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1.
Nano Lett ; 24(33): 10106-10113, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39053013

RESUMEN

Strain-free GaAs/AlGaAs semiconductor quantum dots (QDs) grown by droplet etching and nanohole infilling (DENI) are highly promising candidates for the on-demand generation of indistinguishable and entangled photon sources. The spectroscopic fingerprint and quantum optical properties of QDs are significantly influenced by their morphology. The effects of nanohole geometry and infilled material on the exciton binding energies and fine structure splitting are well-understood. However, a comprehensive understanding of GaAs/AlGaAs QD morphology remains elusive. To address this, we employ high-resolution scanning transmission electron microscopy (STEM) and reverse engineering through selective chemical etching and atomic force microscopy (AFM). Cross-sectional STEM of uncapped QDs reveals an inverted conical nanohole with Al-rich sidewalls and defect-free interfaces. Subsequent selective chemical etching and AFM measurements further reveal asymmetries in element distribution. This study enhances the understanding of DENI QD morphology and provides a fundamental three-dimensional structural model for simulating and optimizing their optoelectronic properties.

2.
Small ; : e2403284, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037367

RESUMEN

Thrombus causes a serious condition characterized by the formation of blood clots in blood vessels or heart, potentially leading to life-threatening emergencies. Photothermal therapy (PTT) serves as a treatment for thrombosis that provides noninvasive thrombus dissolution and fewer bleeding side effects. However, the high temperatures generated by PTT can exacerbate vascular inflammation and promote thrombus recurrence. In this study, a photothermal hydrogen sulfide (H2S) nanogenerator (PSA@ADT-OH) is constructed using a perylene-cored photothermal agent (PSA) coassembled with a H2S donor ADT-OH. The system PSA@ADT-OH demonstrates outstanding targeting and accumulation efficiency against blood flow shear forces. It also provides sustained H2S release at thrombus sites, contributing to antiplatelet aggregation, reactive oxygen species clearance, and vascular healing. This approach opens up new possibilities for advanced thrombus treatment.

3.
Fish Shellfish Immunol ; 147: 109423, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38341117

RESUMEN

Cystatins comprise a vast superfamily of evolutionary conserved proteins, predominantly recognized for their roles as endogenous inhibitors by regulating the activity of cysteine proteases. Emerging lines of research evidence also provides insight into their alternative roles in a spectrum of biological and pathological processes, including neurodegenerative disorders, tumor progression, inflammatory diseases, and immune response. Nowadays, various type-1 cystatins (stefins) have been demonstrated among a variety of discovered vertebrate groups, while little is known about the related homologue in cephalochordate amphioxus, which are repositioned at the base of the chordate phylum. In the present study, a single type-1 cystatin homologue in Branchiostoma japonicum was first successfully cloned and designated as Bjcystatin-1. The deduced Bjcystatin-1 protein is structurally characterized by the presence of typical wedge-shaped cystatin features, including the 'QxVxG' and 'Px' motif, as well as the conserved N-terminal glycine residue. Phylogenomic analyses utilizing different cystatin counterparts affirmed the close evolutionary relationship of Bjcystatin-1 and type-1 cystatin homologue. Bjcystatin-1 was predominantly expressed in the gills and hind-gut in a tissue-specific pattern, and its expression was remarkably up-regulated in response to challenge with bacteria or their signature molecules LPS and LTA, suggesting the involvement in immune response. Additionally, the recombinant Bjcystatin-1 (rBjcystatin-1) protein showed significant inhibitory activity towards papain and binding ability to LPS and LTA, indicating its hypothesized role as a pattern recognition receptor in immune response. Subcellular localization results also showed that Bjcystatin-1 was located in the cytoplasm and nucleus, and its overexpression could attenuate the activation of LPS-induced nuclear transcription factors NF-κB. Taken together, our study suggests that amphioxus Bjcystatin-1 acts as a dual role in protease inhibitor and an immunocompetent factor, providing new insights into the immune defense effect of type-1 cystatin in amphioxus.


