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1.
Antibiotics (Basel) ; 12(12)2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38136742

RESUMEN

With the increasing challenge of controlling infectious diseases due to the emergence of antibiotic-resistant strains, the importance of discovering new antimicrobial agents is rapidly increasing. Animal venoms contain a variety of functional peptides, making them a promising platform for pharmaceutical development. In this study, a novel toxin peptide with antibacterial and anti-inflammatory activities was discovered from the spider venom gland transcriptome by implementing computational approaches. Lycotoxin-Pa2a (Lytx-Pa2a) showed homology to known-spider toxin, where functional prediction indicated the potential of both antibacterial and anti-inflammatory peptides without hemolytic activity. The colony-forming assay and minimum inhibitory concentration test showed that Lytx-Pa2a exhibited comparable or stronger antibacterial activity against pathogenic strains than melittin. Following mechanistic studies revealed that Lytx-Pa2a disrupts both cytoplasmic and outer membranes of bacteria while simultaneously inducing the accumulation of reactive oxygen species. The peptide exerted no significant toxicity when treated to human primary cells, murine macrophages, and bovine red blood cells. Moreover, Lytx-Pa2a alleviated lipopolysaccharide-induced inflammation in mouse macrophages by suppressing the expression of inflammatory mediators. These findings not only suggested that Lytx-Pa2a with dual activity can be utilized as a new antimicrobial agent for infectious diseases but also demonstrated the implementation of in silico methods for discovering a novel functional peptide, which may enhance the future utilization of biological resources.

2.
Toxins (Basel) ; 15(12)2023 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-38133172

RESUMEN

The escalating prevalence of antibiotic-resistant bacteria poses an immediate and grave threat to public health. Antimicrobial peptides (AMPs) have gained significant attention as a promising alternative to conventional antibiotics. Animal venom comprises a diverse array of bioactive compounds, which can be a rich source for identifying new functional peptides. In this study, we identified a toxin peptide, Lycotoxin-Pa1a (Lytx-Pa1a), from the transcriptome of the Pardosa astrigera spider venom gland. To enhance its functional properties, we employed an in silico approach to design a novel hybrid peptide, KFH-Pa1a, by predicting antibacterial and cytotoxic functionalities and incorporating the amino-terminal Cu(II)- and Ni(II) (ATCUN)-binding motif. KFH-Pa1a demonstrated markedly superior antimicrobial efficacy against pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa, compared to Lytx-Pa1a. Notably, KFH-Pa1a exerted several distinct mechanisms, including the disruption of the bacterial cytoplasmic membrane, the generation of intracellular ROS, and the cleavage and inhibition of bacterial DNA. Additionally, the hybrid peptide showed synergistic activity when combined with conventional antibiotics. Our research not only identified a novel toxin peptide from spider venom but demonstrated in silico-based design of hybrid AMP with strong antimicrobial activity that can contribute to combating MDR pathogens, broadening the utilization of biological resources by incorporating computational approaches.


Asunto(s)
Antiinfecciosos , Venenos de Araña , Animales , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Pseudomonas aeruginosa , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Bacterias , Venenos de Araña/farmacología , Pruebas de Sensibilidad Microbiana
3.
Bioengineering (Basel) ; 10(8)2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37627813

RESUMEN

Accurate segmentation of infected lesions in chest images remains a challenging task due to the lack of utilization of lung region information, which could serve as a strong location hint for infection. In this paper, we propose a novel segmentation network Co-ERA-Net for infections in chest images that leverages lung region information by enhancing supervised information and fusing multi-scale lung region and infection information at different levels. To achieve this, we introduce a Co-supervision scheme incorporating lung region information to guide the network to accurately locate infections within the lung region. Furthermore, we design an Enhanced Region Attention Module (ERAM) to highlight regions with a high probability of infection by incorporating infection information into the lung region information. The effectiveness of the proposed scheme is demonstrated using COVID-19 CT and X-ray datasets, with the results showing that the proposed schemes and modules are promising. Based on the baseline, the Co-supervision scheme, when integrated with lung region information, improves the Dice coefficient by 7.41% and 2.22%, and the IoU by 8.20% and 3.00% in CT and X-ray datasets respectively. Moreover, when this scheme is combined with the Enhanced Region Attention Module, the Dice coefficient sees further improvement of 14.24% and 2.97%, with the IoU increasing by 28.64% and 4.49% for the same datasets. In comparison with existing approaches across various datasets, our proposed method achieves better segmentation performance in all main metrics and exhibits the best generalization and comprehensive performance.

