RESUMEN
Our previous research revealed that androgen receptor (AR) activation reduces endothelial cell proliferation via non-genomic pathways. We hypothesized that AR activation might also affect endothelial cell migration, a critical step in angiogenesis. Our data demonstrates that treatment of human umbilical vein endothelial cells (HUVECs) with AR agonists, metribolone (R1881) or dihydrotestosterone (DHT), results in a dose-dependent reduction in migration, which can be reversed by AR antagonists or AR knockdown. Mechanistically, R1881 inhibits HUVEC migration by suppressing RhoA activity through the cSrc/FAK/paxillin pathway and promoting RhoA degradation via RhoA-p27 complex formation, ultimately resulting in RhoA ubiquitination. Transfection with constitutively active RhoA-V14 rescues the inhibitory effect of R1881 on HUVEC migration. Furthermore, R1881 elevates intracellular vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) levels but reduces VEGF secretion from HUVECs. This reduction is attributed to the formation of VEGF-CTGF complexes in the cytosol induced by R1881. Transfection with RhoA-V14 reduces CTGF levels and VEGF-CTGF complex formation, leading to enhanced VEGF secretion. Pre-treatment with WP631, a CTGF inhibitor, mitigates the R1881-induced reduction in VEGF secretion and HUVECs migration. In vivo assessments using zebrafish angiogenesis and mouse matrigel plug assays validate the anti-angiogenic effects of R1881. These findings provide insight into the molecular mechanisms through which AR activation modulates endothelial cell migration and angiogenesis.
RESUMEN
During the COVID-19 pandemic, the use of lateral flow assays (LFAs) expanded significantly, offering testing beyond traditional health care. Their appeal lies in the ease of use, affordability, and quick results. However, LFAs often have lower sensitivity and specificity compared with ELISA and PCR tests. Efforts to improve LFAs have increased detection times and complexity, limiting their use in large-scale point-of-care settings. To address this, we propose a novel approach using probes that generate multiple signals to enhance the sensitivity and selectivity. This concept also allows multiplexed LFAs to detect multiple analytes concurrently. We developed a trimodal probe that integrates fluorescence, color, and magnetism into a single nanohybrid. The strong plasmonic absorption and high fluorescence of Au nanoparticles and polymer dots enable qualitative and semiquantitative diagnosis, while the magnetic signal facilitates accurate quantitative measurements. As proof-of-concept targets, we selected CYFRA 21-1 and CA15-3, biomarkers for lung and breast cancer, respectively. This trimodal LFA demonstrated a remarkable detection limit of 0.26 ng/mL for CYFRA 21-1 and 2.8 U/mL for CA15-3. To the best of our knowledge, this is the first platform of a trimodal LFA with multiplexing ability. The platform's accuracy and reliability were validated using clinical serum samples, showing excellent consistency with electrochemiluminescence immunoassay results. This universal concept can be applied to other targets, paving the way for the next-generation LFAs.
RESUMEN
Intricate signaling cascades involving chemokines and their cognate receptors on neoplastic and immune constituents within tumor microenvironment have garnered substantial research interest. Our investigation delineates the contribution of Chemokine (C-C motif) ligand 16 (CCL16) to the clinico-pathological features and tumorigenesis of hepatocellular carcinoma (HCC). Analysis of 237 pairs of HCC specimens unraveled a significant association between CCL16 expression and vascular invasion, early-stage clinicopathological features, and diminished recurrence-free survival among HCC patients. Immunohistochemical (IHC) assays of the clinical HCC specimens indicated elevated CCL16 in tumorous versus normal hepatic tissues. Our in vivo experiments demonstrated CCL16 overexpression fostered tumor proliferation, whereas in vitro assays elucidated that CCL16-mediated chemotactic recruitment of monocytes and M2 macrophages was orchestrated via CCR1 and CCR5. In contrast to previous claims that CCL16 is physiologically irrelevant and has minimal affinity for its receptors (CCR1, CCR2, CCR5, CCR8), our findings unravel that inhibition of CCL16/CCR1 and CCL16/CCR5 interactions through receptor-specific antagonists markedly impeded CCL16-directed chemotaxis, migration, adhesion, and leukocyte recruitment. Moreover, CCL16-overexpression in HCCs significantly augmented levels of several cytokines implicated in tumor progression, namely IL-6, IL-10 and VEGFA. IHC analysis of CCL16-overexpressing xenografts elicited greatly enhanced levels of VEGFA and IL-6, while assessments of HCC specimens confirmed a positive correlation between CCL16 expression and IL-6 and VEGFA levels. Collectively, our study highlights oncogenic role of CCL16 in hepatocarcinogenesis and provides a foundational basis for novel therapeutic interventions targeting the CCL16/CCR1/CCR5 axis.
