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1.
J Trace Elem Med Biol ; 86: 127524, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39293108

RESUMEN

BACKGROUND: Recent studies have shown an association between trace elements and systemic lupus erythematosus (SLE), but the relationship between trace elements and SLE is still unclear. This study aims to determine the distribution of plasma trace elements in newly diagnosed SLE patients and the association between these essential and toxic element mixtures and SLE. METHODS: In total, 110 SLE patients and 110 healthy controls were included. Blood samples were collected. 15 plasma trace elements were quantified using an inductively coupled plasma mass spectrometer (ICP-MS). Multivariate logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) are used to analyze the association between single and mixed exposure of elements and SLE. RESULTS: The logistic regression model shows that, plasma lithium (Li) [OR (95 % CI): 1.963 (1.49-2.586)], vanadium (V) [OR (95 % CI): 2.617(1.645-4.166)] and lead (Pb) [OR (95 % CI): 1.603(1.197-2.145)] were positively correlated with SLE, while selenium (Se) [OR (95 % CI): 0.055(0.019-0.157)] and barium (Ba) [OR (95 % CI): 0.792(0.656-0.957)] had been identified as protective factors for SLE. RCS results showed a non-linear correlation between the elements Li, V, Ni, copper, Se, rubidium and SLE. In addition, WQS regression, qgcomp, and BKMR models consistently revealed significant positive effects of plasma Li and Pb on SLE, as well as significant negative effects of plasma Se. CONCLUSIONS: Exposure to heavy metals such as Li and Pb is significantly positively correlated with SLE, but Se may be protective factors for SLE. In addition, there is a nonlinear correlation between the elements Li and Se and SLE, and there are complex interactions between the elements. In the future, larger populations and prospective studies are needed to confirm these associations.

2.
Nat Commun ; 15(1): 7652, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227563

RESUMEN

P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor's ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3's physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3ß domain of the ICD. PSFL77 modulated pain perception in P2rx3+/+, but not in P2rx3-/-, mice, indicating that the 1α3ß, a "tunable" region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.


Asunto(s)
Sitio Alostérico , Dominios Proteicos , Receptores Purinérgicos P2X3 , Animales , Receptores Purinérgicos P2X3/metabolismo , Receptores Purinérgicos P2X3/química , Receptores Purinérgicos P2X3/genética , Humanos , Ratones , Células HEK293 , Adenosina Trifosfato/metabolismo , Masculino , Ratones Endogámicos C57BL , Regulación Alostérica
3.
Front Endocrinol (Lausanne) ; 15: 1461317, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39229374

RESUMEN

Introduction: This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). Materials and methods: A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. Results: We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. Conclusion: GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.


Asunto(s)
Tasa de Natalidad , Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Recuperación del Oocito , Síndrome de Hiperestimulación Ovárica , Inducción de la Ovulación , Humanos , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Adulto , Recuperación del Oocito/métodos , Inducción de la Ovulación/métodos , Estudios Retrospectivos , Embarazo , Estudios de Casos y Controles , Fertilización In Vitro/métodos , Síndrome de Hiperestimulación Ovárica/prevención & control , Síndrome de Hiperestimulación Ovárica/epidemiología , Nacimiento Vivo/epidemiología , Índice de Embarazo , Fármacos para la Fertilidad Femenina/uso terapéutico , Fármacos para la Fertilidad Femenina/administración & dosificación , Taiwán/epidemiología , Inyecciones de Esperma Intracitoplasmáticas/métodos
4.
ACS Biomater Sci Eng ; 10(9): 5474-5495, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39171865

RESUMEN

Cancer remains a significant challenge in extending human life expectancy in the 21st century, with staggering numbers projected by the International Agency for Research on Cancer for upcoming years. While conventional cancer therapies exist, their limitations, in terms of efficacy and side effects, demand the development of novel treatments that selectively target cancer cells. Tumor immunotherapy has emerged as a promising approach, but low response rates and immune-related side effects present significant clinical challenges. Researchers have begun combining immunotherapy with nanomaterials to optimize tumor-killing effects. Stimuli-responsive nanomaterials have become a focus of cancer immunotherapy research due to their unique properties. These nanomaterials target specific signals in the tumor microenvironment, such as pH or temperature changes, to precisely deliver therapeutic agents and minimize damage to healthy tissue. This article reviews the recent developments and clinical applications of endogenous and exogenous stimuli-responsive nanomaterials for tumor immunotherapy, analyzing the advantages and limitations of these materials and highlighting their potential for enhancing the immune response to cancer and improving patient outcomes.