4.
Front Microbiol ; 14: 1249175, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37577428

RESUMEN

As the emergence and prevalence of antibiotic-resistant strains have resulted in a global crisis, there is an urgent need for new antimicrobial agents. Antimicrobial peptides (AMPs) exhibit inhibitory activity against a wide spectrum of pathogens and can be utilized as an alternative to conventional antibiotics. In this study, two novel AMPs were identified from the venom transcriptome of the spider Argiope bruennichi (Scopoli, 1772) using in silico methods, and their antimicrobial activity was experimentally validated. Aranetoxin-Ab2a (AATX-Ab2a) and Aranetoxin-Ab3a (AATX-Ab3a) were identified by homology analysis and were predicted to have high levels of antimicrobial activity based on in silico analysis. Both peptides were found to have antibacterial effect against Gram-positive and -negative strains, and, in particular, showed significant inhibitory activity against multidrug-resistant Pseudomonas aeruginosa isolates. In addition, AATX-Ab2a and AATX-Ab3a inhibited animal and vegetable fungal strains, while showing low toxicity to normal human cells. The antimicrobial activity of the peptides was attributed to the increased permeability of microbial membranes. The study described the discovery of novel antibiotic candidates, AATX-Ab2a and AATX-Ab3a, using the spider venom gland transcriptome, and validated an in silico-based method for identifying functional substances from biological resources.

5.
Zootaxa ; 5239(3): 301-357, 2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-37045095

RESUMEN

A key to the six Australian genera of the wolf spider (Lycosidae Sundevall, 1833) subfamily Artoriinae Framenau, 2007 is provided, now including Artoria Thorell, 1877, Artoriopsis Framenau, 2007, Diahogna Roewer, 1960, Kangarosa Framenau, 2010, Kochosa gen. nov. and Tetralycosa Roewer, 1960. Kochosa gen. nov. is described to include 16 species: K. australia sp. nov. (type species; from New South Wales, Queensland, South Australia, Victoria, Western Australia), K. aero sp. nov. (Western Australia), K. asterix sp. nov. (New South Wales, Queensland, Tasmania and Victoria), K. confusa sp. nov. (Queensland), K. erratum sp. nov. (Queensland), K. fleurae sp. nov. (Victoria), K. mendum sp. nov. (Australian Capital Territory, New South Wales, Queensland), K. nigra sp. nov. (Queensland), K. obelix sp. nov. (Western Australia), K. queenslandica sp. nov. (Queensland), K. sharae sp. nov. (South Australia), K. tanakai sp. nov. (New South Wales, Queensland), K. tasmaniensis sp. nov. (Tasmania), K. timwintoni sp. nov. (Western Australia), K. tongiorgii sp. nov., (Queensland), and K. westralia sp. nov. (Western Australia). Kochosa gen. nov. differs distinctly from all other genera within the Artoriinae by somatic and genitalic morphology. Most conspicuous is a distinct off-white or yellowish-white cardiac mark on an otherwise generally uniformly dark abdomen. The cardiac mark is rendered by thick black setae, which are particularly dense posteriorly. The tegular apophysis of the male pedipalp is heavily reduced, generally forming a semi-transparent small lobe. In turn, the embolic division is often complex with a variety of apophyses. Kochosa gen. nov. generally inhabit mesic habitats such as temperate and tropical shrubs and forests along the eastern and south-eastern coast and in the south-western parts of Australia.


Asunto(s)
Arañas , Animales
6.
Zookeys ; 1178: 97-114, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38318118

RESUMEN

Five new spider species of the genus Pholcus Walckenaer, 1805, P.duryunsp. nov., P.hwaamsp. nov., P.mohangsp. nov., P.woraksp. nov., and P.yangpyeongsp. nov., belonging to the P.phungiformes group in the family Pholcidae C. L. Koch, 1850, are newly described from South Korea. These new species were collected from mixed forests in mountainous, hilly, and coastal terrains. This study provides the diagnoses, detailed descriptions, distribution maps, and taxonomic photographs of these new species.

