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1.
Am J Physiol Cell Physiol ; 326(2): C400-C413, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38105755

RESUMEN

Kidney fibrosis is a prominent pathological feature of hypertensive kidney diseases (HKD). Recent studies have highlighted the role of ubiquitinating/deubiquitinating protein modification in kidney pathophysiology. Ovarian tumor domain-containing protein 6 A (OTUD6A) is a deubiquitinating enzyme involved in tumor progression. However, its role in kidney pathophysiology remains elusive. We aimed to investigate the role and underlying mechanism of OTUD6A during kidney fibrosis in HKD. The results revealed higher OTUD6A expression in kidney tissues of nephropathy patients and mice with chronic angiotensin II (Ang II) administration than that from the control ones. OTUD6A was mainly located in tubular epithelial cells. Moreover, OTUD6A deficiency significantly protected mice against Ang II-induced kidney dysfunction and fibrosis. Also, knocking OTUD6A down suppressed Ang II-induced fibrosis in cultured tubular epithelial cells, whereas overexpression of OTUD6A enhanced fibrogenic responses. Mechanistically, OTUD6A bounded to signal transducer and activator of transcription 3 (STAT3) and removed K63-linked-ubiquitin chains to promote STAT3 phosphorylation at tyrosine 705 position and nuclear translocation, which then induced profibrotic gene transcription in epithelial cells. These studies identified STAT3 as a direct substrate of OTUD6A and highlighted the pivotal role of OTUD6A in Ang II-induced kidney injury, indicating OTUD6A as a potential therapeutic target for HKD.NEW & NOTEWORTHY Ovarian tumor domain-containing protein 6 A (OTUD6A) knockout mice are protected against angiotensin II-induced kidney dysfunction and fibrosis. OTUD6A promotes pathological kidney remodeling and dysfunction by deubiquitinating signal transducer and activator of transcription 3 (STAT3). OTUD6A binds to and removes K63-linked-ubiquitin chains of STAT3 to promote its phosphorylation and activation, and subsequently enhances kidney fibrosis.


Asunto(s)
Hipertensión Renal , Nefritis , Neoplasias Ováricas , Humanos , Ratones , Animales , Femenino , Angiotensina II/farmacología , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Riñón/metabolismo , Hipertensión Renal/metabolismo , Hipertensión Renal/patología , Células Epiteliales/metabolismo , Fibrosis , Neoplasias Ováricas/metabolismo , Ubiquitinas/metabolismo , Ratones Endogámicos C57BL
2.
J Transl Med ; 21(1): 328, 2023 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-37198593

RESUMEN

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent and fatal oral cancers. Mitochondria-targeting therapies represent promising strategies against various cancers, but their applications in treating OSCC are limited. Alantolactone (ALT) possesses anticancer properties and also regulates mitochondrial events. In this study, we explored the effects of ALT on OSCC and the related mechanisms. METHODS: The OSCC cells were treated with varying concentrations and duration of ALT and N-Acetyl-L-cysteine (NAC). The cell viability and colony formation were assessed. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double staining. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production and DAF-FM DA to investigate reactive nitrogen species (RNS) level. Mitochondrial function was reflected by mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. KEGG enrichment analyses determined the mitochondrial-related hub genes involved in OSCC progression. Dynamin-related protein 1 (Drp1) overexpression plasmids were further transfected into the cells to analyze the role of Drp1 in OSCC progression. Immunohistochemistry staining and western blot verified the expression of the protein. RESULTS: ALT exerted anti-proliferative and pro-apoptosis effects on OSCC cells. Mechanistically, ALT elicited cell injury by promoting ROS production, mitochondrial membrane depolarization, and ATP depletion, which were reversed by NAC. Bioinformatics analysis showed that Drp1 played a crucial role in OSCC progression. OSCC patients with low Drp1 expression had a higher survival rate. The OSCC cancer tissues presented higher phosphorylated-Drp1 and Drp1 levels than the normal tissues. The results further showed that ALT suppressed Drp1 phosphorylation in OSCC cells. Moreover, Drp1 overexpression abolished the reduced Drp1 phosphorylation by ALT and promoted the cell viability of ALT-treated cells. Drp1 overexpression also reversed the mitochondrial dysfunction induced by ALT, with decreased ROS production, and increased mitochondrial membrane potential and ATP level. CONCLUSIONS: ALT inhibited proliferation and promoted apoptosis of oral squamous cell carcinoma cells via impairment of mitochondrial homeostasis and regulation of Drp1. The results provide a solid basis for ALT as a therapeutic candidate for treating OSCC, with Drp1 being a novel therapeutic target in treating OSCC.


Asunto(s)
Dinaminas , Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Adenosina Trifosfato/metabolismo , Apoptosis , Línea Celular Tumoral , Regulación hacia Abajo , Dinaminas/metabolismo , Dinaminas/farmacología , Dinaminas/uso terapéutico , Mitocondrias/metabolismo , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
3.
Calcif Tissue Int ; 112(5): 543-562, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36877247

RESUMEN

Mounting evidence has supported osteoporosis (OP) as a metabolic disorder. Recent metabolomics studies have discovered numerous metabolites related to bone mineral density (BMD). However, the causal effects of metabolites on BMD at distinct sites remained underexplored. Leveraging genome-wide association datasets, we conducted two-sample Mendelian randomization (MR) analyses to investigate the causal relationship between 486 blood metabolites and bone mineral density at five skeletal sites including heel (H), total body (TB), lumbar spine (LS), femoral neck (FN), and ultra-distal forearm (FA). Sensitivity analyses were performed to test the presence of the heterogeneity and the pleiotropy. To exclude the influences of reverse causation, genetic correlation, and linkage disequilibrium (LD), we further performed reverse MR, linkage disequilibrium regression score (LDSC), and colocalization analyses. In the primary MR analyses, 22, 10, 3, 7, and 2 metabolite associations were established respectively for H-BMD, TB-BMD, LS-BMD, FN-BMD, and FA-BMD at the nominal significance level (IVW, P < 0.05) and passing sensitivity analyses. Among these, one metabolite, androsterone sulfate showed a strong effect on four out of five BMD phenotypes (Odds ratio [OR] for H-BMD = 1.045 [1.020, 1.071]; Odds ratio [OR] for TB-BMD = 1.061 [1.017, 1.107]; Odds ratio [OR] for LS-BMD = 1.088 [1.023, 1.159]; Odds ratio [OR] for FN-BMD = 1.114 [1.054, 1.177]). Reverse MR analysis provided no evidence for the causal effects of BMD measurements on these metabolites. Colocalization analysis have found that several metabolite associations might be driven by shared genetic variants such as mannose for TB-BMD. This study identified some metabolites causally related to BMD at distinct sites and several key metabolic pathways, which shed light on predictive biomarkers and drug targets for OP.


Asunto(s)
Densidad Ósea , Osteoporosis , Humanos , Densidad Ósea/genética , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Osteoporosis/genética , Osteoporosis/metabolismo , Metaboloma , Polimorfismo de Nucleótido Simple
4.
J Clin Periodontol ; 50(7): 964-979, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36940707

RESUMEN

AIM: To investigate whether silibinin impacts diabetic periodontitis (DP) via mitochondrial regulation. MATERIALS AND METHODS: In vivo, rats were divided into control, diabetes, DP and DP combined with silibinin groups. Diabetes and periodontitis were induced by streptozocin and silk ligation, respectively. Bone turnover was evaluated by microcomputed tomography, histology and immunohistochemistry. In vitro, human periodontal ligament cells (hPDLCs) were exposed to hydrogen peroxide (H2 O2 ) with or without silibinin. Osteogenic function was analysed by Alizarin Red and alkaline phosphatase staining. Mitochondrial function and biogenesis were investigated by mitochondrial imaging assays and quantitative polymerase chain reaction. Activator and lentivirus-mediated knockdown of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha (PGC-1α), a critical regulator of mitochondria biogenesis, was used to explore the mitochondrial mechanisms. RESULTS: Silibinin attenuated periodontal destruction and mitochondrial dysfunction and enhanced mitochondrial biogenesis and PGC-1α expression in rats with DP. Meanwhile, silibinin promoted cell proliferation, osteogenesis and mitochondrial biogenesis and increased the PGC-1α level in hPDLCs exposed to H2 O2 . Silibinin also protected PGC-1α from proteolysis in hPDLCs. Furthermore, both silibinin and activator of PGC-1α ameliorated cellular injury and mitochondrial abnormalities in hPDLCs, while knockdown of PGC-1α abolished the beneficial effect of silibinin. CONCLUSIONS: Silibinin attenuated DP through the promotion of PGC-1α-dependent mitochondrial biogenesis.


Asunto(s)
Diabetes Mellitus Tipo 1 , Factores de Transcripción , Ratas , Animales , Humanos , Factores de Transcripción/metabolismo , Silibina/farmacología , Silibina/uso terapéutico , Biogénesis de Organelos , Microtomografía por Rayos X , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo
5.
Comput Commun ; 206: 101-109, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37197298

RESUMEN

Federated learning is a machine learning method that can break the data island. Its inherent privacy-preserving property has an important role in training medical image models. However, federated learning requires frequent communication, which incur high communication costs. Moreover, the data is heterogeneous due to different users' preferences, which may degrade the performance of models. To address the problem of statistical heterogeneity, we propose FedUC, an algorithm to control the uploaded updates for federated learning, where a client scheduling method is made on the basis of weight divergence, update increment, and loss. We also balance the local data of the clients by image augmentation to mitigate the impact of the non-independently identically distribution. The server assigns compression thresholds to the clients based on the weight divergence and update increment of the models for gradient compression to reduce the wireless communication costs. Finally, based on the weight divergence, update increment and accuracy, the server dynamically assigns weights to the model parameters for the aggregation. Simulation and analysis utilizing a publicly available chest disease dataset containing COVID-19 are compared with existing federated learning methods. Experimental results show that our proposed strategy has better training performance in improving model accuracy and reducing wireless communication costs.

6.
BMC Anesthesiol ; 22(1): 231, 2022 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-35854215

RESUMEN

BACKGROUND: To use gastric ultrasound to evaluate function and to determine the start time of enteral nutrition (EN) in patients with acute gastrointestinal injury (AGI). METHODS: We reviewed records from 105 patients who suffered AGI levels two (AGI II). We recorded several data points, including ultrasonographic transverse area of gastric antrum (CSA), left descending colonic or right ascending colonic diameter (Diam), peristatic frequency (Peri), EN start time, EN dose, prealbumin (PA), and EN complications. The recovery of intestinal function after EN treatment was judged as success. If there was EN treatment complication, this was judged as failure. We analyzed the changes in gastrointestinal function after EN treatment, to determine feeding time. RESULTS: There were 69 patients in the successful group, and 36 in the failure group. There were no significant differences between the two groups in age, intra abdominal pressure (IAP), APACHE II, PA and disease composition (p > 0.05).There were significant differences in terms of EN startup time, CSA, Diam, Peri, and PA, between the EN success and failure groups. We found IAP does not reflect gastrointestinal function;CSA ≤ 9cm2, Diam ≤ 2.9 cm, Peri > 3 bpm, indicated that the three indexes could reflect the recovery of gastrointestinal function. Receiver operating curve analysis showed that combined CSA, Diam, Peri evaluation determined the best time to start EN. CONCLUSIONS: Monitoring gastric antrum transversal area, colonic diameter, colonic peristatic frequency using ultrasound can guide the timing of initiation of enteral nutrition treatment.


Asunto(s)
Nutrición Enteral , Unidades de Cuidados Intensivos , APACHE , Enfermedad Crítica/terapia , Nutrición Enteral/efectos adversos , Humanos , Ultrasonografía
7.
Ann Plast Surg ; 89(1): 59-62, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35502975

RESUMEN

OBJECTIVE: Tai Chi is an ancient philosophy used to explain the universe. The Tai Chi symbol is represented by Yin/Yang fishes. The authors describe a novel radial forearm flap (RFF) design for the reconstruction of circular defects based on the Tai Chi symbol. METHODS: Eleven consecutive patients with craniofacial skin or mucus defects underwent reconstruction with a Tai Chi RFF. Patient perioperative and follow-up information was collected. RESULTS: The diameter of the Tai Chi RFF was 5 to 6 cm. All flaps healed uneventfully without ischemic problems, and all donor site defects were closed primarily without skin grafts. Remarkably, 2 patients received a tattoo to mark the Tai Chi symbol and greatly appreciate the shape of the flap. CONCLUSIONS: The Tai Chi flap is an economically friendly flap design that can be used to prevent skin grafts while providing psychological comfort to patients.


Asunto(s)
Procedimientos de Cirugía Plástica , Taichi Chuan , Antebrazo/cirugía , Humanos , Trasplante de Piel , Colgajos Quirúrgicos/cirugía
8.
Am J Physiol Endocrinol Metab ; 319(1): E34-E42, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32228319

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) amplifies the risk of various liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis, and ultimately hepatocellular carcinoma. Accumulating evidence suggests the involvement of aberrant microRNAs (miRNAs or miRs) in the activation of cellular stress, inflammation, and fibrogenesis in hepatic cells at different stages of NAFLD and liver fibrosis. Here, we explored the potential role of miR-130b-5p in the pathogenesis of NAFLD, including lipid accumulation and insulin resistance, as well as the underlying mechanism. Initially, the expression of miR-130b-5p and insulin-like growth factor binding protein 2 (IGFBP2) was examined in the established high-fat diet-induced NAFLD mouse models. Then, the interaction between miR-130b-5p and IGFBP2 was validated using dual luciferase reporter assay. The effects of miR-130b-5p and IGFBP2 on lipid accumulation and insulin resistance, as well as the AKT pathway-related proteins, were evaluated using gain or loss-of-function approaches. miR-130b-5p was upregulated, and IGFBP2 was downregulated in liver tissues of NAFLD mice. miR-130b-5p targeted IGFBP2 and downregulated its expression. MiR-130b-5p inhibition or IGFBP2 overexpression reduced the expression of SREBP-1, LXRα, ChREBP, stearoyl CoA desaturase 1, acetyl CoA carboxylase 1, and fatty acid synthase, and levels of fasting blood glucose, fasting insulin, and homeostasis model assessment-insulin resistance, while increasing the ratio of p-AKT/AKT in NAFLD mice. Overall, downregulation of miR-130b-5p can prevent hepatic lipid accumulation and insulin resistance in NAFLD by activating IGFBP2-dependent AKT pathway, highlighting the potential use of anti-miR-130b-5p as therapeutic approaches for the prevention and treatment of NAFLD.


Asunto(s)
Dieta Alta en Grasa , Resistencia a la Insulina/genética , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Hígado/metabolismo , MicroARNs/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Acetil-CoA Carboxilasa/genética , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Glucemia/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Acido Graso Sintasa Tipo I/genética , Expresión Génica , Regulación de la Expresión Génica , Insulina/metabolismo , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Metabolismo de los Lípidos/genética , Receptores X del Hígado/genética , Ratones , MicroARNs/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Estearoil-CoA Desaturasa/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética
9.
J Cell Mol Med ; 23(9): 5895-5906, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31287224

RESUMEN

Gestational diabetes mellitus (GDM) is known as different degree glucose intolerance that is initially identified during pregnancy. MicroRNAs (miRs) may be a potential candidate for treatment of GDM. Herein, we suggested that miR-351 could be an inhibitor in the progression of GDM via the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Microarray analysis was used to identify differentially expressed genes and predict miRs regulating flotillin 2 (FLOT2). Target relationship between miR-351 and FLOT2 was verified. Gestational diabetes mellitus mice were treated with a series of mimic, inhibitor and small interfering RNA to explore the effect of miR-351 on insulin resistance (IR), cell apoptosis in pancreatic tissues and liver gluconeogenesis through evaluating GDM-related biochemical indexes, as well as expression of miR-351, FLOT2, PI3K/AKT pathway-, IR- and liver gluconeogenesis-related genes. MiR-351 and FLOT2 were reported to be involved in GDM. FLOT2 was the target gene of miR-351. Gestational diabetes mellitus mice exhibited IR and liver gluconeogenesis, up-regulated FLOT2, activated PI3K/AKT pathway and down-regulated miR-351 in liver tissues. Additionally, miR-351 overexpression and FLOT2 silencing decreased the levels of FLOT2, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fasting blood glucose, fasting insulin, total cholesterol, triglyceride, glyeosylated haemoglobin and homeostasis model of assessment for IR index (HOMA-IR), extent of PI3K and AKT phosphorylation, yet increased the levels of HOMA for islet ß-cell function, HOMA for insulin sensitivity index and glucose transporter 2 expression, indicating reduced cell apoptosis in pancreatic tissues and alleviated IR and liver gluconeogenesis. Our results reveal that up-regulation of miR-351 protects against IR and liver gluconeogenesis by repressing the PI3K/AKT pathway through regulating FLOT2 in GDM mice, which identifies miR-351 as a potential therapeutic target for the clinical management of GDM.


Asunto(s)
Diabetes Gestacional/patología , Gluconeogénesis/fisiología , Resistencia a la Insulina/fisiología , Proteínas de la Membrana/antagonistas & inhibidores , MicroARNs/genética , Animales , Diabetes Mellitus/genética , Diabetes Mellitus/patología , Diabetes Gestacional/genética , Modelos Animales de Enfermedad , Femenino , Gluconeogénesis/genética , Glucosa-6-Fosfatasa/metabolismo , Insulina/metabolismo , Resistencia a la Insulina/genética , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Transducción de Señal
10.
J Cell Physiol ; 234(3): 2795-2806, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30145806

RESUMEN

Diabetes mellitus is one of the most prevalent metabolic diseases globally and it is increasing in prevalence. It is one of the most expensive diseases with respect to total health care costs per patient as a result of its chronic nature and its severe complications. To provide a more effective treatment of type 2 diabetes mellitus (T2DM), this study aims to compare different efficacies of six kinds of hypoglycemic drugs based on metformin, including glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin, in T2DM by a network meta-analysis that were verified by randomized-controlled trials (RCTs). Eight eligible RCT in consistency with the aforementioned six hypoglycemic drugs for T2DM were included. The results of network meta-analysis demonstrated that the exenatide + metformin and vildagliptin + metformin regimens presented with better efficacy. Patients with T2DM with unsatisfactory blood glucose control based on diet control, proper exercise, and metformin treatment were included. The original regimen and dose of medication were unchanged, followed by the addition of glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin. The results of RCTs showed that all these six kinds of drugs reduced the HbA1c level. Compared with other regimens, exenatide + metformin reduced fasting plasma glucose (FPG), fasting plasma insulin (FPI), total cholesterol (TC), and homeostasis model assessment insulin resistance index (HOMA-IR) levels, but increased the high-density lipoprotein (HDL) level; vildagliptin + metformin decreased FPI and low-density lipoprotein (LDL) levels; glibenclamide + metformin decreased the FPG level, but promoted HDL; and glimepiride + metformin decreased the TC level and rosiglitazone + metformin reduced the LDL level. Our findings indicated that exenatide + metformin and vildagliptin + metformin have better efficacy in T2DM since they can improve insulin sensitivity.


Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/uso terapéutico , Metformina/uso terapéutico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Combinación de Medicamentos , Femenino , Gliburida/uso terapéutico , Humanos , Masculino , Metaanálisis en Red , Pioglitazona/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Rosiglitazona/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Vildagliptina/uso terapéutico
11.
Horm Metab Res ; 50(9): 661-670, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30081425

RESUMEN

Obesity is associated with decreased testosterone levels in males. Testosterone is synthesized by testosterone synthetic enzymes, which are stimulated by luteinizing hormone (LH). Testosterone can also be converted to estradiol via the aromatase. The objective of this study was to examine the factors related to testosterone synthesis and conversion, and to systematically evaluate the key processes that influence testosterone levels in male obesity. Three hundred and two male subjects (aged 25-45 years old) were divided according to BMI into normal weight (18.5-23.9 kg/m2), overweight (24-27.9 kg/m2), and obese (≥28 kg/m2) groups; or divided following WHR into non-abdominal obesity and abdominal obesity groups (WHR: ≥0.9). Male C57BL/6 mice were divided into normal diet (ND) and high-fat diet (HFD)-induced obesity group. Serum sex hormones and aromatase levels were measured using ELISAs. Testosterone synthetic enzymes in the testes were measured by qRT-PCR. The testosterone levels in obese men and abdominal obesity men were lower than normal men. In abdominal obesity men serum LH levels were decreased and associated with testosterone levels after multivariate regression analysis. Serum aromatase levels were increased in abdominal obesity males. In mice, compared to the ND group, the HFD group had decreased steroidogenic acute regulatory protein (StAR). However, aromatase levels in subcutaneous adipose tissue were higher in the ND group than HFD group. In conclusion, according to this study decreased testicular synthesis function and the conversion of testosterone may explain the reduction in testosterone levels in male obesity, and the decrease of testicular synthesis may change first.


Asunto(s)
Aromatasa/metabolismo , Índice de Masa Corporal , Obesidad Abdominal/sangre , Fosfoproteínas/metabolismo , Grasa Subcutánea/metabolismo , Testosterona/sangre , Adulto , Animales , Humanos , Masculino , Ratones , Persona de Mediana Edad
12.
J Biomed Inform ; 85: 155-167, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30071317

RESUMEN

MOTIVATION: Prior research has shown that minor errors and deviations from recommended guidelines in complex medical processes can accumulate to increase the likelihood that a major error will go uncorrected and lead to an adverse outcome. Real-time automatic and accurate detection of process deviations may help medical teams better prevent or mitigate the effect of errors and improve patient outcomes. Our goal was to develop an approach for automatic detection of errors and process deviations in trauma resuscitation. METHODS: Using video review, we coded activity traces of 95 pediatric trauma resuscitations collected in a Level 1 trauma center over two years (2014-2016). Twenty-four randomly selected activity traces were compared with a knowledge-driven model of trauma resuscitation workflow using a phase-based conformance checking algorithm for detecting true and false deviations (alarms). An analysis of false alarms identified three types of causes: (1) model gaps or discrepancies between the model ("work as imagined") and actual practice ("work as done"), (2) errors in activity traces coding, and (3) algorithm limitations. We repaired the system to remove model gaps, reduce coding errors, and address algorithm limitations. The repaired system was first evaluated with another 20 traces and then applied to the entire dataset of 95 traces. RESULTS: During the training, we detected 573 process deviations in 24 activity traces that include 1099 activities. Among these deviations, only 27% represented true deviations and the remaining 73% were false alarms. This initial deviation detection accuracy was only 66.6%, with a F1-score of 0.42. Detection accuracy of the repaired system increased to 95.2% (0.85 F1-score) during system validation and to 98.5% (0.96 F1-score) during testing. After deploying the repaired deviation detection system to all 95 activity traces, we detected 1060 process deviations in 5659 activities (11.2 deviations per resuscitation). Among the 5659 activities in these traces, 4893 fit the repaired knowledge-driven workflow model, 294 were errors of omission, 538 were errors of commission, and 228 were scheduling errors. CONCLUSION: Our approach to automatic deviation detection provides a method for identifying repeated, omitted and out-of-sequence activities that can be included in the design of decision support systems for complex medical processes. Our findings show the importance of assessing detected deviations for repairing a knowledge-driven model that best represents "work as done."


Asunto(s)
Errores Médicos/prevención & control , Algoritmos , Niño , Biología Computacional , Sistemas de Computación , Sistemas de Apoyo a Decisiones Clínicas , Humanos , Errores Médicos/estadística & datos numéricos , Evaluación de Procesos, Atención de Salud , Resucitación/efectos adversos , Resucitación/métodos , Centros Traumatológicos , Grabación en Video , Flujo de Trabajo
13.
Pestic Biochem Physiol ; 128: 82-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26969444

RESUMEN

The study was to assess the long-term toxic effects of acetochlor on rats. Two different doses (42.96 and 107.4 mg/kg body weight/day) of acetochlor were administered to Wistar rats through their food for over 24 weeks. Rat urine samples were collected at two time-points for the measurements of the metabonomics profiles with ultra-performance liquid chromatography-mass spectrometry (UPLC-MSMS). The results of clinical chemistry and histopathology suggested that long-term use of acetochlor in rats caused liver and kidney damage, and dysfunction of antioxidant system. The urinary metabonomics analysis indicated that the high and low-dose exposure of acetochlor could cause alterations of these metabonomics in urine in the rat. Significant changes of the levels of hippuric acid (0.403-fold decrease), citric acid (0.430-fold decrease), pantothenic acid (0.486-fold decrease), uracil (0.419-fold decrease), ß-Alanine (0.325-fold decrease), nonanedioic acid (0.445-fold decrease), L-tyrosine (0.410-fold decrease), D-glucuronic acid (8.389-fold increase) and 2-ethyl-6-methyl-N-methyl-2-chloro-acetanilide in urine were observed. In addition, it may interfere with the fatty acid synthesis, the pyrimidine degradation and pantothenate biosynthesis. The level of 2-ethyl-6-methyl-N-methyl-2-chloro-acetanilide is detected in all treated groups which is not found in the control groups, indicating which can be used as an early, sensitive marker of acetochlor exposure in rat. This study illustrates the important utility of metabonomics approaches to understand the toxicity of long-term exposure of acetochlor.


Asunto(s)
Cromatografía Liquida/métodos , Metabolómica , Espectrometría de Masas en Tándem/métodos , Animales , Ratas
14.
PLoS One ; 19(2): e0298381, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38422104

RESUMEN

The core objective of a successful product supply strategy is to determine the mechanism through which consumers' psychological effects influence customer demand. As stated in the theory of supply and demand, a higher level of dynamic equilibrium should be formed in which demand drives supply and supply creates demand. There is a lack of systematic research in the literature on the identification of consumer goods demand attributes and the formation of influencing factors in consumer goods supply chains. In this paper, we use the literature on demand functions and product pricing functions to establish three mathematical models to study the factors that influence retailers in designing and planning product supply strategies for different customers under nonessential demand patterns and to solve the profit maximization problem. The results of numerical examples validate the validity of the model. The research results can help retailers develop different supply strategies according to different types of customers and different demand patterns, thereby improving business performance. The theoretical contribution of this study is the construction of value ranges and a demand function diagram for identifying consumer product demand attributes.

15.
Gene ; 918: 148476, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38657876

RESUMEN

AIMS: To investigate the association between mitochondrial events and immune response in periodontitis and related regulatory genes. MAIN METHODS: Gene expression profiles in gingival tissues were retrieved from the Gene Expression Omnibus. Mitochondria-immune response-related differentially expressed genes (MIR-DEGs) between the healthy and periodontitis samples were determined. WGCNA, GO, and KEGG were used to investigate the function and the enriched pathways of MIR-DEGs. The correlation between MIR-DEGs expression and clinical probing pocket depth was analyzed. The MIR-DEGs were further identified and verified in animal samples. A periodontitis model was established in C57BL/6 mice with silk ligation. Micro-computed tomography was used to assess alveolar bone loss. Western blot, quantitative real-time polymerase chain reaction, and immunohistochemical analyses further validated the differential expression of the MIR-DEGs. KEY FINDINGS: A total of ten MIR-DEGs (CYP24A1, PRDX4, GLDC, PDK1, BCL2A1, CBR3, ARMCX3, BNIP3, IFI27, and UNG) were identified, the expression of which could effectively distinguish patients with periodontitis from the healthy controls. Enhanced immune response was detected in the periodontitis group with that in the healthy controls, especially in B cells. PDK1 was a critical MIR-DEG correlated with B cell immune response and clinical periodontal probing pocket depth. Both animal and clinical periodontal samples presented higher gene and protein expression of PDK1 than the control samples. Additionally, PDK1 colocalized with B cells in both animal and clinical periodontal tissues. SIGNIFICANCE: Mitochondria participate in the regulation of the immune response in periodontitis. PDK1 may be the key mitochondria-related gene regulating B-cell immune response in periodontitis.


Asunto(s)
Ratones Endogámicos C57BL , MicroARNs , Mitocondrias , Periodontitis , Animales , Periodontitis/genética , Periodontitis/inmunología , Periodontitis/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Encía/metabolismo , Encía/patología , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/genética , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Masculino , Linfocitos B/metabolismo , Linfocitos B/inmunología , Perfilación de la Expresión Génica , Femenino , Transcriptoma , Serina-Treonina Quinasa 3 , Regulación de la Expresión Génica
16.
Shock ; 60(2): 315-324, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37342876

RESUMEN

ABSTRACT: Many patients with cardiac arrest (CA) experience severe kidney injury after the return of spontaneous circulation. This study aimed to compare the renal protective effect of conventional cardiopulmonary resuscitation (CCPR), extracorporeal cardiopulmonary resuscitation (ECPR), and ECPR with therapeutic hypothermia (ECPR+T) in a CA rat model. Twenty-four adult male Sprague-Dawley rats were randomly and equally allocated into the sham, CCPR, ECPR, and ECPR+T groups. The sham group underwent basic surgical procedures without asphyxia-induced CA. The other three groups were treated with asphyxiation to establish the CA model. Subsequently, they were rescued using three different therapeutic methods. The end points were 1 h after return of spontaneous circulation or death. Renal injury was evaluated by histopathology. Oxidative stress, endoplasmic reticulum stress, necroptosis, inflammatory, and apoptosis-related genes, and proteins were detected using western blotting, ELISA, and assay kit. Compared with CCPR, ECPR and ECPR+T alleviated oxidative stress by upregulating nuclear factor erythroid 2-related factor 2, superoxide dismutase, glutathione and downregulating heme oxygenase-1, and malondialdehyde. Expression of endoplasmic reticulum stress-related proteins, glucose-regulated protein 78, and CCAAT/enhancer-binding protein homologous protein was lower in ECPR and ECPR+T groups than that in the CCPR group, along with levels of TNF-α, IL-6, and IL-ß, and necroptosis proteins (receptor-interacting serine/threonine kinases 1 and 3). Furthermore, the ECPR and ECPR+T groups had significantly increased B-cell lymphoma 2 and decreased B-cell lymphoma 2-associated X levels compared with the CCPR group. Extracorporeal cardiopulmonary resuscitation and ECPR+T alleviate kidney damage after CA in rats compared with CCPR. Furthermore, ECPR+T had a better renal protective effect.


Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco , Hipotermia Inducida , Animales , Ratas , Masculino , Ratas Sprague-Dawley , Paro Cardíaco/terapia , Reanimación Cardiopulmonar/métodos , Riñón , Proteínas Proto-Oncogénicas c-bcl-2
17.
Yao Xue Xue Bao ; 47(2): 206-9, 2012 Feb.
Artículo en Zh | MEDLINE | ID: mdl-22512032

RESUMEN

To study the coumarins of Anemone raddeana Regel, the compounds were separated by silica gel column chromatography and HPLC. Their structures were identified by their physicochemical property and spectral analysis. Two new compounds were isolated and identified as 4, 7-dimethoxyl-5-methyl-6-hydroxy coumarin (1) and 4, 7-dimethoxyl-5-formyl-6-hydroxycoumarin (2). The bioassays indicated that compounds 1 and 2 could significantly inhibit the proliferation of cancer cell, and showed the agonist effect on the transactivity of retinoic acid receptor-alpha (RARalpha). In addition, the two compounds had inhibitory effect against human leukocyte elastase (HLE).


Asunto(s)
Anemone/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Cumarinas/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cumarinas/química , Cumarinas/farmacología , Humanos , Concentración 50 Inhibidora , Elastasa de Leucocito/metabolismo , Estructura Molecular , Plantas Medicinales/química , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Rizoma/química , Activación Transcripcional
18.
Front Genet ; 13: 951893, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36468019

RESUMEN

Objective: To study whether ankylosing spondylitis (AS) has a causal effect on the risk of atrial fibrillation (AF) using two-sample Mendelian randomization (MR) analysis. Methods: Single nucleotide polymorphisms (SNPs) were selected as independent instrumental variables (IVs) from a GWAS study of AS. Summary data from a large-scale GWAS meta-analysis of AF was utilized as the outcome dataset. Inverse-variance weighted (IVW) model was used for the primary analysis. Multiple sensitivity and heterogeneity tests were conducted to confirm the robustness of the results. Results: In total, 18 SNPs were identified as IVs for MR analysis. Five MR methods consistently found that ankylosing spondylitis was not causally associated with atrial fibrillation (IVW: OR = 0.983 (0.894, 1.080), p = 0.718; MR-Egger: OR = 1.190 (0.973, 1.456), p = 0.109; Simple mode: OR = 0.888 (0.718, 1.098), p = 0.287; Weighted mode: OR = 0.989 (0.854, 1.147), p = 0.890; Weight median: OR = 0.963 (0.852, 1.088), p = 0.545). Leave-one-out analysis supported the stability of MR results. Both the MR-Egger intercept and MR-PRESSO method revealed the absence of horizontal pleiotropy. Conclusion: The two-sample MR analysis did not support a causal relationship between AS and the risk of AF.

19.
Immunol Lett ; 241: 23-34, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34740720

RESUMEN

Emerging evidence has demonstrated that several microvesicles (MVs) are secreted in bronchoalveolar lavage fluid (BALF) during the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the impact of alveolar macrophage (AM)-derived MVs on epithelial cells and their in vivo effects on ALI/ARDS require further exploration. In this study, MVs were isolated from BALF of mice or mouse alveolar macrophage (MHS) cells by sequential centrifugation and then delivered to epithelial cells or mice. Enzyme-linked immunosorbent assay revealed that BALF-derived MVs (BALF-MVs) and MHS-derived MVs (AM-MVs) were rich in tumor necrosis factor-α (TNF-α) at the early stage of lung injury. In vitro, both inflammatory BALF-MVs and AM-MVs decreased the expression of α subunit of epithelial sodium channel (α-ENaC), γ-ENaC, and Na+,K+-ATPase α1 and ß1 in lung epithelial cells. However, antibodies against TNF-α inhibited the effects of inflammatory AM-MVs in epithelial cells. In vivo, the inflammatory AM-MVs, delivered intratracheally to mice, impaired lung tissues and increased the injury score. They also resulted in decreased alveolar fluid clearance and increased lung wet weight/dry weight ratio. Furthermore, inflammatory AM-MVs downregulated the α-ENaC, γ-ENaC, and Na+,K+-ATPase α1 and ß1 levels in lung tissues. According to our results, inflammatory AM-derived MVs may potentially contribute to lung injury and pulmonary edema, thereby indicating a potential novel therapeutic approach against ALI/ARDS based on AM-MVs.


Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Células Epiteliales/inmunología , Inflamación/inmunología , Pulmón/patología , Macrófagos Alveolares/inmunología , Edema Pulmonar/inmunología , Síndrome de Dificultad Respiratoria/inmunología , Animales , Células Cultivadas , Canales Epiteliales de Sodio/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
20.
Artículo en Inglés | MEDLINE | ID: mdl-33716575

RESUMEN

Most current speech enhancement models use spectrogram features that require an expensive transformation and result in phase information loss. Previous work has overcome these issues by using convolutional networks to learn the temporal correlations across high-resolution waveforms. These models, however, are limited by memory-intensive dilated convolution and aliasing artifacts from upsampling. We introduce an end-to-end fully recurrent neural network for single-channel speech enhancement. The network structured as an hourglass-shape that can efficiently capture long-range temporal dependencies by reducing the features resolution without information loss. Also, we use residual connections to prevent gradient decay over layers and improve the model generalization. Experimental results show that our model outperforms state-of-the-art approaches in six quantitative evaluation metrics.

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