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1.
J Nanobiotechnology ; 22(1): 296, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811964

RESUMEN

BACKGROUND: Combination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot tumors to benefit from immunotherapy. To achieve drug synergy, we developed a homologous cancer cell membrane vesicle (CM)-coated metal-organic framework (MOF) nanodelivery platform for the codelivery of a TLR7/8 agonist with an epigenetic inhibitor. METHODS: A novel biomimetic codelivery system (MCM@UN) was constructed by MOF nanoparticles UiO-66 loading with a bromodomain-containing protein 4 (BRD4) inhibitor and then coated with the membrane vesicles of homologous cancer cells that embedding the 18 C lipid tail of 3M-052 (M). The antitumor immune ability and tumor suppressive effect of MCM@UN were evaluated in a mouse model of triple-negative breast cancer (TNBC) and in vitro. The tumor immune microenvironment was analyzed by multicolor immunofluorescence staining. RESULTS: In vitro and in vivo data showed that MCM@UN specifically targeted to TNBC cells and was superior to the free drug in terms of tumor growth inhibition and antitumor immune activity. In terms of mechanism, MCM@UN blocked BRD4 and PD-L1 to prompt dying tumor cells to disintegrate and expose tumor antigens. The disintegrated tumor cells released damage-associated molecular patterns (DAMPs), recruited dendritic cells (DCs) to efficiently activate CD8+ T cells to mediate effective and long-lasting antitumor immunity. In addition, TLR7/8 agonist on MCM@UN enhanced lymphocytes infiltration and immunogenic cell death and decreased regulatory T-cells (Tregs). On clinical specimens, we found that mature DCs infiltrating tumor tissues of TNBC patients were negatively correlated with the expression of BRD4, which was consistent with the result in animal model. CONCLUSION: MCM@UN specifically targeted to TNBC cells and remodeled tumor immune microenvironment to inhibit malignant behaviors of TNBC.


Asunto(s)
Receptor Toll-Like 7 , Receptor Toll-Like 8 , Neoplasias de la Mama Triple Negativas , Microambiente Tumoral , Animales , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Receptor Toll-Like 7/agonistas , Receptor Toll-Like 8/agonistas , Ratones , Femenino , Humanos , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos , Nanopartículas/química , Factores de Transcripción/metabolismo , Ratones Endogámicos BALB C , Proteínas de Ciclo Celular/metabolismo , Inmunoterapia/métodos , Epigénesis Genética/efectos de los fármacos , Proteínas que Contienen Bromodominio
2.
Ann Noninvasive Electrocardiol ; 29(4): e13128, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38872457

RESUMEN

BACKGROUND: The aim was to evaluate the effect of beta-blockers (BB) on the response of heart rate (HR) to 6-min walk test (6MWT) in atrial fibrillation (AF) and whether the AF patients treated with BB have a similar HR response to 6MWT as the AF and sinus rhythm (SR) patients without BB treatment at the same resting HR level. METHODS: The before-after study involving 74 AF patients was to evaluate the effect of BB treatment (pre-BB and with BB). The comparison study included 74 BB-treated AF patients (with BB), 74 matched AF patients without BB (no BB), and 74 SR patients. The percentage increase amplitude of HR (HR-PIA) in 6MWT was calculated: [(the exercise HR - the resting HR)/(the resting HR)] × 100%. RESULTS: The before-after study showed that BB treatment decreased the resting and mean exercise HR (98.6 ± 15.2 vs. 85.5 ± 11.2 bpm and 121.3 ± 17.3 vs. 109.0 ± 16.7 bpm) during 6MWT. The comparison study demonstrated that against the SR, the AF with BB and no BB groups have higher mean exercise HR-PIA (28.2 ± 17.1% and 22.0 ± 9.6%, vs. 6.9 ± 3.7%) when their resting HR is similar. Moreover, the mean exercise HR-PIA was also significantly higher in the with BB group than in the no BB group. CONCLUSION: In AF patients with relatively higher resting HR, BB treatment could decrease the resting and exercise HR during 6MWT. However, BB treatment could not effectively attenuate the exercise HR rise as compared with AF without BB treatment, even with similar resting HR levels.


