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1.
J Med Chem ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258312

RESUMEN

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123. This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC50 = 2.1 nM) and FLT3-ITD (IC50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC50 = 0.98 nM) and MV4-11 (IC50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39265086

RESUMEN

In this study, the effects of Cl2 radicals on dry development of spin-coated metal oxide resist (MOR) and changes in its surface binding states were investigated to verify the mechanism of dry development. Dry development characteristics of tin hydroxide (Tin OH), which is one of the MOR candidates for next generation lithography, were investigated as functions of process time and temperature using a Cl2 radicals source. Non-UV-exposed Tin OH film showed a linear etch rate (1.77 nm/min) from the initial thickness of ∼50 nm, while the UV-exposed film showed slower etch behavior (1.46 nm/min) in addition to the increase of film thickness for up to 3 min during the Cl2 radical dry development. UV-exposed photoresist (PR) contained more oxygen (Sn-O bonding) in the film due to the removal of butyl compounds from the clusters during the UV exposure process. Therefore, due to the lower reaction of chlorine radicals with Sn-O in the UV-exposed Tin OH than the other bindings, the non-UV-exposed PR was preferentially removed compared to the UV-exposed PR. As the temperature decreases, the overall etch rate decreases, but the difference in etch rate between exposed and unexposed Tin OH becomes larger. Finally, at a substrate temperature of -20 °C, the non-UV-exposed Tin OH with a thickness of 50 nm was completely removed, while ∼30 nm thick PR remained for UV-exposed Tin OH. Eventually, a negative tone development was possible with Cl2 radical plasma due to the difference in activation energy between the UV-exposed and non-UV-exposed films. It is believed that dry development using Cl2 radicals will be one of the most important process techniques for next-generation patterning to remove problems such as pattern leaning, line edge roughness, residue, etc., caused by wet development.

3.
J Ophthalmol ; 2024: 3654690, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220230

RESUMEN

Purpose: This study aimed to evaluate the expression of microRNAs (miRNAs) and inflammasomes in diabetes-induced retinal cells and to determine their role in the pathogenesis of diabetic retinopathy (DR). Methods: To establish diabetes-induced cell models, ARPE-19 cells were treated with high glucose. The expression levels of five miRNAs (miR-185, miR-17, miR-20a, miR-15a, and miR-15b) were measured in high glucose-treated ARPE-19 cells using real-time quantitative polymerase chain reaction. Western blotting was performed to measure inflammasome expression in cellular models. miR-17 was selected as the target miRNA, and inflammasome expression was measured following the transfection of an miR-17 mimic into high glucose-treated ARPE-19 cells. Results: In high glucose-treated ARPE-19 cells, miRNA expression was substantially downregulated, whereas that of inflammasome components was significantly increased. Following the transfection of the miR-17 mimic into high glucose-treated ARPE-19 cells, the levels of inflammasome components were significantly decreased. Conclusions: This study investigated the relationship between miRNAs and inflammasomes in diabetes-induced cells using high glucose-treated ARPE-19 cells. These findings suggested that miR-17 suppresses inflammasomes, thereby reducing the subsequent inflammatory response and indicating that miRNAs and inflammasomes could serve as new therapeutic targets for DR.

