RESUMEN

Phthalate esters (PAEs), recognized as endocrine disruptors, are released into the environment during usage, thereby exerting adverse ecological effects. This study investigates the occurrence, sources, and risk assessment of PAEs in surface water obtained from 36 sampling points within the Yellow River and Yangtze River basins. The total concentration of PAEs in the Yellow River spans from 124.5 to 836.5 ng/L, with Dimethyl phthalate (DMP) (75.4 ± 102.7 ng/L) and Diisobutyl phthalate (DiBP) (263.4 ± 103.1 ng/L) emerging as the predominant types. Concentrations exhibit a pattern of upstream (512.9 ± 202.1 ng/L) > midstream (344.5 ± 135.3 ng/L) > downstream (177.8 ± 46.7 ng/L). In the Yangtze River, the total concentration ranges from 81.9 to 441.6 ng/L, with DMP (46.1 ± 23.4 ng/L), Diethyl phthalate (DEP) (93.3 ± 45.2 ng/L), and DiBP (174.2 ± 67.6 ng/L) as the primary components. Concentration levels follow a midstream (324.8 ± 107.3 ng/L) > upstream (200.8 ± 51.8 ng/L) > downstream (165.8 ± 71.6 ng/L) pattern. Attention should be directed towards the moderate ecological risks of DiBP in the upstream of HH, and both the upstream and midstream of CJ need consideration for the moderate ecological risks associated with Di-n-octyl phthalate (DNOP). Conversely, in other regions, the associated risk with PAEs is either low or negligible. The main source of PAEs in Yellow River is attributed to the release of construction land, while in the Yangtze River Basin, it stems from the accumulation of pollutants in lakes and forests discharged into the river. These findings are instrumental for pinpointing sources of PAEs pollution and formulating control strategies in the Yellow and Yangtze Rivers, providing valuable insights for global PAEs research in other major rivers.

Asunto(s)

Monitoreo del Ambiente , Ésteres , Ácidos Ftálicos , Ríos , Contaminantes Químicos del Agua , Ácidos Ftálicos/análisis , Ríos/química , China , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , Ésteres/análisis , Disruptores Endocrinos/análisis , Dibutil Ftalato/análisis , Dibutil Ftalato/análogos & derivados

RESUMEN

Implant-associated infection (IAI) has become an intractable challenge in clinic. The healing of IAI is a complex physiological process involving a series of spatiotemporal connected events. However, existing titanium-based implants in clinic suffer from poor antibacterial effect and single function. Herein, a versatile surface platform based on the presentation of sequential function is developed. Fabrication of titania nanotubes and poly-γ-glutamic acid (γ-PGA) achieves the efficient incorporation of silver ions (Ag+) and the pH-sensitive release in response to acidic bone infection microenvironment. The optimized PGA/Ag platform exhibits satisfactory biocompatibility and converts macrophages from pro-inflammatory M1 to pro-healing M2 phenotype during the subsequent healing stage, which creates a beneficial osteoimmune microenvironment and promotes angio/osteogenesis. Furthermore, the PGA/Ag platform mediates osteoblast/osteoclast coupling through inhibiting CCL3/CCR1 signaling. These biological effects synergistically improve osseointegration under bacterial infection in vivo, matching the healing process of IAI. Overall, the novel integrated PGA/Ag surface platform proposed in this study fulfills function cascades under pathological state and shows great potential in IAI therapy.

Asunto(s)

Antibacterianos , Ácido Poliglutámico , Plata , Titanio , Animales , Titanio/química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ratones , Ácido Poliglutámico/química , Ácido Poliglutámico/análogos & derivados , Plata/química , Plata/farmacología , Propiedades de Superficie , Nanotubos/química , Células RAW 264.7 , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Oseointegración/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Cicatrización de Heridas/efectos de los fármacos , Prótesis e Implantes

RESUMEN

Drug resistance is a significant challenge in cancer chemotherapy and is a primary factor contributing to poor recovery for cancer patients. Although drug-loaded nanoparticles have shown promise in overcoming chemotherapy resistance, they often carry a combination of drugs and require advanced design and manufacturing processes. Furthermore, they seldom approach chemotherapy-resistant tumors from an immunotherapy perspective. In this study, we developed a therapeutic nanovaccine composed solely of chemotherapy-induced resistant tumor antigens (CIRTAs) and the immune adjuvant Toll-like receptor (TLR) 7/8 agonist R848 (CIRTAs@R848). This nanovaccine does not require additional carriers and has a simple production process. It efficiently delivers antigens and immune stimulants to dendritic cells (DCs) simultaneously, promoting DCs maturation. CIRTAs@R848 demonstrated significant tumor suppression, particularly when used in combination with the immune checkpoint blockade (ICB) anti-PD-1 (αPD-1). The combined therapy increased the infiltration of T cells into the tumor while decreasing the proportion of regulatory T cells (Tregs) and modulating the tumor microenvironment, resulting in long-term immune memory. Overall, this study introduces an innovative strategy for treating chemotherapy-resistant tumors from a novel perspective, with potential applications in personalized immunotherapy and precision medicine.

Asunto(s)

Vacunas contra el Cáncer , Desoxicitidina , Resistencia a Antineoplásicos , Gemcitabina , Inmunoterapia , Nanopartículas , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/farmacología , Animales , Inmunoterapia/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Nanopartículas/química , Ratones , Humanos , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Línea Celular Tumoral , Ratones Endogámicos C57BL , Femenino , Imidazoles/farmacología , Imidazoles/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Antígenos de Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Nanovacunas

RESUMEN

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Asunto(s)

Diabetes Mellitus Tipo 2 , Humanos , Persona de Mediana Edad , Masculino , Femenino , Estudios de Casos y Controles , Insecticidas , Glucemia/análisis , Malatión/análogos & derivados , Compuestos Organotiofosforados , China , Adulto , Inflamación

RESUMEN

Foodborne pathogens are responsible for foodborne diseases and food poisoning and thus pose a great threat to food safety. These microorganisms can adhere to surface and form a biofilm composed of an extracellular matrix. This matrix protects bacterial cells from industrial environmental stress factors such as cleaning and disinfection operations. Moreover, during these environmental stresses, many bacterial species can be entered in a viable but nonculturable (VBNC) state. VBNC cells are characterized by an active metabolism and a loss of cultivability on conventional bacteriological agar. This leads to an underestimation of total viable cells in environmental samples and thus may pose a risk for public health. In this chapter, we present a method to detect viable population of foodborne pathogens in industrial environmental samples using a molecular method combining propidium monoazide (PMA) and quantitative PCR (qPCR) and a fluorescence microscopic method associated with the LIVE/DEAD BacLight™ viability stain.

Asunto(s)

Azidas , Microbiología de Alimentos , Viabilidad Microbiana , Propidio , Reacción en Cadena en Tiempo Real de la Polimerasa , Microbiología de Alimentos/métodos , Azidas/química , Propidio/análogos & derivados , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Bacterias/genética , Bacterias/aislamiento & purificación , Enfermedades Transmitidas por los Alimentos/microbiología , Microscopía Fluorescente/métodos , Humanos

RESUMEN

Tyramine signaling amplification (TSA) technology is generally applied in immunofluorescence, enzyme-linked immunoassays, in situ hybridization techniques, etc. Successful amplification of fluoresence signals cannot be achieved without excellent fluorescent dyes. BODIPY fluorophore is an ideal probe for cell fluorescence imaging, but pristine BODIPY cannot be direct used in the TSA system. In the paper, the new red-shifted tyramide-conjugated BODIPY (BDP-B/C/D) was synthesized via the Knoevenagel condensation reaction, which based on the tyramide-conjugated BODIPY (BDP-A). The synthesized dyes were combined with tyramine to obtain which could be used as a fluorescent substrate for enzymatic reaction of TSA. By using the selected substrate (BDP-C) in TSA, we found it to be more sensitive than the commercial dye 594 styramide for the detection of low-abundance antigen proteins.

Asunto(s)

Compuestos de Boro , Colorantes Fluorescentes , Porfobilinógeno , Tiramina , Tiramina/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Compuestos de Boro/química , Compuestos de Boro/síntesis química , Porfobilinógeno/análogos & derivados , Porfobilinógeno/química , Células HeLa , Espectrometría de Fluorescencia , Imagen Óptica

