HAND2 activated the angiogenesis-related gene Aggf1. Conversely, silencing Hand2 inhibited the diosgenin-induced migration of hypoxic endothelial cells and angiogenesis. In summary, these findings provide new insights into the protective role of diosgenin in MI, validating its effect on angiogenic activity and providing a theoretical basis for clinical treatment strategies.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Diosgenina , Ratones Endogámicos C57BL , Infarto del Miocardio , Neovascularización Fisiológica , Animales , Diosgenina/farmacología , Diosgenina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Neovascularización Fisiológica/efectos de los fármacos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Masculino , Ratones , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Humanos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Angiogénesis
2.
Artículo en Inglés | MEDLINE | ID: mdl-38606576

RESUMEN

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

3.
Gastric Cancer ; 27(1): 49-71, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37897508

RESUMEN

BACKGROUND: Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC. METHODS: OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays. RESULTS: In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway. CONCLUSIONS: In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.


Asunto(s)
MicroARNs , Neoplasias Gástricas , Humanos , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Glucólisis , MicroARNs/genética , Neoplasias Gástricas/genética
4.
Sleep Breath ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38772968

RESUMEN

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

5.
J Am Chem Soc ; 145(2): 1292-1300, 2023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36577119

RESUMEN

The DNA-origami technique has enabled the engineering of transmembrane nanopores with programmable size and functionality, showing promise in building biosensors and synthetic cells. However, it remains challenging to build large (>10 nm), functionalizable nanopores that spontaneously perforate lipid membranes. Here, we take advantage of pneumolysin (PLY), a bacterial toxin that potently forms wide ring-like channels on cell membranes, to construct hybrid DNA-protein nanopores. This PLY-DNA-origami complex, in which a DNA-origami ring corrals up to 48 copies of PLY, targets the cholesterol-rich membranes of liposomes and red blood cells, readily forming uniformly sized pores with an average inner diameter of ∼22 nm. Such hybrid nanopores facilitate the exchange of macromolecules between perforated liposomes and their environment, with the exchange rate negatively correlating with the macromolecule size (diameters of gyration: 8-22 nm). Additionally, the DNA ring can be decorated with intrinsically disordered nucleoporins to further restrict the diffusion of traversing molecules, highlighting the programmability of the hybrid nanopores. PLY-DNA pores provide an enabling biophysical tool for studying the cross-membrane translocation of ultralarge molecules and open new opportunities for analytical chemistry, synthetic biology, and nanomedicine.


Asunto(s)
Nanoporos , Liposomas/metabolismo , Membrana Celular/metabolismo , Difusión , ADN/química
6.
Lab Invest ; 103(9): 100210, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37406931

RESUMEN

Pheochromocytoma/paraganglioma (PPGL) is an endocrine-related tumor associated with excessive catecholamine release and has limited treatment options once metastasis occurs. Although recent phase 2 clinical trials of immune checkpoint inhibitors in the treatment of PPGL have preliminarily shown promising results, the fundamentals of immunotherapy for PPGL have not yet been established. In the early research, using bulk RNA sequencing of tumor samples from 7 PPGL patients, we found that PPGL tumor tissues exhibited high PD-L1 mRNA expression compared with adjacent normal adrenal medulla tissues, and this was related to T-cell exhaustion biomarkers. To further validate the association, in this study (n = 60), we first stratified all PPGL samples according to PD-L1 expression as determined by immunohistochemical staining, and then subjected 23 fresh PPGL tumor samples from the cohort to a quantitative polymerase chain reaction (n = 16), flow cytometry (n = 7), and multiplex-immunofluorescence staining. Subsequently, we evaluated the pathological manifestations of all 60 PPGL tumor samples and analyzed the correlation among PD-L1 expression, adverse pathological behavior, various clinicopathological data, and genotypes in PPGL. The results showed that PD-L1-positive expression correlated with the exhaustion of tumor-infiltrating T cells, preoperative abnormal elevation of plasma norepinephrine, high Ki67 index, and adverse pathological behavior in PPGL but not with genetic mutation or metastatic disease, possibly due to the limitation of the small number of patients with metastatic disease (n = 4) in the study cohort. In conclusion, our findings reveal that PD-L1 expression is associated with T-cell exhaustion and adverse pathological behavior in PPGL. These results are expected to provide a new theoretical basis and clinical guidance for the treatment of PPGL.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/genética , Antígeno B7-H1/genética , Agotamiento de Células T , Neoplasias de las Glándulas Suprarrenales/genética , Linfocitos Infiltrantes de Tumor
7.
Chemistry ; 29(28): e202300331, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-36853088

