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1.
Proc Natl Acad Sci U S A ; 120(34): e2300856120, 2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37579165

RESUMEN

Space heating and cooling consume ~13% of global energy every year. The development of advanced materials that promote energy savings in heating and cooling is gaining increasing attention. To thermally isolate the space of concern and minimize the heat exchange with the outside environment has been recognized as one effective solution. To this end, here, we develop a universal category of colorful low-emissivity paints to form bilayer coatings consisting of an infrared (IR)-reflective bottom layer and an IR-transparent top layer in colors. The colorful visual appearance ensures the aesthetical effect comparable to conventional paints. High mid-infrared reflectance (up to ~80%) is achieved, which is more than 10 times as conventional paints in the same colors, efficiently reducing both heat gain and loss from/to the outside environment. The high near-IR reflectance also benefits reducing solar heat gain in hot days. The advantageous features of these paints strike a balance between energy savings and penalties for heating and cooling throughout the year, providing a comprehensive year-round energy-saving solution adaptable to a wide variety of climatic zones. Taking a typical midrise apartment building as an example, the application of our colorful low-emissivity paints can realize positive heating, ventilation, and air conditioning energy saving, up to 27.24 MJ/m2/y (corresponding to the 7.4% saving ratio). Moreover, the versatility of the paint, along with its applicability to diverse surfaces of various shapes and materials, makes the paints extensively useful in a range of scenarios, including building envelopes, transportation, and storage.

2.
EMBO J ; 39(18): e105246, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32974937

RESUMEN

Tetraspanins, including CD53 and CD81, regulate a multitude of cellular processes through organizing an interaction network on cell membranes. Here, we report the crystal structure of CD53 in an open conformation poised for partner interaction. The large extracellular domain (EC2) of CD53 protrudes away from the membrane surface and exposes a variable region, which is identified by hydrogen-deuterium exchange as the common interface for CD53 and CD81 to bind partners. The EC2 orientation in CD53 is supported by an extracellular loop (EC1). At the closed conformation of CD81, however, EC2 disengages from EC1 and rotates toward the membrane, thereby preventing partner interaction. Structural simulation shows that EC1-EC2 interaction also supports the open conformation of CD81. Disrupting this interaction in CD81 impairs the accurate glycosylation of its CD19 partner, the target for leukemia immunotherapies. Moreover, EC1 mutations in CD53 prevent the chemotaxis of pre-B cells toward a chemokine that supports B-cell trafficking and homing within the bone marrow, a major CD53 function identified here. Overall, an open conformation is required for tetraspanin-partner interactions to support myriad cellular processes.


Asunto(s)
Movimiento Celular , Células Precursoras de Linfocitos B/metabolismo , Tetraspanina 25 , Tetraspanina 28 , Animales , Antígenos CD19/química , Antígenos CD19/genética , Antígenos CD19/metabolismo , Humanos , Ratones , Ratones Noqueados , Dominios Proteicos , Tetraspanina 25/química , Tetraspanina 25/genética , Tetraspanina 25/metabolismo , Tetraspanina 28/química , Tetraspanina 28/genética , Tetraspanina 28/metabolismo
3.
Bioorg Chem ; 143: 107034, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38118299

RESUMEN

In continuation of our program to search for novel potential anti-ischemic stroke agents, a series of 1,3,4-oxadiazole and sulfoxide hybrids of phthalide derivatives was designed and synthesized in this study to evaluate their anti-ischemic stroke activity. Among them, compounds 5b, 5d, 5 l, and 5 m exhibited excellent inhibitory effects on platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid (AA). In particular, compound 5b possessed considerable antithrombotic activity in animal models, as demonstrated by the effective alleviation of carrageenan-induced and FeCl3-induced thrombosis in tail and carotid arteries, respectively. Notably, intraperitoneal administration of compound 5b could better protect the brain from injury caused by ischemia/reperfusion in rats compared with precursor 3-n-butylphthalide. Further pharmacokinetics, liver microsomal stability, and PAMPA-BBB assays also indicated that compound 5b had relatively high bioavailability, metabolic stability, and BBB permeability. Moreover, compound 5b showed a safety profile that was superior to the clinical drugs clopidogrel, aspirin, and 3-n-butylphthalide in the mouse-tail bleeding assay. Finally, molecular docking predicted that the potential target of the antiplatelet aggregation activity of compound 5b was P2Y12 receptor. This research provides a novel candidate compound for the treatment of ischemic stroke.