Asunto(s)
Antagonistas Adrenérgicos beta , Fibrilación Atrial , Prueba de Esfuerzo , Frecuencia Cardíaca , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Femenino , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta/farmacología , Anciano , Persona de Mediana Edad , Prueba de Esfuerzo/métodos , Prueba de Esfuerzo/efectos de los fármacos , Prueba de Paso/métodos , Caminata/fisiología , Resultado del Tratamiento , Electrocardiografía/métodos , Electrocardiografía/efectos de los fármacos
3.
Small ; 19(4): e2206155, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36437043

RESUMEN

Atomic heating on single atoms (SAs) to maximize the catalytic efficiency of each active site would be a fascinating solution to break the bottleneck for the performance improvement of single-atom catalysts (SACs) but highly challenging task. Here, based on the Gd@MoS2 SACs synthesized by a facile laser molecular beam epitaxy method, high-frequency alternating magnetic field (AMF) technology is employed to induce atomic magnetic heating on Gd SAs that is meanwhile demonstrated to be the catalytic active center. Significant improvement in catalytic kinetics under AMF excitation (3.9 mT) is achieved, yielding a remarkable enhancement of hydrogen evolution reaction magnetothermal-current by ≈924%. Through theoretical calculations and spin-related electrochemical experiments, such promotion in catalyst activity can be attributed to spin flip (or canting) in Gd SAs leading to the atomic magnetic heating effect on catalytic active center. Together with the embodied high stability, the implement of AMF to the SAs field is demonstrated in this work, and the precisely atomic magnetic heating on specific SAs offers unprecedented thinking for further improvement of SACs performance in the future.

4.
Cell Biol Int ; 47(2): 417-427, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36251276

RESUMEN

Ulcerative colitis (UC) is a disorder of the bowel that is characterized by a chronic inflammatory response. The traditional Chinese herbal medicine ferulic acid (FA) is known for its antioxidant, antiapoptotic, and antiinflammatory properties. However, its role in UC is still unclear. Thus, the current study was conducted to investigate the role of FA in UC. Rats were treated with 2,4,6-triabrobenzene sulfonic acid to induce UC and subjected to FA. Human intestinal microvascular endothelial cells (HIMECs) were treated with tumor necrosis factor-α (TNF-α) and pretreated with FA. Pathological changes in colonic tissues were visualized via hematoxylin-eosin staining. Enzyme linked immunosorbent assay was conducted to detect interleukin (IL)-6, IL-12, and IL-1ß levels. Cell morphology was visualized by using a microscope, and viability was detected by using MTT. The percentage of apoptosis was detected via flow cytometry. Western blot analysis was performed to detect the expression of the apoptosis-related proteins thioredoxin-interacting protein (TXNIP) and NOD-like receptor pyrin domain-containing 3 (NLRP3). In vivo FA administration alleviated intestinal injury in UC rats and inhibited inflammatory factor levels (IL-6, IL-12, and IL-1ß), apoptosis-related protein expression (caspase-1 and caspase-3) and the TXNIP/NLRP3 signaling pathway. In vitro, TNF-α treatment reduced HIMEC viability, increased cell apoptosis and inflammatory factor levels and activated the TXNIP/NLRP3 signaling pathway. However, FA treatment restored the viability of HIMECs, reduced TNF-α-induced cell apoptosis and inflammation and inhibited the TXNIP/NLRP3 signaling pathway. Furthermore, with increasing FA concentration, the effects were stronger. In summary, FA inhibits the inflammatory injury of endothelial cells in ulcerative colitis or alleviates TNF-α-induced HIMEC injury by inhibiting the TXNIP/NLRP3 signaling pathway.


