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1.
Anat Cell Biol ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39164249

RESUMEN

Platelet-rich plasma (PRP) is a promising biomaterial rich in bioactive growth factors, offering potential as a therapeutic agent for various diseases. However, its effectiveness in central nervous system disorders like vascular dementia (VaD) remains underexplored. This study investigated the potential of PRP to mitigate VaD progression in vivo. A rat model of VaD was established via bilateral common carotid artery occlusion and hypovolemia operation. Rats were randomly assigned to receive either PRP or platelet-poor plasma (PPP)-the latter being a byproduct of PRP preparation and used as a reference standard-resulting in the groups designated as 'operated group (OP)+PRP' and 'OP+PPP', respectively. PRP or PPP (500 µl) was administered intraperitoneally on the day of the operation and postoperative days 2, 4, 6, and 8. Cognitive function was assessed using the Y-maze, Barnes maze, and passive avoidance tests. On postoperative day 8, hippocampal samples were subjected to histological and semi-quantitative analyses. OP exhibited significant memory decline compared to controls, while the 'OP+PRP' group showed notable improvement. Histological analysis revealed increased neuronal loss and neuroinflammation in OP hippocampi, mitigated in 'OP+PRP'. Semi-quantitative analysis showed decreased expression of brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) in OP, restored in 'OP+PPP' and further in 'OP+PRP'. These results highlight PRP's protective effects against VaD-induced hippocampal damage and cognitive impairment, partially attributed to BDNF/TrkB pathway upregulation.

2.
J Gastric Cancer ; 24(3): 257-266, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38960885

RESUMEN

PURPOSE: We conducted a randomized prospective trial (KLASS-07 trial) to compare laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. In this interim report, we describe short-term results in terms of morbidity and mortality. METHODS AND METHODS: The sample size was 442 participants. At the time of the interim analysis, 314 patients were enrolled and randomized. After excluding patients who did not undergo planned surgeries, we performed a modified per-protocol analysis of 151 and 145 patients in the LADG and TLDG groups, respectively. RESULTS: The baseline characteristics, including comorbidity status, did not differ between the LADG and TLDG groups. Blood loss was somewhat higher in the LADG group, but statistical significance was not attained (76.76±72.63 vs. 62.91±65.68 mL; P=0.087). Neither the required transfusion level nor the operation or reconstruction time differed between the 2 groups. The mini-laparotomy incision in the LADG group was significantly longer than the extended umbilical incision required for specimen removal in the TLDG group (4.79±0.82 vs. 3.89±0.83 cm; P<0.001). There were no between-group differences in the time to solid food intake, hospital stay, pain score, or complications within 30 days postoperatively. No mortality was observed in either group. CONCLUSIONS: Short-term morbidity and mortality rates did not differ between the LADG and TLDG groups. The KLASS-07 trial is currently underway. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03393182.


Asunto(s)
Gastrectomía , Laparoscopía , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/mortalidad , Gastrectomía/métodos , Gastrectomía/efectos adversos , Gastrectomía/mortalidad , Laparoscopía/métodos , Laparoscopía/efectos adversos , Laparoscopía/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/etiología , Morbilidad , Adulto
3.
Int J Surg ; 110(8): 4810-4820, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38716987

RESUMEN

BACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). The authors performed an RCT to confirm if TLDG is different from LADG. METHODS: The KLASS-07 trial is a multi-centre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enroled from 21 cancer care centres in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was quality of life (QoL) for 1 year. This trial is registered at ClinicalTrials.gov (NCT03393182). RESULTS: Four hundred forty-two patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complications but has the advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months.


JOURNAL/ijos/04.03/01279778-202408000-00031/figure1/v/2024-08-13T152924Z/r/image-jpeg.


