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BACKGROUND: /Aims: Polypectomy is a procedure associated with a high risk of bleeding. Guidelines recommend uninterrupted aspirin use during polypectomy, whereas cessation of clopidogrel 5-7 days before polypectomy is recommended. The cold snare resection technique, with or without submucosal injection, is considered safer than conventional polypectomy using electrocoagulation for post-polypectomy bleeding. In this study, we aimed to compare the bleeding complications associated with cold snare resection between clopidogrel and aspirin users. METHODS: This multicenter, prospective cohort study was conducted in five academic hospitals in Korea and included clopidogrel and aspirin users who underwent polypectomy. Antiplatelet agents were used without interruption, with ≤ 3 days of interruption defined as continuous use. The primary endpoint was delayed bleeding, which was defined as bleeding occurring several hours after polypectomy, whereas immediate bleeding was defined as bleeding requiring hemostasis 2 min after polypectomy. Risk factors for immediate bleeding were investigated for each polyp. RESULTS: Among the 263 patients (clopidogrel, n = 129; aspirin, n = 134), 509 underwent polypectomies. The rate of delayed bleeding per patient in the clopidogrel and aspirin groups was 0.8% and 0.7%, respectively, meeting noninferiority (rate difference 0.03% [95% confidence interval: -2.07% to 2.13%]). Hemostasis was achieved in 100 patients who underwent polypectomy (19.8%). Immediate bleeding risk factors included female sex, end-stage renal disease, submucosal injection before resection, and polyp size ≥ 5 mm. CONCLUSIONS: This multicenter prospective study demonstrated the safety of cold snare resection in patients treated with uninterrupted clopidogrel and aspirin (NCT04328987).
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BACKGROUND: Forehead flatness is common in Korean populations, and one of the most straightforward techniques for adding volume and achieving a concave forehead is injecting hyaluronic acid (HA) filler. However, definitive guidelines for this procedure are lacking, and careful attention to the arterial anatomy is required to avoid vascular complications. OBJECTIVE: The authors aimed to establish guidelines for performing forehead augmentation using Doppler ultrasound to identify vasculature before HA injection. METHODS AND MATERIALS: Arterial mapping of the faces of 34 patients was performed using Doppler ultrasound. Each anatomic layer (skin, subcutaneous fat, and galea aponeurotica) of the forehead with blood vessels was identified. An average volume of 2.85 mL of HA filler was injected. Postoperative complications, such as infection, hematoma, bruising, nodules, skin necrosis, and blindness, were evaluated. RESULTS: Using Doppler ultrasound, the authors successfully traced all 3 blood vessels (supraorbital, supratrochlear, and frontal branch of the superficial temporal arteries) and avoided them during HA injection. None of the patients experienced arterial complications. CONCLUSION: Doppler ultrasound proves to be an effective technique for arterial mapping, enabling the identification and avoidance of the major blood vessels of the forehead before HA filler injection.
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Técnicas Cosméticas , Rellenos Dérmicos , Frente , Ácido Hialurónico , Ultrasonografía Doppler , Humanos , Frente/irrigación sanguínea , Femenino , Rellenos Dérmicos/administración & dosificación , Persona de Mediana Edad , Adulto , Masculino , Ácido Hialurónico/administración & dosificación , República de Corea , Técnicas Cosméticas/efectos adversos , Arterias Temporales/diagnóstico por imagen , Arterias/diagnóstico por imagenRESUMEN
Sialylation during N-glycosylation plays an important role in the half-life of therapeutic glycoproteins in vivo and has sparked interest in the production of therapeutic proteins using recombinant Chinese hamster ovary (rCHO) cells. To improve the sialylation of therapeutic proteins, we examined the effect of sialyllactose supplementation on sialylation of Fc-fusion glycoproteins produced in rCHO cells. Two enzymatically-synthesized sialyllactoses, 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), were administered separately to two rCHO cell lines producing the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44, respectively. Two sialyllactoses successfully increased sialylation of Fc-fusion glycoprotein in both cell lines, as evidenced by isoform distribution, sialylated N-glycan formation, and sialic acid content. Increased sialylation by adding sialyllactose was likely the result of increased amount of intracellular CMP-sialic acid (CMP-SA), the direct nucleotide sugar for sialylation. Furthermore, the degree of sialylation enhanced by sialyllactoses was slightly effective or nearly similar compared with the addition of N-acetylmannosamine (ManNAc), a representative nucleotide sugar precursor, to increase sialylation of glycoproteins. The effectiveness of sialyllactose was also confirmed using three commercially available CHO cell culture media. Taken together, these results suggest that enzymatically-synthesized sialyllactose represents a promising candidate for culture media supplementation to increase sialylation of glycoproteins in rCHO cell culture.
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Cricetulus , Fragmentos Fc de Inmunoglobulinas , Lactosa , Animales , Células CHO , Lactosa/análogos & derivados , Lactosa/metabolismo , Fragmentos Fc de Inmunoglobulinas/genética , Fragmentos Fc de Inmunoglobulinas/metabolismo , Cricetinae , Glicosilación , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/genética , Glicoproteínas/metabolismo , Glicoproteínas/genética , Medios de Cultivo/química , Ácidos Siálicos/metabolismo , Ácido N-Acetilneuramínico/metabolismo , OligosacáridosRESUMEN
OBJECTIVES: The elapse time between the completion of bowel cleansing and colonoscopy is one of the important factors for proper bowel cleansing. Although several studies have reported that a short time interval resulted in a favorable bowel cleansing, no randomized controlled trial (RCT) has been conducted to determine the effect of the elapse time. Consequently, we performed an RCT to investigate the efficacy of bowel preparation of participants who underwent colonoscopy according to the different time intervals between the completion of bowel preparation and colonoscopy. METHODS: In this single-center RCT, study participants were randomized to complete bowel preparation either 2-4 h or 4-8 h before colonoscopy. The primary end-point was successful bowel preparation, rated using the Boston Bowel Preparation Scale (BBPS). RESULTS: A total of 504 individuals were included (2-4 h, 255; 4-8 h, 249). The rate of successful bowel preparation in the 2-4 h group showed noninferiority compared with that of the 4-8 h group (97.6% vs. 95.2%; rate difference, 2.5% [-0.8% to 5.7%]; Pfor noninferiority < 0.001, Pfor superiority = 0.136). The rate for perfect cleansing (a BBPS score of 9) was higher in the 2-4 h group (56.5% vs. 39.8%, P < 0.001). CONCLUSION: When bowel cleansing was finished 2-4 h before the start of colonoscopy, the overall bowel cleansing was noninferior, and perfect cleansing was superior, compared to that when cleansing was finished 4-8 h before colonoscopy.
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OBJECTIVES: Unlike the initial plan, some patients with oesophageal squamous cell carcinoma cannot or do not receive surgery after neoadjuvant chemoradiotherapy (nCRT). This study aimed to report the epidemiology of patients not receiving surgery after nCRT and to evaluate the potential risk of refusing surgery. METHODS: We analysed patients with clinical stage T3-T4aN0M0 or T1-T4aN1-N3M0 oesophageal squamous cell carcinoma who underwent nCRT as an initial treatment intent between January 2005 and March 2020. Patients not receiving surgery were categorized using predefined criteria. To evaluate the risk of refusing surgery, a propensity-matched comparison with those who received surgery was performed. Recurrence-free (RFS) and overall survival (OS) was compared between groups, according to clinical response to nCRT. RESULTS: Among the study population (n = 715), 105 patients (14.7%) eventually failed to reach surgery. There were three major patterns of not receiving surgery: disease progression before surgery (n = 25), functional deterioration at reassessment (n = 47), and patient's refusal without contraindications (n = 33). After propensity-score matching, the RFS curves of the surgery group and the refusal group were significantly different (P < 0.001), while OS curves were not significantly different (P = 0.069). In patients who achieved clinical complete response on re-evaluation, no significant difference in the RFS curves (P = 0.382) and in the OS curves (P = 0.290) was observed between the surgery group and the refusal group. However, among patients who showed partial response or stable disease on re-evaluation, the RFS and OS curves of the refusal group were overall significantly inferior compared to those of the surgery group (both P < 0.001). The 5-year RFS rates were 10.3% for the refusal group and 48.2% for the surgery group, and the 5-year OS rates were 8.2% for the refusal group and 46.1% for the surgery group. CONCLUSIONS: Patient's refusal remains one of the major obstacles in completing the trimodality therapy for oesophageal squamous cell carcinoma. Refusing surgery when offered may jeopardize oncological outcome, particularly in those with residual disease on re-evaluation after nCRT. These results provide significant implications for consulting patients who are reluctant to oesophagectomy after nCRT.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Terapia Neoadyuvante , Humanos , Masculino , Femenino , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Persona de Mediana Edad , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Terapia Neoadyuvante/estadística & datos numéricos , Anciano , Estudios Retrospectivos , Estadificación de Neoplasias , Puntaje de Propensión , Quimioradioterapia Adyuvante/estadística & datos numéricos , Negativa del Paciente al Tratamiento/estadística & datos numéricos , QuimioradioterapiaRESUMEN
AIM: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. RESULTS: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. CONCLUSIONS: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.
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Adamantano , Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Dipéptidos , Quimioterapia Combinada , Glucósidos , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Metformina/uso terapéutico , Metformina/administración & dosificación , Metformina/efectos adversos , Glucósidos/administración & dosificación , Glucósidos/efectos adversos , Glucósidos/uso terapéutico , Masculino , Femenino , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/efectos adversos , Persona de Mediana Edad , Dipéptidos/efectos adversos , Dipéptidos/administración & dosificación , Dipéptidos/uso terapéutico , Adamantano/análogos & derivados , Adamantano/administración & dosificación , Adamantano/efectos adversos , Adamantano/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Anciano , Resultado del Tratamiento , Hipoglucemia/inducido químicamente , Compuestos de Sulfonilurea/uso terapéutico , Compuestos de Sulfonilurea/administración & dosificación , Compuestos de Sulfonilurea/efectos adversos , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Adulto , Aumento de Peso/efectos de los fármacos , Fosfato de Sitagliptina/uso terapéutico , Fosfato de Sitagliptina/administración & dosificación , Fosfato de Sitagliptina/efectos adversosRESUMEN
The crystal structure and phase stability of a host lattice plays an important role in efficient upconversion phenomena. In stable hosts, lanthanides doping should not generally change the crystal structure of the host itself. But when phase of a system drastically changes after lanthanide doping resulting in multiple phases, accurate identification of upconverting phase remains a challenge. Herein, an attempt to synthesize lanthanide-doped NiMoO4 by microwave hydrothermal method produced MoO3/Yb2Mo4O15/NiMoO4 micro-nano composite upconversion phosphor. A combined approach of density functional theory (DFT) calculations and single-particle-level upconversion imaging has been employed to elucidate the phase stability of different phases and upconversion properties within the composite. Through single-particle-level imaging under 980 nm excitation, an unprecedented resolution in visualizing individual emitting and non-emitting regions within the composite has been achieved, thereby allowing to accurately assign the Yb2Mo4O15 as a sole upconversion emitting phase in the composite. Result of the DFT calculation further shows that the Yb2Mo4O15 phase is the most thermodynamically preferred over other lanthanide-doped phases in the composite. This comprehensive understanding not only advances the knowledge of upconversion emission from composite materials but also holds promise for tailoring optical properties of materials for various applications, including bioimaging, sensing, and photonics, where controlled light emission is crucial.
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Chest wall reconstruction is challenging due to the complex shape and large defect size. The three-dimensional printing technology enables the fabrication of customized implants, and 3D-printed pure-titanium could provide superior mechanical properties to conventional materials. The aim of this study was to evaluate long-term outcomes of patients undergoing chest wall reconstruction with a 3D-printed pure-titanium implant. Between August 2018 and May 2021, 5 patients underwent surgery due to sternal metastasis (n = 3), postoperative sternal wound infection (n = 1) and deformity (n = 1). The customized implant was designed and constructed based on the size and shape of the chest wall defect measured on computed tomography. All patients demonstrated uneventful recovery without complications during the hospital course. During the median follow-up of 20 months, 1 patient underwent revision surgery due to implant breakage, and 1 removed the implant due to trauma-related chest wall infection. One patient died from cancer progression, while 3 patients are alive without any implant-related complications. Chest wall reconstruction using a 3D-printed pure-titanium implant could be a novel alternative for patients with various conditions affecting the sternum and ribs.
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Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.
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Neoplasias Esofágicas , Síndrome de Dificultad Respiratoria , Humanos , Esofagectomía/efectos adversos , Estudios Retrospectivos , Pulmón/cirugía , Volumen Espiratorio Forzado , Síndrome de Dificultad Respiratoria/etiología , Neoplasias Esofágicas/complicaciones , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: The upright head roll test (UHRT) is a recently introduced diagnostic maneuver for lateral semicircular canal benign paroxysmal positional vertigo (LSC-BPPV). OBJECTIVE: This study aimed to evaluate the reliability and validity of the UHRT. METHODS: Two separate studies were conducted. Study 1 analyzed 827 results of videonystagmography (VNG) to assess UHRT reliability, and Study 2 analyzed 130 LSC-BPPV cases to evaluate UHRT validity. RESULTS: The inter-test reliability between UHRT and the supine head roll test (SHRT) showed substantial agreement (Cohen's kappaâ=â0.753) in direction-changing positional nystagmus (DCPN) and almost perfect agreement (Cohen's kappaâ=â0.836) in distinguishing the direction of DCPN. The validity assessment of UHRT showed high accuracy in diagnosing LSC-BPPV (80.0%) and in differentiating the variant types (74.6%). UHRT was highly accurate in diagnosing the canalolithiasis type in LSC-BPPV patients (Cohen's kappaâ=â0.835); however, it showed only moderate accuracy in diagnosing the cupulolithiasis type (Cohen's kappaâ=â0.415). The intensity of nystagmus in UHRT was relatively weaker than that in SHRT (Pâ<â0.05). CONCLUSION: UHRT is a reliable test for diagnosing LSC-BPPV and distinguishing subtypes. However, UHRT has a limitation in discriminating the affected side owing to a weaker intensity of nystagmus than SHRT.
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Vértigo Posicional Paroxístico Benigno , Canales Semicirculares , Pruebas de Función Vestibular , Humanos , Vértigo Posicional Paroxístico Benigno/diagnóstico , Vértigo Posicional Paroxístico Benigno/fisiopatología , Masculino , Femenino , Reproducibilidad de los Resultados , Persona de Mediana Edad , Canales Semicirculares/fisiopatología , Anciano , Adulto , Pruebas de Función Vestibular/métodos , Pruebas de Función Vestibular/normas , Movimientos de la Cabeza/fisiología , Anciano de 80 o más Años , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/fisiopatología , Adulto Joven , Nistagmo Fisiológico/fisiologíaRESUMEN
PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) serve as the standard first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC). Despite the sustained clinical benefits achieved through optimal EGFR-TKI treatments, including the third-generation EGFR-TKI osimertinib, resistance inevitably develops. Currently, there are no targeted therapeutic options available postprogression on osimertinib. Here, we assessed the preclinical efficacy of BI-4732, a novel fourth-generation EGFR-TKI, using patient-derived preclinical models reflecting various clinical scenarios. EXPERIMENTAL DESIGN: The antitumor activity of BI-4732 was evaluated using Ba/F3 cells and patient-derived cell/organoid/xenograft models with diverse EGFR mutations. Intracranial antitumor activity of BI-4732 was evaluated in a brain-metastasis mouse model. RESULTS: We demonstrated the remarkable antitumor efficacy of BI-4732 as a single agent in various patient-derived models with EGFR_C797S-mediated osimertinib resistance. Moreover, BI-4732 exhibited activity comparable to osimertinib in inhibiting EGFR-activating (E19del and L858R) and T790M mutations. In a combination treatment strategy with osimertinib, BI-4732 exhibited a synergistic effect at significantly lower concentrations than those used in monotherapy. Importantly, BI-4732 displayed potent antitumor activity in an intracranial model, with low efflux at the blood-brain barrier. CONCLUSIONS: Our findings highlight the potential of BI-4732, a selective EGFR-TKI with high blood-brain barrier penetration, targeting a broad range of EGFR mutations, including C797S, warranting clinical development.