RESUMEN
BACKGROUND: The kojyl 3-aminopropylphosphonic acid (KAP) was synthesized by kojic acid (KA) with a 3-aminopropylphosphonic acid. Which is more stable than KA and showed better skin penetration and anti-pigmentation efficacy in melanocytes. However, up till now, there have been no studies aimed at incorporating KAP into an emulsion system and evaluating its effectiveness. OBJECTIVE: We develop a novel skin-lightening agent using KAP as the active ingredient and a low-cytotoxic nanoemulsion as the delivery system in this study. METHOD: The sorbitan monooleate and polysorbate surfactants with polyethylene glycol (PEG) co-surfactant were used to generate a nanoemulsion system. RESULT: The transparency and particle size stability over various storage times indicate that the formulated nanoemulsions are suitable for long-term storage. Besides, results demonstrate that the anti-pigmentation function of KA and KAP-containing nanoemulsions (NE-KA and NEKAP) evidently outperformed that of the non-packed KA and KAP group. Despite having the lowest concentration among other treatments, NE-KAP was able to reduce melanin content to approximately 80% of the blank. CONCLUSION: Our findings suggest that this newly developed nanoemulsion containing KAP could potentially serve as a sustainable alternative to hydroquinone for treating dermal hyperpigmentation disorders in future applications.
RESUMEN
Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV's involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan's National Health Research Institutes, 2.7% (8/300) tested anti-HDV positive, with 62.7% (5/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial-mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.
Asunto(s)
Carcinoma Hepatocelular , Variación Genética , Genotipo , Virus de la Hepatitis Delta , Neoplasias Hepáticas , Carcinoma Hepatocelular/virología , Virus de la Hepatitis Delta/genética , Humanos , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Carcinogénesis/genética , Femenino , Taiwán , Evolución Molecular , Replicación Viral , Filogenia , ARN Viral/genética , Hepatitis D/virología , Anciano , Virus de la Hepatitis B/genéticaRESUMEN
BACKGROUND: Second-generation antipsychotics increase the risk of atrial fibrillation. This study explores whether the atypical antipsychotic ziprasidone triggers inflammasome signaling, leading to atrial arrhythmia. METHODS: Electromechanical and pharmacological assessments were conducted on the rabbit left atria (LA). The patch-clamp technique was used to measure ionic channel currents in single cardiomyocytes. Detection of cytosolic reactive oxygen species production was performed in atrial cardiomyocytes. RESULTS: The duration of action potentials at 50 % and 90 % repolarization was dose-dependently shortened in ziprasidone-treated LA. Diastolic tension in LA increased after ziprasidone treatment. Ziprasidone-treated LA showed rapid atrial pacing (RAP) triggered activity. PI3K inhibitor, Akt inhibitor and mTOR inhibitor abolished the triggered activity elicited by ziprasidone in LA. The NLRP3 inhibitor MCC950 suppressed the ziprasidone-induced post-RAP-triggered activity. MCC950 treatment reduced the reverse-mode Na+/Ca2+ exchanger current in ziprasidone-treated myocytes. Cytosolic reactive oxygen species production decreased in ziprasidone-treated atrial myocytes after MCC950 treatment. Protein levels of inflammasomes and proinflammatory cytokines, including NLRP3, caspase-1, IL-1ß, IL-18, and IL-6 were observed to be upregulated in myocytes treated with ziprasidone. CONCLUSIONS: Our findings suggest ziprasidone induces atrial arrhythmia, potentially through upregulation of the NLRP3 inflammasome and enhancement of reactive oxygen species production via the PI3K/Akt/mTOR pathway.