5.
Parkinsonism Relat Disord ; 128: 107150, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39278122

RESUMEN

BACKGROUND: The effects of long-term care insurance (LTCI) in reducing medical costs and utilization among older adults have been reported. This study aims to investigate the mortality in patients with Parkinson's disease (PD) requiring LTCI and its relationships with economic status. METHODS: This study was conducted using the database of the Korean National Health Insurance Service (NHIS)-Senior Cohort between 2008 and 2019. A total of 5937 patients with PD were included. Hazard ratios (HRs) of mortality associated with LTCI were estimated using a Cox regression model. Potential confounders such as demographics and comorbidities were adjusted. RESULTS: Out of 5937 PD patients, 821 required LTCI, and 5116 did not. Compared to PD patients without LTCI, PD patients with LTCI were older and exhibited a higher comorbidity burden. The overall incidence rate of mortality was 18.63 per 100 person-years in PD patients with LTCI. PD patients requiring LTCI were associated with an increased HR of 3.61 (95 % CI = 3.13-4.16) for mortality compared to PD patients not eligible for LTCI. Low-income status with LTCI was associated with the highest mortality risk (HR = 4.54, 95 % CI = 3.38-6.09), compared to middle-income status (HR = 3.47, 95 % CI = 2.64-4.61) and high-income status (HR = 3.53, 95 % CI = 2.91-4.91). CONCLUSIONS: Our study suggests that older PD patients requiring LTCI with low economic status have a higher risk of death. Continuous policy efforts to reduce the mortality risk in this group are needed.

6.
Int J Nanomedicine ; 19: 9195-9211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267725

RESUMEN

Purpose: Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers. Methods: We prepared and compared polyethylene glycol (PEG)-coated micelles with micelles where cell-penetrating peptide (CPP) is conjugated to PEG. Systematic investigations of the physicochemical and aerosolization properties, performance, in vitro release, mucus and cell penetration, lung function, and pharmacokinetics/pharmacodynamics (PK/PD) of polymeric micelles were performed to evaluate their interaction with the respiratory tract. Results: The nano-micelles, with a particle size of <100 nm, exhibited a sustained-release profile. Interestingly, PEG-coated micelles exhibited higher diffusion and deeper penetration across the mucus layer. In addition, CPP-modified micelles showed enhanced in vitro cell penetration. Finally, in the PK/PD studies, the micellar solution demonstrated higher maximum concentration (Cmax) and AUC0-8h values than subcutaneously administered INS solution, along with a sustained blood glucose-lowering effect that lasted for more than 8 h. Conclusion: This study proposes the use of mucus-penetrating micelle formulations as prospective inhalation nano-carriers capable of efficiently transporting peptides to the respiratory tract.


Asunto(s)
Péptidos de Penetración Celular , Insulina , Micelas , Polietilenglicoles , Insulina/administración & dosificación , Insulina/farmacocinética , Insulina/química , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Animales , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/farmacocinética , Humanos , Tamaño de la Partícula , Administración por Inhalación , Masculino , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Ratas Sprague-Dawley , Moco/química , Moco/metabolismo , Moco/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Glucemia/efectos de los fármacos , Glucemia/análisis
7.
Genes Genomics ; 46(10): 1253-1265, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39259487

RESUMEN

Lilies are highly regarded for their ornamental appeal and striking flowers, which are of significant importance in horticulture. Understanding the genetic makeup of these plants is crucial for breeding and developing new cultivars. This study presents a comprehensive cytogenetic analysis of 45 S and 5 S rDNA loci in 34 wild Lilium species. To reveal the genetic relationships within the genus, advanced visualization methods, such as heatmaps and 3D network plots, were utilized. The results of this study identified both conserved and divergent genetic features, which offer insights into the evolutionary history and potential genetic compatibility of these species. Notably, the clustering of species based on rDNA locus patterns highlights the need for potential taxonomic re-evaluation and reveals candidates for cross-breeding. This integrated approach emphasizes the importance of combining cytogenetic data with traditional morphological classifications to refine our understanding of the Lilium species. Future research should expand the range of analyzed species, incorporate additional molecular markers to further elucidate genetic relationships, and support the development of resilient and diverse ornamental crops. The findings of this study provide a novel framework for genetic analysis of Lilium, offering valuable insights for both scientific understanding and practical breeding programs.