7.
J Immunother Cancer ; 10(9)2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36096527

RESUMEN

BACKGROUND: Immunotherapy is revolutionizing cancer treatment from conventional radiotherapies and chemotherapies to immune checkpoint inhibitors which use patients' immune system to recognize and attack cancer cells. Despite the huge clinical success and vigorous development of immunotherapies, there is a significant unmet need for a robust tool to identify responders to specific immunotherapy. Early and accurate monitoring of immunotherapy response is indispensable for personalized treatment and effective drug development. METHODS: We established a label-free metabolic intravital imaging (LMII) technique to detect two-photon excited autofluorescence signals from two coenzymes, NAD(P)H (reduced nicotinamide adenine dinucleotide (phosphate) hydrogen) and FAD (flavin adenine dinucleotide) as robust imaging markers to monitor metabolic responses to immunotherapy. Murine models of triple-negative breast cancer (TNBC) were established and tested with different therapeutic regimens including anti-cluster of differentiation 47 (CD47) immunotherapy to monitor time-course treatment responses using the developed metabolic imaging technique. RESULTS: We first imaged the mechanisms of the CD47-signal regulatory protein alpha pathway in vivo, which unravels macrophage-mediated antibody-dependent cellular phagocytosis and illustrates the metabolism of TNBC cells and macrophages. We further visualized the autofluorescence of NAD(P)H and FAD and found a significant increase during tumor growth. Following anti-CD47 immunotherapy, the imaging signal was dramatically decreased demonstrating the sensitive monitoring capability of NAD(P)H and FAD imaging for therapeutic response. NAD(P)H and FAD intravital imaging also showed a marked decrease after chemotherapy and radiotherapy. A comparative study with conventional whole-body bioluminescence and fluorescent glucose imaging demonstrated superior sensitivity of metabolic imaging. Flow cytometry validated metabolic imaging results. In vivo immunofluorescent staining revealed the targeting ability of NAD(P)H imaging mainly for tumor cells and a small portion of immune-active cells and that of FAD imaging mainly for immunosuppressive cells such as M2-like tumor-associated macrophages. CONCLUSIONS: Collectively, this study showcases the potential of the LMII technique as a powerful tool to visualize dynamic changes of heterogeneous cell metabolism of cancer cells and immune infiltrates in response to immunotherapy thus providing sensitive and complete monitoring. Leveraged on ability to differentiate cancer cells and immunosuppressive macrophages, the presented imaging approach provides particularly useful imaging biomarkers for emerged innate immune checkpoint inhibitors such as anti-CD47 therapy.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Animales , Flavina-Adenina Dinucleótido/metabolismo , Humanos , Inhibidores de Puntos de Control Inmunológico , Factores Inmunológicos , Inmunoterapia/métodos , Ratones , NAD , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico
8.
Front Microbiol ; 13: 971503, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36090084

RESUMEN

Antimicrobial peptides (AMPs) show promises as valuable compounds for developing therapeutic agents to control the worldwide health threat posed by the increasing prevalence of antibiotic-resistant bacteria. Animal venom can be a useful source for screening AMPs due to its various bioactive components. Here, the deep learning model was developed to predict species-specific antimicrobial activity. To overcome the data deficiency, a multi-task learning method was implemented, achieving F1 scores of 0.818, 0.696, 0.814, 0.787, and 0.719 for Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, respectively. Peptides PA-Full and PA-Win were identified from the model using different inputs of full and partial sequences, broadening the application of transcriptome data of the spider Pardosa astrigera. Two peptides exhibited strong antimicrobial activity against all five strains along with cytocompatibility. Our approach enables excavating AMPs with high potency, which can be expanded into the fields of biology to address data insufficiency.

9.
Cancers (Basel) ; 14(15)2022 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-35954443

RESUMEN

The implementation of DP will revolutionize current practice by providing pathologists with additional tools and algorithms to improve workflow. Furthermore, DP will open up opportunities for development of AI-based tools for more precise and reproducible diagnosis through computational pathology. One of the key features of AI is its capability to generate perceptions and recognize patterns beyond the human senses. Thus, the incorporation of AI into DP can reveal additional morphological features and information. At the current rate of AI development and adoption of DP, the interest in computational pathology is expected to rise in tandem. There have already been promising developments related to AI-based solutions in prostate cancer detection; however, in the GI tract, development of more sophisticated algorithms is required to facilitate histological assessment of GI specimens for early and accurate diagnosis. In this review, we aim to provide an overview of the current histological practices in AP laboratories with respect to challenges faced in image preprocessing, present the existing AI-based algorithms, discuss their limitations and present clinical insight with respect to the application of AI in early detection and diagnosis of GI cancer.

