Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
J Med Chem ; 67(9): 7130-7145, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38630077

RESUMEN

Multitarget medications represent an appealing therapy against the disease with multifactorial abnormalities─cancer. Therefore, simultaneously targeting son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR), two aberrantly expressed proteins crucial for the oncogenesis and progression of prostate cancer, may achieve active antitumor effects. Here, we discovered dual SOS1/EGFR-targeting compounds via pharmacophore-based docking screening. The most prominent compound SE-9 exhibited nanomolar inhibition activity against both SOS1 and EGFR and efficiently suppressed the phosphorylation of ERK and AKT in prostate cancer cells PC-3. Cellular assays also revealed that SE-9 displayed strong antiproliferative activities through diverse mechanisms, such as induction of cell apoptosis and G1 phase cell cycle arrest, as well as reduction of angiogenesis and migration. Further in vivo findings showed that SE-9 potently inhibited tumor growth in PC-3 xenografts without obvious toxicity. Overall, SE-9 is a novel dual-targeting SOS1/EGFR inhibitor that represents a promising treatment strategy for prostate cancer.


Asunto(s)
Antineoplásicos , Proliferación Celular , Receptores ErbB , Neoplasias de la Próstata , Proteína SOS1 , Masculino , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Proteína SOS1/antagonistas & inhibidores , Proteína SOS1/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones , Apoptosis/efectos de los fármacos , Descubrimiento de Drogas , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/uso terapéutico , Ratones Desnudos , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C
2.
J Med Chem ; 66(23): 16187-16200, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38093696

RESUMEN

Dual inhibition of tubulin and neuropilin-1 (NRP1) may become an effective method for cancer treatment by simultaneously killing tumor cells and inhibiting tumor angiogenesis. Herein, we identified dual tubulin/NRP1-targeting inhibitor TN-2, which exhibited good inhibitory activity against both tubulin polymerization (IC50 = 0.71 ± 0.03 µM) and NRP1 (IC50 = 0.85 ± 0.04 µM). Importantly, it significantly inhibited the viability of several human prostate tumor cell lines. Further mechanism studies indicated that TN-2 could inhibit tubulin polymerization and cause G2/M arrest, thereby inducing cell apoptosis. It could also suppress cell tube formation, migration, and invasion. Moreover, TN-2 showed obvious antitumor effects on the PC-3 cell-derived xenograft model with negligible side effects and good pharmacokinetic profiles. These data demonstrate that TN-2 could be a promising dual-target chemotherapeutic agent for the treatment of prostate cancer.


Asunto(s)
Antineoplásicos , Tubulina (Proteína) , Humanos , Línea Celular Tumoral , Tubulina (Proteína)/metabolismo , Neuropilina-1 , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Ensayos de Selección de Medicamentos Antitumorales , Apoptosis , Farmacóforo , Proliferación Celular , Puntos de Control de la Fase G2 del Ciclo Celular , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/uso terapéutico , Moduladores de Tubulina/química , Polimerizacion , Relación Estructura-Actividad
3.
J Cancer Res Clin Oncol ; 149(18): 16717-16727, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37725241

RESUMEN

PURPOSE: We used proteomic sequencing and experimental verification to identify the potential ferroptosis-related proteins in ameloblastoma. METHODS: Samples of ameloblastoma (n = 14) and normal gingival tissues (n = 5) were collected for proteomic sequencing to identify differentially expressed proteins (DEPs) in ameloblastoma. Ferroptosis-related genes were downloaded from FerrDb V2, which were then compared with DEPs to obtain ferroptosis-related DEPs (FR-DEPs). A functional enrichment analysis was performed, and a protein-protein interaction network was built. The hub proteins were screened using the Cytoscape software, and potential drugs targeting them were retrieved from the DrugBank database. A hub protein was selected for immunohistochemical validation, and its expression was assessed in ameloblastomas, odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. The primary ameloblastoma cells were cultured to explore the effect of the protein on the migratory properties of the tumour cells. RESULTS: A total of 58 FR-DEPs were screened, and six hub proteins were identified: mTOR, NFE2L2, PRKCA, STAT3, EGFR, and CDH1. Immunohistochemical analysis showed that mTOR expression was upregulated in ameloblastomas compared with that in odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. p-mTOR was highly expressed in ameloblastomas, with a positivity rate of 83.3%. In addition, rapamycin, an inhibitor of mTOR, can inhibit the migratory capacity of primary cultured ameloblastoma cells. CONCLUSION: Our results revealed the ferroptosis-related proteins in ameloblastomas and their underlying biological processes. Additionally, mTOR was overexpressed and was found to be associated with the aggressiveness of ameloblastomas, which may be a potential target for future treatments.


