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1.
Jpn J Radiol ; 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39436504

RESUMEN

PURPOSE: To explore the diagnostic characteristics of cystitis glandularis (CG) using magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective study was conducted on pathologically confirmed patients who underwent bladder MRI examination between January 2019 and November 2023. Image analysis was jointly conducted, with emphasis on lesion location, morphology, size, signal intensity, and pattern of enhancement, by two genitourinary radiologists with 22 and 15 years of experience, respectively. RESULTS: A total of 27 patients with 27 lesions were included (median age 47 years, 24 males). The lesions were mostly located in the bladder trigone area (18/27). The lesions could be categorized as focal thickening (17/27), nodular (8/27), and diffuse thickening of the entire bladder (2/27) in morphological terms. On T2-weighted imaging (T2WI), 15 of 17 focal thickening lesions appeared as a slightly hyperintense thickened inner layer, with a higher signal in the center of the thickened inner layer, resembling a sandwich sign, and 6 of 8 nodular lesions were slightly hyperintense. On T1-weighted imaging (T1WI), 19 patients showed slight hypointensity. The lesions on DWI showed mainly high (5/27) and slightly high signal (21/27), with an average mean apparent diffusion coefficient (mADC) value of 2.171 ± 0.052 × 10-3mm2/s. Among the 23 patients who underwent dynamic contrast-enhanced (DCE) scanning, 18 lesions showed mild enhancement in the arterial phase (average 1.7 times comparing to unenhanced phase), and the degree of enhancement gradually increased in the venous and delayed phases (average 2.2 and 2.3 times compared to the unenhanced phase, respectively), showing a progressive enhancement pattern. CONCLUSION: On MRI, the majority of CG manifest as focal thickening or nodules in the bladder trigone area, showing slight hyperintensity on T2WI, slight hypointensity on T1WI, and a progressive enhancement pattern, without significant restriction on DWI. Focal thickening lesions may exhibit a special sandwich sign.

2.
Br J Hosp Med (Lond) ; 85(10): 1-13, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39475029

RESUMEN

Aims/Background Lung cancer (LC) remains one of the most common malignant tumours worldwide, and assessment of its progression is important for ensuring better prognostic outcomes for patients. This study was designed to explore the prognostic role of certain indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) in patients with LC, to help clinics to better determine the prognosis of patients with LC, and to allow them to intervene in a timely manner. Methods A retrospective analysis of 116 initially diagnosed patients with LC in China from 2018 to 2020 was conducted. The counts of neutrophils (NEU), lymphocytes (LYM), and monocytes (MON), as well as albumin levels, were obtained from laboratory databases. The PNI was calculated using a specific formula. The progression-free survival (PFS) curves were plotted using the Kaplan-Meier method, and the Log-rank test was used to compare survival among different groups. The potential prognostic role of these indicators was assessed with univariate and multivariate regression analysis. Results Multivariate Cox regression demonstrated that the PNI (hazard ratio (HR): 0.513, 95% confidence interval (CI): 0.288-0.917, p = 0.024), NLR (HR: 2.038, 95% CI: 1.128-3.682, p = 0.018), and tumour type (small cell lung cancer vs. non-small cell lung cancer) (HR: 2.145, 95% CI: 1.308-3.520, p = 0.003) were significantly associated with PFS. The median PFS for patients with low and high PNI was 10 and 11.5 months, respectively. Conclusion The NLR, PLR, and PNI are all significantly associated with the prognostic survival of LC patients.


