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1.
Sci Rep ; 14(1): 21244, 2024 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261636

RESUMEN

We aimed to investigate the association between health-related behaviors and obstructive sleep apnea (OSA) among Korean adults. A cross-sectional design using national open data was employed. Data from 8,096 adults aged 40 years and above who participated in the Korea National Health and Nutrition Examination Survey between 2019 and 2021 were analyzed. The participants' OSA risk level was assessed using the STOP-Bang questionnaire. A logistic regression analysis was performed to investigate the association between health-related behaviors and high risk for OSA. The association between health-related behaviors and OSA risk remained significant for former smokers (OR = 1.643) and high-risk drinking (OR = 1.365), after adjusting for variables that showed significant differences in general and metabolic characteristics. Implementing lifestyle modifications is crucial for mitigating the health and societal impact of OSA. Understanding and addressing modifiable risk factors, including high-risk drinking and smoking, should be prioritized in nursing intervention. Nursing interventions are critical for preventing and managing OSA among Korean adults. Prioritizing high-risk behaviors through cessation programs and education is essential. Vulnerability of individuals living alone must be addressed through community outreach and support services. Emphasizing routine screenings for pre-hypertension and pre-diabetes, promoting balanced nutrition, and encouraging physical activity are crucial.


Asunto(s)
Conductas Relacionadas con la Salud , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/epidemiología , República de Corea/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Transversales , Factores de Riesgo , Anciano , Fumar/efectos adversos , Fumar/epidemiología , Encuestas Nutricionales , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/efectos adversos , Ejercicio Físico , Encuestas y Cuestionarios
2.
Nutrients ; 16(17)2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39275149

RESUMEN

Recent studies suggest that lactate intake has a positive effect on glycogen recovery after exercise. However, it is important to verify the effect of lactate supplementation alone and the timing of glycogen recovery. Therefore, in this study, we aimed to examine the effect of lactate supplementation immediately after exercise on glycogen recovery in mice liver and skeletal muscle at 1, 3, and 5 h after exercise. Mice were randomly divided into the sedentary, exercise-only, lactate, and saline-treated groups. mRNA expression and activation of glycogen synthesis and lactate transport-related factors in the liver and skeletal muscle were assessed using real-time polymerase chain reaction. Skeletal muscle glycogen concentration showed an increasing trend in the lactate group compared with that in the control group at 3 and 5 h after post-supplementation. Additionally, exogenous lactate supplementation significantly increased the expression of core glycogen synthesis enzymes, lactate transporters, and pyruvate dehydrogenase E1 alpha 1 in the skeletal muscles. Conversely, glycogen synthesis, lactate transport, and glycogen oxidation to acetyl-CoA were not significantly affected in the liver by exogenous lactate supplementation. Overall, these results suggest that post-exercise lactate supplement enables glycogen synthesis and recovery in skeletal muscles.


Asunto(s)
Glucógeno , Ácido Láctico , Hígado , Condicionamiento Físico Animal , Animales , Glucógeno/metabolismo , Ácido Láctico/metabolismo , Condicionamiento Físico Animal/fisiología , Masculino , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Ratones Endogámicos C57BL , Transportadores de Ácidos Monocarboxílicos/metabolismo
3.
Taiwan J Obstet Gynecol ; 63(5): 781-784, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39266166

RESUMEN

OBJECTIVE: Female urethral diverticulum (UD), an evagination of the urethral mucosa into the surrounding connective tissue, is extremely rare in pregnancy. No clear guidelines on the optimal management of UD have been established, except for a common conservative approach. Here, we discuss how to manage UD with pregnancy. CASE REPORT: A 39-year-old gravida 4, para 0, abortion 3 (G4P0A3) woman at 34+0 gestational weeks (GW) visited our outpatient department with a 6-cm septate vaginal mass. Transvaginal ultrasound sonography (TVUS) revealed a 5.5 x 4.9-cm multicystic mass, which was confirmed as UD with pelvic MRI. She was admitted because of preterm labor. A cesarean section was performed at 36+5 GW due to a previous myomectomy, and a healthy male baby was born. UD was still observed in the patient two months after delivery. Periurethral diverticulectomy was performed, and pathological analysis revealed UD with chronic inflammation and edema. CONCLUSION: Previous reports and our case report show that UD can develop during pregnancy and that pelvic MRI is suitable for its accurate diagnosis. Vaginal delivery is possible in pregnant women with the small size of the UD. UD aspiration can permit vaginal delivery in a few cases; however, pus can occur at the aspirated site after the operation. If UD is still observed after delivery, urethral diverticulectomy is recommended.