10.
Front Immunol ; 13: 821070, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35432369

RESUMEN

As spider venom is composed of various bioactive substances, it can be utilized as a platform for discovering future therapeutics. Host defense peptides are great candidates for developing novel antimicrobial agents due to their multifunctional properties. In this study, novel functional peptides were rationally designed to have dual antibacterial and anti-inflammatory activities with high cytocompatibility. Based on a template sequence from the transcriptome of spider Agelena koreana, a series of via in silico analysis were conducted, incorporating web-based machine learning tools along with the alteration of amino acid residues. Two peptides, Ak-N' and Ak-N'm, were designed and were subjected to functional validation. The peptides inhibited gram-negative and gram-positive bacteria by disrupting the outer and bacterial cytoplasmic membrane. Moreover, the peptides down-regulated the expression of pro-inflammatory mediators, tumor necrosis factor-α, interleukin (IL)-1ß, and IL6. Along with low cytotoxicity, Ak-N'm was shown to interact with macrophage surface receptors, inhibiting both Myeloid differentiation primary response 88-dependent and TIR-domain-containing adapter-inducing interferon-ß-dependent pathways of Toll-like receptor 4 signaling on lipopolysaccharide-stimulated THP-1-derived macrophages. Here, we rationally designed functional peptides based on the suggested in silico strategy, demonstrating new insights for utilizing biological resources as well as developing therapeutic agents with enhanced properties.


Asunto(s)
Antiinfecciosos , Lipopolisacáridos , Antibacterianos , Antiinflamatorios/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Lipopolisacáridos/farmacología
11.
Zootaxa ; 4966(4): 458468, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-34186603

RESUMEN

The males of four new species of Cybaeus L. Koch, 1868 (Cybaeus yeongwolensis sp. nov., Cybaeus culter sp. nov., Cybaeus vanimaculatus sp. nov., and Cybaeus pseudoauriculatus sp. nov.) are described from leaf litter habitats in South Korea. We provide diagnoses, detailed descriptions, a key to the males of Korean Cybaeus species, and a distribution map for these new species. They appear to be endemic to South Korea and were collected from mixed forests in hilly and mountainous terrain.


Asunto(s)
Arañas/clasificación , Distribución Animal , Animales , Bosques , Masculino , República de Corea
12.
Zookeys ; 1010: 97-116, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33531858

RESUMEN

Five new leptonetid species belonging to Falcileptoneta Komatsu, 1970 and Longileptoneta Seo, 2015 are newly described from South Korea: F. dolsan sp. nov. (Jeollanam-do), F. naejangsan sp. nov. (Jeollabuk-do), L. buyongsan sp. nov. (Chungcheongbuk-do), L. byeonsanbando sp. nov. (Jeollabuk-do) and L. jirisan sp. nov. (Gyeongsangnam-do). All new species are found in leaf litter and described from both male and female specimens.

13.
Front Pharmacol ; 12: 777395, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35299724

RESUMEN

Many clinical studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have renoprotective properties by ameliorating albuminuria and increasing glomerular filtration rate in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) by lowering ectopic lipid accumulation in the kidney. However, the mechanism of GLP-1RAs was hitherto unknown. Here, we conducted an unbiased lipidomic analysis using ultra-high-performance liquid chromatography/electrospray ionization-quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to reveal the changes of lipid composition and distribution in the kidneys of high-fat diet-fed mice after treatment with a long-acting GLP-1RA dulaglutide for 4 weeks. Treatment of dulaglutide dramatically improved hyperglycemia and albuminuria, but there was no substantial improvement in dyslipidemia and ectopic lipid accumulation in the kidney as compared with controls. Intriguingly, treatment of dulaglutide increases the level of an essential phospholipid constituent of inner mitochondrial membrane cardiolipin at the cortex region of the kidneys by inducing the expression of key cardiolipin biosynthesis enzymes. Previous studies demonstrated that lowered renal cardiolipin level impairs kidney function via mitochondrial damage. Our untargeted lipidomic analysis presents evidence for a new mechanism of how GLP-1RAs stimulate mitochondrial bioenergetics via increasing cardiolipin level and provides new insights into the therapeutic potential of GLP-1RAs in mitochondrial-related diseases.

