RESUMO
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12944-020-01416-2.
RESUMO
The composition and potency of the high temperature (40 â) stress induced size variants of a recombinant humanized monoclonal antibody(rhumAb1) were characterized by means of SEC-HPLC, non- reduced CE-SDS, liquid chromatography coupled with mass spectrometry (LC-MS) and antibody dependent cell-mediated cytotoxicity (ADCC) assay. The molecular masses of the four size variants (SEC-1-SEC-4) separated by SEC-HPLC and seven size variants(NR-1-NR-7) detected by non-reduced CE-SDS were all characterized by LC-MS. The major low molecular weight variants were generated due to the hinge region fragmentation of heavy chain. The hinge region cleavage was found mainly in the Ser221-Cys-Asp-Lys-Thr- His-Thr-Cys228 sequence, in which C222-D223 and H226-T227 were the major cleavage sites. The size variants of rhumAb1, namely dimer and fragments, have significantly reduced ADCC activity in comparison with the intact rhumAb1 drug product. This study provided insights into the stability profiling for rhumAb1 drug product. The study protocols presented here may be applicable to the analytical characterization of other monoclonal antibody-based therapeutic products.
Assuntos
Anticorpos Monoclonais Humanizados/química , Citotoxicidade Celular Dependente de Anticorpos , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Peso Molecular , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80% of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20% suggesting poor prognosis. METHODS: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. RESULTS: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 µM with an IC50 of 20 µM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 µM RACC was decreased by 49 and 76% respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. CONCLUSIONS: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma.
Assuntos
Quitosana/química , Cicloexanonas/uso terapêutico , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Tretinoína/análogos & derivados , Tretinoína/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cicloexanonas/química , Proteína Potenciadora do Homólogo 2 de Zeste , Humanos , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Osteossarcoma/patologia , Fosforilação/efeitos dos fármacos , Complexo Repressor Polycomb 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Tempo , Transfecção , Tretinoína/químicaRESUMO
OBJECTIVE: To develop and validate a computed tomography (CT)-based scoring system for evaluating the risk of dural defects (DDs) in anterior surgery for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: We retrospectively analyzed CT imaging features of 114 OPLL patients in our institute who received anterior decompression surgery. Intraoperative DDs were found in 16 patients. A multivariable logistic regression was used to evaluate the predictors. According to the odd ratio of the included risk factors, we developed a CT scoring system for evaluating the risk of DDs in anterior OPLL surgery. The system was further validated in an independent group of 39 OPLL patients. RESULTS: We developed a CT scoring system as follows: hook sign (2 points), K-line (-) (1 point) and broad base (1 point). Thus, the system comprised 4 total points, and patients were at high risks of dural defects when the score ≥3 points. The operating characteristics of a score ≥3 for predicting DDs in the validation group were: sensitivity of 0.83, specificity of 0.94, LR positive of 13.75, LR negative of 0.18 and AUC of 0.886. The discriminatory ability of the proposed score could be demonstrated in the validation cohort. CONCLUSIONS: The relatively simple and easy-to-use scoring system we propose integrates the 3 most reliable spinal CT findings observed in patients with OPLL and a DD. The likelihood to identify the underlying risks of spinal CSF leaks may be useful to triage patients who may benefit from indirect decompression techniques.
Assuntos
Vértebras Cervicais , Descompressão Cirúrgica , Dura-Máter , Ossificação do Ligamento Longitudinal Posterior , Tomografia Computadorizada por Raios X , Humanos , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tomografia Computadorizada por Raios X/métodos , Dura-Máter/cirurgia , Dura-Máter/diagnóstico por imagem , Descompressão Cirúrgica/métodos , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Adulto , Fatores de RiscoRESUMO
Background: The outbreak of severe respiratory syndrome coronavirus 2 (SARS-COV-2) has led to long periods of social isolation for individuals across the world. Although medical students generally have a high prevalence of mental health problems, they have received less attention than other groups concerning the impact of SARS-COV-2. Therefore, the present study investigated the mental health status, risk factors, and protective factors for mental health problems in medical students in North China during the SARS-COV-2 pandemic. Methods: A WeChat-based survey, which included the Depression Anxiety Stress Scale-21 and measures of social demographics, was performed twice. Risk and protective factors were identified by binary logistic regression analysis. Results: A total of 702 effective questionnaires were collected in two separate surveys. In total, 24.55% of medical students were suffering anxiety to different degrees of severity, 13.18% were suffering depression in the first survey, and 3.71% wanted to give up working in primary medical care during the SARS-COV-2 pandemic in the second survey. In contrast, during the SARS-COV-2 pandemic, a risk factor for anxiety and depression was gender which is male, while being knowledgeable about the SARS-COV-2 pandemic and having a lower academic burden were both protective factors. Conclusions: Measures are required to prevent increases in mental health problems in medical students. Our findings suggest that increasing knowledge about the SARS-COV-2 pandemic and reducing academic burden in medical students is extremely important during the SARS-COV-2 pandemic.