Asunto(s)
Benzofuranos , Accidente Cerebrovascular Isquémico , Oxadiazoles , Inhibidores de Agregación Plaquetaria , Ratones , Ratas , Animales , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Simulación del Acoplamiento Molecular , Accidente Cerebrovascular Isquémico/tratamiento farmacológico
4.
Cryobiology ; 115: 104895, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38616031

RESUMEN

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.


Asunto(s)
Glándulas Suprarrenales , Criopreservación , Hidrocortisona , Trasplante Heterólogo , Animales , Glándulas Suprarrenales/metabolismo , Trasplante Heterólogo/métodos , Criopreservación/métodos , Porcinos , Hidrocortisona/sangre , Ratas , Glucemia/metabolismo , Glucemia/análisis , Aldosterona/sangre , Aldosterona/metabolismo , Masculino , Glucógeno/metabolismo , Resucitación/métodos , Preservación de Órganos/métodos , Crioprotectores/farmacología , Dimetilsulfóxido/farmacología
5.
Skin Res Technol ; 30(4): e13698, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38634154

RESUMEN

BACKGROUND: Dermoscopy is a common method of scalp psoriasis diagnosis, and several artificial intelligence techniques have been used to assist dermoscopy in the diagnosis of nail fungus disease, the most commonly used being the convolutional neural network algorithm; however, convolutional neural networks are only the most basic algorithm, and the use of object detection algorithms to assist dermoscopy in the diagnosis of scalp psoriasis has not been reported. OBJECTIVES: Establishment of a dermoscopic modality diagnostic framework for scalp psoriasis based on object detection technology and image enhancement to improve diagnostic efficiency and accuracy. METHODS: We analyzed the dermoscopic patterns of scalp psoriasis diagnosed at 72nd Group army hospital of PLA from January 1, 2020 to December 31, 2021, and selected scalp seborrheic dermatitis as a control group. Based on dermoscopic images and major dermoscopic patterns of scalp psoriasis and scalp seborrheic dermatitis, we investigated a multi-network fusion object detection framework based on the object detection technique Faster R-CNN and the image enhancement technique contrast limited adaptive histogram equalization (CLAHE), for assisting in the diagnosis of scalp psoriasis and scalp seborrheic dermatitis, as well as to differentiate the major dermoscopic patterns of the two diseases. The diagnostic performance of the multi-network fusion object detection framework was compared with that between dermatologists. RESULTS: A total of 1876 dermoscopic images were collected, including 1218 for scalp psoriasis versus 658 for scalp seborrheic dermatitis. Based on these images, training and testing are performed using a multi-network fusion object detection framework. The results showed that the test accuracy, specificity, sensitivity, and Youden index for the diagnosis of scalp psoriasis was: 91.0%, 89.5%, 91.0%, and 0.805, and for the main dermoscopic patterns of scalp psoriasis and scalp seborrheic dermatitis, the diagnostic results were: 89.9%, 97.7%, 89.9%, and 0.876. Comparing the diagnostic results with those of five dermatologists, the fusion framework performs better than the dermatologists' diagnoses. CONCLUSIONS: Studies have shown some differences in dermoscopic patterns between scalp psoriasis and scalp seborrheic dermatitis. The proposed multi-network fusion object detection framework has higher diagnostic performance for scalp psoriasis than for dermatologists.