Asunto(s)
Gastrectomía , Laparoscopía , Complicaciones Posoperatorias , Calidad de Vida , Neoplasias Gástricas , Humanos , Gastrectomía/métodos , Gastrectomía/efectos adversos , Laparoscopía/métodos , Laparoscopía/efectos adversos , Masculino , Femenino , Neoplasias Gástricas/cirugía , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , República de Corea , Resultado del Tratamiento , Adulto
4.
J Med Chem ; 67(10): 8445-8459, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38706130

RESUMEN

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is responsible for 90% of cases. Approximately 30% of patients diagnosed with HCC are identified as displaying an aberrant expression of fibroblast growth factor 19 (FGF19)-fibroblast growth factor receptor 4 (FGFR4) as an oncogenic-driver pathway. Therefore, the control of the FGF19-FGFR4 signaling pathway with selective FGFR4 inhibitors can be a promising therapy for the treatment of HCC. We herein disclose the design and synthesis of novel FGFR4 inhibitors containing a 2,6-naphthyridine scaffold. Compound 11 displayed a nanomolar potency against Huh7 cell lines and high selectivity over FGFR1-3 that were comparable to that of fisogatinib (8) as a reference standard. Additionally, compound 11 demonstrated remarkable antitumor efficacy in the Huh7 and Hep3B HCC xenograft mouse model. Moreover, bioluminescence imaging experiments with the orthotopic mouse model support that compound 11 can be considered a promising candidate for treating HCC.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Naftiridinas , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Animales , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Ratones , Naftiridinas/farmacología , Naftiridinas/síntesis química , Naftiridinas/química , Naftiridinas/uso terapéutico , Línea Celular Tumoral , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/uso terapéutico , Proliferación Celular/efectos de los fármacos , Descubrimiento de Drogas , Ratones Desnudos , Ensayos de Selección de Medicamentos Antitumorales
5.
Nat Commun ; 15(1): 1671, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38396037

RESUMEN

InP/ZnSe/ZnS quantum dots (QDs) stand as promising candidates for advancing QD-organic light-emitting diodes (QLED), but low emission efficiency due to their susceptibility to oxidation impedes applications. Structural defects play important roles in the emission efficiency degradation of QDs, but the formation mechanism of defects in oxidized QDs has been less investigated. Here, we investigated the impact of diverse structural defects formation on individual QDs and propagation during UV-facilitated oxidation using high-resolution (scanning) transmission electron microscopy. UV-facilitated oxidation of the QDs alters shell morphology by the formation of surface oxides, leaving ZnSe surfaces poorly passivated. Further oxidation leads to the formation of structural defects, such as dislocations, and induces strain at the oxide-QD interfaces, facilitating In diffusion from the QD core. These changes in the QD structures result in emission quenching. This study provides insight into the formation of structural defects through photo-oxidation, and their effects on emission properties of QDs.

6.
Trials ; 25(1): 7, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167216

RESUMEN

BACKGROUND: Petersen's hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien-Dindo classification grade III due to Petersen's hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. METHODS: This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen's defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen's hernia within 3 years after laparoscopic or robotic gastrectomy. DISCUSSION: This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen's defect without increased postoperative complications compared to the conventional method. TRIAL REGISTRATION: ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.


Asunto(s)
Derivación Gástrica , Hernia Abdominal , Laparoscopía , Obesidad Mórbida , Humanos , Hernia Abdominal/diagnóstico por imagen , Hernia Abdominal/etiología , Hernia Abdominal/prevención & control , Estudios Prospectivos , Método Simple Ciego , Mesenterio/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Derivación Gástrica/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Obesidad Mórbida/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
7.
Int J Surg ; 110(1): 32-44, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37755373

RESUMEN

BACKGROUNDS: This study aimed to compare the incidence of bile reflux, quality of life (QoL), and nutritional status among Billroth II (BII), Billroth II with Braun anastomosis (BII-B), and Roux-en-Y (RY) reconstruction after laparoscopic distal gastrectomy (LDG). MATERIALS AND METHODS: We reviewed the prospective data of 397 patients from a multicentre database who underwent LDG for gastric cancer between 2018 and 2020 at 20 tertiary teaching hospitals in Korea. Postoperative endoscopic findings, QoL surveys using the European Organization for Research and Treatment of Cancer questionnaire (C30 and STO22), and nutritional and surgical outcomes were compared among groups. RESULTS: In endoscopic findings, bile reflux was the lowest in the RY group ( n =67), followed by the BII-B ( n =183) and BII groups ( n =147) at 1 year (3.0 vs. 67.8 vs. 84.4%, all P <0.05). The anti-reflux capability of BII-B was statistically better than that of BII, but not as perfect as that of RY. From the perspective of QoL, BII-B was not inferior to RY, but better than BII reconstruction in causing fewer STO22 reflux symptoms at 6 and 12 months. However, only RY caused fewer C30 nausea symptoms than BII at 6 and 12 months, but not BII-B. Nutritional status and morbidities were similar among the three groups, and the operative time did not differ between the BII-B and RY groups. CONCLUSIONS: BII-B cannot substitute for RY in preventing bile reflux, shortening the operative time, or reducing morbidities. Regarding short-term QoL, BII-B was sufficient to reduce STO22 reflux symptoms but failed to reduce C30 nausea symptoms postoperatively.


Asunto(s)
Reflujo Biliar , Neoplasias Gástricas , Humanos , Calidad de Vida , Gastrectomía/efectos adversos , Reflujo Biliar/prevención & control , Reflujo Biliar/cirugía , Estudios Prospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Gastroenterostomía/efectos adversos , Anastomosis en-Y de Roux/efectos adversos , Neoplasias Gástricas/cirugía , Náusea , Resultado del Tratamiento
8.
Eur J Med Chem ; 261: 115840, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37783102

RESUMEN

Epidermal growth factor receptor (EGFR)-targeted therapy is used to treat EGFR mutation-induced non-small cell lung cancer (NSCLC). However, its efficacy does not last beyond a certain period due to the development of primary and secondary resistance. First and second-generation inhibitors (e.g., gefitinib, erlotinib, and afatinib) induce EGFR T790M mutations, while third-generation inhibitors (e.g., osimertinib) induce C797S as a major target resistance mutation. Therefore, the C797S mutation is being actively researched. In this study, we investigated the structure-activity relationship of several synthesized compounds as fourth-generation inhibitors against the C797S mutation. We identified a compound 13k that displayed nanomolar potency and high selectivity. Moreover, we used a triple mutant xenograft mouse model to evaluate the in vivo efficacy of 13k in inhibiting EGFR C797S, which demonstrated exceptional profiles and satisfactory EGFR C797S inhibition efficacy. Based on its excellent in vitro and in vivo profiles, compound 13k can be considered a promising candidate for treating EGFR C797S mutations.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Mutación , Neoplasias Pulmonares/metabolismo , Receptores ErbB , Inhibidores de Proteínas Quinasas/farmacología , Resistencia a Antineoplásicos , Compuestos de Anilina/farmacología
9.
Curr Issues Mol Biol ; 45(10): 8427-8443, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37886974

RESUMEN

Focal cerebral ischemia (fCI) can result in brain injury and sensorimotor deficits. Brown algae are currently garnering scientific attention as potential therapeutic candidates for fCI. This study investigated the therapeutic effects of the hot water extract of Petalonia binghamiae (wPB), a brown alga, in in vitro and in vivo models of fCI. The neuroprotective efficacy of wPB was evaluated in an in vitro excitotoxicity model established using HT-22 cells challenged with glutamate. Afterward, C57/BL6 mice were administered wPB for 7 days (10 or 100 mg/kg, intragastric) and subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) operation, which was used as an in vivo fCI model. wPB co-incubation significantly inhibited cell death, oxidative stress, and apoptosis, as well as stimulated the expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, and the nuclear translocation of its upstream regulator, nuclear factor erythroid 2-related factor 2 (Nrf2) in HT-22 cells challenged with glutamate-induced excitotoxicity. Pretreatment with either dose of wPB significantly attenuated infarction volume, neuronal death, and sensorimotor deficits in an in vivo fCI model. Furthermore, the attenuation of oxidative stress and apoptosis in the ischemic lesion accompanied the wPB-associated protection. This study suggests that wPB can counteract fCI via an antioxidative effect, upregulating the Nrf2/HO-1 pathway.

10.
Anat Cell Biol ; 56(4): 494-507, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37743615

RESUMEN

Vascular dementia (VaD) is characterized by progressive memory impairment, which is associated with microglia-mediated neuroinflammation. Polyphenol-rich natural plants, which possess anti-inflammatory activities, have attracted scientific interest worldwide. This study investigated whether Rubus fruticosus leaf extract (RFLE) can attenuate VaD. Sprague-Dawley rats were separated into five groups: SO, sham-operated and treated with vehicle; OP, operated and treated with vehicle; RFLE-L, operated and treated with low dose (30 mg/kg) of RFLE; RFLE-M, operated and treated with medium dose (60 mg/kg) of RFLE; and RFLE-H, operated and treated with high dose (90 mg/kg) of RFLE. Bilateral common carotid artery and hypotension were used as a modeling procedure, and the RFLE were intraorally administered for 5 days (preoperative 2 and postoperative 3 days). The rats then underwent memory tests including the novel object recognition, Y-maze, Barnes maze, and passive avoidance tests, and neuronal viability and neuroinflammation were quantified in their hippocampi. The results showed that the OP group exhibited VaD-associated memory deficits, neuronal death, and microglial activation in hippocampi, while the RFLE-treated groups showed significant attenuation in all above parameters. Next, using BV-2 microglial cells challenged with lipopolysaccharide (LPS), we evaluated the effects of RFLE in dynamics of proinflammatory mediators and the upstream signaling pathway. RFLE pretreatment significantly inhibited the LPS-induced release of nitric oxide, TNF-α, and IL-6 and upregulation of the MAPKs/NF-κB/iNOS pathway. Collectively, we suggest that RFLE can attenuate the histologic alterations and memory deficits accompanied by VaD, and these roles are, partly due to the attenuation of microglial activation.

11.
Opt Express ; 31(18): 29589-29595, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37710755

RESUMEN

We report a microlens array camera with variable apertures (MACVA) for high dynamic range (HDR) imaging by using microlens arrays with various sizes of apertures. The MACVA comprises variable apertures, microlens arrays, gap spacers, and a CMOS image sensor. The microlenses with variable apertures capture low dynamic range (LDR) images with different f-stops under single-shot exposure. The reconstructed HDR images clearly exhibit expanded dynamic ranges surpassing LDR images as well as high resolution without motion artifacts, comparable to the maximum MTF50 value observed among the LDR images. This compact camera provides, what we believe to be, a new perspective for various machine vision or mobile devices applications.

12.
Curr Issues Mol Biol ; 45(8): 6775-6789, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37623247

RESUMEN

Alzheimer's disease (AD) is characterized by memory impairment and existence of amyloid-ß (Aß) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM)-Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus-cultivated on a barley medium was assessed for its anti-AD effects. Neuron-like PC12 cells, which were subjected to Zn2+, an Aß aggregator, were employed as an in vitro AD model. The cells pretreated with or without MMMM were assayed for Aß immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. Then, 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aß immunofluorescence, ROS accumulation, and apoptosis, and incrementation in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aß plaque accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aß plaque accumulation and neuroinflammation, by impeding Aß-induced neurotoxicity.

13.
Ann Surg Treat Res ; 104(3): 156-163, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36910563

RESUMEN

Purpose: Laparoscopic right colectomy (LRC) with extracorporeal anastomosis (ECA) remains the most widely adopted technique despite mounting evidence that intracorporeal anastomosis (ICA) offers several advantages. This study aimed to compare the postoperative outcomes of ICA and ECA and to investigate the effect of ICA on postoperative ileus after LRC. Methods: This retrospective study included 45 patients who underwent ICA and 63 who underwent ECA in LRC for right-sided colonic diseases between January 2015 and December 2019. Results: There were no significant differences in total operation time, blood loss, total length of incisions, tolerance of diet, postoperative pain score on postoperative days 1 and 2, or length of hospital stays between the 2 groups. However, the ICA group had a significantly shorter time to first flatus passage (3.0 ± 0.9 days vs. 3.8 ± 1.9 days, P = 0.013). The rate of postoperative ileus was significantly higher in the ECA group (2.2% vs. 14.3%, P = 0.033); however, there was no significant difference in the overall morbidity within 30 days after surgery. Multivariate logistic regression analysis showed that the ECA technique (odds ratio [OR], 0.098; 95% confidence interval [CI]; 0.011-0.883, P = 0.038) and previous abdominal operation (OR, 5.269; 95% CI, 1.193-23.262; P = 0.028) were independent risk factors for postoperative ileus. Conclusion: The postoperative outcomes of patients who underwent LRC with ICA or ECA were comparable, and ICA could reduce the incidence of postoperative ileus after LRC compared with ECA.

14.
Clin Exp Metastasis ; 40(2): 137-148, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36763292

RESUMEN

Brain metastasis is a common complication in melanoma patients with BRAF and NRAS mutations and has a poor prognosis. Although BRAF inhibitors are clinically approved, their poor brain penetration limits their efficacy in brain metastasis. Thus, melanoma brain metastasis still requires better treatment. Belvarafenib, a pan-RAF inhibitor, has reported antitumor activity in melanoma with RAF and RAS mutations in animal models and patients. However, brain permeability and antitumor efficacy on brain metastasis have not been determined. This study confirmed the brain penetration of belvarafenib, the antitumor activity on BRAF and NRAS mutant melanoma, and the efficacy on melanoma within the brain. Belvarafenib strongly suppressed melanoma in BRAF V600E mutant A375SM tumor-bearing mice. It also significantly inhibited tumor growth in NRAS mutant SK-MEL-30 and K1735 tumor-bearing mice and synergized to enhance the antitumor activity combined with cobimetinib or atezolizumab. Belvarafenib was penetrated at considerable levels into the brains of mice and rats following oral administration. The exposure of belvarafenib in the brain was similar to or higher than that in plasma, and this high brain penetration differed significantly from that of other BRAF inhibitors with low brain penetration. Most importantly, belvarafenib strongly reduced tumor burden and markedly improved survival benefits in mice intracranially implanted with A375SM melanoma. These results demonstrated that belvarafenib, which has favorable BBB permeability, and potent antitumor activity on the tumors with BRAF/NRAS mutations, may be a promising therapeutic option for patients with BRAF/NRAS mutant melanoma brain metastasis.


Asunto(s)
Neoplasias Encefálicas , Melanoma , Neoplasias Cutáneas , Ratones , Ratas , Animales , Proteínas Proto-Oncogénicas B-raf/genética , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Mutación , Línea Celular Tumoral , Neoplasias Cutáneas/patología
15.
Biomater Res ; 27(1): 4, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36670488

RESUMEN

BACKGROUND: Obesity, a serious threat to public health, is linked to chronic metabolic complications including insulin resistance, type-2 diabetes, and metabolic dysfunction-associated fatty liver disease (MAFLD). Current obesity medications are challenged by poor effectiveness, poor patient compliance, and potential side effects. Verapamil is an inhibitor of L-type calcium channels, FDA-approved for the treatment of hypertension. We previously investigated the effect of verapamil on modulating autophagy to treat obesity-associated lipotoxicity. This study aims to develop a verapamil transdermal patch and to evaluate its anti-obesity effects. METHODS: Verapamil is loaded in biomimetic vascular bundle-like carboxymethyl pullulan-based supramolecular hydrogel patches cross-linked with citric acid and glycerol linkages (CLCMP). The investigation was then carried out to determine the therapeutic effect of verapamil-loaded CLCMP (Vera@CLCMP) on diet-induced obese mice. RESULTS: Vera@CLCMP hydrogel patches with hierarchically organized and anisotropic pore structures not only improved verapamil bioavailability without modifying its chemical structure but also enhanced verapamil release through the stratum corneum barrier. Vera@CLCMP patches exhibit low toxicity and high effectiveness at delivering verapamil into the systemic circulation through the dermis in a sustained manner. Specifically, transdermal administration of this patch into diet-induced obese mice drastically improved glucose tolerance and insulin sensitivity and alleviated metabolic derangements associated with MAFLD. Furthermore, we uncovered a distinct molecular mechanism underlying the anti-obesity effects associated with the hepatic NLR family pyrin domain-containing 3 (NLRP3) inflammasome and autophagic clearance by the vera@CLCMP hydrogel patches. CONCLUSION: The current study provides promising drug delivery platforms for long-term family treatment of chronic diseases, including obesity and metabolic dysfunctions.