Asunto(s)
Fibrilación Atrial , Inflamasomas , Miocitos Cardíacos , Piperazinas , Proteínas Proto-Oncogénicas c-akt , Especies Reactivas de Oxígeno , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Conejos , Especies Reactivas de Oxígeno/metabolismo , Piperazinas/farmacología , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Tiazoles/farmacología , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Potenciales de Acción/efectos de los fármacos , Antipsicóticos/farmacologíaRESUMEN
Lipopolysaccharide (LPS) triggers an inflammatory response, causing impairment of cardiomyocyte Ca2+ and Na + regulation. This study aimed to determine whether piscidin-1 (PCD-1), an antimicrobial peptide, improves intracellular Ca2+ and Na + regulation in LPS-challenged atrial cardiomyocytes. Rabbit atrial cardiomyocytes were enzymatically isolated from the left atria. Patch-clamp ionic current recording, intracellular Ca2+ monitoring using Fluo-3, and detection of cytosolic reactive oxygen species production were conducted in control, LPS-challenged, and LPS + PCD-1-treated atrial cardiomyocytes. LPS-challenged cardiomyocytes showed shortened durations of action potential at their 50% and 90% repolarizations, which was reversed by PCD-1 treatment. LPS-challenged cardiomyocytes showed decreased L-type Ca2+ channel currents and larger Na+/Ca2+ exchange currents compared to controls. While LPS did not affect the sodium current, an enhanced late sodium current with increased cytosolic Na+ levels was observed in LPS-challenged cardiomyocytes. These LPS-induced alterations in the ionic current were ameliorated by PCD-1 treatment. LPS-challenged cardiomyocytes displayed lowered Ca2+ transient amplitudes and decreased Ca2+ stores and greater Ca2+ leakage in the sarcoplasmic reticulum compared to the control. Exposure to PCD-1 attenuated LPS-induced alterations in Ca2+ regulation. The elevated reactive oxygen species levels observed in LPS-challenged myocytes were suppressed after PCD-1 treatment. The protein levels of NF-κB and IL-6 increased following LPS treatment. Decreased sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a protein levels were observed in LPS-challenged cardiomyocytes. PCD-1 modulates LPS-induced alterations in inflammatory and Ca2+ regulatory protein levels. Our results suggest that PCD-1 modulates LPS-induced alterations in intracellular Ca2+ and Na + homeostasis, reactive oxygen species production, and the NF-κB inflammatory pathway in atrial cardiomyocytes.
Asunto(s)
Calcio , Atrios Cardíacos , Lipopolisacáridos , Miocitos Cardíacos , Estrés Oxidativo , Especies Reactivas de Oxígeno , Sodio , Animales , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Lipopolisacáridos/farmacología , Conejos , Calcio/metabolismo , Sodio/metabolismo , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Atrios Cardíacos/citología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/metabolismo , Masculino , Potenciales de Acción/efectos de los fármacos , Retículo Sarcoplasmático/metabolismo , Retículo Sarcoplasmático/efectos de los fármacosRESUMEN
Emerging organic molecules with emissions in the second near-infrared (NIR-II) region are garnering significant attention. Unfortunately, achieving accountable organic emission intensity over the NIR-IIa (1300 nm) region faces challenges due to the intrinsic energy gap law. Up to the current stage, all reported organic NIR-IIa emitters belong to polymethine-based dyes with small Stokes shifts (<50 nm) and low quantum yield (QY; ≤0.015%). However, such polymethines have proved to cause self-absorption with constrained emission brightness, limiting advanced development in deep-tissue imaging. Here a new NIR-IIa scaffold based on rigid and highly conjugated dibenzofluoran core terminated by amino-containing moieties that reveal emission peaks of 1230-1305 nm is designed. The QY is at least 10 times higher than all synthesized or reported NIR-IIa polymethines with extraordinarily large Stokes shifts of 370-446 nm. DBF-BJ is further prepared as a polymer dot to demonstrate its in vivo 3D stereo imaging of mouse vasculature with a 1400 nm long-pass filter.
