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1.
Biomaterials ; 313: 122768, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39232332

RESUMEN

As the most prominent and ideal modality in female fertility preservation, ovarian tissue cryopreservation, and transplantation often confront the challenge of ischemic damage and follicular loss from avascular transplantation. To surmount this impediment, we engineered a novel platelet-derived factors-encapsulated fibrin hydrogel (PFH), a paradigmatic biomaterial. PFH encapsulates autologous platelet-derived factors, utilizing the physiological blood coagulation cascade for precise local delivery of bioactive molecules. In our study, PFH markedly bolstered the success of avascular ovarian tissue transplantation. Notably, the quantity and quality of follicles were preserved with improved neovascularization, accompanied by decreased DNA damage, increased ovulation, and superior embryonic development rates under a Low-concentration Platelet-rich plasma-derived factors encapsulated fibrin hydrogel (L-PFH) regimen. At a stabilized point of tissue engraftment, gene expression analysis mirrored normal ovarian tissue profiles, underscoring the effectiveness of L-PFH in mitigating the initial ischemic insult. This autologous blood-derived biomaterial, inspired by nature, capitalizes on the blood coagulation cascade, and combines biodegradability, biocompatibility, safety, and cost-effectiveness. The adjustable properties of this biomaterial, even in injectable form, extend its potential applications into the broader realm of personalized regenerative medicine. PFH emerges as a promising strategy to counter ischemic damage in tissue transplantation, signifying a broader therapeutic prospect. (197 words).


Asunto(s)
Preservación de la Fertilidad , Hidrogeles , Isquemia , Neovascularización Fisiológica , Ovario , Femenino , Animales , Preservación de la Fertilidad/métodos , Neovascularización Fisiológica/efectos de los fármacos , Ovario/efectos de los fármacos , Hidrogeles/química , Isquemia/terapia , Humanos , Fibrina/química , Plasma Rico en Plaquetas/metabolismo
2.
J Invest Dermatol ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39241981

RESUMEN

Blue light, a high-energy radiation in the visible light spectrum, was recently reported to induce skin pigmentation. In this study, we investigated the involvement of TRPV1-mediated signaling along with OPN3 in blue light-induced melanogenesis, as well as its signaling pathway. Operating downstream target of OPN3 in blue light-induced melanogenesis, blue light activated TRPV1 and upregulated its expression, resulting in calcium influx. [Ca2+] induced activation of CaMKII and MAPK. It also downregulated clusterin expression, leading to the nuclear translocation of PAX3, ultimately affecting melanin synthesis. In addition, blue light interfered with autophagy-mediated regulation of melanosomes by decreasing not only the interaction between CLU and LC3B but the expression of ATF family. These findings demonstrate that the pigmenting effects of blue light are mediated by CaMKII- and MAPK-mediated signaling, as well as CLU-dependent inhibition of autophagy through OPN3-TRPV1-calcium influx, suggesting a new signaling pathway by which blue light regulates melanocyte biology. Furthermore, these results suggest that TRPV1 and CLU could be potential therapeutic targets for blue light-induced pigmentation due to prolonged exposure to blue light.

3.
Front Nutr ; 11: 1432647, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296502

RESUMEN

Introduction: Colorectal adenomas are recognized as precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying modifiable dietary factors that may inhibit cancer progression is critical, but epidemiologic studies in Asian populations are scarce. Methods: This study explored the impact of fish and meat intake on colorectal adenoma risk among Koreans. The study enrolled asymptomatic adults who visited Seoul National University Hospital Healthcare System Gangnam Center for health check-ups from May to December 2011. All participants underwent screening colonoscopy and completed a validated food frequency questionnaire. The study included 536 adenoma patients, 135 high-risk adenoma patients and 1,122 adenoma-free controls. Using multivariate logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for fish and meat intake related to colorectal adenoma status, significant at p < 0.05. Results: The intake of total fish, meat, red meat, chicken or processed meat showed no clear association with the prevalence of colorectal adenoma after adjusting for age, education, smoking status, alcohol intake, physical activity, body mass index, metabolic syndrome, colorectal cancer family history, total energy intake, and total fruit and vegetable intake. However, higher fish intake was associated with lower odds of high-risk colorectal adenoma, with a significant trend observed across quartiles (P for trend = 0.04). This trend was more pronounced among men than women (P for trend = 0.01). Conclusion: In conclusion, we observed a significant inverse association between high fish intake and the prevalence of high-risk adenoma, but there were no clear associations between red and processed meat or chicken in the Korean population.

4.
Lancet ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39288779

RESUMEN

BACKGROUND: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. METHODS: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

5.
Yonsei Med J ; 65(10): 619-622, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39313453

RESUMEN

Lenacapavir is a novel, first-in-class, capsid inhibitor, which has been approved as an adjunctive therapy for multidrug-resistant human immunodeficiency virus (HIV)-1 virus in combination with optimized background regimen (OBR). Lenacapavir has demonstrated a significant decrease in viral load and high rate of virologic suppression in patients with multidrug-resistant HIV-1 infection with limited treatment options. Here, we report a case of 43-year-old male who was diagnosed with HIV-1 infection in 2005 but failed to achieve viral suppression due to multiclass resistance. After lenacapavir use with OBR, viral suppression was achieved, and recovery of CD4+ T-cell count was observed for 8 months. This case report shows the first lenacapavir experience in Asia in a heavily treatment-experienced HIV patient with limited treatment options.


Asunto(s)
Fármacos Anti-VIH , Farmacorresistencia Viral Múltiple , Infecciones por VIH , VIH-1 , Carga Viral , Humanos , Masculino , Adulto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Fármacos Anti-VIH/uso terapéutico , Carga Viral/efectos de los fármacos , Recuento de Linfocito CD4 , Asia
6.
PLoS One ; 19(9): e0308515, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39298433

RESUMEN

Dyadic conditions of patients with heart failure and their caregivers may affect both patient self-care and caregiver contribution to patient self-care (CCPS). The purpose of this study was to examine the relationships of patient-caregiver physical function and depressive symptoms to the patient self-care (maintenance and management) and CCPS. Data from 55 were analyzed using an Actor-Partner Interdependence Model to address the aim through AMOS. Patient self-care was very poor. Better patient physical function was related to better patient self-care management (actor effect) and poorer CCPS maintenance (partner effect). Better caregiver physical function was related to CCPS management (actor effect). Severer patient depressive symptoms were related to poorer patient self-care maintenance (actor effect) and poorer CCPS management (partner effect). Physical function and depressive symptoms in patient-caregiver dyads were related to patient self-care and CCPS. To improve patient self-care and CCPS, dyadic support for physical function and depressive symptoms is needed.


Asunto(s)
Cuidadores , Depresión , Insuficiencia Cardíaca , Autocuidado , Humanos , Insuficiencia Cardíaca/psicología , Insuficiencia Cardíaca/terapia , Cuidadores/psicología , Autocuidado/psicología , Masculino , Femenino , Depresión/psicología , Depresión/terapia , Anciano , Persona de Mediana Edad , Adulto , Anciano de 80 o más Años
7.
Sci Adv ; 10(38): eadr1099, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303034

RESUMEN

In the rapidly evolving field of human-machine interfaces (HMIs), high-resolution wearable electronic skin (e-skin) is essential for user interaction. However, traditional array-structured tactile interfaces require increased number of interconnects, while soft material-based computational methods have limited functionalities. Here, we introduce a thin and soft e-skin for tactile interfaces, offering high mapping capabilities through electrical impedance tomography (EIT). We employed an organic/inorganic hybrid structure with simple, cost-effective fabrication processes, ensuring flexibility and stability. The conductive and stretchable sensing domain includes a micropatterned multiwall carbon nanotube and elastomer composite. The skin-like tactile interface effectively detects pressure-induced conductivity changes, offering superior spatiotemporal resolution with fewer interconnects (pixel/interconnects >57). This EIT-based tactile interface discerns external pressures to a submillimeter degree and vertical deformations of a few hundred micrometers. It sustains stable functions under external damage or environmental changes, confirming its suitability for persistent wearable use. We demonstrate practical applications in real-time HMIs: handwriting recognition and drone control.


Asunto(s)
Impedancia Eléctrica , Tomografía , Tacto , Dispositivos Electrónicos Vestibles , Humanos , Tomografía/métodos , Tomografía/instrumentación , Tacto/fisiología , Nanotubos de Carbono/química , Piel
8.
Curr Opin Nephrol Hypertens ; 33(6): 636-640, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39234876

RESUMEN

PURPOSE OF REVIEW: Disasters, natural and man-made, are rising in frequency and pose significant challenges to the provision of renal care worldwide. Patients with kidney disease, particularly those on dialysis, are extremely vulnerable during disasters. This timely review summarizes the potential roles international renal disaster preparedness working groups have in addressing these challenges. RECENT FINDINGS: The vulnerability of kidney patients has galvanized the evolution of global response mechanisms and the contemporary efforts of various organizations. In this review, the importance of preparedness, networking, and collaborations at all levels are highlighted, citing recent crises. It will also note key areas for improvement, including an enhanced engagement with global health organizations. Finally, it is imperative to urge the international community to recognize that individuals with kidney disease are often among the first patient groups to suffer in disaster zones. These messages are intended to persuade global stakeholders that kidney patients, including pediatric ones, should be prioritized as requiring immediate support during disasters. SUMMARY: The unique and life-threatening challenges faced by individuals with kidney disease in natural disaster- or war-torn areas demand special consideration in humanitarian efforts and international crisis response strategies. International organizations can play a major role in this regard.


Asunto(s)
Planificación en Desastres , Humanos , Planificación en Desastres/organización & administración , Salud Global , Cooperación Internacional , Diálisis Renal/métodos , Enfermedades Renales/terapia
9.
Mol Oncol ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39297393

RESUMEN

To enhance the efficacy of radiotherapy (RT) in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), we explored targeting ferroptosis, a regulated cell death process. We developed a gene signature associated with ferroptosis using Cox proportional hazard modeling in HPV-negative HNSCC patients who underwent RT. This ferroptosis-related gene signature (FRGS) was a significant predictor of overall survival and recurrence-free survival in HPV-negative HNSCC patients who received RT. Subtype B of the FRGS, characterized by decreased expression of ferroptosis inducers [nuclear receptor coactivator 4 (NCOA4) and natural resistance-associated macrophage protein 2 homolog/divalent metal transporter 1 (NRAMP2/DMT1)] and increased expression of suppressors [phospholipid hydroperoxide glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1)], was associated with poorer prognosis, potentially indicating the inhibition of ferroptosis. Furthermore, our in vitro and in vivo studies demonstrated that treatment with statins, such as atorvastatin and simvastatin, induced ferroptosis and sensitized radioresistant HNSCC cells to irradiation, improving radiosensitivity and potentially enhancing the response to RT. Additionally, in xenograft models, the combination of statins and RT led to a significant reduction in tumor initiation. These findings provide valuable insights for enhancing treatment and improving prognosis in HPV-negative HNSCC by targeting ferroptosis and utilizing statins to sensitize tumors to RT-induced cell death.

10.
Artículo en Inglés | MEDLINE | ID: mdl-39297854

RESUMEN

BACKGROUND: Thrombus aspiration (TA) is used to decrease large thrombus burden (LTB), but it can cause distal embolization. OBJECTIVES: The aim of this study was to investigate the impact of TA failure on defective myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) and LTB. METHODS: In total, 812 consecutive patients with STEMI and LTB (thrombus grade ≥3) were enrolled, who underwent manual TA during the primary percutaneous coronary intervention. TA failure was defined as the absence of thrombus retrieval, presence of prestenting thrombus residue, or distal embolization. The final TIMI (Thrombolysis In Myocardial Infarction) flow grades and other myocardial perfusion parameters of the failed TA group were matched with those of the successful TA group. RESULTS: The proportion of final TIMI flow grade 3 was lower (74.6% vs 82.2%; P = 0.011) in the failed TA group (n = 279 [34.4%]) than in the successful TA group (n = 533 [65.6%]). The failed TA group also had lower myocardial blush grade, lower ST-segment resolution, and a higher incidence of microvascular obstruction than the successful TA group. TA failure was independently associated with low final TIMI flow grade (risk ratio: 1.525; 95% CI: 1.048-2.218; P = 0.027). Old age, Killip class ≥III, vessel tortuosity, calcification, and a culprit vessel other than the left anterior descending coronary artery were associated with TA failure. CONCLUSIONS: TA failure is associated with reduced myocardial perfusion in patients with STEMI and LTB. Advanced age, hemodynamic instability, hostile coronary anatomy such as tortuosity or calcification, and non-left anterior descending coronary artery status might attenuate TA performance. (Gangwon PCI Prospective Registry [GWPCI]; NCT02038127).

11.
Int J Infect Dis ; : 107249, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307179

RESUMEN

OBJECTIVES: We evaluated the vaccine effectiveness of monovalent XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and the need for oxygen therapy in South Korea. DESIGN: This study employed a test-negative case-control design. COVID-19 test results in symptomatic subjects from six university hospitals across South Korea were collected (October 26-December 31, 2023). The adjusted absolute and relative vaccine effectiveness were assessed. RESULTS: In total, 5,516 subjects were enrolled: 4,824 were unvaccinated with XBB.1.5, and 692 were vaccinated with XBB.1.5 COVID-19 mRNA vaccines. The absolute vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 65.2% (95% CI, 36.1-81.0), 77.3% (95% CI, 51.1-89.5), and 85.3% (95% CI, 57.8-94.9), respectively. The relative vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no XBB.1.5 vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 57.7% (95% CI, 34.7-72.6), 64.3% (95% CI, 35.9-80.2), and 65.5% (95% CI, 27.0-83.7), respectively. CONCLUSIONS: The short-term effectiveness of the XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and receipt of oxygen therapy in South Korea was significant. Long-term vaccine effectiveness warrants evaluation, and these assessments should be conducted regularly.

12.
J Am Chem Soc ; 146(38): 26131-26138, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39276081

RESUMEN

Creating nanomachines capable of precisely capturing, organizing, and regulating the activity of target biomolecules holds profound significance for advancing nanotechnology and therapeutics. Here, we develop a multistage reconfigurable DNA nanocage that can enclose and modulate proteins through multivalent interactions, activated by specific molecular signals. By strategically designing and manipulating the strut architecture of the DNA nanocages, we can achieve precise control over their reconfiguration among pyramid, square, and linear branch shapes. Additionally, we demonstrated its ability to capture thrombin and effectively inhibit its coagulation activity by incorporating two thrombin-targeting aptamers into the designed arms of the DNA nanocage. The activity of thrombin can be recovered by rearranging the conformation of the DNA nanocage and exposing the protein, thereby activating the coagulation process. This approach enriches the design toolbox for dynamic nanomachines and inspires a new strategy for protein encapsulation and regulation with potential future therapeutic applications.


Asunto(s)
Aptámeros de Nucleótidos , ADN , Nanoestructuras , Trombina , Trombina/química , Trombina/metabolismo , ADN/química , Nanoestructuras/química , Aptámeros de Nucleótidos/química , Nanotecnología/métodos , Humanos
14.
J Korean Med Sci ; 39(35): e242, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252684

RESUMEN

BACKGROUND: The vegetative state (VS) after severe acute brain injury (SABI) is associated with significant prognostic uncertainty and poor long-term functional outcomes. However, it is generally distinguished from imminent death and is exempt from the Life-Sustaining Treatment (LST) Decisions Act in Korea. Here, we aimed to examine the perspectives of the general population (GP) and clinicians regarding decisions on mechanical ventilator withdrawal in patients in a VS after SABI. METHODS: A cross-sectional survey was undertaken, utilizing a self-reported online questionnaire based on a case vignette. Nationally selected by quota sampling, the GP comprised 500 individuals aged 20 to 69 years. There were 200 doctors from a tertiary university hospital in the clinician sample. Participants were asked what they thought about mechanical ventilator withdrawal in patients in VS 2 months and 3 years after SABI. RESULTS: Two months after SABI in the case, 79% of the GP and 83.5% of clinicians had positive attitudes toward mechanical ventilator withdrawal. In the GP, attitudes were associated with spirituality, household income, religion, the number of household members. On the other hand, clinicians' attitudes were related to their experience of completing advance directives (AD) and making decisions about LST. In this case, 3 years after SABI, 92% of the GP and 94% of clinicians were more accepting of ventilator withdrawal compared to previous responses, based on the assumption that the patient had written AD. However, it appeared that the proportion of positive responses to ventilator withdrawal decreased when the patients had only verbal expressions (82% of the GP; 75.5% of clinicians) or had not previously expressed an opinion regarding LST (58% of the GP; 39.5% of clinicians). CONCLUSION: More than three quarters of both the GP and clinicians had positive opinions regarding ventilator withdrawal in patients in a VS after SABI, which was reinforced with time and the presence of AD. Legislative adjustments are needed to ensure that previous wishes for those patients are more respected and reflected in treatment decisions.


Asunto(s)
Estado Vegetativo Persistente , Humanos , Adulto , Persona de Mediana Edad , Masculino , Femenino , Estudios Transversales , Encuestas y Cuestionarios , Anciano , Lesiones Encefálicas , Respiración Artificial , Adulto Joven , Directivas Anticipadas , Toma de Decisiones , Privación de Tratamiento , Actitud del Personal de Salud , Médicos/psicología
15.
Artículo en Inglés | MEDLINE | ID: mdl-39264719

RESUMEN

BACKGROUND: Ultrafiltration with continuous kidney replacement therapy (CKRT) can be used to manage fluid balance in critically ill patients with acute kidney injury (AKI). We aimed to assess whether bioimpedance analysis (BIA)-guided volume management was more efficacious than conventional management for achieving estimated euvolemia (e-euvolemia) in CKRT-treated patients. METHODS: In a multi-center randomized controlled trial from July 2017 to July 2020, the patients with AKI requiring CKRT were eligible if the weight at the start of CKRT had increased by ≥5% compared to the weight at the time of admission, or total body water (TBW)/ height (H)2 ≥13 L/m2. We randomly assigned 208 patients to the control (conventional fluid management; N=103) and intervention groups (BIA-guided fluid management; N=105). Primary outcome was the proportion of attaining e-euvolemia seven days post-randomization. E-euvolemia was defined as the difference between TBW/H2 D7 and D0 was <-2.1 L/m2, or when TBW/H2 measured on D7 was <13 L/m2. The 28-, 60-, and 90-day mortality rate were secondary outcomes. RESULTS: The primary outcome occurred in 34 patients in the intervention group and 27 in the control group (47% versus 41%; P=0.50). The mean value of TBW/H2 measured on D7 was the same at 13.9 L/m2 in both groups. The differences between TBW/H2 D7 and D0 were -1.13 L/m2 in the intervention group and -1.08 L/m2 in the control group (P=0.84). Patients in the intervention group had a significantly higher proportion of reaching e-euvolemia on D1 than those in the control group (13% versus 4%, P=0.02). Adverse events did not differ significantly between the groups. CONCLUSIONS: BIA-guided volume management did not affect the proportion of reaching the estimated euvolemia at seven days of the start of CKRT. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03330626 (Registered on 6 November 2017; Seven study participants were retrospectively registered; nonetheless, IRB approval of each institution was completed before study participant registration).

16.
PLoS One ; 19(9): e0307499, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39236042

RESUMEN

Fibroblast growth factor 2 (FGF2) is an attractive biomaterial for pharmaceuticals and functional cosmetics. To improve the thermo-stability of FGF2, we designed two mutants harboring four-point mutations: FGF2-M1 (D28E/C78L/C96I/S137P) and FGF2-M2 (D28E/C78I/C96I/S137P) through bioinformatics, molecular thermodynamics, and molecular modeling. The D28E mutation reduced fragmentation of the FGF2 wild type during preparation, and the substitution of a whale-specific amino acid, S137P, enhanced the thermal stability of FGF2. Surface-exposed cysteines that participate in oligomerization through intermolecular disulfide bond formation were substituted with hydrophobic residues (C78L/C78I and C96I) using the in silico method. High-resolution crystal structures revealed at the atomic level that the introduction of mutations stabilizes each local region by forming more favorable interactions with neighboring residues. In particular, P137 forms CH-π interactions with the side chain indole ring of W123, which seems to stabilize a ß-hairpin structure, containing a heparin-binding site of FGF2. Compared to the wild type, both FGF2-M1 and FGF2-M2 maintained greater solubility after a week at 45 °C, with their Tm values rising by ~ 5 °C. Furthermore, the duration for FGF2-M1 and FGF2-M2 to reach 50% residual activity at 45 °C extended to 8.8- and 8.2-fold longer, respectively, than that of the wild type. Interestingly, the hydrophobic substitution of surface-exposed cysteine in both FGF2 mutants makes them more resistant to proteolytic cleavage by trypsin, subtilisin, proteinase K, and actinase than the wild type and the Cys → Ser substitution. The hydrophobic replacements can influence protease resistance as well as oligomerization and thermal stability. It is notable that hydrophobic substitutions of surface-exposed cysteines, as well as D28E and S137P of the FGF2 mutants, were designed through various approaches with structural implications. Therefore, the engineering strategies and structural insights adopted in this study could be applied to improve the stability of other proteins.


Asunto(s)
Cisteína , Factor 2 de Crecimiento de Fibroblastos , Interacciones Hidrofóbicas e Hidrofílicas , Estabilidad Proteica , Cisteína/química , Cisteína/genética , Factor 2 de Crecimiento de Fibroblastos/química , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Mutación , Modelos Moleculares , Cristalografía por Rayos X , Sustitución de Aminoácidos , Humanos , Termodinámica
17.
Maxillofac Plast Reconstr Surg ; 46(1): 33, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254790

RESUMEN

BACKGROUND: The purpose of this study is to analyze changes in mandibular width and frontal view ramus inclination using cone beam CT in patients with skeletal class III malocclusion who underwent BSSRO, with the removal of bone interference between segments. METHODS: For all 20 subjects, cone-beam CT imaging was performed prior to surgery (T1), immediately post-surgery (T2), and 6 months after surgery (T3). Reorientation was performed using R2GATE software (MegaGen, Seoul, Korea). The gonion and antegonial notch were used as reference points in the sagittal view, and the most lateral point of the condyle head was used as the reference point in the frontal view. All measurements were recorded in the frontal view. RESULTS: Inter-gonial width decreased by 2.64 mm at T3-T2 (P < .001) and by 2.58 mm at T3-T1 (P < .05). Inter-antegonial width decreased by 1.75 mm at T3-T2 (P < .05) and by 3.5 mm at T3-T1 (P < .001). In the frontal view, the right ramus inclination based on the gonion increased by 2.07° at T3-T1 (P < .05). The left ramus inclination based on gonion increased by 2.45° at T2-T1 (P < .05) and by 3.94° at T3-T1 (P < .001). The right ramus inclination based on antegonial notch increased by 2.35° at T2-T1 (P < .05) and by 3.04° at T3-T1 (P < .01). The left ramus inclination based on antegonial notch increased by 2.73° at T2-T1 (P < .001) and by 3.18° at T3-T1 (P < .001). CONCLUSIONS: During bilateral sagittal split osteotomy, removing bone interference between the proximal and distal segments results in a reduction of postoperative mandibular width and an increase in frontal view ramus inclination.

18.
J Photochem Photobiol B ; 259: 113021, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39222549

RESUMEN

Alzheimer's disease, a prevalent neurodegenerative condition primarily affecting older adults, remains incurable. Its principle pathological hallmark is the accelerated accumulation of amyloid ß (Aß) protein. This study investigates the potential of photobiomodulation using near infrared light to counteract Aß1-42-induced synaptic degeneration and neurotoxicity. We focused on the effect of 808 nm near-infrared laser diode (LD) on Aß1-42 cytotoxicity in primary cultured cortical neurons. We assessed cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, observing substantial benefits from LD irradiation with a power of 10 mW and a dose of 30 J. Cells exposed to Aß1-42 exhibited morphological changes indicative of synaptic damage and a significant decrease in the number of postsynaptic density protein-95 (PSD-95) contacts, which were significantly improved with near-infrared LD therapy. Furthermore, this therapy reduced Aß and phosphorylated tau (P-tau) protein accumulation. Additionally, near-infrared LD irradiation substantially lessened the Aß1-42-induced rise in glial fibrillary acid protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) in astrocytes and microglia. Remarkably, near-infrared LD irradiation effectively inhibited phosphorylation of key proteins involved in Aß1-42-induced necroptosis, namely Receptor-interacting protein kinase-3 (RIP3) and Mixed Lineage Kinase domain-Like protein (MLKL). Our findings suggest that near-infrared LD treatment significantly reduces neurodegeneration by reducing glial overactivation and neuronal necroptosis triggered by Aß1-42. Thus, near-infrared LD treatment emerges as a promising approach for slowing or treating Alzheimer's disease, offering new avenues in its management.


Asunto(s)
Péptidos beta-Amiloides , Supervivencia Celular , Rayos Infrarrojos , Neuronas , Fragmentos de Péptidos , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Animales , Neuronas/efectos de la radiación , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Fragmentos de Péptidos/metabolismo , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Ratas , Láseres de Semiconductores , Proteínas tau/metabolismo , Terapia por Luz de Baja Intensidad , Células Cultivadas , Homólogo 4 de la Proteína Discs Large/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Corteza Cerebral/citología , Corteza Cerebral/efectos de la radiación , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/efectos de la radiación
19.
Mar Pollut Bull ; 208: 117017, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39317107

RESUMEN

For four decades, cordgrass (Spartina alterniflora) has invaded salt marshes in the Yellow Sea, altering physical, biogeochemical, and biological processes. Here, we investigated the ecological effects of S. alterniflora invasion on benthic environments compared to native halophytes. S. alterniflora contributed to higher carbon accumulation rates compared with bare tidal flat in sediments (3.4 times), through greater primary production and root biomass, compared to Suaeda japonica (2.5 times) and Phragmites australis (2.4 times) over the given period. The results showed that S. alterniflora eradication treatments inhibited its growth but did not significantly affect the benthic communities. Compared to P. australis and bare tidal flats, S. alterniflora invasion resulted in lower greenhouse gas emission and higher contributions to macrobenthos nutrition, and increased sediment stability and carbon burial. Overall, these multiple lines of evidence provide new insights on S. alterniflora invasion, suggesting that the current eradication policy would be carefully reviewed.

20.
J Int Soc Sports Nutr ; 21(1): 2405159, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39287144

RESUMEN

BACKGROUND: This study was conducted to investigate the nutritional knowledge of elite athletes undergoing weight loss and to identify differences in weight-loss strategies according to nutritional knowledge. METHODS: The participants included 22 coaches and 88 elite athletes registered under the same affiliation. The survey involved translating the General Nutrition Knowledge Questionnaire (GNKQ), and interviews were used to confirm the diet and weight loss patterns of the athletes. The coaches and athletes were divided into high-rank (12 coaches and 57 athletes) and low-rank (10 coaches and 31 athletes) groups based on GNKQ scores. Paired t-tests, correlation analysis, and logistic regression analysis were performed. RESULTS: GNKQ results showed significant differences between high-ranking and low-ranking coaches (p < 0.001). Furthermore, a significant difference in nutrition knowledge scores was also noticed between athletes with high-ranking and low-ranking coaches (p < 0.001). A strong correlation was observed between the GNKQ scores of coaches and athletes (r = 0.369; p < 0.001). The nutritional knowledge of coaches was also correlated with weight-loss strategies (weight loss attempt frequency; r = -0.235; p = 0.027; weight loss duration; r = -0.268; p = 0.012). Additionally, differences were observed in the intake of all nutrients (carbohydrates, proteins, and fat) in the diets of athletes (p < 0.001). CONCLUSION: Our study suggests that the nutritional knowledge of coaches indirectly affects athletes. Coaches have significant influence over athletes and possess experience with diet and weight-loss patterns. This insight should be effectively utilized to enhance the training and performance of athletes and coaches.


Asunto(s)
Atletas , Conocimientos, Actitudes y Práctica en Salud , Pérdida de Peso , Humanos , Masculino , Adulto , Femenino , Encuestas y Cuestionarios , Fenómenos Fisiológicos en la Nutrición Deportiva , Dieta , Adulto Joven , Tutoría , Ciencias de la Nutrición y del Deporte/educación , Deportes/fisiología
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