RESUMEN

The aqueous metal-sulfide batteries (AMSBs) have attracted research interest due to their high capacity, environmentally friendly qualities, and the accessibility of raw materials. However, the design strategies for metal-sulfide cathode have rarely been reported. Here, the copper-activated sphalerite in which Zn2+ is substituted by Cu2+ through ion exchange has been introduced for the first time as cathode for aqueous Cu/ZnS batteries. After sphalerite transformed to CuS, a two-step conversion of CuS→Cu7 S4 →Cu2 S storage mechanism has been proposed. At 0.7 A g-1 current density, the capacity can reach 532.4 mAh g-1 after 100 cycles. When cycled once at a current density of 35 mA g-1 , the initial reversible capacity can reach 461 mAh g-1 under 1 A g-1 . Furthermore, the assembled Zn//ZnS hybrid ion cell delivers an energy of up to 460 Wh kg-1 , which is better than for many AMSBs.

8.
Langmuir ; 39(33): 11782-11787, 2023 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-37562139

RESUMEN

Tile-based DNA self-assembly is a cost-effective fabrication method for large-scale nanopatterns. Herein, we report a protocol to directly assemble DNA 2D arrays on silicon wafers and then use the DNA nanostructures as molds to fabricate the corresponding nanostructures on the silicon wafers by hydrogen fluoride (HF) etching. Similar HF etching has been used with robust large DNA origami structures as templates. This work demonstrates that DNA nanostructures assembled from small tiles are sufficiently stable for this process. The resulting feature size (∼8.6 nm) approaches the sizes of e-beam lithography. While the reported method is parallel and inexpensive, e-beam lithography is a serial method and is expensive. We expect that this method will be very useful for preparing fine nanopatterns in large areas.


Asunto(s)
Nanoestructuras , Silicio , Silicio/química , Porosidad , Nanoestructuras/química , ADN/química
9.
Pak J Med Sci ; 39(6): 1847-1852, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37936761

RESUMEN

Objectives: To investigate the impact of combining lenvatinib with transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC). Methods: This was a retrospective observational study which reviewed the medical records of 103 unresectable HCC patients from January 2017 to June 2020 in The First Affiliated Hospital of Soochow University. It included 46 patients who received TACE plus lenvatinib and 57 patients who received TACE alone. The levels of serum indicators, clinical effect, adverse events, overall survival (OS), and progression-free survival (PFS) were compared between the two groups. Results: AFP and VEGF levels in the TACE+lenvatinib group post-treatment were significantly lower than the TACE group (P<0.05). The clinical efficacy in the TACE+lenvatinib group (69.57%) was higher than that in the TACE group (40.35%) post-treatment (P<0.05). There were significant differences in hypertension, diarrhea, and bleeding (gingiva) between the two groups (P<0.05). There were no significant differences in one or two year PFS rate or one year OS between groups (P>0.05), while the two years survival rate in the TACE+lenvatinib group was significantly higher than that in the TACE group (P<0.05). Conclusions: TACE combined with lenvatinib have a high clinical effective rate, with reduced AFP and VEGF levels, higher two year survival rate, and acceptable incidence of adverse events.

