Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
Molecules ; 29(6)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38542957

RESUMEN

In order to evaluate the physical and chemical properties of polymer surfactants and analyze their oil displacement mechanisms, three types of poly-surfactant used in the Daqing oil field were chosen to be researched, and the oil displacement effects were studied using poly-surfactants of different viscosity, dehydrating rate, and core permeability. The main purpose is to determine the reasonable range of different characteristic indexes of polymeric surfactant flooding. The oil displacement effect of 15 cores was analyzed, and the effects of viscosity, the dehydrating rate of emulsion, and permeability on EOR (Enhanced Oil Recovery) were analyzed. The oil displacement mechanisms of polymeric surfactants were researched using a photolithographic glass core. This paper explores the mechanism underlying production enhancement as an EOR target, while simultaneously conducting laboratory tests to assess the physical and chemical properties of polymeric surfactants. The poly-surfactant agents exhibit a notable increase in viscosity, with the optimal displacement effect observed at a core effective permeability exceeding 400 mD, resulting in a potential EOR of 15% or higher. Moreover, at a viscosity ranging between 40 and 70 mPa·s, the total EOR can reach 73%, with the peak efficiency occurring at a viscosity of 60 mPa·s. The water loss rate of the emulsion, ranging between 30% and 70%, achieves optimal performance at 50%. The poly-surfactants' higher viscosity extends the oil sweep area, enhancing recovery efficiency, and noticeably reducing residual oil compared to water flooding. During poly-surfactant flooding, a substantial amount of residual oil is extracted and transformed into droplets. The rapid emulsification of the polymeric surfactant solution with crude oil forms a stable emulsion, contributing to its significant oil recovery effect. This research provides valuable technical support for EOR in thin and low-quality reservoirs of onshore multi-layered sandstone reservoirs.

2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(1): 99-102, 2022 Jan 10.
Artículo en Zh | MEDLINE | ID: mdl-34964978

RESUMEN

Isovaleric acidemia is a type of organic acidemia for which the earliest definite diagnosis was attained. It features an autosomal recessive inheritance, with the onset of age varying from newborn to adulthood. The clinical manifestations are complex and variable, which include feeding difficulty, vomiting, lethargy, coma, metabolic acidosis, sweaty feet odor and mental retardation. The mortality and mobility rates of isovaleric acidemia are quite high, and early diagnosis and rational treatment can significantly improve the prognosis. This article has provided a summary for the current understanding and research progress on isovaleric acidemia.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Adulto , Errores Innatos del Metabolismo de los Aminoácidos/genética , Humanos , Recién Nacido , Isovaleril-CoA Deshidrogenasa/deficiencia , Isovaleril-CoA Deshidrogenasa/genética
3.
Biochem Biophys Res Commun ; 534: 367-373, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33279112

RESUMEN

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) play a critical role in most translational and clinical applications. Although glucose starvation (GS) has been evaluated during cellular purification, there has been no comprehensive evaluation of the transcriptional heterogeneity of these cells. Here, we applied GS for 3 days starting at day 10 of differentiation, and then, harvested hiPSC-CMs at day 20 for single-cell RNA sequencing (scRNA-seq). We found that GS dramatically reduced the proportion of non-cardiomyocytes cells and increased the number of late-stage cardiomyocytes. We also recorded an increase in the expression of MYH6, MYH7, ACTN2, TNNT2, and several other genes associated with the structural and functional maturation of cardiomyocytes. Further analysis indicated that these changes were focused on the signaling pathways involved in the regulation of the actin cytoskeleton, cardiac muscle development, and cardiac muscle contraction. Finally, pseudotime analysis revealed that GS hiPSC-CMs developed in a more mature direction. Together, these results suggest that GS treatment improves the purity and maturation of hiPSC-CMs, which should increase the feasibility of hiPSC-CMs applications.


