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1.
Adv Mater ; : e2407443, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39385641

RESUMEN

Interest in all-solid-state batteries (ASSBs), particularly the anode-less type, has grown alongside the expansion of the electric vehicle (EV) market, because they offer advantages in terms of their energy density and manufacturing cost. However, in most anode-less ASSBs, the anode is covered by a protective layer to ensure stable lithium (Li) deposition, thus requiring high temperatures to ensure adequate Li ion diffusion kinetics through the protective layer. This study proposes a dual-seed protective layer consisting of silver (Ag) and zinc oxide (ZnO) nanoparticles for sulfide-based anode-less ASSBs. This dual-seed-based protective layer not only facilitates Li diffusion via multiple lithiation pathways over a wide range of potentials, but also enhances the mechanical stability of the anode interface through the in situ formation of a Ag-Zn alloy with high ductility. The capacity retention during full-cell evaluation is 80.8% for 100 cycles when cycled at 1 mA cm-2 with 3 mAh cm-2 at room temperature. The dual-seed approach provides useful insights into the design of multi-seed concepts in which, from a mechanochemical perspective, various lithiophilic materials synergistically impact upon the anode-less interface.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39396671

RESUMEN

PURPOSE: To reduce falls in hospitalized patients with mental disorders, the patients should be sensitive to fall risk perception. This study identified the sensitivity to fall risk perceptions and associated factors, including demographic, clinical, and fall-related factors, among inpatients with mental disorders. METHODS: We used a descriptive, cross-sectional design, recruiting 170 inpatients with mental disorders from two psychiatric hospitals in South Korea. Sensitivity to fall risk perception was classified using fall occurrence and the Fall Risk Perception Questionnaire. RESULTS: The prevalence of falls was 16.5%. Approximately 47% of falls occurred within 10 days of hospitalization, 67.9% within 1 month, and 85.7% within 2 months. Among the 28 participants who fell, 60.7% had inadequate-low sensitivity to fall risk perception. Among the 142 participants who did not fall, 11.3% had inadequate-high sensitivity to fall risk perception. Low sensitivity to fall risk perception was related to diagnosis, psychiatric symptoms, and fall history due to the mental disorder. High sensitivity to fall risk perception was related to age at onset of the mental disorder, urinary or bowel problems, and fear of falling. The multiple logistic regression found that the diagnosis and fall history due to the mental disorder were associated with inadequate-low sensitivity, and age at onset and fear of falling were associated with inadequate-high sensitivity to fall risk perception. CONCLUSIONS: Over 60% of patients who fell had low sensitivity to fall risk perception. Inadequate-low and high sensitivity to fall risk perception are related to the demographic, clinical, and fall-related characteristics among inpatients with mental disorders. Therefore, nurses should assess fall risk perception, consider these factors together during this assessment, and manage them appropriately in hospitalized patients with mental disorders.

3.
J Biol Eng ; 18(1): 56, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39390586

RESUMEN

BACKGROUND: Schizochytrium, a group of eukaryotic marine protists, is an oleaginous strain, making it a highly promising candidate for the production of lipid-derived products such as biofuels and omega-3 fatty acids. However, the insufficient advancement of genetic engineering tools has hindered further advancements. Therefore, the development and application of genetic engineering tools for lipid enhancement are crucial for industrial production. RESULTS: Transgene expression in Schizochytrium often encounters challenges such as instability due to positional effects. To overcome this, we developed a safe-harbor transgene expression system. Initially, the sfGFP gene was integrated randomly, and high-expressing transformants were identified using fluorescence-activated cell sorting. Notably, HRsite 2, located approximately 3.2 kb upstream of cytochrome c, demonstrated enhanced sfGFP expression and homologous recombination efficiency. We then introduced the 3-ketoacyl-ACP reductase (KR) gene at HRsite 2, resulting in improved lipid and docosahexaenoic acid (DHA) production. Transformants with KR at HRsite 2 exhibited stable growth, increased glucose utilization, and a higher lipid content compared to those with randomly integrated transgenes. Notably, these transformants showed a 25% increase in DHA content compared to the wild-type strain. CONCLUSION: This study successfully established a robust homologous recombination system in Schizochytrium sp. by identifying a reliable safe harbor site for gene integration. The targeted expression of the KR gene at this site not only enhanced DHA production but also maintained growth and glucose consumption rates, validating the efficacy of the safe-harbor approach. This advancement in synthetic biology and metabolic engineering paves the way for more efficient biotechnological applications in Schizochytrium sp.

4.
Int J Mol Sci ; 25(19)2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39409038

RESUMEN

The skin is an essential organ that protects the body from external aggressions; therefore, damage from various wounds can significantly impair its function, and effective methods for regenerating and restoring its barrier function are crucial. This study aimed to mass-produce wound-healing exosomes using a fragment of the fibroblast growth factor 2 (FGF2)-derived peptide (FP2) to enhance cell proliferation and exosome production. Our experiments demonstrated increased cell proliferation when Wharton's jelly mesenchymal stem cells (WJ MSCs) were coated with FP2. Exosomes from FP2-coated WJ MSCs were analyzed using nanoparticle-tracking analysis, transmission electron microscopy, and Western blotting. Subsequently, fibroblasts were treated with these exosomes, and their viability and migration effects were compared. Anti-inflammatory effects were also evaluated by inducing pro-inflammatory factors in RAW264.7 cells. The treatment of fibroblasts with FP2-coated WJ MSC-derived exosomes (FP2-exo) increased the expression of FGF2, confirming their wound-healing effect in vivo. Overall, the results of this study highlight the significant impact of FP2 on the proliferation of WJ MSCs and the anti-inflammatory and wound-healing effects of exosomes, suggesting potential applications beyond wound healing.


Asunto(s)
Proliferación Celular , Exosomas , Factor 2 de Crecimiento de Fibroblastos , Células Madre Mesenquimatosas , Gelatina de Wharton , Cicatrización de Heridas , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Ratones , Gelatina de Wharton/citología , Animales , Exosomas/metabolismo , Vesículas Extracelulares/metabolismo , Células RAW 264.7 , Fibroblastos/metabolismo , Fibroblastos/citología , Movimiento Celular , Péptidos/química , Células Cultivadas , Supervivencia Celular
5.
Ann Surg Treat Res ; 107(4): 212-220, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39416886

RESUMEN

Purpose: This study aimed to investigate the optimal withdrawal time (WT) for initial surveillance colonoscopy after curative resection for colorectal cancer (CRC) by comparing anterior/low anterior resection (AR/LAR) and right hemicolectomy (RHC) groups. Methods: This retrospective study analyzed 1,212 patients who underwent initial surveillance colonoscopy after CRC resection between 2015 and 2022. The patients were divided into the AR/LAR (n = 846) and RHC (n = 366) groups. The optimal WT was determined using receiver operating characteristic curve analysis and validated using logistic regression models. The adenoma and advanced neoplasia detection rates (ADR/ANDR) were evaluated based on the optimal WT. Results: The optimal WT was 7 and 6 minutes in the AR/LAR and RHC groups, respectively. In multivariate analysis, WT ≥7 and ≥6 minutes in the AR/LAR (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.75-3.24; P < 0.001) and RHC (OR, 2.64; 95% CI, 1.59-4.39; P = 0.001) groups, respectively, were significant factors for adenoma detection. In the AR/LAR group, ADR was 41.5% for WT ≥7 minutes compared to 21.9% for WT <7 minutes (P < 0.001). In the RHC group, ADR for WT ≥6 minutes was 33.9% compared to 15.8% for WT <6 minutes (P < 0.001). The ANDR also significantly improved with longer WTs in both groups. Conclusion: This study suggests that a minimum WT of 7 and 6 minutes for AR/LAR and RHC patients, respectively, during the initial surveillance colonoscopy after CRC resection is optimal for maintaining a satisfactory ADR and ANDR. These findings highlight the importance of tailoring colonoscopic procedures according to the type of surgical resection.

6.
Antioxidants (Basel) ; 13(10)2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39456507

RESUMEN

Reactive oxygen species (ROS) are generated during normal cellular energy production and play a critical role in maintaining cellular function. However, excessive ROS can damage cells and tissues, contributing to the development of diseases such as cardiovascular, inflammatory, and neurodegenerative disorders. This review explores the potential of nuclear medicine imaging techniques for detecting ROS and evaluates various radiopharmaceuticals used in these applications. Radiopharmaceuticals, which are drugs labeled with radionuclides, can bind to specific biomarkers, facilitating their identification in vivo using nuclear medicine equipment, i.e., positron emission tomography and single photon emission computed tomography, for diagnostic purposes. This review includes a comprehensive search of PubMed, covering radiopharmaceuticals such as analogs of fluorescent probes and antioxidant vitamin C, and biomarkers targeting mitochondrial complex I or cystine/glutamate transporter.

7.
Materials (Basel) ; 17(20)2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39459737

RESUMEN

As vehicle body structures become stronger and part designs more complex for lightweight, controlling frictional properties in automotive press forming has gained critical importance. Friction, a key factor in formability, is influenced by variables such as contact pressure, sliding velocity, sheet strength, and coatings. This study investigates the friction characteristics of steels with tensile strengths of 340 MPa and 980 MPa, under galvanized (GI) and galvannealed (GA) zinc coatings. Experimental results reveal that asperity flattening, a significant factor in determining friction, increases with contact pressure normalized by tensile strength, particularly for GI-coated steels. However, the relationship between friction and surface flattening deviates from conventional expectations, with the friction coefficient initially rising with increased flattening area up to ~20% before decreasing as flattening progresses. These findings suggest that traditional empirical formulas may not fully capture friction behavior under specific conditions. By understanding this inflection point, where friction reduces under high contact pressure, the study provides valuable insights for optimizing formability and improving sheet metal forming processes, especially in scenarios where precise friction control is critical for producing high-quality automotive parts.

8.
Endocrine ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313708

RESUMEN

PURPOSE: This study aimed to evaluate the efficacy of postoperative radioactive iodine (RAI) and its impact on recurrence rates and survival benefits in low- to intermediate-risk papillary thyroid carcinoma (PTC). METHODS: This retrospective study involved the examination of 1286 patients diagnosed with low- to intermediate-risk PTC who underwent total thyroidectomy with or without neck dissection, supplemented with postoperative RAI therapy or not between the years 2000 and 2021. RESULTS: From the patient pool, 589 (45%) were classified as low-risk and 697 (55%) as intermediate-risk according to the 2015 American Thyroid Association guidelines. Among the low-risk group, 375 (63.7%) underwent postoperative RAI, while in the intermediate-risk group, 566 (82.2%) underwent the procedure. The overall survival and disease-free survival rates were not statistically different between the groups that received RAI and those that did not, in both the low- and intermediate-risk categories. In a subgroup analysis, within the intermediate-risk category, postoperative RAI was significantly correlated with decreased recurrence in two subgroups: patients over 55 years with pN1b disease (hazard ratio 0.043, 95% confidence interval 0.004-0.500, p = 0.012) and patients over 55 years with five or more metastatic lymph nodes (hazard ratio 0.060, 95% confidence interval 0.005-0.675, p = 0.023). CONCLUSION: Our findings suggest that, while post-total thyroidectomy RAI does not substantially influence recurrence or survival rates in most low-risk and intermediate-risk PTC patients, it may be beneficial in specific subgroups, particularly patients over 55 with pN1b disease or those presenting with five or more metastatic lymph nodes.

9.
J Hazard Mater ; 480: 135957, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39332259

RESUMEN

Pesticide residues in fishery products are a concern due to environmental contamination. However, it is not sufficiently managed because of a lack of established standards. This study was conducted to monitor pesticide residues in fishery and seaweed product samples and assess the risk to humans. A total of 454 fishery products and 38 seaweed products were examined, and seven pesticides were detected. Among these, ethoxyquin was the most frequently detected. The risk of ethoxyquin via chronic exposure was 0.16 % and 83 % for the average and 97.5th intake, respectively. A risk exceeding 80 % is concerning; however, this concentration is considered safe in real-world circumstances, such as washing and cooking processes. Therefore, the detected pesticide residues in this study were assessed to be safe level for Korean intake level of fishery products. However, DDT, the prohibited pesticide decades ago, was still found and it is necessary to keep monitor considering persistent of pesticides. Considering newly regulated pesticides, sufficient monitoring and risk assessment data such as this study should be provided for policy standards setting and management.

10.
Toxicol Res ; 40(4): 519-531, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39345735

RESUMEN

The number of available drugs for treating aquatic animals is insufficient, given the occurrence of a variety of parasites and difficulties in developing appropriate treatments, such as vaccines or immunostimulants. Consequently, repurposing livestock drugs for treating aquatic animals is a viable alternative. Several studies have demonstrated that albendazole (ABZ) is a good anthelmintic for humans and animals such as ruminants, poultry, and honeybees. Therefore, we investigated the toxicological studies, metabolic and residue depletion studies, and efficacy trials of ABZ in aquatic animals to identify its application potential as a drug for aquatic animals. ABZ was depleted within 24 h in the muscle tissues of hybrid striped bass, rainbow trout, and tilapia. In muscle tissue with adhering skin obtained from tilapia and largemouth bass, a significant quantity of the amino-sulfone metabolite of ABZ (ABZ-SO2NH2) was present, while no ABZ-SO2NH2 was detected in hybrid striped bass, channel catfish, and patinga. Fish exposed only to high doses of ABZ showed reduced red blood cell counts and hemoglobin levels and increased lymphocytes. Such signs of toxicity have also been observed in human patients and animal studies. At a dose of 100 mg/L, ABZ showed 100% efficacy in eels. In addition, albendazole sulfoxide (ABZSO) demonstrated efficacies of 96.1% and 100% in pirapatinga and ray-finned fish, respectively, at a dose 500 mg/L. ABZ was also highly effective in treating an intracellular parasite E. hepatopenaei in white shrimp. The application of ABZ in aquatic animals under the low-dose and short-term conditions is considered a reasonable solution to manage parasite infections. The types and residual periods of degradation products differed among fish species, suggesting dissimilar metabolic pathways. With a high demand for new alternative veterinary drugs in aquaculture by fish farmers, this review offers important evidence for considering the use of ABZ in Korean farmed fish, taking food safety issues into account.

11.
Ann Pediatr Endocrinol Metab ; 29(4): 227-233, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39231484

RESUMEN

PURPOSE: Data regarding the association between metabolically healthy obesity (MHO) and preclinical atherosclerosis in childhood are lacking. Carotid intima-media thickness (cIMT) is a noninvasive method used to assess cardiovascular risk. This study examined the relationships among cIMT, metabolic phenotypes, and cardiometabolic risk factors (CMRFs) in overweight and obese adolescents. METHODS: Anthropometric, biochemical, and cIMT data were collected. The study participants were categorized as MHO or metabolically unhealthy obesity (MUO) based on insulin resistance. CMRFs were assessed using blood pressure (BP); levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), and fasting plasma glucose; or a diagnosis of diabetes mellitus. Differences in cIMT values were evaluated according to the metabolic phenotype and factors associated with cIMT. RESULTS: Among the 111 participants (80 boys, 72.1%), 23 (20.7%) were classified as MHO and 88 (79.3%) as MUO. The MHO group exhibited lower glycated hemoglobin and triglyceride levels and higher HDL-C levels compared to those exhibited by the MUO group (all P<0.01). The cIMT values did not differ significantly between the MHO and MUO groups. The high cIMT tertile group revealed higher systolic BP compared to that exhibited by the low cIMT tertile group (123.7±2.1 mmHg vs. 116.9±1.6 mmHg, P=0.028). Mean cIMT was positively correlated with age (ß=0.009) and body mass index (BMI) (ß=0.033) after adjusting for covariates (both P<0.05). CONCLUSION: In overweight and obese Korean adolescents, cIMT was associated with age and BMI but not with metabolic phenotype or CMRFs. Further research is warranted to determine the relationship between cIMT during adolescence and cardiovascular outcomes during adulthood.

12.
Sci Rep ; 14(1): 22358, 2024 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333166

RESUMEN

Hepatocellular carcinoma (HCC) often arises in the cirrhotic livers, highlighting the intricate link between hepatic fibrosis and carcinogenesis. Reactive oxygen species produced by NADPH oxidase 4 (NOX4) contribute to liver injury leading to hepatic fibrosis. Paradoxically, NOX4 is known to inhibit HCC progression. This study aims to elucidate the role of NOX4 in hepatocarcinogenesis in the background of hepatic fibrosis. We established the mouse model of HCC arising from the fibrotic liver by administering diethylnitrosamine and carbon tetrachloride to wild-type (WT) or NOX4-/- mice. Hepatic fibrogenesis, tumorigenesis, and macrophage polarization were assessed by immunohistochemistry, PCR, and flow cytometry using in vivo and in vitro models. In NOX4-/- mice, hepatic fibrosis was attenuated, while the number of tumors and the proliferation of HCC cells were increased compared to WT mice. Notably, a significant increase in M2-polarized macrophages was observed in NOX4-/- mice through immunohistochemistry and PCR analysis. Subsequent experiments demonstrated that NOX4-silenced HCC cells promote macrophage polarization toward M2. In addition to attenuating hepatic fibrogenesis, NOX4 deficiency triggers macrophage polarization towards the M2 phenotype in the fibrotic liver, thereby promoting hepatocellular carcinogenesis. These findings provide novel insights into the mechanism of NOX4-mediated tumor suppression in HCC arising from fibrotic livers.


Asunto(s)
Carcinoma Hepatocelular , Cirrosis Hepática , Neoplasias Hepáticas , Macrófagos , NADPH Oxidasa 4 , Microambiente Tumoral , Animales , NADPH Oxidasa 4/metabolismo , NADPH Oxidasa 4/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/genética , Ratones , Macrófagos/metabolismo , Macrófagos/patología , Ratones Noqueados , Humanos , Masculino , Modelos Animales de Enfermedad , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL , Tetracloruro de Carbono , Carcinogénesis/patología , Carcinogénesis/genética , Línea Celular Tumoral
13.
Environ Sci Technol ; 58(37): 16642-16655, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39226236

RESUMEN

This study demonstrated that NiO and Ni(OH)2 as Ni(II) catalysts exhibited significant activity for organic oxidation in the presence of various oxyanions, such as hypochlorous acid (HOCl), peroxymonosulfate (PMS), and peroxydisulfate (PDS), which markedly contrasted with Co-based counterparts exclusively activating PMS to yield sulfate radicals. The oxidizing capacity of the Ni catalyst/oxyanion varied depending on the oxyanion type. Ni catalyst/PMS (or HOCl) degraded a broad spectrum of organics, whereas PDS enabled selective phenol oxidation. This stemmed from the differential reactivity of two high-valent Ni intermediates, Ni(III) and Ni(IV). A high similarity with Ni(III)OOH in a substrate-specific reactivity indicated the role of Ni(III) as the primary oxidant of Ni-activated PDS. With the minor progress of redox reactions with radical probes and multiple spectroscopic evidence on moderate Ni(III) accumulation, the significant elimination of non-phenolic contaminants by NiOOH/PMS (or HOCl) suggested the involvement of Ni(IV) in the substrate-insensitive treatment capability of Ni catalyst/PMS (or HOCl). Since the electron-transfer oxidation of organics by high-valent Ni species involved Ni(II) regeneration, the loss of the treatment efficiency of Ni/oxyanion was marginal over multiple catalytic cycles.


Asunto(s)
Níquel , Oxidación-Reducción , Níquel/química , Catálisis , Aniones , Compuestos Orgánicos/química , Peróxidos/química , Ácido Hipocloroso/química
14.
J Appl Stat ; 51(12): 2382-2401, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267716

RESUMEN

Manufacturing and testing of pharmaceutical products frequently occur in multiple facilities within a company's network. It is of interest to demonstrate equivalence among the alternative testing/manufacturing facilities to ensure product consistency and quality regardless of the facility where it was manufactured/tested. In the Frequentist framework, equivalence testing is well established when comparing two labs or manufacturing facilities; however, when considering more than two labs or production sites, the Frequentist approach may not always offer appropriate or interpretable estimates for demonstrating equivalence among all of them simultaneously. This paper demonstrates the utility of Bayesian methods to the equivalence assessment of multiple groups means, with a comparison against traditional Frequentist methods. We conclude that a Bayesian strategy is very useful for addressing the problem of multi-group equivalence. While it is not our intention to argue that Bayesian methods should always replace Frequentist ones, we show that among the advantages of a Bayesian analysis is that it provides a more nuanced understanding of the degree of similarity among sites than the hypothesis testing underpinning the Frequentist approach.

15.
Food Chem ; 460(Pt 3): 140705, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39098221

RESUMEN

Veterinary drugs play a crucial role in the treatment of various animal diseases. However, their residues, stemming from issues, such as withdrawal period lapses, overuse, or abuse, can jeopardize food safety and human health. This study addresses recent regulations in Korea concerning specific veterinary drugs (anacolin, ephedrine, menichlopholan, piperonyl butoxide, and etisazole HCl) and their ongoing discussions. This study aimed to validate two pre-developed methods for quantifying residues in livestock and fishery products using QuEChERS and liquid chromatography-tandem mass spectrometry. Both methods exhibited excellent linearity, recoveries (70.3-119%), and coefficient of variations (1.3-28%), along with low limits of detection and quantification (0.3-4 ng/g and 1-12 ng/g). This study is significant for its contribution to the detection of veterinary drugs in livestock and fishery products, given the limited research available on the methods for analyzing these substances.


Asunto(s)
Residuos de Medicamentos , Contaminación de Alimentos , Ganado , Espectrometría de Masas en Tándem , Drogas Veterinarias , Residuos de Medicamentos/análisis , Drogas Veterinarias/análisis , República de Corea , Animales , Espectrometría de Masas en Tándem/métodos , Contaminación de Alimentos/análisis , Límite de Detección , Cromatografía Líquida de Alta Presión , Explotaciones Pesqueras
16.
iScience ; 27(8): 110380, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39165843

RESUMEN

Histone H3K9 methylated heterochromatin silences repetitive non-coding sequences and lineage-specific genes during development, but how tissue-specific genes escape from heterochromatin in differentiated cells is unclear. Here, we examine age-dependent transcriptomic profiling of terminally differentiated mouse retina to identify epigenetic regulators involved in heterochromatin reorganization. The single-cell RNA sequencing analysis reveals a gradual downregulation of Kdm3b in cone photoreceptors during aging. Disruption of Kdm3b (Kdm3b +/- ) of 12-month-old mouse retina leads to the decreasing number of cones via apoptosis, and it changes the morphology of cone ribbon synapses. Integration of the transcriptome with epigenomic analysis in Kdm3b +/- retinas demonstrates gains of heterochromatin features in synapse assembly and vesicle transport genes that are downregulated via the accumulation of H3K9me1/2. Contrarily, losses of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that the KDM3B-centered epigenomic network is crucial for balancing of cone photoreceptor homeostasis via the modulation of gene set-specific heterochromatin features during aging.

17.
J Transl Med ; 22(1): 800, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210440

RESUMEN

BACKGROUND: Recycling of integrin via endosomal vesicles is critical for the migration of cancer cells, which leads to the metastasis of pancreatic cancer and devastating cancer-related death. So, new diagnostic and therapeutic molecules which target the recycling of endosomal vesicles need to be developed. METHODS: Public databases including TCGA, ICGC, GSE21501, GSE28735, and GENT are analyzed to derive diagnostic and therapeutic targets. To reveal biological roles and underlying mechanisms of molecular targets, various molecular biological experiments were conducted. RESULTS: First, we identified UNC13D's overexpression in patients with pancreatic cancer (n = 824) and its prognostic significance and high hazard ratio (HR) in four independent pancreatic cancer cohorts (TCGA, n = 178, p = 0.014, HR = 3.629; ICGC, n = 91, p = 0.000, HR = 4.362; GSE21501, n = 102, p = 0.002, HR = 2.339; GSE28735, n = 45, p = 0.022, HR = 2.681). Additionally, its expression is associated with the clinicopathological progression of pancreatic cancer. Further biological studies have shown that UNC13D regulates the migration of pancreatic cancer cells by coupling the exocytosis of recycling endosomes with focal adhesion turnover via the regulation of FAK phosphorylation. Immunoprecipitation and immunocytochemistry showed the formation of the RAB11-UNC13D-FAK axis in endosomes during integrin recycling. We observed that UNC13D directly interacted with the FERM domain of FAK and regulated FAK phosphorylation in a calcium-dependent manner. Finally, we found co-expression of UNC13D and FAK showed the poorest survival (TCGA, p = 0.000; ICGC, p = 0.036; GSE28735, p = 0.006). CONCLUSIONS: We highlight that UNC13D, a novel prognostic factor, promotes pancreatic cancer progression by coupling integrin recycling with focal adhesion turnover via the RAB11-UNC13D-FAK axis for the migration of pancreatic cancer cells.


Asunto(s)
Movimiento Celular , Adhesiones Focales , Integrinas , Neoplasias Pancreáticas , Proteínas de Unión al GTP rab , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Proteínas de Unión al GTP rab/metabolismo , Línea Celular Tumoral , Adhesiones Focales/metabolismo , Integrinas/metabolismo , Quinasa 1 de Adhesión Focal/metabolismo , Femenino , Masculino , Transducción de Señal , Persona de Mediana Edad , Pronóstico , Regulación Neoplásica de la Expresión Génica , Endosomas/metabolismo , Progresión de la Enfermedad
18.
BMC Geriatr ; 24(1): 674, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127641

RESUMEN

BACKGROUND: Calf circumference is currently recommended as a case-finding marker for sarcopenia, but its usefulness has not been determined in chronic pain conditions. Therefore, the present study aimed to evaluate the predictive performance of calf circumference in diagnosing sarcopenia in older patients with chronic low back pain. METHODS: Ambulatory adult patients aged ≥ 65 years with chronic low back pain were enrolled. A diagnosis of sarcopenia was established based on the criteria outlined by the Asian Working Group for Sarcopenia in 2019. Patient demographics, pain-related factors, clinical factors, and sarcopenia-related measurements were compared between non-sarcopenic and sarcopenic patients. Linear regression analysis was used to evaluate the correlation of calf circumference with muscle mass, strength, and physical performance. Also, a receiver operating characteristic curve analysis for calf circumference in predicting sarcopenia was conducted; and area under the curve (AUC) values, along with their corresponding 95% confidence intervals (CI), were calculated. RESULTS: Data from 592 patients were included in the analysis. Eighty-five patients were diagnosed with sarcopenia (14.3%), 71 of whom had severe sarcopenia (11.9%). A higher prevalence of sarcopenia was observed in female patients (9.0% vs. 16.7%, p = 0.016). After adjusting for age, BMI, and comorbidities, calf circumference correlated positively with muscle mass but not with muscle strength and physical performance. The AUC values for sarcopenia were 0.754 (95% CI = 0.636-0.871, p = 0.001) in males and 0.721 (95% CI = 0.657-0.786, p < 0.001) in females. The cut-offs for calf circumference in predicting sarcopenia were 34 cm (sensitivity 67.1%, specificity 70.6%) in males, and 31 cm (sensitivity 82.5%, specificity 51.5%) in females. CONCLUSIONS: Even though sex differences in its predictive value for sarcopenia should be considered, our findings suggest that calf circumference can be used as an indicator for predicting muscle mass and may serve as a potential marker for identifying sarcopenia in older patients with chronic low back pain.


Asunto(s)
Pierna , Dolor de la Región Lumbar , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Masculino , Femenino , Anciano , Estudios Transversales , Estudios Retrospectivos , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/epidemiología , Dolor Crónico/diagnóstico , Dolor Crónico/epidemiología , Fuerza Muscular/fisiología , Anciano de 80 o más Años , Valor Predictivo de las Pruebas , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología
19.
Korean J Fam Med ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39090808

RESUMEN

Background: The Korean Journal of Family Medicine (KJFM), which is an official journal of the Korean Academy of Family Medicine, is an English-text medical journal published since 2009. Although nearly 15 years have passed since the journal was launched, to the best of our knowledge, no study has reviewed articles published in the KJFM. Accordingly, we analyzed articles published in the KJFM for the first time. Methods: Articles published in the KJFM between January 2018 and November 2023 were categorized according to article type. Information about author affiliations, study subjects, research methods, and modes of data collection was then scrutinized. Moreover, we compared the frequencies of subjects, research methods and modes of data collection before, during, and after the coronavirus disease 2019 pandemic. Results: Original article was the most common article type. Approximately 52% of the articles were published by authors affiliated with departments other than family medicine, and 40% were published by family medicine. Approximately 60% and 38% of the articles were published by Korean authors and authors of international affiliations, respectively. Throughout the pandemic periods, research subjects focusing on "diseases & symptoms" have diminished, while "principles of family medicine" have progressively increased. Additionally, the use of cross-sectional study methods has declined. In terms of data collection, the use of "big data," "medical records," and "questionnaires" has decreased, whereas the use of "study results" has increased. Conclusion: KJFM is journal with wide and international participation covering various research subjects and study methods. We believe that our study provides valuable data for the future direction and development of the KJFM.

20.
Mol Cancer Ther ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172730

RESUMEN

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced disease in which patients ultimately fail standard of care androgen-deprivation therapies and exhibit poor survival rates. The prostate-specific membrane antigen (PSMA) has been validated as a mCRPC tumor antigen with over-expression in tumors and low expression in healthy tissues. Using our proprietary technology for incorporating synthetic amino acids (SAAs) into proteins at selected sites, we have developed ARX517, an antibody drug conjugate (ADC) which is composed of a humanized anti-PSMA antibody site-specifically conjugated to a tubulin inhibitor at a drug-to-antibody ratio of 2. After binding PSMA, ARX517 is internalized and catabolized, leading to cytotoxic payload delivery and apoptosis. To minimize premature payload release and maximize delivery to tumor cells, ARX517 employs a non-cleavable PEG linker and stable oxime conjugation enabled via SAA protein incorporation to ensure its overall stability. In vitro studies demonstrate that ARX517 selectively induces cytotoxicity of PSMA-expressing tumor cell lines. ARX517 exhibited a long terminal half-life and high serum exposure in mice, and dose-dependent anti-tumor activity in both enzalutamide-sensitive and -resistant CDX and PDX prostate cancer models. Repeat dose toxicokinetic studies in non-human primates demonstrated ARX517 was tolerated at exposures well above therapeutic exposures in mouse pharmacology studies, indicating a wide therapeutic index. In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on the encouraging preclinical data, ARX517 is currently being evaluated in a Phase 1 clinical trial ([NCT04662580]).

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