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Acrilamidas , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Ratones , Animales , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Resistencia a Antineoplásicos/genética , Compuestos de AnilinaRESUMEN
The occurrence of autophagy in recombinant Chinese hamster ovary (rCHO) cell culture has attracted attention due to its effects on therapeutic protein production. Given the significance of glycosylation in therapeutic proteins, this study examined the effects of autophagy-inhibiting chemicals on sialylation of Fc-fusion glycoproteins in rCHO cells. Three chemical autophagy inhibitors known to inhibit different stages were separately treated with two rCHO cell lines that produce the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44. All autophagy inhibitors significantly decreased the sialylation of Fc-fusion glycoprotein in both cell lines. The decrease in sialylation of Fc-fusion glycoprotein is unlikely to be attributed to the release of intracellular enzymes, given the high cell viability and low activity of extracellular sialidases. Interestingly, the five intracellular nucleotide sugars remained abundant in cells treated with autophagy inhibitors. In the mRNA expression profiles of 27 N-glycosylation-related genes using the NanoString nCounter system, no significant differences in gene expression were noted. With the positive effect of supplementing nucleotide sugar precursors on sialylation, attempts were made to enhance the levels of intracellular nucleotide sugars by supplying these precursors. The addition of nucleotide sugar precursors to cultures treated with inhibitors successfully enhanced the sialylation of Fc-fusion glycoproteins compared to the control culture. This was particularly evident under mild stress conditions and not under relatively severe stress conditions, which were characterized by a high decrease in sialylation. These results suggest that inhibiting autophagy in rCHO cell culture decreases sialylation of Fc-fusion glycoprotein by constraining the availability of intracellular nucleotide sugars. KEY POINTS: ⢠The autophagy inhibition in rCHO cell culture leads to a significant reduction in the sialylation of Fc-fusion glycoprotein. ⢠The pool of five intracellular nucleotide sugars remained highly abundant in cells treated with autophagy inhibitors. ⢠Supplementation of nucleotide sugar precursors effectively restores decreased sialylation, particularly under mild stress conditions but not in relatively severe stress conditions.
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Autofagia , Glicoproteínas , Animales , Cricetinae , Células CHO , Cricetulus , Glicoproteínas/genética , Nucleótidos , AzúcaresRESUMEN
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as novel cardioprotective agents. However, their direct impact on cardiomyocyte injury is yet to be studied. In this work, we investigate the underlying molecular mechanisms of empagliflozin (EMPA), an SGLT2 inhibitor, in mitigating palmitate (PA)-induced cardiomyocyte injury in H9c2 cells. We found that EMPA significantly attenuated PA-induced impairments in insulin sensitivity, ER stress, inflammatory cytokine gene expression, and cellular apoptosis. Additionally, EMPA elevated AMP levels, activated the AMPK pathway, and increased carnitine palmitoyl transferase1 (CPT1) gene expression, which collectively enhanced fatty acid oxidation and reduced stress signals. This study reveals a novel mechanism of EMPA's protective effects against PA-induced cardiomyocyte injury, providing new therapeutic insights into EMPA as a cardioprotective agent.
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BACKGROUND: Current therapies to effectively treat long-bone defects and extensive bone tissue loss remains limited. In this study, we created a new bone substitute by integrating advanced technologies such as structure patterning, controlled release of a bone growth factor and conjugation system for clinically effective bone regeneration. This novel bioactive bone substitute was evaluated for its safety and efficacy using a rabbit ulna model. METHODS: A three dimensional bone patterned cylindrical structure with 1.5 cm in length and 5 mm in diameter was printed using poly(L-lactic acid)(PLLA) as a weight-bearing support and space-filling scaffold. And a bone morphogenetic protein 2 (BMP2) was employed to enhance bone regeneration, and coated to a 3D PLLA using alginate catechol and collagen to prolong the release kinetics. This novel bone substitute (BS)was evaluated for its physico-chemical and biological properties in vitro, and histological analysis and radiographical analysis such as X-ray, CT and micro-CT image analysis were performed to evaluate new bone formation in vivo. RESULTS: The BS possesses an ideal shape and mechanically suitable proeperties for clinical use, with an easy-to-grab and break-resistant design at both ends, 80 ± 10 MPa of compression strength, and BMP2 release for two months. Histological analysis demonstrated the biocompability of BS with minimal inflammation and immune response, and X-ray, CT and micro-CT demonstrated effective new bone formation in rabbit ulna defect model. CONCLUSION: The preclinical study of a novel bioactive bone substitute has shown its safe and effective properties in an animal model suggesting its clinical potential.
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Sustitutos de Huesos , Animales , Conejos , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Andamios del Tejido/química , Regeneración Ósea , Cúbito/patología , Microtomografía por Rayos XRESUMEN
Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla, Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.
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Perilla , Humanos , Perilla/genética , Perilla/metabolismo , Ácidos Grasos/genética , Ácidos Grasos/metabolismo , Fitomejoramiento , Hormonas , República de CoreaRESUMEN
In vanadium redox flow batteries (VRFBs), simultaneously achieving high proton conductivity, low vanadium-ion permeability, and outstanding chemical stability using electrolyte membranes is a significant challenge. In this study, we report the fabrication of a tri-directional poly(2,5-benzimidazole) (T-ABPBI) membrane using a direct casting method. The direct-cast T-ABPBI (D-T-ABPBI) membrane was fabricated by modifying the microstructure of the membrane while retaining the chemical structure of ABPBI, having outstanding chemical stability. The D-T-ABPBI membrane exhibited lower crystallinity and an expanded free volume compared to the general solvent-cast T-ABPBI (S-T-ABPBI) membrane, resulting in enhanced hydrophilic absorption capabilities. Compared to the S-T-ABPBI membrane, the enhanced hydrophilic absorption capability of the D-T-ABPBI membrane resulted in a decrease in the specific resistance (the area-specific resistance of S-T-ABPBI and D-T-ABPBI membrane is 1.75 and 0.98 Ωcm2, respectively). Additionally, the D-T-ABPBI membrane showed lower vanadium permeability (3.40 × 10-7 cm2 min-1) compared to that of Nafion 115 (5.20 × 10-7 cm2 min-1) due to the Donnan exclusion effect. Owing to the synergistic effects of these properties, the VRFB assembled with D-T-ABPBI membrane had higher or equivalent coulomb efficiencies (>97%) and energy efficiencies (70-91%) than Nafion 115 at various current densities (200-40 mA cm-2). Furthermore, the D-T-ABPBI membrane exhibited stable performance for over 300 cycles at 100 mA cm-2, suggesting its outstanding chemical stability against the highly oxidizing VO2+ ions during practical VRFB operation. These results indicate that the newly fabricated D-T-ABPBI membranes are promising candidates for VRFB application.
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High-quality molecular markers are essential for marker-assisted selection to accelerate breeding progress. Compared with diploid species, recently diverged polyploid crop species tend to have highly similar homeologous subgenomes, which is expected to limit the development of broadly applicable locus-specific single-nucleotide polymorphism (SNP) assays. Furthermore, it is particularly challenging to make genome-wide marker sets for species that lack a reference genome. Here, we report the development of a genome-wide set of kompetitive allele specific PCR (KASP) markers for marker-assisted recurrent selection (MARS) in the tetraploid minor crop perilla. To find locus-specific SNP markers across the perilla genome, we used genotyping-by-sequencing (GBS) to construct linkage maps of two F2 populations. The two resulting high-resolution linkage maps comprised 2326 and 2454 SNP markers that spanned a total genetic distance of 2133 cM across 16 linkage groups and 2169 cM across 21 linkage groups, respectively. We then obtained a final genetic map consisting of 22 linkage groups with 1123 common markers from the two genetic maps. We selected 96 genome-wide markers for MARS and confirmed the accuracy of markers in the two F2 populations using a high-throughput Fluidigm system. We confirmed that 91.8% of the SNP genotyping results from the Fluidigm assay were the same as the results obtained through GBS. These results provide a foundation for marker-assisted backcrossing and the development of new varieties of perilla.
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Perilla , Tetraploidía , Genotipo , Perilla/genética , Polimorfismo de Nucleótido Simple/genética , Fitomejoramiento , Ligamiento Genético , Genoma de Planta/genéticaRESUMEN
BACKGROUND/AIMS: Due to the possible metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia. METHODS: Medical records were reviewed retrospectively in patients who underwent endoscopic resection for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into two groups; annual surveillance vs. biannual surveillance. The incidence of metachronous gastric neoplasia was identified, and the risk factors for metachronous gastric neoplasia were investigated. RESULTS: Among the 1,533 patients who underwent endoscopic resection for gastric neoplasia, 677 patients were enrolled in this study (annual surveillance 302, biannual surveillance 375). Metachronous gastric neoplasia was observed in 61 patients (annual surveillance 26/302, biannual surveillance 32/375, P = 0.989), and metachronous gastric adenocarcinoma was observed in 26 patients (annual surveillance 13/302, biannual surveillance 13/375, P = 0.582). All the lesions were removed by endoscopic resection successfully. In a multivariate analysis, severe atrophic gastritis on gastroscopy was an independent risk factor for metachronous gastric adenocarcinoma (odds ratio 3.8, 95% confidence interval 1.4â10.1; P = 0.008). CONCLUSIONS: Meticulous observation to detect the metachronous gastric neoplasia is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after endoscopic resection for gastric neoplasia. Annual surveillance gastroscopy might be enough after endoscopic resection for gastric neoplasia.
Asunto(s)
Adenocarcinoma , Gastritis Atrófica , Infecciones por Helicobacter , Neoplasias Primarias Secundarias , Neoplasias Gástricas , Humanos , Gastroscopía/efectos adversos , Gastritis Atrófica/complicaciones , Gastritis Atrófica/patología , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/patología , Factores de Riesgo , Adenocarcinoma/patología , Mucosa Gástrica/cirugíaRESUMEN
Phase-change random-access memory is a promising non-volatile memory technology. However repeated phase-change operations can cause durability issues owing to defects formed by long-distance atom diffusion. To mitigate these issues, phase-change heterostructure (PCH) devices with confinement material (CM) layers based on transition metal dichalcogenides (TMDs) such as TiTe2 have been proposed. This study implements PCH devices with additional TMDs, including NiTe2 and MoTe2 , alongside TiTe2 , and analyzes their characteristics by examining the differences in the CM layers. The results show that the NiTe2 -based PCH device demonstrates a RESET current of 1.4 mA, 38% lower than that of the TiTe2 -based device, enabling low-power operation. Furthermore, the MoTe2 -based PCH device exhibits a cycling endurance exceeding 107 cycles, a five-fold improvement in durability compare with the TiTe2 -based device. The performance differences observe in each PCH device can be attributed to the variation in the material properties, such as the cohesive energy and electrical conductivity, of the TMDs used as the CM layer. These results provide critical clues to improve the performance and reliability of conventional PCH memory devices.