Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 544
Filtrar
1.
Onco Targets Ther ; 14: 5309-5314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34848973

RESUMO

PD-1/PD-L1 inhibitors activate immunological response and have become one of the main modalities of cancer treatment. However, they may result in the immune-related adverse events (irAEs). Immune-related cardiotoxicity is relatively rare but may become fatal. We will present a case of a male patient who experienced immunotherapy-related cardiotoxicity one year after received pembrolizumab treatment. The patient had atypical symptom presentation initially, but his condition deteriorated worsened rapidly and he developed severe cardiac disease. The patient experienced significant relief after corticosteroid treatment. Unfortunately, he experienced a reoccurence of the severe adverse event when discontinuing the use of corticosteroids. Ultimately, larger doses and longer courses of corticosteroid treatment cured the heart damage. Fortunately, we observed that lesions were stable and maintained for a long time after cessation of using pembrolizumab for eight months.

2.
Gland Surg ; 10(9): 2695-2704, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733719

RESUMO

Background: This study sought to examine the suppression of the NK4 (which is a fragment that originates from the trypsin digestion of the hepatocyte growth factor) gene as mediated by new nano material polyamidoamine (PAMAM) dendrimers in the growth of breast cancer cells MDA-MB-231 and MCF-7, and the therapeutic effects in a nude mice model of transplanted tumor cell MDA-MB-231. Methods: We built PAMAM-NK4 nano particles and detected the in vitro transfection rate. Nano complexes and blank plasmid PAMAM dendrimers were transfected to MDA-MB-231 and MCF-7 cells, respectively. The western-blotting method, MTT experiment method, and bead method were used to detect the effects of the nano complexes on NK4 protein expression, cell proliferation, and cell apoptosis. The nude mice model of transplanted tumor cell MDA-MB-231 comprised 40 nude female mice who were subject to injections. The mice were randomly divided into four groups, comprising 10 mice per group. The control, blank plasmid and treatment groups were subcutaneously injected with 0.2 mL of 0.9% NaCl (Sodium chloride) solution, 0.2 mL of plasmid solution (including 100 µg PAMAM pcDNA3.1(-) blank plasmid nano complexes) and 0.2 mL of plasmid solution (including PAMAM-NK4 100 µg) beside the tumor inoculation spot, respectively. The positive control group was intraperitoneally injected with 0.2 mL of doxorubicin solution, including 100 µg doxorubicin. Western blotting was used to detect the NK4 protein expression of the transplanted tumor tissues of the various groups. Results: NK4 protein was successfully expressed in MDA-MB-231 and MCF-7 cells transfected with PAMAM-NK4 nano particles, and cell proliferation was suppressed and cell apoptosis was induced. The tumor volumes and masses of the treatment and positive control groups were obviously smaller than those of the control group. The differences were statistically significant (P<0.05). The treatment group had an obviously higher mean value of NK4 protein expression than the control group. The differences were statistically significant (P<0.05). Conclusions: PAMAM-NK4 nano complexes suppress the growth of the breast cancer cells MDA-MB-231 and MCF-7, and had a treatment effect on this tumor nude mice model of breast cancer cells.

3.
IEEE Access ; 9: 28646-28657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34812380

RESUMO

Studying the spatiotemporal differences in coronavirus disease (COVID-19) between social groups such as healthcare workers (HCWs) and patients can aid in formulating epidemic containment policies. Most previous studies of the spatiotemporal characteristics of COVID-19 were conducted in a single group and did not explore the differences between groups. To fill this research gap, this study assessed the spatiotemporal characteristics and differences among patients and HCWs infection in Wuhan, Hubei (excluding Wuhan), and China (excluding Hubei). The temporal difference was greater in Wuhan than in the rest of Hubei, and was greater in Hubei (excluding Wuhan) than in the rest of China. The incidence was high in healthcare workers in the early stages of the epidemic. Therefore, it is important to strengthen the protective measures for healthcare workers in the early stage of the epidemic. The spatial difference was less in Wuhan than in the rest of Hubei, and less in Hubei (excluding Wuhan) than in the rest of China. The spatial distribution of healthcare worker infections can be used to infer the spatial distribution of the epidemic in the early stage and to formulate control measures accordingly.

4.
Nat Commun ; 12(1): 6426, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741039

RESUMO

Many toxic secondary metabolites produced by phytopathogens can subvert host immunity, and some of them are recognized as pathogenicity factors. Fusarium head blight and Verticillium wilt are destructive plant diseases worldwide. Using toxins produced by the causal fungi Fusarium graminearum and Verticillium dahliae as screening agents, here we show that the Arabidopsis P4 ATPases AtALA1 and AtALA7 are responsible for cellular detoxification of mycotoxins. Through AtALA1-/AtALA7-mediated vesicle transport, toxins are sequestered in vacuoles for degradation. Overexpression of AtALA1 and AtALA7 significantly increases the resistance of transgenic plants to F. graminearum and V. dahliae, respectively. Notably, the concentration of deoxynivalenol, a mycotoxin harmful to the health of humans and animals, was decreased in transgenic Arabidopsis siliques and maize seeds. This vesicle-mediated cell detoxification process provides a strategy to increase plant resistance against different toxin-associated diseases and to reduce the mycotoxin contamination in food and feed.

5.
Theor Appl Genet ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34775519

RESUMO

KEY MESSAGE: An autopolyploid-suitable polyBSA-seq strategy was developed for screening candidate genetic markers linked to leaf blight resistance in sugarcane. Due to the complex genome architecture, the quantitative trait loci mappings and linkage marker selections for agronomic traits of autopolyploid crops were mainly limited to the time-consuming and cost intensive construction of genetic maps. To map resistance-linked markers for sugarcane leaf blight (SLB) caused by Stagonospora tainanensis, the autopolyploid-suitable bulk-segregant analysis based on the sequencing (polyBSA-seq) strategy was successfully applied for the first time. Resistant- and susceptible-bulks (R- and S-bulks) constructed from the extreme-phenotypic sugarcane F1 lines of YT93-159 × ROC22 were deep sequenced with 195.0 × for bulks and 74.4 × for parents. Informative single-dose variants (ISDVs) present as one copy in one parent and null in the other parent were detected based on the genome sequence of LA Purple, an autooctoploid Saccharum officinarum, to screen candidate linkage markers (CLMs). The proportion of the number of short reads harboring ISDVs in the total short reads covering a given genomic position was defined as ISDV index and the ISDVs with indices met the threshold set in this study (0.04-0.14) were selected as CLMs. In total, three resistance- and one susceptibility-related CLMs for SLB resistance were identified by the polyBSA-seq. Among them, two markers on chromosome 10 were less than 300 Kb apart. Furthermore, the RNA-seq was used to calculate the expression level of genes within 1.0 Mb from the aforementioned four CLMs, which demonstrated that twelve genes were differentially expressed between resistant and susceptible clones, including a receptor-like kinase and an ethylene-responsive transcription factor. This is the first reported polyBSA-seq in autopolyploid sugarcane, which specifically tailored for the fast selection of the CLMs and causal genes associated with important agronomic traits.

6.
Chin Geogr Sci ; 31(6): 1029-1044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776712

RESUMO

Poverty eradication is a realistic requirement for the addressing of the urban-rural development imbalance. It consolidates the achievements of the poverty alleviation, and accelerates the realization of the United Nations Sustainable Development Goals. In research that deals with poverty, qualitative analysis is often used to study the connection between a single influencing factor and poverty reduction, and to solve regional poverty through government measures. However, these studies usually ignore the multidimensional nature of poverty, and the fact that poverty alleviation also needs to be approached from multiple perspectives. By constructing a theoretical framework of poverty alleviation performance from the perspective of sustainable development, this study selects contiguous poverty-stricken areas in the Hunan Province, China as the empirical study area, constructs an evaluation index system from the three dimensions of economic development, infrastructure and people's livelihood security, and selects influencing factors from three aspects of 'population', 'land' and 'industry'. The spatial differentiation characteristics and influencing factors of poverty alleviation performance in poverty-stricken areas were studied by using the methods of entropy weight method and geodetector. The results show: firstly, in the concentrated and contiguous poverty-stricken areas of the Hunan Province, the performance of poverty alleviation in the economic development makes little difference, showing a 'high-medium-low' cross-distribution pattern. The poverty alleviation performance of the infrastructure presents a distribution pattern of 'low in the middle and high on both sides. The poverty alleviation performance of people's livelihood security has significant spatial differentiation characteristics, which all present a reunion distribution. The overall poverty alleviation performance varies greatly, showing a funnel-shaped distribution in space. Secondly, the spatial differentiation of poverty alleviation performance in the concentrated and contiguous poverty-stricken areas of the Hunan Province is the result of the combined effects of multiple factors. 'Population' is the dominant factor affecting the performance of poverty alleviation, 'land' is the basic factor that causes the spatial differentiation of poverty alleviation performance, and 'industry' is the key factor for the improvement of the poverty alleviation ability.

7.
Cancer Sci ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839558

RESUMO

Small ubiquitin-like modifier (SUMO)ylation is one of the posttranslational modifications and is implicated in many tumor types. Modulation of SUMOylation can affect tumor progression, but the underlying mechanisms remain unclear. Here, we show that, for the first time, in uveal melanoma (UM), the most common intraocular malignancy in adults, global SUMOylation is upregulated and participates in tumor growth. Inhibition of SUMOylation in UM is sufficient to reduce tumor growth both in vitro and in vivo. Furthermore, we found that retinoblastoma protein (Rb) is a target protein and a critical downstream effector of the upregulated SUMOylation activity in UM. Increased SUMOylation of the Rb protein leads to its hyperphosphorylation and inactivation in UM cells, promoting UM cell proliferation. In summary, our results provide novel insight into the mechanism underlying SUMOylation-regulated tumor growth in UM.

8.
Acta Pharmacol Sin ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795412

RESUMO

Neurovascular unit (NVU) is organized multi-cellular and multi-component networks that are essential for brain health and brain homeostasis maintaining. Neurovascular unit dysfunction is the central pathogenesis process of ischemic stroke. Thus integrated protection of NVU holds great therapeutic potential for ischemic stroke. Catalpol, classified into the iridoid monosaccharide glycoside, is the main active ingredient of the radix from traditional Chinese medicine, Rehmannia glutinosa Libosch, that exhibits protective effects in several brain-related diseases. In the present study, we investigated whether catalpol exerted protective effects for NVU in ischemic stroke and the underlying mechanisms. MCAO rats were administered catalpol (2.5, 5.0, 10.0 mg·kg-1·d-1, i.v.) for 14 days. We showed that catalpol treatment dose-dependently reduced the infarction volume and significantly attenuated neurological deficits score in MCAO rats. Furthermore, catalpol treatment significantly ameliorated impaired NVU in ischemic region by protecting vessel-neuron-astrocyte structures and morphology, and promoting angiogenesis and neurogenesis to replenish lost vessels and neurons. Moreover, catalpol treatment significantly increased the expression of vascular endothelial growth factor (VEGF) through up-regulating PI3K/AKT signaling, followed by increasing FAK and Paxillin and activating PI3K/AKT and MEK1/2/ERK1/2 pathways. The protective mechanisms of catalpol were confirmed in an in vitro three-dimensional NVU model subjected to oxygen-glucose deprivation. In conclusion, catalpol protects NVU in ischemic region via activation of PI3K/AKT signaling and increased VEGF production; VEGF further enhances PI3K/AKT and MEK1/2/ERK1/2 signaling, which may trigger a partly feed-forward loop to protect NVU from ischemic stroke.

9.
Arch Public Health ; 79(1): 172, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620222

RESUMO

BACKGROUND: In collaboration with building developers, the Housing for Health team is contributing to the design of community-based congregate living facilities to support healthy living in older adults. There may also be opportunities to improve the surrounding neighbourhoods by collaborating with the municipalities where the developments are located. We will evaluate whether one or more of these comprehensive interventions lead to changes in the perceived, microscale, and macroscale neighbourhood-built environment (BE) and amenities, and impacts on the physical activity (PA), healthy eating, and social connections of residents. In parallel, we will gather qualitative data to provide a more in-depth understanding of how the BE may facilitate or hinder resident's healthy living outcomes. METHODS: This project employs a quasi-experimental pre-post design with at least one or more intervention and control sites. The quantitative BE evaluation will include pre- and post-intervention assessments of neighbourhood macroscale (e.g., layout of communities) and microscale (e.g., street details and characteristics) changes using Geographical Information Systems (GIS) and Microscale Audit Pedestrian Streetscapes (MAPS) audits, respectively. The quantitative resident evaluation will include self-report (i.e., surveys) and objective assessments (i.e., accelerometers, Global Positioning System [GPS]) of residents at baseline (3-6-months pre-move-in) and follow-up (3-6-months and 9-12-months post-move-in if possible). The qualitative resident-environment component will involve in-depth semi-structured interviews post-intervention with building residents, family members, and stakeholders involved in the design/development and/or operation of the intervention site(s). Participant observations will be completed in the building and neighbourhood environments of the intervention site(s). DISCUSSION: Findings will provide evidence on whether and how comprehensive changes to the BE and amenities of at least one congregate living facility and the surrounding neighbourhood can impact PA, healthy eating, and social connections of older adults. Successful intervention elements will be scaled up in future work. We will disseminate findings to a broad audience including the scientific community via peer-reviewed publications, conference presentations, and discussion panels; and the private, public, and not-for-profit sectors via reports, public presentations, and/or communications via our partners and their networks. TRIAL REGISTRATION: Protocol ID: 1819-HQ-000051. ClinicalTrials.gov ID: NCT05031273. Registered 29 June 2021 with ClinicalTrials.gov.

10.
BMC Health Serv Res ; 21(1): 1043, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600508

RESUMO

BACKGROUND: Demand for eye care has increased in recent decades in China due to rapid socioeconomic development and demographic shift. Knowledge of output and productivity of ophthalmic services would allow policymakers to optimize resource allocation, and is therefore essential. This study sought to map the landscape of ophthalmic services available in Shanghai, China. METHODS: In 2018, a government-led survey was conducted of all 86 tertiary/secondary hospitals and five major private hospitals providing eye care in Shanghai in the form of electronic questionnaire, which encompassed ophthalmic services (outpatient and emergency room [ER] visit, inpatient admissions, and surgical volume) and service productivity in terms of annual outpatient and ER visits per doctor, inpatient admissions per bed, and surgical volume per doctor. Comparisons were made among different levels of hospitals with categorical variables tested by Chi-square analysis. RESULTS: The response rate was 85.7%. The Eye and Ear, Nose, and Throat (EENT) Hospital was the largest tertiary specialty hospital, and alone contributed to the highest 21.0% of annual ophthalmic outpatient and ER visits (visits per doctor: 5460), compared with other 26 tertiary hospitals, 46 secondary hospitals and five private hospitals (visits per doctor: 3683, 4651 and 1876). The annual inpatient admission was 20,103, 56,992, 14,090, and 52,047 for the EENT Hospital, all the other tertiary hospitals, secondary hospitals and five private hospitals, respectively. Turnover rates were highest for the EENT Hospital and private hospitals. The average surgical volume at the EENT Hospital was 72,666, exceeding that of private (15,874.8) and other tertiary hospitals (3366.7). The EENT Hospital and private hospitals performed 16,982 (14.2%) and 55,538 (46.6%) of all cataract surgeries. Proportions of both complicated cataractous cases and complicated cataract surgeries at the EENT Hospital was the highest, followed by other tertiary and secondary/private hospitals (P < 0.0001). CONCLUSIONS: In Shanghai, public providers dominate ophthalmic services especially for complicated cases, with almost one fifth of services provided by the EENT Hospital alone, while private sectors, though not large in number, still effectively help meet large proportions of eye care demand. Optimization of hierarchical medical system is warranted to improve the efficiency and standardization of ophthalmic services.


Assuntos
Catarata , China/epidemiologia , Hospitais Privados , Humanos , Governo Local , Inquéritos e Questionários
11.
J Health Psychol ; : 13591053211044824, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34658282

RESUMO

The study aimed to investigate the level of life satisfaction (LS) among Chinese female workers after resuming work during the COVID-19 epidemic, and to further explore the potential mediating and moderating roles in the association between family stress and LS. Self-reported questionnaires were completed by 10,175 participants. Results showed that the level of LS decreased. The family stress had a negative effect on LS, and the effect was mediated by anxiety symptoms. Additionally, age moderated the direct and indirect effects within this relationship. Interventions aiming to improve LS should consider these aspects and younger workers should be given special attention.

12.
Natl Sci Rev ; 8(4): nwaa128, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34691609

RESUMO

Fast and catalyst-free cross-linking strategy is of great significance for construction of covalently cross-linked hydrogels. Here, we report the condensation reaction between o-phthalaldehyde (OPA) and N-nucleophiles (primary amine, hydrazide and aminooxy) for hydrogel formation for the first time. When four-arm poly(ethylene glycol) (4aPEG) capped with OPA was mixed with various N-nucleophile-terminated 4aPEG as building blocks, hydrogels were formed with superfast gelation rate, higher mechanical strength and markedly lower critical gelation concentrations, compared to benzaldehyde-based counterparts. Small molecule model reactions indicate the key to these cross-links is the fast formation of heterocycle phthalimidine product or isoindole (bis)hemiaminal intermediates, depending on the N-nucleophiles. The second-order rate constant for the formation of phthalimidine linkage (4.3 M-1 s-1) is over 3000 times and 200 times higher than those for acylhydrazone and oxime formation from benzaldehyde, respectively, and comparable to many cycloaddition click reactions. Based on the versatile OPA chemistry, various hydrogels can be readily prepared from naturally derived polysaccharides, proteins or synthetic polymers without complicated chemical modification. Moreover, biofunctionality is facilely imparted to the hydrogels by introducing amine-bearing peptides via the reaction between OPA and amino group.

13.
Biomed Chromatogr ; : e5257, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611921

RESUMO

Hui Medicine ZhaLi NuSi Prescription (ZLNS) is described in "Hui Hui Prescription," and it has been used to treat cerebral infarction in Hui Region, China. In this study, a rapid and reliable ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) method was established and applied to simultaneously determine geniposidic acid, oxypaeoniflorin, hydroxysafflor yellow A, caffeic acid, magnoflorine, paeoniflorin, ferulic acid, ß-ecdysterone, icariin, rhein, and baohuoside I in rat plasma. The pharmacokinetic parameters of these components and the influence of essential oils (EOs) on them were investigated in normal rats. The results showed that the pharmacokinetic parameters (AUC0 - t , AUC0 - ∞ , t1/2 , tmax , cmax ) of the aforementioned compounds were significantly changed after co-administering with ZLNS EO. The AUC values of oxypaeoniflorin, paeoniflorin, ferulic acid, and baohuoside I with EOs were decreased significantly. This is the first report for the comparative pharmacokinetic study of ZLNS bioactive components in normal rats, which may provide the basis for drug interaction study in vivo and insight into their clinical applications.

14.
Micromachines (Basel) ; 12(10)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34683211

RESUMO

Direct writing is a rapidly developing manufacturing technology that is convenient, adaptable and automated. It has been used in energetic composites to manufacture complex structures, improve product safety, and reduce waste. This work is aimed at probing the formability properties and combustion performances of aluminum/ammonium perchlorate with a high solid content for direct writing fabrication. Four kinds of samples with different solid content were successfully printed by adjusting printing parameters and inks formulas with excellent rheological behavior and combustion properties. A high solid content of 91% was manufactured and facile processed into complex structures. Micromorphology, rheology, density, burning rate, heat of combustion and combustion performance were evaluated to characterized four kinds of samples. As the solid content increases, the density, burning rate and heat of combustion are greatly enhanced. Based on 3D direct writing technology, complex energetic 3D structures with 91% solid content are shaped easier and more flexibly than in traditional manufacturing process, which provides a novel way for the manufacture of complicated structures of energetic components.

15.
Front Med (Lausanne) ; 8: 693959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671612

RESUMO

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and unfavorable prognosis. Ferroptosis is a form of regulated cell death with an iron-dependent way that is involved in the development of various diseases. Whereas the prognostic value of ferroptosis-related genes (FRGs) in IPF remains uncertain and needs to be further elucidated. Methods: The FerrDb database and the previous studies were screened to explore the FRGs. The data of patients with IPF were obtained from the GSE70866 dataset. Wilcoxon's test and univariate Cox regression analysis were applied to identify the FRGs that are differentially expressed between normal and patients with IPF and associated with prognosis. Next, a multigene signature was constructed by the least absolute shrinkage and selection operator (LASSO)-penalized Cox model in the training cohort and evaluated by using calibration and receiver operating characteristic (ROC) curves. Then, 30% of the dataset samples were randomly selected for internal validation. Finally, the potential function and pathways that might be affected by the risk score-related differently expressed genes (DEGs) were further explored. Results: A total of 183 FRGs were identified by the FerrDb database and the previous studies, and 19 of them were differentially expressed in bronchoalveolar lavage fluid (BALF) between IPF and healthy controls and associated with prognosis (p < 0.05). There were five FRGs (aconitase 1 [ACO1], neuroblastoma RAS viral (v-ras) oncogene homolog [NRAS], Ectonucleotide pyrophosphatase/phosphodiesterase 2 [ENPP2], Mucin 1 [MUC1], and ZFP36 ring finger protein [ZFP36]) identified as risk signatures and stratified patients with IPF into the two risk groups. The overall survival rate in patients with high risk was significantly lower than that in patients with low risk (p < 0.001). The calibration and ROC curve analysis confirmed the predictive capacity of this signature, and the results were further verified in the validation group. Risk score-related DEGs were found enriched in ECM-receptor interaction and focal adhesion pathways. Conclusion: The five FRGs in BALF can be used for prognostic prediction in IPF, which may contribute to improving the management strategies of IPF.

16.
Front Med (Lausanne) ; 8: 715519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671616

RESUMO

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests. Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient's clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged. Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients.

17.
Int J Biol Macromol ; 193(Pt A): 510-518, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34710477

RESUMO

In this study, we investigated the effect of three-dimensional of naringin/gelatin microspheres/nano-hydroxyapatite/silk fibroin (NG/GMs/nHA/SF) scaffolds on repair of a critical-size bone defect of lumbar 6 in osteoporotic rats. In this work, a cell-free scaffold for bone-tissue engineering based on a silk fibroin (SF)/nano-hydroxyapatite (nHA) scaffold was developed. The scaffold was fabricated by lyophilization. Naringin (NG) was loaded into gelatin microspheres (GMs), which were encapsulated in the nHA/SF scaffolds. The materials were characterized using x ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. Moreover, the biomechanics, degradation, and drug-release profile of the scaffold were also evaluated. In vitro, the effect of the scaffold on the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) was evaluated. In vivo, at 3 months after ovariectomy, a critical-size lumbar defect was indued in the rats to evaluate scaffold therapeutic potential. A 3-mm defect in L6 developed in 60 SD rats, which were randomly divided into SF scaffold, nHA/SF scaffold, NG/nHA/SF scaffold, NG/GMs/nHA/SF scaffold, and blank groups (n = 12 each). At 4, 8, 12, and 16 weeks postoperatively, osteogenesis was evaluated by X-ray, micro-computed tomography, hematoxylin-eosin staining, and fast green staining, and by analysis of BMP-2, Runx2, and Ocn protein levels at 16 weeks. In our results, NG/GM/nHA/SF scaffolds exhibited good biocompatibility, biomechanical strength, and promoted BMSC adhesion, proliferation, and calcium nodule formation in vitro. Moreover, NG/GMs/nHA/SF scaffolds showed greater osteogenic differentiation potential than the other scaffolds in vitro. In vivo, gradual new bone formation was observed, and bone defects recovered by 16 weeks in the experimental group. In the blank group, limited bone formation was observed, and the bone defect was obvious. In conclusion, NG/GMs/nHA/SF scaffolds promoted repair of a lumbar 6 defect in osteoporotic rats. Therefore, the NG/GMs/nHA/SF biocomposite scaffold has potential as a bone-defect-filling biomaterial for bone regeneration.

18.
Saudi J Biol Sci ; 28(9): 4908-4915, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34466065

RESUMO

Background: Osteosarcoma (OS) is the most common malignant bone cancer with more metastasis and increased occurrence in children and teen-agers and being responsible for more number of morbidity and mortality worldwide. Objective: The current exploration was planned study the in vitro anticancer actions of dieckol against human OS MG-63 cells via PI3K/AKT/mTOR signaling inhibition. Methodology: The cytotoxicity of dieckol was scrutinized by MTT assay. Effects of dieckol on the ROS accumulation, apoptotic cell death, and MMP level in the MG-63 cells were studied by respective fluorescence staining assays. The levels of proliferative, inflammatory, and apoptotic markers in the dieckol treated MG-63 cells were scrutinized by marker specific kits. The expressions of PI3K, AKT, and mTOR was assayed by RT-PCR. Results: The MTT assay revealed that the dieckol dose dependently prevented MG-63 cells viability and the IC50 was found at 15 µM. Dieckol treatment effectively reduced the MMP level and improved the ROS generation and apoptosis in MG-63 cells. Dieckol also regulated the proliferative (cyclin D1), inflammatory (COX-2, IL-6, TNF-α, and NF-κB), and apoptotic (caspase-3, Bax, Bcl-2) markers in the MG-63 cells. The PI3K/AKT/mTOR signaling in the MG-63 cells were effectively inhibited by the dieckol treatment. Conclusion: In conclusion, our findings from this study recommends that the dieckol could be a talented anticancer candidate for the OS management in the future.

19.
Nat Med ; 27(10): 1735-1743, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34526699

RESUMO

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site's data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare.


Assuntos
COVID-19/fisiopatologia , Aprendizado de Máquina , Avaliação de Resultados em Cuidados de Saúde , COVID-19/terapia , COVID-19/virologia , Registros Eletrônicos de Saúde , Humanos , Prognóstico , SARS-CoV-2/isolamento & purificação
20.
Artigo em Inglês | MEDLINE | ID: mdl-34589132

RESUMO

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis (P < 0.05), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included (P < 0.05), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3-9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...