Asunto(s)
Polímeros , Animales , Ratones , Polímeros/química , Imagenología Tridimensional/métodos , Colorantes Fluorescentes/química , Espectroscopía Infrarroja Corta/métodosRESUMEN
Aims: Hypopharyngeal cancer (HPC) is associated with the worst prognosis of all head and neck cancers and is typically identified in an advanced stage at the time of diagnosis. While oxidative stress might contribute to the onset of HPC in patients using tobacco or alcohol, the extent of this influence and the characteristics of HPC cells in advanced stage remain to be investigated. In this study, we explored whether HPC cells survived from necrotic xenograft tumors at late stage would display increased tumor resistance along with altered tolerance to oxidative stress. Results: The remnant living HPC cells isolated from a late-stage xenograft tumor, named FaDu ex vivo cells, showed stronger chemo- and radioresistance, tumorigenesis, and invasiveness compared with parental FaDu cells. FaDu ex vivo cells also displayed increased angiogenic ability after re-transplantation in mice visualized by in vivo near infrared-II fluorescence imaging modality. Moreover, FaDu ex vivo cells exhibited significant tumor-initiating cell (TIC)-related properties accompanied by a reduction of the level of reactive oxygen species, which was associated with the upregulation of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Interestingly, inhibition of Nrf2 by the RNA interference and the chemical inhibitor could reduce the TIC-related properties of FaDu ex vivo cells. Innovation: Oxidative stress potentially initiates HPC, but elevation of Nrf2-associated antioxidant mechanisms would be essential to mitigate this effect for promoting and sustaining the stemness of HPC at the advanced stage. Conclusion: Present data suggest that the antioxidant potency of advanced HPC would be a therapeutic target for the design of adjuvant treatment.
RESUMEN
Altered gene expression as well as mislocalization of a gene's encoded product (proteins or noncoding RNAs (ncRNAs)) can lead to disease and cancer formation. Multiple studies have indicated that exosomes and their contents act as cell-to-cell communicators and play a key role in cancer progression. Moreover, exosomes contain several functional molecules, including ncRNAs. NcRNAs function as master regulators to coordinate cell growth, cell motility and drug resistance. However, intracellular ncRNAs, which can be transferred to recipient cells via exosomes (exosomal ncRNAs), mediate common/distinct downstream molecules, signaling pathways and functions that are less emphasized concepts in cancer development research. In this study, by using exosomes as a model, we comprehensively discuss the current knowledge regarding (1) the functional role of ncRNAs, both their intracellular and exosomal forms, in cancer progression, (2) the possible mechanism of ncRNA incorporation into exosomes and (3) the therapeutic applications and limitations of exosomes based on current knowledge.