10.
FASEB J ; 35(7): e21751, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34156114

RESUMEN

Rat Thy-1 nephritis (Thy-1N) is an animal model of human mesangioproliferative glomerulonephritis (MsPGN), accompanied by glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) deposition. Although sublytic C5b-9 formed on GMC membrane could induce cell proliferation, the mechanism is still unclear. In this study, we first demonstrated that the level of SRY related HMG-BOX gene 9 (SOX9), general control nonderepressible 5 (GCN5), fibroblast growth factor 1 (FGF1) and platelet-derived growth factor α (PDGFα) was all elevated both in the renal tissues of Thy-1N rats (in vivo) and in the GMCs (in vitro) with sublytic C5b-9 stimulation. Then, we not only discovered that sublytic C5b-9 caused GMC proliferation through increasing SOX9, GCN5, FGF1 and PDGFα expression, but also proved that SOX9 and GCN5 formed a complex and combined with FGF1 and PDGFα promoters, leading to FGF1 and PDGFα gene transcription. More importantly, GCN5 could mediate SOX9 acetylation at lysine 62 (K62) to enhance SOX9 binding to FGF1 or PDGFα promoter and promote FGF1 or PDGFα synthesis and GMC proliferation. Besides, the experiments in vivo also showed that FGF1 and PDGFα expression, GMC proliferation and urinary protein secretion in Thy-1N rats were greatly reduced by silencing renal SOX9, GCN5, FGF1 or PDGFα gene. Furthermore, the renal tissues of MsPGN patients also exhibited positive expression of these genes mentioned above. Collectively, our findings indicate that GCN5, SOX9 and FGF1/PDGFα can form an axis and play an essential role in sublytic C5b-9-triggered GMC proliferation, which might provide a novel insight into the pathogenesis of Thy-1N and MsPGN.


Asunto(s)
Proliferación Celular/genética , Proliferación Celular/fisiología , Complejo de Ataque a Membrana del Sistema Complemento/genética , Riñón/fisiología , Células Mesangiales/fisiología , Nefritis/genética , Transcripción Genética/genética , Acetilación , Animales , Línea Celular , Matriz Extracelular/genética , Factor 1 de Crecimiento de Fibroblastos/genética , Humanos , Masculino , Factor de Crecimiento Derivado de Plaquetas/genética , Regiones Promotoras Genéticas/genética , Ratas , Ratas Sprague-Dawley , Factor de Transcripción SOX9/genética , Antígenos Thy-1/genética , Factores de Transcripción p300-CBP/genética
11.
World J Urol ; 40(2): 385-390, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34655306

RESUMEN

PURPOSE: Paraganglioma of the urinary bladder (UBPGL) is a rare neuroendocrine tumor diagnosed in many patients only after surgery. We, therefore, assessed clinical clues relevant to presurgical diagnosis and clinical consequences in patients with a missed presurgical diagnosis of UBPGL. MATERIALS AND METHODS: Case reports describing a UBPGL (published from 1-1-2001 and 31-12-2020) were identified in Pubmed. Two authors independently performed data extraction and assessed data quality according to the PRISMA guideline. Patients were divided into two groups: UBPGL diagnosis before and after surgery. RESULTS: We included 177 articles reporting 194 cases. In 90 (46.4%) patients, the UBPGL was diagnosed before and in 104 (53.6%) after surgery. In presurgically diagnosed UBPGL, hypertension and catecholamine-associated symptoms were 2- to 3-fold (p < 0.001) more frequent than in postsurgically diagnosed patients whereas hematuria was twofold (p = 0.003) more prevalent in those with postsurgical diagnosis. Hypertension was an independent factor for presurgical biochemical testing (OR 4.45, 95% CI 1.66-11.94) while hematuria (OR 0.23, 95% CI 0.09-0.60) was an independent factor for not performing presurgical biochemical testing. Most patients diagnosed after surgery were not pretreated with alpha-adrenoceptor blockade (95.2%), underwent more frequently transurethral resection instead of cystectomy (70.2% vs. 23.1%) and had more frequent peroperative complications and residual tumor mass. CONCLUSIONS: In nearly half of all patients with a UBPGL, the diagnosis was not established before surgery. Hypertension and hematuria contributed independently to a presurgical diagnosis. Postsurgical diagnosis, which was associated with suboptimal presurgical and surgical management, resulted in more peroperative complications and incomplete tumor resections.


