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1.
J Antimicrob Chemother ; 79(8): 2048-2052, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38906827

RESUMEN

BACKGROUND: Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring antimicrobial combinations for coverage. However, possible antagonistic interactions between antibiotics have not been thoroughly explored. This study aimed to evaluate the effectiveness of antimicrobial combinations against Elizabethkingia infections, focusing on their impact on pathogenicity, including biofilm production and cell adhesion. METHODS: Double-disc diffusion, time-kill, and chequerboard assays were used for evaluating the combination effects of antibiotics against Elizabethkingia spp. We further examined the antagonistic effects of antibiotic combinations on biofilm formation and adherence to A549 human respiratory epithelial cells. Further validation of the antibiotic interactions and their implications was performed using ex vivo hamster precision-cut lung sections (PCLSs) to mimic in vivo conditions. RESULTS: Antagonistic effects were observed between cefoxitin, imipenem and amoxicillin/clavulanic acid in combination with vancomycin. The antagonism of imipenem toward vancomycin was specific to its effects on the genus Elizabethkingia. Imipenem further hampered the bactericidal effect of vancomycin and impaired its inhibition of biofilm formation and the adhesion of Elizabethkingia meningoseptica ATCC 13253 to human cells. In the ex vivo PCLS model, vancomycin exhibited dose-dependent bactericidal effects; however, the addition of imipenem also reduced the effect of vancomycin. CONCLUSIONS: Imipenem reduced the bactericidal efficacy of vancomycin against Elizabethkingia spp. and compromised its capacity to inhibit biofilm formation, thereby enhancing bacterial adhesion. Clinicians should be aware of the potential issues with the use of these antibiotic combinations when treating Elizabethkingia infections.


Asunto(s)
Antibacterianos , Biopelículas , Infecciones por Flavobacteriaceae , Imipenem , Pruebas de Sensibilidad Microbiana , Vancomicina , Animales , Imipenem/farmacología , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Humanos , Vancomicina/farmacología , Infecciones por Flavobacteriaceae/microbiología , Infecciones por Flavobacteriaceae/tratamiento farmacológico , Flavobacteriaceae/efectos de los fármacos , Adhesión Bacteriana/efectos de los fármacos , Células A549 , Cricetinae , Interacciones Farmacológicas , Pulmón/microbiología
2.
Infection ; 52(3): 955-983, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38133713

RESUMEN

PURPOSE: The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles. METHODS: Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay. RESULTS: The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-ß, SDF-1α, TNF-α, TNF-ß, VEGF, PDGF-BB, TRAIL, ß-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients. CONCLUSION: Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.


Asunto(s)
COVID-19 , Proteínas de la Nucleocápside de Coronavirus , Citocinas , Células Epiteliales , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , COVID-19/inmunología , COVID-19/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , SARS-CoV-2/inmunología , Citocinas/sangre , Femenino , Masculino , Persona de Mediana Edad , Células Epiteliales/virología , Células Epiteliales/inmunología , Proteínas de la Nucleocápside de Coronavirus/inmunología , Anciano , Células A549 , Pulmón/patología , Pulmón/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/sangre , Adulto , Anticuerpos Antivirales/sangre , Fosfoproteínas
3.
Vet Surg ; 53(4): 586-595, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38558417

RESUMEN

OBJECTIVE: To describe patient characteristics, etiology, treatment outcomes and complications of caudoventral hip luxation (CvHL) in a large cohort of dogs and investigate factors associated with nonsurgical treatment outcomes. STUDY DESIGN: Multicenter retrospective case series. ANIMAL POPULATION: A total of 160 client-owned dogs (170 limbs). METHODS: Medical records from 2003 to 2023 were reviewed for signalment, history, treatment outcomes and complications. Logistic regression was performed to investigate factors associated with nonsurgical treatment outcome. RESULTS: Low-trauma accidents accounted for 82.9% of cases. Over-represented breeds included poodles (38.1%) and poodle crosses (11.3%). On a per-treatment basis, success rates of closed reduction alone, closed reduction/Ehmer sling, closed reduction/hobbles were 9.1%, 15.2% and 48.8%, respectively. When accounting for repeated attempts using closed reduction alone, Ehmer sling, or hobbles, eventual success rate increased to 10.3%, 18.5% and 61.8%, respectively. Success rate for toggle rod stabilization was 88.2%. Complication rate of hobbles was 31.9% versus 60.6% for Ehmer slings. Use of hobbles (OR:7.62, p = .001, CI:2.23-26.05), treatment by specialist surgeons (OR:2.68, p = .047, CI: 1.01-7.08) and increasing age (OR:1.15, p < .005, CI: 1.08-1.23) were associated with successful nonsurgical treatments. CONCLUSION: Low-trauma etiology, and poodles and their crosses were over-represented in cases of CvHL. Success rate of nonsurgical treatments was lower than previously reported. Hobbles were 7.6 times more likely to be successful when compared to dogs treated without hobbles and remains a viable noninvasive first-line treatment. CLINICAL SIGNIFICANCE/IMPACT: Hobbles are recommended as a low-morbidity first-line treatment for CvHL. An Ehmer sling is not recommended. Toggle rod stabilization is an effective surgical treatment for CvHL.


Asunto(s)
Luxación de la Cadera , Animales , Perros/lesiones , Estudios Retrospectivos , Femenino , Masculino , Luxación de la Cadera/veterinaria , Resultado del Tratamiento , Enfermedades de los Perros/terapia
4.
Molecules ; 29(11)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38893339

RESUMEN

Six ionone glycosides (1-3 and 5-7), including three new ones, named capitsesqsides A-C (1-3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8-10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.


Asunto(s)
Glicósidos , Rhododendron , Rhododendron/química , Ratones , Glicósidos/química , Glicósidos/farmacología , Glicósidos/aislamiento & purificación , Células RAW 264.7 , Animales , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Norisoprenoides/química , Norisoprenoides/farmacología , Norisoprenoides/aislamiento & purificación , Estructura Molecular , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología
5.
Aesthetic Plast Surg ; 47(5): 2117-2129, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37400586

RESUMEN

BACKGROUND: Cryopreserved fat has limited clinical applications due to its rapid absorption, high degree of fibrosis, and risk of complications after grafting. Many studies have verified that Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) can improve fresh fat graft survival. This study assessed whether ADSC-Exos could improve the survival of cryopreserved fat grafts. METHODS: Exosomes were isolated from human ADSCs were subcutaneously engrafted with adipose tissues stored under different conditions (fresh; cryopreserved for 1 month) into the backs of BALB/c nude mice (n = 24), and exosomes or PBS were administered weekly. Grafts were harvested at 1, 2, 4, and 8 weeks, and fat retention rate, histologic, and immunohistochemical analyses were conducted. RESULTS: At 1, 2, and 4 weeks after the transfer, cryopreserved fat grafts in groups of exosome-treated showed better fat integrity, fewer oil cysts, and reduced fibrosis. Further investigations of macrophage infiltration and neovascularization revealed that those exosomes increased the number of M2 macrophages at 2 and 4 weeks (p<0.05), but had limited impact on vascularization (p>0.05). It's important to note that no significant differences (p>0.05) were observed between the two groups in both histological and immunohistochemical evaluations at 8 weeks post-transplantation. CONCLUSIONS: This study suggests that ADSC-Exos could improve the survival of cryopreserved fat grafts in the short term (within 4 weeks), but the overall improvement was poor (after 8 weeks). This suggests that the utility of using ADSC-Exos to treat cryopreserved adipose tissue grafts is limited. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Exosomas , Supervivencia de Injerto , Ratones , Animales , Humanos , Exosomas/trasplante , Ratones Desnudos , Tejido Adiposo/trasplante , Criopreservación , Células Madre , Fibrosis
6.
Opt Express ; 30(15): 28170-28181, 2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-36236970

RESUMEN

Doppler-free spectroscopy of 40Ca+ on the transition 3D3/2 → 4P1/2 known as the frequency standard for repumping beam of Calcium ion trap was performed by means of optogalvanic detection. This reference signal was applied to measure the frequency stability of laser locked to the resonance of an ultra-low expansion (ULE) glass made cavity. Lamb dip spectrum fitting of this Calcium ion spectra revealed that the long-term drift of our laser system is below 2 MHz per hour. A simple setup for frequency locking of dual colour of lasers at 866 nm and 780 nm was also demonstrated. Consistencies of the frequency difference between these two lasers were measured less than 2 MHz in a hour after stabilizing both lasers to the cavity.

7.
Bioorg Chem ; 121: 105689, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35217377

RESUMEN

Ganoderma resinaceum, as a traditional edible mushroom, has been widely reported to improve neurodegenerative diseases characterized by oxidative stress and inflammation. In this study, five new terpenoids, including four lanostane triterpenoids, named ganoresinoid A-D (1-4) and one meroterpenoid, named ganoresinoid E (5), along with 27 known compounds (6-32), were isolated from the fruiting bodies of edible mushroom G. resinaceum. These structures were identified by NMR, HRESIMS data analysis. All metabolites were evaluated for anti-inflammatory, antioxidative and anti-apoptosis activities. Among them, ganoresinoid A showed notably restrained nitric oxide (NO), IL-1ß, IL-6 and TNF-α levels in LPS-activated BV-2 microglial cells via suppressing TLR-4/ NF-κB and MAPK signaling pathway. Simultaneously, ganoresinoid A remarkably alleviated LPS-induced apoptosis by means of the decrease of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). In addition, ganoresinoid A demonstrated antioxidant effects in H2O2-induced SH-SY5Y cells by activating the Akt/GSK-3ß/Nrf2 signaling pathway. Taken together, these results may provide a stronger theoretical basis for ganoresinoid A from G. resinaceum as nutrition intervention to alleviate neurodegenerative diseases.


Asunto(s)
Triterpenos , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Ganoderma , Glucógeno Sintasa Quinasa 3 beta , Peróxido de Hidrógeno , Lipopolisacáridos/farmacología , Triterpenos/química , Triterpenos/farmacología
8.
Environ Geochem Health ; 44(3): 1161-1173, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34195906

RESUMEN

This is the first investigation that identified seasonal variation, possible sources and health risk of 16 PAHs in street dust sampled park area (PA), educational area (EA), commercial area (CA), residential area (RA), and traffic area (TA) of Chengdu, one of the new first-tier cities in China. The total PAHs (∑16PAHs) concentrations of averaging over two seasons varied from 2.15 to 10.6 mg/kg with a median value of 4.61 mg/kg and in winter (5.48 ± 1.52 mg/kg) were significantly higher than that in summer (4.04 ± 0.91 mg/kg). The highest ∑16PAHs concentration was found in TA (median 6.74 mg/kg). Statistical analysis results indicated that mixture sources of petroleum combustion and combustion of biomass and coal seem to be the primary source of the PAHs in street dust. Carcinogenic risk by incremental lifetime cancer risk (ILCR) model for PAHs in street dust indicates an acceptable potential cancer risk for residents. The same sequences of cancer risk to be observed for both children and adults among different functional areas: TA > CA > EA > RA > PA. The results provided advice for habitants in Chengdu to encourage outdoor activities in parks and residential areas and minimize traffic areas and commercial areas.


Asunto(s)
Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Adulto , Contaminantes Atmosféricos/análisis , Niño , China/epidemiología , Ciudades , Polvo/análisis , Monitoreo del Ambiente/métodos , Humanos , Hidrocarburos Policíclicos Aromáticos/análisis , Medición de Riesgo , Estaciones del Año
9.
Zhongguo Zhong Yao Za Zhi ; 47(17): 4574-4582, 2022 Sep.
Artículo en Zh | MEDLINE | ID: mdl-36164862

RESUMEN

Carthamus tinctorius is proved potent in treating ischemic stroke. Flavonoids, such as safflower yellow, hydroxysafflor yellow A(HSYA), nicotiflorin, safflower yellow B, and kaempferol-3-O-rutinoside, are the main substance basis of C. tinctorius in the treatment of ischemic stroke, and HSYA is the research hotspot. Current studies have shown that C. tinctorius can prevent and treat ischemic stroke by reducing inflammation, oxidative stress, and endoplasmic reticulum stress, inhibiting neuronal apoptosis and platelet aggregation, as well as increasing blood flow. C. tinctorius can regulate the pathways including nuclear factor(NF)-κB, mitogen-activated protein kinase(MAPK), signal transducer and activator of transcription protein 3(STAT3), and NF-κB/NLR family pyrin domain containing 3(NLRP3), and inhibit the activation of cyclooxygenase-2(COX-2)/prostaglandin D2/D prostanoid receptor pathway to alleviate the inflammatory development during ischemic stroke. Additionally, C. tinctorius can relieve oxidative stress injury by inhibiting oxidation and nitrification, regulating free radicals, and mediating nitric oxide(NO)/inducible nitric oxide synthase(iNOS) signals. Furthermore, mediating the activation of Janus kinase 2(JAK2)/STAT3/suppressor of cytokine signaling 3(SOCS3) signaling pathway and phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt)/glycogen synthase kinase-3ß(GSK3ß) signaling pathway and regulating the release of matrix metalloproteinase(MMP) inhibitor/MMP are main ways that C. tinctorius inhibits neuronal apoptosis. In addition, C. tinctorius exerts the therapeutic effect on ischemic stroke by regulating autophagy and endoplasmic reticulum stress. The present study reviewed the molecular mechanisms of C. tinctorius in the treatment of ischemic stroke to provide references for the clinical application of C. tinctorius.


Asunto(s)
Carthamus tinctorius , Chalcona , Flavonoides , Accidente Cerebrovascular Isquémico , Carthamus tinctorius/química , Chalcona/análogos & derivados , Chalcona/farmacología , Chalcona/uso terapéutico , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Flavonoides/farmacología , Flavonoides/uso terapéutico , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Janus Quinasa 2/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Prostaglandina D2 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinonas/farmacología
10.
J Antimicrob Chemother ; 76(2): 312-321, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33128052

RESUMEN

OBJECTIVES: Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii. PATIENTS AND METHODS: This retrospective study enrolled 80 adults with A. seifertii bloodstream infection (BSI) at four medical centres over an 8 year period. Species identification was confirmed by MALDI-TOF MS, rpoB sequencing and WGS. Molecular typing was performed by MLST. Clinical information, antimicrobial susceptibility and the mechanisms of carbapenem and colistin resistance were analysed. Transmissibility of the carbapenem-resistance determinants was examined by conjugation experiments. RESULTS: The main source of A. seifertii BSI was the respiratory tract (46.3%). The 28 day and in-hospital mortality rates of A. seifertii BSI were 18.8% and 30.0%, respectively. High APACHE II scores and immunosuppressant therapy were independent risk factors for 28 day mortality. The most common MLST type was ST553 (58.8%). Most A. seifertii isolates were susceptible to levofloxacin (86.2%), and only 37.5% were susceptible to colistin. Carbapenem resistance was observed in 16.3% of isolates, mostly caused by the plasmid-borne ISAba1-blaOXA-51-like genetic structure. A. seifertii could transfer various carbapenem-resistance determinants to A. baumannii, Acinetobacter nosocomialis and other A. seifertii isolates. Variations of pmrCAB and lpxCAD genes were not associated with colistin resistance of A. seifertii. CONCLUSIONS: Levofloxacin and carbapenems, but not colistin, have the potential to be the drug of choice for A. seifertii infections. A. seifertii can transfer carbapenem-resistance determinants to other species of the A. baumannii group and warrants close monitoring.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Acinetobacter , Acinetobacter/genética , Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/genética , Adulto , Antibacterianos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Estudios Retrospectivos , Taiwán/epidemiología , beta-Lactamasas
11.
Nanotechnology ; 33(9)2021 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-34798622

RESUMEN

Quantum interference (QI) in single molecular junctions shows a promising perspective for realizing conceptual nanoelectronics. However, controlling and modulating the QI remains a big challenge. Herein, two-type substituents at different positions ofmeta-linked benzene, namely electron-donating methoxy (-OMe) and electron-withdrawing nitryl (-NO2), are designed and synthesized to investigate the substituent effects on QI. The calculated transmission coefficientsT(E) indicates that -OMe and -NO2could remove the antiresonance and destructive quantum interference (DQI)-induced transmission dips at position 2. -OMe could raise the antiresonance energy at position 4 while -NO2groups removes the DQI features. For substituents at position 5, both of them are nonactive for tuning QI. The conductance measurements by scanning tunneling microscopy break junction show a good agreement with the theoretical prediction. More than two order of magnitude single-molecule conductance on/off ratio could be achieved at the different positions of -NO2substituent groups at room temperature. The present work proves chemical substituents can be used for tuning QI features in single molecular junctions, which provides a feasible way toward realization of high-performance molecular devices.

12.
Phytother Res ; 35(8): 4511-4525, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34236105

RESUMEN

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1  day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.


Asunto(s)
Bibencilos/farmacología , Neoplasias Pulmonares , Fenol/farmacología , Transducción de Señal/efectos de los fármacos , Células A549 , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Dendrobium , Humanos , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , Ratones , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TOR
13.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-34576032

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.


Asunto(s)
COVID-19/complicaciones , Enfermedades Cardiovasculares/inmunología , Síndrome de Liberación de Citoquinas/inmunología , SARS-CoV-2/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/inmunología , COVID-19/patología , COVID-19/virología , Enfermedades Cardiovasculares/virología , Diferenciación Celular , Línea Celular , Biología Computacional , Proteínas de la Nucleocápside de Coronavirus/metabolismo , Síndrome de Liberación de Citoquinas/patología , Síndrome de Liberación de Citoquinas/virología , Humanos , Células Madre Pluripotentes Inducidas , Miocardio/citología , Miocardio/inmunología , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/virología , Fosfoproteínas/metabolismo , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidad , Serina Endopeptidasas/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Regulación hacia Arriba/inmunología , Internalización del Virus/efectos de los fármacos
14.
Int J Mol Sci ; 22(21)2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34769137

RESUMEN

Cisplatin-based chemotherapy is the standard treatment for bladder urothelial carcinoma (UC). Most patients experience chemoresistance, the primary cause of treatment failure, which leads to disease relapse. The underlying mechanism of chemoresistance involves reduced apoptosis. In this study, we investigated the antitumor effect of the deubiquitylating enzyme inhibitor PR-619 in cisplatin-resistant bladder UC. Deubiquitinase (ubiquitin-specific protease 14 (USP14) and USP21) immunohistochemical staining demonstrated that deubiquitination is related to chemoresistance in patients with metastatic UC and may be a target for overcoming chemoresistance. Cytotoxicity and apoptosis were assessed using fluorescence-activated flow cytometry and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay, and PR-619 was found to enhance the cytotoxic and apoptotic effects of cisplatin in cisplatin-resistant T24/R cells. Mitigated cisplatin chemoresistance was associated with the concurrent suppression of c-Myc expression in T24/R cells. Moreover, the expression of c-Myc was upregulated in human bladder UC specimens from patients with chemoresistance. Experiments in a xenograft nude mouse model confirmed that PR-619 enhanced the antitumor effects of cisplatin. These results are promising for the development of therapeutic strategies to prevent UC chemoresistance through the combined use of chemotherapeutic agents/deubiquitination inhibitors (PR-619) by targeting the c-Myc pathway.


Asunto(s)
Aminopiridinas/uso terapéutico , Carcinoma/tratamiento farmacológico , Enzimas Desubicuitinizantes/antagonistas & inhibidores , Resistencia a Antineoplásicos/efectos de los fármacos , Tiocianatos/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Aminopiridinas/farmacología , Animales , Antineoplásicos/uso terapéutico , Carcinoma/metabolismo , Línea Celular Tumoral , Cisplatino/uso terapéutico , Humanos , Ratones Desnudos , Tiocianatos/farmacología , Ubiquitina Tiolesterasa/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
15.
J Xray Sci Technol ; 28(4): 683-694, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32568166

RESUMEN

BACKGROUND: In regular examinations, it may be difficult to visually identify benign and malignant liver tumors based on plain computed tomography (CT) images. RCAD (radiomics-based computer-aided diagnosis) has proven to be helpful and provide interpretability in clinical use. OBJECTIVE: This work aims to develop a CT-based radiomics signature and investigate its correlation with malignant/benign liver tumors. METHODS: We retrospectively analyzed 168 patients of hepatocellular carcinoma (malignant) and 117 patients of hepatic hemangioma (benign). Texture features were extracted from plain CT images and used as candidate features. A radiomics signature was developed from the candidate features. We performed logistic regression analysis and used a multiple-regression coefficient (termed as R) to assess the correlation between the developed radiomics signature and malignant/benign liver tumors. Finally, we built a logistic regression model to classify benign and malignant liver tumors. RESULTS: Thirteen features were chosen from 1223 candidate features to constitute the radiomics signature. The logistic regression analysis achieved an R = 0.6745, which was much larger than Rα = 0.3703 (the critical value of R at significant level α = 0.001). The logistic regression model achieved an average AUC of 0.87. CONCLUSIONS: The developed radiomics signature was statistically significantly correlated with malignant/benign liver tumors (p < 0.001). It has potential to help enhance physicians' diagnostic abilities and play an important role in RCADs.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Hemangioma/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Diagnóstico Diferencial , Humanos , Análisis de Regresión , Sensibilidad y Especificidad
17.
Eur J Clin Microbiol Infect Dis ; 38(11): 2045-2052, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31352669

RESUMEN

Elizabethkingia genus is emerging in hospitals and resistant to multiple antibiotics. The intrinsic imipenem resistance of Elizabethkingia genus is related to two chromosome-encoded metallo-beta-lactamases (MBLs), BlaB and GOB. This study was aimed to investigate the in vitro activity of imipenem, vancomycin, and rifampicin in clinical Elizabethkingia species. The distribution and heterogeneity of MBLs responsible for imipenem resistance were also evaluated. A total of 167 Elizabethkingia isolates from different patients were collected, including E. anophelis (142), E. meningoseptica (11), and E. miricola (14). All isolates were evaluated by the broth microdilution assay, ethylenediaminetetraacetic acid (EDTA) combination disk test, and EDTA-based microdilution test. The characteristics of BlaB and GOB were evaluated in phylogenetic analysis and heterologous expression experiments. Most of the isolates were susceptible to rifampin (94%), whereas none of the isolates were susceptible to imipenem. Vancomycin showed intermediate effectiveness. EDTA could reduce 4 folds or more minimum inhibitory concentrations (MICs) of imipenem in 105 isolates (62.9%). Of the isolates, the amino acid sequences of BlaB and GOB were divided into 22 and 25 different types, respectively. Phylogenetic analysis showed BlaB and GOB are species-specific proteins. Furthermore, GOB and BlaB from E. anophelis showed higher imipenem hydrolysis efficiency than those from the other two species. Rifampicin remained the most active agent in the current study. The mechanism of Elizabethkingia resistance to imipenem primarily stemmed from MBLs but other mechanisms could also exist, which requires further investigation.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Infecciones por Flavobacteriaceae/microbiología , Flavobacteriaceae/efectos de los fármacos , Flavobacteriaceae/aislamiento & purificación , beta-Lactamasas/metabolismo , Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Ácido Edético/farmacología , Flavobacteriaceae/clasificación , Flavobacteriaceae/enzimología , Humanos , Imipenem/farmacología , Pruebas de Sensibilidad Microbiana , Filogenia , Rifampin/farmacología , Especificidad de la Especie , Vancomicina/farmacología , beta-Lactamasas/genética
18.
J Nanosci Nanotechnol ; 19(5): 2794-2798, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30501782

RESUMEN

In this paper, single molecular junctions of Para-phthalic acid and Meta-phthalic acid with Au electrodes were studied by STM break junction approach. Conductance values of 10-3.55 G0 and 10-3.70 G0 were found for Para-phthalic acid and Meta-phthalic acid, respectively. The conductance order between Para-phthalic acid and Meta-phthalic acid with Au is different from that with Cu, which can be contributed to the different coupling between molecules and electrodes; different through-space interaction is proposed for such phenomenon between Cu and Au electrodes. Furthermore, the breaking off distances can reflect the length of molecules. The current work presents the important role of electrode in single molecular junctions with different position anchoring groups.

19.
J Intensive Care Med ; 33(6): 361-369, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27872410

RESUMEN

PURPOSE: Bloodstream infections (BSIs) caused by Acinetobacter species have been extensively reported, however, which majorly focused on respiratory tract infections. The risk of mortality and the effect of early catheter removal on survival in catheter-related BSIs (CRBSIs) caused by Acinetobacter spp. remain unclear. This study aims to investigate that. METHODS: This is a retrospective multicentric study conducted in Taiwan from 2012 to 2014. Patients with at least 1 positive blood culture and catheter culture for the same Acinetobacter spp., showing symptoms and signs of CRBSIs, were included (n = 119). Risk factors for 30-day mortality were analyzed using a logistic regression model. The characteristics of patients with early catheter removal (within 48 hours after CRBSIs) were compared to those without removal matching for age, sex, and disease severity. RESULTS: There were no differences in 30-day mortality with regard to causative Acinetobacter spp., catheter type, site, and appropriateness of antimicrobial therapy. Patients with higher Acute Physiologic and Chronic Health Evaluation (APACHE) II scores (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.02-1.23; P = .014), shock (OR: 6.43; 95% CI: 1.28-32.33; P = .024), and longer hospitalization before CRBSIs (OR: 1.04; 95% CI: 1.00-1.08; P = .027) had a significantly higher 30-day mortality rate. Early removal of catheters after CRBSIs was not associated with better survival benefits. CONCLUSION: Higher disease severity (APACHE II score), shock, and longer hospitalization before bacteremia were independently associated with a higher 30-day mortality in CRBSIs caused by Acinetobacter spp. In previous published guidelines, infected catheters were suggested to be removed in CRBSIs caused by gram-negative bacilli. Even though early removal of catheters did not associate with a better survival outcome in current results, it should be judiciously evaluated according to the clinical conditions and risks individually. For better elucidation of these issues, further well-controlled prospective study may be warranted.


Asunto(s)
Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/mortalidad , Acinetobacter/aislamiento & purificación , Antiinfecciosos/uso terapéutico , Infecciones Relacionadas con Catéteres/microbiología , Infecciones Relacionadas con Catéteres/mortalidad , Cuidados Críticos , Remoción de Dispositivos/estadística & datos numéricos , APACHE , Infecciones por Acinetobacter/terapia , Adulto , Anciano , Infecciones Relacionadas con Catéteres/terapia , Remoción de Dispositivos/mortalidad , Femenino , Guías como Asunto , Mortalidad Hospitalaria , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Taiwán
20.
Proc Natl Acad Sci U S A ; 112(50): 15510-5, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26621710

RESUMEN

We propose and test a theoretical perspective in which a universal hallmark of successful literacy acquisition is the convergence of the speech and orthographic processing systems onto a common network of neural structures, regardless of how spoken words are represented orthographically in a writing system. During functional MRI, skilled adult readers of four distinct and highly contrasting languages, Spanish, English, Hebrew, and Chinese, performed an identical semantic categorization task to spoken and written words. Results from three complementary analytic approaches demonstrate limited language variation, with speech-print convergence emerging as a common brain signature of reading proficiency across the wide spectrum of selected languages, whether their writing system is alphabetic or logographic, whether it is opaque or transparent, and regardless of the phonological and morphological structure it represents.


Asunto(s)
Encéfalo/fisiología , Lenguaje , Lectura , Análisis de Varianza , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Habla , Análisis y Desempeño de Tareas , Adulto Joven
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