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1.
Pharmacol Res ; 205: 107236, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797358

RESUMO

The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here, we show that ketamine rapidlyalleviated depression-like behaviors and normalized abnormal expression of pTyr1472NR2B and striatal-enriched protein tyrosine phosphatase (STEP) 61 within and outside synapses in the medial prefrontal cortex (mPFC) induced by chronic unpredictable stress (CUS) and conditional knockdown of STEP 61, a key phosphatase of NR2B, within 1 hour after administration Together, our results delineate the rapid initiation of ketamine's antidepressant effects results from the restoration of NR2B phosphorylation homeostasis within and outside synapses. The dynamic regulation of phosphorylation of NR2B provides a new perspective for developing new antidepressant strategies.


Assuntos
Antidepressivos , Depressão , Ketamina , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal , Receptores de N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato/metabolismo , Ketamina/farmacologia , Animais , Fosforilação/efeitos dos fármacos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Masculino , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Depressão/tratamento farmacológico , Depressão/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/genética , Tirosina/metabolismo , Camundongos , Estresse Psicológico/metabolismo , Estresse Psicológico/tratamento farmacológico , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Comportamento Animal/efeitos dos fármacos
2.
Angew Chem Int Ed Engl ; 63(17): e202318800, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38443316

RESUMO

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).


Assuntos
Nanopartículas , Ácidos Nucleicos , Corantes Fluorescentes/química , Nanopartículas/química , Técnicas de Amplificação de Ácido Nucleico
3.
J Med Internet Res ; 25: e36477, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36716097

RESUMO

BACKGROUND: The key to effective stroke management is timely diagnosis and triage. Machine learning (ML) methods developed to assist in detecting stroke have focused on interpreting detailed clinical data such as clinical notes and diagnostic imaging results. However, such information may not be readily available when patients are initially triaged, particularly in rural and underserved communities. OBJECTIVE: This study aimed to develop an ML stroke prediction algorithm based on data widely available at the time of patients' hospital presentations and assess the added value of social determinants of health (SDoH) in stroke prediction. METHODS: We conducted a retrospective study of the emergency department and hospitalization records from 2012 to 2014 from all the acute care hospitals in the state of Florida, merged with the SDoH data from the American Community Survey. A case-control design was adopted to construct stroke and stroke mimic cohorts. We compared the algorithm performance and feature importance measures of the ML models (ie, gradient boosting machine and random forest) with those of the logistic regression model based on 3 sets of predictors. To provide insights into the prediction and ultimately assist care providers in decision-making, we used TreeSHAP for tree-based ML models to explain the stroke prediction. RESULTS: Our analysis included 143,203 hospital visits of unique patients, and it was confirmed based on the principal diagnosis at discharge that 73% (n=104,662) of these patients had a stroke. The approach proposed in this study has high sensitivity and is particularly effective at reducing the misdiagnosis of dangerous stroke chameleons (false-negative rate <4%). ML classifiers consistently outperformed the benchmark logistic regression in all 3 input combinations. We found significant consistency across the models in the features that explain their performance. The most important features are age, the number of chronic conditions on admission, and primary payer (eg, Medicare or private insurance). Although both the individual- and community-level SDoH features helped improve the predictive performance of the models, the inclusion of the individual-level SDoH features led to a much larger improvement (area under the receiver operating characteristic curve increased from 0.694 to 0.823) than the inclusion of the community-level SDoH features (area under the receiver operating characteristic curve increased from 0.823 to 0.829). CONCLUSIONS: Using data widely available at the time of patients' hospital presentations, we developed a stroke prediction model with high sensitivity and reasonable specificity. The prediction algorithm uses variables that are routinely collected by providers and payers and might be useful in underresourced hospitals with limited availability of sensitive diagnostic tools or incomplete data-gathering capabilities.