Asunto(s)
Paraganglioma , Neoplasias de la Vejiga Urinaria , Cistectomía/métodos , Hematuria , Humanos , Paraganglioma/diagnóstico , Paraganglioma/patología , Paraganglioma/cirugía , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía
12.
Eur Radiol ; 32(7): 4919-4930, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35124718

RESUMEN

OBJECTIVES: To identify specific imaging and clinicopathological features of a rare potentially malignant epithelioid variant of renal lipid-poor angiomyolipoma (E-lpAML). METHODS: A total of 20 patients with E-lpAML and 43 patients with other lpAML were retrospectively included. Multiphase computed tomography (CT) imaging features and clinicopathological findings were recorded. Independent predictors for E-lpAML were identified using multivariate logistic regression and were used to construct a diagnostic score for differentiation of E-lpAML from other lpAML. RESULTS: The E-lpAML group consisted of 6 men and 14 women (age median ± SD: 39.45 ± 15.70, range: 16.0-68.0 years). E-lpAML tended to appear as hyperdense mass lesions located at the renal sinus (n = 8, 40%) or at the renal cortex (n = 12, 60%), with a "fast-in and slow-out" enhancement pattern (n = 20, 100%), cystic degeneration (n = 18, 90%), "eyeball" sign (n = 11, 55%), and tumor neo-vasculature (n = 15, 75%) on CT. Multivariate logistic regression analysis showed that the independent predictors for diagnosing E-lpAML were cystic degeneration on CT imaging and CT value of the tumor in corticomedullary phase of enhancement. A predictive model was built with the two predictors, achieving an area under the curve (AUC) of 93.5% (95% confidence interval (95%CI): 84.3-98.2%) with a sensitivity of 95.0% (95%CI: 75.1-99.9%) and a specificity of 83.72% (95%CI: 69.3-93.2%). CONCLUSION: We identified specific CT imaging features and predictors that could contribute to the correct diagnosis of E-lpAML. Our findings should be helpful for clinical management of E-lpAML which could potentially be malignant and may require nephron-sparing surgery while other lpAML tumors which are benign require no intervention. KEY POINTS: • It is important to differentiate renal epithelioid lipid-poor angiomyolipoma (E-lpAML) from other lpAML because of differences in clinical management. • E-lpAML tumors tend to be large hyperdense tumors in the renal sinus with cystic degeneration and "fast-in and slow-out" pattern of enhancement. • Our CT imaging-based predictive model was robust in its performance for predicting E-lpAML from other lpAML tumors.


Asunto(s)
Angiomiolipoma , Carcinoma de Células Renales , Neoplasias Renales , Adolescente , Adulto , Anciano , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/patología , Carcinoma de Células Renales/patología , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Renales/patología , Lípidos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Adulto Joven
13.
Acta Biochim Biophys Sin (Shanghai) ; 54(4): 452-462, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35607960

RESUMEN

The long non-coding RNA (lncRNA) forebrain embryonic zinc finger protein 1 antisense RNA1 (FEZF1-AS1) was recently identified as an oncogenic gene in several types of tumors. The biological function of FEZF1-AS1 in rectal cancer progression, however, remains unknown. In the present study, we discover that FEZF1-AS1 is significantly upregulated in rectal cancer tissues and cells. Knocking down of FEZF1-AS1 suppresses cell proliferation, migration, and invasion , and tumorigenesis . Furthermore, FEZF1-AS1 functions as a competing endogenous RNA (ceRNA) for miR-632, resulting in the suppression of family with sequence similarity 83, member A (FAM83A). Overall, our findings reveal that FEZF1-AS1/miR-632/FAM83A axis plays an oncogenic role in rectal cancer progression, suggesting that it may be a novel therapeutic target for rectal cancer.