Asunto(s)
Cesárea , Divertículo , Complicaciones del Embarazo , Enfermedades Uretrales , Humanos , Embarazo , Femenino , Divertículo/cirugía , Divertículo/diagnóstico por imagen , Divertículo/diagnóstico , Adulto , Enfermedades Uretrales/cirugía , Enfermedades Uretrales/diagnóstico por imagen , Enfermedades Uretrales/diagnóstico , Complicaciones del Embarazo/cirugía , Complicaciones del Embarazo/diagnóstico por imagen , Complicaciones del Embarazo/diagnóstico , Imagen por Resonancia Magnética
4.
Biomater Sci ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39253746

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is a form of hepatic steatosis in which more than 5% of the liver's weight is fat, primarily due to the overconsumption of soft drinks and a Western diet. In this study, we investigate the potential of plant-derived exosome-like nanovesicles (PENs) to prevent liver fibrosis and leaky gut resulting from NAFLD. Specifically, we examine whether hemp sprout-derived exosome-like nanovesicles (HSNVs) grown on smart farms could exert protective effects against NAFLD by inhibiting liver fibrosis. HSNVs ranging from 100-200 nm were measured using nanoparticle tracking analysis (NTA). HSNVs (1 mg kg-1) were orally administered for 5 weeks to mice with NAFLD induced by feeding them a Western diet (WD; a fat- and cholesterol-rich diet) and fat-, fructose-, and cholesterol-rich (FFC) diet for 8 weeks. Importantly, the administration of HSNVs markedly reduced oxidative stress and fibrosis marker proteins in NAFLD mouse models and LX2 cells. Furthermore, treatment with HSNVs prevented a significant decrease in the quantity of gut barrier proteins and endotoxin levels in NAFLD mouse models. For the first time, these results demonstrate that HSNVs can exhibit a hepatoprotective effect against gut leakiness and WD/FFC-induced liver fibrosis by inhibiting oxidative stress and reducing fibrosis marker proteins.

5.
Biomed Pharmacother ; 179: 117393, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39260326

RESUMEN

This study was conducted to evaluate the effects of Allium hookeri (AH) leaves cultivated with different light-emitting diode (LED) intensities (L: low, 100 µmol/m2/s; M: medium, 150 µmol/m2/s; H: high, 200 µmol/m2/s). Alliin concentration increased as light intensity increased in AH and showed the highest level at LED-H condition. The anti-obesity and immunomodulatory properties of AH were evaluated in a cyclophosphamide (CPA)-induced immunosuppressed obese animal model. C57BL/6 J mice were randomly divided into control (CON), high-fat diet (HFD) control (CON-H), negative control (NC), positive control (PC, ß-glucan, 50 mg/kg body weight (BW)), AH L, M, and H groups. The three kinds of AH extracts were orally administered to the mice at 300 mg/kg BW for 2 weeks. Except for CON and CON-H, all the other groups were intraperitoneally treated with CPA. Epididymal and abdominal fat weight decreased as LED intensity increased while spleen weight increased in the AH groups. Serum glucose decreased as LED intensity increased in the AH groups and H group showed the lowest level. Triglycerides, total, and LDL-cholesterol levels decreased while HDL-cholesterol level increased in the AH groups compared to the NC group. Moreover, AH effectively reduced serum ALT and AST levels and increased the total white blood cell count, particularly elevating lymphocyte and monocyte levels. Furthermore, NK cell activity was higher in the AH groups. These findings suggest that AH cultivated at optimal LED intensity could be used as a novel biomedicine and in pharmacotherapy to treat related diseases to improve public health without any toxicity.