Asunto(s)
Análisis Citogenético , Lilium , Lilium/genética , Análisis Citogenético/métodos , Cromosomas de las Plantas/genética , ADN Ribosómico/genética , Filogenia , Fitomejoramiento/métodos
8.
Nutr Res Pract ; 18(4): 523-533, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39109196

RESUMEN

BACKGROUND/OBJECTIVES: Given that adolescents watch Mukbang (eating broadcast) more frequently than other age groups, interest in the potential health effects of watching Mukbang and Cookbang (cooking broadcast) is growing. This study aimed to determine the status of watching Mukbang and Cookbang among Korean adolescents and its relationship with their dietary behaviors. SUBJECTS/METHODS: We used data from the 18th Korea Youth Risk Behavior Survey, conducted in 2022 (n = 51,850). The study included the frequency of watching Mukbang and Cookbang and the self-rated impact of watching them. Dietary behaviors included consumption of the following items: fruits (≥ once a day), vegetables (≥ 3 times a day), fast foods (≥ 3 times a week), late-night snacks (≥ 3 times a week), caffeinated drinks (≥ 3 times a week), and sweet-flavored drinks (≥ 3 times a week). Furthermore, obesity, weight loss attempts during the past 30 days, body image distortion, and inappropriate methods to control weight were also included. RESULTS: Among adolescents, 70.6% watched Mukbang and Cookbang, and 13.2% watched them more than 5 times a week. Approximately 27.6% of the adolescents responded that they were influenced by watching Mukbang and Cookbang. Adolescents who frequently watched Mukbang and Cookbang consumed less vegetable and fruit; however, the likelihood of consuming fast food, late-night snacks, sugary drinks, and caffeinated drinks increased. In addition, they were more likely to attempt inappropriate weight-loss methods and become obese. Adolescents who responded that their eating habits were influenced by watching Mukbang and Cookbang were more likely to have unhealthy eating behavior compared to the group who responded that their habits were not influenced by these shows. CONCLUSION: Watching Mukbang and Cookbang is common among Korean adolescents and is associated with unhealthy dietary behaviors. Prospective studies, including broadcasting content, should evaluate the impact of Mukbang and Cookbang on health.

9.
Small Methods ; : e2400902, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39092676

RESUMEN

The systemic delivery of oligonucleotide therapeutics to the brain is challenging but highly desirable for the treatment of brain diseases undruggable with traditional small-molecule drugs. In this study, a set of DNA nanostructures is prepared and screened them to develop a protein corona-assisted platform for the brain delivery of oligonucleotide therapeutics. The biodistribution analysis of intravenously injected DNA nanostructures reveals that a cube-shaped DNA nanostructure (D-Cb) can penetrate the brain-blood barrier (BBB) and reach the brain tissue. The brain distribution level of D-Cb is comparable to that of other previous nanoparticles conjugated with brain-targeting ligands. Proteomic analysis of the protein corona formed on D-Cb suggests that its brain distribution is driven by endothelial receptor-targeting ligands in the protein corona, which mediate transcytosis for crossing the BBB. D-Cb is subsequently used to deliver an antisense oligonucleotide (ASO) to treat glioblastoma multiforme (GBM) in mice. While free ASO is unable to reach the brain, ASO loaded onto D-Cb is delivered efficiently to the brain tumor region, where it downregulates the target gene and exerts an anti-tumor effect on GBM. D-Cb is expected to serve as a viable platform based on protein corona formation for systemic brain delivery of oligonucleotide therapeutics.

10.
Carbohydr Polym ; 343: 122447, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39174126

RESUMEN

Polysaccharides and polyphenols are bioactive components that co-exist in many plant foods. Their binary interaction in terms of the structure-function relationships, however, has not been well clarified. This study elucidated the correlation between the structural and physiological properties of galactomannan (GM) -catechin monomer complexes and GM with different branching or molecular weight (Mw). Results indicated that locus bean gum with lower branching degree (Gal/Man is 0.259) bound more readily to EGCG with adsorption rate of 19.42 %. EGCG and ECG containing galloyl groups were more inclined to form hydrogen bonds with GMs, significantly improving the adsorption by GMs. The introduction of EGCG could enhance the antioxidant activity and starch digestion inhibition of GM, which positively correlated with the adsorption capacity of EGCG. The guar gum (GG) with higher Mw (7384.3 kDa) could transport 71.51 % EGCG into the colon, while the retention rate of EGCG reaching the colon alone was only 46.33 %. Conversely, GM-EGCG complex with lower Mw (6.9 kDa) could be readily utilized by gut microbiota, and increased production of short-chain fatty acids (SCFAs). This study elucidated the structure-properties relationship of GM-EGCG complexes, and provide a new idea for the development and precision nutrition of polysaccharides-polyphenol complexes fortified functional foods.


Asunto(s)
Catequina , Galactanos , Galactosa , Mananos , Peso Molecular , Gomas de Plantas , Mananos/química , Mananos/farmacología , Galactosa/análogos & derivados , Galactosa/química , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Gomas de Plantas/química , Gomas de Plantas/farmacología , Galactanos/química , Galactanos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/química , Adsorción , Almidón/química , Almidón/análogos & derivados , Colon/efectos de los fármacos , Colon/metabolismo , Ratones , Masculino
11.
Vet Sci ; 11(8)2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39195832

RESUMEN

This report describes the successful intrahepatic duct incision and closure for the treatment of multiple cholelithiasis in a dog with untreated hypothyroidism. A 12-year-old spayed female Spitz dog weighing 11.3 kg was diagnosed with multiple cholelithiasis, and a quadrate liver lobectomy and cholecystectomy were performed. Large gallstones were located in the left liver lobe's intrahepatic duct distal to the anastomosis of the intrahepatic ducts of the left medial and lateral lobes. The dilated intrahepatic duct was packed off with wet gauze, and incision and closure were performed on the most dilated section, which was proximal to the largest gallstone. After surgery, the patient showed normal liver function and was discharged with normal total bilirubin and C-reactive protein levels. On postoperative day 83, no stones were observed in the dilated common bile duct (CBD), and the degree of dilatation of the CBD had decreased from 9 mm to 4 mm, with no obstructions. Right intrahepatic gallstones were confirmed without dilatation. Hypothyroidism was managed medically. Hepatic duct incision and closure can be performed in dogs with multiple cholelithiasis. Although not the first option, intrahepatic bile duct incision proves to be a new alternative for the successful treatment of cholelithiasis in dogs.

12.
J Korean Med Sci ; 39(28): e206, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39048301

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV), a highly transmissible virus, is the leading cause of lower respiratory tract infections. We examined molecular changes in the RSV genome before and after the coronavirus disease 2019 (COVID-19) pandemic in Korea, and investigated whether drug-resistant mutations were present. METHODS: In this prospective, single-center study, RSV-positive respiratory samples were collected between September 2019 and December 2022. Long-read whole-genome sequencing (WGS) was performed, and the presence of known drug-resistant substitutions for palivizumab, nirsevimab, and suptavumab was investigated. RESULTS: Overall, 288 respiratory samples were collected from 276 children. WGS data were available for 133 samples (71 and 62 samples from the pre- and post-pandemic periods, respectively). All RSV-A strains (n = 56) belonged to the GA2.3.5 (ON1) genotype, whereas all RSV-B strains (n = 77) belonged to the GB5.0.5a (BA) genotype. No significant differences in genotypes were observed between the pre- and post-pandemic periods. In addition, no notable mutations related to nirsevimab or palivizumab resistance were detected in the F gene. However, the L172Q and S173L substitutions, which are known to confer resistance to suptavumab, were present in all RSV-B samples. CONCLUSION: Despite the unprecedented interruption of RSV seasonality, there were no significant molecular changes in circulating RSV strains in Korea related to nirsevimab or palivizumab resistance before and after the COVID-19 pandemic. However, RSV-specific drug-resistance substitutions for suptavumab were identified.


Asunto(s)
COVID-19 , Genotipo , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , SARS-CoV-2 , Secuenciación Completa del Genoma , Humanos , Estudios Prospectivos , República de Corea/epidemiología , COVID-19/virología , COVID-19/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Farmacorresistencia Viral/genética , Antivirales/uso terapéutico , Genoma Viral , Palivizumab/uso terapéutico , Femenino , Mutación , Masculino , Niño , Preescolar , Lactante , Anticuerpos Monoclonales Humanizados/uso terapéutico
13.
Sci Rep ; 14(1): 15639, 2024 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977719

RESUMEN

Desertification is known to be a major threat to biodiversity, yet our understanding of the consequent decline in biodiversity remains insufficient. Here, we predicted climate change-induced range shifts and genetic diversity losses in three model dung beetles: Colobopterus erraticus, Cheironitis eumenes, and Gymnopleurus mopsus, distributed across the Gobi Desert and Mongolian Steppe, areas known for desertification. Phylogeographic analyses of mitochondrial COI sequences and species distribution modeling, based on extensive field investigations spanning 14 years, were performed. Species confined to a single biome were predicted to contract and shift their distribution in response to climate change, whereas widespread species was predicted to expand even if affected by range shifts. We indicated that all species are expected to experience significant haplotype losses, yet the presence of high singleton frequencies and low genetic divergence across geographic configurations and lineages mitigate loss of genetic diversity. Notably, Cheironitis eumenes, a desert species with low genetic diversity, appears to be the most vulnerable to climate change due to the extensive degradation in the Gobi Desert. This is the first study to predict the response of insects to desertification in the Gobi Desert. Our findings highlight that dung beetles in the Gobi Desert and Mongolian Steppe might experience high rates of occupancy turnover and genetic loss, which could reshuffle the species composition.


Asunto(s)
Cambio Climático , Escarabajos , Clima Desértico , Variación Genética , Escarabajos/genética , Escarabajos/clasificación , Escarabajos/fisiología , Animales , Mongolia , Biodiversidad , Filogeografía , Haplotipos , Pradera , Filogenia
14.
ACS Appl Mater Interfaces ; 16(31): 41642-41652, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39069792

RESUMEN

High-aspect-ratio patterns are required for next-generation three-dimensional (3D) semiconductor devices. However, it is challenging to eliminate voids and seams during gap-filling of these high-aspect-ratio patterns, such as deep trenches, especially for nanoscale high-aspect-ratio patterns. In this study, a SiO2 plasma-enhanced atomic layer deposition process incorporated with ion collision using bias power to the substrate was used for bottom-up trench gap-filling. The effect of bias power frequency on SiO2 trench gap-filling was then investigated. Results showed that changes in bias power frequency did not significantly change the process rate, such as SiO2 growth per cycle. At relatively low bias power frequencies, high-energy ions formed an overhang at the entrance of the high-aspect-ratio trench pattern through sputter etching and redeposition, blocking the pattern entrance. However, at relatively high-frequency bias power, overhang formation due to sputtering did not occur. In the trench interior, due to a scattering effect of ions, deposition was thicker at the bottom of the trench than that at the top, achieving bottom-up gap-filling and void-free gap-filling.

15.
Diagnostics (Basel) ; 14(13)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39001308

RESUMEN

Glaucoma remains the primary cause of long-term blindness. While diabetes mellitus (DM) and hypertension (HTN) are known to influence glaucoma, other factors such as age and sex may be involved. In this retrospective study, we aimed to investigate the associations between age, sex, DM, HTN, and glaucoma risk. We employed optical coherence tomography (OCT) conducted using a 200 × 200-pixel optic cube (Cirrus HD OCT 6000, version 10.0; Carl Zeiss Meditec, Dublin, CA, USA). Effects obscured by low-test signals were disregarded. Data were amassed from 1337 patients. Among them, 218 and 402 patients had DM and HTN, respectively, with 133 (10%) exhibiting both. A sex-based comparison revealed slightly greater retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness in females. Patients without DM and HTN were predominantly in their 50 s and 60 s, whereas DM and HTN were most prevalent in those in their 60 s and 70 s. Both RNFL and GCIPL thicknesses decreased with advancing age in most patients. The study revealed that older individuals were more prone to glaucoma than younger individuals, with a higher incidence among patients with DM and HTN and reduced RNFL and GCIPL thicknesses. Furthermore, early detection before advancing age could furnish valuable preventive insights.

16.
World J Clin Oncol ; 15(7): 806-810, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39071462

RESUMEN

Poly (ADP-ribose) (PAR), a polymer of ADP-ribose, is synthesized by PAR polymerase and is crucial for the survival of cancer cells due to its vital functions in DNA repair and post-translational modifications. Beyond its supportive role, PAR also triggers cancer cell death by excessive accumulation of PAR leading to an energy crisis and parthanatos. This phenomenon underscores the potential of targeting PAR regulation as a novel anticancer strategy, and the rationale would present an engaging topic in the field of anticancer research. Therefore, this editorial provides an overview of the mechanisms determining cancer cell fate, emphasizing the central role of PAR. It further introduces promising methods for modulating PAR concentrations that may pave the way for innovative anticancer therapies.

17.
J Rheum Dis ; 31(3): 171-177, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38957361

RESUMEN

Objective: The purpose of this study is to evaluate the impact of tumor necrosis factor (TNF)-α blocker therapy on the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) among patients who have failed conventional nonsteroidal anti-inflammatory drugs. Methods: A comparative study was conducted involving axial spondyloarthritis (axSpA) patients treated with either TNF-α blocker or conventional therapy. Patient data, including demographics, disease characteristics, and ASAS-HI scores, were collected before and after treatment. Statistical analysis was performed to compare changes in ASAS-HI scores between the TNF-α blocker and the conventional therapy group. Results: The study population consisted of patients with axSpA, with a mean age of 38.3 years in conventional treatment group and 29.3 years in TNF-α blocker group. Most variables, including C-reactive protein levels, other comorbidities, and disease assessment scores showed no significant difference between groups. Longitudinal analysis within each treatment group from Week 0 to 12 showed no significant change in the conventional treatment group, whereas the TNF-α blocker group experienced a significant reduction in ASAS-HI scores, demonstrating the effectiveness of the treatment. The TNF-α blocker group exhibited a significantly greater improvement in ASAS-HI scores compared to the conventional therapy group. The Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index demonstrated strong positive correlations with ASAS-HI scores, indicating higher disease activity and functional limitation are associated with worse health outcomes in patients. Conclusion: The research demonstrates that ASAS-HI scores significantly improve with TNF-α blocker therapy in axSpA patients, underscoring ASAS-HI's effectiveness as a tool for evaluating drug responses.

18.
Exp Dermatol ; 33(6): e15092, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38888196

RESUMEN

Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that SPOCK2 plays important roles in the progression of various human cancers; however, the role of SPOCK2 in melanoma remains unknown. Therefore, this study investigated the roles of SPOCK2 and the related mechanisms in melanoma progression. To evaluate the clinical significance of SPOCK2 expression in patients with melanoma, we analysed the association between SPOCK2 expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of Spock2 in melanoma progression in vitro and in vivo, we knocked down Spock2 in the B16F10 melanoma cell line. High SPOCK2 levels were positively associated with good prognosis and long survival rate of patients with melanoma. Spock2 knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, Spock2 downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1-MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in Spock2 knockdown cells. Therefore, Spock2 could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, Spock2 knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that SPOCK2 plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.


Asunto(s)
Apoptosis , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Melanoma , Neoplasias Cutáneas , Animales , Femenino , Humanos , Masculino , Ratones , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Ciclo Celular , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 14 de la Matriz/metabolismo , Metaloproteinasa 14 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Melanoma/genética , Melanoma/patología , Melanoma/metabolismo , Melanoma Experimental/genética , Melanoma Experimental/patología , Melanoma Experimental/metabolismo , Ratones Endogámicos C57BL , Invasividad Neoplásica , Pronóstico , Proteoglicanos/metabolismo , Proteoglicanos/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo
19.
Sci Rep ; 14(1): 12648, 2024 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-38825629

RESUMEN

Observational studies have shown controversial associations between alcohol intake and radiographic osteoarthritis (OA). This study investigated whether this association was causal using a Mendelian randomization (MR) study in a population-based cohort in Korean. The study enrolled 2429 subjects (1058 men, 1371 women) from the Dong-gu Study. X-rays of the hand and knee joints were scored using a semi-quantitative grading system to calculate the total score of the hand and knee joints. ALDH2 rs671 genotyping was performed by high-resolution melting analysis. MR instrumental variable analysis and observational multivariable regression analysis were used to estimate the association between genetically predicted alcohol intake and the radiographic severity of OA. Subjects with the G/G genotype had a higher current alcohol intake than those with the G/A and A/A genotypes in both men and women (all P < 0.001). Men with the G/G genotype had higher total knee (P < 0.001) and hand scores (P = 0.042) compared to those with the G/A and A/A genotypes after adjusting for age and body mass index, but not in women. In the observational multivariable regression analysis, each alcohol drink per day in men was associated with increased knee (P = 0.001) and hand joint scores (P = 0.013) after adjustment, but not in women. In our MR analysis, utilizing ALDH2 rs671 genotypes as instrumental variables for alcohol consumption, has shown a significant link between each additional daily alcohol drink and increased radiographic joint severity in men.


Asunto(s)
Consumo de Bebidas Alcohólicas , Aldehído Deshidrogenasa Mitocondrial , Osteoartritis de la Rodilla , Humanos , Masculino , Consumo de Bebidas Alcohólicas/efectos adversos , Femenino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/genética , Aldehído Deshidrogenasa Mitocondrial/genética , Osteoartritis/genética , Osteoartritis/diagnóstico por imagen , Anciano , Radiografía , Índice de Severidad de la Enfermedad , Articulaciones de la Mano/diagnóstico por imagen , Articulaciones de la Mano/patología , Genotipo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología
20.
World J Clin Cases ; 12(16): 2837-2841, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38899302

RESUMEN

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder characterized by fever, arthritis, skin rash, and systemic symptoms. The etiology of AOSD is unknown; however, it is thought to be related to immune dysregulation. Although a rare disease, AOSD can significantly impact reproductive health, particularly during pregnancy. This case study assesses the implications of pregnancy in a patient with AOSD, as well as the potential for heredity of the disease. Neonatal hemophagocytic lympho-histiocytosis (HLH) is a rare and life-threatening disorder characterized by hyperinflammation and uncontrolled activation of immune cells, leading to multiple organ dysfunction. This case report aimed to introduce neonatal HLH from a mother with AOSD. CASE SUMMARY: This case study presents a 29-year-old female with AOSD who became pregnant and gave birth to a premature infant who was diagnosed with neonatal HLH. AOSD can significantly impact pregnancy and childbirth, as it may become more severe during pregnancy, with an increased risk of fetal loss and preterm birth. The management of AOSD during pregnancy involves the use of nonsteroidal anti-inflammatory drugs and glucocorticoids, as well as immunosuppressive agents in severe cases. However, the use of immunosuppressive agents during pregnancy may be associated with potential risks to the fetus. The hereditary implications of AOSD are unclear; however, available evidence suggests that genetic factors may play a role in the disease development. CONCLUSION: AOSD can have significant implications for pregnancy and childbirth, including an increased risk of fetal loss and preterm birth. Neonatal HLH, a complication of AOSD in pregnancy, requires prompt diagnosis and management. Women with AOSD who are considering pregnancy should discuss their options with their healthcare provider and develop a management plan that addresses the potential risks to both mother and fetus.

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