Asunto(s)
MicroARNs , Proteínas de Neoplasias , ARN Largo no Codificante , Neoplasias del Recto , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Proteínas de Neoplasias/genética , ARN Largo no Codificante/genética , Neoplasias del Recto/genética
14.
J Am Chem Soc ; 143(37): 14987-14991, 2021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-34516099

RESUMEN

Sticky-end cohesion plays a critical role in molecular biology and nucleic acid nanotechnology. Although free energy calculations and molecular mechanics can predict these interactions, chemical modification would compromise such predictions. Herein, we have used rationally designed 3D DNA crystals as a tool to experimentally investigate the modulation of 5'-phosphorylation on sticky-end cohesions. We have found that 5'-phosphorylation strengthens the sticky-end cohesion: in a DNA crystal self-assembled exclusively via sticky-end cohesions, 5'-phosphorylation not only promotes the crystallization process, in general, but also accelerates the crystal growth along designed directions. Such a finding allows the fine-tuning of DNA crystallization kinetics and the control of DNA crystal morphology. It also suggests a potential difference in self-assembly kinetics between natural DNA (with 5'-phosphorylation) and synthetic DNA (without 5'-phosphorylation).

15.
J Am Chem Soc ; 143(48): 20363-20367, 2021 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-34808053

RESUMEN

DNA origami is a powerful method for constructing DNA nanostructures. It requires long single-stranded DNAs. The preparation of such long DNA strands is often quite tedious and has a limited production yield. In contrast, duplex DNAs can be easily prepared via enzymatic reactions in large quantities. Thus, we ask a question: can we design DNA nanostructures in such a way that the two complementary strands can simultaneously fold into the designed structures in the same solution instead of hybridizing with each other to form a DNA duplex? By engineering DNA interaction kinetics, herein we are able to provide multiple examples to concretely demonstrate a positive answer to this question. The resulting DNA nanostructures have been thoroughly characterized by electrophoresis and atomic force microscopy imaging. The reported strategy is compatible with the DNA cloning method and thus would provide a convenient method for the large-scale production of the designed DNA nanostructures.


Asunto(s)
ADN Complementario/química , Nanoestructuras/química , Conformación de Ácido Nucleico , Hibridación de Ácido Nucleico
16.
Nat Mater ; 19(9): 1012-1018, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32661383

RESUMEN

The diversity of DNA duplex structures is limited by a binary pair of hydrogen-bonded motifs. Here we show that poly(thymine) self-associates into antiparallel, right-handed duplexes in the presence of melamine, a small molecule that presents a triplicate set of the hydrogen-bonding face of adenine. X-ray crystallography shows that in the complex two poly(thymine) strands wrap around a helical column of melamine, which hydrogen bonds to thymine residues on two of its three faces. The mechanical strength of the thymine-melamine-thymine triplet surpasses that of adenine-thymine base pairs, which enables a sensitive detection of melamine at 3 pM. The poly(thymine)-melamine duplex is orthogonal to native DNA base pairing and can undergo strand displacement without the need for overhangs. Its incorporation into two-dimensional grids and hybrid DNA-small-molecule polymers highlights the poly(thymine)-melamine duplex as an additional tool for DNA nanotechnology.


Asunto(s)
ADN/química , Nanoestructuras/química , Timina/química , Triazinas/química , Enlace de Hidrógeno
17.
J Nanobiotechnology ; 19(1): 388, 2021 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-34823537

RESUMEN

BACKGROUND: Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. RESULTS: Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. CONCLUSION: This strategy may provide a practical approach for targeted therapy of ESCC.


Asunto(s)
Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , MicroARNs , Terapia Molecular Dirigida/métodos , Nanopartículas , Animales , Apoptosis/efectos de los fármacos , Aptámeros de Péptidos/metabolismo , Aptámeros de Péptidos/farmacocinética , Línea Celular Tumoral , Receptores ErbB/metabolismo , Receptores ErbB/farmacocinética , Femenino , Humanos , Ratones , Ratones Desnudos , MicroARNs/química , MicroARNs/farmacocinética , MicroARNs/farmacología , Sistema de Administración de Fármacos con Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/farmacocinética , Sistema de Administración de Fármacos con Nanopartículas/farmacología
18.
Ecotoxicol Environ Saf ; 217: 112233, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33862430