Asunto(s)
Colitis Ulcerosa , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas , Humanos , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Células Endoteliales/metabolismo , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Inflamación/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Interleucina-12/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo
5.
Environ Res ; 216(Pt 2): 114590, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36252834

RESUMEN

Reactive red 2 (RR2) azo dye wastewater poses a serious hazard to the water environment health, so using a novel and efficient Electro- Ce(III) (E- Ce(III)) process takes on a critical significance in treating RR2 dye wastewater. In this study, the effects of a variety of single-factor conditions on RR2 removal efficiency were evaluated in depth. The results indicated that the optimal experimental conditions are as reaction temperature of 25 °C, Na2SO4 concentration of 25 mM, Ce(III) concentration of 0.3 mM, pH of 4.0, and current density of 40.0 mA/cm2. When the RR2 dye wastewater was treated for 40 min under the optimal experimental conditions, a high removal rate of 99.8% for RR2 was obtained. It is suggested that the background ion PO43- in the dye wastewater inhibits the E-Ce (III) process, whereas Cl- facilitates this process. Moreover, the yield of Ce(IV) increases with the increase of the current density. At the current density of 40.0 mA/cm2, a reasonable energy consumption of 3.85 kW h/gTOC for the process was obtained after the 3-h treatment. The effects of different degradation processes (including Direct Electrooxidation (DEO), single Ce(III), and E-Ce (III)) on RR2 removal efficiency and TOC change were compared. The types of oxidizing substances in the E-Ce (III) process were detected, and the mechanism of RR2 oxidative degradation in the E-Ce (III) process was summarized. The result suggests that the E-Ce (III) process has low power consumption. Meanwhile, in the E-Ce (III) process, free reactive Ce(IV) with strong oxidation is continuously generated, RR2 can be efficiently degraded. And the continuous cycle transformation between Ce(III) and Ce(IV) maintains the strong oxidation of the process. The contribution of free reactive Ce(IV) and DEO to RR2 degradation was obtained as 58.8% and 39.8%, respectively. The combined effect of Ce(IV) and DEO played a major role in the E-Ce (III) process, while ·OH exhibited a relatively weak effect (nearly 1.4%). RR2 was comprised of 13 major intermediates, and the biodegradability of wastewater was improved significantly after treatment, thus facilitating the further mineralization and biodegradation of the products. The E- Ce(III) process is novel, efficient, and environment-friendly, and has a large market application space, suggesting that it can be applied as an efficient, economic, and sustainable water treatment process.


Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Aguas Residuales/química , Colorantes/química , Naftalenosulfonatos , Compuestos Azo/química , Oxidación-Reducción , Contaminantes Químicos del Agua/análisis
6.
Nano Lett ; 22(23): 9411-9417, 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36410739

RESUMEN

Alternating magnetic field (AMF) is a promising methodology for further improving magnetic single-atom catalyst (SAC) activity toward oxygen evolution reaction (OER). Herein, the anchoring of Co single atoms on MoS2 support (Co@MoS2), leading to the appearance of in-plane room-temperature ferromagnetic properties, is favorable for the parallel spin arrangement of oxygen atoms when a magnetic field is applied. Moreover, field-assisted electrocatalytic experiments confirmed that the spin direction of Co@MoS2 is changing with the applied magnetic field. On this basis, under AMF, the active sites in ferromagnetic Co@MoS2 were heated by exploiting the magnetic heating generated from spin polarization flip of these SACs to further expedite OER efficiency, with overpotential at 10 mA cm-2 reduced from 317 mV to 250 mV. This work introduces a feasible and efficient approach to enhance the OER performance of Co@MoS2 by AMF, shedding some light on the further development of magnetic SACs for energy conversion.

7.
Plant J ; 108(1): 40-54, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34252236

RESUMEN

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 Mb) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. In total, we obtained 5818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: "missing a small part" in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein, which is specifically required for Fe transport. Increased accumulation of Fe and reactive oxygen species as well as ferroptosis-like cell death were detected in qk1 endosperm. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.