Asunto(s)
Ameloblastoma , Quiste Dentígero , Ferroptosis , Quistes Odontogénicos , Humanos , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Ameloblastoma/genética , Ameloblastoma/metabolismo , Ameloblastoma/patología , Proteómica , Inmunohistoquímica , Quistes Odontogénicos/metabolismo , Quistes Odontogénicos/patología , Serina-Treonina Quinasas TOR/genética
4.
Heliyon ; 9(7): e18047, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37539284

RESUMEN

Objective: To evaluate a rabbit model of mandibular box-shaped defects created through an intraoral approach and determine the minimum size defect that would not spontaneously heal during the rabbit's natural life (or critical-sized defect, CSD). Methods: Forty-five 6-month-old rabbits were randomly divided into five defect size groups (nine each). Mandibular box-shaped defects of different sizes (4, 5, 6, 8, and 10 mm) were created in each hemimandible, with the same width and depth (3 and 2 mm, respectively). Four, 8, and 12 weeks post-surgery, three animals per group were euthanized. New bone formation was assessed using micro-computed tomography (MCT) and histomorphometric analyses. Results: Box-shaped defects were successfully created in the buccal region between the incisor area and the anterior part of the mental foramen in rabbit mandibles. Twelve weeks post-surgery, MCT analysis showed that the defects in the 4, 5, and 6 mm groups were filled with new bone, while those in the 8 and 10 mm groups remained underfilled. Quantitative analysis revealed that the bone mass recovery percentage in the 8 and 10 mm groups was significantly lower than that in the other groups (p < 0.05). There was no significant difference in the bone mass recovery percentage between the 8 and 10 mm groups (p > 0.05). Histomorphometric analysis indicated that the area of new bone formation in the 8 and 10 mm groups was significantly lower than that in the remaining groups (p < 0.05). There was no significant difference in the new bone area between the 8 and 10 mm groups (p > 0.05). Conclusions: The dimensions of box-shaped CSD created in the rabbit mandible through an intraoral approach were 8 mm × 3 mm × 2 mm. This model may provide a clinically relevant base for future tissue engineering efforts in the mandible.

5.
Int J Mol Sci ; 24(14)2023 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-37510993

RESUMEN

Immunotherapies including adaptive immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have developed the treatment of cancer in clinic, and most of them focus on activating T cell immunity. Although these strategies have obtained unprecedented clinical responses, only limited subsets of cancer patients could receive long-term benefits, highlighting the demand for identifying novel targets for the new era of tumor immunotherapy. Innate immunity has been demonstrated to play a determinative role in the tumor microenvironment (TME) and influence the clinical outcomes of tumor patients. A thorough comprehension of the innate immune cells that infiltrate tumors would allow for the development of new therapeutics. In this review, we outline the role and mechanism of innate immunity in TME. Moreover, we discuss innate immunity-based cancer immunotherapy in basic and clinical studies. Finally, we summarize the challenges in sufficiently motivating innate immune responses and the corresponding strategies and measures to improve anti-tumor efficacy. This review could aid the comprehension of innate immunity and inspire the creation of brand-new immunotherapies for the treatment of cancer.


Asunto(s)
Neoplasias , Humanos , Neoplasias/patología , Inmunidad Innata , Inmunoterapia , Linfocitos T , Biología , Microambiente Tumoral
6.
J Stomatol Oral Maxillofac Surg ; 124(6): 101472, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37061040

RESUMEN

PURPOSE: To evaluate the effects of concentrated growth factor (CGF), combined with a mixture of iliac cancellous and composite bone materials, on the repair of extensive mandibular defects. PATIENTS AND METHODS: This clinical trial involved patients with mandibular defects caused by large cystic lesions. The test group comprised 16 patients who underwent CGF combined with iliac cancellous bone and composite bone materials to repair extensive mandibular defects, whereas the control group comprised eight patients who underwent vascularised free fibula grafts for mandibular segmental defects. Postoperative exudatum was collected from patients on the 1st, 2nd, 3rd, and 4th days postoperatively, and osteogenic factor, including alkaline phosphatase (ALP), osteocalcin (BGP), and procollagen type I N-terminal propeptide (PINP), and inflammatory cytokines were performed. Additionally, regular cone beam computed tomography (CBCT) scans were conducted before and after surgery. RESULTS: On postoperative days 1-4, the expression levels of ALP, BGP, and PINP were higher in the test group, while those of IL-1α, IL-1ß, IL-6, IL-8, and TNF-α, which were identified as co-differentially expressing inflammatory cytokines, were all down-regulated in the exudatum of the test group. Regular CBCT radiological scans revealed a significant osteogenic effect in the test group. CONCLUSION: The use of CGF combined with iliac cancellous bone and composite bone materials to repair extensive mandibular jaw defects facilitates bone formation and reductions in inflammation in the defect area in the short term, which deserves further research in clinical practice.


Asunto(s)
Hueso Esponjoso , Osteogénesis , Humanos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Citocinas/farmacología , Inflamación/cirugía
7.
Zhongguo Zhong Yao Za Zhi ; 48(1): 183-192, 2023 Jan.
Artículo en Chino | MEDLINE | ID: mdl-36725270

RESUMEN

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1ß, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.


Asunto(s)
Medicamentos Herbarios Chinos , Farmacología en Red , Animales , Ratones , Proteínas Quinasas Activadas por AMP , Cromatografía Líquida de Alta Presión , Proteína con Dominio Pirina 3 de la Familia NLR , Sirtuina 1 , Medicamentos Herbarios Chinos/farmacología , Simulación del Acoplamiento Molecular
8.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-970513

RESUMEN

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.


Asunto(s)
Animales , Ratones , Farmacología en Red , Proteínas Quinasas Activadas por AMP , Cromatografía Líquida de Alta Presión , Proteína con Dominio Pirina 3 de la Familia NLR , Sirtuina 1 , Medicamentos Herbarios Chinos/farmacología , Simulación del Acoplamiento Molecular
9.
Front Pharmacol ; 13: 1037993, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36408220

RESUMEN

Available vaccine-based immunity may at high risk of being evaded due to substantial mutations in the variant Omicron. The main protease (Mpro) of SARS-CoV-2 and human neuropilin-1 (NRP1), two less mutable proteins, have been reported to be crucial for SARS-CoV-2 replication and entry into host cells, respectively. Their dual blockade may avoid vaccine failure caused by continuous mutations of the SARS-CoV-2 genome and exert synergistic antiviral efficacy. Herein, four cyclic peptides non-covalently targeting both Mpro and NRP1 were identified using virtual screening. Among them, MN-2 showed highly potent affinity to Mpro (K d = 18.2 ± 1.9 nM) and NRP1 (K d = 12.3 ± 1.2 nM), which was about 3,478-fold and 74-fold stronger than that of the positive inhibitors Peptide-21 and EG3287. Furthermore, MN-2 exhibited significant inhibitory activity against Mpro and remarkable anti-infective activity against the pseudotyped variant Omicron BA.2.75 without obvious cytotoxicity. These data demonstrated that MN-2, a novel non-covalent cyclic peptide, is a promising agent against Omicron BA.2.75.

10.
J Am Chem Soc ; 144(16): 7117-7128, 2022 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-35417174

RESUMEN

The application of peptide drugs in cancer therapy is impeded by their poor biostability and weak cell permeability. Therefore, it is imperative to find biostable and cell-permeable peptide drugs for cancer treatment. Here, we identified a potent, selective, biostable, and cell-permeable cyclic d-peptide, NKTP-3, that targets NRP1 and KRASG12D using structure-based virtual screening. NKTP-3 exhibited strong biostability and cellular uptake ability. Importantly, it significantly inhibited the growth of A427 cells with the KRASG12D mutation. Moreover, NKTP-3 showed strong antitumor activity against A427 cell-derived xenograft and KRASG12D-driven primary lung cancer models without obvious toxicity. This study demonstrates that the dual NRP1/KRASG12D-targeting cyclic d-peptide NKTP-3 may be used as a potential chemotherapeutic agent for KRASG12D-driven lung cancer treatment.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Neoplasias Pulmonares/patología , Mutación , Péptidos/genética , Proteínas Proto-Oncogénicas p21(ras)/genética
11.
Molecules ; 27(5)2022 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-35268809

