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Smartphone addiction, emerging from excessive use of smartphones, poses a challenge to inhibitory control functions within society. This research employed transcranial direct current stimulation (tDCS) as an intervention alongside the stop signal task (SST) to explore behavioral distinctions between individuals with smartphone addiction and a non-addicted control group, focusing on the efficacy of tDCS intervention. The participant cohort comprised 80 individuals, divided into an addiction group (39 participants, with 19 receiving active tDCS and 20 receiving sham tDCS) and a control group (41 participants, with 20 receiving active tDCS and 21 receiving sham tDCS), with anodal stimulation applied over the right dorsolateral prefrontal cortex (dlPFC) and cathodal placement over the left arm. The findings indicate that university students struggling with smartphone addiction exhibit reduced inhibitory control compared to their non-addicted peers, while maintaining similar levels of general cognitive control. Remarkably, tDCS interventions were observed to enhance inhibitory control in both groups. Although the improvement in the addiction group appeared more pronounced numerically than in the control group, no significant interaction with group was noted. However, a higher percentage of participants in the smartphone addiction (SA) group exhibited enhanced response inhibition under active tDCS. This study demonstrates the inhibitory control deficits in individuals addicted to smartphones and underscores the potential of tDCS in enhancing response inhibition. It provides a valuable reference for future tDCS research targeting smartphone addiction and highlights the importance of developing healthier smartphone usage habits.
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Teléfono Inteligente , Estudiantes , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Masculino , Femenino , Adulto Joven , Adulto , Universidades , Inhibición Psicológica , Trastorno de Adicción a Internet/terapia , Trastorno de Adicción a Internet/fisiopatología , Conducta Adictiva/terapia , Conducta Adictiva/fisiopatología , Corteza Prefontal Dorsolateral/fisiologíaRESUMEN
Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.
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The pervasive use of smartphones, while enhancing accessibility to information and communication, has raised concerns about its potential negative effects on physical and mental health, including the impairment of decision-making abilities. This study investigates the influence of smartphone addiction on decision-making in college students. A sample of 80 individuals aged 17 to 26 was selected and divided into two groups based on their Smartphone Addiction Scale-Short Version (SAS-SV) scores. Participants underwent the Iowa Gambling Task (IGT) to evaluate their decision-making in risky and uncertain conditions, while fNIRS recorded their prefrontal cortex activity. The study found that individuals prone to smartphone addiction tend to make riskier choices in risky situations. However, when faced with decisions based on ambiguity, the smartphone addiction group showed increased brain activity in the dlPFC (specifically in channels 4, 9, and 11) compared to when making risky decisions. Despite this increased brain activation, there was no observable difference in behavior between the addiction-prone and control groups in ambiguous scenarios. Notably, the left dlPFC (e.g., channel 4) exhibited significantly higher activation in the addiction group compared to the control group. Findings suggest that smartphone addiction can detrimentally influence decision-making, behaviorally and neurologically, particularly in uncertain contexts. This study supports the classification of smartphone addiction as a genuine addiction and underscores its significance in psychiatric research. In essence, our research underscores the adverse effects of excessive smartphone use on decision-making processes, reinforcing the necessity to treat smartphone addiction as a pressing public health issue.
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Cerebrotein hydrolysate-1 (CH-1), a mixture of small peptides, polypeptides, and various amino acids derived from porcine brain, has been widely used in the treatment of cerebral injury. However, the bioactive composition and pharmacokinetics of CH-1 are still unexplored because of their complicated composition and relatively tiny amounts in vivo. Herein, NanoLC Orbitrap Fusion Lumos Tribrid Mass Spectrometer was firstly used to qualitatively analyze the components of CH-1. A total of 1347 peptides were identified, of which 43 peptides were characterized by high mass spectrometry (MS) intensity and identification accuracy. We then innovatively synthesized four main peptides for activity verification, and the results suggested that Pep72 (NYEPPTVVPGGDL) had the strongest neuroprotective effect on both in vivo and in vitro models. Next, a quantitative method for Pep72 was established based on liquid chromatography tandem mass spectrometry (LC-MS/MS) with the aid of Skyline software and then used in its pharmacokinetic studies. The results revealed that Pep72 had a high elimination rate and low exposure in rats. In addition, a hCMEC/D3-based in vitro model was built and firstly used to investigate the transport of Pep72. We found that Pep72 had extremely low blood-brain barrier permeability and was not a substrate of efflux transporters. The biotransformation of Pep72 in rat fresh plasma and tissues was investigated to explore the contradiction between pharmacokinetics and efficacy. A total of 11 main metabolites were structurally identified, with PGGDL and EPPTVPGGDL being the main metabolites of Pep72. Notably, metalloproteinase and cysteine protease were confirmed to be the main enzymes mediating Pep72 metabolism in rat tissues. SIGNIFICANCE STATEMENT: The NanoLC Orbitrap Fusion Lumos Tribrid Mass Spectrometer was firstly applied to discover the components of CH-1, and one main peptide Pep72 (NYEPPTVVPGGDL) was innovatively synthesized and firstly found to have the strongest neuroprotective effect among 1347 peptides identified from CH-1. Our study is the first time to identify and verify the active ingredient of CH-1 from the perspective of pharmacokinetics and pharmacodynamics, and provides a systematic technical platforms and strategies for the active substance research of other protein hydrolysates.
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Fármacos Neuroprotectores , Espectrometría de Masas en Tándem , Ratas , Animales , Porcinos , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Fármacos Neuroprotectores/farmacología , Péptidos/farmacología , Péptidos/metabolismo , Barrera Hematoencefálica/metabolismoRESUMEN
Smartphone Addiction is a social issue caused by excessive smartphone use, affecting decision-making processes. Current research on the risky decision-making abilities of smartphone addicts is limited. This study used the functional Near-Infrared Spectroscopy (fNIRS) brain imaging technique and a Sequential Risk-Taking Task experimental paradigm to investigate the decision-making behavior and brain activity of smartphone addicts under varying risk levels. Using a mixed experimental design, the research assessed decision-making ability and brain activation levels as dependent variables across two groups (addiction and control), two risk amounts (high and low), and two outcomes (gain and loss). The study included 42 participants, with 25 in the addiction group and 17 in the control group. Results indicated that risk level significantly impacted the decision-making ability of smartphone addicts, with high-risk levels leading to weaker decision-making ability and increased risk-taking. However, at low-risk levels, decision-making abilities between addicts and healthy individuals showed no significant difference. Furthermore, brain imaging results using fNIRS revealed stronger brain activation in the dorsolateral Prefrontal Cortex (dlPFC) region for smartphone addicts under loss outcome conditions, with no significant differences between the two groups in terms of brain activation at varying risk volumes. These findings are critical in promoting healthy smartphone use, guiding clinical treatment, and advancing brain mechanism research.
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Epigenetics, including histone modifications and noncoding RNAs, affects abnormal placental function in pre-eclampsia (PE). This study was conducted to explore the role of histone deacetylase 4 (HDAC4) in trophoblast invasion and migration. The expression levels of HDAC4, microRNA (miR)-134-5p, and forkhead box protein M1 (FOXM1) in placentas from PE patients and healthy controls and their correlations were examined. HTR8/SVneo cells were cultured and underwent gene intervention. Then, trophoblast proliferation, invasion, and migration were evaluated by 5-ethynyl-2'deoxyuridine, Transwell, and scratch assays. The enrichments of HDAC4 and acetylated histone H3 at lysine 9 (H3K9Ac) on the miR-134-5p promoter were quantified by chromatin immunoprecipitation. The binding of miR-134-5p to FOXM1 was analyzed by dual-luciferase assay. HDAC4 and FOXM1 were downregulated while miR-134-5p was upregulated in PE placentas. HDAC4 downregulation impaired trophoblast proliferation, invasion, and migration while HDAC4 overexpression played the opposite role. Mechanically, HDAC4 deacetylated H3K9Ac to repress miR-134-5p expression by erasing H3K9Ac, reduced the binding of miR-134-5p to FOXM1, and then promoted FOXM1 transcription. miR-134-5p overexpression or FOXM1 downregulation abrogated the promotive role of HDAC overexpression in trophoblast invasion and migration. Our study unraveled a novel mechanism of trophoblast proliferation, invasion, and migration and proposed that HDAC4 may be a promising target for the treatment of PE.
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MicroARNs , Preeclampsia , Humanos , Embarazo , Femenino , Placenta/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Preeclampsia/genética , Preeclampsia/metabolismo , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Proliferación Celular/genética , Trofoblastos/metabolismo , Movimiento Celular/genética , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Proteínas RepresorasRESUMEN
Many studies have explored the role of lncRNA X inactivation-specific transcript (XIST) in diabetes. This study was designed to unravel the regulatory mechanism of XIST on animal models of gestational diabetes mellitus (GDM) progression via the microRNA (miR)-181b-5p/N-myc downstream-regulated gene 2 (NDRG2) axis. XIST, miR-181b-5p, and NDRG2 expression levels in GDM mice were detected. The GDM mice were subjected to gain- and loss-of-function assays to examine the change of glucose metabolism indices (fasting blood glucose (FBG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR)), serum oxidative stress factors (glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA)), serum inflammatory factors (interleukin-1 ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α)), pathological changes of pancreatic tissues, and apoptotic cells in pancreatic islets in GDM mice. XIST and NDRG2 expression were elevated while miR-181b-5p expression was depleted in GDM mice. Down-regulated XIST or NDRG2 or up-regulated miR-181b-5p reduced the FBG level, HOMA-IR, and serum IL-1ß, IL-6, and TNF-α, and MDA contents, elevated the FINS, GSH, and SOD level, mitigated pathological changes in pancreatic tissues, and decelerated apoptotic cells in pancreatic islets in GDM mice. Silenced XIST dampens insulin resistance in GDM mice via the modulation of the miR-181b-5p/NDRG2 axis.
