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1.
Front Immunol ; 11: 1746, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013828

RESUMO

Innate immune memory is a part of the innate immune system that facilitates the elimination of pathogens. However, it may exacerbate neuropathology. In this study, we found that innate immune memory is detrimental in stroke, because it promotes the acute immune response and exacerbates ischemic infarcts. Mesenchymal stem cell therapy has been widely studied for its therapeutic potential in various diseases including stroke, but whether it diminishes innate immune memory has not been studied. Here, our study demonstrates that, after the activation of innate immune memory by lipopolysaccharide, mesenchymal stem cell therapy can diminish innate immune memory though down-regulation of H3 methylation and subsequently protect against stroke. Our results demonstrate that innate immune memory is detrimental in stroke, and we describe a novel potential therapeutic target involving the use of mesenchymal stem cells to treat stroke patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33014887

RESUMO

Salmonella spp. are a major cause of foodborne illness throughout the world. Traditional serotyping by antisera agglutination has been used as a standard identification method for many years but newer nucleic acid-based tests have become available that may provide advantages in workflow and test turnaround time. In this study, we evaluated the Luminex® xMAP® Salmonella Serotyping Assay (SSA), a multiplex nucleic acid test capable of identifying 85% of the most common Salmonella serotypes, in comparison to the traditional serum agglutination test (SAT) on 4 standard strains and 255 isolates from human (224), environmental, and food (31) samples. Of the total of 259 isolates, 256 could be typed by the SSA. Of these, 197 (77.0%) were fully typed and 59 (23.0%) were partially typed. By SAT, 246 of the 259 isolates (95%) were successfully typed. Sixty isolates had discrepant results between SAT and SSA and were resolved using whole genome sequencing (WGS). By SAT, 80.0% (48/60) of the isolates were consistent with WGS while by SSA 91.7% (55/60) were partially consistent with WGS. By serovar, all 30 serovars except one tested were fully or partially typable. The workflow comparison showed that SSA provided advantages over SAT with a hands-on time (HOT) of 3.5 min and total turnaround time (TAT) of 6 h, as compared to 1 h HOT and 2-6 days TAT for SAT. Overall, this study showed that molecular serotyping is promising as a rapid method for Salmonella serotyping with good accuracy for typing most common Salmonella serovars circulating in China.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33022872

RESUMO

Using gem -difluoromethylene alkynes as effectors, unprecedented diverse C-H activation/[4+2] annulations of simple benzoic acids are reported here. Remarkably, the chemodivergent reaction outcomes are well-tuned by Rh/Ir-catalyzed system; in the Rh(III) catalysis, 3-alkenyl-1 H -isochromen-1-one and 3,4-dialkylideneisochroman-1-one skeletons are afforded in a solvent-dependent manner whereas difluoromethylene-substituted 1 H -isochromen-1-ones are generated under the Ir(III)-catalyzed system. Mechanistic studies revealed that unusually double ß-F eliminations and fluorine effect-induced regioselective reductive elimination are independently involved to enable distinct reaction modes for divergent product formations. Besides, synthetic application in both the derivatization of obtained diene products and the on-DNA synthesis of DNA-tagged difluorinated isocoumarin have been demonstrated, which manifested great potential for synthetic utility of the developed protocols.