Asunto(s)
Genoma de Planta/genética , Zea mays/genética , Productos Agrícolas , Endospermo/genética , Endospermo/metabolismo , Endogamia , Mutación , Fenotipo , Fitomejoramiento , Banco de Semillas , Semillas/genética , Semillas/metabolismo , Almidón/metabolismo , Zea mays/metabolismo
8.
Small ; 18(51): e2203064, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36333115

RESUMEN

Diabetic wound is one of the common complications in diabetic patients, which exhibits chronic, hard-to-heal characteristics. The healing process of wounds is impaired by several factors, including excessive oxidative stress, blocked angiogenesis, and bacterial infection. The therapeutic effects of traditional microneedle patches remain not satisfactory, due to their difficulty simultaneously targeting multiple targets to treat diabetic wounds. As such, there is an urgent need to develop a multifunctional microneedle (MN) patch for promoting the healing of diabetic wounds. A multifunctional MN patch with antioxidant, proangiogenesis, and antibacterial capacities was fabricated to target the pathogenesis of diabetic wounds. Silk fibroin methacryloyl, which has excellent biocompatibility, stable mechanical properties, and well processability, and is selected as the base material for multifunctional MN patches. Prussian blue nanozymes (PBNs) and vascular endothelial growth factor (VEGF) are encapsulated in tips of MN patches, Polymyxin is encapsulated in base layers of MN patches. Based on synergic properties of these components, multifunctional MN patches exhibit excellent biocompatibility, drug-sustained release, proangiogenesis, antioxidant, and antibacterial properties. The developed multifunctional MN patches accelerate diabetic wound healing, providing a potential therapeutic approach.


Asunto(s)
Diabetes Mellitus , Fibroínas , Humanos , Factor A de Crecimiento Endotelial Vascular/farmacología , Antioxidantes/farmacología , Cicatrización de Heridas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Seda
9.
Inorg Chem ; 61(4): 2360-2367, 2022 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-35044753

RESUMEN

Nanoclusters are ideal electrocatalysts due to their high surface activity. However, their high activities also lead to serious agglomeration and performance attenuation during the catalytic process. Here, highly dispersed Ni nanoclusters (∼3 nm) confined in an amorphous carbon matrix are successfully fabricated by pulsed laser deposition, followed by rapid temperature annealing treatment. Then, the Ni nanoclusters are further doped with nitrogen element through a clean N2 radio frequency plasma technology. It is found that the nitrogen-doped Ni nanoclusters obtained under optimized conditions showed superior OER performance with a very low overpotential of 240 mV at a current density of 10 mA/cm2, together with good stability. The excellent OER performance of the nanoclusters can be attributed to the unique confined structure and nitrogen doping, which not only provide more active sites but also improve the conductivity. Our work provides a controllable method for the construction of a novel confined structure with controllable nitrogen doping, which can be used as a high-efficiency OER electrocatalyst.

10.
Nano Lett ; 21(24): 10486-10493, 2021 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-34859672

RESUMEN

Ferromagnetic (FM) electrocatalysts have been demonstrated to reduce the kinetic barrier of oxygen evolution reaction (OER) by spin-dependent kinetics and thus enhance the efficiency fundamentally. Accordingly, FM two-dimensional (2D) materials with unique physicochemical properties are expected to be promising oxygen-evolution catalysts; however, related research is yet to be reported due to their air-instabilities and low Curie temperatures (TC). Here, based on the synthesis of 2D air-stable FM Cr2Te3 nanosheets with a low TC around 200 K, room-temperature ferromagnetism is achieved in Cr2Te3 by proximity to an antiferromagnetic (AFM) CrOOH, demonstrating the accomplishment of long-ranged FM ordering in Cr2Te3 because the magnetic proximity effect stems from paramagnetic (PM)/AFM heterostructure. Therefore, the OER performance can be permanently promoted (without applied magnetic field due to nonvolatile nature of spin) after magnetization. This work demonstrates that a representative PM/AFM 2D heterostructure, Cr2Te3/CrOOH, is expected to be a high-efficient magnetic heterostructure catalysts for oxygen-evolution.