Asunto(s)
Cistatinas , Anfioxos , Animales , Lipopolisacáridos , Cistatinas/genética , Evolución Biológica , Factores de Transcripción
4.
Environ Sci Technol ; 58(31): 13961-13972, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39037720

RESUMEN

Earthworms are critical in regulating soil processes and act as filters for antibiotic resistance genes (ARGs). Yet, the geographic patterns and main drivers of earthworm gut ARGs remain largely unknown. We collected 52 earthworm and soil samples from arable and forest ecosystems along a 3000 km transect across China, analyzing the diversity and abundance of ARGs using shotgun metagenomics. Earthworm guts harbored a lower diversity and abundance of ARGs compared to soil, resulting in a stronger distance-decay rate of ARGs in the gut. Greater deterministic assembly processes of ARGs were found in the gut than in soil. The earthworm gut had a lower frequency of co-occurrence patterns between ARGs and mobile genetic elements (MGEs) in forest than in arable systems. Viral diversity was higher in the gut compared to soil and was negatively correlated with bacterial diversity. Bacteria such as Streptomyces and Pseudomonas were potential hosts of both viruses and ARGs. Viruses had negative effects on the diversity and abundance of ARGs, likely due to the lysis on ARG-bearing bacteria. These findings provide new insights into the variations of ARGs in the earthworm gut and highlight the vital role of viruses in the regulation of ARGs in the soil ecosystem.


Asunto(s)
Oligoquetos , Microbiología del Suelo , Animales , Farmacorresistencia Microbiana/genética , Bacterias/efectos de los fármacos , Bacterias/genética , Antibacterianos/farmacología , Suelo , China , Metagenómica
5.
Microsurgery ; 44(1): e31044, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36999280

RESUMEN

BACKGROUND: The free peroneal artery perforator (FPAP) flap is used for soft tissue defects after burns and trauma. However, the use of FPAP flaps to repair limb soft tissue defects for immediate reconstruction was rarely reported previously. Therefore, the purpose of this report is to evaluate free peroneal artery perforator flap to reconstruct traumatic limb soft tissue defects for immediate reconstruction. PATIENTS AND METHODS: A total of 25 cases of limb soft tissue defects undergoing immediate reconstruction of FPAP flap transfer were retrospectively evaluated from January 2019 to June 2019 in our institute. The locations of defects included the palm (10 cases), finger (5 cases), foot (7 cases), ankle (2 cases) and wrist (1 case). The sizes of defect varied from 3 × 2 cm to 15 × 7 cm (54.1 cm2 in average). Flaps were harvested based on the peroneal perforator vessels, initially marked using hand-held Doppler. RESULTS: Average size of harvested flap was 9.7 × 6.2 cm (ranging from 3.5 × 2 cm to 16 × 8 cm). All perforators were harvested from the peroneal artery and the arterial diameter ranged from 0.8 to 1.7 mm. The average pedicle length was 3.04 cm (range, 1.85-4.75 cm). Five vascular thrombosis were found including three cases of arterial thrombosis and two cases of venous thrombosis which were successfully salvaged by re-operation and vein graft. Satisfying functional outcome and acceptable appearance were achieved at 6 months or longer after surgery (range, 6-15 months, 12 months in average). All flaps survived at the end-point. CONCLUSIONS: The FPAP flap is a reliable and thin fasciocutaneous flap, which can be used for repairing limb soft tissue defects. The FPAP flap can be used for covering defects with various appearances, locations, and sizes.


Asunto(s)
Colgajo Perforante , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Trombosis , Humanos , Estudios Retrospectivos , Trasplante de Piel , Colgajo Perforante/irrigación sanguínea , Traumatismos de los Tejidos Blandos/cirugía , Arterias Tibiales/cirugía , Trombosis/cirugía , Resultado del Tratamiento
6.
Angew Chem Int Ed Engl ; 63(23): e202404395, 2024 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-38577995

RESUMEN

Reactive oxygen species (ROS) have become an effective tool for tumor treatment. The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) takes advantage of various ROS and enhances therapeutic effects. However, the activation of CDT usually occurs before PDT, which hinders the sustained maintenance of hydroxyl radicals (⋅OH) and reduces the treatment efficiency. Herein, we present a light-triggered nano-system based on molecular aggregation regulation for converting cancer therapy from PDT/photothermal therapy (PTT) to a long-lasting CDT. The ordered J-aggregation enhances the photodynamic properties of the cyanine moiety while simultaneously suppressing the chemodynamic capabilities of the copper-porphyrin moiety. Upon light irradiation, Cu-PCy JNPs demonstrate strong photodynamic and photothermal effects. Meanwhile, light triggers a rapid degradation of the cyanine backbone, leading to the destruction of the J-aggregation. As a result, a long-lasting CDT is sequentially activated, and the sustained generation of ⋅OH is observed for up to 48 hours, causing potent cellular oxidative stress and apoptosis. Due to their excellent tumor accumulation, Cu-PCy JNPs exhibit effective in vivo tumor ablation through the converting therapy. This work provides a new approach for effectively prolonging the chemodynamic activity in ROS-based cancer therapy.


Asunto(s)
Fotoquimioterapia , Fármacos Fotosensibilizantes , Terapia Fototérmica , Animales , Humanos , Ratones , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Cobre/química , Cobre/farmacología , Luz , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/terapia , Carbocianinas/química , Carbocianinas/farmacología , Supervivencia Celular/efectos de los fármacos
7.
Expert Opin Emerg Drugs ; 28(4): 297-309, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38129984

RESUMEN

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates. AREAS COVERED: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated. EXPERT OPINION: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.


Asunto(s)
Uveítis , Humanos , Uveítis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Ensayos Clínicos Fase II como Asunto
8.
Med Teach ; 45(6): 658-663, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36420808

RESUMEN

BACKGROUND: COVID-19's infection control policies have hindered the Deliberate Practice of clinical examinations. Guided Mental Rehearsal (GMR) may overcome this obstacle by facilitating independent, repetitive practice. Underpinned by the 'Motor Simulation Theory,' GMR reinforces similar neuro-circuit activations during physical practice and was proven effective in surgical training. METHODS: This prospective, randomized controlled study evaluated the efficacy of GMR versus 'peer-learning' of Confrontational Visual Field Examination (CVFE). Third-year medical-students without clinical Ophthalmology experience were recruited. Controls (n = 40) watched an e-learning instructional video (8-min CVFE tutorial) followed by 6-min of 'peer-learning.' GMR-students (n = 40) had 'peer-learning' replaced by a 6-min GMR audio-recording (CVFE running commentary). Pre-test and post-test MCQs were administered to determine baseline knowledge and knowledge acquisition, respectively. 28 controls and 26 GMR-students performed CVFE on simulated patients with right homonymous hemianopia. Four Ophthalmologists graded their performances using a checklist-based marking scheme. RESULTS: Both groups did not exhibit a significant difference in pre-test scores (8.550 vs. 7.947, p = 0.266); outcome of sub-group analysis of CVFE-performing candidates was similar (8.214 vs. 7.833, p = 0.561). Post-test scores were significantly higher than pre-test in both groups (all p < .001), without inter-group difference (14.000 vs. 15.000, p = 0.715). GMR-group had significantly higher scores on CVFE performance than controls (85.354 vs. 73.679%, p = .001). CONCLUSIONS: GMR improved psychomotor but not cognitive aspect of learning CVFE. This may be attributable to GMR's theoretical resemblance with physical practice, with additional expert guidance. By enabling independent learning, GMR may also reduce the demand for teaching manpower and thus education cost in the future.


Asunto(s)
COVID-19 , Instrucción por Computador , Estudiantes de Medicina , Humanos , Estudios Prospectivos , Pandemias , Competencia Clínica
9.
Small ; 18(19): e2201223, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35373912

RESUMEN

Long-lived room temperature phosphorescence (RTP) materials are widely utilized in the field of biological and chemical sensing, due to their unique characteristics of long-lived luminescence and no background autofluorescence. However, the realization of full-color RTP in aqueous solution still remains a great challenge. Herein, a feasible strategy for achieving high stability and full-color RTP of carbon dots (CDs)-based composite materials in aqueous environment is reported by constructing a rigid hydrogen bonds' network. The obtained m,p-CDs@CA composite materials exhibit deep-blue RTP with phosphorescence quantum yield of 23.2% and lifetime of 1.74 s, and the afterglow can last for over 12 s. More importantly, the m,p-CDs@CA composite materials are desirable in the detection of biomarkers, because of excellent stability, dispersion, and long-lived RTP properties. The m,p-CDs@CA suspension also displays excellent sensitivity, and a limitation of detection as low as 5.61 and 550 nm for biomarkers 5-hydroxyindole-3-acetic acid (HIAA) and serotonin (5-hydroxytryptamine, HT), respectively. Meanwhile, the sensing performance exhibits excellent selectivity even in the presence of other competitive species in blood plasma and urine. With superior selectivity, the long-lived phosphorescence probe based on m,p-CDs@CA suspension can be as an effective biomarker for carcinoid identification, which has potential application in clinical analysis.


Asunto(s)
Carbono , Carbono/química , Enlace de Hidrógeno , Temperatura
10.
Int J Hyperthermia ; 39(1): 490-496, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35285391

RESUMEN

OBJECTIVE: To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). METHODS: This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. RESULTS: After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. CONCLUSIONS: RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.


Asunto(s)
Hiperparatiroidismo Primario , Ablación por Radiofrecuencia , Calcio , Humanos , Hiperparatiroidismo Primario/cirugía , Hormona Paratiroidea , Paratiroidectomía , Ablación por Radiofrecuencia/efectos adversos , Estudios Retrospectivos , Factores de Riesgo
11.
Biomed Chromatogr ; 36(4): e5300, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34921409

RESUMEN

Liver injury induced by Polygonum multiflorum root (PMR) is an immediate issue requiring global attention. UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors are suspected to additively contribute to the hepatotoxicity of PMR. This study was deliberately designed to simultaneously screen UGT1A1 inhibitors from PMR, and their co-contribution to hepatotoxicity was determined. Using ultrafiltration coupled to LC-MS method, four compounds, namely cis-2,3,5,4'-tetrahydroxystilbene-2-O-ß-glucoside, trans-2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside, emodin-8-O-ß-d-glucoside, and emodin, were screened, exhibiting the in vitro inhibitory activities against UGT1A1 with IC50 values of 76.23, 18.70, 62.18, and 34.02 µM, respectively. The varying activities of the screened UGT1A1 inhibitors were demonstrated by performing a molecular docking simulation. Finally, zebrafish larvae and mice assays demonstrated that the UGT1A1 inhibitors co-contributed to the hepatotoxicity of PMR. These findings are conducive to understand the role of UGT1A1 inhibitors in PMR-induced hepatotoxicity.


Asunto(s)
Fallopia multiflora , Animales , Cromatografía Liquida , Ratones , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem , Ultrafiltración , Pez Cebra
12.
J Microencapsul ; 39(4): 341-351, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35670223

RESUMEN

AIM: In this investigation, Zinc-silicon carbide (Zn-SiC) materials were fabricated by a simple approach by using Zn nanoparticles (Zn-NPs) loaded on silicon carbide (SiC) with enhanced antibacterial and healing activity. METHODS: Zn-NPs loaded on SiC fabricated by the DIY laser melting technique. The TEM and Zeta-sizer confirmed the morphology and size of the nanoparticles. The characterisation was done using Fourier transforms infra-red spectroscopy, and X-ray diffraction, thermogravimetric analysis. Further, the fabricated nanoparticles were evaluated for their mechanical properties and biocompatibility under storage conditions. In vivo wound healing was measured by observing a percentage reduction in the wound. RESULTS: Zn-SiC NPs have 54.6 ± 5.25 nm mean particle size, -15.9 ± 2.35 mV zeta potential with 0.187 ± 0.05 polydispersity index. The nanoparticles showed good biocompatibility and in vivo wound healing properties. CONCLUSIONS: These results strongly support the possibility of using these Zn particles loaded on SiC NPs as a promising wound healing agent after caesarean section.


Asunto(s)
Nanocompuestos , Zinc , Vendajes , Compuestos Inorgánicos de Carbono , Supervivencia Celular , Cesárea , Femenino , Humanos , Embarazo , Compuestos de Silicona , Zinc/química
13.
Angew Chem Int Ed Engl ; 61(27): e202202532, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35357065

RESUMEN

Chirality is a particularly important concept in nature and exists at all length scales, ranging from the molecular level to the supramolecular level. Over the last two decades, various design strategies have been developed to construct chiral materials based on perylene diimides (PDIs) and to mimic the chiral assembly process in biological systems, but applications of these chiral aggregates are still at an early stage. This Minireview summarizes recent progress in the synthesis and properties of chiral PDIs. The chirality in PDI-based materials can be generated by three different approaches: from the twisted planes of PDIs, the chiral substituents of PDIs, and the co-assembly of achiral PDIs and chiral guests. A comprehensive understanding of the applications of chiral PDIs as well as potential future developments is also provided.


Asunto(s)
Perileno , Imidas
14.
Angew Chem Int Ed Engl ; 61(32): e202203254, 2022 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-35420726

RESUMEN

Materials exhibiting ultralong luminescent lifetime show promising applications in the fields of information encryption, sensing, and bioimaging. Herein, we present a low-cost and general strategy to achieve stimulus-responsive ultralong organic phosphorescence (UOP) based on pyrene chromophores doped into polymer matrices. The UOP of the resulted systems presents radiation-, concentration-, time-, and excitation-dependent characteristics. The UOP color can be turned from blue to red by changing the excitation wavelength or the concentration of chromophores. Experimental results prove that these characteristics are attributed to the consumption of triplet oxygen and the different aggregation states of chromophores in the polymer matrices. Finally, we demonstrate that these systems could be applied for multilevel information encryption. This work would promote further development of multi-responsive long-lived luminescent materials.


Asunto(s)
Mediciones Luminiscentes , Polímeros , Luminiscencia , Pirenos
15.
J Am Chem Soc ; 143(34): 13675-13685, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34410121

RESUMEN

Polymer-based room-temperature phosphorescence (RTP) materials with high flexibility and large-area producibility are highly promising for applications in organic electronics. However, achieving such photophysical materials is challenging because of difficulties in populating and stabilizing susceptible triplet excited states at room temperature. Herein large-area, flexible, transparent, and long-lived RTP systems prepared by doping rationally selected organic chromophores in a poly(vinyl alcohol) (PVA) matrix were realized through a hydrogen-bonding and coassembly strategy. In particular, the 3,6-diphenyl-9H-carbazole (DPCz)-doped PVA film shows long-lived phosphorescence emission (up to 2044.86 ms) and a remarkable duration of afterglow (over 20 s) under ambient conditions. Meanwhile, the 7H-dibenzo[c,g]carbazole (DBCz)-doped PVA film exhibits high absolute luminance of 158.4 mcd m2 after the ultraviolet excitation source is removed. The RTP results not only from suppressing the nonradiative decay by abundant hydrogen-bonding interactions in the PVA matrix but also from minimizing the energy gap (ΔEST) between the singlet state and the triplet state through the coassembly effect. On account of the outstanding mechanical properties and the afterglow performance of these RTP materials, they were applied in the fabrication of flexible 3D objects with repeatable folding and curling properties. Importantly, the multichannel afterglow light-emitting diode arrays were established under ambient conditions. The present long-lived phosphorescent systems demonstrate a bright opportunity for the production of large-area, flexible, and transparent emitting materials.

16.
Bioorg Chem ; 116: 105357, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34562675

RESUMEN

Gynostemma pentaphyllum (Thunb.) Makino (Cucurbitaceae family) is a perennial creeping plant with a common Chinese name of "south ginseng". To date, more than 250 individual saponins with dammarane-type skeleton have been isolated from G. pentaphyllum. The purpose of this study was the isolation and structural characterization of novel, minor gypenosides from G. pentaphyllum and evaluation of their Sirt1 agonist activity. Individual saponins from G. pentaphyllum were isolated and purified by a variety of chromatography techniques, and their structures were elucidated by means of various spectroscopic analysis and comparision with the reported data. Sirt1 enzyme activity detection kit was used to preliminarily evaluate the Sirt1 agonist activity of thirty three individual saponins purified from G. pentaphyllum. Fourteen new triterpenoid saponins named gypenoside CII-CXV (1-14) along with twenty six known compounds (15-40) were isolated from G. pentaphyllum. Thirty three of all the isolates were screened for Sirt1 agonist activity, and the results showed that three dammarane-type saponins (2, 18, 37) and one cucurbitane-type saponin 33 exhibited satisfactory Sirt1 agonist activity. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule Sirt1 agonist and facilitate their utilization as "south ginseng".