5.
BMC Microbiol ; 20(1): 312, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054754

RESUMO

BACKGROUND: Stenotrophomonas maltophilia, an opportunistic pathogen, is ubiquitously present in various environments, signifying its high capability of environmental adaptation. Two-component regulatory system (TCS) is a powerful implement to help organisms to survive in different environments. In clinic, treatment of S. maltophilia infection is difficult because it is naturally resistant to many antibiotics, highlighting the necessity to develop novel drugs or adjuvants. Given their critical and extensively regulatory role, TCS system has been proposed as a convincing target for novel drugs or adjuvants. PhoPQ TCS, a highly conserved TCS in several pathogens, plays crucial roles in low-magnesium adaption, polymyxin resistance, and virulence. In this study, we aimed to characterize the role of PhoPQ TCS of S. maltophilia in antibiotic susceptibility, physiology, stress adaptation, and virulence. RESULTS: To characterize PhoPQ system, phoP single mutant as well as phoP and phoQ double mutant were constructed. Distinct from most phoPQ systems of other microorganisms, two features were observed during the construction of phoP and phoQ single deletion mutant. Firstly, the phoQ mutant was not successfully obtained. Secondly, the compromised phenotypes of phoP mutant were not reverted by complementing an intact phoP gene, but were partially restored by complementing a phoPQ operon. Thus, wild-type KJ, phoP mutant (KJΔPhoP), phoPQ mutant (KJΔPhoPQ), and complemented strain (KJΔPhoPQ (pPhoPQ)) were used for functional assays, including antibiotic susceptibility, physiology (swimming motility and secreted protease activity), stress adaptation (oxidative, envelope, and iron-depletion stresses), and virulence to Caenorhabditis elegans. KJΔPhoPQ totally lost swimming motility, had enhanced secreted protease activity, increased susceptibility to antibiotics (ß-lactam, quinolone, aminoglycoside, macrolide, chloramphenicol, and sulfamethoxazole/ trimethoprim), menadione, H2O2, SDS, and 2,2'-dipyridyl, as well as attenuated virulence to C. elegans. Trans-complementation of KJΔPhoPQ with phoPQ reverted these altered phenotypes to the wild-type levels. CONCLUSIONS: Given the critical and global roles of PhoPQ TCS in antibiotic susceptibility, physiology, stress adaptation, and virulence, PhoPQ is a potential target for the design of drugs or adjuvants.

6.
Medicine (Baltimore) ; 99(42): e22624, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080697

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder involving hyperandrogenism, menstrual disorder, metabolic problems, infertility, obesity, and acne. The main aim of this study was to assess the reporting quality of clinical practice guidelines (CPGs) in the field of PCOS to provide a reporting specification for this study. METHODS: We evaluated the reporting quality of clinical guidelines of PCOS using the Reporting Items for Practice Guidelines in HealThcare (RIGHT) checklist. Nine databases and 3 medical associations were searched. These included Medline, Embase, PubMed, National Institute for Health and Care Excellence (NICE), Guidelines International Network (GIN), National Guideline Clearinghouse (NGC), China National Knowledge Infrastructure, Wanfang and Chinese Science, and Technology Journal Database (VIP). Three medical associations included the European Society of Human Reproduction and Embryology, the American Society for Reproductive Medicine and the Agency for Healthcare Research and Quality. Two independent authors assessed the reporting quality of PCOS CPGs by the RIGHT checklist, and Spearman's correlation was used to assess inter-rater reliability. RESULTS: Twelve PCOS CPGs were included. On average, 20.0 (57.1%) of the 35 items in the RIGHT checklist were reported. All items were fully reported by one of these CPGs. The number of reported items ranged from 10 (28.6%) to 35 (100%). Overall, 16.7%, 66.7%, and 16.7% of included guidelines were of high, medium, and low quality, respectively. The reporting proportions of the 7 domains (i.e., Basic information, Background, Evidence, Recommendations, Reviewand quality assurance, Funding and declaration and management of interests, and Other information) in the RIGHT checklist were 62.0%, 69.1%, 53.3%, 60.7%, 33.3%, 31.2%, and 69.4%, respectively. CONCLUSIONS: The evaluation of these CPGs by the RIGHT checklist revealed that the reporting quality varied among guidelines. Low quality items were the processes of evidence decision and the declaration of funding in most included CPGs. Guideline developers should pay more attention to these items to disseminate and implement better guidelines in near future. TRIAL REGISTRATION NUMBER: registration at PROSPERO CRD42020163435.

7.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097529

RESUMO

Poor wound healing after diabetes or extensive burn remains a challenging problem. Recently, we presented a physical approach to fabricate ultrasmall silver particles from Ångstrom scale to nanoscale and determined the antitumor efficacy of Ångstrom-scale silver particles (AgÅPs) in the smallest size range. Here we used the medium-sized AgÅPs (65.9 ± 31.6 Å) to prepare carbomer gel incorporated with these larger AgÅPs (L-AgÅPs-gel) and demonstrated the potent broad-spectrum antibacterial activity of L-AgÅPs-gel without obvious toxicity on wound healing-related cells. Induction of reactive oxygen species contributed to L-AgÅPs-gel-induced bacterial death. Topical application of L-AgÅPs-gel to mouse skin triggered much stronger effects than the commercial silver nanoparticles (AgNPs)-gel to prevent bacterial colonization, reduce inflammation, and accelerate diabetic and burn wound healing. L-AgÅPs were distributed locally in skin without inducing systemic toxicities. This study suggests that L-AgÅPs-gel represents an effective and safe antibacterial and anti-inflammatory material for wound therapy.

