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1.
Small ; : e2403284, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037367

RESUMO

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.

2.
Fish Shellfish Immunol ; 147: 109423, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341117

RESUMO

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.


Assuntos
Cistatinas , Anfioxos , Animais , Lipopolissacarídeos , Cistatinas/genética , Evolução Biológica , Fatores de Transcrição
3.
Environ Sci Technol ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037720

RESUMO

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.

4.
Microsurgery ; 44(1): e31044, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36999280

RESUMO

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.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Trombose , Humanos , Estudos Retrospectivos , Transplante de Pele , Retalho Perfurante/irrigação sanguínea , Lesões dos Tecidos Moles/cirurgia , Artérias da Tíbia/cirurgia , Trombose/cirurgia , Resultado do Tratamento
5.
Angew Chem Int Ed Engl ; 63(23): e202404395, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38577995

RESUMO

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.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Terapia Fototérmica , Animais , Humanos , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Cobre/química , Cobre/farmacologia , Luz , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/terapia , Carbocianinas/química , Carbocianinas/farmacologia , Sobrevivência Celular/efeitos dos fármacos
6.
Expert Opin Emerg Drugs ; 28(4): 297-309, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38129984

RESUMO

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.


Assuntos
Uveíte , Humanos , Uveíte/tratamento farmacológico , Inflamação/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Ensaios Clínicos Fase II como Assunto
7.
Med Teach ; 45(6): 658-663, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36420808

RESUMO

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.


Assuntos
COVID-19 , Instrução por Computador , Estudantes de Medicina , Humanos , Estudos Prospectivos , Pandemias , Competência Clínica
8.
Small ; 18(19): e2201223, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35373912

RESUMO

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.


Assuntos
Carbono , Carbono/química , Ligação de Hidrogênio , Temperatura
9.
Int J Hyperthermia ; 39(1): 490-496, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35285391

RESUMO

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.


Assuntos
Hiperparatireoidismo Primário , Ablação por Radiofrequência , Cálcio , Humanos , Hiperparatireoidismo Primário/cirurgia , Hormônio Paratireóideo , Paratireoidectomia , Ablação por Radiofrequência/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
10.
Biomed Chromatogr ; 36(4): e5300, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34921409

RESUMO

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.


Assuntos
Fallopia multiflora , Animais , Cromatografia Líquida , Camundongos , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Ultrafiltração , Peixe-Zebra
11.
J Microencapsul ; 39(4): 341-351, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35670223

RESUMO

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.


Assuntos
Nanocompostos , Zinco , Bandagens , Compostos Inorgânicos de Carbono , Sobrevivência Celular , Cesárea , Feminino , Humanos , Gravidez , Compostos de Silício , Zinco/química
12.
Angew Chem Int Ed Engl ; 61(27): e202202532, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35357065

RESUMO

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.


Assuntos
Perileno , Imidas
13.
Angew Chem Int Ed Engl ; 61(32): e202203254, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35420726

RESUMO

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.


Assuntos
Medições Luminescentes , Polímeros , Luminescência , Pirenos
14.
J Am Chem Soc ; 143(34): 13675-13685, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34410121

RESUMO

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.

15.
Bioorg Chem ; 116: 105357, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34562675

RESUMO

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".


Assuntos
Gynostemma/química , Saponinas/farmacologia , Sirtuína 1/metabolismo , Triterpenos/farmacologia , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Saponinas/química , Saponinas/isolamento & purificação , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação , Damaranos
16.
Acta Pharmacol Sin ; 42(5): 701-714, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32796955

RESUMO

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.


Assuntos
Autofagia/efeitos dos fármacos , Cardiomegalia/tratamento farmacológico , Cardiotônicos/uso terapêutico , Flavanonas/uso terapêutico , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Catalase/metabolismo , Proteína Forkhead Box O3/metabolismo , Isoproterenol , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo
17.
BMC Musculoskelet Disord ; 22(1): 60, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430847

RESUMO

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.


Assuntos
Fraturas Ósseas , Fraturas Cominutivas , Parafusos Ósseos , Fios Ortopédicos , Estudos de Coortes , Fixação Interna de Fraturas/efeitos adversos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/cirurgia , Humanos , Patela/diagnóstico por imagem , Patela/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prevalência , Estudos Retrospectivos
18.
Neurochem Res ; 45(12): 3034-3044, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33095438

RESUMO

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.


Assuntos
Epilepsia do Lobo Temporal/metabolismo , Fatores de Transcrição Forkhead/metabolismo , MicroRNAs/metabolismo , RNA Circular/metabolismo , Proteínas Repressoras/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Ratos Wistar , Convulsões/metabolismo , Regulação para Cima
19.
Bioorg Med Chem Lett ; 30(13): 127237, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32386981

RESUMO

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.


Assuntos
Anti-Inflamatórios/uso terapêutico , Benzotiazóis/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Inflamação/tratamento farmacológico , Oxidiazóis/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/metabolismo , Benzotiazóis/síntese química , Benzotiazóis/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/metabolismo , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/metabolismo , Relação Estrutura-Atividade
20.
Epilepsy Behav ; 113: 107576, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33232895

RESUMO

PURPOSE: Given the importance of adolescents' participation in the care of their chronic diseases during their transitional period in the healthcare system, the present study investigated the degree of participation in healthcare behavior by Chinese adolescents with chronic epilepsy and identified factors that should be addressed by health interventions. METHODS: The study used a convenience sample of 1238 adolescent patients with epilepsy, who were hospitalized in 17 tertiary A-level children or maternal and child specialty hospitals in China between January 2017 and March 2020. Several scales were used to measure their degree of participation in healthcare behavior and the factors that influence it. Data collection was conducted after uniform training of the investigators. The adolescents who met the inclusion and exclusion criteria could scan the QR code of the questionnaire via a mobile phone. RESULTS: The age of the participants ranged from 12.2 to 17.8 years (mean 14.2 years), and the sample had a male-to-female ratio of 1.25:1. The patients' average total score of participation in healthcare behavior was 125.58 (SD = 12.25), which was lower than the norm for China. Their scores on the six dimensions of participation were highest for information interaction, followed in descending order by medical decision-making, treatment and care, appeal, diagnosis and treatment decision-making, and questioning supervision. Multiple linear regression found significant associations between health-care participation and five personal and disease variables (gender, age, course of disease, number of comorbid diseases, type of family structure), self-efficacy, and coping styles (cognitive-palliative and acceptance), which explained 52.1% of the variance in patients' total scores on participating in healthcare behavior. CONCLUSIONS: The participation of young Chinese patients with epilepsy in transitional healthcare behavior needs to be improved. Participation was positively associated with being female, a longer course of disease, fewer comorbidities, and living in a nuclear family. Patients who used cognitive-palliative and acceptance coping styles and those who had higher self-efficacy also had significantly higher levels of participation in healthcare behavior. The study provides useful reference points for adolescents with chronic disease to participate in healthcare programs, in order to achieve a smooth transition from childhood to adulthood.


Assuntos
Adaptação Psicológica , Comportamento do Adolescente , Epilepsia/terapia , Participação do Paciente , Transição para Assistência do Adulto , Adolescente , Criança , China , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários
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