6.
BMC Womens Health ; 24(1): 466, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39182070

RESUMEN

BACKGROUND: Despite the well-known health benefits of exercise, women's participation in exercise is low worldwide. As women are at risk of developing various chronic diseases as they age, suggesting effective exercise methods that can maximize energy consumption is needed to prevent such conditions. Excess post-exercise oxygen consumption (EPOC) can maximize energy consumption. In this crossover, randomized controlled trial, we aimed to compare the EPOC for different exercise modalities including continuous exercise (CE), interval exercise (IE), and accumulated exercise (AE) that spent the homogenized energy expenditure during exercise in healthy women. METHODS: Forty-four participants (age, 36.09 ± 11.73 years) were recruited and randomly allocated to three groups. The intensity of each modality was set as follows: CE was performed for 30 min at 60% peak oxygen uptake (VO2peak). IE was performed once for 2 min at 80% VO2peak, followed by 3 min at 80% VO2peak, and 1 min at 40% VO2peak, for a total of six times over 26 min. AE was performed for 10 min with a 60% VO2peak and was measured thrice a day. RESULTS: During exercise, energy metabolism was higher for IE and CE than that for AE. However, this was reversed for AE during EPOC. Consequently, the greatest energy metabolism was shown for AE during total time (exercise and EPOC). CONCLUSIONS: By encouraging regular exercises, AE can help maintain and improve body composition by increasing compliance with exercise participation, given its short exercise times, and by efficiently increasing energy consumption through the accumulation of EPOC. TRIAL REGISTRATION: Clinical number (KCT0007298), 18/05/2022, Institutional Review Board of Konkuk University (7001355-202201-E-160).


Asunto(s)
Estudios Cruzados , Metabolismo Energético , Ejercicio Físico , Consumo de Oxígeno , Humanos , Femenino , Consumo de Oxígeno/fisiología , Adulto , Ejercicio Físico/fisiología , Metabolismo Energético/fisiología , Persona de Mediana Edad , Adulto Joven
7.
J Korean Soc Radiol ; 85(4): 754-768, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39130791

RESUMEN

Purpose: To identify clinical and MR predictors of retro-odontoid pseudotumor (ROP) regression after posterior fixation in patients with atlantoaxial instability. Materials and Methods: We included patients who had undergone posterior fixation for atlantoaxial instability and preoperative and postoperative MR imaging. Patients were classified into two groups according to the degree of ROP regression after posterior fixation: regression (≥ 10% reduction) and no regression (< 10% reduction). Mann-Whitney and Fisher's exact tests were performed to identify the clinical (age and sex) and MR predictors (preoperative ROP thickness, ROP type, MR signal homogeneity of the ROP, spinal cord signal change, spinal cord atrophy, ossified posterior longitudinal ligament, os odontoideum, and atlantodental interval) associated with ROP regression. Results: We retrospectively assessed 11 consecutive patients (7 female; median age, 66 years [range, 31-84 years]). Posterior fixation induced ROP regression in eight (72.7%) patients. Older age and greater preoperative ROP thickness significantly correlated with ROP regression (p = 0.024 and 0.012, respectively). All patients with preoperative ROP thickness > 5 mm exhibited ROP regression. The other variables were not significantly associated with ROP regression. Conclusion: Older age and thicker preoperative ROP are associated with ROP regression after posterior fixation in patients with atlantoaxial instability.

8.
J Hazard Mater ; 478: 135474, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39173370

RESUMEN

This study developed a continuous reactor system employing a hybrid hydrogel composite synthesized using a complex sludge microbiome and an adsorbent (HSA). This HSA-based system effectively eliminated the environmental risks associated with a mixture of the antibiotics ciprofloxacin and sulfamethoxazole, which exhibited higher toxicity in combination than individually at environmentally relevant levels. Analytical chemistry experiments revealed the in-situ generation of various byproducts (BPs) within the bioreactor system, with two of these BPs recording toxicity levels that surpassed those of their parent compound. The HSA approach successfully prevented the functional microbiome from being washed out of the reactor, while HSA efficiently removed antibiotic residues in their original and BP forms through synergistic adsorptive and biotransformation mechanisms, ultimately reducing the overall ecotoxicity. The use of HSA thus demonstrates promise not only as a mean to reduce the threat posed by toxic antibiotic residues to aquatic ecosystems but also as a practical solution to operational challenges, such as biomass loss/washout, that are frequently encountered in various environmental bioprocesses.