11.
Mol Cell Biochem ; 476(5): 2011-2020, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33515198

RESUMEN

Cytochrome P450 2C9 (CYP2C9) is involved in the metabolism of cancer drugs and exogenous carcinogens. In our study, CYP2C9 was downregulated in multiple cohorts of human esophageal squamous cell carcinoma (ESCC). Until now, its role and epigenetic regulation of CYP2C9 repression in ESCC remain poorly understood. CYP2C9 repression in collected ESCC patient tumor tissues was demonstrated by RT-qPCR and Western blot. The histone acetylation level was carried out by the treatment of histone deacetylase inhibitor TSA and RNA interference. Epigenetic analysis revealed that the increased expression of CYP2C9 in KYSE-150 and TE1 cells was characterized by inhibition of HDAC8 and HDAC1, respectively. TSA decreased the levels of HDAC occupancy around CYP2C9 promoter region greatly. Overexpression of CYP2C9 reduced the invasion and migration of ESCC cells.


Asunto(s)
Movimiento Celular , Citocromo P-450 CYP2C9/metabolismo , Regulación hacia Abajo , Neoplasias Esofágicas/enzimología , Carcinoma de Células Escamosas de Esófago/enzimología , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Histona Desacetilasas/biosíntesis , Proteínas de Neoplasias/metabolismo , Línea Celular Tumoral , Citocromo P-450 CYP2C9/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Histona Desacetilasas/genética , Humanos , Invasividad Neoplásica , Proteínas de Neoplasias/genética
12.
Inorg Chem ; 60(3): 1991-1997, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33428395

RESUMEN

The high recombination rate of photoinduced electron-hole pairs limits the hydrogen production efficiency of the MoS2 catalyst in photoelectrochemical (PEC) water splitting. The strategy of prolonging the lifetime of photoinduced carriers is of great significance to the promotion of photoelectrocatalytic hydrogen production. An ideal approach is to utilize edge defects, which can capture photoinduced electrons and thus slow down the recombination rate. However, for two-dimensional MoS2, most of the surface areas are inert basal planes. Here, a simple method for preparing one-dimensional MoS2 nanoribbons with abundant inherent edges is proposed. The MoS2 nanoribbon-based device has a good spectral response in the range of 400-500 nm and has a longer lifetime of photoinduced carriers than other MoS2 nanostructure-based photodetectors. An improved PEC catalytic performance of these MoS2 nanoribbons is also experimentally verified under the illumination of 405 nm by using the electrochemical microcell technique. This work provides a new strategy to prolong the lifetime of photoinduced carriers for further improvement of PEC activity, and the evaluation of photoelectric performance provides a feasible way for transition-metal dichalcogenides to be widely used in the energy field.

13.
Inorg Chem ; 60(4): 2704-2715, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33513000

RESUMEN

Solvothermal assembly of copper(II) cations and 5-(pyridine-3-yl)isophthalate linkers bearing different position-substituted methyl groups afforded four ligand-induced metal-organic framework (MOF) isomers as a platform for investigating diverse selective gas adsorption properties and understanding the positional effect of methyl functionality. Single-crystal X-ray diffraction (SCXRD) analyses showed that, when the methyl substituent is at the para position with respect to the pyridinic N atom, the resultant framework compound ZJNU-27 features an eea-type topology, while the other three solids possess an isoreticular structure with an rtl-type topology when the methyl group is situated at the other positions. As revealed by N2 physi-adsorption measurements at 77 K, they exhibit moderate specific surface areas ranging from 584 to 1182 m2 g-1 and distinct degrees of framework flexibility, which are heavily dependent on the methyl position. Comprehensive gas adsorption studies show that they are capable of effectively separating three pairs of binary gas mixtures including C2H2-CH4, CO2-CH4, and CO2-N2 couples. Moreover, their uptake capacities and adsorption selectivities can be tailored by altering the methyl position. In addition, their framework hydro-stability is also influenced by the methyl position. Compared to ZJNU-27 and ZJNU-28, ZJNU-26 and ZJNU-29 exhibit poorer stability against H2O, although the methyl group is more close to inorganic secondary building units (SBUs), which are believed to originate from the steric effect of the methyl group. Overall, the four MOFs display the methyl position-dependent network architectures, framework flexibilities, and selective gas adsorption properties as well as hydrostabilities. The findings observed in this work not only demonstrate the importance of the positional effect of the functional group but also highlight that engineering the substituent position is a potential strategy for achieving the modulation of MOF structures and properties.