Asunto(s)
Dermatitis Seborreica , Psoriasis , Neoplasias Cutáneas , Humanos , Cuero Cabelludo , Inteligencia Artificial , Redes Neurales de la Computación , Dermoscopía/métodos , Neoplasias Cutáneas/diagnóstico
6.
Chem Biodivers ; 21(5): e202400110, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38424689

RESUMEN

Drugs with anti-platelet aggregation and neuroprotection are of great significance for the treatment of ischemic stroke. A series of edaravone and 6-phenyl-4,5-dihydropyridazin-3(2H)-one hybrids were designed and synthesized. Among them, 6g showed the most effective cytoprotective effect against oxygen-glucose deprivation/reoxygenation-induced damage in BV2 cells and an excellent inhibitory effect on platelet aggregation induced by adenosine diphosphate and arachidonic acid. Additionally, 6g could prevent thrombosis caused by ferric chloride in rats and pose a lower risk of causing bleeding compared with aspirin. It provides better protection against ischemia/reperfusion injury in rats compared with edaravone and alleviates the oxidative stress related to cerebral ischemia/reperfusion by increasing the GSH and SOD levels and decreasing the MDA concentration. Finally, molecular docking results showed that 6g probably acts on PDE3 A and plays an anti-platelet aggregation effect. Overall, 6g could be a potential candidate compound for the treatment of ischemic stroke.


Asunto(s)
Edaravona , Accidente Cerebrovascular Isquémico , Fármacos Neuroprotectores , Inhibidores de Agregación Plaquetaria , Agregación Plaquetaria , Animales , Edaravona/farmacología , Edaravona/química , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Ratas , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/química , Inhibidores de Agregación Plaquetaria/síntesis química , Agregación Plaquetaria/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/síntesis química , Simulación del Acoplamiento Molecular , Masculino , Ratones , Estructura Molecular , Relación Estructura-Actividad , Ratas Sprague-Dawley , Descubrimiento de Drogas , Piridazinas/farmacología , Piridazinas/química , Estrés Oxidativo/efectos de los fármacos
7.
Chem Biodivers ; 21(3): e202400043, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38361278

RESUMEN

Four series of novel 1,3,4-oxadiazole/1,2,4-triazole hybrids of phthalide derivatives were designed and synthesized to search for novel potential antifungal agents. Preliminary antifungal activity assay results showed that compounds 4 a, 4 b, 4 m, 5 b, 5 f, 5 h, and 7 h exhibited moderate to excellent inhibitory activity against some phytopathogenic fungi. Among them, compound 5 b displayed the most outstanding antifungal effects against V. mali and S. sclerotiorum, with the EC50 mean of 3.96 µg/mL and 5.60 µg/mL, respectively, which was superior to those of commercial fungicides hymexazol and chlorothalonil. Furthermore, compound 5 b could completely suppress the spore germination of V. mali at a concentration of 10 µg/mL. Finally, molecular docking revealed that the potential target for the antifungal activity of compound 5 b was succinate dehydrogenase (SDH). This research provides novel candidate compounds for the prevention of phytopathogenic fungi.


Asunto(s)
Antifúngicos , Benzofuranos , Hongos , Oxadiazoles , Triazoles , Antifúngicos/farmacología , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular
8.
Development ; 147(17)2020 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-32747435

RESUMEN

Homeostasis of intestinal stem cells (ISCs) is maintained by the orchestration of niche factors and intrinsic signaling networks. Here, we have found that deletion of Erk1 and Erk2 (Erk1/2) in intestinal epithelial cells at embryonic stages resulted in an unexpected increase in cell proliferation and migration, expansion of ISCs, and formation of polyp-like structures, leading to postnatal death. Deficiency of epithelial Erk1/2 results in defects in secretory cell differentiation as well as impaired mesenchymal cell proliferation and maturation. Deletion of Erk1/2 strongly activated Wnt signaling through both cell-autonomous and non-autonomous mechanisms. In epithelial cells, Erk1/2 depletion resulted in loss of feedback regulation, leading to Ras/Raf cascade activation that transactivated Akt activity to stimulate the mTor and Wnt/ß-catenin pathways. Moreover, Erk1/2 deficiency reduced the levels of Indian hedgehog and the expression of downstream pathway components, including mesenchymal Bmp4 - a Wnt suppressor in intestines. Inhibition of mTor signaling by rapamycin partially rescued Erk1/2 depletion-induced intestinal defects and significantly prolonged the lifespan of mutant mice. These data demonstrate that Erk/Mapk signaling functions as a key modulator of Wnt signaling through coordination of epithelial-mesenchymal interactions during intestinal development.


Asunto(s)
Intestinos/embriología , Sistema de Señalización de MAP Quinasas , Vía de Señalización Wnt , Animales , Proteína Morfogenética Ósea 4/genética , Proteína Morfogenética Ósea 4/metabolismo , Ratones , Ratones Noqueados , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Quinasas raf/genética , Quinasas raf/metabolismo
9.
Mol Divers ; 27(2): 589-601, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35639225

RESUMEN

In order to find novel environment-friendly and effective antifungal agents, four series of 2,2-dimethyl-2H-chromene derivatives were designed, synthesized and characterized by spectroscopic analysis. The antifungal activities of all the target compounds against nine phytopathogenic fungi were evaluated in vitro. Preliminary results indicated that most of the target compounds exhibited obvious antifungal activity at the concentration of 50 µg/mL. Among them, compound 4j displayed more promising antifungal potency against Fusarium solani, Pyricularia oryzae, Alternaria brassicae, Valsa mali and Alternaria alternata strains than the two commercially available fungicides chlorothalonil and hymexazol, with the corresponding EC50 values of 6.3, 7.7, 7.1, 7.5, 4.0 µg/mL, respectively. Moreover, the cell experiments results suggested that the target compounds had low cytotoxicity to the PC12 cell. This research will provide theoretical basis for the future application of 2,2-dimethyl-2H-chromenes as botanical fungicides in agriculture. Four series of novel, potent and low-toxicity 2,2-dimethyl-2H-chromene derivatives were designed and synthesized as agricultural antifungal agents. The in vitro antifungal experiments showed that compound 4j exhibited higher antifungal efficacy against five strains than the two commercially-available fungicides chlorothalonil and hymexazol.


Asunto(s)
Antifúngicos , Fungicidas Industriales , Relación Estructura-Actividad , Nitrilos , Hongos , Pruebas de Sensibilidad Microbiana
10.
Mol Divers ; 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37847466

RESUMEN

To discover novel and effective potential agricultural antifungal agents, various kinds of imidazo[1,2-a]quinoxaline derivatives were designed, and synthesized from available and inexpensive reagents. Their antifungal activities were first evaluated against ten typical phytopathogenic fungi. The in vitro antifungal activity showed that some compounds exhibited more obvious broad-spectrum fungicidal activity than the two commercially-available fungicides chlorothalonil and hymexazol. Valsa mali and Botrytis cinerea strains exhibited the highest susceptibility with EC50 values of 1.4-27.0 µg/mL to more than ten compounds. Compounds 5c and 5f showed the most promising inhibitory effects against Valsa mali (EC50 = 5.6 µg/mL) and Fusarium solani (EC50 = 5.1 µg/mL), respectively. Preliminary studies on the mechanism of action indicated that the imidazo[1,2-a]quinoxaline skeleton likely exerted its antifungal effects by disrupting hyphal differentiation, spore germination, and germ tube growth. Moreover, the cell experiment results indicated that these target compounds possessed good safety to BV2 cells. Overall, compounds 5c and 5f can be considered candidate compounds against specific fungi for further detailed research. This study can provide a theoretical basis for the application of imidazo[1,2-a]quinoxaline scaffolds as novel fungicides in agriculture.

11.
Adv Exp Med Biol ; 1433: 69-86, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37751136

RESUMEN

Methylation of histone H3 lysine 9 (H3K9) is a repressive histone mark and associated with inhibition of gene expression. KDM3 is a subfamily of the JmjC histone demethylases. It specifically removes the mono- or di-methyl marks from H3K9 and thus contributes to activation of gene expression. KDM3 subfamily includes three members: KDM3A, KDM3B and KDM3C. As KDM3A (also known as JMJD1A or JHDM2A) is the best studied, this chapter will mainly focus on the role of KDM3A-mediated gene regulation in the biology of normal and cancer cells. Knockout mouse studies have revealed that KDM3A plays a role in the physiological processes such as spermatogenesis, metabolism and sex determination. KDM3A is upregulated in several types of cancers and has been shown to promote cancer development, progression and metastasis. KDM3A can enhance the expression or activity of transcription factors through its histone demethylase activity, thereby altering the transcriptional program and promoting cancer cell proliferation and survival. We conclude that KDM3A may serve as a promising target for anti-cancer therapies.


