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1.
Genes Dev ; 35(1-2): 59-64, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33303641

RESUMEN

Here, we showed that the acetylation-defective p53-4KR mice, lacking the ability of cell cycle arrest, senescence, apoptosis, and ferroptosis, were tumor prone but failed to develop early-onset tumors. By identifying a novel p53 acetylation site at lysine K136, we found that simultaneous mutations at all five acetylation sites (p53-5KR) diminished its remaining tumor suppression function. Moreover, the embryonic lethality caused by the deficiency of mdm2 was fully rescued in the background of p535KR/5KR , but not p534KR/4KR background. p53-4KR retained the ability to suppress mTOR function but this activity was abolished in p53-5KR cells. Notably, the early-onset tumor formation observed in p535KR/5KR and p53-null mice was suppressed upon the treatment of the mTOR inhibitor. These results suggest that p53-mediated mTOR regulation plays an important role in both embryonic development and tumor suppression, independent of cell cycle arrest, senescence, apoptosis, and ferroptosis.


Asunto(s)
Puntos de Control del Ciclo Celular/genética , Neoplasias/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Acetilación , Animales , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Embrión de Mamíferos , Lisina/genética , Lisina/metabolismo , Ratones , Mutación/genética , Neoplasias/fisiopatología , Proteínas Proto-Oncogénicas c-mdm2/deficiencia , Proteínas Proto-Oncogénicas c-mdm2/genética , Sirolimus/farmacología , Análisis de Supervivencia
2.
Proc Natl Acad Sci U S A ; 121(15): e2313921121, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38568968

RESUMEN

Malvaceae comprise some 4,225 species in 243 genera and nine subfamilies and include economically important species, such as cacao, cotton, durian, and jute, with cotton an important model system for studying the domestication of polyploids. Here, we use chromosome-level genome assemblies from representatives of five or six subfamilies (depending on the placement of Ochroma) to differentiate coexisting subgenomes and their evolution during the family's deep history. The results reveal that the allohexaploid Helicteroideae partially derive from an allotetraploid Sterculioideae and also form a component of the allodecaploid Bombacoideae and Malvoideae. The ancestral Malvaceae karyotype consists of 11 protochromosomes. Four subfamilies share a unique reciprocal chromosome translocation, and two other subfamilies share a chromosome fusion. DNA alignments of single-copy nuclear genes do not yield the same relationships as inferred from chromosome structural traits, probably because of genes originating from different ancestral subgenomes. These results illustrate how chromosome-structural data can unravel the evolutionary history of groups with ancient hybrid genomes.


Asunto(s)
Genoma de Planta , Gossypium , Genoma de Planta/genética , Gossypium/genética , Genómica/métodos , Poliploidía , Cariotipo , Evolución Molecular
3.
Biochem Biophys Res Commun ; 708: 149786, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38493545

RESUMEN

Ectopic lipid deposition (ELD) and mitochondrial dysfunction are common causes of metabolic disorders in humans. Consuming too much fructose can result in mitochondrial dysfunction and metabolic disorders. 6-Gingerol, the main component of ginger (Zingiber officinale Roscoe), has been proven to alleviate metabolic disorders. This study seeks to examine the effects of 6-gingerol on metabolic disorders caused by fructose and uncover the underlying molecular mechanisms. In this study, the results showed that 6-Gingerol ameliorated high-fructose-induced metabolic disorders. Moreover, it inhibited CD36 membrane translocation, increased CD36 expression in the mitochondria, and decreased the O-GlcNAc modification of CD36 and OGT expression in vitro and vivo. In addition, 6-Gingerol enhanced the performance of mitochondria in the skeletal muscle and boosted the respiratory capability of L6 myotubes. This study provides a theoretical basis and new insights for the development of lipid-lowering drugs in clinical practice.


Asunto(s)
Enfermedades Metabólicas , Enfermedades Mitocondriales , Humanos , Músculo Esquelético/metabolismo , Mitocondrias/metabolismo , Alcoholes Grasos/farmacología , Alcoholes Grasos/metabolismo , Catecoles/farmacología , Fructosa/metabolismo , Enfermedades Metabólicas/metabolismo , Enfermedades Mitocondriales/metabolismo
4.
Small ; 20(25): e2309276, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38247194

RESUMEN

Macrophage dysfunction is one of the primary factors leading to the delayed healing of diabetic wounds. Hypoxic bone marrow mesenchymal stem cells-derived exosomes (hyBMSC-Exos) have been shown to play an active role in regulating cellular function through the carried microRNAs. However, the administration of hyBMSC-Exos alone in diabetic wounds usually brings little effect, because the exosomes are inherently unstable and have a short retention time at the wounds. In this study, a multifunctional hydrogel based on gallic acid (GA) conjugated chitosan (Chi-GA) and partially oxidized hyaluronic acid (OHA) is prepared for sustained release of hyBMSC-Exos. The hydrogel not only exhibits needs-satisfying physicochemical properties, but also displays outstanding biological performances such as low hemolysis rate, strong antibacterial capacity, great antioxidant ability, and excellent biocompatibility. It has the ability to boost the stability of hyBMSC-Exos, leading to a continuous and gradual release of the exosomes at wound locations, ultimately enhancing the exosomes' uptake efficiency by target cells. Most importantly, hyBMSC-Exos loaded hydrogel shows an excellent ability to promote diabetic wound healing by regulating macrophage polarization toward M2 phenotype. This may be because exosomal miR-4645-5p and antioxidant property of the hydrogel synergistically inhibit SREBP2 activity in macrophages. This study presents a productive approach for managing diabetic wounds.


Asunto(s)
Complicaciones de la Diabetes , Exosomas , Hidrogeles , Células Madre Mesenquimatosas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Exosomas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/patología , Piel/efectos de los fármacos , Piel/lesiones , Humanos , Supervivencia Celular/efectos de los fármacos , Bacterias/efectos de los fármacos
5.
Cerebrovasc Dis ; 53(1): 115-124, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37276846

RESUMEN

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.


Asunto(s)
Fibrilación Atrial , Foramen Oval Permeable , Accidente Cerebrovascular , Humanos , Proyectos Piloto , Factores de Riesgo , Cateterismo Cardíaco/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/etiología , Foramen Oval Permeable/diagnóstico , Foramen Oval Permeable/diagnóstico por imagen , Fibrilación Atrial/diagnóstico , Prevención Secundaria , Encéfalo , Resultado del Tratamiento , Recurrencia
6.
Environ Res ; 242: 117739, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38007076

RESUMEN

In wastewater treatment plants (WWTPs), ammonia oxidation is primarily carried out by three types of ammonia oxidation microorganisms (AOMs): ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and comammox (CMX). Antibiotic resistance genes (ARGs), which pose an important public health concern, have been identified at every stage of wastewater treatment. However, few studies have focused on the impact of ARGs on ammonia removal performance. Therefore, our study sought to investigate the effect of the representative multidrug-resistant plasmid RP4 on the functional microorganisms involved in ammonia oxidation. Using an inhibitor-based method, we first evaluated the contributions of AOA, AOB, and CMX to ammonia oxidation in activated sludge, which were determined to be 13.7%, 41.1%, and 39.1%, respectively. The inhibitory effects of C2H2, C8H14, and 3,4-dimethylpyrazole phosphate (DMPP) were then validated by qPCR. After adding donor strains to the sludge, fluorescence in situ hybridization (FISH) imaging analysis demonstrated the co-localization of RP4 plasmids and all three AOMs, thus confirming the horizontal gene transfer (HGT) of the RP4 plasmid among these microorganisms. Significant inhibitory effects of the RP4 plasmid on the ammonia nitrogen consumption of AOA, AOB, and CMX were also observed, with inhibition rates of 39.7%, 36.2%, and 49.7%, respectively. Moreover, amoA expression in AOB and CMX was variably inhibited by the RP4 plasmid, whereas AOA amoA expression was not inhibited. These results demonstrate the adverse environmental effects of the RP4 plasmid and provide indirect evidence supporting plasmid-mediated conjugation transfer from bacteria to archaea.


Asunto(s)
Archaea , Betaproteobacteria , Archaea/genética , Archaea/metabolismo , Aguas del Alcantarillado/microbiología , Amoníaco , Nitrógeno/metabolismo , Desnitrificación , Hibridación Fluorescente in Situ , Oxidación-Reducción , Bacterias/genética , Bacterias/metabolismo , Plásmidos/genética , Betaproteobacteria/genética , Betaproteobacteria/metabolismo , Antibacterianos , Filogenia , Microbiología del Suelo
7.
Lipids Health Dis ; 23(1): 52, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378566

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (T2DM) is closely linked to metabolic syndrome, characterised by insulin resistance, hyperglycaemia, abnormal lipid metabolism, and chronic inflammation. Diabetic ulcers (DUs) comprise consequential complications that arise as a result of T2DM. To investigate, db/db mice were used for the disease model. The findings demonstrated that a scaffold made from a combination of rhubarb charcoal-crosslinked chitosan and silk fibroin, designated as RCS/SF, was able to improve the healing process of diabetic wounds in db/db mice. However, previous studies have primarily concentrated on investigating the impacts of the RSC/SF scaffold on wound healing only, while its influence on the entire body has not been fully elucidated. MATERIAL AND METHODS: The silk fibroin/chitosan sponge scaffold containing rhubarb charcoal was fabricated in the present study using a freeze-drying approach. Subsequently, an incision with a diameter of 8 mm was made on the dorsal skin of the mice, and the RCS/SF scaffold was applied directly to the wound for 14 days. Subsequently, the impact of RCS/SF scaffold therapy on hepatic lipid metabolism was assessed through analysis of serum and liver biochemistry, histopathology, quantitative real-time PCR (qRT-PCR), immunohistochemistry, and Western blotting. RESULTS: The use of the RCS/SF scaffold led to an enhancement in the conditions associated with serum glucolipid metabolism in db/db mice. An assessment of hepatic histopathology further confirmed this enhancement. Additionally, the qRT-PCR analysis revealed that treatment with RCS/SF scaffold resulted in the downregulation of genes associated with fatty acid synthesis, fatty acid uptake, triglyceride (TG) synthesis, gluconeogenesis, and inflammatory factors. Moreover, the beneficial effect of the RCS/SF scaffold on oxidative stress was shown by assessing antioxidant enzymes and lipid peroxidation. Additionally, the network pharmacology analysis verified that the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway had a vital function in mitigating non-alcoholic fatty liver disease (NAFLD) by utilizing R. officinale. The measurement of AMPK, sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) gene and protein expression provided support for this discovery. Furthermore, the molecular docking investigations revealed a robust affinity between the active components of rhubarb and the downstream targets of AMPK (SREBP1 and FASN). CONCLUSION: By regulating the AMPK signalling pathway, the RCS/SF scaffold applied topically effectively mitigated hepatic lipid accumulation, decreased inflammation, and attenuated oxidative stress. The present study, therefore, emphasises the crucial role of the topical RCS/SF scaffold in regulating hepatic lipid metabolism, thereby confirming the concept of "external and internal reshaping".


Asunto(s)
Quitosano , Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2 , Fibroínas , Enfermedad del Hígado Graso no Alcohólico , Rheum , Ratones , Animales , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Rheum/metabolismo , Carbón Orgánico/metabolismo , Carbón Orgánico/farmacología , Carbón Orgánico/uso terapéutico , Fibroínas/metabolismo , Fibroínas/farmacología , Fibroínas/uso terapéutico , Diabetes Mellitus Tipo 2/metabolismo , Simulación del Acoplamiento Molecular , Úlcera/metabolismo , Úlcera/patología , Hígado/metabolismo , Metabolismo de los Lípidos , Enfermedad del Hígado Graso no Alcohólico/patología , Complicaciones de la Diabetes/patología , Inflamación/patología , Ácidos Grasos/metabolismo , Lípidos/uso terapéutico
8.
Postgrad Med J ; 100(1184): 421-426, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38366658

RESUMEN

BACKGROUND: Conflicting results were shown on the relationship between cerebral microbleeds (CMBs) burden and functional outcomes in patients treated with intravenous tissues plasminogen activator (IV tPA). We aimed to investigate the relationship between CMBs burden and functional outcomes using the Microbleed Anatomical Rating Scale (MARS) and determine its optimal cutoff value. METHODS: A retrospective study was conducted to include patients treated with IV tPA in our stroke center, and the MARS was used to assess the CMBs burden. Other clinical data including demographic factors, stroke severity, vascular risk factors, and clinical outcomes were also documented. Another mediation analysis was performed to investigate whether early neurological improvement could mediate the association between MARS and functional outcomes. RESULTS: A total of 408 patients were included. A cutoff value of 1.5 could predict functional outcomes in patients treated with IV tPA. Based on that cutoff value, MARS showed an independent relationship with functional outcomes [adjusted OR (Odds Ratio) 0.841, 95% confidence interval (CI) 0.720-0.982, P = .029]. A shift analysis showed that higher MARS score (MARS ≥1.5) was related with poor functional outcome according to mRS score distribution (OR = 0.519, 95% CI 0.336-0.803, P = .003). Total effect (indirect + direct effect) was calculated and showed in figure. Early neurological improvement mediated 24% of the effect of MARS score on functional outcomes. CONCLUSION: Our study showed that MARS could be a potential method to assess the functional outcome based on CMBs in patients treated with IV tPA, and MARS score ≥ 1.5 might be an optimal threshold for poor functional outcome.


Asunto(s)
Fibrinolíticos , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Femenino , Masculino , Estudios Retrospectivos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Anciano , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Terapia Trombolítica/métodos , Persona de Mediana Edad , Hemorragia Cerebral , Índice de Severidad de la Enfermedad , Administración Intravenosa , Resultado del Tratamiento , Relevancia Clínica
9.
Tohoku J Exp Med ; 263(1): 27-34, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38220169

RESUMEN

This study aimed to investigate the effects of a Roy adaptation model (RAM)-based cognitive stimulation therapy (CST) intervention on elderly patients diagnosed with primary non-small cell lung cancer (NSCLC) undergoing curative resection. A total of 280 patients diagnosed with primary NSCLC were randomized into RAM-based CST group and control group. Outcomes were assessed at three intervals: pre-surgery, discharge, and one-month post-discharge. Cognitive function was evaluated using Mini-Cognitive test. Postoperative delirium prevalence was determined within 48 hours post-surgery using Nursing Delirium Screening Scale. The Hospital Anxiety and Depression Scale evaluated anxiety and depression symptoms, while Quality of Life (QoL) was assessed via Short Form-36 (SF36) Health Survey. The RAM-based CST group demonstrated significantly higher Mini-Cog test scores than the control group upon discharge and post-intervention. Patients with RAM-based CST exhibited a decrease in postoperative delirium compared to the control group. The RAM-based CST intervention yielded an improvement in anxiety and depression at discharge and 1-month post-discharge compared to preoperative levels. Additionally, the RAM-based CST group exhibited substantial enhancements in SF36 subcategory scores at 1-month post-discharge compared to pre-surgery. At post-intervention, the RAM-based CST group demonstrated significantly higher scores than the control group across various health-related domains, including role limitations due to emotional problems, mental health, general health perception, bodily pain, and role limitations due to physical problems. The RAM-based CST intervention in elderly NSCLC patients undergoing curative resection yielded significant enhancements in cognitive function, reduced delirium incidence, improved emotional well-being, and better QoL postoperatively.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Calidad de Vida , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Anciano , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/psicología , Masculino , Resultado del Tratamiento , Terapia Cognitivo-Conductual/métodos , Depresión/terapia , Cognición , Ansiedad/terapia , Anciano de 80 o más Años , Delirio
10.
Ecotoxicol Environ Saf ; 276: 116288, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38581909

RESUMEN

Cylindrospermopsin (CYN), a cyanobacterial toxin, has been detected in the global water environment. However, information concerning the potential environmental risk of CYN is limited, since the majority of previous studies have mainly focused on the adverse health effects of CYN through contaminated drinking water. The present study reported that CYN at environmentally relevant levels (0.1-100 µg/L) can significantly enhance the conjugative transfer of RP4 plasmid in Escherichia coli genera, wherein application of 10 µg/L of CYN led to maximum fold change of ∼6.5- fold at 16 h of exposure. Meanwhile, evaluation of underlying mechanisms revealed that environmental concentration of CYN exposure could increase oxidative stress in the bacterial cells, resulting in ROS overproduction. In turn, this led to an upregulation of antioxidant enzyme-related genes to avoid ROS attack. Further, inhibition of the synthesis of glutathione (GSH) was also detected, which led to the rapid depletion of GSH in cells and thus triggered the SOS response and promoted the conjugative transfer process. Increase in cell membrane permeability, upregulation of expression of genes related to pilus generation, ATP synthesis, and RP4 gene expression were also observed. These results highlight the potential impact on the spread of antimicrobial resistance in water environments.


Asunto(s)
Alcaloides , Toxinas Bacterianas , Toxinas de Cianobacterias , Escherichia coli , Glutatión , Plásmidos , Uracilo , Plásmidos/genética , Glutatión/metabolismo , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Toxinas Bacterianas/toxicidad , Uracilo/análogos & derivados , Uracilo/toxicidad , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Conjugación Genética , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética
11.
J Asian Nat Prod Res ; 26(2): 195-203, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38193216

RESUMEN

A 1,2:3,4:9,10:9,19-tetraseco-cycloartane triterpene spiroketal lactone, pseudoamaolide P (1), two new labdane-type diterpenoids, pseudoamains A and B (2-3), and four known cembrane-type diterpenoids (4-7) were isolated from the seeds of Pseudolarix amabilis. The structures of these compounds were elucidated by spectroscopic analyses, including HRESIMS, 1D-, and 2D-NMR. The anti-inflammatory activities of the compounds were evaluated by suppressing the transcription of the NF-κB-dependent reporter gene in LPS-induced 293 T/NF-κB-luc cells. All compounds do not show potent activity.


Asunto(s)
Diterpenos , Furanos , Compuestos de Espiro , Triterpenos , Lactonas/farmacología , FN-kappa B , Triterpenos/farmacología , Triterpenos/química , Diterpenos/farmacología , Diterpenos/química , Semillas , Estructura Molecular
13.
Int J Mol Sci ; 25(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38732044

RESUMEN

High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and hub-gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that PRKDC gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of PRKDC, has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of PRKDC in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. PRKDC and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC.


Asunto(s)
Aneuploidia , Cromosomas Humanos Par 8 , Variaciones en el Número de Copia de ADN , Progresión de la Enfermedad , Neoplasias Ováricas , Femenino , Humanos , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Cromosomas Humanos Par 8/genética , Regulación Neoplásica de la Expresión Génica , Hibridación Fluorescente in Situ , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología
14.
J Sci Food Agric ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597278

RESUMEN

BACKGROUND: Browning is the key problem hindering the industrialization of pear wine. The use of high-yield glutathione Saccharomyces cerevisiae in the fermentation of pear wine can inhibit browning. Glutathione reductase (GR) can ensure the reduction of glutathione. Spore immobilization of enzymes is a new technology. It is a new attempt to apply spore-immobilized GR in combination with high-yield glutathione S. cerevisiae to inhibit browning of pear wine. RESULTS: Saccharomyces cerevisiae spore immobilization enzyme technology was used to immobilize GR in the spores of mutant S. cerevisiae dit1∆, osw2∆ and chs3∆ and wild-type S. cerevisiae. The enzyme activity of GR immobilized by chs3∆ spores was the highest of 3.08 U mg-1 min-1. The chs3∆ spore-immobilized GR had certain resistance to ethanol, citric acid, sucrose, glucose and proteinase K. Electron microscopy analysis showed that the spore wall of chs3∆ had moderate size holes, which might be the main reason why it immobilized GR with the highest enzyme activity. And the GR was immobilized between the prespore membrane and mannoprotein layer of the spore wall. When chs3∆ spore-immobilized GR (chs3∆-GR) was added to Dangshan pear wine fermented by high-yield glutathione S. cerevisiae JN32-9, the presence of chs3∆-GR could further protect amino acids, polyphenols and glucose from oxidation, thereby reducing the browning of the pear wine during storage by 47.32%. CONCLUSION: GR immobilized by S. cerevisiae spores was effective in inhibiting the browning of pear wine. The method was simple, green and effective and did not increase the production cost of pear wine. © 2024 Society of Chemical Industry.

15.
Int Wound J ; 21(4): e14867, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38597295

RESUMEN

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.


Asunto(s)
Diabetes Mellitus Experimental , Oxigenoterapia Hiperbárica , Humanos , Animales , Ratones , Cicatrización de Heridas/fisiología , Diabetes Mellitus Experimental/terapia , Células Endoteliales de la Vena Umbilical Humana , Tejido Adiposo Blanco
16.
J Am Chem Soc ; 145(9): 4934-4939, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36811995

RESUMEN

Iron porphyrin carbenes (IPCs) have been extensively recognized as the reactive intermediates in various iron porphyrin-catalyzed carbene transfer reactions. While donor-acceptor diazo compounds have been frequently used for such transformations, the structures and reactivities of donor-acceptor IPCs are less explored. To date, no crystal structures of donor-acceptor IPC complexes have been reported, and therefore, the involvement of IPC intermediacy for such transformations lacks direct evidence. Here we report the synthesis and NMR characterization of several donor-acceptor IPC complexes from iron porphyrin and corresponding donor-acceptor diazo compounds. The X-ray crystal structure of an IPC complex derived from a morpholine-substituted diazo amide was obtained. The carbene transfer reactivities of those IPCs were tested by the N-H insertion reactions with aniline or morpholine as well as the three-component reaction with aniline and γ,δ-unsaturated α-keto ester based on electrophilic trapping of an ammonium ylide intermediate. Based on these results, IPCs were identified as the real intermediates for iron porphyrin-catalyzed carbene transfer reactions from donor-acceptor diazo compounds.

17.
Cancer Sci ; 114(8): 3318-3329, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37302808

RESUMEN

WDR54 has been recently identified as a novel oncogene in colorectal and bladder cancers. However, the expression and function of WDR54 in T-cell acute lymphoblastic leukemia (T-ALL) were not reported. In this study, we investigated the expression of WDR54 in T-ALL, as well as its function in T-ALL pathogenesis using cell lines and T-ALL xenograft. Bioinformatics analysis indicated high mRNA expression of WDR54 in T-ALL. We further confirmed that the expression of WDR54 was significantly elevated in T-ALL. Depletion of WDR54 dramatically inhibited cell viability and induced apoptosis and cell cycle arrest at S phase in T-ALL cells in vitro. Moreover, knockdown of WDR54 impeded the process of leukemogenesis in a Jurkat xenograft model in vivo. Mechanistically, the expression of PDPK1, phospho-AKT (p-AKT), total AKT, phospho-ERK (p-ERK), Bcl-2 and Bcl-xL were downregulated, while cleaved caspase-3 and cleaved caspase-9 were upregulated in T-ALL cells with WDR54 knockdown. Additionally, RNA-seq analysis indicated that WDR54 might regulate the expression of some oncogenic genes involved in multiple signaling pathways. Taken together, these findings suggest that WDR54 may be involved in the pathogenesis of T-ALL and serve as a potential therapeutic target for the treatment of T-ALL.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Apoptosis/genética , Linfocitos T/metabolismo , Proteínas Quinasas Dependientes de 3-Fosfoinosítido
18.
Small ; 19(25): e2300759, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36919820

RESUMEN

SiOx anode has a more durable cycle life than Si, being considered competitive to replace the conventional graphite. SiOx usually serves as composites with carbon to achieve more extended cycle life. However, the carbon microstructure dependent Li-ion storage behaviors in SiOx /C anode have received insufficient attention. Herein, this work demonstrates that the disorder of carbon can determine the ratio of inter- and intragranular Li-ion diffusions. The resulted variation of platform characteristics will result in different compatibility when matching SiOx . Rational disorder induced intergranular diffusion can benefit phase transition of SiOx /C, benefiting the electrochemical performance. Through a series of quantitative calculations and in situ X-ray diffraction characterizations, this work proposes the rational strategy for the future optimization, thus achieving preferable performance of SiOx /C anode.

19.
Small ; 19(37): e2302644, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37144432

RESUMEN

Silicon oxide (SiOx ), inheriting the high-capacity characteristic of silicon-based materials but possessing superior cycling stability, is a promising anode material for next-generation Li-ion batteries. SiOx is typically applied in combination with graphite (Gr), but the limited cycling durability of the SiOx /Gr composites curtails large-scale applications. In this work, this limited durability is demonstrated in part related to the presence of a bidirectional diffusion at the SiOx /Gr interface, which is driven by their intrinsic working potential differences and the concentration gradients. When Li on the Li-rich surface of SiOx is captured by Gr, the SiOx surface shrinks, hindering further lithiation. The use of soft carbon (SC) instead of Gr can prevent such instability is further demonstrated. The higher working potential of SC avoids bidirectional diffusion and surface compression thus allowing further lithiation. In this scenario, the evolution of the Li concentration gradient in SiOx conforms to its spontaneous lithiation process, benefiting the electrochemical performance. These results highlight the focus on the working potential of carbon as a strategy for rational optimization of SiOx /C composites toward improved battery performance.

20.
Reproduction ; 165(2): R25-R37, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36318634

RESUMEN

In brief: In vivo imaging of gametes and embryos in the oviduct enables new studies of the native processes that lead to fertilization and pregnancy. This review article discusses recent advancements in the in vivo imaging methods and insights which contribute to understanding the oviductal function. Abstract: Understanding the physiological dynamics of gametes and embryos in the fallopian tube (oviduct) has significant implications for managing reproductive disorders and improving assisted reproductive technologies. Recent advancements in imaging of the mouse oviduct in vivo uncovered fascinating dynamics of gametes and embryos in their native states. These new imaging approaches and observations are bringing exciting momentum to uncover the otherwise-hidden processes orchestrating fertilization and pregnancy. For mechanistic investigations, in vivo imaging in genetic mouse models enables dynamic phenotyping of gene functions in the reproductive process. Here, we review these imaging methods, discuss insights recently revealed by in vivo imaging, and comment on emerging directions, aiming to stimulate new in vivo studies of reproductive dynamics.


Asunto(s)
Trompas Uterinas , Oviductos , Embarazo , Humanos , Femenino , Animales , Ratones , Trompas Uterinas/diagnóstico por imagen , Trompas Uterinas/fisiología , Oviductos/fisiología , Células Germinativas , Reproducción , Diagnóstico por Imagen
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