14.
Inorg Chem ; 60(11): 8111-8122, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34019764

RESUMEN

To push forward the structural development and fully explore the potential utility, it is highly desired but challenging to regulate in a controllable manner the structures and properties of MOFs. In this work, we reported the structural and functional modulation of Cu(II)-tricarboxylate frameworks by employing a strategy of engineering the functionalities and their positions. Two pairs of unsymmetrical biaryl tricarboxylate ligands modified with a methyl group and a pyridinic-N atom at distinct positions were logically designed and synthesized, and their corresponding Cu(II)-based MOFs were solvothermally constructed. Diffraction analyses revealed that the variation of functionalities and their positions furnished three different types of topological structures, which we ascribed to the steric effect exerted by the methyl group and the chelating effect involving the pyridinic-N atom. Furthermore, gas adsorption studies showed that three of them are potential candidates as solid separation media for acetylene (C2H2) purification, with the separation potential tailorable by altering functionalities and their locations. At 106.7 kPa and 298 K, the C2H2 uptake capacity varies from 64.1 to 132.4 cm3 (STP) g-1, while the adsorption selectivities of C2H2 over its coexisting components of CO2 and CH4 fall in the ranges of 3.28-4.60 and 14.1-21.9, respectively.

15.
Zhongguo Zhong Yao Za Zhi ; 46(1): 130-138, 2021 Jan.
Artículo en Zh | MEDLINE | ID: mdl-33645062

RESUMEN

As a precious traditional Chinese medicine(TCM), snake bile has been widely used in numerous Chinese medicine prescriptions. Bile acid(BA) derivatives have been demonstrated as the primary chemical family in snake bile. In-depth chemical characterization of BAs is of great importance towards the establishment of quality standards and clarification of the effective material basis for snake bile. This study firstly employed ~1H-NMR to preliminarily analyze the chemical profiles of snake bile, an automated fraction collector was subsequently implemented to obtain the fractions-of-interest. The fraction was then concentrated and re-analyzed by LC-MS. Based on ~1H-NMR, BAs were found to be the main components of snake bile, and six BAs including CDCA, CA, TCDCA, TCA, TDCA and GCA were tentatively identified from the representative spectrum with the assistance of literature and reference compounds. Whereas the content of TCA in snake bile was too great, resulting in a great obstacle for the detection of trace components, the automated fraction collector was subsequently implemented to obtain the fractions-of-interest for LC-MS analysis. According to matching MS/MS information and retention time with reference compounds as well as database retrieval, a total of 57 BAs were detected and annotated. Because of the combination of ~1H-NMR and LC-MS platforms, the findings are beneficial for the in-depth characterization of BAs in snake bile, which provides references for the establishment of quality control and evaluation methods of snake bile.


Asunto(s)
Ácidos y Sales Biliares , Espectrometría de Masas en Tándem , Animales , Bilis , Cromatografía Liquida , Serpientes
16.
Anticancer Drugs ; 31(8): 776-784, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32796403

RESUMEN

Cisplatin is a widely used chemotherapeutic drug in lung cancer treatment. Most cancer patients eventually develop cisplatin resistance, resulting in a poor prognosis. Previously, we identified a novel marker, family with sequence similarity 60A (FAM60A), that was responsible for resistance in cisplatin-resistant human lung adenocarcinoma A549 (A549/DDP) cells. Here, we investigated the biological effects of FAM60A in A549/DDP cells and explored the underlying molecular mechanisms to understand its functional role in cisplatin resistance. Real-time quantitative PCR and western blot analysis were used to determine the expression levels of FAM60A in A549/DDP cells. FAM60A and SKP2 were knockdown with small-interfering RNA (siRNA). Cancer cell viability was analyzed with flow cytometry. The mRNA and protein expression levels of FAM60A increased significantly and dose-dependently in A549/DDP cells following cisplatin treatment. FAM60A overexpression up-regulated MDR1 expression, inhibited caspase 3, cleaved-caspase 3, and caspase 8 expression, and prevented cancer cell death. Microarray analysis of cells transfected with siRNA against the FAM60A transcript and control samples showed that SKP2 expression was positively regulated by FAM60A. SKP2 knockdown using a short-hairpin RNA reversed the functions induced by FAM60A. These results suggest that overexpression of FAM60A in A549/DDP cells led to SKP2 upregulation and enhanced cisplatin resistance in cancer cells. These provide new insights into chemoresistance and may contribute to reversing cisplatin resistance during lung cancer treatment.


Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Proteínas de Unión al ADN/metabolismo , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Proteínas de Unión al ADN/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Quinasas Asociadas a Fase-S/genética , Células Tumorales Cultivadas
17.
Med Sci Monit ; 26: e924582, 2020 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-32653890

RESUMEN

In December 2019, an outbreak of coronavirus infection emerged in Wuhan, Hubei Province of China, which is now named Coronavirus Disease 2019 (COVID-19). The outbreak spread rapidly within mainland China and globally. This paper reviews the different imaging modalities used in the diagnosis and treatment process of COVID-19, such as chest radiography, computerized tomography (CT) scan, ultrasound examination, and positron emission tomography (PET/CT) scan. A chest radiograph is not recommended as a first-line imaging modality for COVID-19 infection due to its lack of sensitivity, especially in the early stages of infection. Chest CT imaging is reported to be a more reliable, rapid, and practical method for diagnosis of COVID-19, and it can assess the severity of the disease and follow up the disease time course. Ultrasound, on the other hand, is portable and involves no radiation, and thus can be used in critically ill patients to assess cardiorespiratory function, guide mechanical ventilation, and identify the presence of deep venous thrombosis and secondary pulmonary thromboembolism. Supplementary information can be provided by PET/CT. In the absence of vaccines and treatments for COVID-19, prompt diagnosis and appropriate treatment are essential. Therefore, it is important to exploit the advantages of different imaging modalities in the fight against COVID-19.


Asunto(s)
Betacoronavirus , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico por imagen , Pandemias , Neumonía Viral/diagnóstico por imagen , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , COVID-19 , Prueba de COVID-19 , China/epidemiología , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Diagnóstico Diferencial , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/etiología , Neumonía/diagnóstico por imagen , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiografía Torácica , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/etiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Ultrasonografía
18.
BMC Genomics ; 20(1): 611, 2019 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-31345182

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) cells are heterogeneous, easily develop radioresistance, and recur. Single-cell RNA-seq (scRNA-seq) is a next-generation sequencing method that can delineate diverse gene expression profiles of individual cells and mining their heterogeneous behaviors in response to irradiation. Our aim was using scRNA-seq to describe the difference between parental cells and cells that acquired radioresistance, and to investigate the dynamic changes of the transcriptome of cells in response to FIR. RESULTS: We sequenced ESCC cell lines KYSE180 with and without fractionated irradiation (FIR). A total of 218 scRNA-seq libraries were obtained from 88 cells exposed to 12 Gy (KYSE-180-12 Gy), 89 exposed to 30 Gy (KYSE-180-30 Gy), and 41 parental KYSE-180 cells not exposed to FIR. Dynamic gene expression patterns were determined by comprehensive consideration of genes and pathways. Biological experiments showed that KYSE-180 cells became radioresistant after FIR. PCA analysis of scRNA-seq data showed KYSE-180, KYSE-180-12 Gy and KYSE-180-30 Gy cells were discrete away from each other. Two sub-populations found in KYSE-180-12 Gy and only one remained in KYSE-180-30 Gy. This sub-population genes exposure to FIR through 12 Gy to 30 Gy were relevant to the PI3K-AKT pathway, pathways evading apoptosis, tumor cell migration, metastasis, or invasion pathways, and cell differentiation and proliferation pathways. We validated DEGs, such as CFLAR, LAMA5, ITGA6, ITGB4, and SDC4 genes, in these five pathways as radioresistant genes in bulk cell RNA-seq data from ESCC tissue of a ESCC patient treated with radiotherapy and from KYSE-150 cell lines. CONCLUSIONS: Our results delineated the divergent gene expression patterns of individual ESCC cells exposure to FIR, and displayed genes and pathways related to development of radioresistance.