16.
Health Info Libr J ; 40(2): 223-227, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36578153

RESUMEN

NHS knowledge and library staff are a highly specialist workforce delivering an economic benefit of £77 million per annum to the health service in England. To achieve their full potential and meet the changing needs of the NHS, it is vital that the workforce remains up to date through the continuing development of their skills, knowledge, and behaviours. This article outlines the work of Health Education England to gain Chartered Institute of Library and Information Professionals (CILIP-The Library and Information Association) quality accreditation for the short course offers delivered through the NHS Knowledge for Healthcare Learning Academy. It summarises the benefits of this accreditation for Health Education England, for employers, and for knowledge and library staff participating in the short courses. Learning points from the experience of the accreditation process are described and shared.


Asunto(s)
Acreditación , Educación Continua , Bibliotecólogos , Asociaciones de Bibliotecas , Humanos , Atención a la Salud , Inglaterra , Aprendizaje , Medicina Estatal
17.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-966309

RESUMEN

Purpose@#Laparoscopic right colectomy (LRC) with extracorporeal anastomosis (ECA) remains the most widely adopted technique despite mounting evidence that intracorporeal anastomosis (ICA) offers several advantages. This study aimed to compare the postoperative outcomes of ICA and ECA and to investigate the effect of ICA on postoperative ileus after LRC. @*Methods@#This retrospective study included 45 patients who underwent ICA and 63 who underwent ECA in LRC for rightsided colonic diseases between January 2015 and December 2019. @*Results@#There were no significant differences in total operation time, blood loss, total length of incisions, tolerance of diet, postoperative pain score on postoperative days 1 and 2, or length of hospital stays between the 2 groups. However, the ICA group had a significantly shorter time to first flatus passage (3.0 ± 0.9 days vs. 3.8 ± 1.9 days, P = 0.013). The rate of postoperative ileus was significantly higher in the ECA group (2.2% vs. 14.3%, P = 0.033); however, there was no significant difference in the overall morbidity within 30 days after surgery. Multivariate logistic regression analysis showed that the ECA technique (odds ratio [OR], 0.098; 95% confidence interval [CI]; 0.011–0.883, P = 0.038) and previous abdominal operation (OR, 5.269; 95% CI, 1.193–23.262; P = 0.028) were independent risk factors for postoperative ileus. @*Conclusion@#The postoperative outcomes of patients who underwent LRC with ICA or ECA were comparable, and ICA could reduce the incidence of postoperative ileus after LRC compared with ECA.

18.
Int J Mol Sci ; 23(24)2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36555596

RESUMEN

The core-shell structure of poly(St-co-MAA) nanoparticles containing ß-diketonate Eu3+ complexes were synthesized by a step-wise process. The ß-diketonate Eu3+ complexes of Eu (TFTB)2(MAA)P(Oct)3 [europium (III); 4,4,4-Trifluoro-1-(2-thienyl)-1,3-butanedione = TFTB; trioctylphosphine = (P(Oct)3); methacrylic acid = MAA] were incorporated to poly(St-co-MAA). The poly(St-co-MAA) has highly monodispersed with a size of 300 nm, and surface charges of the poly(St-co-MAA) are near to neutral. The narrow particle size distribution was due to the constant ionic strength of the polymerization medium. The activated carboxylic acid of poly(St-co-MAA) further chelated with europium complex and polymerize between acrylic groups of poly(St-co-MAA) and Eu(TFTB)2(MAA)P(Oct)3. The Em spectra of europium complexes consist of multiple bands of Em at 585, 597, 612 and 650 nm, which are assigned to 5D0→7FJ (J = 0-3) transitions of Eu3+, respectively. The maximum Em peak is at 621 nm, which indicates a strong red Em characteristic associated with the electric dipole 5D0→7F2 transition of Eu3+ complexes. The cell-specific fluorescence of Eu(TFTB)2(MAA)P(Oct)3@poly(St-co-MAA) indicated endocytosis of Eu(TFTB)2(MAA)P(Oct)3@poly(St-co-MAA). There are fewer early apoptotic, late apoptotic and necrotic cells in each sample compared with live cells, regardless of the culture period. Eu(TFTB)2(MAA)P(Oct)3@poly(St-co-MAA) synthesized in this work can be excited in the full UV range with a maximum Em at 619 nm. Moreover, these particles can substitute red luminescent organic dyes for intracellular trafficking and cellular imaging agents.


Asunto(s)
Europio , Nanopartículas , Europio/química , Luminiscencia , Fluorescencia , Colorantes
19.
Sci Rep ; 12(1): 20681, 2022 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-36450778

RESUMEN

We developed and validated a new staging system that includes metabolic information from pretreatment [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) for predicting disease-specific survival (DSS) in gastric cancer (GC) patients. Overall, 731 GC patients undergoing preoperative [18F]FDG PET/CT were enrolled and divided into the training (n = 543) and validation (n = 188) cohorts. A metabolic score (MS) was developed by combining the maximum standardized uptake value (SUVmax) of the primary tumor (T_SUVmax) and metastatic lymph node (N_SUVmax). A new staging system incorporating the MS and tumor-node-metastasis (TNM) stage was developed using conditional inference tree analysis. The MS was stratified as follows: score 1 (T_SUVmax ≤ 4.5 and N_SUVmax ≤ 1.9), score 2 (T_SUVmax > 4.5 and N_SUVmax ≤ 1.9), score 3 (T_SUVmax ≤ 4.5 and N_SUVmax > 1.9), and score 4 (T_SUVmax > 4.5 and N_SUVmax > 1.9) in the training cohort. The new staging system yielded five risk categories: category I (TNM I, II and MS 1), category II (TNM I, II and MS 2), category III (TNM I, II and MS ≥ 3), category IV (TNM III, IV and MS ≤ 3), and category V (TNM III, IV and MS 4) in the training cohort. DSS differed significantly between both staging systems; the new staging system showed better prognostic performance in both training and validation cohorts. The MS was an independent prognostic factor for DSS, and discriminatory power of the new staging system for DSS was better than that of the conventional TNM staging system alone.


Asunto(s)
Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Gástricas , Humanos , Fluorodesoxiglucosa F18 , Pronóstico , Neoplasias Gástricas/diagnóstico por imagen , Ganglios Linfáticos
20.
Health Info Libr J ; 39(4): 336-346, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35808921

RESUMEN

BACKGROUND: Responding to the COVID-19 pandemic, Health Education England (HEE) mobilised a group of expert searchers from NHS libraries in England to develop a platform for librarians to share peer reviewed search strategies and results on the Knowledge for Healthcare website. OBJECTIVES: (1) To document the origins of the COVID-19 search bank, (2) evaluate attitudes of NHS librarians in England towards the search bank and (3) identify lessons learned and consider whether the initiative might be developed further. METHODS: Structured interviews with the peer reviewers (n = 10) were conducted, and a questionnaire survey of the NHS library community using the search bank was undertaken. RESULTS: The interviews confirmed the value of collaboration. Expert searchers worked in pairs to peer review submitted search strategies. The survey (85 responses) indicated that a majority had used the search bank, and approved of the project, with some differences of opinion on functionality and future developments. DISCUSSION: Collaborative working for the search bank probably saved time for individual NHS librarians. The quality of the searches submitted was variable as were librarians' approaches to presentation and development of search strategies. Peer review benefits from a buddy approach among expert searchers and agreement about feedback provided to contributors. CONCLUSION: Search strategies are the most useful element of a search bank. Peer review can be challenging and would benefit from a formal structure, but it is professionally rewarding.


Asunto(s)
COVID-19 , Bibliotecólogos , Bibliotecas Médicas , Humanos , Medicina Estatal , Pandemias , Revisión por Pares
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