Asunto(s)
Antibacterianos , Reactores Biológicos , Ciprofloxacina , Microbiota , Aguas del Alcantarillado , Sulfametoxazol , Contaminantes Químicos del Agua , Antibacterianos/química , Antibacterianos/toxicidad , Microbiota/efectos de los fármacos , Sulfametoxazol/toxicidad , Ciprofloxacina/toxicidad , Ciprofloxacina/química , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/química , Aguas del Alcantarillado/microbiología , Adsorción , Carbón Orgánico/química , Hidrogeles/química
9.
Immune Netw ; 24(3): e26, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38974210

RESUMEN

Recent advancements in various technologies have shed light on the critical role of metabolism in immune cells, paving the way for innovative disease treatment strategies through immunometabolism modulation. This review emphasizes the glucose metabolism of myeloid-derived suppressor cells (MDSCs), an emerging pivotal immunosuppressive factor especially within the tumor microenvironment. MDSCs, an immature and heterogeneous myeloid cell population, act as a double-edged sword by exacerbating tumors or mitigating inflammatory diseases through their immune-suppressive functions. Numerous recent studies have centered on glycolysis of MDSC, investigating the regulation of altered glycolytic pathways to manage diseases. However, the specific changes in MDSC glycolysis and their exact functions continue to be areas of ongoing discussion yet. In this paper, we review a range of current findings, including the latest research on the alteration of glycolysis in MDSCs, the consequential functional alterations in these cells, and the outcomes of attempts to modulate MDSC functions by regulating glycolysis. Ultimately, we will provide insights into whether these research efforts could be translated into clinical applications.

10.
Plast Reconstr Surg ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39023555

RESUMEN

BACKGROUND: Step-off deformity is a suboptimal aesthetic outcome at the donor site following abdominal flap harvesting for breast reconstruction. This study assessed the prevalence of step-off deformities post-autologous breast reconstruction and explored the associated risk factors. METHODS: This retrospective study evaluated step-off deformities among consecutive patients who had undergone autologous abdominal flap-based breast reconstruction between January 2019 and December 2022. The postoperative evaluation utilized medical records and photos, defining step-off deformity as a thickness discrepancy in the upper and lower abdominal tissue with reference to the scar line and angles <165°. Moreover, we explored potential risk factors, including abdominal subcutaneous tissue thickness based on computed tomography. RESULTS: In total, 187 patients underwent abdominal flap-based breast reconstruction; 38 exhibited step-off deformity. The case group exhibited significantly higher body mass index (BMI) and greater subcutaneous layer thickness in both the upper and lower abdomen compared to those of the control group. The groups did not differ significantly in postoperative complications, including abdominal bulging or hernia. Multivariable analysis revealed notable risk factors for step-off deformity development: BMI (p=0.026), presence of preoperative abdominal fold (p=0.028) and thickness differences between the upper and lower abdomen (p=0.011). The cut-off values were 26.1 kg/m2 for BMI and 9.5 mm for thickness differences. CONCLUSIONS: Higher BMI, presence of abdominal fold, and significant upper-lower abdomen tissue thickness differences may be associated with an increased risk of donor step-off deformity after abdominal flap harvest. Our findings may inform patient counseling and warrant attention when closing donor wounds in high-risk individuals.

11.
Vet Med Sci ; 10(4): e1521, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952271

RESUMEN

BACKGROUND: Cynomolgus monkeys (Macaca fascicularis) are essential in biomedical research, including reproductive studies. However, the application of human estimated foetal weight (EFW) formulas using ultrasonography (USG) in these non-human primates is not well established. OBJECTIVES: This study aims to evaluate the applicability of human EFW formulas for estimating foetal weight in cynomolgus monkeys at approximately 130 days of gestation. METHODS: Our study involved nine pregnant cynomolgus monkeys. We measured foetal parameters, including biparietal diameter, head circumference, abdominal circumference and femur length using USG. The EFW was calculated using 11 human EFW formulas. The actual birthweight (ABW) was recorded following Cesarean section, the day after the EFW calculation. For comparing EFW and ABW, we employed statistical methods such as mean absolute percentage error (APE) and Bland-Altman analysis. RESULTS: The ABW ranged between 200.36 and 291.33 g. Among the 11 formulas, the Combs formula showed the lowest APE (4.3%) and highest correlation with ABW (p < 0.001). Notably, EFW and ABW differences for the Combs formula were ≤5% in 66.7% and ≤10% in 100% of cases. The Bland-Altman analysis supported these results, showing that all cases fell within the limits of agreement. CONCLUSIONS: The Combs formula is applicable for estimating the weight of cynomolgus monkey fetuses with USG at approximately 130 days of gestation. Our observations suggest that the Combs formula can be applied in the prenatal care and biomedical research of this species.


Asunto(s)
Peso al Nacer , Peso Fetal , Macaca fascicularis , Ultrasonografía Prenatal , Animales , Macaca fascicularis/embriología , Macaca fascicularis/fisiología , Femenino , Peso Fetal/fisiología , Embarazo , Ultrasonografía Prenatal/veterinaria , Humanos
12.
Biomolecules ; 14(7)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-39062520

RESUMEN

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder. While metformin has demonstrated the ability to inhibit cyst growth in animal models of ADPKD via activation of adenosine monophosphate-activated protein kinase (AMPK), its effectiveness in humans is limited due to its low potency. This study explored the impact of HL156A, a new and more potent AMPK activator, in a mouse model of ADPKD. METHODS: To investigate whether HL156A inhibits the proliferation of renal cyst cells in ADPKD in vitro, exogenous human telomerase reverse transcriptase (hTERT)-immortalized renal cyst cells from ADPKD patients were treated with HL156A, and an MTT (dimethylthiazol-diphenyltetrazolium bromide) assay was performed. To assess the cyst-inhibitory effect of HL156A in vivo, we generated Pkd1 conditional knockout (KO) mice with aquaporin 2 (AQP2)-Cre, which selectively expresses Cre recombinase in the collecting duct. The effectiveness of HL156A in inhibiting cyst growth and improving renal function was confirmed by measuring the number of cysts and blood urea nitrogen (BUN) levels in the collecting duct-specific Pkd1 KO mice. RESULTS: When cyst cells were treated with up to 20 µM of metformin or HL156A, HL156A reduced cell viability by 25% starting at a concentration of 5 µM, whereas metformin showed no effect. When AQP2-Cre male mice were crossed with Pkd1flox/flox female mice, and when AQP2-Cre female mice were crossed with Pkd1flox/flox male mice, the number of litters produced by both groups was comparable. In collecting duct-specific Pkd1 KO mice, HL156A was found to inhibit cyst growth, reducing both the number and size of cysts. Furthermore, it was confirmed that kidney function improved as HL156A treatment led to a reduction in elevated BUN levels. Lastly, it was observed that the increase in AMPK phosphorylation induced by HL156A decreased ERK phosphorylation and α-SMA expression. CONCLUSION: HL156A has potential as a drug that can restore kidney function in ADPKD patients by inhibiting cyst growth.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Riñón Poliquístico Autosómico Dominante , Animales , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Riñón Poliquístico Autosómico Dominante/metabolismo , Riñón Poliquístico Autosómico Dominante/patología , Riñón Poliquístico Autosómico Dominante/genética , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Humanos , Ratones Noqueados , Proliferación Celular/efectos de los fármacos , Masculino , Modelos Animales de Enfermedad , Quistes/tratamiento farmacológico , Quistes/patología , Quistes/metabolismo
13.
JAMA Netw Open ; 7(7): e2424299, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39058486