Asunto(s)
Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Tolerancia a Radiación , Transcriptoma , Línea Celular Tumoral/efectos de la radiación , Humanos , Redes y Vías Metabólicas , RNA-Seq
19.
Nanotechnology ; 30(31): 315702, 2019 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-30991364

RESUMEN

Designing and building new micro/nanomotors are among the most exciting challenges facing nanotechnology. Considering the expensive equipment and the high cost associated with noble metals, a scalable and reliable fabrication method is desired for the fabrication of Janus particles. In this work, we report on the preparation and characterization of self-propelled micromotors based on Janus TiO2/MnO2 nanoparticles. The Janus micromotor is constructed by growing propulsion material MnO2 nanoflakes in situ on one hemisphere of TiO2 by photoreduction of KMnO4 under aerobic conditions. The MnO2 nanoflakes can catalytically decompose hydrogen peroxide fuel to generate oxygen bubbles, which consequently repel the micromotors forward in the solution. Thus, the Janus TiO2/MnO2 nanoparticle represents a promising material for the preparation of micromotors for various biomedical or environmental applications.

20.
Cardiovasc Drugs Ther ; 33(1): 45-54, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30675709

RESUMEN

Myocardial ischemia/reperfusion (I/R) injury is a serious threat to the health of people around the world. Recent evidence has indicated that high-mobility group box-1 (HMGB1) is involved in I/R-induced inflammation, and inflammation can cause necroptosis of cells. Interestingly, dexmedetomidine (DEX) has anti-inflammatory properties. Therefore, we speculated that DEX preconditioning may suppress H/R-induced necroptosis by inhibiting expression of HMGB1 in cardiomyocytes. We found that hypoxia/reoxygenation (H/R) significantly increased cellular damage, as measured by cell viability (100 ± 3.26% vs. 53.33 ± 3.29, p < 0.01), CK-MB (1 vs. 3.25 ± 0.26, p < 0.01), cTnI (1 vs. 2.69 ± 0.31, p < 0.01), inflammation as indicated by TNF-α (1 ± 0.09 vs. 2.57 ± 0.12, p < 0.01), IL-1ß (1 ± 0.33 vs. 3.87 ± 0.41, p < 0.01) and IL-6 (1 ± 0.36 vs. 3.60 ± 0.45, p < 0.01), and necroptosis, which were accompanied by significantly increased protein levels of HMGB1. These changes [cellular damage as measured by cell viability (53.33 ± 3.29% vs. 67.59 ± 2.69%, p < 0.01), CK-MB (3.25 ± 0.26 vs. 2.27 ± 0.22, p < 0.01), cTnI (2.69 ± 0.31 vs. 1.90 ± 0.25, p < 0.01), inflammation as indicated by TNF-α (2.57 ± 0.12 vs. 1.75 ± 0.15, p < 0.01), IL-1ß (3.87 ± 0.41 vs. 2.09 ± 0.36, p < 0.01) and IL-6 (3.60 ± 0.45 vs. 2.21 ± 0.39, p < 0.01), and necroptosis proteins] were inhibited by DEX preconditioning. We also found that silencing expression of HMGB1 reinforced the protective effects of DEX preconditioning and overexpression of HMGB1 counteracted the protective effects of DEX preconditioning. Thus, we concluded that DEX preconditioning inhibits H/R-induced necroptosis by inhibiting expression of HMGB1 in cardiomyocytes.


Asunto(s)
Antiinflamatorios/farmacología , Dexmedetomidina/farmacología , Proteína HMGB1/antagonistas & inhibidores , Mediadores de Inflamación/antagonistas & inhibidores , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Animales , Muerte Celular/efectos de los fármacos , Hipoxia de la Célula , Línea Celular , Microambiente Celular , Citocinas/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Mediadores de Inflamación/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas , Transducción de Señal/efectos de los fármacos
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