Asunto(s)
Neoplasias Pulmonares , Linfocitos , Neutrófilos , Evaluación Nutricional , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Anciano , Recuento de Linfocitos , Recuento de Plaquetas , Plaquetas , China/epidemiología , Adulto , Estimación de Kaplan-Meier , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Recuento de Leucocitos
3.
Eur J Med Chem ; 279: 116852, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39276584

RESUMEN

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) play a pivotal role in regulating kynurenine catabolism pathway and immunosuppressive environment, which are promising drug targets for cancer immunotherapy. In this work, a variety of isoquinoline derivatives were designed, synthesized and evaluated for the inhibitory activity against IDO1 and TDO. The enzymatic assay and structure-activity relationship studies led to the most potent compound 43b with IC50 values of 0.31 µM for IDO1 and 0.08 µM for TDO, respectively. Surface plasmon resonance (SPR) revealed direct binding affinity of compound 43b to IDO1 and TDO and molecular docking studies were performed to predict the possible binding mode. Further pharmacokinetic study and biological evaluation in vivo showed that 43b displayed acceptable pharmacokinetic profiles and potent antitumor efficacy with low toxicity in B16-F10 tumor model, which might provide some insights into the discovery of novel IDO1/TDO inhibitors for cancer immunotherapy.


Asunto(s)
Antineoplásicos , Inhibidores Enzimáticos , Indolamina-Pirrol 2,3,-Dioxigenasa , Isoquinolinas , Simulación del Acoplamiento Molecular , Triptófano Oxigenasa , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Relación Estructura-Actividad , Animales , Isoquinolinas/química , Isoquinolinas/farmacología , Isoquinolinas/síntesis química , Ratones , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Triptófano Oxigenasa/antagonistas & inhibidores , Triptófano Oxigenasa/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Humanos , Estructura Molecular , Descubrimiento de Drogas , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos C57BL
4.
Org Lett ; 26(36): 7638-7643, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39230392

RESUMEN

Herein, we disclose a visible-light-driven photoredox-catalyzed protocol for site-selective alkylation of glycine derivatives via 1,2-hydrogen atom transfer, which is distinguished by metal free and mild conditions, high chemoselectivity, and good functional group compatibility. This protocol provides a unique approach for synthesizing valuable α,ß-diamino acid derivatives. Furthermore, the potential synthetic merit of this transformation is proven by a scale-up reaction and late-stage functionalization of peptides.

5.
Bioorg Chem ; 153: 107791, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39244974

RESUMEN

Resveratrol (Res) has long been discovered to have antioxidant effects to prevent such as oxidation, inflammation, neurodegeneration and age-related diseases. However, its poor water solubility, low bioavailability and instability have become a barrier to its pharmaceutical application. In order to improve the neuroprotective effects and develop more potential usage of Res, three Res derivatives containing one or two glucose groups, i.e., Res-Glu1, Res-Glu2 and Res-Glu3, were designed and synthesized through click reaction. Res-Glu1, Res-Glu2 and Res-Glu3 were tested being better water solubility and stability compared to Res. Res derivatives reduced •OH radicals-induced DNA damage. PC12 assays indicated that glucosylated Res derivatives could alleviate H2O2-induced neurotoxicity and reduce intracellular ROS generation, demonstrating their neuroprotective effects. In addition, Res derivatives enhanced the protective effects on cerebral ischemia-reperfusion injury in rats. Res-Glu3 displayed the best neuroprotective effects among the three derivatives.

6.
Int J Ophthalmol ; 17(9): 1689-1695, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296562

RESUMEN

AIM: To report the clinical profile, endoscopic dacryocystorhinostomy (En-DCR) management, and acute dacryocystitis (AD) outcomes in China. METHODS: Clinical data of 554 adult AD patients (554 eyes) who presented in 7 tertiary eye care centers for 10y from Jan 2010 to Mar 2020 were retrospectively analyzed. Clinical profile, En-DCR management, and outcomes of all cases were recorded. The anatomical and functional success were evaluated for 12mo post-operation. RESULTS: The analysis included 149 males and 368 females with a median age of 55.2y (range: 18-84y). There were 459 eyes with a history of epiphora or purulent secretion. The time between a symptom of lacrimal duct obstruction and acute onset was 1 to 540 (66.1±58.2)mo. Fifty-nine eyes had a history of the previous acute attack. Seventy-four eyes developed a cutaneous fistula, while 11 eyes had post septal cellulitis pre-operation. En-DCR with an anatomical success of 91.7% and functional success of 90.1%. The success rate of the patients with a history of acute episodes and the preoperative fistula was lower than the overall success rates. CONCLUSION: En-DCR can be performed during an acute episode in AD with a success rate of over 90%.