14.
Cancers (Basel) ; 12(9)2020 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-32824974

RESUMEN

Glioblastoma is the most lethal intracranial primary malignancy by no optimal treatment option. Cancer immunotherapy has achieved remarkable survival benefits against various advanced tumors, such as melanoma and non-small-cell lung cancer, thus triggering great interest as a new therapeutic strategy for glioblastoma. Moreover, the central nervous system has been rediscovered recently as a region for active immunosurveillance. There are vibrant investigations for successful glioblastoma immunotherapy despite the fact that initial clinical trial results are somewhat disappointing with unique challenges including T-cell dysfunction in the patients. This review will explore the potential of current immunotherapy modalities for glioblastoma treatment, especially focusing on major immune checkpoint inhibitors and the future strategies with novel targets and combo therapies. Immune-related adverse events and clinical challenges in glioblastoma immunotherapy are also summarized. Glioblastoma provides persistent difficulties for immunotherapy with a complex state of patients' immune dysfunction and a variety of constraints in drug delivery to the central nervous system. However, rational design of combinational regimens and new focuses on myeloid cells and novel targets to circumvent current limitations hold promise to advent truly viable immunotherapy for glioblastoma.

15.
Zookeys ; 872: 1-12, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31496883

RESUMEN

Three new species of the genus Falcileptoneta Komatsu, 1970 belonging to the spider family Leptonetidae Simon 1890 are described from Korea. All species were collected from wet leaf litter layers.

16.
Eur J Pharm Sci ; 139: 105047, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31422171

RESUMEN

The translocator protein 18 kDa (TSPO) is mainly located in outer membrane of mitochondria and results highly expressed in a variety of tumor including breast, colon, prostate, ovarian and brain (such as glioblastoma). Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor. Although GBM patients had currently available therapies, the median survival is <14 months. Complete surgical resection of GBM is critical to improve GBM treatment. In this study, we performed the one-step synthesis of water-dispersible ultra-small iron oxide nanoparticles (USPIONs) and combine them with an imidazopyridine based TSPO ligand and a fluorescent dye. The optical and structural characteristics of TSPO targeted-USPIONs were properly evaluated at each step of preparation demonstrating the high colloidal stability in physiological media and the ability to preserve the relevant optical properties in the NIR region. The cellular uptake in TSPO expressing cells was assessed by confocal microscopy. The TSPO selectivity was confirmed in vivo by competition studies with the TSPO ligand PK 11195. In vivo fluorescence imaging of U87-MG xenograft models were performed to highlight the great potential of the new NIR imaging nanosystem for diagnosis and successful delineation of GBM.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Compuestos Férricos/administración & dosificación , Glioblastoma/diagnóstico por imagen , Nanopartículas/administración & dosificación , Receptores de GABA/metabolismo , Animales , Neoplasias Encefálicas/metabolismo , Carbocianinas/administración & dosificación , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colorantes Fluorescentes/administración & dosificación , Glioblastoma/metabolismo , Humanos , Isoquinolinas/farmacología , Ligandos , Masculino , Ratones Endogámicos BALB C , Imagen Óptica
17.
Sci Rep ; 8(1): 11122, 2018 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-30042406

RESUMEN

Glioblastoma multiforme (GBM) is the most aggressive and lethal type of human brain cancer. Surgery is a current gold standard for GBM treatment but the complete surgical resection of GBM is almost impossible due to their diffusive characteristics into surrounded normal brain tissues. There is an urgent need to develop a sensitive imaging tool for accurate delineation of GBM in the operating room to guide surgeons. Here we illustrate the feasibility of using near-infrared fluorescent silica coated iron oxide nanoparticles (NF-SIONs) with high water dispersion capacity and strong fluorescence stability for intraoperative imaging of GBM by targeting tumor-associated macrophages. Abundant macrophage infiltration is a key feature of GBM margins and it is well associated with poor prognosis. We synthesized NF-SIONs of about 37 nm to maximize endocytosis activity for macrophage uptake. The NF-SIONs selectively visualized tumor-associated macrophage populations by in vitro live-cell imaging and in vivo fluorescence imaging. In the orthotopic GBM xenograft models, the NF-SIONs could successfully penetrate blood-brain barrier and delineated tumor burden specifically. Taken together, this study showcased the potential applications in GBM treatment for improved intraoperative staging and more radical surgery as well as dual modality benefit in order to circumvent previous clinical failure.


Asunto(s)
Barrera Hematoencefálica/diagnóstico por imagen , Glioblastoma/diagnóstico por imagen , Macrófagos/efectos de los fármacos , Nanopartículas del Metal/administración & dosificación , Animales , Barrera Hematoencefálica/efectos de los fármacos , Línea Celular Tumoral , Imagen de Difusión por Resonancia Magnética , Compuestos Férricos/administración & dosificación , Compuestos Férricos/química , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Nanopartículas del Metal/química , Ratones , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/química , Ensayos Antitumor por Modelo de Xenoinjerto
18.
J Mater Chem B ; 5(3): 586-594, 2017 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-32263674

RESUMEN

Cancer nanomedicine involving nanotechnology-based drugs and in vivo imaging agents is an active field of nanoscience that provides new ways of enhancing therapeutic and diagnostic efficacy. Translating cancer nanomedicine mainly comes from rational and scalable design of nanoparticles to achieve versatile properties including specific size because nanomaterials whose properties confer unique advantages can only optimize clinical impact. Here, a facile scalable synthesis of highly monodisperse small silica nanoparticles was developed by screening various alkaline buffer solutions as catalysts. The size of silica nanoparticles ranging from 7 to 30 nm was finely controlled by varying the reaction temperature. Moderate sized silica nanoparticles in the range of 30 to 50 nm and large sized silica nanoparticles (>100 nm) were readily synthesized by in situ adding tetraethylorthosilicate (TEOS) and applying the Stöber method in the reaction solution using small silica nanoparticles as the seeds, respectively. Having shown the ability to precisely synthesize size controlled silica nanoparticles with a process compatible with good manufacturing practices, we performed in vivo fluorescence imaging and immunofluorescence analysis of sentinel lymph nodes (SLNs) with the synthesized nanoparticles having different sizes to investigate the size effect for effective identification of SLNs. The synthesized nanoparticles with a diameter of 12 nm showed effective SLN uptake within 10 min after intradermal injection both in noninvasive and in intraoperative imaging mode and were localized evenly inside the SLN, whereas the 120 nm sized nanoparticles failed to identify the SLN with noninvasive imaging at 10 min post-injection and distributed only in the medulla region not in the superficial cortex of the SLN. Taken together, a new facile scalable synthesis technique to achieve fine size controlling capability from very small silica nanoparticles (7 nm) was developed and it made possible to investigate the optimal size of nanoparticles for efficient SLN mapping which is still controversial.

19.
Sci Rep ; 6: 27520, 2016 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-27283041

RESUMEN

Cardiac healing after myocardial ischemia is a complex biological process. Advances in understanding of wound healing response have paved the way for clinical testing of novel molecular imaging to improve clinical outcomes. A key factor for assessing myocardial viability after ischemic injury is the evaluation of angiogenesis accompanying increased expression of integrin αvß3. Here, we describe the capability of an αvß3 integrin-targeting SPECT agent, (99m)Tc-IDA-D-[c(RGDfK)]2, for identification of ischemic but viable myocardium, i.e., hibernating myocardium which is crucial to predict functional recovery after revascularization, the standard care of cardiovascular medicine. In vivo SPECT imaging of rat models with transient coronary occlusion showed significantly high uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 in the ischemic region. Comparative measurements with (201)Tl SPECT and (18)F-FDG PET, then, proved that such prominent uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 was non-inferior to that of (18)F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of (99m)Tc-IDA-D-[c(RGDfK)]2 corresponded to the vibrant angiogenic events with elevated expression of αvß3 integrin. Together, these results establish that (99m)Tc-IDA-D-[c(RGDfK)]2 SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization.


Asunto(s)
Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Neovascularización Patológica/metabolismo , Oligopéptidos/metabolismo , Animales , Fluorodesoxiglucosa F18/metabolismo , Integrina alfaVbeta3/metabolismo , Masculino , Isquemia Miocárdica/metabolismo , Compuestos de Organotecnecio/metabolismo , Radiofármacos/metabolismo , Ratas , Ratas Sprague-Dawley , Tomografía Computarizada de Emisión de Fotón Único/métodos
20.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(3): 1878-9, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-25319303

RESUMEN

The complete mitochondrial genome (KM507783) of the green crab spider Oxytate striatipes was determined. The mitochondrial genome of O. striatipes was 14,407 bp long with a total base composition of 35.80% A, 42.40% T, 8.60% C, and 13.20% G. Total length of 13 protein-coding genes was 10,801 bp and 9 of them were encoded on heavy strand. COX1 started with TTA, uncommon start codon in invertebrate mitogenomes. The total length of 22 tRNA genes was 1202 bp, varying from 46 bp (tRNA(Thr)) to 67 bp (tRNA(Trp) and tRNA(Gln)). The standard cloverleaf secondary structure was found in 8 tRNA genes and TV-replacement loop was not found in the other 14 tRNA genes.


Asunto(s)
Genoma Mitocondrial , Arañas/genética , Animales , Composición de Base/genética , Emparejamiento Base/genética , ADN Mitocondrial/genética , Genes Mitocondriales , Anotación de Secuencia Molecular , ARN de Transferencia/genética
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