Assuntos
Acidente Vascular Cerebral , Triagem , Idoso , Humanos , Estados Unidos , Estudos Retrospectivos , Triagem/métodos , Determinantes Sociais da Saúde , Medicare , Aprendizado de Máquina , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Hospitais
4.
Br J Neurosurg ; 37(5): 1206-1210, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33054413

RESUMO

Primary meningeal melanoma is a rare type of melanocytic cancer originating from the melanocytes of the leptomeninges. It commonly presents as a solitary mass, and multifocal amelanotic lesions were scarcely reported. Diagnosis of multifocal melanoma is particularly challenging, clinically and diagnostically, especially in the absence of cutaneous nevi and melanin pigment. Surgical biopsy result is the gold standard. In this case study, we present an uncommon case of multifocal primary amelanotic meningeal melanomas mimicking lymphomas in the skull base and near the Sylvian fissure, which serves to provide reference value to the clinical diagnosis. Physicians should be aware of the existence of this special type in the clinical work.


Assuntos
Linfoma , Melanoma Amelanótico , Neoplasias Cutâneas , Humanos , Melanoma Amelanótico/diagnóstico , Melanoma Amelanótico/cirurgia , Melanoma Amelanótico/patologia
5.
Malays J Med Sci ; 30(6): 147-155, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38239245

RESUMO

Background: Certified training must be provided for lay vision screeners prior to their conduct of a vision screening programme. However, the effectiveness of trained lay screeners does deteriorate over time. This study aims to evaluate the effectiveness of a recertification vision screening training module using the KieVision™ Preschool Vision Screening Kit for preschool teachers in Malaysia. Methods: This was a randomised control trial. Fifty-nine preschool teachers previously enrolled in a Knowledge Transfer Programme were divided into a Study Group (n = 31) to receive recertification training and a Control Group (n = 28) to attend briefing sessions. Subjects was then asked to perform vision screening on 15 preschool children aged 4 years old-6 years old at their respective premises, then verified by optometrists after 2 weeks from the initial screening on the same children. Results: A total of 894 children were screened, with the Study Group and Control Group screened 49.7% and 50.3%, respectively. There was higher validity in vision screening findings from the Study Group (sensitivity = 66.7%, positive predictive value (PPV) = 61.5%) compared to the Control Group (sensitivity = 36.0 %, PPV = 40.9%). Conclusion: Teachers who received recertification training were more competent in detecting children's vision impairment using KieVision™ Preschool Vision Screening Kit. Thus, timely recertification training should be emphasised to ensure sustainable consistency and reliability of vision screening programmes conducted by lay vision screeners.

6.
Lancet ; 397(10277): 892-901, 2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676628

RESUMO

BACKGROUND: Covalent Bruton's tyrosine kinase (BTK) inhibitors are efficacious in multiple B-cell malignancies, but patients discontinue these agents due to resistance and intolerance. We evaluated the safety and efficacy of pirtobrutinib (working name; formerly known as LOXO-305), a highly selective, reversible BTK inhibitor, in these patients. METHODS: Patients with previously treated B-cell malignancies were enrolled in a first-in-human, multicentre, open-label, phase 1/2 trial of the BTK inhibitor pirtobrutinib. The primary endpoint was the maximum tolerated dose (phase 1) and overall response rate (ORR; phase 2). This trial is registered with ClinicalTrials.gov, NCT03740529. FINDINGS: 323 patients were treated with pirtobrutinib across seven dose levels (25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg once per day) with linear dose-proportional exposures. No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. The recommended phase 2 dose was 200 mg daily. Adverse events in at least 10% of 323 patients were fatigue (65 [20%]), diarrhoea (55 [17%]), and contusion (42 [13%]). The most common adverse event of grade 3 or higher was neutropenia (32 [10%]). There was no correlation between pirtobrutinib exposure and the frequency of grade 3 treatment-related adverse events. Grade 3 atrial fibrillation or flutter was not observed, and grade 3 haemorrhage was observed in one patient in the setting of mechanical trauma. Five (1%) patients discontinued treatment due to a treatment-related adverse event. In 121 efficacy evaluable patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) treated with a previous covalent BTK inhibitor (median previous lines of treatment 4), the ORR with pirtobrutinib was 62% (95% CI 53-71). The ORR was similar in CLL patients with previous covalent BTK inhibitor resistance (53 [67%] of 79), covalent BTK inhibitor intolerance (22 [52%] of 42), BTK C481-mutant (17 [71%] of 24) and BTK wild-type (43 [66%] of 65) disease. In 52 efficacy evaluable patients with mantle cell lymphoma (MCL) previously treated with covalent BTK inhibitors, the ORR was 52% (95% CI 38-66). Of 117 patients with CLL, SLL, or MCL who responded, all but eight remain progression-free to date. INTERPRETATION: Pirtobrutinib was safe and active in multiple B-cell malignancies, including patients previously treated with covalent BTK inhibitors. Pirtobrutinib might address a growing unmet need for alternative therapies for these patients. FUNDING: Loxo Oncology.