7.
Sci Rep ; 14(1): 22068, 2024 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333332

RESUMEN

This study addresses the distribution and antimicrobial resistance of Acinetobacter baumannii (A. baumannii) in a medical facility in Haikou City, aiming to provide essential insights for enhancing in-hospital treatment and prevention strategies. We conducted a retrospective analysis of 513 A. baumannii isolates collected from a tertiary care hospital in Haikou between January 2018 and December 2020, focusing on their antimicrobial resistance patterns. Random Amplified Polymorphic DNA (RAPD) analysis was performed on 48 randomly selected A. baumannii strains. Using Gel-pro4.0 and NTSYSspc2.10 software, we constructed dendrograms to assess the genetic diversity of these strains. Our results indicate that males between 60 and 70 years old are particularly vulnerable to A. baumannii infections, which are most frequently detected in sputum samples, with a detection rate exceeding 70%. Alarmingly, over 50% of the isolates were identified as multi-drug resistant. The RAPD-PCR fingerprinting cluster analysis demonstrated substantial genetic diversity among the strains. Using primer OPA-02 at a 45% similarity coefficient, the strains were categorized into four groups (A-D), with group A being predominant (39 strains). high-prevalence areas like the Neurosurgery and Intensive Care Medicine Wards require enhanced surveillance and targeted interventions to manage Group C infections effectively. Additionally, the varied presence of other groups necessitates customized strategies to address the specific risks in each ward. Similarly, primer 270 at a 52% similarity coefficient classified the strains into five groups (E-I), with group E being most common (36 strains). The study highlights a concerning prevalence of antimicrobial resistance, particularly multi-drug resistance, among A. baumannii strains in the Haikou hospital. The significant genetic diversity, especially within groups A and E, underscores the need for tailored hospital treatment protocols and prevention measures. These findings contribute to the growing body of research on antimicrobial resistance, emphasizing the urgent need for effective management strategies in healthcare settings.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Variación Genética , Centros de Atención Terciaria , Acinetobacter baumannii/genética , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Humanos , Masculino , Anciano , Persona de Mediana Edad , Femenino , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/tratamiento farmacológico , Estudios Retrospectivos , Antibacterianos/farmacología , Adulto , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad Microbiana , Anciano de 80 o más Años , Técnica del ADN Polimorfo Amplificado Aleatorio , Adolescente , Adulto Joven , Niño , Preescolar , Lactante , Farmacorresistencia Bacteriana/genética
8.
EMBO J ; 43(20): 4492-4521, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39192032

RESUMEN

Glioma cells hijack developmental programs to control cell state. Here, we uncover a glioma cell state-specific metabolic liability that can be therapeutically targeted. To model cell conditions at brain tumor inception, we generated genetically engineered murine gliomas, with deletion of p53 alone (p53) or with constitutively active Notch signaling (N1IC), a pathway critical in controlling astrocyte differentiation during brain development. N1IC tumors harbored quiescent astrocyte-like transformed cell populations while p53 tumors were predominantly comprised of proliferating progenitor-like cell states. Further, N1IC transformed cells exhibited increased mitochondrial lipid peroxidation, high ROS production and depletion of reduced glutathione. This altered mitochondrial phenotype rendered the astrocyte-like, quiescent populations more sensitive to pharmacologic or genetic inhibition of the lipid hydroperoxidase GPX4 and induction of ferroptosis. Treatment of patient-derived early-passage cell lines and glioma slice cultures generated from surgical samples with a GPX4 inhibitor induced selective depletion of quiescent astrocyte-like glioma cell populations with similar metabolic profiles. Collectively, these findings reveal a specific therapeutic vulnerability to ferroptosis linked to mitochondrial redox imbalance in a subpopulation of quiescent astrocyte-like glioma cells resistant to standard forms of treatment.


Asunto(s)
Ferroptosis , Glioblastoma , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Animales , Ratones , Glioblastoma/metabolismo , Glioblastoma/patología , Glioblastoma/genética , Humanos , Mitocondrias/metabolismo , Astrocitos/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Peroxidación de Lípido , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
9.
Environ Pollut ; 361: 124783, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39173864

RESUMEN

Understanding the factors that drive PM2.5 concentrations in cities with varying population and land areas is crucial for promoting sustainable urban population health. This knowledge is particularly important for countries where air pollution is a significant challenge. Most existing studies have investigated either anthropogenic or environmental factors in isolation, often in limited geographic contexts; however, this study fills this knowledge gap. We employed a multimethodological approach, using both multiple linear regression models and geographically weighted regression (GWR), to assess the combined and individual effects of these factors across different cities in China. The variables considered were urban built-up area, land consumption rate (LCR), population size, population growth rate (PGR), longitude, and latitude. Compared with other studies, this study provides a more comprehensive understanding of PM2.5 drivers. The findings of this study showed that PGR and population size are key factors affecting PM2.5 concentrations in smaller cities. In addition, the extent of urban built-up areas exerts significant influence in medium and large cities. Latitude was found to be a positive predictor for PM2.5 concentrations across all city sizes. Interestingly, the northeast, south, and southwest regions demonstrated lower PM2.5 levels than the central, east, north, and northwest regions. The GWR model underscored the importance of considering spatial heterogeneity in policy interventions. However, this research is not without limitations. For instance, international pollution transfers were not considered. Despite the limitation, this study advances the existing literature by providing an understanding of how both anthropogenic and environmental factors, in conjunction with city scale, shape PM2.5 concentrations. This integrated approach offers invaluable insights for tailoring more effective air pollution management strategies across cities of different sizes and characteristics.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ciudades , Monitoreo del Ambiente , Material Particulado , China , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Humanos
10.
Org Lett ; 26(32): 6847-6852, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39110700

RESUMEN

We reported the visible-light-mediated photoredox-catalyzed oxidative radical-polar crossover and 1,5-hydrogen atom transfer combined site-selective remote C(sp3)-N cross-coupling alkylamination of alkenes. Various anilines and hydroxamides (1,5-hydrogen atom transfer reagents) could be tolerated. The mechanistic studies indicated the radical nature of the reaction and the indispensability of light and photocatalyst. Stern-Volmer fluorescence quenching and cyclic voltammetry experiments have been used to outline the proposed reaction pathway.

11.
Br J Hosp Med (Lond) ; 85(8): 1-41, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212571

RESUMEN

Osteoarthritis and rheumatoid arthritis, though etiologically distinct, are both inflammatory joint diseases that cause progressive joint injury, chronic pain, and loss of function. Therefore, long-term treatment with a focus on relieving symptoms is needed. At present, the primary treatment for arthritis is drug therapy, both oral and intravenous. Although significant progress has been achieved for these treatment methods in alleviating symptoms, certain prominent drawbacks such as the substantial side effects and limited absorption of medications call for an urgent need for improved drug delivery methods. Injected hydrogels can be used as a delivery system to deliver drugs to the joint cavity in a controlled manner and continuously release them, thereby enhancing drug retention in the joint cavity to improve therapeutic effectiveness, which is attributed to the desirable attributes of the delivery system such as low immunogenicity, good biodegradability and biocompatibility. This review summarizes the types of injectable hydrogels and analyzes their applications as delivery systems in arthritis treatment. We also explored how hydrogels counteract inflammation, bone and cartilage degradation, and oxidative stress, while promoting joint cartilage regeneration in the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA). This review also highlights new approaches to developing injectable hydrogels as delivery systems for OA and RA.


Asunto(s)
Artritis Reumatoide , Sistemas de Liberación de Medicamentos , Hidrogeles , Osteoartritis , Hidrogeles/administración & dosificación , Humanos , Artritis Reumatoide/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Inyecciones Intraarticulares , Antirreumáticos/administración & dosificación
12.
Fish Shellfish Immunol ; 153: 109830, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39142374

RESUMEN

Cuticle proteins (CPs) are the vital components of the cuticle and chitin lining covering the digestive tract of crustaceans. In this study, four new CP genes (designated as EsCP3, EsCP4, EsCP5, and EsCP8) were initially cloned and identified from the Chinese mitten crab Eriocheir sinensis. EsCP3/4/5/8 included 375, 411, 381, and 570 bp open reading frame encoding 124, 136, 126, and 189 amino acid proteins, respectively. Except for EsCP8, EsCP3/4/5 all contained a Chitin_bind_4 domain. EsCP3/4/5/8 were clustered into different groups in the phylogenetic tree. Quantitative real-time PCR results indicated that four EsCP genes have different patterns of tissue distribution. Changes in the expression levels of these four EsCP genes were observed in the intestine of crabs under Vibrio parahaemolyticus challenge. RNA interference assay showed that the knockdown of EsCPs in the intestine could inhibit the expression of antimicrobial peptides (AMPs), including crustins and anti-lipopolysaccharide factors. In addition, the knockdown of EsRelish in the intestine decreased the expression levels of these four EsCP genes. These results indicated that EsCPs were involved in regulating the expression of AMPs, and EsCPs were regulated by EsRelish.


Asunto(s)
Proteínas de Artrópodos , Braquiuros , Regulación de la Expresión Génica , Vibrio parahaemolyticus , Animales , Secuencia de Aminoácidos , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/inmunología , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Proteínas de Artrópodos/química , Secuencia de Bases , Braquiuros/genética , Braquiuros/inmunología , Braquiuros/microbiología , Clonación Molecular , ADN Complementario/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Filogenia , Alineación de Secuencia/veterinaria , Vibrio parahaemolyticus/fisiología
13.
J Org Chem ; 89(18): 13401-13411, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39215394

RESUMEN

Hydrogen-bonded aggregates of B(C6F5)3 and water are proven as strong Brønsted acid catalysts, which have the advantages of low toxicity and broad compatibility. Sulfoxonium ylides are stable surrogates of diazo compounds, which participate in various reactions due to their versatile reactivity. Based on these characteristics, a strategy for C-N bond or C-C bond construction of aromatic amines with sulfoxonium ylides under metal-free catalytic conditions was established. This method has advantages of mild conditions and excellent yield, which is suitable for the N-H or C-H functionalization of various aromatic amine compounds.

14.
Clin Rheumatol ; 43(9): 2807-2815, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39093523

RESUMEN

This study aims to test the hypothesis that disease duration may affect the response to generic tofacitinib (TOF) and investigate the influence of concomitant medications with TOF on elderly rheumatoid arthritis (RA). This study retrospectively collected 76 elderly patients (age > 60) treated with TOF from 2019 to 2023 and grouped them according to age of disease onset. Data were collected from baseline to the last follow-up visit within 24 months. The demographic characteristics and follow-up results were compared. TOF retention and the effect of concomitant drugs (methotrexate, MTX, prednisone) were analyzed using Kaplan-Meier plots and COX regression analysis. Canonical correlation analysis (CCA) was used to explore the correlation among demographic characteristics, medication regimen, and improved clinical outcomes. There was no significant difference in the proportion of patients achieving low disease activity (LDA) between different disease duration groups. Patients in the group of MTX had a shorter time of using TOF in follow-up (log-rank p = 0.041). Prednisone dosage at baseline had a predictive value for functionally disabled situation. We found significant associations between discontinuation of TOF in the last follow-up and getting LDA. A total result of CCA yielded a significant positive correlation with set 1 (demographic characteristics and medication regimen) and set 2 (improved clinical outcomes) (canonical coefficient = 0.887, p < 0.001). Disease duration may not affect response to generic TOF and medication regimen was the factor related to efficacy of generic TOF in elderly RA in the real world. Demographic characteristics and medication regimen were correlated positively with improved clinical outcomes. Key Points • There is scarce data from the western area of China regarding the use of tofacitinib in elderly rheumatoid arthritis patients, despite widespread use. • In this retrospective analysis of 76 elderly patients at a single center, we found disease duration may not affect response to generic TOF. • Concomitant MTX might contribute to better control of the disease activity. • Concomitant prednisone dosage at baseline was the independent risk factor for functionally disabled situation.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Metotrexato , Piperidinas , Pirimidinas , Humanos , Artritis Reumatoide/tratamiento farmacológico , Pirimidinas/uso terapéutico , Masculino , Femenino , Anciano , Piperidinas/uso terapéutico , Estudios Retrospectivos , Antirreumáticos/uso terapéutico , Metotrexato/uso terapéutico , Resultado del Tratamiento , Persona de Mediana Edad , Prednisona/uso terapéutico , Quimioterapia Combinada , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano de 80 o más Años
15.
J Org Chem ; 89(14): 10012-10020, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38952027