Asunto(s)
Inmunoterapia , Nanoestructuras , Neoplasias , Microambiente Tumoral , Humanos , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Nanoestructuras/uso terapéutico , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Animales , Concentración de Iones de Hidrógeno
5.
J Formos Med Assoc ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39138104

RESUMEN

BACKGROUND: Breast cancer treatments often have negative effects on fertility, which pose challenges among patients who want to be parents in the future. This study aimed to examine the efficacy of oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation in patients with breast cancer. METHODS: This retrospective review evaluated 42 patients with breast cancer who underwent fertility preservation at our center from January 2012 to December 2022. This review encompassed the demographic characteristics of the patients, cancer stages, treatment details, and types of fertility preservation procedures and their outcomes. RESULTS: The average age at disease diagnosis was 33.4 years. Approximately 90.4% of patients presented with early-stage cancer (≤2). Of 42 patients, 26 underwent oocyte cryopreservation; 17, embryo cryopreservation; and 2, ovarian tissue cryopreservation. Further, three patients received mixed treatment. The overall live birth rate was 63.2%. There are more live births in embryo cryopreservation group. The successful pregnancy group was significantly younger and had a remarkably higher quantity of preserved oocytes/embryos than the nonsuccessful pregnancy group. The oocyte and embryo utilization rates in cryopreservation were 7.69% and 52.94%, respectively. These findings underscored the importance of prompt, informed discussions about fertility preservation options. CONCLUSION: Fertility preservation in patients with breast cancer have promising reproductive outcomes, with embryo cryopreservation being particularly effective. Prompt counseling and individualized fertility preservation strategies are important for improving the likelihood of posttreatment pregnancy. Nevertheless, future research on the long-term psychological and emotional effects of different fertility preservation methods must be performed.

6.
Pediatr Neonatol ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39107217

RESUMEN

BACKGROUND: Premature and small-for-gestational-age (SGA) infants tend to have long-term growth morbidities such as short stature, failure to thrive, and obesity. Although most of these infants show catch-up growth at 2-4 years of age, they are still more susceptible to childhood obesity and related metabolic disorders. Those who fail to achieve catch-up will suffer from pathological short stature and neurodevelopmental impairment through adulthood. This study aims to depict the growth pattern of premature or SGA infants and their growth morbidities in Taiwan. METHODS: Data were obtained from a nationally representative cohort of 24,200 pairs of postpartum women and newborns in the Taiwan Birth Cohort Study (TBCS), using structured questionnaire interviews. A total of 16,358 infants were included and three follow-up surveys were completed at 6, 18, and 36 months after the deliveries. We constructed growth curves to conduct an in-depth investigation into anthropometric data, applying a linear mixed model. Logistic regression was used to model the relevant outcomes, with adjustment for various potential confounding factors. RESULTS: Despite being born shorter and lighter, preterm and SGA infants generally showed catch-up growth and had no higher odds ratios (ORs) of developing short stature or failure to thrive compared to appropriate-for-gestational-age (AGA) term infants before 3 years of age. Preterm SGA infants, particularly females, had higher ORs for obesity at the 36-month follow-up. CONCLUSION: This is the first nationwide population-based study depicting the growth of SGA infants in Taiwan. The growth patterns of preterm and term SGA infants are different from those of preterm and term AGA infants. Further research is necessary to understand the growth trajectories of preterm and SGA infants and their associations with later diseases.