Asunto(s)
Exosomas , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , Exosomas/genética , Exosomas/metabolismo , Transducción de SeñalRESUMEN
INTRODUCTION: CCN1 is an immediate-early gene product pivotal for arthritis progression. We have previously shown that sirtuin 6 (SIRT6) inhibited hypoxia-induced CCN1 expression in osteoblasts. Herein we examined the contribution of cyclic AMP-responsive element binding protein (CREB)/CRE to this suppressive action and the influence of CCN1 on cyclooxygenase (COX) 2 synthesis. MATERIALS AND METHODS: MC3T3-E1 murine osteoblasts were cultured under normoxia (21% oxygen) or hypoxia (2% oxygen). Expressions of CCN1, phospho-CREB (Ser133), COX2 and relevant kinases were assessed by Western blot. SIRT6 was overexpressed in cultured osteoblasts and arthritic joints by a lentiviral-based technique. Activities of CCN1 gene promoter constructs were examined by luciferase reporter assay. Interaction between CREB and CCN1 promoter was assessed by chromatin immunoprecipitation (ChIP). Collagen-induced arthritis (CIA) was established in 20 rats to evaluate the effects of SIRT6 therapy on osteoblastic expressions of phospho-CREB, CCN1 and COX2. RESULTS: SIRT6 suppressed hypoxia-enhanced CCN1 expression and CREB phosphorylation. Attenuation of calcium/calmodulin-dependent protein kinase II (CaMKII) may be responsible for SIRT6-induced CREB inhibition. CRE at - 286 bp upstream of the ATG start codon was essential for CCN1 expression under hypoxia and SIRT6 reduced hypoxia-stimulated CREB/CRE interaction. Forced expression of CREB rescued SIRT6-suppressed CCN1 synthesis. CCN1 induced COX2 expression in osteoblasts. In rat CIA, the therapeutic effect of SIRT6 was accompanied by decreases in osteoblastic expressions of phospho-CREB, CCN1 and COX2. CONCLUSION: Our study indicated that the benefits of SIRT6 to inflammatory arthritis and bone resorption are at least partially derived from its modulation of CREB/CCN1/COX2 pathway in osteoblasts.
Asunto(s)
Artritis Experimental , Sirtuinas , Ratas , Ratones , Animales , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/farmacología , Osteoblastos/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/farmacología , Hipoxia , Artritis Experimental/genética , Artritis Experimental/metabolismo , Fosforilación , Oxígeno/metabolismo , Oxígeno/farmacología , Sirtuinas/metabolismo , Sirtuinas/farmacología , AMP Cíclico/metabolismo , AMP Cíclico/farmacologíaAsunto(s)
Neoplasias de la Mama , Ganglio Linfático Centinela , Humanos , Femenino , Verde de Indocianina , Ganglio Linfático Centinela/patología , Neoplasias de la Mama/patología , Fluorescencia , Biopsia del Ganglio Linfático Centinela/métodos , Ganglios Linfáticos/patología , Colorantes , Imagen Óptica/métodosRESUMEN
BACKGROUND: Near-infrared (NIR) fluorescence-guided surgery with indocyanine green (ICG) has been demonstrated to provide high sensitivity in sentinel lymph node biopsy (SLNB) for breast cancer but has several limitations, such as unstable pharmacokinetics, limited fluorescence brightness, and undesired diffusion to neighboring tissues. This paper investigates the use of Voluven® as the solvent for ICG fluorescence-guided SLNB (ICG-SLNB). METHODS: The photophysical properties of ICG in water and Voluven® were evaluated in laboratory experiments and in a mouse model. Nine patients with early breast cancer underwent subareolar injection of diluted ICG (0.25 mg/ml) for ICG-SLNB. Six of the nine patients received ICG dissolved in Voluven® (ICG:Voluven®), while three were administered ICG dissolved in water (ICG:water); a repetitive injection-observation protocol was followed for all patients. The mapping image quality was evaluated. RESULTS: Laboratory experiments and in vivo mouse study showed improved fluorescence and better targeting using Voluven® as the solvent. ICG-SLNB with a repetitive injection-observation protocol was successfully performed in all nine patients. ICG:Voluven® administration had an overall better signal-to-background ratio (SBR) in sequential sentinel lymph nodes. The rates of transportation within the lymphatics were also improved using ICG:Voluven® compared with ICG:water. CONCLUSIONS: From basic research to animal models to in-human trial, our study proposes a repetitive injection-observation technique with ICG:Voluven®, which is characterized by better transportation and more stable mapping quality for ICG-SLNB in breast cancer patients.
Asunto(s)
Neoplasias de la Mama , Ganglio Linfático Centinela , Humanos , Animales , Ratones , Femenino , Verde de Indocianina , Ganglio Linfático Centinela/patología , Neoplasias de la Mama/cirugía , Fluorescencia , Biopsia del Ganglio Linfático Centinela/métodos , Solventes , Agua , Colorantes , Ganglios Linfáticos/patologíaRESUMEN
We designed polymer dot-magnetic nanoparticle nanohybrids for signal enhancement in a test strip platform. Besides, the multicolor emissions of the Pdots embed multiplexing ability for this test strip. Two mycotoxins, aflatoxin B1 and zearalenone, were tested with the determined limits of detection of 2.15 ng mL-1 and 4.87 ng mL-1, respectively.
Asunto(s)
Nanopartículas de Magnetita , Micotoxinas , Zearalenona , Micotoxinas/análisis , Polímeros , Inmunoensayo , Límite de Detección , Aflatoxina B1/análisis , Contaminación de Alimentos/análisisRESUMEN
INTRODUCTION: We have previously demonstrated that auxiliary metformin therapy promotes healing of apical periodontitis. Here we aimed to investigate the effects of metformin on osteoblast differentiation and osteoclast formation in cultured cells and rat apical periodontitis. METHODS: Murine pre-osteoblasts MC3T3-E1 and macrophages RAW264.7 were cultured under hypoxia (2% oxygen) or normoxia (21% oxygen) and stimulated with receptor activator of nuclear factor-κB ligand (RANKL) when indicated. Metformin was added to the cultures to evaluate its anti-hypoxic effects. Expressions of osteoblast differentiation regulator runt-related transcription factor 2 (RUNX2), RANKL, and osteoclast marker tartrate-resistant acid phosphatase (TRAP) were assessed by Western blot. Apical periodontitis was induced in mandibular first molars of 10 Sprague-Dawley rats. Root canal therapy with or without metformin supplement was performed. Periapical bone resorption was measured by micro-computed tomography. Immunohistochemistry was used to examine RUNX2, RANKL, and TRAP expressions. RESULTS: Hypoxia suppressed RUNX2 expression and enhanced RANKL synthesis in pre-osteoblasts. TRAP production increased in macrophages after hypoxia and/or RANKL stimulation. Metformin reversed hypoxia-induced RUNX2 suppression and RANKL synthesis in pre-osteoblasts. Metformin also inhibited hypoxia and RANKL-enhanced TRAP synthesis in macrophages. Intracanal metformin diminished bone loss in rat apical periodontitis. Comparing with vehicle control, cells lining bone surfaces in metformin-treated lesions had significantly stronger expression of RUNX2 and decreased synthesis of RANKL and TRAP. CONCLUSIONS: Alleviation of bone resorption by intracanal metformin was associated with enhanced osteoblast differentiation and diminished osteoclast formation in rat apical periodontitis. Our results endorsed the role of metformin as an effective medicament for inflammatory bone diseases.
Asunto(s)
Resorción Ósea , Metformina , Periodontitis Periapical , Ratas , Ratones , Animales , Osteoclastos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Microtomografía por Rayos X , Ratas Sprague-Dawley , Resorción Ósea/metabolismo , Osteoblastos , Periodontitis Periapical/patología , Diferenciación Celular , Hipoxia/metabolismo , Oxígeno/metabolismo , Ligando RANK/metabolismoRESUMEN
Significance: Optical imaging in the second near-infrared (NIR-II, 1000 to 1700 nm) region is capable of deep tumor vascular imaging due to low light scattering and low autofluorescence. Non-invasive real-time NIR-II fluorescence imaging is instrumental in monitoring tumor status. Aim: Our aim is to develop an NIR-II fluorescence rotational stereo imaging system for 360-deg three-dimensional (3D) imaging of whole-body blood vessels, tumor vessels, and 3D contour of mice. Approach: Our study combined an NIR-II camera with a 360-deg rotational stereovision technique for tumor vascular imaging and 3D surface contour for mice. Moreover, self-made NIR-II fluorescent polymer dots were applied in high-contrast NIR-II vascular imaging, along with a 3D blood vessel enhancement algorithm for acquiring high-resolution 3D blood vessel images. The system was validated with a custom-made 3D printing phantom and in vivo experiments of 4T1 tumor-bearing mice. Results: The results showed that the NIR-II 3D 360-deg tumor blood vessels and mice contour could be reconstructed with 0.15 mm spatial resolution, 0.3 mm depth resolution, and 5 mm imaging depth in an ex vivo experiment. Conclusions: The pioneering development of an NIR-II 3D 360-deg rotational stereo imaging system was first applied in small animal tumor blood vessel imaging and 3D surface contour imaging, demonstrating its capability of reconstructing tumor blood vessels and mice contour. Therefore, the 3D imaging system can be instrumental in monitoring tumor therapy effects.
Asunto(s)
Neoplasias , Animales , Ratones , Neoplasias/diagnóstico por imagen , Neoplasias/irrigación sanguínea , Imagen Óptica/métodos , Colorantes , Imagenología Tridimensional/métodos , Vasos SanguíneosRESUMEN
Creating infection resistant polymer brushes possessing antiadhesive, bactericidal and cell-compatible features can be regarded as a promising approach to prevent biomaterial-associated infections. In this work, polysulfobetaine type zwitterionic homo- and copolymer brushes with varying spacer lengths (charge separation distance between zwitterions, n = 3, 6 or 12) were allowed to grow onto a tartaric acid based aliphatic polyester substrate using surface initiated atom transfer radical polymerization. All of the brush modified surfaces were thoroughly characterized and assessed for their anti-infective performances in vitro. Strikingly, a suitable copolymer composition, i.e., polyZ6-co-Z12 (50/50 copolymer of polysulfobetaine methacrylates with 6 and 12 spacer lengths), was observed to inhibit bacterial growth completely and its activity was sustained for a long time (>3 months). Surprisingly, its antibacterial effect was found to be bactericidal, as is evident from live-dead staining of residual dead bacterial cells that can be easily released by exposing the surface to salt solution, thereby regenerating the surface. However, all of the other copolymer as well as homopolymer brushes exhibited bacteriostatic behavior. An attempt was made to understand the peculiar behavior of this particular brush composition. Nevertheless, the biocidal and also protein repellent brush did not display any cytotoxicity towards human cells, making it an ideal substrate to be used as an infection resistant biomedical implant. Animal studies further confirmed that this particular copolymeric brush modified scaffold can be a promising anti-infective wound dressing material with rapid wound healing effects as compared to the unmodified scaffold.
Asunto(s)
Betaína , Metacrilatos , Animales , Humanos , Metacrilatos/química , Antibacterianos/farmacología , Antibacterianos/química , Polímeros/química , Cicatrización de Heridas , Propiedades de SuperficieRESUMEN
Although titanium (Ti) alloys have been widely employed as biomedical materials, they cannot achieve satisfactory osseointegration when implanted in the human body due to their biologically inert nature. Surface modification can enhance both their bioactivity and corrosion resistance. The present study employed a Ti-5Nb-5Mo alloy with a metastable αâ³ phase. This alloy may undergo phase changes after conventional high-temperature heat treatment, which can deteriorate its properties. This study heat-treated the anodized Ti-5Nb-5Mo alloy by using a low-temperature hydrothermal or vapor thermal method to analyze the effects of heat treatment on its apatite induction. The results revealed that the porous nanotube structure on the surface of the alloy was transformed into anatase nanoparticles after hydrothermal or vapor thermal treatment at 150 °C for 6 h. After immersion in simulated body fluid (SBF) for 7 days, the amount of apatite deposited on the surface of the vapor thermal-treated alloy exceeded that on the hydrothermal-treated alloy. Therefore, post-heat treatment of anodized Ti-5Nb-5Mo by using the vapor thermal method can enhance its apatite inductivity without altering its structure.
RESUMEN
BACKGROUND: Basic life support (BLS) education is essential for improving bystander cardiopulmonary resuscitation (CPR) rates, but the imparting of such education faces obstacles during the outbreak of emerging infectious diseases, such as COVID-19. When face-to-face teaching is limited, distance learning-blended learning (BL) or an online-only model-is encouraged. However, evidence regarding the effect of online-only CPR training is scarce, and comparative studies on classroom-based BL (CBL) are lacking. While other strategies have recommended self-directed learning and deliberate practice to enhance CPR education, no previous studies have incorporated all of these instructional methods into a BLS course. OBJECTIVE: This study aimed to demonstrate a novel BLS training model-remote practice BL (RBL)-and compare its educational outcomes with those of the conventional CBL model. METHODS: A static-group comparison study was conducted. It included RBL and CBL courses that shared the same paradigm, comprising online lectures, a deliberate practice session with Little Anne quality CPR (QCPR) manikin feedback, and a final assessment session. In the main intervention, the RBL group was required to perform distant self-directed deliberate practice and complete the final assessment via an online video conference. Manikin-rated CPR scores were measured as the primary outcome; the number of retakes of the final examination was the secondary outcome. RESULTS: A total of 52 and 104 participants from the RBL and CBL groups, respectively, were eligible for data analysis. A comparison of the 2 groups revealed that there were more women in the RBL group than the CBL group (36/52, 69.2% vs 51/104, 49%, respectively; P=.02). After adjustment, there were no significant differences in scores for QCPR release (96.9 vs 96.4, respectively; P=.61), QCPR depth (99.2 vs 99.5, respectively; P=.27), or QCPR rate (94.9 vs 95.5, respectively; P=.83). The RBL group spent more days practicing before the final assessment (12.4 vs 8.9 days, respectively; P<.001) and also had a higher number of retakes (1.4 vs 1.1 times, respectively; P<.001). CONCLUSIONS: We developed a remote practice BL-based method for online-only distant BLS CPR training. In terms of CPR performance, using remote self-directed deliberate practice was not inferior to the conventional classroom-based instructor-led method, although it tended to take more time to achieve the same effect. TRIAL REGISTRATION: Not applicable.
Asunto(s)
COVID-19 , Reanimación Cardiopulmonar , Humanos , Femenino , Reanimación Cardiopulmonar/educación , Evaluación Educacional/métodos , Aprendizaje , Retroalimentación , ManiquíesRESUMEN
Cardiopulmonary resuscitation (CPR) education for the public may improve bystander intention to perform CPR on cardiac arrest patients. Studies have shown that different CPR education intervention methods can improve learning performance, with key indicators including attitude toward to CPR, intention to perform CPR, and degree of CPR knowledge and skills. The present study compared the traditional face-to-face method to hybrid and virtual reality (VR) methods to observe difference in learning performance and length of performance retention. This study adopted randomized controlled trial to compare CPR learning performance between traditional face-to-face, hybrid, and VR methods. Participants from each intervention group completed a pretest and 2 posttests. The measurement tools included an attitude and intention questionnaire, knowledge examination, and skill examination with a RESUSCI ANNE QCPR ® manikin. The performance among all participants in pretest showed no significant difference between the intervention groups, indicating no difference in their background attitude, knowledge, and skill level. Significant differences were observed in the average degree of intention to perform CPR between the hybrid and traditional groups in 1st and 2nd posttest. Compared to the pretest results, the posttests revealed significantly higher attitude toward CPR, intention to perform CPR, knowledge examination results, accuracy of overall chest compression, accuracy of CPR procedure, accuracy of AED usage, accuracy of chest compression rate, and accuracy of chest compression depth. The average time to reattending CPR learning and practice session was 11-12 weeks reported by participants. The hybrid and VR methods to CPR education resulted in the same level of improvement in learning performance as traditional face-to-face teaching. The suggested frequency for renewing CPR knowledge and skills is 12 weeks which may be considered in new strategies aimed at promoting CPR education and exposure to the public.