Asunto(s)
Histona Demetilasas con Dominio de Jumonji , Neoplasias , Animales , Masculino , Ratones , Regulación de la Expresión Génica , Ratones Noqueados , Neoplasias/genética , Factores de Transcripción , Histona Demetilasas con Dominio de Jumonji/genética
12.
Chem Biodivers ; 20(1): e202201002, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36424354

RESUMEN

In order to find novel antiplatelet drugs for the treatment of ischemic stroke, a series of 3-butylphthalide derivatives containing isopentenylphenol moiety were designed, synthesized and characterized with spectroscopic analyses. The in vitro antiplatelet activity results indicated that compound 3 better inhibited the arachidonic acid (AA) induced platelet aggregation than aspirin (ASP) and 3-butylphthalide (NBP). Additionally, compared with precursor NBP, compound 3 possessed outstanding antithrombotic activity in the animal experiment model, which could effectively alleviate the formation of tail thrombus and carotid artery thrombus in mice. More importantly, intraperitoneal administration of compound 3 can well protected the rats against ischemia/reperfusion-induced brain injury. Further pharmacokinetic (PK) assay indicated that compound 3 had good absorption characteristics and metabolic stability in vivo. Overall, the present research provides a new candidate compound for the treatment of ischemic stroke caused by platelet aggregation.


Asunto(s)
Accidente Cerebrovascular Isquémico , Trombosis , Ratas , Ratones , Animales , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/química , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Agregación Plaquetaria , Trombosis/tratamiento farmacológico
13.
Opt Express ; 30(4): 6142-6160, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35209557

RESUMEN

Understanding the frequency spectrum of the optical force is important for controlling and manipulating micro- and nano-scale objects using light. Spectral resonances of these objects can significantly influence the optical force spectrum. In this paper, we develop a theoretical formalism based on the temporal coupled-mode theory that analytically describes the lineshapes of force spectra and their dependencies on resonant scatterers for arbitrary incident wavefronts. We obtain closed-form formulae and discuss the conditions for achieving symmetric as well as asymmetric lineshapes, pertaining, respectively, to a Lorentzian and Fano resonance. The relevance of formalism as a design tool is exemplified for a conceptual scheme of the size-sorting mechanism of small particles, which plays a role in biomedical diagnosis.

14.
Pharmacol Res ; 179: 106123, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35150861

RESUMEN

Diabetic retinopathy (DR) manifests as a complicated and blinding complication in diabetes mellitus. First-line treatments for advanced DR have shown ocular side-effects in some patients. Ginsenoside Rd (Rd), an active ingredient isolated from Panax notoginseng and P. ginseng, has demonstrated diverse and powerful activities on neuroprotection, anticancer and anti-inflammation, but its vascular protective effects have rarely been reported. Herein, this study aims to investigate the protective effects of Rd on retinal endothelial injury with emphasis on AMPK/SIRT1 interaction. The results indicated that Rd promoted AMPK activation and SIRT1 expression. Besides, Rd strengthened the interaction between AMPK and SIRT1 by increasing NAD+/NADH levels and LKB1 deacetylation in endothelial cells. Moreover, Rd reversed high glucose-induced activation of NOX2, oxidative stress, mitochondrial dysfunction, and endothelial apoptosis in an AMPK/SIRT1-interdependent manner. Hyperglycemia induced loss of endothelial cells and other retinal damage, which was restored by Rd via activating AMPK and SIRT1 in vivo. The enhancement of AMPK/SIRT1 interaction by Rd beneficially modulated oxidative stress and apoptosis, and ameliorated diabetes-driven vascular damage. These data also supported the evidence for Rd clinical development of pharmacological interventions and provided a novel potential vascular protective drug for early DR.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Panax notoginseng , Proteínas Quinasas Activadas por AMP/metabolismo , Células Endoteliales/metabolismo , Ginsenósidos , Glucosa , Humanos , Sirtuina 1/metabolismo
15.
Nanotechnology ; 33(13)2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-34933287

RESUMEN

Flexible conductive thin films have recently become a research area of focus in both academia and industry. In this study, a method of preparing nanofiber conductive films by centrifugal spinning is proposed. Polyurethane (PU) nanofiber films were prepared by centrifugal spinning as the flexible substrate film, and carbon nanotubes (CNTs) were used as the conducting medium, to obtain CNTs/PU nanofiber conductive films with good conductivity and elasticity. The effects of different CNT concentrations on the properties of the nanofiber films were investigated. It was found that the conductivity of the nanofiber conductive films was optimal when an impregnation concentration of 9% CNTs was used in the stretching process. Cyclic tensile resistance tests showed that the nanofiber conductive films have good durability and repeatability. Physical and structural property analysis of the CNT/PU conductive films indicate that the adsorption of the CNTs on the PU surface was successful and the CNTs were evenly dispersed on the surface of the matrix. Moreover, the CNTs improved the thermal stability of the PU membrane. The CNT/PU conductive films were pasted onto a human finger joint, wrist joint, and Adam's apple to test the detection of movement. The results showed that finger bending, wrist bending, and laryngeal prominence movement all caused a change in resistance of the conductive film, with an approximately linear curve. The results indicate that the CNT/PU nanofiber conductive film developed in this study can be used to test the motion of human joints.

16.
Cell Mol Biol (Noisy-le-grand) ; 68(7): 160-164, 2022 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-36495502

RESUMEN

It has been noted that temozolomide resistance occurs in a number of malignancies, including glioma, although the underlying cause of this is unknown. The goal of the study in vivo investigation to show that increased CD147 expression in glioma cells is a factor in their resistance to the chemotherapy drug temozolomide. Proliferation assays, TUNEL assays, reactive oxygen species assays, protein degradation assays, immunohistochemistry, Western blotting, quantitative polymerase chain reactions, and tumorigenicity assays were all carried out. Using the human protein atlas databases, the expression levels of CD147 in different kinds of malignancies were examined. For immunohistochemistry, a total of 7, 12, 19, 15, and 16 glioma samples were taken from para-carcinoma tissue, representing stage I, stage II, stage III, and stage IV gliomas, respectively. The expression of CD147 proteins is correlated with the tumor's aggressiveness. Cell development was slowed by suppressing the expression of the CD147 protein. The expression of the CD147 protein contributed to the emergence of temozolomide resistance. Expression of the CD147 protein reduced mRNA expression. The growth-inhibitory impact of temozolomide on glioma cells was enhanced by the suppression of CD147 protein.  Nuclear factor E2-related factor 2 expression and CD147 protein expression showed a significant reciprocal connection with each other (p 0.0001, r2 = 0.3254). In glioma, resistance to temozolomide is due to overexpression of CD147 protein and induction of nuclear factor E2-related factor 2.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Temozolomida/farmacología , Temozolomida/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/metabolismo , Inmunohistoquímica , Línea Celular Tumoral , Resistencia a Antineoplásicos , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Apoptosis
17.
Mol Divers ; 26(2): 981-992, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33811571

RESUMEN

In order to discover novel antifungal agents, three series of simple 2-aminobenzoxazole derivatives were designed, synthesized and evaluated for their antifungal activities against eight phytopathogenic fungi. The in vitro antifungal results showed that most of the target compounds exhibited excellent and broad-spectrum antifungal activities to all the tested fungi. Particularly, the six compounds 3a, 3b, 3c, 3e, 3m and 3v displayed the most potent antifungal activity, with EC50 value of 1.48-16.6 µg/mL, which were much superior to the positive control hymexazol. The in vivo study further confirmed that compounds 3a, 3c, 3e and 3m displayed good preventative effect against Botrytis cinerea at the concentration of 100 µg/mL. The structure-activity relationships research provides significant reference for the further structural optimization of 2-aminobenzoxazole as potential fungicides. Forty-four 2-aminobenzoxazole derivatives were designed and synthesized as agricultural antifungal agents, the in vitro and in vivo antifungal experiments showed that compounds 3a, 3b, 3c, 3e, 3m and 3v exhibited excellent and broad-spectrum antifungal activities compare with the commercial fungicide hymexazol.


Asunto(s)
Antifúngicos , Fungicidas Industriales , Hongos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad
18.
Chem Biodivers ; 19(11): e202200802, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36146898

RESUMEN

Aiming to search for novel potential antifungal agents, forty 2H-chromene analogs were designed, synthesized and their antifungal activity against some typical plant pathogenic fungi were firstly evaluated. The in vitro antifungal bioassays showed that some of the target compounds exhibited comparable or better inhibition activities than the commercial agricultural fungicide hymexazol. Especially compound 1m displayed more promising fungicidal effect against Alternaria alternate (EC50 =9.9 µg/mL) and Botrytis cinerea (EC50 =9.4 µg/mL), which was significantly superior to hymexazol. Moreover, in vivo protective effects results also indicated that compound 1m had an excellent potential for further development as a new botanical pesticide.


Asunto(s)
Productos Biológicos , Fungicidas Industriales , Fungicidas Industriales/farmacología , Antifúngicos/farmacología , Productos Biológicos/farmacología , Relación Estructura-Actividad , Botrytis , Plantas
19.
Int Ophthalmol ; 42(1): 211-218, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34423405

RESUMEN

PURPOSES: To quantitatively evaluate the vessel density of macular microvasculature, choriocapillary, and foveal avascular zone (FAZ) in both eyes of patients with unilateral retinal vein occlusion (RVO) using the optical coherence tomography angiography (OCTA) compared with the normal controls. METHODS: A retrospective review was conducted on 72 patients with unilateral RVO (72 eyes with RVO and 72 RVO fellow eyes) and 72 healthy individuals (72 normal control eyes). The 3 × 3 mm macular angiogram was acquired using the OCTA. The vessel densities of the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillary plexus (CCP) were measured, and FAZ was quantified. RESULTS: The RVO eyes compared to their fellow eyes, and the fellow eyes compared to the normal controls, showed a significantly lower vessel density in both the SCP and DCP in the whole image and parafovea (P < 0.05) and the CCP (P < 0.05), except for the foveal region (P > 0.05). No significant differences between the RVO eyes and the fellow eyes in the FAZ area and perimeter (P > 0.05) were observed, while the acircularity index in the RVO eyes was significantly higher than the fellow eyes (P < 0.05). Additionally, the FD-300 in the RVO eyes was significantly lower than their fellow eyes (P < 0.05). CONCLUSIONS: The OCTA reveals that the macular microvasculature of the RVO fellow eyes can be impaired in both the superficial and deep retinal layer as well as the choriocapillary, suggesting the influence of systemic factors in the development of RVO.


Asunto(s)
Oclusión de la Vena Retiniana , Angiografía con Fluoresceína , Humanos , Microvasos/diagnóstico por imagen , Oclusión de la Vena Retiniana/diagnóstico , Vasos Retinianos/diagnóstico por imagen , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual
20.
Bioorg Chem ; 115: 105172, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34303898

RESUMEN

Two series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An investigation of the potential mechanism indicated that 12b may exhibit hypoglycemic activity via activation of the AMPK pathway. Metabolic stability assays revealed that 12b showed good stability profiles in both artificial gastrointestinal fluids and blood plasma from SD rats. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 12b was a potent hypoglycemic agent.


Asunto(s)
Carbazoles/química , Diseño de Fármacos , Hipoglucemiantes/síntesis química , Proteínas Quinasas Activadas por AMP/química , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Sitios de Unión , Carbazoles/farmacología , Carbazoles/uso terapéutico , Estabilidad de Medicamentos , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Semivida , Células Hep G2 , Hepatocitos/citología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Simulación de Dinámica Molecular , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad
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