7.
BMC Nephrol ; 25(1): 263, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39143548

RESUMEN

BACKGROUND: A better understanding of the association between chronic kidney disease (CKD) and glaucoma is required to optimize clinical outcomes. Therefore, this study aimed to investigate the association of chronic kidney disease (CKD) with new diagnoses of glaucoma over time from January 2009 to December 2019. METHOD: This retrospective propensity-matched cohort study utilizing Taiwanese electronic health records examined the incidence of newly diagnosed glaucoma in patients with and without chronic kidney disease (CKD). The exposure variable was the diagnosis of CKD, identified through diagnostic codes. The primary outcome was the incidence of new-onset glaucoma. Subgroup analyses on glaucoma risk included age, gender, comorbidities, glaucoma subtypes, and dialysis status. Statistical analyses included Kaplan-Meier analysis, Cox proportional hazards models, and Poisson regression models, with the associated hazard ratios and confidence intervals reported. RESULTS: Seven hundred twenty-three thousand two hundred sixteen patients with CKD (42.3% female; mean [SD] age at index, 66.3 [15.6] years) and 723,216 patients without CKD (42.3% female; mean [SD] age at index, 66.3 [15.7]) were recruited. We showed a significantly increased risk of glaucoma irrespective of subtypes in CKD patients compared to those without CKD (HR: 1.29 [CI: 1.26-1.32], p < 0.001). Kaplan-Meier curves revealed a significantly increased glaucoma risk in both the dialytic subtype and non-dialytic CKD patients when compared to their non-CKD counterparts (p < 0.001). We also showed that all genders (aHR 1.17 [CI: 1.13-1.21] for females vs. aHR 1.39 [CI:1.35-1.43] for males), all ages (< = 49: aHR 1.49 [CI: 1.37-1.62]; 50-59: aHR 1.48 [CI: 1.40-1.56]; 60-69: aHR 1.30 [CI: 1.25-1.6]; 70-79: aHR 1.21 [CI: 1.17-1.26]; > 80: aHR 1.29 [CI: 1.21-1.37]); all income brackets and all urbanization status were associated with significantly increased risk of glaucoma from among the CKD cohort when compared to their respective non-CKD cohort (p < 0.001). CONCLUSIONS: Our cohort study spanning 12 years showed an elevated glaucoma risk following a CKD diagnosis compared to a frequency-matched non-CKD cohort. Our findings have relevance for the clinical practice of at-risk CKD patients. TRIAL REGISTRATION: Due to the retrospective nature of the study, no registration was necessary.


Asunto(s)
Glaucoma , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Insuficiencia Renal Crónica/epidemiología , Persona de Mediana Edad , Taiwán/epidemiología , Estudios Retrospectivos , Anciano , Glaucoma/epidemiología , Incidencia , Estudios de Cohortes , Factores de Riesgo , Medición de Riesgo/métodos , Anciano de 80 o más Años , Modelos de Riesgos Proporcionales , Comorbilidad , Adulto
8.
J Sep Sci ; 47(15): e2400222, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39091177

RESUMEN

Drug-resistant bacterial infections pose a significant challenge in the field of bacterial disease treatment. Finding new antibacterial pathways and targets to combat drug-resistant bacteria is crucial. The bacterial quorum sensing (QS) system regulates the expression of bacterial virulence factors. Inhibiting bacterial QS and reducing bacterial virulence can achieve antibacterial therapeutic effects, making QS inhibition an effective strategy to control bacterial pathogenicity. This article mainly focused on the PqsA protein in the QS system of Pseudomonas aeruginosa. An affinity chromatography medium was developed using the SpyTag/SpyCatcher heteropeptide bond system. Berberine, which can interact with the PqsA target, was screened from Phellodendron amurense by affinity chromatography. We characterized its structure, verified its inhibitory activity on P. aeruginosa, and preliminarily analyzed its mechanism using molecular docking technology. This method can also be widely applied to the immobilization of various protein targets and the effective screening of active substances.