RESUMEN

A microwave (MA) irradiation-persulfate-formate system was constructed to detoxify Cr contamination and solidify the geopolymerization of the alkali-activated composite material. Three series of experiments were correspondingly conducted to evaluate the treatment for the chromate-contaminated soil. The changes in the molar ratios of formate to persulfate and the mass rates of fortifier to soil led to a significantly greater reduction of CrVI in the detoxification experiments. The increase of blast furnace slag from 50% to 80% in the composite cementitious materials (CCM) intensified the immobilization efficiencies of chromate and the compressive strengths of geopolymer blocks. MA irradiation potentially enhanced the binding of Ca cations to the aluminosilicate compounds. The degree of reaction in the phenomenological kinetics model mathematically verified the geopolymerization process. Ettringite was formed within the structure of the geopolymer in the coupling system. Sulfate radicals released from persulfate not only contributed to the detoxification process but also strengthened the immobilization process.


Asunto(s)
Cromatos/análisis , Restauración y Remediación Ambiental/métodos , Microondas , Contaminantes del Suelo/análisis , Álcalis , Silicatos de Aluminio , Contaminación Ambiental , Formiatos , Suelo/química , Sulfatos
19.
Ecotoxicol Environ Saf ; 213: 112003, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33588188

RESUMEN

A green rust-coated expanded perlite (GR-coated Exp-p) microelectrode was synthesized and incorporated into a column-mode three-dimensional electrokinetic (3D-EK) platform to effectively pursue a continuous Cr(VI) removal from the aqueous solution. Brucite-like layers of GR were decorated onto the Exp-p material. The molar ratio of Fe(II) to Fe(III) played a most vital role among the three synthesis factors in influencing the performance of the particle electrode. For the equilibrium adsorption experiments, the target maximum adsorption capacity of 122 mg/g was predicted by a target optimizer and desirability function at the conditions following the pH of 4.7, the initial concentration of 172.4 mg/L, the dosage of 0.28 g/L, and the temperature of 28.96 °C, respectively. SO42-, Cl-, and NO3- fiercely competed with Cr(VI) anions in the acidic conditions for the locally positive sites. A low concentration and a slow flow were favored in the column-mode 3D-EK platform. The pseudo-first-order and Langmuir models were suitable for describing the kinetics and isotherms of the adsorption process, respectively. Cr(VI) anions were electrostatically attracted to the silanol groups and GR surface of the adsorbent, subsequently reduced in both heterogeneity and homogeneity, and finally immobilized by coordinating with silanediol groups and silanetriol groups.


Asunto(s)
Cromo/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Adsorción , Óxido de Aluminio , Aniones , Electrodos , Compuestos Férricos , Concentración de Iones de Hidrógeno , Cinética , Dióxido de Silicio , Temperatura , Agua , Contaminantes Químicos del Agua/análisis
20.
J Environ Manage ; 280: 111697, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33246753

RESUMEN

Biohazard performance of Sr radionuclide can be significantly magnified by its release from the contaminated sedimentation. In this study, hydroxyapatite nanoparticle-functionalized activated carbon electrode (AC-HAP) was synthesized and stacked to the cathode compartment of the electrokinetic (EK) system to develop a unipolar three-dimensional (3D) electrochemical process for Sr2+ removal from spiked soils. Sr2+ adsorption by AC-HAP can be fitted by the pseudo-first-order and pseudo-second-order kinetic models and the Langmuir, Freundlich, and Temkin isotherm models. The largest monolayer adsorption capacity of AC-HAP of 69.49 mg g-1 was evaluated in the pH range of 10-12 and at 40 °C. 3D EK further intensified the adsorption process of AC-HAP and the corresponding Sr2+ removal from aqueous environments. Voltage gradients and proposing time had a significant effect on the migration and transmission of Sr2+ in the electrolyzer. The influence of competitive ions on Sr2+ removal in the stock solutions followed Al3+ < Mg2+ < K+ < Na+ < Ca2+ while followed Al3+ < Na+ < K+ < Mg2+ < Ca2+ in 3D EK. The first three cycles for AC-HAP had taken roughly 50% of the reusability percentage. Sr2+ removal from spiked samples in 3D EK was achieved by acid dissolution, electromigration, and selective uptake on particle electrode.


Asunto(s)
Carbón Orgánico , Nanopartículas , Adsorción , Durapatita , Electrodos , Suelo , Estroncio
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