RESUMEN

Importance: Meticulous postoperative flap monitoring is essential for preventing flap failure and achieving optimal results in free flap operations, for which physical examination has remained the criterion standard. Despite the high reliability of physical examination, the requirement of excessive use of clinician time has been considered a main drawback. Objective: To develop an automated free flap monitoring system using artificial intelligence (AI), minimizing human involvement while maintaining efficiency. Design, Setting, and Participants: In this prognostic study, the designed system involves a smartphone camera installed in a location with optimal flap visibility to capture photographs at regular intervals. The automated program identifies the flap area, checks for notable abnormalities in its appearance, and notifies medical staff if abnormalities are detected. Implementation requires 2 AI-based models: a segmentation model for automatic flap recognition in photographs and a grading model for evaluating the perfusion status of the identified flap. To develop this system, flap photographs captured for monitoring were collected from patients who underwent free flap-based reconstruction from March 1, 2020, to August 31, 2023. After the 2 models were developed, they were integrated to construct the system, which was applied in a clinical setting in November 2023. Exposure: Conducting the developed automated AI-based flap monitoring system. Main Outcomes and Measures: Accuracy of the developed models and feasibility of clinical application of the system. Results: Photographs were obtained from 305 patients (median age, 62 years [range, 8-86 years]; 178 [58.4%] were male). Based on 2068 photographs, the FS-net program (a customized model) was developed for flap segmentation, demonstrating a mean (SD) Dice similarity coefficient of 0.970 (0.001) with 5-fold cross-validation. For the flap grading system, 11 112 photographs from the 305 patients were used, encompassing 10 115 photographs with normal features and 997 with abnormal features. Tested on 5506 photographs, the DenseNet121 model demonstrated the highest performance with an area under the receiver operating characteristic curve of 0.960 (95% CI, 0.951-0.969). The sensitivity for detecting venous insufficiency was 97.5% and for arterial insufficiency was 92.8%. When applied to 10 patients, the system successfully conducted 143 automated monitoring sessions without significant issues. Conclusions and Relevance: The findings of this study suggest that a novel automated system may enable efficient flap monitoring with minimal use of clinician time. It may be anticipated to serve as an effective surveillance tool for postoperative free flap monitoring. Further studies are required to verify its reliability.


Asunto(s)
Inteligencia Artificial , Colgajos Tisulares Libres , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Fotograbar/métodos , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentación , Adulto Joven , Adolescente , Procedimientos de Cirugía Plástica/métodos , Reproducibilidad de los Resultados
14.
Adv Sci (Weinh) ; : e2403663, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073756

RESUMEN

Clinical translation of current cancer vaccine research has been hampered by limited antitumor immune responses due to inefficient antigen delivery and presentation, suboptimal DC and T cell activation. Biomaterial-based nanovaccine offers targeted antigen delivery, protection from degradation in vivo, and prolonged tumor therapeutic efficacy. This study introduces a lipid-coated deoxycholic acid-survivin nanoassembly (DA-L-DSA). Survivin, overexpressed in several cancer cells and involved in cancer cell growth and immune evasion, is selected as a tumor-associated antigen. An major histocompatibility complex class I binding epitope of survivin is engineered into the nanoassembly. R848, TLR 7/8 agonist, and SD-208, TGF-beta receptor1 kinase inhibitor, are coencapsulated into the nanoassembly as potent adjuvants to boost DC maturation and enhance antigen presentation. The DA-L-DSA effectively stimulates the maturation of dendritic cells, migrates into lymph nodes, and enhances T-cell activation and Th1 response. A substantial influx of cytotoxic T lymphocytes into primary tumors is observed in a murine melanoma model and demonstrates anti-metastatic effects in a spontaneous breast cancer metastasis model. Furthermore, DA-L-DSA exhibits a remarkable synergistic effect in the combination therapy with immune checkpoint inhibitors alleviating immunosuppressive tumor microenvironment. Taken together, these findings suggest DA-L-DSA as a promising immuno-therapeutic platform that could be applicable to diverse intractable cancers.

15.
Pharmaceutics ; 16(6)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38931905

RESUMEN

Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles. Formulations with crystalline itraconazole (ITZ) and LEU were made via co-jet milling and HME followed by jet milling. The LEU ratio varied, comparing solubility, homogenization, and aerodynamic performance enhancements. In HME, ITZ solubility increased, and crystallinity decreased. Higher LEU ratios in HME formulations reduced the contact angle, enhancing mass median aerodynamic diameter (MMAD) size and aerodynamic performance synergistically. Achieving a maximum extra fine particle fraction of 33.68 ± 1.31% enabled stable deep lung delivery. This study shows that HME combined with LEU effectively produces inhalable particles, which is promising for improved drug dispersion and delivery.

16.
Mar Pollut Bull ; 205: 116553, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38880034

RESUMEN

This study reports the effects of bisphenol A (BPA) on the rotifer Brachionus plicatilis, focusing on growth performance, reproductive output, oxidative stress responses, and lipid metabolism genes. High BPA levels disrupted peak daily offspring production and led to oxidative stress and increased superoxide dismutase and catalase activity. The research identified distinctive monoacylglycerol O-acyltransferase (MGAT) and diacylglycerol O-acyltransferase (DGAT) genes in B. plicatilis, B. rotundiformis, and B. koreanus, enhancing understanding of lipid metabolism in these species. BPA exposure significantly altered MGAT and DGAT expression, and feeding status affected these regulatory patterns. When food was unavailable, BPA reduced DGAT2 and MGAT2a expression. However, under feeding conditions, DGAT2 and MGAT1 levels increased, indicating that nutritional status and BPA exposure interact to affect gene expression.


Asunto(s)
Compuestos de Bencidrilo , Metabolismo de los Lípidos , Estrés Oxidativo , Fenoles , Reproducción , Rotíferos , Contaminantes Químicos del Agua , Animales , Compuestos de Bencidrilo/toxicidad , Estrés Oxidativo/efectos de los fármacos , Fenoles/toxicidad , Reproducción/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Rotíferos/efectos de los fármacos , Rotíferos/fisiología , Contaminantes Químicos del Agua/toxicidad , Diacilglicerol O-Acetiltransferasa/genética , Diacilglicerol O-Acetiltransferasa/metabolismo
17.
JMIR Public Health Surveill ; 10: e52103, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941611

RESUMEN

BACKGROUND: Globally, over 39% of individuals are obese. Metabolic syndrome, usually accompanied by obesity, is regarded as a major contributor to noncommunicable diseases. Given this relationship, the concepts of metabolically healthy and unhealthy obesity, considering metabolic status, have been evolving. Attention is being directed to metabolically healthy people with obesity who have relatively low transition rates to noncommunicable diseases. As obesity rates continue to rise and unhealthy behaviors prevail among young adults, there is a growing need for obesity management that considers these metabolic statuses. A nomogram can be used as an effective tool to predict the risk of transitioning to metabolically unhealthy obesity from a metabolically healthy status. OBJECTIVE: The study aimed to identify demographic factors, health behaviors, and 5 metabolic statuses related to the transition from metabolically healthy obesity to unhealthy obesity among people aged between 20 and 44 years and to develop a screening tool to predict this transition. METHODS: This secondary analysis study used national health data from the National Health Insurance System in South Korea. We analyzed the customized data using SAS (SAS Institute Inc) and conducted logistic regression to identify factors related to the transition from metabolically healthy to unhealthy obesity. A nomogram was developed to predict the transition using the identified factors. RESULTS: Among 3,351,989 people, there was a significant association between the transition from metabolically healthy to unhealthy obesity and general characteristics, health behaviors, and metabolic components. Male participants showed a 1.30 higher odds ratio for transitioning to metabolically unhealthy obesity than female participants, and people in the lowest economic status were also at risk for the transition (odds ratio 1.08, 95% CI 1.05-1.1). Smoking status, consuming >30 g of alcohol, and insufficient regular exercise were negatively associated with the transition. Each relevant variable was assigned a point value. When the nomogram total points reached 295, the shift from metabolically healthy to unhealthy obesity had a prediction rate of >50%. CONCLUSIONS: This study identified key factors for young adults transitioning from healthy to unhealthy obesity, creating a predictive nomogram. This nomogram, including triglycerides, waist circumference, high-density lipoprotein-cholesterol, blood pressure, and fasting glucose, allows easy assessment of obesity risk even for the general population. This tool simplifies predictions amid rising obesity rates and interventions.


Asunto(s)
Obesidad Metabólica Benigna , Humanos , República de Corea/epidemiología , Masculino , Femenino , Adulto , Adulto Joven , Obesidad Metabólica Benigna/epidemiología , Síndrome Metabólico/epidemiología , Nomogramas , Obesidad/epidemiología , Conductas Relacionadas con la Salud , Factores de Riesgo
18.
Nucleic Acids Res ; 52(14): e62, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38922688

RESUMEN

Genome-level clonal decomposition of a single specimen has been widely studied; however, it is mostly limited to cancer research. In this study, we developed a new algorithm CLEMENT, which conducts accurate decomposition and reconstruction of multiple subclones in genome sequencing of non-tumor (normal) samples. CLEMENT employs the Expectation-Maximization (EM) algorithm with optimization strategies specific to non-tumor subclones, including false variant call identification, non-disparate clone fuzzy clustering, and clonal allele fraction confinement. In the simulation and in vitro cell line mixture data, CLEMENT outperformed current cancer decomposition algorithms in estimating the number of clones (root-mean-square-error = 0.58-0.78 versus 1.43-3.34) and in the variant-clone membership agreement (∼85.5% versus 70.1-76.7%). Additional testing on human multi-clonal normal tissue sequencing confirmed the accurate identification of subclones that originated from different cell types. Clone-level analysis, including mutational burden and signatures, provided a new understanding of normal-tissue composition. We expect that CLEMENT will serve as a crucial tool in the currently emerging field of non-tumor genome analysis.


Asunto(s)
Algoritmos , Genómica , Humanos , Genómica/métodos , Neoplasias/genética , Mutación , Genoma Humano , Células Clonales
19.
Front Public Health ; 12: 1396598, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887258

RESUMEN

Introduction: This study assesses the impact of dietary modification, specifically sugary snack restriction, in conjunction with a brisk walking program on overweight management in young overweight women, with a focus on changes in body composition and glucose metabolism. Method: An 8-week randomized controlled trial was conducted amidst the COVID-19 pandemic, utilizing a remote intervention approach to comply with health guidelines and ensure participant safety. The study's remote nature highlights adaptability in health interventions during challenging periods, such as the COVID-19 pandemic. Twenty-one overweight Korean women aged 20-39, with an average BMI of 24.6, were selected for the study. They were divided into two groups: one engaging in brisk walking and the other combining this exercise with a sugary snack restriction, demonstrating the study's focus on comparative intervention efficacy. Results: The exercise-only group showed notable reductions in glucose, insulin, HOMA-IR (p < 0.05), and total cholesterol levels (p < 0.01). In contrast, the group that combined exercise with dietary modification displayed more pronounced improvements in body weight, fat mass, and waist circumference (p < 0.05). This differential outcome emphasizes the added benefit of integrating dietary control with physical activity. Discussion: The findings suggest that adding a dietary component, particularly a sugary snack restriction, to an exercise regimen can significantly enhance the effectiveness of overweight management in young women. This study underscores the importance of holistic lifestyle interventions that combine dietary and physical activity modifications for improved health outcomes.


Asunto(s)
Composición Corporal , COVID-19 , Sobrepeso , Bocadillos , Caminata , Humanos , Femenino , COVID-19/prevención & control , Adulto , Sobrepeso/terapia , Adulto Joven , República de Corea , SARS-CoV-2 , Índice de Masa Corporal , Glucemia/metabolismo , Ejercicio Físico
20.
Cell Commun Signal ; 22(1): 334, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890646

RESUMEN

INTRODUCTION: Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity. In this study, we fabricated the hybrid BDEs fused with liposomes containing silymarin (SM) to enhance the synergistic effect on inhibition of acetaminophen-induced hepatotoxicity (APAP). OBJECTIVE: Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with SM. Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules. METHODS: Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated. RESULTS: BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity. CONCLUSION: From this study, we know that BDEs are reliable and safe nanovesicles containing natural metabolites derived from balloon flower, and they can facilitate intercellular communication. BDEs are also easily modified to enhance drug loading capacity, targeting effects, and long-term accumulation in vivo. BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death and toxicity. They can be efficiently delivered to the liver and effectively inhibit APAP-induced hepatotoxicity by inhibiting the MAPK signaling pathway and apoptosis, which accelerates liver recovery in the APAP-induced acute liver injury model. These findings highlight that BDEs represent an attractive delivery vehicle for drug delivery.


Asunto(s)
Acetaminofén , Apoptosis , Exosomas , Hepatocitos , Sistema de Señalización de MAP Quinasas , Nanopartículas , Silimarina , Apoptosis/efectos de los fármacos , Animales , Nanopartículas/química , Exosomas/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Silimarina/farmacología , Silimarina/administración & dosificación , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Humanos , Liposomas/química , Masculino , Raíces de Plantas , Ratones Endogámicos C57BL
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