RESUMEN

A visible-light-induced radical-radical cross-coupling reaction between 1,3,4-oxadiazoles and hydroxamic acid derivatives has been realized under base- and metal-free conditions. The protocol was characterized by broad substrate scope, excellent functional group tolerance, and simple operation procedures. By using this protocol, a variety of biologically important 5-aryl-1,3,4-oxadiazole-2-methylamines were obtained in good yields with excellent chemoselectivity.

16.
Poult Sci ; 103(9): 103991, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38991387

RESUMEN

The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.


Asunto(s)
Pollos , Infecciones por Coronavirus , Virus de la Bronquitis Infecciosa , Enfermedades de las Aves de Corral , Virus de la Bronquitis Infecciosa/genética , Virus de la Bronquitis Infecciosa/patogenicidad , Virus de la Bronquitis Infecciosa/fisiología , Animales , Glicosilación , Enfermedades de las Aves de Corral/virología , Virulencia , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Replicación Viral , Sustitución de Aminoácidos
17.
Front Endocrinol (Lausanne) ; 15: 1429338, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39072274

RESUMEN

Background: In the progestin-primed ovarian stimulation protocol, the oral administration of medroxyprogesterone acetate has been observed to effectively inhibit the LH surge during ovarian stimulation in patients experiencing infertility. Nevertheless, the use of utilizing medroxyprogesterone acetate during ovarian stimulation can result in more pronounced pituitary suppression, potentially necessitating increased doses of gonadotropins and extended treatment durations. Therefore, it is necessary to determine the optimal dose of medroxyprogesterone acetate, aiming to use relatively lower concentrations of medroxyprogesterone acetate to effectively and safely suppress early LH surges. Method: This retrospective cohort study included 710 patients who underwent cycles of in vitro fertilization or intracytoplasmic sperm injection and were subjected the progestin-primed ovarian stimulation protocol utilizing letrozole between from 1st January 2021 to 31st December 2021. The study population was divided into low, medium, and high concentration groups based on the daily dosage of medroxyprogesterone acetate.The primary focus of this investigation was on the cumulative live birth rate. Secondary outcomes encompassed the occurrence of a premature surge in luteinizing hormone, the quantity of retrieved oocytes, viable embryos, and high-quality embryos, as well as clinical pregnancy rate, abortion rate, ectopic pregnancy rate, and multiple pregnancy rate. Results: In this study, significant differences were observed among three groups in various parameters including body mass index, baseline levels of Anti-Müllerian hormone and luteinizing hormone, antral follicle count, total dose of gonadotropin, and duration of gonadotropin administration (p<0.05). The number of oocytes and viable embryos were significantly higher in medium group and higher than those in the low dose group. Following adjustments for confounding factors related to medroxyprogesterone acetate for various outcome measures, we conducted multiple regression analysis to investigate the independent effects of daily medroxyprogesterone acetate dosage within the combined progestin-primed ovarian stimulation and letrozole protocol. Following multivariable regression analysis, no disparities were found in embryo characteristics (number of oocytes retrieved, number of available embryos, number of high-quality embryos) or pregnancy outcomes (clinical pregnancy rate, cumulative live birth rate) among the three groups. Conclusion: Progestin-primed ovarian stimulation with letrozole using different dose of medroxyprogesterone acetate per day was comparable in terms of the number of oocytes retrieved, the number of high-quality embryos, clinical pregnancy rate and cumulative live birth rate after frozen embryo transfer.


Asunto(s)
Letrozol , Acetato de Medroxiprogesterona , Inducción de la Ovulación , Índice de Embarazo , Progestinas , Humanos , Femenino , Inducción de la Ovulación/métodos , Estudios Retrospectivos , Acetato de Medroxiprogesterona/administración & dosificación , Letrozol/administración & dosificación , Adulto , Embarazo , Progestinas/administración & dosificación , Fertilización In Vitro/métodos , Estudios de Cohortes , Relación Dosis-Respuesta a Droga
18.
J Dig Dis ; 25(5): 285-297, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38946678

RESUMEN

OBJECTIVES: Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD. METHODS: We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship. RESULTS: A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively. CONCLUSION: Higher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels.


Asunto(s)
Ferritinas , Resistencia a la Insulina , Hierro , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Femenino , Ferritinas/sangre , Hierro/sangre , Hierro/metabolismo , Persona de Mediana Edad , Adulto , Encuestas Nutricionales , Análisis de Mediación , Estudios Transversales , Receptores de Transferrina/sangre , Biomarcadores/sangre
19.
Sci Total Environ ; 928: 172473, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38615773

RESUMEN

Nanotechnology has emerged as a transformative force in modern agriculture, offering innovative solutions to address challenges related to fungal plant diseases and overall agricultural productivity. Specifically, the antifungal activities of metal, metal oxide, bio-nanoparticles, and polymer nanoparticles were examined, highlighting their unique mechanisms of action against fungal pathogens. Nanoparticles can be used as carriers for fungicides, offering advantages in controlled release, targeted delivery, and reduced environmental toxicity. Nano-pesticides and nano-fertilizers can enhance nutrient uptake, plant health, and disease resistance were explored. The development of nanosensors, especially those utilizing quantum dots and plasmonic nanoparticles, promises early and accurate detection of fungal pathogens, a crucial step in timely disease management. However, concerns about their potential toxic effects on non-target organisms, environmental impacts, and regulatory hurdles underscore the importance of rigorous research and impact assessments. The review concludes by emphasizing the significant prospects of nanotechnology in reshaping the future of agriculture but advocates for a balanced approach that prioritizes safety, sustainability, and environmental stewardship.


Asunto(s)
Agricultura , Nanotecnología , Enfermedades de las Plantas , Agricultura/métodos , Nanotecnología/métodos , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Monitoreo del Ambiente/métodos , Hongos , Nanopartículas
20.
J Int Med Res ; 52(4): 3000605241234555, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38587813

RESUMEN

Among the various manifestations of COVID-19, the neurological implications of SARS-CoV-2 infection are of significant concern. Marchiafava-Bignami disease (MBD), a neurodegenerative disorder, exhibits a clinical spectrum ranging from mild progressive dementia in its chronic form to states of acute coma and varied mortality rates. Acute MBD primarily occurs in chronic alcoholics and malnourished individuals and is characterized by sudden loss of consciousness, seizures, confusion, and psychosis. We herein report a case of MBD presenting as acute loss of consciousness after the development of COVID-19. The patient presented with a history of fever and upper respiratory infection and was diagnosed with SARS-CoV-2 infection. He developed a neurological syndrome characterized by altered consciousness and convulsions, and brain magnetic resonance imaging revealed abnormal signals in the corpus callosum and frontoparietal lobes. Considering his alcohol intake history and the absence of other differential diagnoses, we diagnosed him with acute MBD triggered by COVID-19. After high-dose vitamin B1 and corticosteroid therapy, his clinical symptoms improved. In this case, we observed a temporal sequence between the development of COVID-19 and acute exacerbation of MBD. This case adds to the mounting evidence suggesting the potential effect of SARS-CoV-2 on the neurological system.


Asunto(s)
COVID-19 , Demencia , Enfermedad de Marchiafava-Bignami , Humanos , Masculino , Estado de Conciencia , Enfermedad de Marchiafava-Bignami/diagnóstico , Enfermedad de Marchiafava-Bignami/diagnóstico por imagen , COVID-19/complicaciones , SARS-CoV-2 , Coma
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