RESUMEN

Proper postharvest storage preserves horticultural products, including tea, until they can be processed. However, few studies have focused on the physiology of ripening and senescence during postharvest storage, which affects the flavor and quality of tea. In this study, physiological and biochemical indexes of the leaves of tea cultivar 'Yinghong 9' preserved at a low temperature and high relative humidity (15-18 °C and 85-95%, PTL) were compared to those of leaves stored at ambient conditions (24 ± 2 °C and relative humidity of 65% ± 5%, UTL). Water content, chromatism, chlorophyll fluorescence, and key metabolites (caffeine, theanine, and catechins) were analyzed over a period of 24 h, and volatilized compounds were determined after 24 h. In addition, the expression of key biosynthesis genes for catechin, caffeine, theanine, and terpene were quantified. The results showed that water content, chromatism, and chlorophyll fluorescence of preserved leaves were more similar to fresh tea leaves than unpreserved tea leaves. After 24 h, the content of aroma volatiles and caffeine significantly increased, while theanine decreased in both groups. Multiple catechin monomers showed distinct changes within 24 h, and EGCG was significantly higher in preserved tea. The expression levels of CsFAS and CsTSI were consistent with the content of farnesene and theanine, respectively, but TCS1 and TCS2 expression did not correlate with caffeine content. Principal component analysis considered results from multiple indexes and suggested that the freshness of PTL was superior to that of UTL. Taken together, preservation conditions in postharvest storage caused a series of physiological and metabolic variations of tea leaves, which were different from those of unpreserved tea leaves. Comprehensive evaluation showed that the preservation conditions used in this study were effective at maintaining the freshness of tea leaves for 2-6 h. This study illustrates the metabolic changes that occur in postharvest tea leaves, which will provide a foundation for improvements to postharvest practices for tea leaves.


Asunto(s)
Camellia sinensis , Catequina , Camellia sinensis/química , Catequina/metabolismo , Expresión Génica , Fenotipo , Hojas de la Planta/química , Proteínas de Plantas/metabolismo , Té/metabolismo
12.
Int J Mol Sci ; 22(23)2021 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-34884722

RESUMEN

The inner cell mass of the pre-implantation blastocyst consists of the epiblast and hypoblast from which embryonic stem cells (ESCs) and extra-embryonic endoderm (XEN) stem cells, respectively, can be derived. Importantly, each stem cell type retains the defining properties and lineage restriction of its in vivo tissue origin. We have developed a novel approach for deriving porcine XEN (pXEN) cells via culturing the blastocysts with a chemical cocktail culture system. The pXEN cells were positive for XEN markers, including Gata4, Gata6, Sox17, and Sall4, but not for pluripotent markers Oct4, Sox2, and Nanog. The pXEN cells also retained the ability to undergo visceral endoderm (VE) and parietal endoderm (PE) differentiation in vitro. The maintenance of pXEN required FGF/MEK+TGFß signaling pathways. The pXEN cells showed a stable phenotype through more than 50 passages in culture and could be established repeatedly from blastocysts or converted from the naïve-like ESCs established in our lab. These cells provide a new tool for exploring the pathways of porcine embryo development and differentiation and providing further reference to the establishment of porcine ESCs with potency of germline chimerism and gamete development.


Asunto(s)
Técnicas de Cultivo de Embriones , Embrión de Mamíferos/citología , Endodermo/citología , Animales , Diferenciación Celular , Línea Celular , Desarrollo Embrionario , Células Madre Multipotentes , Transducción de Señal , Porcinos
13.
Rev Sci Instrum ; 92(5): 053707, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-34243332

RESUMEN

We developed a practical Line-Scanning Chromatic Confocal Sensor (LSCCS) that can generate three-dimensional (3D) points with up to 32 000/s with a high-precision motion device. An optical route of line-scanning confocal spectroscopy is designed and verified by simulation. The LSCCS is composed of a white laser source, a chromatic confocal optics, and a self-developed spectrometer. The chromatic confocal optics consists of a slit, a chromatic lens (dispersive objective lens), and a beam splitter, and the spectrometer consists of an adjustable slit, a collimating lens, a blazed grating, a focusing lens, a CMOS, and an image processing circuit. The slit and the chromatic lens are designed for a line focus, and the polarizing beam splitter is selected to maximize the white light power collected by the CMOS. The motion device is made to realize the full-field 3D scanning. The key algorithms involved are developed to accurately restore the peak wavelength that includes the position information of the measured surface from the collected spectral image. Theoretical analysis and simulation showed that the corresponding resolutions in Z (depth), X (direction of optical fibers layout), and Y (direction of line-scanning) directions are 0.6, 10, and 5 µm, with a line length of 8 mm and a depth field of 2.4 mm. Experimental results showed that the sensor produces a measurement accuracy of 0.886 µm and a scanning speed of 90 fps. It is of great significance for the accurate measurement of the 3D profile and thickness on the highly reflective materials in the fields of optics, semiconductors, or micromechanics.

14.
J Tradit Chin Med ; 41(3): 471-478, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34114406

RESUMEN

OBJECTIVE: To investigate the efficacy of icariin for healing skull defects in rabbit models. METHODS: Thirty-six 3-month-old female New Zealand white rabbits, weighing 1.8-2.0 kg each, were randomly divided into either the control or experimental group. Skull defect models were constructed in both groups, with the experimental group receiving oral icariin afterwards. At 4, 8 and 12 postoperative weeks, the rabbits were euthanized, and X-rays and samples were taken. Tissue sections were stained using hematoxylin and eosin, followed by additional processing using histological and bone metrological methods for observing the rate and quality of the bone formation. RESULTS: Histologically, additional mature lamellar bone formed in the defect area in the experimental group compared with that of the control group. Bone metrological methods showed that the bone mass, trabecular bone width and number of osteoblasts in the experimental group were significantly higher than those of the control group (P < 0.01). The number of osteoclasts did not significantly differ between the two groups (P > 0.05). CONCLUSION: Icariin increased the bone mass and improved the condition of the defect area in the rabbit skulls.


Asunto(s)
Cráneo , Cicatrización de Heridas , Animales , Femenino , Conejos , Flavonoides , Osteogénesis
15.
Front Genet ; 12: 664799, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33868391

RESUMEN

Many ion channels participate in controlling insulin synthesis and secretion of pancreatic ß-cells. Epithelial sodium channel (ENaC) expressed in human pancreatic tissue, but the biological role of ENaC in pancreatic ß-cells is still unclear. Here, we applied the CRISPR/Cas9 gene editing technique to knockout α-ENaC gene in a murine pancreatic ß-cell line (MIN6 cell). Four single-guide RNA (sgRNA) sites were designed for the exons of α-ENaC. The sgRNA1 and sgRNA3 with the higher activity were constructed and co-transfected into MIN6 cells. Through processing a series of experiment flow included drug screening, cloning, and sequencing, the α-ENaC gene-knockout (α-ENaC-/-) in MIN6 cells were obtained. Compared with the wild-type MIN6 cells, the cell viability and insulin content were significantly increased in α-ENaC-/- MIN6 cells. Therefore, α-ENaC-/- MIN6 cells generated by CRISPR/Cas9 technology added an effective tool to study the biological function of α-ENaC in pancreatic ß-cells.

16.
Orthop Surg ; 12(6): 1826-1834, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33073495

RESUMEN

OBJECTIVE: To present a novel method called triplanar chevron osteotomy to treat hallux valgus (HV). METHODS: This is a retrospective study. In this study, the CT data of HV patients with painful callosities were evaluated retrospectively between 1 June 2018 and 1 June 2020. CT data from 49 consecutive patients (59 feet) with HV were evaluated. The average age at the time of surgery was 49.6 years (range, 30-63 years). The apex of the chevron osteotomy procedure was located at the center of the first metatarsal and was defined as the line formed by the central point perpendicular to the fourth metatarsal bone. The cut planes of the plantarward oblique chevron osteotomy (POCO) were defined as follows: chevron osteotomy along with 20° of plantarward obliquity. The triplanar osteotomy incision was made using the POCO method, with the direction inclined by 10° distally. The intermetatarsal angle (IMA), the HV angle (HVA), the projection of the second metatarsal (PSM), the metatarsal protrusion index (MPI), and the metatarsal protrusion distance (MPD) were all calculated before and after the operations. The length of the first metatarsal was measured and calculated with an equation. RESULTS: The results showed that the HVA was significantly decreased after surgery (32.7° ± 4.6° vs 14.9° ± 2.1°, t = 25.583, P < 0.001) in the triplanar, traditional, and POCO groups. The IMA was also significantly decreased (14.7° ± 2.0°) compared with the results before surgery (8.0° ± 1.1°, t = 22.739, P < 0.001) in these groups. Compared with traditional osteotomy and POCO, there were no differences in correcting deformities on axial planes for the HVA (14.5° ± 1.7° vs 14.9° ± 2.1°, t = 1.835, P = 0.072) and IMA (8.1° ± 1.1° vs 8.0° ± 1.1°, t = -0.97, P = 0.336). There was a statistically significant decrease following surgery in terms of the PSM, MPI, and MPD after triplanar osteotomy. The length of the first metatarsal increased (10.9 ± 1.3 mm), as measured through three-dimensional images in the triplanar osteotomy group. The length was calculated as follows: H = L2 * Tan θ ≈ L/COS ß * Tan θ. CONCLUSION: The new triplanar osteotomy technique is safe and effective for treating HV, and in simulation experiments reveals potential benefits of correction and preventing transfer metatarsalgia.


Asunto(s)
Hallux Valgus/cirugía , Osteotomía/métodos , Adulto , Humanos , Persona de Mediana Edad , Rango del Movimiento Articular , Estudios Retrospectivos
17.
Fitoterapia ; 146: 104701, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32763365

RESUMEN

Phytochemical investigation of an extract of the rhizome of Curcuma longa L., resulted in the identification of four undescribed bisabolane sesquiterpenoids, namely as bisacurone D-G (1-4). With the aid of comprehensive spectroscopic techniques (NMR, IR, UV, MS), the structures of all isolated compounds were elucidated and subsequently screened for both anti-inflammatory and cytotoxic biological activities, Compounds 1 and 2 showed moderate inhibitory activity toward LPS-induced NO production on RAW 264.7 macrophages.


Asunto(s)
Curcuma/química , Sesquiterpenos Monocíclicos/farmacología , Rizoma/química , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Línea Celular Tumoral , China , Ciclohexanoles , Humanos , Ratones , Estructura Molecular , Sesquiterpenos Monocíclicos/aislamiento & purificación , Óxido Nítrico/metabolismo , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/química , Células RAW 264.7 , Sesquiterpenos
19.
J Clin Invest ; 130(9): 4935-4946, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32516135

RESUMEN

Leber's hereditary optic neuropathy (LHON) is a maternally inherited eye disease. X-linked nuclear modifiers were proposed to modify the phenotypic manifestation of LHON-associated mitochondrial DNA (mtDNA) mutations. By whole-exome sequencing, we identified the X-linked LHON modifier (c.157C>T, p.Arg53Trp) in PRICKLE3 encoding a mitochondrial protein linked to biogenesis of ATPase in 3 Chinese families. All affected individuals carried both ND4 11778G>A and p.Arg53Trp mutations, while subjects bearing only a single mutation exhibited normal vision. The cells carrying the p.Arg53Trp mutation exhibited defective assembly, stability, and function of ATP synthase, verified by PRICKLE3-knockdown cells. Coimmunoprecipitation indicated the direct interaction of PRICKLE3 with ATP synthase via ATP8. Strikingly, cells bearing both p.Arg53Trp and m.11778G>A mutations displayed greater mitochondrial dysfunction than those carrying only a single mutation. This finding indicated that the p.Arg53Trp mutation acted in synergy with the m.11778G>A mutation and deteriorated mitochondrial dysfunctions necessary for the expression of LHON. Furthermore, we demonstrated that Prickle3-deficient mice exhibited pronounced ATPase deficiencies. Prickle3-knockout mice recapitulated LHON phenotypes with retinal deficiencies, including degeneration of retinal ganglion cells and abnormal vasculature. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutations and X-linked nuclear modifiers.


Asunto(s)
Adenosina Trifosfatasas , Proteínas con Dominio LIM , Proteínas Mitocondriales , Mutación Missense , Atrofia Óptica Hereditaria de Leber , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Animales , Niño , Femenino , Humanos , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Atrofia Óptica Hereditaria de Leber/genética , Atrofia Óptica Hereditaria de Leber/metabolismo , Atrofia Óptica Hereditaria de Leber/patología
20.
Nurs Health Sci ; 22(3): 629-638, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32125080

RESUMEN

Self-management helps patients understand their illnesses and learn about disease-related skills so they can better manage their situation. However, published studies on the effectiveness of self-management for chronic obstructive pulmonary disease (COPD) are heterogeneous. Quasi-experimental design was used to investigate the effectiveness of a self-management program in self-care efficacy and quality of life in patients with COPD. Sixty participants who had experienced COPD were assigned to control group (usual care) or experimental group (self-care program) (1:1 ratio) according to a purposeful sampling at a Medical Center in Taiwan. The Medical Research Council dyspnea scale, the COPD Self-Efficacy Scale, the Clinical COPD Questionnaire were used to analyze data. The Medical Research Council dyspnea scale was more significant improvement in the 2 months after discharge in the experimental group than in the control group. The COPD Self-Efficacy Scale and Clinical COPD Questionnaire scores in the experimental group within 3 months after discharge were significantly improved compared with the control group. These findings demonstrate the application and initial effect of this self-management program.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida/psicología , Autocuidado/normas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/psicología , Autocuidado/psicología , Autocuidado/estadística & datos numéricos , Taiwán
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA