Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 191
Filtrar
Más filtros

Base de datos
Tipo del documento
Intervalo de año de publicación
1.
Digit Health ; 10: 20552076241287842, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39376945

RESUMEN

Purpose: The objective of this study was to assess the accuracy of FreeStyle Libre Pro (FSL-Pro) flash continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI). Methods: A single-arm, single-center prospective study was conducted in the cardiac care unit from January 2021 to September 2023. Patients underwent finger-prick blood glucose (FPBG) testing before breakfast (6:00 am) and after meals (at 9:00, 13:00, 19:00 pm), along with CGM during their hospitalization. Statistical analyses included mean differences (MDs), mean absolute relative difference (MARDs) of blood glucose levels, and hypoglycemia occurrences. A Bland-Altman plot analysis and Pearson correlation were performed. Results: Ninety-seven T2DM and AMI patients underwent CGM for up to 72 h (1142 monitoring point). Mean daily BG, Fasting plasma glucose (FPG) and mean postprandial plasma glucose (PPG) were significantly lower by CGM than by FPBG with an estimated MD of -0.89 mmol/L in BG, -0.88 mmol/L in FPG, and -0.90 mmol/L in PPG, respectively. The maximum effect was mainly in the first day and then the difference was gradually declined (falling range, Day1, -1.24; Day 2, -0.70; Day 3, -0.68, mmol/L, respectively). The incidence rates of hypoglycemia and potential hypoglycemia was 1.57% and 8.5% higher, respectively, in CGM than in FBPG. A Bland-Altman Plot revealed some variability and bias between the two methods of measurement of glucose monitoring (p < .001). Pearson's correlation coefficient demonstrated a significant correlation between the mean BG, FPG, and PPG of CGM and FBPG (Pearson's coefficient: 0.92, 0.87, 0.92, respectively, p < .001). Conclusion: Compared with FPBG, FSL Pro-CGM showed lower mean glucose and higher hypoglycemia detection in T2DM and AMI patients, especially in the first 24 h.

2.
Hum Vaccin Immunother ; 20(1): 2399382, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39254005

RESUMEN

Genetic polymorphisms have been linked to the differential waning of vaccine-induced immunity against COVID-19 following vaccination. Despite this, evidence on the mechanisms behind this waning and its implications for vaccination policy remains limited. We hypothesize that specific gene variants may modulate the development of vaccine-initiated immunity, leading to impaired immune function. This study investigates genetic determinants influencing the sustainability of immunity post-mRNA vaccination through a genome-wide association study (GWAS). Utilizing a hospital-based, test negative case-control design, we enrolled 1,119 participants from the Taiwan Precision Medicine Initiative (TPMI) cohort, all of whom completed a full mRNA COVID-19 vaccination regimen and underwent PCR testing during the Omicron outbreak. Participants were classified into breakthrough and protected groups based on PCR results. Genetic samples were analyzed using SNP arrays with rigorous quality control. Cox regression identified significant single nucleotide polymorphisms (SNPs) associated with breakthrough infections, affecting 743 genes involved in processes such as antigenic protein translation, B cell activation, and T cell function. Key genes identified include CD247, TRPV1, MYH9, CCL16, and RPTOR, which are vital for immune responses. Polygenic risk score (PRS) analysis revealed that individuals with higher PRS are at greater risk of breakthrough infections post-vaccination, demonstrating a high predictability (AUC = 0.787) in validating population. This finding confirms the significant influence of genetic variations on the durability of immune responses and vaccine effectiveness. This study highlights the importance of considering genetic polymorphisms in evaluating vaccine-induced immunity and proposes potential personalized vaccination strategies by tailoring regimens to individual genetic profiles.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Estudios de Casos y Controles , Adulto , Eficacia de las Vacunas , Anciano , Vacunas de ARNm , Taiwán , Vacunación , Medicina de Precisión , Infección Irruptiva
3.
Nat Commun ; 15(1): 7796, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39242635

RESUMEN

Epigenetic modifications are crucial for plant development. EFD (Exine Formation Defect) encodes a SAM-dependent methyltransferase that is essential for the pollen wall pattern formation and male fertility in Arabidopsis. In this study, we find that the expression of DRM2, a de novo DNA methyltransferase in plants, complements for the defects in efd, suggesting its potential de novo DNA methyltransferase activity. Genetic analysis indicates that EFD functions through HB21, as the knockout of HB21 fully restores fertility in efd mutants. DNA methylation and histone modification analyses reveal that EFD represses the transcription of HB21 through epigenetic mechanisms. Additionally, we demonstrate that HB21 directly represses the expression of genes crucial for pollen formation and anther dehiscence, including CalS5, RPG1/SWEET8, CYP703A2 and NST2. Collectively, our findings unveil a double negative regulatory cascade mediated by epigenetic modifications that coordinates anther development, offering insights into the epigenetic regulation of this process.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Metilación de ADN , Epigénesis Genética , Flores , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Polen/crecimiento & desarrollo , Polen/genética , Polen/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Mutación , Plantas Modificadas Genéticamente
4.
J Plast Reconstr Aesthet Surg ; 98: 37-43, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39232370

RESUMEN

PURPOSE: To explore the influencing factors of syncope in patients after plastic surgery, establish a syncope risk prediction model, and verify its accuracy. METHODS: A total of 265 patients undergoing craniomaxillofacial surgery were included and divided into a syncope group and non-syncope group. Multivariate logistic regression analysis was used to screen for risk factors of syncope, and R language was used to establish a risk prediction nomogram of syncope in craniomaxillofacial surgery patients. The Hosmer-Lemeshow goodness-of-fit test was used to evaluate the fit of the model, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of the model. RESULTS: Syncope occurred in 87 of 265 patients (32.8%), and no syncope occurred in 178 patients (67.8%). Multivariate logistic regression analysis revealed statistical differences in age, orthostatic heart rate, orthostatic diastolic blood pressure, syncope history, weight loss history, and medication history between the 2 groups (P < 0.05). A nomogram was constructed for predicting the risk of syncope after craniomaxillofacial surgery, and the Hosmer-Lemeshow goodness-of-fit test proved that the nomogram fitted well (P = 0.431). The results of ROC curve analysis showed that the alignment graph model had high prediction accuracy; the area under the curve was 0.886 (95% confidence interval, 0.8381-0.9332). CONCLUSION: Evaluating the risk of syncope after craniomaxillofacial surgery is helpful and provides guidance for the formulation of preventive strategies.

6.
Food Technol Biotechnol ; 62(2): 254-263, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39045305

RESUMEN

Research background: Preparation of medicinal fungi for experimental purposes usually involves the extraction and determination of the quality and quantity of bioactive compounds prior to the biological experiment. Water, a common polar solvent, is usually used for traditional preparations for consumption. The application of high temperatures during water extraction can affect the chemical composition and functional properties of the extracts. Therefore, the aim of this study is to compare the differences in composition between extracts obtained with heat-assisted and cold water extractions of six selected species of fungi (Lignosus rhinocerus, Ophiocordyceps sinensis, Inonotus obliquus, Antrodia camphorata, Phellinus linteus and Monascus purpureus) and their cytotoxicity against human lung and breast cancer cells. Experimental approach: The extracts obtained with heat-assisted and cold water extraction of six species of fungi were analysed to determine their protein, carbohydrate and phenolic contents. Their cytotoxicity was tested against lung (A549) and breast (MCF-7 and MDA-MB-231) cancer cell lines. The most potent extract was further separated into its protein and non-protein fractions to determine their respective cytotoxicity. Results and conclusions: The cytotoxicity of the different extracts obtained with heat-assisted and cold water extraction varied. Comparing the two extractions, the cold water extraction resulted in a significantly higher yield of proteins (except M. purpureus) and phenolic compounds (except A. camphorata), while the extracts of I. obliquus and M. purpureus obtained with heat-assisted extraction had a significantly higher carbohydrate mass fraction. Notably, the cold water extract of I. obliquus showed cytotoxicity (IC50=(701±35) µg/mL), which was one of the highest of the extracts tested against A549 cells. The cold water extract of I. obliquus was selected for further studies. Our results showed that cold water extracts generally have higher cytotoxicity against selected human cancer cell lines, with the exception of O. sinensis and A. camphorata extracts. Novelty and scientific contribution: This study reports the advantage of cold water extracts of fungi over those obtained with heat-assisted extraction in terms of cytotoxicity against human cancer cell lines and emphasises the role of extraction conditions, particularly heat, in influencing chemical composition and cytotoxic effects.

7.
Esophagus ; 21(4): 456-463, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39020058

RESUMEN

OBJECTIVE: Assessment of the effect of continuous cuff pressure control on airway injury in middle-aged and elderly patients undergoing endoscopic submucosal dissection (ESD). METHOD: A total of 104 eligible middle-aged and elderly patients requiring esophageal ESD from July 2022-September 2023 at the First Affiliated Hospital of Nanchang University were selected and randomly divided into two groups: the group undergoing general anesthesia tracheal intubation with continuous control of cuff pressure after intubation (Group A, n = 51) and the group undergoing general anesthesia tracheal intubation with continuous monitoring without control of cuff pressure (Group B, n = 53). After endotracheal intubation in Group A, under the guidance of an automatic cuff pressure controller, the air was used to inflate the tracheal cuff until the cuff pressure was 25-30cmH2O. The cuff pressure after intubation was recorded, and then the cuff pressure parameters were directly adjusted in the range of 25-30cmH2O until tracheal extubation after the operation. After endotracheal intubation, patients in Group B inflated the tracheal cuff with clinical experience, then monitored and recorded the cuff pressure with a handheld cuff manometer and instructed the cuff not to be loosened after being connected to the handheld cuff manometer-continuous monitoring until the tracheal extubation, but without any cuff pressure regulation. The patients of the two groups performed esophageal ESD. The left recumbent position was taken before the operation, and the cuff's pressure was recorded. Then, insert the gastrointestinal endoscope to find the lesion site and perform appropriate CO2 inflation to display the diseased esophageal wall for surgical operation fully. After determining the location, the cuff pressure of the two groups was recorded when the cuff pressure was stable. After the operation, the upper gastrointestinal endoscope was removed and the cuff pressure of the two groups was recorded. Postoperative airway injury assessment was performed in both groups, and the incidence of sore throat, hoarseness, cough, and blood in sputum was recorded. The incidence of postoperative airway mucosal injury was also observed and recorded in both groups: typical, episodic congestion spots and patchy local congestion. RESULT: The incidence of normal airway mucosa in Group A was higher than that in Group B (P < 0.05). In comparison, the incidence of occasional hyperemia and local plaque congestion in Group A was lower than in Group B (P < 0.05). CONCLUSION: Continuous cuff pressure control during operation can reduce airway injury in patients with esophageal ESD and accelerate their early recovery after the operation.


Asunto(s)
Resección Endoscópica de la Mucosa , Intubación Intratraqueal , Presión , Humanos , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/métodos , Intubación Intratraqueal/instrumentación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Presión/efectos adversos , Neoplasias Esofágicas/cirugía , Anestesia General/métodos , Anestesia General/efectos adversos , Esófago/cirugía , Esófago/lesiones , Manometría/métodos , Esofagoscopía/métodos , Esofagoscopía/efectos adversos
8.
J Integr Neurosci ; 23(5): 103, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38812389

RESUMEN

Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.


Asunto(s)
Hipoxia-Isquemia Encefálica , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Recién Nacido , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Antioxidantes/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología
9.
Med Sci Monit ; 30: e945269, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38808453

RESUMEN

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Haijin Huang, Cuicui Hu, Lin Xu, Xiaoping Zhu, Lili Zhao, Jia Min. The Effects of Hesperidin on Neuronal Apoptosis and Cognitive Impairment in the Sevoflurane Anesthetized Rat are Mediated Through the PI3/Akt/PTEN and Nuclear Factor-kappaB (NF-kappaB) Signaling Pathways. Med Sci Monit, 2020; 26: e920522. DOI: 10.12659/MSM.920522.


Asunto(s)
Apoptosis , Disfunción Cognitiva , Hesperidina , FN-kappa B , Neuronas , Fosfohidrolasa PTEN , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Sevoflurano , Transducción de Señal , Animales , Sevoflurano/farmacología , Apoptosis/efectos de los fármacos , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Fosfohidrolasa PTEN/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Disfunción Cognitiva/metabolismo , Ratas , Hesperidina/farmacología , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo
10.
Toxicol Res (Camb) ; 13(2): tfae041, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38617713

RESUMEN

Aim: To explore the effect of Dexmedetomidine (DEX) on lung injury in patients undergoing One-lung ventilation (OLV). Methods: Esophageal cancer patients undergoing general anesthesia with OLV were randomly divided into the DEX group and control group, with 30 cases in each group. Mean arterial pressure (MAP), heart rate (HR), arterial partial pressure of oxygen (PO2), and arterial partial pressure of nitrogen dioxide (PCO2) were recorded at the time points after anesthesia induction and before OLV (T1), OLV 30 min (T2), OLV 60 min (T3), OLV 120 min (T4), OLV end before (T5) and before leaving the room (T6) in both groups. Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was applied to detect the levels of CC16 mRNA. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CC16 protein levels. The content of malondialdehyde (MDA) in serum was determined by thio barbituric acid (TBA) method. ELISA was used to measure the concentrations of TNF-α (tumor necrosis factor-alpha)/and IL-6 (interleukin 6). Results: DEX treatment slowed down HR at time points T1-T6 and increased PO2 and PCO2 at time points T2-T5 compared with the control group. Moreover, at time points T2-T6, DEX treatment reduced the levels of club cell secretory protein-16 (CC16) mRNA and serum CC16 protein levels. Furthermore, DEX treatment caused the reduction of MDA, TNF-α and IL-6 concentrations in serum of patients. Conclusion: During the OLV process, DEX could reduce serum CC16 protein levels, inhibit inflammatory reactions and oxidative stress, and improve oxygenation index, indicating a protective effect on lung injury during OLV.

11.
J Ethnopharmacol ; 328: 118073, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38513780

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal mushrooms belonging to the Lignosus spp., colloquially known as Tiger Milk mushrooms (TMMs), are used as traditional medicine by communities across various regions of China and Southeast Asia to enhance immunity and to treat various diseases. At present, three Lignosus species have been identified in Malaysia: L. rhinocerus, L. tigris, and L. cameronensis. Similarities in their macroscopic morphologies and the nearly indistinguishable appearance of their sclerotia often lead to interchangeability between them. Hence, substantiation of their traditional applications via identification of their individual bioactive properties is imperative in ensuring that they are safe for consumption. L. tigris was first identified in 2013. Thus far, studies on L. tigris cultivar sclerotia (Ligno TG-K) have shown that it possesses significant antioxidant activities and has greater antiproliferative action against selected cancer cells in vitro compared to its sister species, L. rhinocerus TM02®. Our previous genomics study also revealed significant genetic dissimilarities between them. Further omics investigations on Ligno TG-K hold immense potential in facilitating the identification of its bioactive compounds and their associated bioactivities. AIM OF STUDY: The overall aim of this study was to investigate the gene expression profile of Ligno TG-K via de novo RNA-seq and pathway analysis. We also aimed to identify highly expressed genes encoding compounds that contribute to its cytotoxic and antioxidant properties, as well as perform a comparative transcriptomics analysis between Ligno TG-K and its sister species, L. rhinocerus TM02®. MATERIALS AND METHODS: Total RNA from fresh 3-month-old cultivated L. tigris sclerotia (Ligno TG-K) was extracted and analyzed via de novo RNA sequencing. Expressed genes were analyzed using InterPro and NCBI-Nr databases for domain identification and homology search. Functional categorization based on gene functions and pathways was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Clusters of Orthologous Genes (COG) databases. Selected genes were subsequently subjected to phylogenetic analysis. RESULTS: Our transcriptomics analysis of Ligno TG-K revealed that 68.06% of its genes are expressed in the sclerotium; 80.38% of these were coding transcripts. Our analysis identified highly expressed transcripts encoding proteins with prospective medicinal properties. These included serine proteases (FPKM = 7356.68), deoxyribonucleases (FPKM = 3777.98), lectins (FPKM = 3690.87), and fungal immunomodulatory proteins (FPKM = 2337.84), all of which have known associations with anticancer activities. Transcripts linked to proteins with antioxidant activities, such as superoxide dismutase (FPKM = 1161.69) and catalase (FPKM = 1905.83), were also highly expressed. Results of our sequence alignments revealed that these genes and their orthologs can be found in other mushrooms. They exhibit significant sequence similarities, suggesting possible parallels in their anticancer and antioxidant bioactivities. CONCLUSION: This study is the first to provide a reference transcriptome profile of genes expressed in the sclerotia of L. tigris. The current study also presents distinct COG profiles of highly expressed genes in Ligno TG-K and L. rhinocerus TM02®, highlighting that any distinctions uncovered may be attributed to their interspecies variations and inherent characteristics that are unique to each species. Our findings suggest that Ligno TG-K contains bioactive compounds with prospective medicinal properties that warrant further investigations. CLASSIFICATION: Systems biology and omics.


Asunto(s)
Agaricales , Polyporaceae , Antioxidantes/metabolismo , Transcriptoma , RNA-Seq , Agaricales/genética , Filogenia , Estudios Prospectivos , Polyporaceae/genética
12.
Acta Pharmacol Sin ; 45(6): 1305-1315, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38383757

RESUMEN

Histone deacetylase inhibitors (HDACis) are important drugs for cancer therapy, but the indistinct resistant mechanisms of solid tumor therapy greatly limit their clinical application. In this study we conducted HDACi-perturbated proteomics and phosphoproteomics analyses in HDACi-sensitive and -resistant cell lines using a tandem mass tag (TMT)-based quantitative proteomic strategy. We found that the ribosome biogenesis proteins MRTO4, PES1, WDR74 and NOP16 vital to tumorigenesis might regulate the tumor sensitivity to HDACi. By integrating HDACi-perturbated protein signature with previously reported proteomics and drug sensitivity data, we predicted and validated a series of drug combination pairs potentially to enhance the sensitivity of HDACi in diverse solid tumor. Functional phosphoproteomic analysis further identified the kinase PDK1 and ROCK as potential HDACi-resistant signatures. Overall, this study reveals the potential HDACi-resistant signatures and may provide promising drug combination strategies to attenuate the resistance of solid tumor to HDACi.


Asunto(s)
Resistencia a Antineoplásicos , Inhibidores de Histona Desacetilasas , Neoplasias , Proteómica , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico
13.
Neurochem Res ; 49(1): 29-37, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37725293

RESUMEN

As one of the most common neuropathic disorders, neuropathic pain often has a negative impact on patients with persistent pain, mood disorders and sleep disturbances. Currently, neuropathic pain is not treated with any specific drug, instead, drugs for other diseases are used as replacements in clinics, but most have adverse effects. In recent years, the role of spinal cord microglia in the pathogenesis of neuropathic pain has been widely recognized, and they are being explored as potential therapeutic targets. Spinal microglia are known to be involved in the pathogenic mechanisms of neuropathic pain through purine signaling, fractalkine signaling, and p38 MAPK signaling. Exercise is a safe and effective treatment, and numerous studies have demonstrated its effectiveness in improving neurological symptoms. Nevertheless, it remains unclear what the exact molecular mechanism is. This review summarized the specific molecular mechanisms of exercise in alleviating neuropathic pain by mediating the activity of spinal microglia and maintaining the phenotypic homeostasis of spinal microglia through purine signaling, fractalkine signaling and p38 MAPK signaling. In addition, it has been proposed that different intensities and types of exercise affect the regulation of the above-mentioned signaling pathways differently, providing a theoretical basis for the improvement of neuropathic pain through exercise.


Asunto(s)
Microglía , Neuralgia , Ratas , Animales , Humanos , Microglía/metabolismo , Quimiocina CX3CL1/metabolismo , Ratas Sprague-Dawley , Neuralgia/metabolismo , Médula Espinal/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Purinas/metabolismo
14.
Neural Regen Res ; 19(4): 881-886, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37843224

RESUMEN

Brain functional impairment after stroke is common; however, the molecular mechanisms of post-stroke recovery remain unclear. It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke. Mounting evidence suggests that axonal regeneration and angiogenesis, the major forms of brain plasticity responsible for post-stroke recovery, diminished with advanced age. Previous studies suggest that Ras-related C3 botulinum toxin substrate (Rac) 1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model. Here, we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged (male, 18 to 22 months old C57BL/6J) brain after ischemic stroke. We found that as mice aged, Rac1 expression declined in the brain. Delayed overexpression of Rac1, using lentivirus encoding Rac1 injected day 1 after ischemic stroke, promoted cognitive (assessed using novel object recognition test) and sensorimotor (assessed using adhesive removal tests) recovery on days 14-28. This was accompanied by the increase of neurite and proliferative endothelial cells in the peri-infarct zone assessed by immunostaining. In a reverse approach, pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells. Furthermore, Rac1 inhibition reduced the activation of p21-activated kinase 1, the protein level of brain-derived neurotrophic factor, and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke. Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

15.
Commun Biol ; 6(1): 920, 2023 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-37684342

RESUMEN

Burkholderia pseudomallei is a highly versatile pathogen with ~25% of its genome annotated to encode hypothetical proteins. One such hypothetical protein, BPSL1038, is conserved across seven bacterial genera and 654 Burkholderia spp. Here, we present a 1.55 Å resolution crystal structure of BPSL1038. The overall structure folded into a modified ßαßßαßα ferredoxin fold similar to known Cas2 nucleases. The Cas2 equivalent catalytic aspartate (D11) pairs are conserved in BPSL1038 although B. pseudomallei has no known CRISPR associated system. Functional analysis revealed that BPSL1038 is a nuclease with endonuclease activity towards double-stranded DNA. The DNase activity is divalent ion independent and optimum at pH 6. The concentration of monovalent ions (Na+ and K+) is crucial for nuclease activity. An active site with a unique D11(X20)SST motif was identified and proposed for BPSL1038 and its orthologs. Structure modelling indicates the catalytic role of the D11(X20)SST motif and that the arginine residues R10 and R30 may interact with the nucleic acid backbone. The structural similarity of BPSL1038 to Cas2 proteins suggests that BPSL1038 may represent a sub-family of nucleases that share a common ancestor with Cas2.


Asunto(s)
Burkholderia pseudomallei , Burkholderia pseudomallei/genética , Arginina , Ácido Aspártico , Catálisis , Endonucleasas
17.
Front Endocrinol (Lausanne) ; 14: 1199960, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37538793

RESUMEN

Background: Acute myocardial infarction (AMI) poses a significant threat to cardiovascular diseases (CVDs), leading to a high risk of heart failure (HF) and cardiovascular death. Growing evidence has unveiled the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors to improve cardiovascular outcomes in patients with CVD regardless of diabetes, but there is limited evidence in AMI patients. Furthermore, it is controversial whether the effects can be ascribed to the amelioration of left ventricular (LV) function, which further complicates the understanding of their underlying mechanism. Methods: This study is a prospective, phase IV, open-label, parallel group, single-center trial conducted in a large tertiary teaching hospital in China. A total of 120 patients with AMI and type 2 diabetes mellitus (T2DM) will be included. Those who received SGLT2 inhibitors are considered as the experimental group, and those taking other antidiabetic agents are considered as the control group. The primary outcome is change in LV end-systolic volume index (LVESVi) measured by cardiac magnetic resonance (CMR) imaging from baseline during 1-year follow-up period. Secondary outcomes include other LV parameters such as LV mass, LV volume, and LV ejection fraction (EF); quality of life and functional capacity such as Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) and EuroQol-5 dimension (EQ-5D); biomarkers associated with diagnostic parameters of AMI and possible mechanisms on cardiovascular protection, such as creatine kinase, troponin T (TnT) level, troponin I (TnI) level, soluble suppression of tumorigenicity-2 (sST2), galectin-3 (Gal-3), fibroblast growth factor 21 (FGF21), and microRNA (miRNA) level. Discussion: This study aims to investigate whether SGLT2 inhibitors could improve LV function by measuring CMR, quality of life, and functional capacity in patients with AMI in real-world settings, providing evidence on the underlying mechanism of SGLT2 inhibitors on cardioprotection. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=173672, identifier ChiCTR2200065792.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Estudios Prospectivos , Calidad de Vida , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
18.
Appl Microbiol Biotechnol ; 107(19): 6057-6070, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37526695

RESUMEN

Poly(butylene adipate-co-terephthalate) (PBAT), a promising biodegradable aliphatic-aromatic copolyester material, can be applied as an alternative material to reduce the adverse effects of conventional plastics. However, the degradation of PBAT plastics in soil is time-consuming, and effective PBAT-degrading microorganisms have rarely been reported. In this study, the biodegradation properties of PBAT by an elite fungal strain and related mechanisms were elucidated. Four PBAT-degrading fungal strains were isolated from farmland soils, and Purpureocillium lilacinum strain BA1S showed a prominent degradation rate. It decomposed approximately 15 wt.% of the PBAT films 30 days after inoculation. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and Liquid chromatography mass spectrometry (LC‒MS) were conducted to analyze the physicochemical properties and composition of the byproducts after biodegradation. In the presence of PBAT, the lipolytic enzyme activities of BA1S were remarkably induced, and its cutinase gene was also significantly upregulated. Of note, the utilization of PBAT in BA1S cells was closely correlated with intracellular cytochrome P450 (CYP) monooxygenase. Furthermore, CreA-mediated carbon catabolite repression was confirmed to be involved in regulating PBAT-degrading hydrolases and affected the degradation efficiency. This study provides new insight into the degradation of PBAT by elite fungal strains and increases knowledge on the mechanism, which can be applied to control the biodegradability of PBAT films in the future. KEY POINTS: • Purpureocillium lilacinum strain BA1S was isolated from farmland soils and degraded PBAT plastic films at a prominent rate. • The lipolytic enzyme activities of strain BA1S were induced during coculture with PBAT, and the cutinase gene was significantly upregulated during PBAT degradation. • CreA-mediated carbon catabolite repression of BA1S plays an essential role in regulating the expression of PBAT-degrading hydrolases.


Asunto(s)
Plásticos , Poliésteres , Poliésteres/metabolismo , Adipatos , Suelo , Hidrolasas
19.
Front Aging Neurosci ; 15: 1123089, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37342357

RESUMEN

Purpose: To compare the effects of remimazolam and dexmedetomidine on early postoperative cognitive dysfunction (POCD) in aged gastric cancer patients. Methods: From June to December 2022, 104 elderly patients (aged 65-80 years) received laparoscopic radical resection of gastric cancer at the First Affiliated Hospital of Nanchang University. Using the random number table approach, the patients were separated into three groups: remimazolam (Group R), dexmedetomidine (Group D), and saline (Group C). The primary outcome was the incidence of POCD, and secondary outcomes included TNF-α and S-100ß protein concentrations, hemodynamics, VAS scores, anesthesia recovery indicators, and the occurrence of adverse events within 48 h postoperatively. Results: At 3 and 7 days after surgery, there were no statistically significant differences in the incidence of POCD, the MMSE and MoCA scores between groups R and D (p > 0.05). However, compared to the saline group, both groups had higher MMSE and MoCA scores and decreased incidences of POCD. These differences were statistically significant (p < 0.05). Between group R and group D, there were no statistically significant changes (p > 0.05) in the levels of TNF-α and S-100ß protein at the three time points (at the end of the surgery, 1 day later, and 3 days later). Even though neither group's concentration of the two factors was as high as that of the saline group, the differences were statistically significant (p < 0.05). At all three time points-following induction (T2), 30 min into the operation (T3), and at the conclusion of the surgery (T4)-the heart rate and blood pressure in group R were greater than those in groups D and C. Statistics showed that the differences were significant (p < 0.05). The incidence of intraoperative hypotension was highest in group D and lowest in group R (p < 0.05). The dose of propofol and remifentanil, group C > group R > group D. Extubation and PACU residence times did not differ statistically significantly (p > 0.05) between the three groups. There was no significant difference in VAS scores between groups R and D after 24 h postoperatively (p > 0.05), although both had lower scores than group C, and the difference was statistically significant (p < 0.05). The VAS scores between the three groups at 72 h (T6) and 7 days (T7) were not statistically significant (p > 0.05). Adverse reactions such as respiratory depression, hypotension, bradycardia, agitation, drowsiness, and nausea and vomiting had the lowest incidence in group R and the highest incidence in group C (p < 0.05). Conclusion: Remimazolam is similarly beneficial as dexmedetomidine in lowering the incidence of early POCD in aged patients after radical gastric cancer resection, probably due to reduced inflammatory response.

20.
Int J Low Extrem Wounds ; : 15347346231183740, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37376875

RESUMEN

INTRODUCTION: Diabetes foot disease (DFD) contributes to poor quality of life, clinical and economic burden. Multidisciplinary diabetes foot teams provide prompt access to specialist teams thereby improving limb salvage. We present a 17-year review of an inpatient multidisciplinary clinical care path (MCCP) for DFD in Singapore. METHODS: This was a retrospective cohort study of patients admitted for DFD and enrolled in our MCCP to a 1700-bed university hospital from 2005 to 2021. RESULTS: There were 9279 patients admitted with DFD with a mean of 545 (±119) admissions per year. The mean age was 64 (±13.3) years, 61% were Chinese, 18% Malay and 17% Indian. There was a higher proportion of Malay (18%) and Indian (17%) patients compared to the country's ethnic composition. A third of the patients had end stage renal disease and prior contralateral minor amputation. There was a reduction in inpatient major lower extremity amputation (LEA) from 18.2% in 2005 to 5.4% in 2021 (odds ratio 0.26, 95% confidence interval 0.16-0.40, P < .001) which was the lowest since pathway inception. Mean time from admission to first surgical intervention was 2.8 days and mean time from decision for revascularization to procedure was 4.8 days. The major-to-minor amputation rate reduced from 1.09 in 2005 to 0.18 in 2021, reflecting diabetic limb salvage efforts. Mean and median length of stay (LOS) for patients in the pathway was 8.2 (±14.9) and 5 (IQR = 3) days, respectively. There was a gradual trend of increase in the mean LOS from 2005 to 2021. Inpatient mortality and readmission rate was stable at 1% and 11%. CONCLUSION: Since the institution of a MCCP, there was a significant improvement in major LEA rate. An inpatient multidisciplinary diabetic foot care path helped to improve care for patients with DFD.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA