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1.
Chem Commun (Camb) ; 60(85): 12421-12424, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39373978

RESUMEN

A novel "Ring-expansion" strategy is proposed to optimize traditional host molecular structures, featuring a rigid molecular skeleton and excellent transport of carriers. Consequently, the two novel host materials facilitate the fabrication of efficient phosphorescent OLEDs with suppressed efficiency roll-off compared to OLEDs based on the conventional host material (mCP).

2.
Int J Ophthalmol ; 17(10): 1869-1879, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39430022

RESUMEN

AIM: To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. METHODS: For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. RESULTS: The OCTA data demonstrated a statistically significant difference (P<0.05) in macular retinal microvessel density between the two groups. Specifically, in the SRL and DRL analyses, the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group (P<0.05). Furthermore, using the hemispheric segmentation method, the ILD group showed notable reductions in SL, SR, and IL in the superficial retina (P<0.05), as well as marked decreases in SL and IR in the deep retina (P<0.05). Similarly, when employing the ETDRS method, the ILD group displayed substantial drops in superficial retinal S and I (P<0.05), along with notable reductions in deep retinal L, I, and R (P<0.05). In the central annuli segmentation method, the ILD group exhibited a significant decrease in the superficial retinal C2-4 region (P<0.05), whereas the deep retina showed a notable reduction in the C3-5 region (P<0.05). Additionally, there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR. Furthermore, there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI (P<0.001). CONCLUSION: Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group. Conversely, their fundus retinal microvascular density is significantly lower. Furthermore, CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group. The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases, thereby enhancing disease management.

3.
Comp Biochem Physiol C Toxicol Pharmacol ; 287: 110040, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265966

RESUMEN

Ammonia is a major pollutant of freshwater environments. Previous studies have indicated that ammonia exposure adversely affects the physiology of freshwater fish. However, its effect on bone mineralization in freshwater fish larvae remains unclear. In this study, zebrafish larvae were used as a model to investigate the effects of different ammonia levels (0, 2.5, 5, and 10 mM NH4Cl) on the survival rate, body length, and bone mineralization of fish. The survival rate of zebrafish embryos exposed to different NH4Cl concentrations for 8 days was not affected. In contrast, the body length and bone mineralization of zebrafish larvae at 8 days post fertilization (dpf) were significantly reduced at 5 and 10 mM NH4Cl exposure. Further investigations revealed that ammonia exposure decreased the mRNA expression of osteoblast-related genes and increased that of osteoclast-related genes. Additionally, exposure to 5 mM and 10 mM NH4Cl induced the production of reactive oxygen species (ROS). 10 mM-but not 5 mM-NH4Cl exposure reduced the calcium and phosphorus content in 8 dpf zebrafish larvae. In conclusion, ammonia exposure induces bone resorption, while decreasing the calcium and phosphorus content of the whole body and bone formation, resulting in impaired bone mineralization in fish larvae.

4.
Trends Biotechnol ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39299833

RESUMEN

Genome design is the foundation of genome synthesis, which provides a new platform for deepening our understanding of biological systems by exploring the fundamental components and structure of the genome. Artificial genome designs can endow unnatural genomes with desired functions. We provide a comprehensive overview of genome design principles ranging from DNA sequences to the 3D structure of chromosomes. Furthermore, we highlight applications of genome design in gene expression, genome structure, genome function, and biocontainment, and discuss the potential of artificial intelligence (AI) in genome design.

5.
Arthrosc Tech ; 13(6): 102970, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39036396

RESUMEN

Injuries of the posterior root of the medial meniscus can be accompanied by damage to the anterior cruciate ligament or often occur independently in cases of degenerative meniscal injury in older individuals. Anchor suture repair can achieve favorable biomechanical effects and clinical outcomes. However, anchor placement is technically challenging and requires a posterior medial approach, which increases the risk of iatrogenic injury. To address these issues, we have utilized the reverse anchor technique to repair the posterior root of the medial meniscus. This technique offers advantages such as reduced surgical time, simplified operation, and reduced risk of the "bungee effect" and iatrogenic injury.

6.
RSC Adv ; 14(31): 22763-22768, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39027035

RESUMEN

At present, mainstream room-temperature phosphorescence (RTP) emission relies on organic materials with long-range charge-transfer effects; therefore, exploring new forms of charge transfer to generate RTP is worth studying. In this work, indole-carbazole was used as the core to ensure the narrowband fluorescence emission of the material based on its characteristic short-range charge-transfer effect. In addition, halogenated carbazoles were introduced into the periphery to construct long-range charge transfer, resulting in VTCzNL-Cl and VTCzNL-Br. By encapsulating these phosphors into a robust host (TPP), two host-guest crystalline systems were further developed, achieving efficient RTP performance with phosphorescence quantum yields of 26% and phosphorescence lifetimes of 3.2 and 39.2 ms, respectively.

7.
Chem Commun (Camb) ; 60(63): 8240-8243, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39007923

RESUMEN

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.


Asunto(s)
Colorantes Fluorescentes , Isoindoles , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Isoindoles/química , Isoindoles/síntesis química , Humanos , beta-N-Acetilhexosaminidasas/metabolismo , beta-N-Acetilhexosaminidasas/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Estructura Molecular , Espectrometría de Fluorescencia
8.
Artículo en Inglés | MEDLINE | ID: mdl-38885808

RESUMEN

Cl- is a major anion in the bodily fluids of vertebrates, and maintaining its homeostasis is essential for normal physiological functions. Fishes inhabiting freshwater (FW) passively lose body fluid ions, including Cl-, to the external environment because of the electrochemical gradient of ions across the body surface. Therefore, FW fishes have to actively absorb Cl- from the surroundings to maintain ion homeostasis in their bodily fluids. Hormonal control is vital for modulating ion uptake in fish. Vitamin D is involved in the regulation of Ca2+ uptake and acid secretion in fish. In the present study, we found that the levels of bioactive vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), significantly increased in zebrafish embryos and adults after exposure to water containing low levels of Cl-. Moreover, the administration of 1α,25(OH)2D3 treatment (20 µg/L) in zebrafish embryos, and intraperitoneal (i.p.) injection of 1α,25(OH)2D3 (5 µg/kg body mass) in zebrafish adults, resulting the increased Cl- content in bodily fluid in zebrafish. Na+-Cl- cotransporter 2b (NCC2b) and Cl- channel 2c (CLC2c) are specifically expressed during Cl- uptake by ionocytes in zebrafish. Our results indicated that the mRNA and protein expression of NCC2b and CLC2c considerably increased in the zebrafish with exogenous 1α,25(OH)2D3 treatment. Additionally, exogenous 1α,25(OH)2D3 administration increased the number of NCC2b- and CLC2c-expressing cells in yolk skins of zebrafish embryos and the gill filaments of zebrafish adults. Transcript signals of vitamin D receptors (VDRs) were identified in NCC2b-expressing cells. Knockdown of VDRa and VDRb significantly reduced the expression of NCC2b and CLC2c and the number of NCC2b- and CLC2c-expressing cells. These results indicate that vitamin D can affect Cl- uptake in zebrafish and extend our knowledge of the role of vitamin D in fish physiology.


Asunto(s)
Cloruros , Vitamina D , Proteínas de Pez Cebra , Pez Cebra , Animales , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Cloruros/metabolismo , Vitamina D/metabolismo , Embrión no Mamífero/metabolismo
9.
J Neurol Sci ; 461: 123056, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38772058

RESUMEN

FMR1 premutation carriers (55-200 CGG repeats) are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with motor and cognitive impairment. Bilateral hyperintensities of the middle cerebellar peduncles (MCP sign) are the major radiological hallmarks of FXTAS. In the general population, enlarged perivascular spaces (PVS) are biomarkers of small vessel disease and glymphatic dysfunction and are associated with cognitive decline. Our aim was to determine if premutation carriers show higher ratings of PVS than controls and whether enlarged PVS are associated with motor and cognitive impairment, MRI features of neurodegeneration, cerebrovascular risk factors and CGG repeat length. We evaluated 655 MRIs (1-10 visits/participant) from 229 carriers (164 with FXTAS and 65 without FXTAS) and 133 controls. PVS in the basal ganglia (BG-EPVS), centrum semiovale, and midbrain were evaluated with a semiquantitative scale. Mixed-effects models were used for statistical analysis adjusting for age. In carriers with FXTAS, we revealed that (1) BG-PVS ratings were higher than those of controls and carriers without FXTAS; (2) BG-PVS severity was associated with brain atrophy, white matter hyperintensities, enlarged ventricles, FXTAS stage and abnormal gait; (3) age-related increase in BG-PVS was associated with cognitive dysfunction; and (4) PVS ratings of all three regions showed robust associations with CGG repeat length and were higher in carriers with the MCP sign than carriers without the sign. This study demonstrates clinical relevance of PVS in FXTAS especially in the basal ganglia region and suggests microangiopathy and dysfunctional cerebrospinal fluid circulation in FXTAS physiopathology.


Asunto(s)
Ataxia , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Sistema Glinfático , Imagen por Resonancia Magnética , Temblor , Humanos , Masculino , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/diagnóstico por imagen , Síndrome del Cromosoma X Frágil/patología , Persona de Mediana Edad , Anciano , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Temblor/genética , Temblor/diagnóstico por imagen , Temblor/patología , Ataxia/genética , Ataxia/diagnóstico por imagen , Ataxia/patología , Sistema Glinfático/diagnóstico por imagen , Sistema Glinfático/patología , Factores de Riesgo , Heterocigoto , Trastornos Cerebrovasculares/genética , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/patología , Disfunción Cognitiva/genética , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Disfunción Cognitiva/etiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología
10.
J Alzheimers Dis ; 98(3): 941-955, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38489185

RESUMEN

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Disfunción Cognitiva , Demencia , Masculino , Femenino , Humanos , Anciano , Estudios de Cohortes , Estudios de Casos y Controles , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Disfunción Cognitiva/epidemiología , China/epidemiología , Material Particulado/efectos adversos , Material Particulado/análisis
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 1-10, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38433624

RESUMEN

Objective To investigate the impact of Pseudomonas aeruginosa(PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P<0.05),down-regulated mRNA level of CDH5(P=0.023),disrupted continuity and down-regulated protein level of VE-cadherin(P<0.001),and elevated lactate level(P=0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5(P=0.043),lowered lactate level(P=0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3(P=0.013 and P=0.003),elevated lactate level(P=0.015),and down-regulated mRNA level of CDH5(P=0.020) and protein level of VE-cadherin(P=0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.


Asunto(s)
Neumonía , Infecciones por Pseudomonas , Humanos , Animales , Ratones , Células Endoteliales , Pseudomonas aeruginosa , Calcio , Factores de Transcripción , Pulmón , Lactatos , ARN Mensajero
12.
BMC Geriatr ; 24(1): 118, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297201

RESUMEN

BACKGROUND: Fine motor skills are closely related to cognitive function. However, there is currently no comprehensive assessment of fine motor movement and how it corresponds with cognitive function. To conduct a complete assessment of fine motor and clarify the relationship between various dimensions of fine motor and cognitive function. METHODS: We conducted a cross-sectional study with 267 community-based participants aged ≥ 60 years in Beijing, China. We assessed four tests performance and gathered detailed fine motor indicators using Micro-Electro-Mechanical System (MEMS) motion capture technology. The wearable MEMS device provided us with precise fine motion metrics, while Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. We adopted logistic regression to analyze the relationship between fine motor movement and cognitive function. RESULTS: 129 (48.3%) of the participants had cognitive impairment. The vast majority of fine motor movements have independent linear correlations with MoCA-BJ scores. According to logistic regression analysis, completion time in the Same-pattern tapping test (OR = 1.033, 95%CI = 1.003-1.063), Completion time of non-dominant hand in the Pieces flipping test (OR = 1.006, 95%CI = 1.000-1.011), and trajectory distance of dominant hand in the Pegboard test (OR = 1.044, 95%CI = 1.010-1.068), which represents dexterity, are related to cognitive impairment. Coordination, represented by lag time between hands in the Same-pattern tapping (OR = 1.663, 95%CI = 1.131-2.444), is correlated with cognitive impairment. Coverage in the Dual-hand drawing test as an important indicator of stability is negatively correlated with cognitive function (OR = 0.709, 95%CI = 0.6501-0.959). Based on the above 5-feature model showed consistently high accuracy and sensitivity at the MoCA-BJ score (ACU = 0.80-0.87). CONCLUSIONS: The results of a comprehensive fine-motor assessment that integrates dexterity, coordination, and stability are closely related to cognitive functioning. Fine motor movement has the potential to be a reliable predictor of cognitive impairment.


Asunto(s)
Cognición , Disfunción Cognitiva , Humanos , Anciano , Estudios Transversales , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , China/epidemiología , Pruebas de Estado Mental y Demencia
13.
Chem Commun (Camb) ; 60(5): 574-577, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38093698

RESUMEN

Benefitting from short-range charge transfer (SR-CT) and through-space charge transfer (TSCT) effects, an efficient green narrowband emitter, BNDCN, was developed. Owing to the synergistic effect of double CT processes, a BNDCN-based organic light-emitting diode showed a high external quantum efficiency of 32.3%.

14.
Int J Implant Dent ; 9(1): 51, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38108942

RESUMEN

OBJECTIVES: Vascularized fibula flap transplantation is the most effective and common method to repair the jaw defects. In addition, implantation is the first choice to restore dentition on the graft fibula. Implants are usually implanted at least 6 months after fibula transplantation. Primary implantation of implants during surgery can restore the dentition earlier, but whether this method can achieve the same restorative effect as secondary implantation is still uncertain. This article aims to compare the survival rate and complications between primary and secondary implantation through meta-analysis. METHODS: This meta-analysis was conducted according to PRISMA protocol and the Cochrane Handbook of Systematic Reviews of Interventions. According to the inclusion and exclusion criteria, we selected the PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM) according to established inclusion and exclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Meta-analysis was conducted to compare the survival rate and postoperative infection rate of primary and secondary implantation. RESULTS: Seven studies were involved in our research, involving 186 patients. Five of the studies detailed implant success in 106 patients (primary implantation 50, secondary implantation 56), and four studies documented infection after implantation in 117 patients (primary implantation 52, secondary implantation 65); the survival rate of the primary implantation was 93.3%, and the incidence of postoperative infection was 17.3%. The survival rate of the secondary implantation was 93.4%, and 23.1% had postoperative infection. Meta-analysis showed that there was no significant difference in the survival rate between primary implantation and secondary implantation, OR = 0.813 (95% CI 0.383-1.725, P = 0.589 > 0.05), and there was no significant difference in the incidence of postoperative infection, OR = 0.614 (95% CI 0.239-1.581, P = 0.312 > 0.05). CONCLUSIONS: Based on the results of this study, the research found no significant difference in the survival rate or infection rates between primary and secondary implantation. After appropriate indications selection, primary implantation can be used to reconstruct the dentition with less waiting time, reduce the impact of radiotherapy, and bring a higher quality of life for patients.


Asunto(s)
Implantes Dentales , Ketamina , Humanos , Tasa de Supervivencia , Peroné/cirugía , Calidad de Vida , Implantes Dentales/efectos adversos , Complicaciones Posoperatorias/epidemiología
15.
Genomics ; 115(6): 110737, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37926353

RESUMEN

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Células Madre Mesenquimatosas , MicroARNs , Humanos , Ratones , Animales , MicroARNs/genética , MicroARNs/metabolismo , Insuficiencia Hepática Crónica Agudizada/genética , Insuficiencia Hepática Crónica Agudizada/terapia , Insuficiencia Hepática Crónica Agudizada/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Madre Mesenquimatosas/metabolismo
16.
Cells ; 12(18)2023 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-37759552

RESUMEN

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.


Asunto(s)
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Humanos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Mutación/genética , ARN Mensajero/metabolismo , Expansión de Repetición de Trinucleótido/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/terapia
17.
Stem Cells ; 41(12): 1171-1184, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-37659098

RESUMEN

Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Células Madre Mesenquimatosas , Ratones , Animales , Insuficiencia Hepática Crónica Agudizada/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Macrófagos/metabolismo , Transducción de Señal , Células Madre Mesenquimatosas/metabolismo , Tirosina Quinasa c-Mer/genética , Tirosina Quinasa c-Mer/metabolismo
18.
Cells ; 12(14)2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37508562

RESUMEN

Brain changes at the end-stage of fragile X-associated tremor/ataxia syndrome (FXTAS) are largely unknown due to mobility impairment. We conducted a postmortem MRI study of FXTAS to quantify cerebrovascular disease, brain atrophy and iron content, and examined their relationships using principal component analysis (PCA). Intracranial hemorrhage (ICH) was observed in 4/17 FXTAS cases, among which one was confirmed by histologic staining. Compared with seven control brains, FXTAS cases showed higher ratings of T2-hyperintensities (indicating cerebral small vessel disease) in the cerebellum, globus pallidus and frontoparietal white matter, and significant atrophy in the cerebellar white matter, red nucleus and dentate nucleus. PCA of FXTAS cases revealed negative associations of T2-hyperintensity ratings with anatomic volumes and iron content in the white matter, hippocampus and amygdala, that were independent from a highly correlated number of regions with ICH and iron content in subcortical nuclei. Post-hoc analysis confirmed PCA findings and further revealed increased iron content in the white matter, hippocampus and amygdala in FXTAS cases compared to controls, after adjusting for T2-hyperintensity ratings. These findings indicate that both ischemic and hemorrhagic brain damage may occur in FXTAS, with the former being marked by demyelination/iron depletion and atrophy, and the latter by ICH and iron accumulation in basal ganglia.


Asunto(s)
Trastornos Cerebrovasculares , Síndrome del Cromosoma X Frágil , Humanos , Temblor/diagnóstico por imagen , Temblor/patología , Hierro , Ataxia/diagnóstico por imagen , Ataxia/patología , Síndrome del Cromosoma X Frágil/diagnóstico por imagen , Síndrome del Cromosoma X Frágil/patología , Imagen por Resonancia Magnética , Atrofia
19.
Front Bioeng Biotechnol ; 11: 1183354, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37214278

RESUMEN

Synthetic biology combines the disciplines of biology, chemistry, information science, and engineering, and has multiple applications in biomedicine, bioenergy, environmental studies, and other fields. Synthetic genomics is an important area of synthetic biology, and mainly includes genome design, synthesis, assembly, and transfer. Genome transfer technology has played an enormous role in the development of synthetic genomics, allowing the transfer of natural or synthetic genomes into cellular environments where the genome can be easily modified. A more comprehensive understanding of genome transfer technology can help to extend its applications to other microorganisms. Here, we summarize the three host platforms for microbial genome transfer, review the recent advances that have been made in genome transfer technology, and discuss the obstacles and prospects for the development of genome transfer.

20.
Res Sq ; 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36711694

RESUMEN

Brain changes at end-stage of fragile X-associated tremor/ataxia syndrome (FXTAS) are largely unknown due to mobility impairment. We conducted a postmortem MRI study of FXTAS to quantify cerebrovascular disease, brain atrophy, and iron content and examined their relationships using principal component analysis (PCA). Intracranial hemorrhage (ICH) was observed in 4/17 FXTAS cases among which one was confirmed by histologic staining. Compared with seven control brains, FXTAS cases showed higher ratings of T2-hyperintensities (indicating cerebral small vessel disease) in the cerebellum, globus pallidus, and frontoparietal white matter and significant atrophy in cerebellar white matter, red nucleus, and dentate nucleus. PCA of FXTAS cases revealed negative associations of T2-hyperintensity ratings with anatomic volumes and iron content in the white matter, hippocampus, and amygdala, that were independent from highly correlated number of regions with ICH and iron content in subcortical nuclei. Post hoc analysis confirmed PCA findings and further revealed increased iron content in the white matter, hippocampus, and amygdala in FXTAS cases than controls after adjusting for T2-hyperintensity ratings. These findings indicate that both ischemic and hemorrhagic brain damage may occur in FXTAS, with the former marked by demyelination/iron depletion and atrophy and the latter, ICH and iron accumulation in basal ganglia.

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