Assuntos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma de Células B/patologia , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Resultado do Tratamento
7.
J Exp Bot ; 73(19): 6727-6743, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-35986920

RESUMO

DELLA proteins are important repressors of gibberellin signaling, regulating plant development and defense responses through crosstalk with various phytohormones. Sugarcane ScGAI encodes a DELLA protein that regulates culm development. However, it is unclear which transcription factors mediate the transcription of ScGAI. Here, we identified two different ScGAI promoter sequences that cooperatively regulate ScGAI transcription. We also identified a nuclear-localized AP2 family transcription factor, ScAIL1, which inhibits the transcription of ScGAI by directly binding to two ScGAI promoters. ScAIL1 was expressed in all sugarcane tissues tested and was induced by gibberellin and various stressors, including NaCl, polyethylene glycol, and pathogenic fungi and bacteria. Overexpression of ScAIL1 in rice significantly improved resistance to bacterial blight and rice blast, while reducing growth and development. In addition, several genes associated with stress responses were significantly up-regulated in transgenic rice overexpressing ScAIL1. Endogenous phytohormone content and expression analysis further revealed that ScAIL1-overexpressing lines improved resistance to bacterial blight and rice blast instead of promoting growth, and that this response was associated with increased jasmonic acid synthesis and gibberellin inactivation. These results provide molecular evidence that the role of ScAIL1 in the plant defense response is related to jasmonic acid and gibberellin signaling.


Assuntos
Oryza , Saccharum , Giberelinas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Saccharum/genética , Saccharum/metabolismo , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Plantas/metabolismo , Proteínas de Plantas/metabolismo , Oryza/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo
8.
Intern Med J ; 52(7): 1242-1250, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-33949777

RESUMO

BACKGROUND: Several international centres have published their experiences with outpatient autologous stem cell transplantation (ASCT) as treatment of haematological malignancies. AIM: In this single-centre retrospective review, we aim to examine the outcomes of outpatient autograft and review healthcare resource utilisation in the pre-cytopenic period. METHODS: Patients undergoing ASCT in Royal Hobart Hospital, Tasmania between 2008 and 2018 had their records reviewed and key outcomes data collected based on whether they received inpatient/outpatient ASCT. An outpatient ASCT was defined as conditioning as an outpatient; patients could then be managed with an elective admission during the cytopenic period or admission only when clinically indicated. RESULTS: Of 231 ASCT performed, 135 (58%) were as outpatients: 59 used carmustine-etoposide-cytarabine-melphalan conditioning for lymphoma (BEAM-ASCT) and 76 used high-dose melphalan for myeloma and amyloidosis (MEL-ASCT). Approximately one-third of patients undergoing outpatient ASCT were admitted electively during nadir period; the majority of patients required minimal interventions prior to this time. The most common causes for unplanned hospitalisation (which occurred in 71 (80%) of the 89 planned outpatient transplants) were febrile neutropenia (39%) and mucositis (35%). Age was the only risk factor identified to increase risk of requiring unplanned hospitalisation. Use of oral antibiotic prophylaxis reduced febrile neutropenia rates among melphalan outpatient ASCT. Outpatient ASCT led to significantly reduced inpatient bed-days and overall cost (approximately A$13 000-A$16 000) compared with inpatient autografts, with no significant differences in engraftment, rates of febrile neutropenia, intensive care admissions or mortality. CONCLUSION: Outpatient autografts may save healthcare resources without compromising patient outcomes.


Assuntos
Neutropenia Febril , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Austrália , Neutropenia Febril/tratamento farmacológico , Hospitais , Humanos , Melfalan , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Pacientes Ambulatoriais , Estudos Retrospectivos , Transplante de Células-Tronco , Tasmânia/epidemiologia , Condicionamento Pré-Transplante , Transplante Autólogo
9.
Mol Breed ; 41(5): 36, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-37309330

RESUMO

As a staple food for more than half of the world's population, the importance of rice is self-evident. Compared with ordinary rice, rice cultivars with superior eating quality and appearance quality are more popular with consumers due to their unique taste and ornamental value, even if their price is much higher. Appearance quality and CEQ (cooking and eating quality) are two very important aspects in the evaluation of rice quality. Here, we performed a genome-wide association study on floury endosperm in a diverse panel of 533 cultivated rice accessions. We identified a batch of potential floury genes and prioritize one (LOC_Os03g48060) for functional analyses. Two floury outer endosperm mutants (flo19-1 and flo19-2) were generated through editing LOC_Os03g48060 (named as FLO19 in this study), which encodes a class I glutamine amidotransferase. The different performances of the two mutants in various storage substances directly led to completely different changes in CEQ. The mutation of FLO19 gene caused the damage of carbon and nitrogen metabolism in rice, which affected the normal growth and development of rice, including decreased plant height and yield loss by decreased grain filling rate. Through haplotype analysis, we identified a haplotype of FLO19 that can improve both CEQ and appearance quality of rice, Hap2, which provides a selection target for rice quality improvement, especially for high-yield indica rice varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01226-z.

10.
Angew Chem Int Ed Engl ; 60(25): 14051-14059, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33797161

RESUMO

Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate the generation of reactive oxygen species (ROS) against tumors, potentially leading to off-target toxicity to normal tissues. We report a transformable core-shell nanosonosensitizer (TiO2 @CaP) that reinvigorates ROS generation and dissolves its CaP shell to release Ca2+ in an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO2 @CaP acts as a smart nanosonosensitizer that specifically induces mitochondrial dysfunction via overloading intracellular Ca2+ ions to synergize with the sonodynamic process in the TME. TiO2 @CaP substantially enhances immunogenic cell death, resulting in enhanced T-cell recruitment and infiltration into the immunogenic cold tumor (4T1). In conjunction with checkpoint blockade therapy (anti-PD 1), TiO2 @CaP-mediated sonodynamic therapy elicits systemic antitumor immunity, leading to regression of non-treated distant tumors and inhibition of lung metastasis. This work paves the way to development of "smart" TME-activatable sonosensitizers with temporospatial control over antitumor responses.


Assuntos
Neoplasias da Mama/metabolismo , Cálcio/metabolismo , Nanopartículas/metabolismo , Titânio/metabolismo , Terapia por Ultrassom , Animais , Neoplasias da Mama/terapia , Cálcio/química , Linhagem Celular Tumoral , Feminino , Camundongos , Nanopartículas/química , Tamanho da Partícula , Titânio/química , Microambiente Tumoral
11.
J Nanobiotechnology ; 17(1): 47, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935403

RESUMO

BACKGROUND: Glioma is a common brain tumor with a high mortality rate. A small population of cells expressing stem-like cell markers in glioma contributes to drug resistance and tumor recurrence. METHODS: Porous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), was combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, we detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO. RESULTS: NCH-421K and C6 cells were more sensitive to the combination treatment. Moreover, the expression of stem-like cell markers and hypoxia related molecules were decreased after combination treatment. The in vivo results were in line with in vitro. The combination treatment presents significant antitumor effects in mice bearing C6 tumor compared with the treatment of TMZ, PTT or TMZ/PSi NPs only. CONCLUSION: These results suggested the TMZ/PSi NPs combined with HBO and PTT could be a potential therapeutic strategy for glioma.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/terapia , Glioma/terapia , Nanopartículas/química , Células-Tronco Neoplásicas/patologia , Silício/química , Temozolomida/farmacologia , Animais , Antineoplásicos Alquilantes/química , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Glioma/patologia , Humanos , Oxigenoterapia Hiperbárica , Hipertermia Induzida , Camundongos Nus , Transplante de Neoplasias , Células-Tronco Neoplásicas/efeitos dos fármacos , Tamanho da Partícula , Porosidade , Ratos , Temozolomida/química
12.
Environ Toxicol ; 33(3): 315-324, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29193611

RESUMO

Overexposure to manganese (Mn) has been known to induce alpha-synuclein (α-Syn) oligomerization, which is degraded mainly depending on endoplasmic reticulum stress (ER stress) and autophagy pathways. However, little data reported the cross-talk between ER stress and autophagy on Mn-induced α-Syn oligomerization. To explore the relationship between ER stress and autophagy, we used 4-phenylbutyric acid (4-PBA, the ER stress inhibitor), rapamycin (Rap, autophagy activator) and 3-methyladenine (3-MA, autophagy inhibitor) in mice model of manganism. After 4 weeks of treatment with Mn, both ER stress and autophagy were activated. Exposed to Mn also resulted in α-Syn oligomerization and neuronal cell damage in the brain tissue of mice, which could be relieved by 4-PBA pretreatment. Moreover, when the ER stress was inhibited, the activation of autophagy was also inhibited. Rap pretreatment significantly activated autophagy and decreased α-Syn oligomers. However, 3-MA pretreatment inhibited autophagy resulting in increase of α-Syn oligomers, and compensatorily activated PERK signaling pathway. Our results also demonstrated that the inhibition of autophagy by 3-MA aggravated neuronal cell damage. The findings clearly demonstrated that the cross-talking between autophagy and ER stress might play an important role in the α-Syn oligomerization and neurotoxicity by Mn.


Assuntos
Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Manganês/toxicidade , alfa-Sinucleína/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Butilaminas/farmacologia , Cloretos/toxicidade , Compostos de Manganês , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fenilbutiratos/farmacologia , Polimerização , Transdução de Sinais , Sirolimo/farmacologia
14.
J Am Acad Dermatol ; 86(6): e257-e258, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-32652191
15.
BMC Surg ; 17(1): 91, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28830403

RESUMO

BACKGROUND: Over the past decade, mini-laparoscopic cholecystectomy (MLC) and single-port laparoscopic cholecystectomy (SILC) have been the two main successful mini-invasive surgical interventions for the treatment of cholecystolithiasis since the advent of laparoscopic cholecystectomy (LC). In this study, we conducted a meta-analysis to compare the two treatment alternatives. METHODS: We searched PubMed, CNKI and the Cochrane library for trials that compared MLC and SILC. Risk difference (RD) and mean difference (MD) were calculated with a 95% confidence interval (CI). RESULTS: Four randomized controlled trials (RCTs) and 2 non-randomized comparative studies (nRCSs) involving 2764 patients were identified. A longer operating time (MD -10.49; 95% CI -18.10, -2.88; P = 0.007) and a shorter wound length (MD 3.65; 95% CI 0.51, 6.78; P = 0.02) were found to be associated with SILC compared with MLC. No significant differences were revealed in conversion, hospital stay, pain relief and cosmetic results. Although a lower incidence of complications was observed with MLC (8.2%) compared with SILC (15.9%), but the difference was not statistically significant (RD -0.06; 95% CI -0.12, 0.00; P = 0.07). CONCLUSIONS: MLC has an advantage over SILC in terms of operating time rather than hospital stay, pain relief, cosmetic results. Though conversion and complication rates were higher with SILC, there existed no statistically differences in the two measures between the two procedures. Whether MLC confers any benefits in terms of conversion or complications still warrants further studies.


Assuntos
Colecistectomia Laparoscópica/métodos , Colecistectomia/métodos , Colecistolitíase/cirurgia , Colecistectomia/efeitos adversos , Colecistectomia Laparoscópica/efeitos adversos , Humanos , Incidência , Tempo de Internação , Duração da Cirurgia , Dor Pós-Operatória/etiologia
16.
Can J Physiol Pharmacol ; 94(3): 245-50, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26610043

RESUMO

Moutan cortex (MC) is a traditional Chinese medicine with diverse biological effects. The present study was performed to investigate the effects of MC on myocardial ischemia/reperfusion (I/R) in rats and to explore its possible mechanisms. Sprague-Dawley rats were administered MC extract (1.98 g/kg, i.g.) for 14 days and underwent a subsequent open-chest procedure involving 30 min of myocardial ischemia and 60 min of reperfusion. The cardioprotective effect of MC was demonstrated by reduced infarct size and marked improvement in the histopathological examination. The increase in the activity of superoxide dismutase (SOD) and glutathione (GSH) as well as the reduction of malondialdehyde (MDA) indicated that MC effectively promoted the anti-oxidative defense system. Increased anti-oxidative defense was accompanied by decreased release of lactate dehydrogenase (LDH) and creatine kinase (CK). The reduction in TUNEL-positive myocytes demonstrated that MC decreased myocardial apoptosis. The mRNA expression of B cell leukemia-2 (Bcl-2) was upregulated by MC and the ratio of Bcl-2/Bcl-2-associated X protein (Bax) mRNA expression was increased. MC pretreatment decreased the mRNA expression of inducible nitric oxide synthase (iNOS). The data from this study suggest that MC exerted protective effects on acute myocardial I/R injury via anti-oxidative and anti-apoptotic activities.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Paeonia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
17.
IEEE Trans Cybern ; 54(5): 2941-2954, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37027647

RESUMO

Given a network, it is well recognized that attributed network embedding represents each node of the network in a low-dimensional space, and, thus, brings considerable benefits for numerous graph mining tasks. In practice, a diverse set of graph tasks can be processed efficiently via the compact representation that preserves content and structure information. The majority of attributed network embedding approaches, especially, the graph neural network (GNN) algorithms, are substantially costly in either time or space due to the expensive learning process, while the randomized hashing technique, locality-sensitive hashing (LSH), which does not need learning, can speedup the embedding process at the expense of losing some accuracy. In this article, we propose the MPSketch model, which bridges the performance gap between the GNN framework and the LSH framework by adopting the LSH technique to pass messages and capture high-order proximity in a larger aggregated information pool from the neighborhood. The extensive experimental results confirm that in node classification and link prediction, the proposed MPSketch algorithm enjoys performance comparable to the state-of-the-art learning-based algorithms and outperforms the existing LSH algorithms, while running faster than the GNN algorithms by 3-4 orders of magnitude. More precisely, MPSketch runs 2121, 1167, and 1155 times faster than GraphSAGE, GraphZoom, and FATNet on average, respectively.

18.
Biochim Biophys Acta Mol Cell Res ; 1871(2): 119641, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37996057

RESUMO

Extracellular vesicles (EVs) are cell-released vesicles that mediate intercellular communication by transferring bioactive cargo. Protein and RNA sorting into EVs has been extensively assessed, while selective enrichment of glycans in EVs remains less explored. In this study, a mass spectrometry-based approach, glycan node analysis (GNA), was applied to broadly assess the sorting of glycan features into EVs. Two metastatic variants (lung and bone) generated in mouse modes from the MDA-MB-231 human breast cancer cell line were assessed, as these EVs are known to contain distinct organotropic biomolecules. EVs were isolated from conditioned cell culture medium by tangential flow filtration and authenticated by standard techniques. GNA analysis revealed selective enrichment of several glycan features in EVs compared to the originating cells, particularly those associated with binding to the extracellular matrix, which was also observed in EVs from the parental MDA-MB-231 cell line (human pleural metastases). The bone-tropic variant displayed enrichment of distinct EV glycan features compared to the lung-tropic one. Additionally, the metastatic variants generated in mouse models displayed reduced EV glycan sorting compared to the parental metastatic cell line. This study represents the first comprehensive assessment of differences in glycan features between EVs and originating cells and provides evidence that the diversity of EV glycan sorting is reduced upon generation of variant cell lines in mouse models. Future research is likely to uncover novel mechanisms of EV glycan sorting, shed light on glycan features for EV authentication or biomarker purposes, and assess functional roles of the EV glycocode in (patho)physiology.


Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Humanos , Animais , Camundongos , Feminino , Vesículas Extracelulares/metabolismo , Neoplasias da Mama/metabolismo , Biomarcadores/metabolismo , Proteínas/metabolismo , Polissacarídeos/análise
19.
Nat Commun ; 15(1): 631, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245527

RESUMO

Lipid droplets (LDs) are dynamic lipid storage organelles that can be degraded by autophagy machinery to release neutral lipids, a process called lipophagy. However, specific receptors and regulation mechanisms for lipophagy remain largely unknown. Here, we identify that ATG14, the core unit of the PI3KC3-C1 complex, also targets LD and acts as an autophagic receptor that facilitates LD degradation. A negative regulator, Syntaxin18 (STX18) binds ATG14, disrupting the ATG14-ATG8 family members interactions and subverting the PI3KC3-C1 complex formation. Knockdown of STX18 activates lipophagy dependent on ATG14 not only as the core unit of PI3KC3-C1 complex but also as the autophagic receptor, resulting in the degradation of LD-associated anti-viral protein Viperin. Furthermore, coronavirus M protein binds STX18 and subverts the STX18-ATG14 interaction to induce lipophagy and degrade Viperin, facilitating virus production. Altogether, our data provide a previously undescribed mechanism for additional roles of ATG14 in lipid metabolism and virus production.


Assuntos
Gotículas Lipídicas , Metabolismo dos Lipídeos , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/fisiologia , Proteínas/metabolismo , Autofagia/fisiologia
20.
J Agric Food Chem ; 72(1): 715-725, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123485

RESUMO

Cd pollution-safe cultivar (Cd-PSC) is a feasible strategy to minimize Cd contamination in leafy vegetables. The shoot Cd concentrations of 23 Lactuca sativa cultivars under Cd stress ranged from 0.124 to 2.155 mg·kg-1 with a maximum cultivar difference of 8 folds. Typical Cd-PSC C16 (L) and high-Cd-accumulating cultivar C13 (H) were screened to investigate the mechanisms of Cd accumulations in L. sativa through determining Cd concentrations, Cd subcellular distributions, phytochelatin profiles, and phytochelatin biosynthesis-related genes' expressions. Higher Cd distribution in a heat stable fraction in C13 (H) indicated that the high Cd accumulation trait of C13 (H) mainly depended on the Cd-phytochelatin complexes. Root phytochelatin concentrations were significantly elevated in C13 (H) (5.83 folds) than in C16 (L) (2.69 folds) (p < 0.05) under Cd stress. Significantly downregulated expressions of glutathione S-transferase rather than the regulation of phytochelatin synthesis genes in the root of C13 (H) might be responsible for sufficient glutathione supply for phytochelatins synthesis. These findings suggested that phytochelatin elevation in C13 (H) would favor the Cd root to shoot transportation, which provides new insights into the phytochelatin-related cultivar-dependent Cd accumulating characteristic in L. sativa.


Assuntos
Fitoquelatinas , Poluentes do Solo , Fitoquelatinas/metabolismo , Cádmio/metabolismo , Lactuca/genética , Poluentes do Solo/metabolismo , Raízes de Plantas/química
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