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1.
BMC Pulm Med ; 24(1): 225, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724980

RESUMO

OBJECTIVE: To explore the potential association between dietary live microbes and the prevalence of Chronic Obstructive Pulmonary Diseases (COPD). METHODS: In this cross-sectional study, data of 9791 participants aged 20 years or older in this study were collected from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018. Participants in this study were classified into three groups according to the Sanders' dietary live microbe classification system: low, medium, and high dietary live microbe groups. COPD was defined by a combination of self-reported physician diagnoses and standardized medical status questionnaires. Logistic regression and subgroup analysis were used to assess whether dietary live microbes were associated with the risk of COPD. RESULTS: Through full adjustment for confounders, participants in the high dietary live microbe group had a low prevalence of COPD in contrast to those in low dietary live microbe group (OR: 0.614, 95% CI: 0.474-0.795, and p < 0.001), but no significant association with COPD was detected in the medium and the low dietary live microbe groups. This inverse relationship between dietary live microbe intake and COPD prevalence was more inclined to occur in smokers, females, participants aged from 40 to 59 years old and non-obese participants. CONCLUSION: A high dietary live microbe intake was associated with a low prevalence of COPD, and this negative correlation was detected especially in smokers, females, participants aged from 40 to 59 years old and non-obese participants.


Assuntos
Inquéritos Nutricionais , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Prevalência , Dieta/estatística & dados numéricos , Idoso , Modelos Logísticos , Estados Unidos/epidemiologia , Fatores de Risco , Adulto Jovem , Fumar/epidemiologia
2.
Insect Sci ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693760

RESUMO

Previous studies have demonstrated that associative learning and experience play important roles in the string-pulling of bumblebees (Bombus terrestris). However, the features of the target (artificial flower with sugar reward) and the string that bees learn in such tasks remain unknown. This study aimed to explore the specific aspects of the string-flower arrangement that bumblebees learn and how they prioritize these features. We show that bumblebees trained with string-pulling are sensitive to the flower stimuli; they exhibit a preference for pulling strings connected to flowers over strings that are not attached to a target. Additionally, they chose to pull strings attached to flowers of the same color and shape as experienced during training. The string feature also plays a crucial role for bumblebees when the flower features are identical. Furthermore, bees prioritized the features of the strings rather than the flowers when both cues were in conflict. Our results show that bumblebees solve string-pulling tasks by acquiring knowledge about the characteristics of both targets and strings, and contribute to a deeper understanding of the cognitive processes employed by bees when tackling non-natural skills.

3.
J Thorac Dis ; 15(4): 1734-1748, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37197500

RESUMO

Background: Non-small cell lung cancer (NSCLC) progression is mediated by changes in gene expression induced by microRNAs. However, the underlying mechanisms remain to be elucidated. In this study, we investigated the roles of miR-183-5p and its target gene in lung cancer development. Methods: Relative levels of miR-183-5p and lysyl oxidase-like 4 (LOXL4) expression in lung cancer cells or tissues were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence or Western blotting as appropriate. The binding of miR-183-5p to LOXL4 sequences was verified by a dual luciferase reporter assay, and cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) and Edu staining. The cell cycle stage and apoptosis were detected by flow cytometry, and Transwell assays were performed to evaluate cell migration and invasion capabilities. The tumorigenic capability of cancer cells was analyzed using a cancer cell line-based xenograft nude mouse model. Results: miR-183-5p expression was decreased in the lung cancer tissues and cell lines and was negatively correlated with elevated LOXL4 expression. Treatment with miR-183-5p mimics suppressed LOXL4 expression, while treatment with an miR-183-5p inhibitor promoted LOXL4 expression in A549 cells. miR-183-5p was found to directly bind to the 3' UTR of the LOXL4 gene in A549 cells. Overexpression of LOXL4 enhanced cell proliferation, cell cycle progression, migration, and invasion, but repressed their apoptosis, and activated extracellular matrix (ECM) and the epithelial mesenchymal transition (EMT) process in A549 cells, while LOXL4 knockdown produced the opposite effects. Treatment with an miR-183-5P inhibitor promoted the proliferation, cell cycle progression, migration, and invasion of A549 cells but suppressed their apoptosis, and activated the ECM and EMT process, while all these effects were abrogated by LOXL4 knockdown. The tumorigenic capability of A540 cells in nude mice was greatly impaired by treatment with miR-183-5p mimics. Conclusions: miR-183-5p repressed the proliferation, migration, invasion, ECM formation, and EMT processes, and promoted the apoptosis of lung cancer cells by targeting LOXL4 expression.

4.
Int J Med Robot ; 19(3): e2496, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36626270

RESUMO

BACKGROUND: Robotic ophthalmic endoscope holders allow surgeons to execute dual-hand operations in eye surgery. To prevent needle-like endoscopes from invading the retina when moving, surgeons expect visual and real-time information about the relative special relationship between the endoscope and fundus. METHODS: This study develops a real-time fundus reconstruction method. First, using deep learning, the method estimates the distance between the fundus part corresponding to every pixel of the RGB endoscopic image and the endoscope. Then, by combining the estimated distance with the kinematics of a robotic holder, the point cloud representing the present fundus area is generated, and by which the size and position of the eyeball are estimated. RESULTS: This method shows a real-time frequency of 10 Hz, which is robust to eyeball movement. The error of fundus reconstruction is about 0.5 mm, and the error of eyeball estimation is about 1 mm. CONCLUSION: Using this fundus reconstruction method can map the position of the endoscope inside the eyeball when using a robotic endoscope holder in eye surgery. The overall accuracy level meets the ophthalmologists' accuracy requirements of ophthalmologists.


Assuntos
Robótica , Cirurgia Assistida por Computador , Humanos , Endoscópios , Endoscopia/métodos , Robótica/métodos , Cirurgia Assistida por Computador/métodos , Desenho de Equipamento
5.
Cell Discov ; 8(1): 131, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494338

RESUMO

The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed. Nevertheless, the antibody response decreased over time, and the Omicron variant exhibited more pronounced resistance to neutralization than the prototype and Delta strains. Moreover, the intensity of the SARS-CoV-2-specific CD4+ T cell response was also increased in recovered patients who received COVID-19 vaccines. Overall, the repeated antigen exposure provided by inactivated COVID-19 vaccination greatly boosted both the potency and breadth of the humoral and cellular immune responses against SARS-CoV-2, effectively protecting recovered individuals from reinfection by circulating SARS-CoV-2 and its variants.

6.
Int Immunopharmacol ; 113(Pt A): 109374, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36279664

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by progressive airflow limitation and abnormal lung function due to noxious particles and gases. Although many measures are available, COPD remains one of the leading causes of morbidity and mortality worldwide. Therefore, there is an urgent need to discover novel potential therapeutic targets for COPD. Protein kinase C delta (PRKCD) is a member of thePKCfamily and possesses various biological properties. Recently, PRKCD has been reported to play an important role in the pathogenesis of COPD. However, the mechanisms of PRKCD on COPD are not fully elucidated. AIM: In this review, we will discuss the roles and mechanisms of PRKCD involved in the development of COPD. METHODS: We systematically summarized the studies on the research progress of PRKCD in COPD based on MEDLINE/PubMed databases. CONCLUSIONS: PRKCD contributes to the development of COPD by promoting inflammatory response, apoptosis, mitochondrial dysfunction and MUC5AC hypersecretion. These data provide evidence that PRKCD might be a potential therapeutic target for COPD.


Assuntos
Proteína Quinase C-delta , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/patologia , Pulmão/patologia , Apoptose
7.
Front Oncol ; 12: 920926, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719945

RESUMO

Background: Glioblastoma multiforme (GBM), the most prevalent and aggressive of primary malignant central nervous system tumors (grade IV), has a poor clinical prognosis. This study aimed to assess and predict the survival of GBM patients by establishing an m6A-related lncRNA signaling model and to validate its validity, accuracy and applicability. Methods: RNA sequencing data and clinical data of GBM patients were obtained from TCGA data. First, m6A-associated lncRNAs were screened and lncRNAs associated with overall survival in GBM patients were obtained. Subsequently, the signal model was established using LASSO regression analysis, and its accuracy and validity are further verified. Finally, GO enrichment analysis was performed, and the influence of this signature on the immune regulation response and anticancer drug sensitivity of GBM patients was discussed. Results: The signature constructed by four lncRNAs AC005229.3, SOX21-AS1, AL133523.1, and AC004847.1 is obtained. Furthermore, the signature proved to be effective and accurate in predicting and assessing the survival of GBM patients and could function independently of other clinical characteristics (Age, Gender and IDH1 mutation). Finally, Immunosuppression-related factors, including APC co-inhibition, T-cell co-inhibition, CCR and Check-point, were found to be significantly up-regulated in GBM patients in the high-risk group. Some chemotherapeutic drugs (Doxorubicin and Methotrexate) and targeted drugs (AZD8055, BI.2536, GW843682X and Vorinostat) were shown to have higher IC50 values in patients in the high-risk group. Conclusion: We constructed an m6A-associated lncRNA risk model to predict the prognosis of GBM patients and provide new ideas for the treatment of GBM. Further biological experiments can be conducted on this basis to validate the clinical value of the model.

8.
Int Immunopharmacol ; 109: 108929, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35700581

RESUMO

Glioblastoma (GBM) is a heterogeneous and invasive WHO grade IV brain tumor. Patients with GBM have a median overall survival (OS) of only 14 to 17 months when treated with surgical resection and chemoradiation. As one of the most promising anti-tumor immunotherapies, dendritic cell (DC) vaccines have demonstrated good efficacy, safety, and tolerability in many clinical trials. However, to date, no Phase III clinical trial has achieved positive endpoints and truly implement clinical development and transformation. Moreover, the survival benefits of DC vaccines for patients with GBM seem to have a delayed effect; therefore, we urgently require strategies to optimize DC vaccines to advance the time point of its survival benefits. Here, we discuss the latest clinical trial progress of DC vaccines in GBM and summarize the benefits and drawbacks of various vaccine design options, as well as the challenges faced in clinical translation. Moreover, we target future combination therapy strategies for DC vaccines in GBM, which provides a new perspective for comprehensively understanding the effectiveness, limitations, and new directions of the development of DC vaccines.


Assuntos
Neoplasias Encefálicas , Vacinas Anticâncer , Glioblastoma , Vacinas Anticâncer/uso terapêutico , Células Dendríticas , Humanos , Imunoterapia
9.
Front Genet ; 13: 863796, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571056

RESUMO

Background: Programmed death ligand-1 (PD-L1) is a biomarker for assessing the immune microenvironment, prognosis, and response to immune checkpoint inhibitors in the clinical treatment of lung adenocarcinoma (LUAD), but it does not work for all patients. This study aims to discover alternative biomarkers. Methods: Public data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) were used to determine the gene modules relevant to tumor immunity. Protein-protein interaction (PPI) network and GO semantic similarity analyses were applied to identify the module hub genes with functional similarities to PD-L1, and we assessed their correlations with immune infiltration, patient prognosis, and immunotherapy response. Immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining were used to validate the outcome at the protein level. Results: We identified an immune response-related module, and two hub genes (PSTPIP1 and PILRA) were selected as potential biomarkers with functional similarities to PD-L1. High expression levels of PSTPIP1 and PILRA were associated with longer overall survival and rich immune infiltration in LUAD patients, and both were significantly high in patients who responded to anti-PD-L1 treatment. Compared to PD-L1-negative LUAD tissues, the protein levels of PSTPIP1 and PILRA were relatively increased in the PD-L1-positive tissues, and the expression of PSTPIP1 and PILRA positively correlated with the tumor-infiltrating lymphocytes. Conclusion: We identified PSTPIP1 and PILRA as prognostic biomarkers relevant to immune infiltration in LUAD, and both are associated with the response to anti-PD-L1 treatment.

10.
Materials (Basel) ; 15(8)2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35454631

RESUMO

Considering that it is difficult for traditional materials to simultaneously meet the requirements for filling grouting of water-filled karst caves and subsequent shield tunneling, an environmentally friendly and controllable new underwater cementitious filling material (NUC-FM) is developed, with abandoned shield mud as the basic raw material. Through laboratory tests, the mechanical property parameters of NUC-FM are tested, and its micromechanism is analyzed. The research results show that there is excellent synergistic interactions among shield mud, cement, flocculant, fly ash and other raw materials. The NUC-FM grouting filling material with superior performance can be prepared when the water binder ratio is between 0.45 and 0.6 and the water consumption is between 270 and 310 kg/m3. It has the characteristics of non-dispersion underwater and moderate consolidated body strength. The compressive strength of the NUC-FM consolidated body samples under each mix proportion is much higher than 0.5 MPa, which meets the technical strength requirements of a construction site, and the microstructure shows that there is an obvious dense and stable block structure inside. The cost of the NUC-FM prepared with an optimized mix proportion is only 34.57 dollars/m3, which is far lower than the market purchase price of concrete and cement mortar. It can be predicted that the NUC-FM is an ideal filling grouting material for water-filled karst caves in shield tunnels in water-rich karst areas.

11.
Adv Sci (Weinh) ; 9(14): e2104333, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35403837

RESUMO

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Globulinas , Animais , COVID-19/terapia , Globulinas/uso terapêutico , Humanos , Imunização Passiva , Camundongos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Soroterapia para COVID-19
12.
Sensors (Basel) ; 23(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36617027

RESUMO

Most haptic devices generate haptic sensation using mechanical actuators. However, the workload and limited workspace handicap the operator from operating freely. Electrical stimulation is an alternative approach to generate haptic sensations without using mechanical actuators. The light weight of the electrodes adhering to the body brings no limitations to free motion. Because a real haptic sensation consists of feelings from several areas, mounting the electrodes to several different body areas can make the sensations more realistic. However, simultaneously stimulating multiple electrodes may result in "noise" sensations. Moreover, the operators may feel tingling because of unstable stimulus signals when using the dry electrodes to help develop an easily mounted haptic device using electrical stimulation. In this study, we first determine the appropriate stimulation areas and stimulus signals to generate a real touch sensation on the forearm. Then, we propose a circuit design guideline for generating stable electrical stimulus signals using a voltage divider resistor. Finally, based on the aforementioned results, we develop a wearable haptic glove prototype. This haptic glove allows the user to experience the haptic sensations of touching objects with five different degrees of stiffness.


Assuntos
Interface Háptica , Dispositivos Eletrônicos Vestíveis , Tecnologia Háptica , Tato/fisiologia , Estimulação Elétrica
13.
Materials (Basel) ; 14(22)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34832221

RESUMO

To investigate the brittle creep failure process of rock material, the time-dependent properties of brittle rocks under the impact of homogeneity are analyzed by the numerical simulation method, RFPA-Creep (2D). Deformation is more palpable for more homogeneous rock material under the uniaxial creep loading condition. At a low stress level, diffusion creep may occur and transition to dislocation creep with increasing applied stress. The law for increasing creep strain with the homogeneity index under a constant confined condition is similar to the uniaxial case, and dislocation creep tends to happen with increasing confining pressure for the same homogeneity index. The dilatancy index reaches its maximum at a high stress level when rock approaches failure, and the evolution of the dilatancy index with the homogeneity index under the same confining pressure is similar to the uniaxial case and is more marked than that under the unconfined condition. Both uniaxial and triaxial creep failure originate from the ductile damage accumulation inside rock. The dominant shear-type failure is exhibited by uniaxial creep and the conventional compression case presents the splitting-based failure mode. Under confining pressure, the creep failure pattern is prone to shear, which is more notable for the rock with higher homogeneity.

15.
Hum Cell ; 34(5): 1478-1489, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34244990

RESUMO

Crosstalk between cancer cells and macrophages plays a crucial role in the development of cancer. In this study, our data showed that M1 macrophages attenuate, while M2 macrophages and tumor-associated macrophages enhance the EGFR-TKIs resistance in non-small cell lung cancer (NSCLC) cell line H1975. Next, long non-coding RNA SOX2 overlapping transcript (SOX2-OT) is highly expressed in NSCLC cells-derived exosomes. NSCLC cells-derived exosomes promote macrophages M2 polarization and inhibit M1 polarization through transferring SOX2-OT to macrophages. Subsequently, our results indicated that NSCLC cells-induced M2-polarized macrophages enhance the EGFR-TKIs resistance in H1975 cells. Furthermore, our data revealed that NSCLC cells-derived exosomes inhibit the expression of miR-627-3p, while promote Smads expression in THP-1 cells. SOX2-OT acts as miR-627-3p sponge to facilitate Smad2, Smad3 and Smad4 expression. Finally, our results indicated that NSCLC cells promote macrophages M2 polarization and suppress M1 polarization through targeting miR-627-3p/Smads signaling pathway by transferring exosomes to THP-1 cells. In conclusion, our data revealed that NSCLC cells promote macrophages M2 polarization through transferring exosomal SOX2-OT, thus to enhance its own EGFR-TKIs resistance. Mechanismly, NSCLC cells-derived exosomal SOX2-OT promotes macrophages M2 polarization via promoting Smads by sponging miR-627-3p. Our data provide a novel therapeutic target for EGFR-TKIs resistance in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , RNA Longo não Codificante/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Receptores ErbB/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , RNA Longo não Codificante/fisiologia
16.
Nat Commun ; 12(1): 4144, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230476

RESUMO

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Receptores Virais/imunologia , SARS-CoV-2/imunologia , Adulto , Animais , Doadores de Sangue , COVID-19/terapia , Linhagem Celular , China , Chlorocebus aethiops , Convalescença , Feminino , Humanos , Imunidade Humoral/imunologia , Imunização Passiva , Memória Imunológica/imunologia , Estudos Longitudinais , Masculino , Fatores Sexuais , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero , Soroterapia para COVID-19
17.
Int J Med Robot ; 17(1): 1-13, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32996194

RESUMO

BACKGROUND: Holding endoscopes by hand when performing eye surgery reduces the dexterity of the surgeon. METHODS: A robotic endoscope holder called "Eye Explorer" is proposed to hold the endoscope and free the surgeon's hand. RESULTS: This device satisfies the engineering and clinical requirements of eye surgery. The force for manual operation is less than 0.5 N. The observable ranges inside the patient's eye considering horizontal and vertical perspectives are 118° and 97°, and the motion of the holder does not interfere with the surgeon's hand and other surgical devices. The self-weight compensation can prevent the endoscope from falling when extra supporting force is released. When comparing the external force exerted on the eye by the Eye Explorer with that in case of manual operation, a decrease of more than 15% can be observed. Moreover, the consumption time of endoscope view adjustment using the Eye Explorer and manual operation does not significantly differ. CONCLUSION: The Eye Explorer allows dual-hand operation, facilitating a successful endoscopic eye surgery.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Endoscópios , Endoscopia , Desenho de Equipamento , Humanos , Procedimentos Cirúrgicos Oftalmológicos
18.
Proc Natl Acad Sci U S A ; 117(17): 9490-9496, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32253318

RESUMO

Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , RNA Viral , SARS-CoV-2 , Carga Viral , Soroterapia para COVID-19
19.
IUBMB Life ; 71(1): 66-80, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30332528

RESUMO

Endoplasmic reticulum stress (ERS)-induced apoptosis of airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Furthermore, autophagy is closely related to ERS under apoptosis. Here, this study aimed to investigate the role of the reciprocal interaction between autophagy and ERS in the cigarette smoke extract (CSE)-induced apoptosis of human bronchial epithelial (HBE) cells. Cell apoptosis was detected by flow cytometry analysis. Protein expression was examined by Western blot. The mRNA expression was detected using real-time quantitative reverse transcription PCR (qRT-PCR). The results showed that CSE treatment induced apoptosis, autophagy, and expression of ERS-related proteins in HBE cells. Furthermore, autophagy inhibition by 3-MA significantly decreased protein expression of GRP78, p-PERK, and p-eIF2α and increased CHOP, ATF4, and caspase-4, whereas ERS inhibition by 4-PBA led to autophagy suppression. Moreover, the CSE-induced autophagy was diminished by knockdown of GRP78, PERK, or eIF2α but enhanced by knockdown of ATF4 or CHOP; however, the CSE-induced HBE apoptosis was enhanced by knockdown of GRP78, PERK, or eIF2α but was attenuated by knockdown of ATF4 or CHOP. Additionally, both sodium hydrosulfide (NaHS) and melatonin attenuated the CSE-induced apoptosis, enhanced the CSE-induced autophagy, increased GRP78, p-PERK, and p-eIF2α, and decreased CHOP, ATF4, and caspase-4, via SIRT1/ORP150 pathway. Collectively, this study provided evidence about the role of the reciprocal interaction between autophagy and ERS in CSE-induced apoptosis of HBE cells. © 2018 IUBMB Life, 71(1):66-80, 2019.


Assuntos
Brônquios/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Nicotiana/química , Doença Pulmonar Obstrutiva Crônica/genética , Fator 4 Ativador da Transcrição/genética , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Brônquios/patologia , Caspases Iniciadoras/genética , Células Cultivadas , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Humanos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/patologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/genética , Fator de Transcrição CHOP/genética , eIF-2 Quinase/genética
20.
Onco Targets Ther ; 12: 51-56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30588029

RESUMO

BACKGROUND: T790M mutation is well known as the most common mechanism for resistance to the first- and second-generation tyrosine kinase inhibitors (TKIs) for EGFR mutation in non-small-cell lung cancer. Several third-generation EGFR TKIs, such as osimertinib, have been explored and approved for conquering this resistance; however, acquired resistance to osimertinib is evident and the resistance mechanisms remain complex and incompletely explored. CASE PRESENTATION: A non-smoking 58-year-old female patient was initially diagnosed with lung adenocarcinoma harboring EGFR exon 19 deletion and clinically responded to initial gefitinib treatment. The patient progressed on gefitinib after >1 year and a T790M mutation was detected in tissue biopsy by next-generation sequencing (NGS). Osimertinib treatment was administrated for several months and an acquired rare EGFR G724S mutation was detected via NGS blood sample after osimertinib resistance. CONCLUSION: The specific mechanisms of acquiring drug resistance for EGFR-TKIs have not been fully explored. EGFR G724S mutation might be associated with osimertinib resistance but more studies about the mechanism should be explored.

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