Asunto(s)
Glucosa/metabolismo , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Actinina/genética , Miosinas Cardíacas/genética , Diferenciación Celular/genética , Separación Celular , Células Cultivadas , Medios de Cultivo , Regulación del Desarrollo de la Expresión Génica , Humanos , Cadenas Pesadas de Miosina/genética , RNA-Seq , Transducción de Señal , Análisis de la Célula Individual , Troponina T/genética
4.
Mikrochim Acta ; 187(12): 649, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33165704

RESUMEN

The development of a novel signal amplification system is described for sensitive determination of α2,6-sialylated glycans (α2,6-sial-Gs), an important prognostic tumor biomarker. First, Fe-based metal-organic frameworks (Fe-MOFs) with silver nanoparticles (AgNPs) decorated onto the outer surface were designed and synthesized with controlled octahedron structures. The new Ag/Fe-MOFs nanocomposite possessed strong conductivity and a large surface area to carry more nanoprobes. To connect the Ag/Fe-MOFs nanocomposite with more groups, the nanocomposite was functionalized by -COOH with SH-PEG-COOH to bind with an α2,6-sial-Gs catcher, M-APBA, via -CONH- bonds. More importantly, the Ag/Fe-MOFs also exhibited an excellent endogenous redox mediator property to produce electrons, which is the fundamental mechanism underlying amplification of an electronic signal. A gold electrode was used to accelerate electron transfer and immobilize the α2,6-sial-Gs lectin (SNA). After the sandwich-type catcher recognition (SNA/α2,6-sial-Gs/M-APBA), the current peak response was provoked in the process of oxidizing AgNPs to Ag+ in the forward anodic potential sweep, while Cl- in a PBS solution was transferred into Ag+ to maintain charge neutrality. Optimized particles were employed for direct fabrication of the sandwich-type affinity biosensor, which was found to show a linear detection range from 1 fg mL-1 to 1 ng mL-1 with a detection limit of 0.09 fg mL-1. Furthermore, the biosensor exhibited excellent specificity and stability, indicating that such a novel nanobiotechnology platform can be used to initiate potential utility for monitoring biomarkers in serum. (A)Schematic presentation of synthesis and surface modification of Ag/Fe-MOFs. The new Ag/Fe-MOFs nanocomposite possessed commendable conductivity and large surface area to carry more nanoprobe; after functionalizing the Ag/MOFs with SH-PEG-COOH, the functionalized endogenous redox mediator (c-Ag/MOFs) realized the possibility that can connect with the biological catcher. (B) Schematic diagram of electrode construction for detecting α2,6-sialylated glycans (α2,6-sial-Gs). By using the c-Ag/Fe-MOFs functional endogenous redox mediator, we successfully implemented the electrochemical detection of α2,6-sial-Gs.


Asunto(s)
Hierro/química , Nanopartículas del Metal/química , Estructuras Metalorgánicas/química , Nanocompuestos/química , Polisacáridos/sangre , Plata/química , Técnicas Biosensibles , Técnicas Electroquímicas/instrumentación , Electrodos , Humanos , Límite de Detección , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Oxidación-Reducción , Análisis Espectral/métodos
5.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(5): 556-564, 2020 Oct 25.
Artículo en Zh | MEDLINE | ID: mdl-33210480

RESUMEN

OBJECTIVE: To investigate the incidence,clinical,biochemical and genetic characteristics of isovaleric acidemia (IVA) in Zhejiang province. METHODS: Between January 2009 and December 2019, a total of 3 510 004 newborns were screened for IVA using tandem mass spectrometry. Patients of IVA were confirmed by urine organic acid and IVD gene detection. IVA patients were given diet and life management, supplemented with L-carnitine and glycine treatment, long-term followed up to observe and evaluate the growth and intellectual development. RESULTS: A total of 15 patients with IVA were diagnosed, with an incidence of 1/234 000. Three patients had acute neonatal IVA, and the rest were asymptomatic. The isovalerylcarnitine (C5) levels were increased in all patients. Twelve children underwent urinary organic acid analysis, of which 11 cases had elevated isovalerylglycine levels, 4 cases with 3-hydroxyisovalerate increased simultaneously. Eleven IVA patients underwent genetic testing, 9 patients were compound heterozygous variants in IVD gene, one with homozygous variants in IVD gene, and one harbored one IVD variant. Nineteen IVD variants (14 missense mutations, 3 intron mutations, 1 code shift mutation, and 1 synonymous mutation) were identified, 11 of which were not reported. Among the 15 IVA patients, one patient died and two patients were followed up locally. The remaining patients had no obvious clinical symptoms during the follow-up (2-79 months). Three patients presented with growth and development delay, the remaining had normal physical and mental development. CONCLUSIONS: The clinical manifestations of IVA are non-specific, and the gene spectrum is scattered. Newborn patients screened by tandem mass spectrometry can receive early diagnosis and treatment, so as to correct metabolic defects and pathophysiological changes.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Isovaleril-CoA Deshidrogenasa/deficiencia , Tamizaje Neonatal , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Niño , China/epidemiología , Humanos , Recién Nacido , Isovaleril-CoA Deshidrogenasa/genética , Mutación , Espectrometría de Masas en Tándem
6.
Biochem Biophys Res Commun ; 519(4): 689-696, 2019 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-31542232

RESUMEN

USP46, a member of the ubiquitin-specific protease family, plays essential roles in cancer cell proliferation and metastasis and is used as a candidate target for cancer therapeutics. However, the effects of USP46 on renal cell carcinoma (RCC) and its underlying molecular mechanism remain unknown. In this study, the predictive and prognostic relevance of USP46 in RCC, patient-derived primary tissues, and normal liver tissues obtained from the TCGA dataset were analyzed for the USP46 mRNA levels or prognostic relevance. Gain-of-function or loss-of-function assays were used to evaluate the vital roles of USP46 in tumor cell proliferation and cell migration. As a result, the USP46 expression level in RCC is highly decreased compared to normal tissues, and the Kaplan-Meier curve showed that USP46 high expression patients had good prognoses. Functionally, the forced expression of USP46 significantly restrained tumor cell proliferation, colony formation, and cell migration. The shRNA mediated USP46 knockdown cells exhibited the opposite results. We further showed that ectopically expressed USP46 obviously inhibited the AKT signaling pathway in cancer cells, while USP46 depletion caused a dramatic increase in AKT activity reflected by phosphorylation in the serine and threonine residues of AKT or downstream p70S6K1. Importantly, MK2206, a specific AKT inhibitor, completely counteracted the effects on cell proliferation, cell migration, and AKT activity in the USP46 depletion cells. We thus revealed a novel mechanism of USP46 regulation in RCC, and our data indicate that USP46 is a tumor suppressor in RCC via AKT signaling pathway inactivation.


Asunto(s)
Carcinogénesis/genética , Carcinoma de Células Renales/genética , Endopeptidasas/genética , Neoplasias Renales/genética , Proteínas Proto-Oncogénicas c-akt/genética , Carcinogénesis/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Endopeptidasas/metabolismo , Células HEK293 , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Transducción de Señal/genética
7.
Angew Chem Int Ed Engl ; 58(36): 12529-12533, 2019 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-31286601

RESUMEN

A rhodium-catalyzed system is introduced for in situ modification of biaryl-type monophosphines with hydrosilanes through a PIII -chelation-assisted dehydrogenative silylation reaction. A series of ligands containing silyl groups with different steric and electronic properties were obtained with excellent regioselectivities. This method offers many advantages, including the use of commercially available phosphines, no requirement for an external ligand or oxidant, a broader substrate scope, high efficiency, and access to a single regioisomer. Based on the outstanding properties of the parent scaffolds, the silyl-substituted phosphines serve as excellent ligands in Pd-catalyzed asymmetric Suzuki coupling reactions.

8.
J Am Chem Soc ; 140(29): 9061-9065, 2018 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-29989802

RESUMEN

A copper-catalyzed system has been introduced for the enantioselective defluoroalkylation of linear 1-(trifluoromethyl)alkenes through C-F activation to synthesize various gem-difluoroalkenes as carbonyl mimics. For the first time, arylboronate-activated alkyl Grignard reagents were uncovered in this cross-coupling reaction. Mechanistic studies confirmed that the tetraorganoborate complexes generated in situ were the key reactive species for this transformation.