Asunto(s)
Gynostemma/química , Saponinas/farmacología , Sirtuina 1/metabolismo , Triterpenos/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Saponinas/química , Saponinas/aislamiento & purificación , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/aislamiento & purificación , Damaranos
17.
Acta Pharmacol Sin ; 42(5): 701-714, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32796955

RESUMEN

Baicalein is a natural flavonoid extracted from the root of Scutellaria baicalensis that exhibits a variety of pharmacological activities. In this study, we investigated the molecular mechanisms underlying the protective effect of baicalein against cardiac hypertrophy in vivo and in vitro. Cardiac hypertrophy was induced in mice by injection of isoproterenol (ISO, 30 mg·kg-1·d-1) for 15 days. The mice received caudal vein injection of baicalein (25 mg/kg) on 3rd, 6th, 9th, 12th, and 15th days. We showed that baicalein administration significantly attenuated ISO-induced cardiac hypertrophy and restored cardiac function. The protective effect of baicalein against cardiac hypertrophy was also observed in neonatal rat cardiomyocytes treated with ISO (10 µM). In cardiomyocytes, ISO treatment markedly increased reactive oxygen species (ROS) and inhibited autophagy, which were greatly alleviated by pretreatment with baicalein (30 µM). We found that baicalein pretreatment increased the expression of catalase and the mitophagy receptor FUN14 domain containing 1 (FUNDC1) to clear ROS and promote autophagy, thus attenuated ISO-induced cardiac hypertrophy. Furthermore, we revealed that baicalein bound to the transcription factor FOXO3a directly, promoting its transcription activity, and transactivated catalase and FUNDC1. In summary, our data provide new evidence for baicalein and FOXO3a in the regulation of ISO-induced cardiac hypertrophy. Baicalein has great potential for the treatment of cardiac hypertrophy.


Asunto(s)
Autofagia/efectos de los fármacos , Cardiomegalia/tratamiento farmacológico , Cardiotónicos/uso terapéutico , Flavanonas/uso terapéutico , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Animales Recién Nacidos , Cardiomegalia/inducido químicamente , Cardiomegalia/metabolismo , Cardiomegalia/patología , Catalasa/metabolismo , Proteína Forkhead Box O3/metabolismo , Isoproterenol , Masculino , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Proteínas Mitocondriales/metabolismo , Miocardio/metabolismo , Miocardio/patología , Ratas , Especies Reactivas de Oxígeno/metabolismo
18.
BMC Musculoskelet Disord ; 22(1): 60, 2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33430847

RESUMEN

BACKGROUND: Displaced patellar fractures are commonly treated with open reduction and fixation with several different types of tension-band (TB) constructs. The main objective of this study was to compare the prevalence of postoperative complications after surgical stabilization of comminuted patellar fractures with either a modified Kirschner-wire tension band (MKTB), a cannulated-screw tension band (CSTB), or a ring-pin tension band (RPTB). METHODS: We conducted a retrospective and consecutive cohort study of comminuted patellar fractures (n = 334) stabilized using a TB construct. Postoperative premature loss of reduction, infection, and skin breakdown were compared according to the type of TB constructs received (MKTB, CSTB, or RPTB). The rate of implant removal due to symptomatic hardware was also evaluated. RESULTS: Fixation failure rate was significantly different among the groups (P = 0.013), with failure rates of 4.7% observed in the MKTB group,14.5% in the CSTB group, and 4.9% in the RPTB group. Skin breakdown and infection were not significantly different among the groups (Ps > 0.05). Due to symptomatic hardware, 40.5% of the patients in the MKTB group, 22.9% in the CSTB group, and 24.3% in the RPTB group underwent implant removal (P = 0.004). After adjusting for age, gender, comorbidities, number of supplementary screws/K-wires, and use of cerclage cables, multivariate regression analysis revealed that CSTB contributed to a 2.08-times greater risk of fixation failure compared to RPTB, while MKTB and RPTB were similar in risk of failure. In addition, it was found that patients who underwent MKTB fixation were more than twice as likely to undergo implant removal for symptomatic hardware compared with RPTB (odds ratio = 2.11, 95% CI = 1.20 to 3.72; P = 0.010). CONCLUSIONS: RPTB have advantage over MKTB and CSTB fixation in terms of symptomatic hardware and premature failure, respectively. LEVEL OF EVIDENCE: Therapeutic Level III.


Asunto(s)
Fracturas Óseas , Fracturas Conminutas , Tornillos Óseos , Hilos Ortopédicos , Estudios de Cohortes , Fijación Interna de Fracturas/efectos adversos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/epidemiología , Fracturas Óseas/cirugía , Humanos , Rótula/diagnóstico por imagen , Rótula/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Prevalencia , Estudios Retrospectivos
19.
Neurochem Res ; 45(12): 3034-3044, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33095438

RESUMEN

Temporal lobe epilepsy (TLE) is common intractable epilepsy that affects the patient's lives. The circular RNA circ_ANKMY2 (circ_ANKMY2) has been reported to be abnormally expressed in TLE. Nevertheless, the role and mechanism of circ_ANKMY2 in TLE are unclear. A human neuroblastoma cell line (SK-N-AS) was used for a series of studies. Expression levels of circ_ANKMY2, miR-106b-5p, and Forkhead Box Protein 1 (FOXP1) mRNA in TLE tissues were assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Cell colony formation, proliferation, and apoptosis were determined by cell colony formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), or flow cytometry assays. The levels of FOXP1 protein, Ki67, B cell lymphoma (Bcl-2), Bcl-2 Associated X (Bax), and Cleaved caspase-3 were evaluated by western blot analysis. The relationship between circ_ANKMY2 or FOXP1 and miR-106b-5p was verified with dual-luciferase reporter assay. We observed that circ_ANKMY2 and FOXP1 expression were reduced while miR-106b-5p expression was increased in TLE tissues. Overexpression of circ_ANKMY2 decreased spontaneous recurrent seizures (SRSs) in rat TLE model and blocked cell colony formation, proliferation, and induced cell apoptosis in SK-N-AS cells. Importantly, circ_ANKMY2 was verified as a sponge for miR-106b-5p. In addition, miR-106b-5p mimics abolished circ_ANKMY2 elevation-mediated effects on colony formation, proliferation, and apoptosis of SK-N-AS cells. Also, FOXP1 served as a target for miR-106b-5p. And FOXP1 silencing overturned the effects of miR-106b-5p inhibitors on the colony formation, proliferation, and apoptosis of SK-N-AS cells. In sum, circ_ANKMY2 modulated TLE advancement via regulation of FOXP1 expression through sponging miR-106b-5p, and circ_ANKMY2 might be an underlying target for the improvement of TLE.


Asunto(s)
Epilepsia del Lóbulo Temporal/metabolismo , Factores de Transcripción Forkhead/metabolismo , MicroARNs/metabolismo , ARN Circular/metabolismo , Proteínas Represoras/metabolismo , Animales , Apoptosis/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Progresión de la Enfermedad , Regulación hacia Abajo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratas Wistar , Convulsiones/metabolismo , Regulación hacia Arriba
20.
Bioorg Med Chem Lett ; 30(13): 127237, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32386981

RESUMEN

Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+ bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.


Asunto(s)
Antiinflamatorios/uso terapéutico , Benzotiazoles/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Inflamación/tratamiento farmacológico , Oxadiazoles/uso terapéutico , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/metabolismo , Benzotiazoles/síntesis química , Benzotiazoles/metabolismo , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/metabolismo , Humanos , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Oxadiazoles/síntesis química , Oxadiazoles/metabolismo , Relación Estructura-Actividad
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