8.
Front Immunol ; 11: 580864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101307

RESUMO

TANK-binding kinase 1 (TBK1), an IKK-related serine/threonine kinase, is pivotal for the induction of antiviral type I interferon (IFN) by TLR and RLR signaling pathways. In a previous study, we demonstrated that TBK1 spliced isoforms (TBK1_tv1 and TBK1_tv2) from zebrafish were dominant negative regulators in the RLR antiviral pathway by targeting the functional TBK1-IRF3 complex formation. In this study, we show that the third TBK1 isoform (namely TBK1_tv3) inhibits zebrafish type I IFN production by promoting TBK1 and IRF3 degradation. First, ectopic expression of TBK1_tv3 suppresses poly(I:C)- and Spring viremia of carp virus-induced type I IFN response, and also inhibits the up-regulation of IFN promoter activities stimulated by RIG-I, MDA5, MAVS, TBK1, and IRF3. Second, TBK1_tv3 targets TBK1 and IRF3 to impair the formation of TBK1 dimer, TBK1-IRF3 complex, and IRF3 dimer. Notably, TBK1_tv3 promotes the degradation of TBK1 through the ubiquitin-proteasome pathway and the degradation of IRF3 through the lysosomal pathway. Further analysis demonstrates that TBK1_tv3 promotes the degradation of TBK1 for K48-linked ubiquitination by targeting the K251, K256, and K271 sites of TBK1. Collectively, our results suggest a novel TBK1 isoform-mediated negative regulation mechanism, which serves to balance the production of type I IFN and ISGs.

9.
Zhongguo Zhen Jiu ; 40(10): 1027-33, 2020 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-33068341

RESUMO

OBJECTIVE: To establish and promote the non-contact doctor-patient interactive diagnosis and treatment mode based on mobile internet for the treatment of coronavirus disease 2019 (COVID-19) with moxibustion therapy, and to observe the feasibility and effectiveness of the model in the pandemic. METHODS: A total of 43 first-line medical staff and 149 suspected and confirmed cases with COVID-19 [18 cases in medical observation period, 17 cases of mild type (cold dampness and stagnation in the lung), 24 cases of ordinary type (cold-dampness accumulated in the lung) and 90 cases in recovery period (qi deficiency of spleen and lung)] were included. A non-contact doctor-patient interactive diagnosis and treatment platform was established for the treatment of COVID-19 with indirect moxibustion plaster based on mobile internet. By the platform, the patients were instructed to use indirect moxibustion plaster in treatment. For the first-line medical staff and patients in the medical observation period, Zusanli (ST 36), Qihai (CV 6) and Zhongwan (CV 12) were selected. For the mild cases (cold dampness and stagnation in the lung) and the cases of ordinary type (cold-dampness accumulated in the lung), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Guanyuan (CV 4) were selected. In the recovery period (qi deficiency of spleen and lung), Dazhui (GV 14), Feishu (BL 13), Geshu (BL 17), Zusanli (ST 36) and Kongzui (LU 6) were used. The treatment was given once daily for 40 min each time. The intervention lasted for 10 days. After intervention, the infection rate and the improvement in the symptoms and psychological status of COVID-19 were observed in clinical first-line medical staff and COVID-19 patients. RESULTS: In 10 days of intervention with indirect moxibustion plaster, there was "zero" infection among medical staff. Of 43 first-line physicians and nurses, 33 cases had some physical symptoms and psychological discomforts, mainly as low back pain, poor sleep and anxiety. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 78.8% (26/33) and the curative rate was 36.4% (12/33). Regarding the improvements in psychological discomforts, the effective rate was 58.3% (14/24) and the curative rate was 37.5 (9/24). Of 149 patients, 133 cases had the symptoms and psychological discomforts. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 81.2% (108/133) and the curative rate was 34.6% (46/133). Regarding the improvements in psychological discomforts, the effective rate was 76.5% (52/68) and the curative rate was 57.4 % (39/68). CONCLUSION: It is feasible to apply the indirect moxibustion plaster technique based on mobile internet to the treatment COVID-19. This mode not only relieves the symptoms such as cough and fatigue, improves psychological state, but also possibly prevents the first-line medical staff from COVID-19.