9.
Sensors (Basel) ; 18(3)2018 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-29518059

RESUMEN

Water quality detection plays an increasingly important role in environmental protection. In this work, a novel colorimeter based on the Beer-Lambert law was designed for chemical element detection in water with high precision and miniaturized structure. As an example, the colorimeter can detect phosphorus, which was accomplished in this article to evaluate the performance. Simultaneously, a modified algorithm was applied to extend the linear measurable range. The colorimeter encompassed a near infrared laser source, a microflow cell based on microfluidic technology and a light-sensitive detector, then Micro-Electro-Mechanical System (MEMS) processing technology was used to form a stable integrated structure. Experiments were performed based on the ammonium molybdate spectrophotometric method, including the preparation of phosphorus standard solution, reducing agent, chromogenic agent and color reaction. The device can obtain a wide linear response range (0.05 mg/L up to 7.60 mg/L), a wide reliable measuring range up to 10.16 mg/L after using a novel algorithm, and a low limit of detection (0.02 mg/L). The size of flow cell in this design is 18 mm × 2.0 mm × 800 µm, obtaining a low reagent consumption of 0.004 mg ascorbic acid and 0.011 mg ammonium molybdate per determination. Achieving these advantages of miniaturized volume, high precision and low cost, the design can also be used in automated in situ detection.

10.
J Lipid Res ; 58(7): 1417-1427, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28536108

RESUMEN

Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD.


Asunto(s)
Antígenos CD36/metabolismo , Obesidad/complicaciones , Insuficiencia Renal Crónica/metabolismo , Animales , Transporte Biológico , Antígenos CD36/deficiencia , Antígenos CD36/genética , Caseínas/efectos adversos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/metabolismo , Técnicas de Inactivación de Genes , Humanos , Inflamación/inducido químicamente , Inflamación/complicaciones , Espacio Intracelular/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Ratones , Ratones Endogámicos C57BL , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología , Regulación hacia Arriba
11.
Tumour Biol ; 39(7): 1010428317711644, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28720063

RESUMEN

STYK1 (Serine/threonine/tyrosine kinase 1), a member of the receptor tyrosine kinase family, exhibits tumorigenicity in many types of cancers. Our study reveals the important role played by STYK1 in nasopharyngeal carcinoma. STYK1 is upregulated in nasopharyngeal carcinoma tissues compared with para-carcinoma. Knockdown of STYK1 inhibits nasopharyngeal carcinoma cell proliferation, migration, and invasion, while ectopic STYK1 expression significantly promoted cell proliferation, migration, and invasion abilities. In addition, we provided lines of evidence supporting the critical role of STYK1 in the regulation of glycolysis via activation of phosphoinositide 3-kinase/AKT pathway. Survival analysis reveals that STYK1 level is an independent prognostic factor for nasopharyngeal carcinoma patients. Our results indicate that STYK1 is a promising therapeutic target in nasopharyngeal carcinoma.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Proliferación Celular/genética , Neoplasias Nasofaríngeas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Adulto , Anciano , Carcinoma/patología , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , Invasividad Neoplásica/genética , Fosfatidilinositol 3-Quinasas/genética , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal
12.
Eur Spine J ; 26(6): 1775-1781, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27844230

RESUMEN

PURPOSE: To explore the compensation mechanisms of immediate postoperative coronal imbalance (CIB) and identify the correlation between preoperative lumbosacral obliquity and postoperative CIB in patients with Lenke 5/6 adolescent idiopathic scoliosis (AIS) during a 2-year follow-up period. METHODS: Medical records of patients with Lenke 5/6 AIS who were admitted in our hospital between Jan. 2008 and Jan. 2013 were reviewed retrospectively. General information of the patients including gender, age, and Risser classification was collected. Patients were divided into coronal balance (CB) and CIB groups according to the postoperative CB. Radiographic assessment included preoperative, postoperative and full-length anteroposterior and lateral radiographs and passive lateral bending radiographs of the spine at the last follow-up. RESULTS: Altogether 80 patients (37 in CIB group and 43 in CB group) were included in this study, of whom 27 patients in CIB group achieved balance at the last follow-up. Binary logistic regression showed that preoperative bending L5 tilt (OR = 1.498) was a potential risk factor of postoperative CIB (p < 0.05). Pearson correlation analysis showed that the distal wedge angle was significantly associated with immediate postoperative CB. CONCLUSIONS: Preoperative L5 tilt on bending radiographs was an important risk factor of postoperative CIB in Lenke 5/6 AIS, which might be compensated by the way similar to that seen in the Lenke 1 distal adding-on phenomenon. Appropriate shortening of the fusion segments may help reduce the occurrence of postoperative CIB in patients with a relatively large L5 tilt on the postoperative bending radiograph.