Asunto(s)
Antibacterianos , Cromatografía de Afinidad , Phellodendron , Pseudomonas aeruginosa , Percepción de Quorum , Percepción de Quorum/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/química , Phellodendron/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Simulación del Acoplamiento Molecular , Evaluación Preclínica de Medicamentos , Pruebas de Sensibilidad Microbiana
9.
Artículo en Inglés | MEDLINE | ID: mdl-39093368

RESUMEN

The promotion of gut health, a pervasive problem in modern animal husbandry, positively affects organismal health, productivity, and economics. Porcine intestinal epithelial cells (IPEC-J2) continuously proliferate to maintain intestinal homeostasis, including barrier, immune, and absorptive functions. Gut homeostasis is fundamental to organismal health. ADP-ribosylation factor 1 (Arf1), a small GTPase, plays a crucial role in coordinating mTORC1 in response to nutrients, especially amino acid availability in the gut. mTORC1 is the central hub of proliferation. Thus, it seems likely that Arf1 promotes IPEC-J2 cell proliferation. However, the exact role of Arf1 in the porcine gut remains unclear. Therefore, we evaluated the functional role and possible mechanisms of Arf1 in the porcine intestine through Arf1 overexpression and knockdown in IPEC-J2 cells. Arf1 overexpression and knockdown significantly enhanced and inhibited, respectively, IPEC-J2 cell viability, and PCNA expression varied with Arf1 expression. Moreover, the proportion of Ki67-positive cells was significantly greater in the Arf1-overexpressing group than in the control group. These results suggest that Arf1 improves IPEC-J2 cell proliferation. The underlying mechanism was explored by Western blotting. Arf1 overexpression and knockdown significantly enhanced and suppressed, respectively, the levels of p-S6K1 and p-RPS6, which are key downstream targets of the mTORC1 signaling pathway. Collectively, our findings reveal the role of the Arf1-mTORC1 axis in IPEC-J2 cell proliferation and its potential function in regulating intestinal homeostasis and health.

10.
Database (Oxford) ; 20242024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39114977

RESUMEN

The BioRED track at BioCreative VIII calls for a community effort to identify, semantically categorize, and highlight the novelty factor of the relationships between biomedical entities in unstructured text. Relation extraction is crucial for many biomedical natural language processing (NLP) applications, from drug discovery to custom medical solutions. The BioRED track simulates a real-world application of biomedical relationship extraction, and as such, considers multiple biomedical entity types, normalized to their specific corresponding database identifiers, as well as defines relationships between them in the documents. The challenge consisted of two subtasks: (i) in Subtask 1, participants were given the article text and human expert annotated entities, and were asked to extract the relation pairs, identify their semantic type and the novelty factor, and (ii) in Subtask 2, participants were given only the article text, and were asked to build an end-to-end system that could identify and categorize the relationships and their novelty. We received a total of 94 submissions from 14 teams worldwide. The highest F-score performances achieved for the Subtask 1 were: 77.17% for relation pair identification, 58.95% for relation type identification, 59.22% for novelty identification, and 44.55% when evaluating all of the above aspects of the comprehensive relation extraction. The highest F-score performances achieved for the Subtask 2 were: 55.84% for relation pair, 43.03% for relation type, 42.74% for novelty, and 32.75% for comprehensive relation extraction. The entire BioRED track dataset and other challenge materials are available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/ and https://codalab.lisn.upsaclay.fr/competitions/13377 and https://codalab.lisn.upsaclay.fr/competitions/13378. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/https://codalab.lisn.upsaclay.fr/competitions/13377https://codalab.lisn.upsaclay.fr/competitions/13378.


Asunto(s)
Minería de Datos , Procesamiento de Lenguaje Natural , Humanos , Minería de Datos/métodos , Bases de Datos Factuales , Semántica
11.
Korean J Fam Med ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39160688

RESUMEN

Background: Insulin resistance contributes to the development of cardiovascular disease and type 2 diabetes mellitus. Smoking leads to an increase in triglyceride levels, which, in turn, increases insulin resistance. Although the number of e-cigarette users has increased in recent years, few studies have investigated the association between ecigarette use and insulin resistance. Therefore, this study aimed to determine the association between e-cigarette use and insulin resistance using the triglyceride-glucose (TyG) index in Korean adults. Methods: This study included 4,404 healthy adults aged ≥20 years who participated in the Korea National Health and Nutrition Examination Survey between 2019 and 2020. Participants were categorized as never-smokers or ecigarette users, and the TyG index was categorized into low- and high-TyG index groups according to the median value (9.22). A logistic regression analysis was performed to determine the association between e-cigarette smoking and insulin resistance. Results: E-cigarette users had a higher TyG index than never smokers (e-cigarette: mean=3.95; never: mean=9.18; P<0.001). The e-cigarette users had a higher risk of being in the high TyG index group than never-smokers (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.03-1.84). In the subgroup analysis stratified by sex, age, and body mass index, a higher OR for a high TyG index was observed in men (OR, 1.46; 95% CI, 1.03-2.08) and individuals aged 60 years or older (OR, 3.74; 95% CI, 1.14-12.30). Conclusion: Our findings suggest that e-cigarette use is significantly associated with insulin resistance.

12.
Int J Biol Macromol ; 275(Pt 2): 133730, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38986973

RESUMEN

The binding of functional groups to antibodies is crucial for disease treatment, diagnosis, and basic scientific research. Traditionally, antibody modifications have focused on the Fc region to maintain antigen-antibody binding activity. However, such modifications may impact critical antibody functions, including immune cell surface receptor activation, cytokine release, and other immune responses. In recent years, modifications targeting the antigen-binding fragment (Fab) region have garnered increasing attention. Precise modifications of the Fab region not only maximize the retention of antigen-antibody binding capacity but also enhance numerous physicochemical properties of antibodies. This paper reviews the chemical, biological, biochemical, and computer-assisted methods for modifying the Fab region of antibodies, discussing their advantages, limitations, recent advances, and future trends.


Asunto(s)
Fragmentos Fab de Inmunoglobulinas , Ingeniería de Proteínas , Fragmentos Fab de Inmunoglobulinas/química , Fragmentos Fab de Inmunoglobulinas/inmunología , Humanos , Ingeniería de Proteínas/métodos , Animales , Anticuerpos/química , Anticuerpos/inmunología
13.
Biomed Chromatogr ; 38(9): e5957, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38973567

RESUMEN

Microbial metabolites are an important source of tyrosinase (TYR) inhibitors because of their rich chemical diversity. However, because of the complex metabolic environment of microbial products, it is difficult to rapidly locate and identify natural TYR inhibitors. Affinity-based ligand screening is an important method for capturing active ingredients in complex samples, but ligand immobilization is an important factor affecting the screening process. In this paper, TYR was used as ligand, and the SpyTag/SpyCatcher coupling system was used to rapidly construct affinity chromatography vectors for screening TYR inhibitors and separating active components from complex samples. We successfully expressed SpyTag-TYR fusion protein and SpyCatcher protein, and incubated SpyCatcher protein with epoxy-activated agarose. The SpyTag-TYR protein was spontaneously coupled with SpyCatcher to obtain an affinity chromatography filler for immobilization of TYR, and the performance of the packaging material was characterized. Finally, compound 1 with enzyme inhibitory activity was successfully obtained from the fermentation product of marine microorganism C. Through HPLC, MS, 1H NMR and 13C NMR analyses, its structure was deduced as azelaic acid, and its activity was analyzed. The results showed that this is a feasible method for screening TYR inhibitors in complex systems.


Asunto(s)
Cromatografía de Afinidad , Inhibidores Enzimáticos , Monofenol Monooxigenasa , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Monofenol Monooxigenasa/química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Cromatografía de Afinidad/métodos , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Enzimas Inmovilizadas/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética
14.
Cells ; 13(13)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38994997

RESUMEN

Extracellular HSP90α (eHSP90α) is a promoter of tumor development and malignant progression. Patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC), have generally shown 5~10-fold increases in serum/plasma eHSP90α levels. In this study, we developed a humanized antibody HH01 to target eHSP90α and evaluated its anticancer efficacy. HH01, with novel complementarity-determining regions, exhibits high binding affinity toward HSP90α. It recognizes HSP90α epitope sites 235AEEKEDKEEE244 and 251ESEDKPEIED260, with critical amino acid residues E237, E239, D240, K241, E253, and K255. HH01 effectively suppressed eHSP90α-induced invasive and spheroid-forming activities of colorectal cancer and PDAC cell lines by blocking eHSP90α's ligation with the cell-surface receptor CD91. In mouse models, HH01 potently inhibited the tumor growth of PDAC cell grafts/xenografts promoted by endothelial-mesenchymal transition-derived cancer-associated fibroblasts while also reducing serum eHSP90α levels, reflecting its anticancer efficacy. HH01 also modulated tumor immunity by reducing M2 macrophages and reinvigorating immune T-cells. Additionally, HH01 showed low aggregation propensity, high water solubility, and a half-life time of >18 days in mouse blood. It was not cytotoxic to retinal pigmented epithelial cells and showed no obvious toxicity in mouse organs. Our data suggest that targeting eHSP90α with HH01 antibody can be a promising novel strategy for PDAC therapy.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Proteínas HSP90 de Choque Térmico , Neoplasias Pancreáticas , Humanos , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Animales , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Ratones , Línea Celular Tumoral , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Adenocarcinoma/patología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/metabolismo , Transición Endotelial-Mesenquimatosa
15.
Angew Chem Int Ed Engl ; : e202410394, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39072967

RESUMEN

Semihydrogenation is a crucial industrial process. Noble metals such as Pd have been extensively studied in semihydrogenation reactions, owing to their unique catalytic activity toward hydrogen activation. However, the overhydrogenation of alkenes to alkanes often happens due to the rather strong adsorption of alkenes on Pd active phases. Herein, we demonstrate that the incorporation of Pd active phases as single-atom sites in perovskite lattices such as SrTiO3 can greatly alternate the electronic structure and coordination environment of Pd active phases to facilitate the desorption of alkenes rather than further hydrogenation. Furthermore, the incorporated Pd sites can be well stabilized without sintering by a strong host-guest interaction with SrTiO3 during the activation of H species in hydrogenation reactions. As a result, the Pd incorporated SrTiO3 (Pd-SrTiO3) exhibits an excellent time-independent selectivity (> 99.9 %) and robust durability for the photocatalytic semihydrogenation of phenylacetylene to styrene. This strategy based on incorporation of active phases in perovskite lattices will have broad implications in the development of high-performance photocatalysts for selective hydrogenation reactions.

16.
Nutrients ; 16(13)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38999914

RESUMEN

Elevated uric acid levels are linked with obesity and diabetes. Existing research mainly examines the relationship between sugar-sweetened carbonated beverage (SSB) consumption and uric acid levels. This study explored the association between the quantity and frequency of SSB consumption and elevated uric acid levels in Korean adults. Data from 2881 participants aged 19-64 years (1066 men and 1815 women) in the 2016 Korea National Health and Nutrition Examination Survey were analyzed. Serum uric acid levels were categorized into quartiles, with the highest defined as high uric acid (men, ≥6.7 mg/dL; women, ≥4.8 mg/dL). SSB consumption was classified into quartiles (almost never, <1 cup (<200 mL), 1-3 cups (200-600 mL), ≥3 cups (≥600 mL)) and frequency into tertiles (almost never, ≤1/week, ≥2/week). Multivariate logistic regression assessed the association, with separate analyses for men and women. Increased daily SSB consumption and frequency were significantly associated with high uric acid levels in men but not in women. After adjusting for sociodemographic and health characteristics, consuming ≥3 cups (≥600 mL) of SSBs per day and SSBs ≥ 2/week were significantly associated with high serum uric acid levels in men, but this association was not observed in women. The study concludes that increased SSB intake is linked to elevated uric acid levels in Korean men, but not in women.