Assuntos
Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Moxibustão , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Consulta Remota , Pontos de Acupuntura , Betacoronavirus , Pessoal de Saúde , Humanos
10.
Exp Lung Res ; : 1-17, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107354

RESUMO

PURPOSE: Malignant pleural mesothelioma (MPM) is a rare and deadly malignancy. Current MPM therapies remain inadequate, and outcomes are often disappointing. New meaningful therapeutic approaches are urgently needed. Accumulating evidence indicates that the cAbl pathway promotes various tumor-stimulating processes in MPM. In this study, we sought to determine ponatinib's potential utility, a clinically approved and potent cAbl inhibitor, in MPM treatment. MATERIAL AND METHODS: Four MPM lines (MSTO211H, H28, H2452, H2052) were treated with ponatinib in vitro, and their growth was assessed. Scratch wound assay was used to investigate the ponatinib effect on cell migration. The expression levels of pAbl and its downstream effectors pCrkL, pAKT, and pSTAT5 were characterized. The in vivo ponatinib effect was evaluated in human MPM cells derived tumor model. RESULTS: In all four MPM lines, significant expression levels of phosphorylated cAbl/Arg and pCrkl were observed. Differentially but strongly, ponatinib inhibited the in vitro cell growth and migration of all four MPM line. Western blot analysis showed that the activation of Abl signaling was blocked in the ponatinib-treated MMP lines. In keeping, the cellular levels of pAbl and its downstream effector pCrkL, pAKT, and pSTAT5 were markedly decrease following ponatinib treatment. Moreover, ponatinib treatment amplified the levels of γH2AX in cells denoting increased double-strand DNA breaks levels. Notably, ponatinib treatment reduced in vivo tumor growth and reduced pCrkl and pSTAT5 levels in tumor samples. CONCLUSION: Ponatinib may offer a new therapeutic strategy for MPM patients based on cAbl signaling pathway inhibition.

11.
J Med Virol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073355

RESUMO

The 2019 novel coronavirus disease (COVID-19) now is considered a global public health emergency. One of the unprecedented challenges is defining optimal therapy for those patients with severe pneumonia and systemic manifestations of COVID-19. Optimal therapy should be largely based on the pathogenesis of infections caused by this novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the onset of COVID-19, there have been many prepublications and publications reviewing the therapy of COVID-19 as well as many prepublications and publications reviewing the pathogenesis of SARS-CoV-2. However, there have been no comprehensive reviews that link COVID-19 therapies to the pathogenic mechanisms of SARS-CoV-2. In order to link COVID-19 therapies to pathogenic mechanisms of SARS-CoV-2, we performed a comprehensive search through MEDLINE, PubMed, medRxiv, EMBASE, Scopus, Google Scholar, and Web of Science using the following keywords: COVID-19, SARS-CoV-2, novel 2019 coronavirus, pathology, pathologic, pathogenesis, pathophysiology, coronavirus pneumonia, coronavirus infection, coronavirus pulmonary infection, coronavirus cardiovascular infection, coronavirus gastroenteritis, coronavirus autopsy findings, viral sepsis, endotheliitis, thrombosis, coagulation abnormalities, immunology, humeral immunity, cellular immunity, inflammation, cytokine storm, superantigen, therapy, treatment, therapeutics, immune-based therapeutics, antiviral agents, respiratory therapy, oxygen therapy, anticoagulation therapy, adjuvant therapy, and preventative therapy. Opinions expressed in this review also are based on personal experience as clinicians, authors, peer reviewers, and editors. This narrative review linking COVID-19 therapies with pathogenic mechanisms of SARS-CoV-2 has resulted in 6 major therapeutic goals for COVID-19 therapy based on pathogenic mechanisms of SARS-CoV-2. These goals are listed below: 1. The first goal is identifying COVID-19 patients that require both testing and therapy. This is best accomplished with a COVID-19 molecular test from symptomatic patients as well as determining the oxygen saturation in such patients with a pulse oximeter. It can be argued that whether a symptomatic respiratory illness is COVID-19, influenza or another respiratory pathogen, an oxygen saturation less that 90% means that the patient requires medical assistance. 2. The second goal is to correct the hypoxia. This goal generally requires hospitalization for oxygen therapy; other respiratory-directed therapies such as prone positioning or mechanical ventilation are often used in the attempt to correct hypoxemia due to COVID-19. 3. The third goal is reducing the viral load of SARS-CoV-2. Ideally, there would be an oral antiviral agent available such as seen with the use of oseltamivir phosphate for influenza. This oral antiviral agent should be taken early in the course of SARS-CoV-2 infection. Such an oral agent is not available yet. Currently, two options are available for reducing the viral load of SARS-CoV-2. These are post-Covid-19 plasma with a high neutralizing antibody titer against SARS-CoV-2 or intravenous remdesivir; both options require hospitalization. 4. The fourth goal is to identify and address the hyperinflammation phase often seen in hospitalized COVID-19 patients. Currently, fever with an elevated C-reactive protein is useful for diagnosing this hyperinflammation syndrome. Low-dose dexamethasone therapy currently is the best therapeutic approach. 5. The fifth goal is to identify and address the hypercoagulability phase seen in many hospitalized COVID-19 patients. Patient who would benefit from anticoagulation therapy can be identified by a marked increase in D-dimer and prothrombin time with a decrease in fibrinogen. To correct this disseminated intravascular coagulation-like phase, anticoagulation therapy with low molecular weight heparin is preferred. Anticoagulation therapy with unfractionated heparin is preferred in COVID-19 patients with acute kidney injuries. 6. The last goal is prophylaxis for persons who are not yet infected. Potential supplements include vitamin D and zinc. Although the data for such supplements is not extremely strong, it can be argued that almost 50% of the population world-wide has a vitamin D deficiency. Correcting this deficiency would be beneficial regardless of any impact of COVID-19. Similarly, zinc is an important supplement that is important in one's diet regardless of any effect on SARS-CoV-2. As emerging therapies are found to be more effective against the SARS-CoV-2 pathogenic mechanisms identified, they can be substituted for those therapies presented in this review. This article is protected by copyright. All rights reserved.

12.
World Neurosurg ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33075574

RESUMO

BACKGROUND: Robotic guidance (RG) pedicle screw placement has been increasingly utilized to improve the rate of insertion accuracy. However, the superiority of RG technique over computer-assisted navigation (CAN) remains debatable. OBJECTIVE: To determine whether Mazor RG technique is superior to CAN in terms of the rate of insertion accuracy and four other clinical indices, namely, intraoperative time, blood loss, complications and revision surgery caused by malposition. METHODS: A search on PubMed, EMBASE, Cochrane, Web of Science, CNKI and WanFang was conducted. We mainly aimed to evaluate the accuracy of pedicle screw placement between the Mazor RG and CAN techniques. The secondary objectives were intraoperative time, blood loss, complications and revision surgery caused by malposition. The meta-analysis was conducted using the RevMan 5.3 and Stata 15.1 software. RESULT: A randomized controlled trial and five comparative cohort studies consisting of 529 patients and 4,081 pedicle screws were included in this meta-analysis. The RG technique has a significantly higher accuracy than CAN in terms of optimal (OR = 2.26, 95% CI of 1.85-2.76, P < 0.01) and clinically acceptable (OR = 1.69, 95% CI of 1.22-2.34, P =0.002) pedicle screw insertions. Furthermore, the RG technique showed significantly less blood loss (MD = -42.49, 95% CI of -78.38 to -6.61, P=0.02) than the CAN technique but has equivalent intraoperative time (MD = 0.75, 95% CI of -5.89 to 7.40, P=0.82), complications (OR = 0.65, 95% CI of 0.32-1.33, P =0.24) and revision surgery caused by malposition (OR = 0.46, 95% CI of 0.15-1.43, P =0.18). CONCLUSION: Mazor RG technique is superior to CAN technique concerning the accuracy of pedicle screw placement. Thus, Mazor RG technique is accurate and safe in clinical application.

13.
Nat Commun ; 11(1): 5054, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028835

RESUMO

Type IVa pili are ubiquitous and versatile bacterial cell surface filaments that undergo cycles of extension, adhesion and retraction powered by the cell-envelope spanning type IVa pilus machine (T4aPM). The overall architecture of the T4aPM and the location of 10 conserved core proteins within this architecture have been elucidated. Here, using genetics, cell biology, proteomics and cryo-electron tomography, we demonstrate that the PilY1 protein and four minor pilins, which are widely conserved in T4aP systems, are essential for pilus extension in Myxococcus xanthus and form a complex that is an integral part of the T4aPM. Moreover, these proteins are part of the extended pilus. Our data support a model whereby the PilY1/minor pilin complex functions as a priming complex in T4aPM for pilus extension, a tip complex in the extended pilus for adhesion, and a cork for terminating retraction to maintain a priming complex for the next round of extension.

14.
PLoS One ; 15(10): e0236503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031375

RESUMO

BACKGROUND: The treatment for stage III non-small cell lung cancer (NSCLC) often involves multi-modality treatment. This retrospective study aimed to evaluate whether multidisciplinary team (MDT) discussion results in better patient survival. MATERIALS AND METHODS: MDT discussion was optional before February 2016 and was actively encouraged by the MDT committee beginning February 2016. We reviewed the medical charts and computer records of patients with stage III NSCLC between January 2013 and December 2018. RESULTS: A total of 515 patients were included. The median survival of all the patients was 33.9 months (M). The median survival of patients who were treated after MDT discussion was 41.2 M and that of patients treated without MDT discussion was 25.7 M (p = 0.018). The median survival of patients treated before February 2016 was 25.7 M and that of patients treated after February 2016 was 33.9 M (p = 0.003). The median survival of patients with stage IIIA tumors and those with stage IIIB tumors was 39.4 M and 25.7 M, respectively (p = 0.141). Multivariate analysis showed that MDT or not (p<0.001), T staging (p = 0.009), performance status (p<0.001), and surgery (p = 0.016) to be significant prognostic factors. CONCLUSION: The results of the study show that MDT discussion results in survival benefit in patients with stage III NSCLC. The MDT discussion, performance status, and if surgery was performed were independent prognostic factors for patients with stage III NSCLC.

15.
J Chin Med Assoc ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33009207

RESUMO

BACKGROUND: Gene therapy is the advance therapeutics for supplying or replaceing the genetic material in patients with inherited disorders. Recent clinical studies have made some progress in a wide range of applications, including monogenic disorders, neurodegenerative diseases, malignant tumors, and congenital diseases. Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. METHODS: Most advances in induced pluripotent stem cell (iPSC) technologies for promoting regenerative medicine and stem cell research. However, the driver molecules of myocardial-lineage differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still an open question. Nanomedicine-based gene delivery provided an crucial platform to carry on the biogenomic materials for equipping functionalities and engineering the living organ environment. Nanodiamond (ND), a carbon-based nanomaterial, has been discovered and shown the high biocompatible and less toxicity for transporting protein, drug, and genomic plasmids. RESULTS: Here, we applied nanodiamond (ND) as a gene delvery vehicle to carry microRNA (miR-181a), and then tranfected into iPS to promote cardiomyocyte-lineage differentiation. Notably. MiR-181a plays a key role in iPS-dervied cardiomyocyte differentiation which directly target Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation. CONCLUSION: Our study demonstrated that miR-181a promotes iPSC differentiation into functional cardiomyocytes. Delivery of NANO-DIAMOND-miR-181a may host clinical potential to enhance the differentiation and recovery of the cardiogenic function in injured cardiomyocytes.

16.
Int J Mol Sci ; 21(19)2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993155

RESUMO

Accurate and rapid identification of microbiotic communities using 16S ribosomal (r)RNA sequencing is a critical task for expanding medical and clinical applications. Next-generation sequencing (NGS) is widely considered a practical approach for direct application to communities without the need for in vitro culturing. In this report, a comparative evaluation of short-read (Illumina) and long-read (Oxford Nanopore Technologies (ONT)) platforms toward 16S rRNA sequencing with the same batch of total genomic DNA extracted from fecal samples is presented. Different 16S gene regions were amplified, bar-coded, and sequenced using the Illumina MiSeq and ONT MinION sequencers and corresponding kits. Mapping of the sequenced amplicon using MinION to the entire 16S rRNA gene was analyzed with the cloud-based EPI2ME algorithm. V3-V4 reads generated using MiSeq were aligned by applying the CLC genomics workbench. More than 90% of sequenced reads generated using distinct sequencers were accurately classified at the genus or species level. The misclassification of sequenced reads at the species level between the two approaches was less substantial as expected. Taken together, the comparative results demonstrate that MinION sequencing platform coupled with the corresponding algorithm could function as a practicable strategy in classifying bacterial community to the species level.

17.
Biomed Environ Sci ; 33(8): 614-619, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32933613

RESUMO

This study aimed to understand the differences in clinical, epidemiological, and laboratory features between the new coronavirus disease 2019 (COVID-2019) and influenza A in children. Data of 23 hospitalized children with COVID-19 (9 boys, 5.7 ± 3.8 years old) were compared with age- and sex-matched 69 hospitalized and 69 outpatient children with influenza A from a hospital in China. The participants' epidemiological history, family cluster, clinical manifestations, and blood test results were assessed. Compared with either inpatients or outpatients with influenza A, children with COVID-19 showed significantly more frequent family infections and higher ratio of low fever (< 37.3 °C), but shorter cough and fever duration, lower body temperature, and lower rates of cough, fever, high fever (> 39 °C), nasal congestion, rhinorrhea, sore throat, vomiting, myalgia or arthralgia, and febrile seizures. They also showed higher counts of lymphocytes, T lymphocyte CD8, and platelets and levels of cholinesterase, aspartate aminotransferase, lactate dehydrogenase, and lactic acid, but lower serum amyloid, C-reactive protein, and fibrinogen levels and erythrocyte sedimentation rate, and shorter prothrombin time. The level of alanine aminotransferase in children with COVID-19 is lower than that in inpatients but higher than that in outpatients with influenza A. Pediatric COVID-19 is associated with more frequent family infection, milder symptoms, and milder immune responses relative to pediatric influenza A.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Influenza Humana/epidemiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Estudos de Casos e Controles , Criança , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Feminino , Humanos , Influenza Humana/sangue , Influenza Humana/imunologia , Masculino , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia
18.
J Headache Pain ; 21(1): 113, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948125

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

19.
Radiother Oncol ; 151: 214-221, 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32866564

RESUMO

PURPOSE: Although patients aged >70 years are subject to early oral cavity squamous cell carcinoma (E-OCSCC), evidence is currently lacking regarding the probable outcomes of definitive radiotherapy (RT) compared to surgery in this population. METHODS: We recruited patients aged ≥70 years with a diagnosis of E-OCSCC from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze all-cause mortality of patients at different age intervals undergoing different treatments. RESULTS: The matching process yielded a final cohort of 604 patients in the definitive RT and surgery cohorts who were eligible for further analysis. These patients were classified as old (70-80 years) and very old (>80 years). In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for surgery compared with definitive RT was 0.465 (0.354-0.610, P < 0.001). The aHR (95% CI) for age >80 years compared with age 70-80 years was 2.370 (1.720, 3.265, P < 0.001). The aHR (95% CI) for T2N0M0 compared with T1N0M0 was 1.752 (1.321-2.32, P < 0.001). The aHR (95% CI) for Charlson Comorbidity Index (CCI) ≥ 2 compared with CCI = 0 was 1.264 (1.137-1.738, P = 0.011). After stratified analysis, the aHRs for surgery compared with definitive RT were 0.484 (0.352-0.665, P < 0.001) and 0.411 (0.232-0.728, P = 0.002) among old and very old patients with E-OCSCC, respectively. CONCLUSIONS: Surgery may be more beneficial than definitive RT in selected elderly patients with E-OCSCC.

20.
FASEB J ; 34(11): 15093-15107, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32918769

RESUMO

Clinical fungal infections always cause a negative impact on human health. Moreover, during the interaction of pathogenic fungi with the environment and host, many biologically active substances are produced. Here, we report a new toxin-like defensin of purlisin derived from a clinical pathogenic isolate of Purpureocillium lilacinum. The analysis of its genomic and mRNA sequences revealed an open reading frame of 444 bp without introns. The deduced precursor peptide was composed of 147 amino acids, and the mature peptide were identified at protein level by LC-ESI-Q-TOF-MS/MS. After posttranslational processing, the precursor peptide of purlisin was split into two independent peptides. The two mature defensins, purlisin-NT and purlisin-CT, are consisting of 36 and 38 amino acid residues, which can form three and four intramolecular disulfide bonds, respectively. The results of circular dichroism and homology modeling revealed that they adopted a representative cysteine-stabilized α-helical and ß-sheet motif. The purlisin-NT showed a dose-dependent selective inhibition of immune-related hKv1.3 target channel with IC50 value of 0.2 ± 0.04 µM but no obvious antibacterial activity, while the purlisin-CT displayed antimicrobial activities against gram-positive bacteria as well as clinical isolates of MRSA and low affinities for potassium channels. Our findings suggest that purlisin-NT with immunosuppressive effects and purlisin-CT possessing antibacterial activities are adapted to the survival and pathogenicity of clinical P lilacinumis. Moreover, they can also be used as templates for the design of novel antibacterial peptide and immunosuppressive agents.

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