RESUMEN

This study presents the contents of α-methylenecyclopropylglycine, a potentially toxic amino acid, in the peel, pulp and seed fractions of two well-known litchi varieties, namely Shahi and China, over a span of three harvest-seasons. For analysing α-methylenecyclopropylglycine, an LC-MS/MS-based method was validated. The method-accuracies fell within 75-110 % (RSD, <15 %) at 0.1 mg/kg (LOQ) and higher levels. A comparative evaluation of the results in peel, pulp and seed at 30 days before harvest (DBH), 15-DBH, and edible-ripe stage revealed that α-methylenecyclopropylglycine content increased as the litchi seeds grew towards maturity, regardless of the cultivar. In arils, at maturity, the concentration of α-methylenecyclopropylglycine ranged from not-detected to 11.7 µg/g dry weight. The Shahi cultivar showed slightly higher α-methylenecyclopropylglycine content in comparison to China litchi. This paper presents the first known analysis of combined seasonal data on different fruit components at various growth stages for the two chosen litchi cultivars grown in India.

Asunto(s)

Frutas , Litchi , Semillas , Espectrometría de Masas en Tándem , Litchi/química , Litchi/crecimiento & desarrollo , Litchi/metabolismo , Frutas/química , Frutas/crecimiento & desarrollo , China , Semillas/química , Semillas/crecimiento & desarrollo , Glicina/análogos & derivados , Glicina/análisis , Cromatografía Líquida de Alta Presión , Ciclopropanos/análisis

RESUMEN

Quantitative monitoring of the concentrations of epigallocatechin gallate (EGCG) and cysteine (Cys) is of great significance for promoting human health. In this study, iron/aluminum bimetallic MOF material MIL-53 (Fe, Al) was rapidly prepared under room temperature using a co-precipitation method, followed by investigating the peroxidase-like (POD-like) activity of MIL-53(Fe, Al) using 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate. The results showed that the Michaelis -Menten constants of TMB and H2O2 as substrates were 0.167 mM and 0.108 mM, respectively. A colorimetric sensing platform for detecting EGCG and Cys was developed and successfully applied for analysis and quantitative detection using a smartphone. The linear detection range for EGCG was 15∼80 µM (R2=0.994) and for Cys was 7∼95 µM (R2=0.998). The limits of detection (LOD) were 0.719 µM and 0.363 µM for EGCG and Cys, respectively. This work provides a new and cost-effective approach for the real-time analysis of catechins and amino acids.

Asunto(s)

Antioxidantes , Técnicas Biosensibles , Catequina , Colorimetría , Teléfono Inteligente , Colorimetría/métodos , Colorimetría/instrumentación , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Antioxidantes/análisis , Antioxidantes/química , Catequina/análisis , Catequina/análogos & derivados , Catequina/química , Cisteína/análisis , Cisteína/análogos & derivados , Límite de Detección , Análisis de los Alimentos/métodos , Análisis de los Alimentos/instrumentación

RESUMEN

BACKGROUND: Paclitaxel is a promising anticancer drug for patients with ovarian, breast, lung, gastrointestinal, genitourinary, prostate, and head-and-neck cancers. Paclitaxel follows nonlinear pharmacokinetics. The major metabolite of paclitaxel is 6-alpha-hydroxy paclitaxel, mediated by CYP2C8, while metabolism to two of its minor metabolites, 3'-p-hydroxypaclitaxel and 6a, 3'- p-dihydroxypaclitaxel, is catalyzed by CYP3A4. Therapeutic drug monitoring of paclitaxel could be a promising approach to improve the efficacy and safety of paclitaxel correct personalized doses and improve the overall benefit-risk ratio. A novel and highly sensitive chromatographic method for the detection of paclitaxel and its metabolite has been proposed that allows quantification in human plasma with 100% accuracy in terms of recovery without significant intraday or interday variations. MATERIALS AND METHODS: The present study was planned following bioanalytical method validation guidance according to the U.S. Food and Drug Administration requirements. The validation of the analytical procedure was performed as per ICH Q2(R1) guidelines. It was done to assure the reliability of the results obtained for various parameters such as linearity, accuracy, precision, limit of detection (LOD), limit of quantification, robustness, stability, and system suitability. RESULTS: The specificity of the method was established by ensuring no interference with peak obtained from paclitaxel and 6-alpha-hydroxy paclitaxel. LOD was found to be 0.05 and 0.033 while the limit of quantitation was 0.14 and 0.099 for paclitaxel and 6-alpha-hydroxy paclitaxel, respectively. Median (±interquartile range) accuracy for paclitaxel and 6-alpha-hydroxy paclitaxel was found to be 102.73 (±13.581) and 100.87 (±7.573), respectively. CONCLUSION: This novel method of simultaneous detection of paclitaxel and its major metabolite 6-alpha-hydroxy paclitaxel demonstrated significant resolution and was sensitive enough for its quantification in human plasma.

Asunto(s)

Antineoplásicos Fitogénicos , Límite de Detección , Paclitaxel , Paclitaxel/sangre , Paclitaxel/farmacocinética , Paclitaxel/análogos & derivados , Humanos , Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los Resultados , Antineoplásicos Fitogénicos/sangre , Antineoplásicos Fitogénicos/farmacocinética , Monitoreo de Drogas/métodos

Asunto(s)

Fármacos Anti-VIH , Farmacorresistencia Viral , Emtricitabina , Infecciones por VIH , VIH-1 , Compuestos Heterocíclicos con 3 Anillos , Oxazinas , Piperazinas , Piridonas , Tenofovir , Humanos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/genética , Emtricitabina/uso terapéutico , Piridonas/uso terapéutico , Piperazinas/uso terapéutico , Tenofovir/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Oxazinas/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Hepatitis B/tratamiento farmacológico , Adenina/análogos & derivados , Adenina/uso terapéutico , Masculino , Femenino , Amidas

RESUMEN

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-ß-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity.

Asunto(s)

Acinetobacter baumannii , Antibacterianos , Glicina , Glifosato , Bacterias Gramnegativas , Herbicidas , Pruebas de Sensibilidad Microbiana , Glicina/análogos & derivados , Glicina/farmacología , Antibacterianos/farmacología , Herbicidas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Acinetobacter baumannii/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Humanos , Escherichia coli/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Ciprofloxacina/farmacología , Enterococcus faecium/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Colistina/farmacología , Vancomicina/farmacología , Enterobacter/efectos de los fármacos , Sinergismo Farmacológico , Meropenem/farmacología , Fenotipo , Gentamicinas/farmacología

RESUMEN

Primary Hyperparathyroidism (PHPT) is characterized by excessive parathormone (PTH) secretion and disrupted calcium homeostasis. Untargeted metabolomics offers a valuable approach to understanding the complex metabolic alterations associated with different diseases, including PHPT. Plasma untargeted metabolomics was applied to investigate the metabolic profiles of PHPT patients compared to a control group. Two complementary liquid-phase separation techniques were employed to comprehensively explore the metabolic landscape in this retrospective, single-center study. The study comprised 28 female patients diagnosed following the current guidelines of PHPT diagnosis and a group of 30 healthy females as a control group. To evaluate their association with PHPT, we identified changes in plasma metabolic profiles in patients with PHPT compared to the control group. The primary outcome measure included detecting plasma metabolites and discriminating PHPT patients from controls. The study unveiled specific metabolic imbalances that may link L-amino acids with peptic ulcer disease, gamma-glutamyls with oxidative stress, and asymmetric dimethylarginine (ADMA) with cardiovascular complications. Several metabolites, such as gamma-glutamyls, caffeine, sex hormones, carnitine, sphingosine-1-phosphate (S-1-P), and steroids, were connected with reduced bone mineral density (BMD). Metabolic profiling identified distinct metabolic patterns between patients with PHPT and healthy controls. These findings provided valuable insights into the pathophysiology of PHPT.

Asunto(s)

Hiperparatiroidismo Primario , Metabolómica , Humanos , Femenino , Hiperparatiroidismo Primario/sangre , Hiperparatiroidismo Primario/metabolismo , Metabolómica/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Metaboloma , Arginina/sangre , Arginina/metabolismo , Arginina/análogos & derivados , Densidad Ósea , Hormona Paratiroidea/sangre , Hormona Paratiroidea/metabolismo , Estudios de Casos y Controles , Adulto , Aminoácidos/sangre , Aminoácidos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/sangre , Esfingosina/metabolismo , Lisofosfolípidos/sangre , Lisofosfolípidos/metabolismo , Biomarcadores/sangre

RESUMEN

BACKGROUND: Sepsis-induced pulmonary injury (SPI) is a common complication of sepsis with a high rate of mortality. N4-acetylcytidine (ac4C) is mediated by the ac4C "writer", N-acetyltransferase (NAT)10, to regulate the stabilization of mRNA. This study aimed to investigate the role of NAT10 in SPI and the underlying mechanism. METHODS: Twenty-three acute respiratory distress syndrome (ARDS) patients and 27 non-ARDS volunteers were recruited. A sepsis rat model was established. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of NAT10 and transferrin receptor (TFRC). Cell viability was detected by cell counting kit-8. The levels of Fe2+, glutathione, and malondialdehyde were assessed by commercial kits. Lipid reactive oxygen species production was measured by flow cytometric analysis. Western blot was used to detect ferroptosis-related protein levels. Haematoxylin & eosin staining was performed to observe the pulmonary pathological symptoms. RESULTS: The results showed that NAT10 was increased in ARDS patients and lipopolysaccharide-treated human lung microvascular endothelial cell line-5a (HULEC-5a) cells. NAT10 inhibition increased cell viability and decreased ferroptosis in HULEC-5a cells. TFRC was a downstream regulatory target of NAT10-mediated ac4C acetylation. Overexpression of TFRC decreased cell viability and promoted ferroptosis. In in vivo study, NAT10 inhibition alleviated SPI. CONCLUSION: NAT10-mediated ac4C acetylation of TFRC aggravated SPI through promoting ferroptosis.

Asunto(s)

Ferroptosis , Receptores de Transferrina , Sepsis , Sepsis/metabolismo , Sepsis/complicaciones , Sepsis/etiología , Acetilación , Animales , Humanos , Ratas , Masculino , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Femenino , Lesión Pulmonar/metabolismo , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Modelos Animales de Enfermedad , Acetiltransferasas/metabolismo , Acetiltransferasas/genética , Persona de Mediana Edad , Antígenos CD/metabolismo , Antígenos CD/genética , Citidina/análogos & derivados , Citidina/farmacología , Línea Celular , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/patología , Ratas Sprague-Dawley , Supervivencia Celular

RESUMEN

OBJECTIVE: To improve health conditions among hypogonadal men ≥70 years of age using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium, and protein. METHODS: This study is a 1-year follow-up of a double-blind RCT lasting 20 weeks, including 148 older men ≥70 years old with low testosterone levels and mobility problems. During 52 weeks, 4 groups received either testosterone therapy (TU) or progressive resistance training (Training), both (Combo), or no intervention (Controls). Physiotherapists supported the training groups until week 20, while these participants continued trained on their own during weeks 21 to 52. The main outcome measure was the 30-s chair stand test. RESULTS: The following numbers of participants completed the trial: 20 (Combo), 20 (Controls), 24 (TU), and 14 (Training). When examining 30-s chair stand test performance within each group at baseline, and at weeks 4, 20 and 52, only the Combo group improved (p = 0.001, Friedman Test). Compared to controls, only the Combo group experienced reduced fatigue and tiredness (p < 0.05). CONCLUSIONS: Fifty-two weeks of testosterone supplementation combined with progressive resistance training may enhance physical performance, alleviate fatigue, and had no notable detrimental impacts among males aged ≥70 suffering from mobility issues and testosterone insufficiency.Trial registration - Clinical Trials NCT02873559.

Asunto(s)

Fatiga , Anciano Frágil , Rendimiento Físico Funcional , Entrenamiento de Fuerza , Testosterona , Humanos , Masculino , Testosterona/uso terapéutico , Testosterona/análogos & derivados , Anciano , Entrenamiento de Fuerza/métodos , Método Doble Ciego , Fatiga/tratamiento farmacológico , Estudios de Seguimiento , Suplementos Dietéticos , Anciano de 80 o más Años , Hipogonadismo/tratamiento farmacológico , Vitamina D/análogos & derivados , Vitamina D/uso terapéutico , Andrógenos/uso terapéutico , Andrógenos/administración & dosificación

RESUMEN

Thyroid hormone (TH) is essential for growth and development, yet its specific role during embryogenesis remains incompletely understood. This study investigates the impact of TH deficiency, induced by thiourea, a known inhibitor of thyroid peroxidase (TPO), on the development of domestic chicks. Thiourea was administered before thyroid gland formation, and its presence in treated embryos was confirmed through liquid chromatography-mass spectrometry. In silico docking revealed a strong interaction between thiourea and the CCP-like domain of TPO, which was corroborated by TPO activity assays showing reduced enzyme function. This reduction in enzyme activity led to lower embryonic TH levels and increased thyroid-stimulating hormone (TSH) secretion. Morphological analysis of newly hatched chicks revealed significant structural anomalies, particularly in lateral plate mesoderm-derived structures, including omphalocele, limb deformities, anophthalmia and craniofacial defects. Alcian blue and Alizarin red staining demonstrated reduced ossification in ribs and forelimbs, while histological analysis showed incomplete abdominal wall closure and abnormal vertebral column development. Haematological profiling of TH-deficient newly hatched chicks revealed significantly lower blood cell counts, highlighting TH's critical role in haematopoiesis. These findings emphasise the multifaceted role of TH in embryonic development, with potential implications for understanding congenital hypothyroidism and its developmental impacts, especially in regions with limited healthcare access.

Asunto(s)

Pollos , Yoduro Peroxidasa , Hormonas Tiroideas , Animales , Embrión de Pollo , Yoduro Peroxidasa/metabolismo , Tiourea/análogos & derivados , Tiourea/farmacología , Tirotropina/sangre , Desarrollo Embrionario/fisiología , Simulación del Acoplamiento Molecular , Hipotiroidismo Congénito/veterinaria , Hipotiroidismo Congénito/patología , Hipotiroidismo Congénito/embriología

RESUMEN

Epigallocatechin gallate (EGCG) is a polyphenol plant metabolite abundant in tea that has demonstrated antifibrotic properties in the lung. In this issue of the JCI, Cohen, Brumwell, and colleagues interrogated the mechanistic action of EGCG by investigating lung biopsies of patients with mild interstitial lung disease (ILD) who had undergone EGCG treatment. EGCG targeted the WNT inhibitor SFRP2, which was enriched in fibrotic fibroblasts and acted as a TGF-ß target, with paracrine effects leading to pathologic basal metaplasia of alveolar epithelial type 2 cells. This study emphasizes the epithelial-mesenchymal trophic unit as a central signaling hub in lung fibrosis. Understanding and simultaneous targeting of interlinked signaling pathways, such as TGF-ß and WNT, paves the road for future treatment options for pulmonary fibrosis.

Asunto(s)

Catequina , Fibroblastos , Catequina/análogos & derivados , Catequina/farmacología , Humanos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroblastos/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Células Epiteliales/efectos de los fármacos , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/patología , Factor de Crecimiento Transformador beta/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética

RESUMEN

The worldwide spread of coronavirus disease 2019 (COVID-19) has resulted in an unparalleled health emergency of global proportions. Around 31% of individuals with COVID-19 experience thrombosis associated with hypercoagulation. COVID-19 patients have shown an increase in platelet activation, but the mechanism has not been fully understood yet. One theory suggests that this could be related to the heparin-induced thrombocytopenia phenomenon, where platelet activation involves anti-PF4 antibodies that are associated with thrombosis. Vitamin D has been established to exert an influence on immunological responses and inflammation. The aim of this study is to analyze the correlation between serum 25-hydroxy-cholecalciferol [25(OH)D] levels and anti-PF4 antibodies among COVID-19 patients. A cross-sectional study was conducted among 160 COVID-19 patients at Cipto Mangunkusumo General Hospital and Wisma Atlit Hospital Jakarta from October 2021 to January 2022. The mean serum 25(OH)D level was 15.1 ng/mL. A significant negative correlation was found between serum 25(OH)D and anti-PF4 levels in mild COVID-19 patients (P = .035; R = -0.236). Remarkably, P-selectin levels were significantly higher in the moderate COVID-19 group compared to the severe group (P = .031). Serum 25(OH)D level had a significant negative correlation with anti-PF4 level in mild COVID-19 patients. Thus, it is highly recommended to ensure that serum 25(OH)D levels are maintained above 30 ng/mL. Remarkably, the P-selectin level was significantly higher in the moderate COVID-19 group compared to the severe group.

Asunto(s)

COVID-19 , Factor Plaquetario 4 , Vitamina D , Humanos , COVID-19/sangre , COVID-19/complicaciones , Femenino , Masculino , Vitamina D/sangre , Vitamina D/análogos & derivados , Estudios Transversales , Persona de Mediana Edad , Factor Plaquetario 4/sangre , Factor Plaquetario 4/inmunología , Adulto , Anciano , SARS-CoV-2 , Autoanticuerpos/sangre , Índice de Severidad de la Enfermedad

RESUMEN

OBJECTIVES: To explore early diagnostic biological markers for Leigh syndrome caused by the m.8993T>G mutation. METHODS: A retrospective analysis was performed on the clinical data of four children diagnosed with m.8993T>G mutation-related mitochondrial disease at the Children's Hospital of Chongqing Medical University from January 2014 to January 2024. Additionally, a literature review was conducted. RESULTS: All four children had plasma amino acid and acylcarnitine analyses that revealed decreased citrulline levels, and one child was initially identified through neonatal genetic metabolic disease screening. According to the literature review, there were 26 children with mitochondrial disease and hypocitrullinemia caused by the m.8993T>G mutation (including the four children in this study). Among these, 12 children exhibited clinical phenotypes of Leigh syndrome or Leigh-like syndrome, while 18 children were identified with hypocitrullinemia and/or elevated levels of 3-hydroxyisovalerylcarnitine (C5-OH) during neonatal genetic metabolic disease screening. CONCLUSIONS: Hypocitrullinemia may serve as a potential biomarker for the early diagnosis of m.8993T>G mutation-associated Leigh syndrome, detectable as early as during neonatal genetic metabolic disease screening.

Asunto(s)

Citrulina , Enfermedad de Leigh , Mutación , Humanos , Enfermedad de Leigh/genética , Masculino , Femenino , Lactante , Citrulina/sangre , Preescolar , Recién Nacido , Carnitina/análogos & derivados , Carnitina/sangre , Estudios Retrospectivos

RESUMEN

OBJECTIVE: The prognosis of extra-nodal NK/T cell lymphoma (ENKTL) is poor, and the optimal therapy remains controversial. This study aims to evaluate the safety and efficacy of a new combined modality therapy. METHODS: Phase-2 study of pegaspargase, etoposide and gemcitabine (PEG) combined with involved field radiation therapy (IFRT) in newly-diagnosed patients with early-stage ENKTL. Patients received 4 course of PEG followed by IFRT. The primary endpoints were complete response (CR), partial response (PR), and objective response rate (ORR) after IFRT. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: 34 consecutive patients with Ann Arbor stage I/II were enrolled. 3 patients progressed on PEG, while the remaining 31 received IFRT. The ORR was 88.2% (30/34), included 28 (82.4%) complete and 2 (5.8%) partial responses. With a median follow-up of 56.0 months (Interquartile Range [IQR], 36.0-66.9 months), the estimated 5-year PFS and OS were 87.4% (95% Confidence Interval [CI],69.5%-94.8%) and 97.1% (95%CI, 80.1%-99.6%), respectively. Most adverse events were hematological and easily managed. CONCLUSIONS: PEG followed by IFRT is a safe and effective initial therapy for early-stage ENKTL, demonstrating impressive PFS and OS rates. This promising approach warrants further validation in a randomized controlled trial (Registered at Clinicaltrials.gov NCT02705508).Trial registration: ClinicalTrials.gov identifier: NCT02705508.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Asparaginasa , Desoxicitidina , Etopósido , Gemcitabina , Linfoma Extranodal de Células NK-T , Polietilenglicoles , Humanos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Linfoma Extranodal de Células NK-T/radioterapia , Linfoma Extranodal de Células NK-T/mortalidad , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/terapia , Masculino , Femenino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Asparaginasa/administración & dosificación , Asparaginasa/uso terapéutico , Asparaginasa/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Estadificación de Neoplasias , Resultado del Tratamiento

RESUMEN

Phenylpiracetam (PP) is a nootropic drug with additional pharmacological effects, including anxiolytic, antiasthenic, antidepressant, anti-inflammatory and anticonvulsant effects. The paper presents the results of an analysis of experimental and clinical studies, which indicate the prospects for the use of PP in cerebral ischemia, neurodegenerative pathologies, epilepsy, asthenia, and mental disorders. The adaptogenic properties and mitochondrial protective effect of PP are considered, assessments of the possible effect of PP on neurotransmitter systems, regulation of carbohydrate and fat metabolism with the prospects for the use of PP in patients with metabolic syndrome.

Asunto(s)

Anticonvulsivantes , Humanos , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/farmacología , Nootrópicos/uso terapéutico , Nootrópicos/farmacología , Pirrolidinonas/uso terapéutico , Pirrolidinonas/farmacología , Epilepsia/tratamiento farmacológico , Antidepresivos/uso terapéutico , Antidepresivos/farmacología , Animales , Astenia/tratamiento farmacológico , Trastornos Mentales/tratamiento farmacológico , Ansiolíticos/uso terapéutico , Ansiolíticos/farmacología , Piracetam/análogos & derivados