Asunto(s)
Bebidas Gaseosas , Encuestas Nutricionales , Bebidas Azucaradas , Ácido Úrico , Humanos , Ácido Úrico/sangre , Femenino , Masculino , República de Corea , Adulto , Persona de Mediana Edad , Bebidas Gaseosas/estadística & datos numéricos , Bebidas Azucaradas/estadística & datos numéricos , Bebidas Azucaradas/efectos adversos , Adulto Joven , Estudios Transversales
17.
JAMA Netw Open ; 7(7): e2419366, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949811

RESUMEN

Importance: The long-term estimated risk of development of cataracts among pediatric patients with uveitis is not clear. Objective: To describe factors associated with the development of cataracts among pediatric patients with uveitis. Design, Setting, and Participants: This cohort study used the international TriNetX database to enroll pediatric patients with and without uveitis from January 1, 2002, to December 31, 2022. The nonuveitis cohort consisted of randomly selected control patients matched by age, sex, race and ethnicity, and specific comorbidities. Exposure: Diagnosis of uveitis, identified using diagnostic codes. Main Outcomes and Measures: The primary outcome was the risk of developing cataracts among the uveitis group compared with the nonuveitis comparison group, with hazard ratios (HRs) and 95% CIs reported. Results: A total of 22 687 pediatric patients with uveitis (mean [SD] age, 10.3 [5.6] years; 54.2% male) and 22 687 comparators without uveitis (mean [SD] age, 10.3 [5.6] years; 54.5% male) were enrolled in the study. The risk of cataracts was increased among pediatric patients with uveitis up to a follow-up duration of 20 years (HR, 17.17; 95%CI, 12.90-22.80) from the index date. Subgroup analyses revealed an elevated cataract risk across age groups: 0 to 6 years (HR, 19.09; 95% CI, 10.10-36.00), 7 to 12 years (HR, 27.16; 95% CI, 15.59-47.20), and 13 to 18 years (HR, 13.39; 95% CI, 8.84-20.30); both female sex (HR, 13.76; 95% CI, 9.60-19.71) and male sex (HR, 11.97; 95% CI, 8.47-16.91); and Asian (HR, 13.80; 95% CI, 3.28-58.07), Black or African American (HR, 10.41; 95% CI, 5.60-19.36), and White (HR, 15.82; 95% CI, 11.05-22.60) race. Furthermore, increased cataract risks were also observed among those with and without a history of immunosuppressive agents (with: HR, 26.52 [95% CI, 16.75-41.90]; without: HR, 17.69 [95% CI: 11.39-27.40]), a history of steroid eye drop use (with: HR, 29.51 [95% CI, 14.56-59.70]; without: HR, 16.49 [95% CI, 11.92-22.70]), and a history of intraocular procedures (with: HR, 11.07 [95%CI, 4.42-27.71]; without: HR, 14.49 [95% CI, 10.11-20.70]). Conclusions and Relevance: In this cohort study of pediatric patients with uveitis, an elevated risk of cataracts following a uveitis diagnosis was found compared with pediatric patients without uveitis. The findings suggest that pediatric patients with uveitis should be monitored for cataract development.


Asunto(s)
Catarata , Uveítis , Humanos , Uveítis/epidemiología , Uveítis/etiología , Catarata/epidemiología , Catarata/complicaciones , Catarata/etiología , Masculino , Femenino , Niño , Adolescente , Preescolar , Factores de Riesgo , Estudios de Cohortes , Lactante , Modelos de Riesgos Proporcionales
18.
Korean J Fam Med ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38965838

RESUMEN

Background: Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker. Methods: A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016-2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely "0-2 breakfasts per week" and "3-7 breakfasts per week"; hs-CRP concentrations were measured through blood tests. Results: Comparing between the "infrequent breakfast consumption (0-2 breakfasts per week)" and "frequent breakfast consumption (3-7 breakfasts per week)" groups, the mean hs-CRP was found to be significantly higher in the "infrequent breakfast consumption" group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036). Conclusion: Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.

19.
Fish Shellfish Immunol ; 152: 109775, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39019126

RESUMEN

Bacterial intestinal inflammation frequently occurs in cultured fish. Nevertheless, research on intestinal barrier dysfunction in the process of intestinal inflammation is deficient. In this study, we explored the changes of intestinal inflammation induced by Aeromonas hydrophila (A. hydrophila) in snakehead and the relationship between intestinal barrier and inflammation. Snakehead [(13.05 ± 2.39) g] were infected via anus with A. hydrophila. Specimens were collected for analysis at 0, 1, 3, 7 and 21 d post-injection. The results showed that with the increase of exposure time, the hindgut underwent stages of normal function, damage, damage deterioration, repair and recovery. Relative to 0 d, the levels of IL-1ß and TNF-α in serum, and the expression of nod1, tlr1, tlr5, nf-κb, tnf-α and il-1ß in intestine were significantly increased, and showed an upward then downward pattern over time. However, the expression of tlr2 and il-10 were markedly decreased, and showed the opposite trend. In addition, with the development of intestinal inflammation, the diversity and richness of species, and the levels of phylum and genus in intestine were obviously altered. The levels of trypsin, LPS, AMS, T-SOD, CAT, GPx, AKP, LZM and C3 in intestine were markedly reduced, and displayed a trend of first decreasing and then rebounding. The ultrastructure observation showed that the microvilli and tight junction structure of intestinal epithelial cells experienced normal function initially, then damage, and finally recovery over time. The expression of claudin-3 and zo-1 in intestine were significantly decreased, and showed a trend of first decreasing and then rebounding. Conversely, the expression of mhc-i, igm, igt and pigr in intestine were markedly increased, and displayed a trend of increasing first and then decreasing. The above results revealed the changes in intestinal barrier during the occurrence and development of intestinal inflammation, which provided a theoretical basis for explaining the relationship between the two.


Asunto(s)
Aeromonas hydrophila , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Intestinos , Animales , Aeromonas hydrophila/fisiología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Peces/inmunología , Peces/microbiología , Microbioma Gastrointestinal , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Inflamación/inmunología , Inflamación/veterinaria , Mucosa Intestinal/inmunología , Intestinos/inmunología , Intestinos/patología
20.
BMC Ophthalmol ; 24(1): 314, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075430

RESUMEN

BACKGROUND: An impaired ocular surface presents substantial challenges in terms of planning for cataract surgery. As a multifactorial ocular disorder, dry eye disease (DED) is common in the general population and prevalent in patients scheduled for lens replacement surgery. Cataract surgery can exacerbate DED and worsen several ocular parameters. Timely diagnosis and appropriate treatment of DED are vital to ensuring positive ophthalmic surgical outcomes. This consensus report of the Taiwan Society of Cataract and Refractive Surgeons (TSCRS) regarding the management of DED before, during, and after cataract surgery highlights the gaps between clinical guidelines and several aspects of DED, including diagnostic testing, diagnostic criteria, and clinical practice treatment. METHODS: An expert panel of five specialists in the field of ophthalmology was recruited to develop consensus statements regarding the management of DED in both the general population and in patients undergoing cataract surgery in Taiwan. Two separate meetings of the five specialists, who were endorsed by the TSCRS, were convened for this purpose. A survey questionnaire consisting of binary or multiple-choice questions was developed through a consensus-driven formulation process. A percentage value was calculated for each statement, and a minimum of 60% agreement (equivalent to three out of five members) was required to achieve consensus. The second discussion meeting involved the presentation of the finalized consensus statements and concluded the consensus development process. Lastly, the finalized consensus statements were approved by all the experts, and the formulated recommendations for DED in the general population and prospective cataract surgery patients were accordingly presented. RESULTS: The optimal algorithm for managing DED in the general population and in patients scheduled for cataract surgery was developed to address the unmet needs of this cohort in Taiwan. CONCLUSION: This report provides recommendations for managing dry eye disease. It is essential to screen and confirm DED through endorsed questionnaires and tests and then diagnose it. Treatment and management of DED should follow a stepwise approach. Screening and diagnosing DED is also recommended before cataract surgery. After cataract surgery, relatively aggressive treatment strategies are recommended to manage DED effectively.


Asunto(s)
Extracción de Catarata , Consenso , Síndromes de Ojo Seco , Humanos , Taiwán/epidemiología , Síndromes de Ojo Seco/terapia , Síndromes de Ojo Seco/diagnóstico , Sociedades Médicas , Oftalmología/normas , Encuestas y Cuestionarios
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