Asunto(s)
Vértebras Lumbares/diagnóstico por imagen , Escoliosis/diagnóstico por imagen , Escoliosis/cirugía , Fusión Vertebral , Vértebras Torácicas/diagnóstico por imagen , Adolescente , Niño , Femenino , Humanos , Modelos Logísticos , Vértebras Lumbares/cirugía , Masculino , Estudios Retrospectivos , Vértebras Torácicas/cirugía , Adulto Joven
13.
World J Clin Cases ; 12(19): 4022-4028, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38994275

RESUMEN

BACKGROUND: Indeterminate dendritic cell tumor (IDCT) is a rare tumor of immune cells, and IDCT patients without skin lesions are rarely reported. Therefore, the clinical course in this type of patient is unclear, and further research on the underlying pathological mechanisms and appropriate treatments is needed. CASE SUMMARY: This study describes a female IDCT patient with bile duct lesions. The strong mimicry of IDCT lesions confused doctors, and consequently, this patient, who had no skin lesions, was first diagnosed with cholangiocarcinoma. Then, she presented with persistent abdominal distension without jaundice. Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination. However, no tumor cells or pathogens were found in the three subsequent ascites analyses. It took 2 years to reach the correct diagnosis, which was eventually obtained by performing surgery for biopsy of the patient's abdominal lymph nodes. However, by then, she was already in a cachexic state. Finally, she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases. CONCLUSION: For IDCT patients without skin lesions, early biopsy is the key to obtaining a correct diagnosis. Moreover, the collective management of IDCT patients is important. Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.

14.
Oncol Lett ; 27(1): 40, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38108070

RESUMEN

Primary cardiac lymphomas display a low frequency, sudden onset, swift progression of illness and elevated mortality rates. The current study presents a unique instance of primary cardiac diffuse large B-cell lymphoma and examines its clinical manifestations, pathological characteristics and differential diagnosis. A 64-year-old male patient sought medical attention due to cardiac debility and exertional dyspnea persisting for >10 days. Chest enhanced computed tomography revealed a moderately enhancing irregular mass in the ventricular area, exhibiting limited demarcation from the pericardium and left atrium, accompanied by irregular thickening of the interventricular septum. The postoperative specimen showed the presence of yellow fish-like tumor tissue. Immunohistochemical analysis revealed the presence of lymphocytes positive for CD20, BCL-2, BCL-6, c-Myc-binding protein, mutated melanoma-associated antigen 1 and CD79a, along with a high Ki-67 proliferation index of 80%. Conversely, CD10, CD30, CD3, pan cytokeratin, cyclin D1, desmin and vimentin marker results were found to be negative. Additionally, in situ hybridization demonstrated a lack of Epstein-Barr virus-encoded small RNA expression. The present case report emphasizes the significance of conducting a thorough analysis of the clinical manifestations of diffuse large B-cell lymphoma to assist clinicians in establishing a diagnosis and determining an effective treatment approach, thereby enhancing the patient's prognosis.

15.
Eur J Pharm Sci ; 192: 106624, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37898394

RESUMEN

The pursuit of single drugs targeting multiple targets has become a prominent trend in modern cancer therapeutics. Natural products, known for their multi-targeting capabilities, accessibility, and cost-effectiveness, hold great potential for the development of multi-target drugs. However, their therapeutic efficacy is often hindered by complex structural modifications and limited anti-tumor activity. In this study, we present a novel approach using celastrol (CST)-based Proteolysis Targeting Chimeras (PROTACs) for breast cancer therapy. Through rational design, we have successfully developed compound 6a, a potent multiple protein degrader capable of selectively degrading GRP94 and CDK1/4 in tumor cells via the endogenous ubiquitin-proteasome system. Furthermore, compound 6a has demonstrated remarkable inhibitory effects on cell proliferation and migration, and induction of apoptosis in 4T1 cells through cell cycle arrest and activation of the Bcl-2/Bax/cleaved Caspase-3 apoptotic pathway. In vivo administration of compound 6a has effectively suppressed tumor growth with an acceptable safety profile. Our findings suggest that the CST-based PROTACs described herein can be readily extended to other natural products, offering a potential avenue for the development of natural product-based PROTACs for cancer treatment.


Asunto(s)
Productos Biológicos , Neoplasias de la Mama Triple Negativas , Humanos , Proteolisis , Quimera Dirigida a la Proteólisis , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2
16.
J Mater Chem B ; 12(10): 2547-2558, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38358131

RESUMEN

Monitoring active membrane cholesterol and lipid raft cholesterol in the inner leaflet of the plasma membrane is significant for understanding the membrane function and cellular physiopathological processes. Limited by existing methods, it is difficult to differentiate active membrane cholesterol and lipid raft cholesterol. A novel dual-monomer solvatochromic probe system (DSPS) that targets two types of cholesterol was developed. Acrylodan-BG/SNAP-D4 composed of SNAP-D4 cholesterol-recognizing monomers and solvatochromic acrylodan-BG-sensing monomers exhibits excellent cholesterol detecting properties in terms of selectivity, accuracy, convenience and economic benefits. Cell imaging revealed that lipid raft cholesterol emitted blue fluorescence, whereas active membrane cholesterol (which partially bobbed in aqueous cytosol) displayed green fluorescence; both the fluorescence emissions increased or decreased in a cholesterol-dependent manner. This system provides a new technology for the determination of two types of cholesterol, which is beneficial for the further study of membrane function, intracellular cholesterol trafficking, and cell signaling.


Asunto(s)
2-Naftilamina/análogos & derivados , Colesterol , Microdominios de Membrana , Membrana Celular/metabolismo , Colesterol/metabolismo , Microdominios de Membrana/metabolismo
17.
J Colloid Interface Sci ; 657: 960-970, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38096779

RESUMEN

Amorphous inorganic solids are traditionally isotropic, thus, it is believed that they only grow in a non-preferential way without the assistance of regulators, leading to the morphologies of nanospheres or irregular aggregates of nanoparticles. However, in the presence of (ortho)phosphate (Pi) and pyrophosphate ions (PPi) which have synergistic roles in biomineralization, the highly elongated amorphous nanowires (denoted ACPPNs) form in a regulator-free aqueous solution (without templates, additives, organics, etc). Based on thorough characterization and tracking of the formation process (e.g., Cryo-TEM, spherical aberration correction high resolution TEM, solid state NMR, high energy resolution monochromated STEM-EELS), the microstructure and its preferential growth behavior are elucidated. In ACPPNs, amorphous calcium orthophosphate and amorphous calcium pyrophosphate are distributed at separated but close sites. The ACPPNs grow via either the preferential attachment of ∼2 nm nanoclusters in a 1-dimension way, or the transformation of bigger nanoparticles, indicating an inherent driving force-governed process. We propose that the anisotropy of ACPPNs microstructure, which is corroborated experimentally, causes their oriented growth. This study proves that, unlike the conventional view, amorphous minerals can form via oriented growth without external regulation, demonstrating a novel insight into the structures and growth behaviors of amorphous minerals.

18.
Histopathology ; 63(5): 696-703, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24025073

RESUMEN

AIMS: The aim of this study was to evaluate the prevalence of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) expression, and explore the prognostic significance of PBK/TOPK expression alone and in combination with Ki67 and p53 expression in non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: We detected PBK/TOPK expression in 30 samples of normal lung tissue, 32 lymph node metastases and 279 primary non-small-cell lung cancers by immunohistochemistry, and analysed the correlation of PBK/TOPK expression with Ki67 and p53 expression in primary tumour tissues. The results showed that PBK/TOPK expression was higher in lymph node metastases (75%) than in primary tumours (44.8%) and normal lung tissues (0%). PBK/TOPK expression was associated with histological type, lymph node metastasis, and TNM stage, and was positively correlated with Ki67 and p53 expression in NSCLC. Univariate and multivariate survival analyses showed that PBK/TOPK expression was significantly associated with an unfavourable prognosis in NSCLC. The prognosis of patients with tumours positive for both PBK/TOPK expression and Ki67 or p53 expression was also significantly unfavourable. CONCLUSIONS: PBK/TOPK expression is positively correlated with Ki67 and p53 expression, and can be used as an independent prognostic factor in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmón/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Antígeno Ki-67/metabolismo , Pulmón/patología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Proteína p53 Supresora de Tumor/metabolismo
19.
Expert Opin Drug Saf ; 22(4): 331-338, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36178050

RESUMEN

BACKGROUND: We study the adverse events (AEs) of bamlanivimab (BAM), bamlanivimab/etesevimab (BAM/ETE) to alert risk factors during coronavirus disease 2019 (COVID-19) treatment and provide references for drug safety. RESEARCH DESIGN AND METHODS: Extract AEs from the COVID-19 Emergency Use Authorization (EUA) FDA Adverse Event Reporting System (FAERS) Public Dashboard. Disproportionality analysis was performed to discover the potential risks of BAM and BAM/ETE. RESULTS: With COVID-19 drugs as the research background, the number of BAM/ETE signals is about half that of BAM, and 80% of signals overlap with BAM. Signals such as atrial fibrillation, tachycardia, and confusional state are present in BAM but not in BAM/ETE. With BAM and BAM/ETE as the research background, potential safety signals of BAM/ETE such as acute respiratory failure, hypersensitivity, and infusion-related reaction require long-term observation, especially acute respiratory failure which is not in the label. CONCLUSIONS: The AEs report on this study confirm most of the label information of BAM and BAM/ETE. BAM/ETE is relatively safe, while the risk signals such as acute respiratory failure and infusion-related reaction require to be monitored.


Asunto(s)
COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Insuficiencia Respiratoria , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos
20.
Medicine (Baltimore) ; 102(22): e33973, 2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37266601

RESUMEN

RATIONALE: Moyamoya disease (MMD) is a cerebrovascular structural disorder characterized by bilateral stenosis and obstruction of the internal carotid artery, anterior cerebral artery, and initial segment of a middle cerebral artery, as well as the aberrant formation of collateral arteries at the base of the brain. Moyamoya disease with distal anterior choroidal artery (AChA) aneurysm is extremely uncommon. At present, the treatment of Moyamoya disease with aneurysm mainly includes conservative treatment and surgical treatment, including revascularization, endovascular therapy and microsurgical clipping or resection. Interventional therapy is the first treatment of choice. For those whose paths are tortuous and inaccessible and intervention fails, I successfully excised them through craniotomy. PATIENT CONCERNS: The 38-year-old male patient, diagnosed with Moyamoya disease 11 years ago and was hospitalized for multiple intraventricular hemorrhages throughout that time. During the 11 years, the patient was hospitalized for intra ventricular hemorrhage for several times. The patient was diagnosed as moyamoya disease for many times by digital subtraction angiography, but he was recommended to come to our hospital for cerebrovascular bypass surgery 3 months after each hemorrhage, but he did not come to our hospital until the next intraventricular hemorrhages. DIAGNOSES: This recurrent intraventricular bleeding was suspected to be caused by MMD, and a digital subtraction angiography of the brain revealed an aneurysm of the distal AChA. INTERVENTIONS: Interventional therapy was the first choice. During the operation, transcatheter aneurysm embolization was tried. Finally, interventional therapy was abandoned because the vessels were too thin and tortuous and the guide wire could not pass through. After detecting the aneurysm using computerized tomography angiography, the distal AChA aneurysm was resected through the lateral interventricular foramen of the corpus callosum, and the corpus callosum was parted along the interhemispheric fissure to access the third ventricle. OUTCOMES: On the 21st postoperative day, the patient improved, recovered to a Glasgow Coma Scale score of 15. LESSONS: We conclude that craniotomy is a satisfying alternative in patients with MMD complicated by perforated distal AChA aneurysm hemorrhage if the vascular prerequisites for endovascular treatment are not accessible and the patient has a favorable prognosis.


Asunto(s)
Aneurisma Intracraneal , Enfermedad de Moyamoya , Masculino , Humanos , Adulto , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/cirugía , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Angiografía Cerebral/métodos , Arterias Cerebrales , Hemorragia Cerebral/complicaciones
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA