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1.
Dis Markers ; 2022: 9367873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035614

RESUMO

Background: Acute kidney injury (AKI) is an important complication in critically ill patients, especially in sepsis and septic shock patients. Early prediction of AKI in septic shock can provide clinicians with sufficient information for timely intervention so that improve the patients' survival rate and quality of life. The aim of this study was to establish a nomogram that predicts the risk of AKI in patients with septic shock in the intensive care unit (ICU). Methods: The data were collected from the Medical Information Mart for Intensive Care III (MIMIC-III) database between 2001 and 2012. The primary outcome was AKI in the 48 h following ICU admission. Univariate and multivariate logistic regression analyses were used to screen the independent risk factors of AKI. The performance of the nomogram was evaluated according to the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis, and clinical impact curve. Results: A total of 2415 patients with septic shock were included in this study. In the training and validation cohort, 1091 (64.48%) of 1690 patients and 475 (65.52%) of 725 patients developed AKI, respectively. The predictive factors for nomogram construction were gender, ethnicity, congestive heart failure, diabetes, obesity, Simplified Acute Physiology Score II (SAPS II), angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs), bilirubin, creatinine, blood urea nitrogen (BUN), and mechanical ventilation. The model had a good discrimination with the area under the ROC curve of 0.756 and 0.760 in the training and validation cohorts, respectively. The calibration curve for probability of AKI in septic shock showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that the nomogram conferred high clinical net benefit. Conclusion: The proposed nomogram can quickly and effectively predict the risk of AKI at an early stage in patients with septic shock in ICU, which can provide information for timely and efficient intervention in patients with septic shock in the ICU setting.

2.
J Dev Behav Pediatr ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013066

RESUMO

OBJECTIVE: The aim of this study was to analyze the secular trends of conduct disorder (CD) incidence in China from 1990 to 2019 under the joinpoint analysis and the age-period-cohort framework. METHODS: The sex-specific incidence rates of CD from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database according to the age group. The joinpoint regression and the age-period-cohort model were conducted using the average annual percent changes and relative risks as size effects, respectively. RESULTS: From 1990 to 2019, age-standardized rates (ASRs) of CD incidence showed an overall increasing trend in both sexes, and this variation trend was observed in almost all age groups. The annual sex-specific ASRs were lower in China than those worldwide but were rapidly growing. Age effects were the most significant risk factor for CD, with the highest risk in adolescents aged 10 to 14 years, followed by children aged 5 to 9 years, but a relatively lower risk in adolescents aged 15 to 19 years than in other age groups. However, period and cohort effects were not statistically significant. CONCLUSION: CD incidence rates in China have been increasing in both sexes from 1990 to 2019. Further studies are necessary to explain the etiology of these increases and promote the early identification of individuals at risk for developing CD.

3.
Stem Cell Res Ther ; 13(1): 9, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012650

RESUMO

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory coronavirus 2 is currently spreading throughout the world with a high rate of infection and mortality and poses a huge threat to global public health. COVID-19 primarily manifests as hypoxic respiratory failure and acute respiratory distress syndrome, which can lead to multiple organ failure. Despite advances in the supportive care approaches, there is still a lack of clinically effective therapies, and there is an urgent need to develop novel strategies to fight this disease. Currently, stem cell therapy and stem cell-derived organoid models have received extensive attention as a new treatment and research method for COVID-19. Here, we discuss how stem cells play a role in the battle against COVID-19 and present a systematic review and prospective of the study on stem cell treatment and organoid models of COVID-19, which provides a reference for the effective control of the COVID-19 pandemic worldwide.


Assuntos
COVID-19 , Pandemias , Humanos , Estudos Prospectivos , SARS-CoV-2 , Células-Tronco
4.
J Pain Res ; 15: 137-146, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35058715

RESUMO

Background: Migraine is a common disorder of the nervous system in China, imposing heavy burdens on individual and societies. Optimal healthcare planning requires understanding the magnitude and changing the trend of migraine incidence in China. However, the secular trend of migraine incidence in China remains unclear. Methods: Data were collected from the Global Burden of Disease Study 2019 in China from 1990 to 2019 to investigate changes in the incidence rate of migraine. The average annual percent change and the relative risk were calculated using the joinpoint regression model and the age-period-cohort model, respectively. Results: From 1990 to 2019, the age-standardized incidence rates of migraine in China increased by 0.26% (95% CI: 0.22 to 0.31) and 0.23% (95% CI: 0.19 to 0.28) per year in males and females, respectively. Age effects exerted the most significant impact on migraine incidence. Period effects showed a slightly decreasing trend in the incidence of migraine. In terms of cohort effects, people born after the 1960s presented a higher risk of migraine as compared with the total cohort, with the incidence risk of migraine increasing with birth cohorts. Conclusion: Migraine incidence shows an overall increasing trend in China, with a significant gender difference. A comprehensive understanding of the risk characteristics and disease pattern of migraine could allow the early detection of persons with a high risk of developing migraine and promote the development of timely intervention measures to relieve this burden effectively.

5.
Eur J Med Chem ; 228: 114037, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34883290

RESUMO

Off-target toxicity is one of the main challenges faced by anticancer chemotherapeutics. For tumor targeted and precision chemotherapy, we take the advantages of the ligand directed tumor active targeting of small molecule drug conjugates (SMDCs) and the passive tumor targeting of nanoparticles via the enhanced penetration and retention (EPR) effects, put forward a branched small molecule drug conjugate (BSMDC) nanomedicine design concept. In a proof of concept, we used pentaerythritol as the branched moiety, galactosamine (GalN) as the hepatocellular carcinoma (HCC) directing ligands, PTX as a payload, and a stearoyl moiety as the amphiphilic property adjusting group, designed and synthesized BSMDC 1 and prepared its NPs. In cellular level, the BSMDC 1 NPs targeted asialoglycoprotein receptor (ASGPR)-overexpressing HepG2 cells, were effectively taken up in the cells and released in tumor microenvironments, inhibited the HepG2 cell proliferation, arrested HepG2 cell in G2/M phase and induced tumor cell apoptosis. In HepG2 xenograft nude mice, the BSMDC 1 NPs were high specific to target the tumor and demonstrated a higher antitumor efficiency than BSMDC 1, having no apparent influences on mice body weights and major organs, supporting our BSMDC nanomedicine design concept. Therefore, this new strategy may find applications for cancer targeted and precision chemotherapy.

6.
Front Med (Lausanne) ; 8: 770836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926512

RESUMO

Background: Esophageal variceal (EV) hemorrhage is a life-threatening consequence of portal hypertension in cirrhotic patients. Screening upper endoscopy and endoscopic variceal ligation to identify and treat EVs have contraindications, complications, and high costs. We sought to identify non-invasive tests (NITs) as alternatives to endoscopic EV screening. Methods: In this case-control study, we retrospectively analyzed 286 cirrhotic patients treated for EVs at the Second People's Hospital of Fuyang City, China from January to December 2019. We applied ROC curve analysis to assess the accuracy of various NITs in predicting EV hemorrhage. Results: There were significant differences between the hemorrhage and non-hemorrhage groups in median serum albumin (ALB) (p < 0.001), median bilirubin (TBIL) (p < 0.046), prothrombin (PT) time (p < 0.001), Golgi protein 73 (GP73; p = 0.012) and Child-Pugh (C-P) scores (p < 0.001). For ALB (cutoff <33.2g/L), PT time (cutoff > 14.2 seconds), GP73 (cutoff > 126.4 ng/ml), and C-P scores, the areas under the ROC curves (AUCs) were 73.4% (95% CI: 67.5-79.2), 68.6% (95% CI: 62.4-74.8), 62.2% (95% CI: 52.8-71.5) and 69.8% (95%CI: 63.8-75.8), respectively, with corresponding sensitives of 71.5, 59.8, 69.8, and 92.2% and specificities of 65.6%, 70.1%, 56.5%, and 38.6%. When ALB was combined with GP73, the AUC was 74.3% (95% CI: 66.1-82.5) with a sensitivity of 65.1% and specificity of 76.5%. When ALB, PT, and C-P scores were combined, the AUC was 76.5% (95% CI: 70.9-82.1) with a sensitivity of 79.5% and specificity of 64.3%. When ALB, PT, GP73, and C-P scores were combined, the AUC was 75.2% (95% CI: 67.3-83.1) with a sensitivity of 54.0% and specificity of 86.9%. Conclusion: ALB, TBIL, GP73, and C-P scores, may be used to predict EV hemorrhage in cirrhotic patients. The combination of multiple NITs is better than a single index and can increase diagnostic performance.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34948680

RESUMO

Efficient risk communication is aimed at improving the supply of risk information to meet the information needs of individuals, thus reducing their vulnerability when facing the risk of emergency. There is little information available in the literature regarding information preference from an individual's need perspective, and there is a lack of differentiation in evaluation between information need and supply. Under the guidance of the crisis stage analysis theory, using multiple response analysis and weighted analysis methods, this study explores earthquake disaster information content and communication channel preferences, and develops an information deviation index (IDI) to evaluate the efficiency of risk communication before, during, and after an earthquake. A questionnaire-based survey of 918 valid respondents in Songyuan, China, which had been hit by a small earthquake swarm, was conducted to provide practical evidence for this study. The results indicated the following. Firstly, the information needs of individuals are highly differentiated in the different stages of an earthquake. From pre-disaster to post-disaster, individuals show a shift in information need from "preparedness and response knowledge" to "disaster information", then to "disaster information and disaster relief information" in parallel, to "reconstruction and reflection information". Based on the above analysis, a composition of the main earthquake disaster information is proposed for different stages. Secondly, by measuring the values of the IDI, we found that most individuals' information needs were met for the earthquake. Thirdly, the TV and the internet were the two preferred commutation channels for acquiring disaster information from among all the effective channels in all the stages.


Assuntos
Planejamento em Desastres , Desastres , Terremotos , China , Humanos , Inquéritos e Questionários
8.
Cancer Sci ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727389

RESUMO

Hepatocellular carcinoma (HCC) is one of the commonest lethal malignancies worldwide, and often diagnosed at an advanced stage, without any curative therapy. Immune checkpoint blockers targeting the programmed death receptor 1 (PD-1) have shown impressive antitumor activity in patients with advanced-stage HCC, while the response rate is only 30%. Inducible PD-L1 overexpression may result in a lack of response to cancer immunotherapy, which is attributed to a mechanism of adaptive immune resistance. Our study investigated that the overexpression of PD-L1 promoted the invasion and migration of liver cancer cells in vitro, and the induced overexpression of PD-L1 in the tumor microenvironment could weaken the effects of anti-PD-1 immunotherapy in a BALB/c mouse model of liver cancer. CPI-203, a small-molecule bromodomain-containing protein 4 (BRD4) inhibitor, which can potently inhibit PD-L1 expression in vitro and in vivo, combined with PD-1 antibody improved the response to immunotherapy in a liver cancer model. Cell transfection and chromatin immunoprecipitation assay manifested that BRD4 plays a key role in PD-L1 expression; CPI-203 can inhibit PD-L1 expression by inhibiting the BRD4 occupation of the PD-L1 promoter region. This study indicates a potential clinical immunotherapy method to reduce the incidence of clinical resistance to immunotherapy in patients with HCC.

9.
Chem Commun (Camb) ; 57(95): 12852-12855, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34788776

RESUMO

Hypoxia is a hallmark of many solid tumors, and it causes the overexpression of a variety of proteins including the epidermal growth factor receptor (EGFR). Many antitumor prodrugs have been designed to target hypoxia. Here we report the identification of a kind of hypoxia-activated proteolysis targeting chimera (ha-PROTAC) by introducing the hypoxia-activated leaving group (1-methyl-2-nitro-1H-imidazol-5-yl)methyl or 4-nitrobenzyl into the structure of an EGFRDel19-based PROTAC. Among the obtained molecules, ha-PROTAC 13 exhibits a more potent degradation activity for EGFRDel19 in hypoxia than in normoxia in HCC4006 cells. This is the first example of identifying a PROTAC to selectively act on tumors utilizing the characteristic of tumor hypoxia and provides a new approach for PROTAC development.

10.
Antibodies (Basel) ; 10(4)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34842612

RESUMO

Monoclonal antibodies (mAbs) are one of the cornerstones of modern medicine, across an increasing range of therapeutic areas. All therapeutic mAbs are glycoproteins, i.e., their polypeptide chain is decorated with glycans, oligosaccharides of extraordinary structural diversity. The presence, absence, and composition of these glycans can have a profound effect on the pharmacodynamic and pharmacokinetic profile of individual mAbs. Approaches for the glycoengineering of therapeutic mAbs-the manipulation and optimisation of mAb glycan structures-are therefore of great interest from a technological, therapeutic, and regulatory perspective. In this review, we provide a brief introduction to the effects of glycosylation on the biological and pharmacological functions of the five classes of immunoglobulins (IgG, IgE, IgA, IgM and IgD) that form the backbone of all current clinical and experimental mAbs, including an overview of common mAb expression systems. We review selected examples for the use of small molecule inhibitors of glycan biosynthesis for mAb glycoengineering, we discuss the potential advantages and challenges of this approach, and we outline potential future applications. The main aim of the review is to showcase the expanding chemical toolbox that is becoming available for mAb glycoengineering to the biology and biotechnology community.

11.
NeuroRehabilitation ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34776425

RESUMO

BACKGROUND: Graded motor imagery (GMI) therapy is a neural rehabilitative physiotherapy that has been shown to alleviate the severity of complex regional pain syndrome, phantom limb pain and disability. OBJECTIVE: To identify neural networks associated with the use of graded mirror therapy (MT) while imagining hand movements. METHODS: We made a block-design functional magnetic resonance imaging study of MT included three experiments: (1) immobile unimanual MT (IU-MT), in which the right hand flexed and made a fist, which then remained immobile; (2) mobilization unimanual MT (MU-MT), in which the right hand performed a flexion-extension movement; and (3) mobilization bimanual MT (MB-MT), in which both hands performed a flexion-extension movement. When subjects started their hand movements, they gazed at the mirror and imagined the same movement behind the mirror. RESULTS: We discovered that the sensorimotor area of the left brain, superior temporal gyrus/middle temporal gyrus (STG/MTG) of the right brain and visual areas were activated by IU-MT. In MU-MT, only the STG/MTG was activated. Furthermore, MB-UT mostly activated the sensorimotor area and STG of the right brain. However, there were no brain areas activated by MU-MT compared with IU-MT or MB-MT; however, MB-MT activated more motor areas than IU-MT. Importantly, we determined that the level of mirror imagery was negatively correlated with signals in the mirror neuron system (MNS) and positively related with the signals in the sensorimotor areas. CONCLUSIONS: We suggest that graded MT might be a sequential therapeutic program that can enhance the sensorimotor cortex. The MNS might have an initiating role in graded MT. Thus, there is the possibility that graded MT is a helpful treatment strategy for the rehabilitation of dysfunctional patients.

12.
Anim Dis ; 1(1): 24, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778885

RESUMO

Coronaviruses (CoVs) are a group of related enveloped RNA viruses that have severe consequences in a wide variety of animals by causing respiratory, enteric or systemic diseases. Porcine epidemic diarrhea virus (PEDV) is an economically important CoV distributed worldwide that causes diarrhea in pigs. nsp14 is a nonstructural protein of PEDV that is involved in regulation of innate immunity and viral replication. However, the function and mechanism by which nsp14 modulates and manipulates host immune responses remain largely unknown. Here, we report that PEDV nsp14 is an NF-κB pathway antagonist. Overexpression PEDV nsp14 protein remarkably decreases SeV-, poly (I:C)- and TNF-α-induced NF-κB activation. Meanwhile, expression of proinflammatory cytokines is suppressed by nsp14. nsp14 inhibits the phosphorylation of IKKs by interacting with IKKs and p65. Furthermore, nsp14 suppresses TNF-α-induced phosphorylation and nuclear import of p65. Overexpression nsp14 considerably increases PEDV replication. These results suggest a novel mechanism employed by PEDV to suppress the host antiviral response, providing insights that can guide the development of antivirals against CoVs.

13.
J Nat Prod ; 84(11): 2990-3000, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34781681

RESUMO

Six new 16-residue peptaibols, acremopeptaibols A-F (1-6), along with five known compounds, were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 grown in the presence of the autoclaved bacterium Pseudomonas aeruginosa on solid rice medium. The peptaibol sequences were established based on comprehensive analysis of 1D and 2D NMR spectroscopic data in conjunction with HRESIMS/MS experiments. The configurations of the amino acid residues were determined by advanced Marfey's analysis. Compounds 1-6 feature the lack of the highly conserved Thr6 and Hyp10 residues in comparison with other members of the SF3 subfamily peptaibols. A plausible biosynthetic pathway of compounds 1-6 was proposed on the basis of genomic analysis. Compounds 1, 5, 7, and 10 exhibited significant antimicrobial activity against Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Candida albicans. Compounds 7-10 showed potent cytotoxicities against the A549 and/or HepG2 cancer cell lines.

14.
Carcinogenesis ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34718437

RESUMO

ATP-dependent chromatin remodeling complexes regulate chromatin structure and play important roles in gene expression, differentiation, development and cancer progression. Dysregulation in the subunits of the complexes often has been found in different cancers, but how they influence cancer initiation and progression is not fully understood. Here we show that Chromatin Accessibility Complex Subunit 1 (CHRAC1), the accessory subunit of chromatin remodeling complex, is highly expressed in lung cancer tissues, which correlates with poor prognosis in lung cancer patients. CHRAC1 overexpression promotes lung cancer cell proliferation and migration in vitro and tumor growth in genetically engineered Kras G12D.LSL lung adenocarcinoma mouse model. Consistent with this, CHRAC1 silencing inhibits cell proliferation and migration in lung cancer cells and suppresses tumor growth in xenograft mouse model. Further, CHRAC1 binds to the transcription co-activator Yes-associated protein (YAP), enhances the transcription of downstream target oncogenes in Hippo pathway and thus promotes the tumor growth. Together, our study defines a critical role of CHRAC1 in promoting YAP transcriptional activity and lung cancer tumorigenesis, which makes it a potential target for lung cancer.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34626114

RESUMO

Metformin, a clinical agent of type 2 diabetes, is reported as a potential geroprotector. Viral infection induces phenotypes of senescence in human T cells, and polyinosinic:polycytidylic acid (poly I:C), a viral mimic, induces upregulation of SA-ß-gal activity in ovary of the annual fish Nothobranchius guentheri. However, the effects and mechanisms of metformin on poly I:C-induced aging-like phenomena are poorly understood in vertebrates. In this study, the activity of SA-ß-gal increased in gut of 12-month-old fish and poly I:C-injected 6-month-old fish, compared to 6-month-old control fish, indicating that poly I:C induces aging-like phenomena in gut of the fish. Metformin supplementation retarded accumulation of SA-ß-gal in gut of old fish and poly I:C-treated young fish. The results of q-PCR analysis showed that metformin reduced NF-κB mediated inflammatory response including decreased level of pro-inflammatory cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in gut of the fish with natural aging and poly I:C-injected 6-month-old fish. Metformin also exhibited antioxidant effects, as it reduced ROS production which is associated with the upregulation of FoxO3a and PGC-1α in gut of 6-month-old fish with poly I:C-injection. Expression of AMPK and SIRT1 was reduced in gut of 6-month-old fish with poly I:C-treatment, and feeding metformin reversed these declines. Taken together, the present study suggested that poly I:C-injection led to aging-like phenomena in gut and metformin activated AMPK and SIRT1 to reduce NF-κB mediated inflammation and resist oxidative stress via enhanced expression of FoxO3a and PGC-1α, and finally delayed gut aging in vertebrates.

16.
Bioengineered ; 12(1): 7276-7285, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34612765

RESUMO

Human stanniocalcin 2 (STC2) is an ortholog of fish stanniocalcins (STCs) and is widely expressed in various organs and tissues. The gene is localized on chromosome 5q33 or 5q35. STC2 has been implicated in glucose homeostasis and phosphorus metabolism. It is also reported to be implicated in various malignancies. STC2 was found to be implicated in breast cancer and gynecologic cancers, suggesting hormone-specific or -dependent activities in these malignancies. Moreover, it was reported to be involved in gastrointestinal tumors, including esophageal, gastric, colorectal, and liver cancers, and respiratory cancers, including laryngeal and lung cancers. It also influenced renal carcinoma and prostate cancer. Notably, as a secreted phosphoprotein, STC2 was detectable in serum and possessed promising predictive value in several malignancies. This review aims to improve the understanding of the role of STC2 in patient diagnosis and prognosis, and tumor development and progression, as well as the mechanisms involved.

17.
Adv Mater ; : e2104226, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655458

RESUMO

Plasmonic photocatalysis has received much attention owing to attractive plasmonic enhancement effects in improving the solar-to-chemical conversion efficiency. However, the photocatalytic efficiencies have remained low mainly due to the short carrier lifetime caused by the rapid recombination of plasmon-generated hot charge carriers. Although plasmonic metal-semiconductor heterostructures can improve the separation of hot charge carriers, a large portion of the hot charge carriers are lost when they cross the Schottky barrier. Herein, a Schottky-barrier-free plasmonic semiconductor photocatalyst, MoO3- x , which allows for efficient N2 photofixation in a "one-stone-two-birds" manner, is demonstrated. The oxygen vacancies in MoO3- x serve as the "stone." They "kill two birds" by functioning as the active sites for the chemisorption of N2 molecules and inducing localized surface plasmon resonance for the generation of hot charge carriers. Benefiting from this unique strategy, plasmonic MoO3- x exhibits a remarkable photoreactivity for NH3 production up to the wavelength of 1064 nm with apparent quantum efficiencies over 1%, and a solar-to-ammonia conversion efficiency of 0.057% without any hole scavenger. This work shows the great potential of plasmonic semiconductors to be directly used for photocatalysis. The concept of the Schottky-barrier-free design will pave a new path for the rational design of efficient photocatalysts.

18.
J Biomed Nanotechnol ; 17(9): 1765-1777, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34688321

RESUMO

Osteosarcoma is one of the most aggressive cancers which greatly threatens the health of adolescents and surgery is difficult to resect the whole piece of tumor tissue. The residual tumor cells might proliferate at the tumor site and invade into the blood circulation, leading to tumor recurrence and metastasis. Besides, the invasion of tumor cells could also lead to bone injury. We designed a recombinant fibronectin-cadherin fusion protein/hydrophobically modified glycol chitosan-PTX nanoparticles (rFN-CDH/HGC-PTX) layer-by-layer self-assembly polymer based on biphasic calcium phosphate ceramic (BCP) (BCP-PEI-(rFN/CDH-PTX/HGC)n-rFN/CDH). The SEM, FTIR, XPS and contact angle experiments proved the successful synthesis of the polymer. The chemotherapy drug PTX and bone-repairing-related rFN/CDH fusion protein could be stably released within one week and the in vitro experiments exhibited the efficacy of the polymer to kill residual tumor cells and promote the proliferation of osteoblast, confirming that our polymer was a superior material for postoperative osteosarcoma therapy.


Assuntos
Neoplasias Ósseas , Quitosana , Nanopartículas , Osteossarcoma , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Caderinas , Linhagem Celular Tumoral , Portadores de Fármacos , Fibronectinas , Humanos , Osteossarcoma/tratamento farmacológico , Paclitaxel/farmacologia
19.
mSphere ; 6(5): e0065821, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34668754

RESUMO

African swine fever (ASF) is a highly contagious and deadly viral disease affecting pigs, with up to a 100% case fatality rate. The causative agent, African swine fever virus (ASFV), is a large multienveloped DNA virus which is the sole member of the family Asfarviridae. The double-stranded DNA genome of ASFV encodes more than 150 proteins; the functions of more than half of these viral proteins remain unknown. In this study, we determined that the uncharacterized protein F317L of ASFV had an antagonistic function against host innate immune response. F317L impaired NF-κB pathway activation by disruption of NF-κB activity. F317L interacted with IκB kinase ß (IKKß) and suppressed its phosphorylation, which subsequently reduced phosphorylation and ubiquitination of IκBα and enhanced IκBα stabilization. The accumulation of IκBα then blocked NF-κB activation and inhibited its nuclear translocation, resulting in decreased expression of various proinflammatory cytokines. As expected, overexpression of F317L promoted ASFV replication, and knockdown of F317L expression suppressed ASFV replication. This also indicated the crucial role of NF-κB pathway signaling in suppression of ASFV replication. Truncation mutation analysis indicated that the region spanning amino acids 109 to 208 of F317L was critical for inhibition of NF-κB activity. This is the first report about the function of F317L protein of ASFV, which provides insights for investigation of ASFV immune evasion mechanisms and development of ASFV live-attenuated vaccine. IMPORTANCE African swine fever (ASF) is one of the most important pig diseases, causing a high case fatality rate and trade restrictions upon reported outbreaks. The limited understanding of the functions of the proteins of the causative agent, African swine fever virus (ASFV), has become a primary barrier to developing available commercial ASFV vaccines. ASFV infection causes severe immunosuppression. However, the mechanisms are still poorly understood. Identification of the viral factors responsible for causing immunosuppression will provide targets for developing ASFV live-attenuated vaccine through deletion of these viral factors. In this study, we determined that the uncharacterized protein F317L of ASFV had an antagonistic function against host innate immune response. Knockdown of F317L expression clearly inhibited ASFV replication. This is the first report about the function of F317L protein of ASFV, which provides new data to understand how ASFV inhibits host innate immune response and provides insights for developing ASFV live-attenuated vaccine.

20.
J Healthc Eng ; 2021: 2917226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567480

RESUMO

To explore the application of natural convalescent factors combined with exercise intelligence management in blood pressure control of patients with hypertension, 102 patients with hypertension who were admitted from January 2017 to August 2019 were selected as the research subjects. According to the odd-even number method, they were divided into two groups with 51 cases in each group. The control group was treated with natural convalescent factor therapy alone, and the observation group was treated with natural convalescent factor combined with motor intelligence management. The application effects of the two groups were compared. Before sports intelligence management, the levels of systolic blood pressure (SBP) in control group and observation group were (145.45 ± 8.44) mmHg (1 mmHg = 0.133 kPa) and (146.55 ± 8.37) mmHg, respectively; the diastolic blood pressure (DBP) levels of the control group and the observation group were (98.47 ± 3.48) mmHg and (98.94 ± 3.48) mmHg, respectively, with no statistical significance (P > 0.05). After the exercise intelligence management, the SBP levels of the control group and the observation group were (132.76 ± 4.48) mmHg and (130.06 ± 2.48) mmHg, respectively. The DBP levels of the control group and the observation group were (85.48 ± 5.38) mmHg and (83.47 ± 3.35) mmHg, respectively. The difference was statistically significant (P < 0.05). The scores of each index of quality of life in the observation group were higher than those in the control group, and the differences of physical function and psychological/mental scores were significant. The scores of physical function in the two groups before administration were (48.36 ± 1.69) and (48.74 ± 1.62), and the differences were not statistically significant (P > 0.05). After management, the physiological function scores of the two groups were (40.32 ± 1.33) and (32.15 ± 1.54) and the difference was statistically significant (P < 0.05). There were no significant differences in the psychological (30.75 ± 1.26)/mental scores (30.26 ± 1.48) between the two groups before management (P > 0.05), but there were significant differences in the psychological (25.30 ± 1.02)/mental scores (18.76 ± 1.36) between the two groups after management (P < 0.05). The combination of natural convalescent factors and intelligent exercise management can effectively control the blood pressure level and improve the quality of life of patients with hypertension, and the clinical application effect is good.


Assuntos
Hipertensão , Qualidade de Vida , Pressão Sanguínea , Exercício Físico , Humanos , Hipertensão/tratamento farmacológico , Inteligência
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