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Diabetes Gestacional , Resistencia a la Insulina , MicroARNs , ARN Largo no Codificante , Animales , Ratones , Femenino , Humanos , Embarazo , Diabetes Gestacional/genética , ARN Largo no Codificante/genética , Interleucina-6 , Factor de Necrosis Tumoral alfa , Glutatión , MicroARNs/genética , Proteínas Supresoras de TumorRESUMEN
Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.
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BACKGROUND: Sanguisorba saponin extract (SSE) is the main active part of Sanguisorba officinalis with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-oxidant. However, its therapeutic role and underlying mechanisms for ulcerative colitis (UC) still need to be elucidated. PURPOSE: This study aims to explore the therapeutic effect, effectiveness-material basis-quality markers (Q-markers) and prospective mechanism of function of SSE on UC. METHODS: Fresh 2.5% dextran sulfate sodium salt (DSS) solution was placed in drinking bottles for 7 days to induce a mouse model of UC. SSE and sulfasalazine (SASP) were supplemented to mice by gavage for consecutive 7 days to investigate the therapeutic role of SSE on UC. Mouse monocyte macrophages (RAW264.7) and human normal colonic epithelial (NCM460) cells were treated with LPS to induce inflammatory responses, followed by pharmacodynamic examination with different concentrations of SSE. Hematoxylin-eosin (HE) and Alcian blue staining were conducted to evaluate the pathological damage of mice colon. Lipidomic technology was conducted to explore the differential lipids closely related to the disease process of UC. Quantitative PCR analysis, immunohistochemistry and ELISA kit were used to measure the expression levels of the corresponding proteins and pro-inflammatory factors. RESULTS: SSE treatment could effectively reduce the elevated expressions of pro-inflammatory factors in RAW264.7 and NCM460 cells due to LPS stimulation. Intragastric administration of SSE was found to significantly alleviate the symptoms of DSS-induced colon injury and low-polar saponins in SSE. Low polarity saponins, especially ZYS-II, were proved to be the main active substances of SSE in treating UC. In addition, SSE could significantly ameliorate the aberrant lipid metabolism in UC mice. The role of phosphatidylcholine (PC)34:1 in the UC pathogenesis has been fully verified in our previous studies. Herein, SSE-dosing effectively reversed the metabolic disorder of PCs in UC mice, and increased the PC34:1 level to normal via up-regulating the expression of phosphocholine cytidylyltransferase (PCYT1α). CONCLUSION: Our data innovatively revealed that SSE could significantly alleviate the symptoms of UC by reversing the disorder of PC metabolism induced by DSS modeling. SSE was proved for the first time to be a promising and effective candidate for UC treatment.
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Colitis Ulcerosa , Colitis , Sanguisorba , Saponinas , Humanos , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Saponinas/efectos adversos , Lipopolisacáridos/farmacología , Metabolismo de los Lípidos , Colon/patología , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Colitis/patologíaRESUMEN
Numerous works have been focused on the bioactivities of protein hydrolysates (PHs) and their application in food or drug formulations, but their composition and pharmacokinetics have never been addressed due to their complex constitutes, short half-life, extremely low concentrations and lack of authentic standards. The present study aims to develop systematic analytical strategy and technical platform with optimized sample preparation, separation and detection protocols for PHs. Lineal peptides (LPs), extraction of the spleen of healthy pigs or calves, were used as cases. First, solvents with polarity gradients were used to globally extract peptides of LP from biological matrix. Non-targeted proteomics based on a high-resolution MS system was used to establish a reliable qualitative analysis workflow for PHs. Based on the developed approach, 247 unique peptides were identified using NanoLC-Orbitrap-MS/MS, and then further verified on the MicroLC-Q-TOF/MS system. In the quantitative analysis workflow, Skyline software was used to predict and optimize the LC-MS/MS detection parameters of LPs followed by investigating the linearity and precision of the developed analytical assay. Note worthily, we innovatively prepared calibration curves by sequential dilution of LP solution to overcome the bottleneck of lacking authentic standards and complex PH composition. All the peptides exhibited good linearity and precision in biological matrix. The established qualitative and quantitative assays were successfully applied to study the distribution characteristics of LPs in mice, and would be conductive to systematically map the profile and pharmacokinetics of peptides in various PHs in vivo and in vitro.
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Hidrolisados de Proteína , Espectrometría de Masas en Tándem , Animales , Bovinos , Ratones , Porcinos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Proteómica/métodos , Lipopolisacáridos , PéptidosRESUMEN
BACKGROUND: Our current study was performed aimed at determining the efficacy and safety profile of robotic surgery (RS) compared to laparoscopic surgery (LPS) and laparotomy (LT) in the treatment of endometrial cancer on the basis of relevant studies. PATIENTS AND METHODS: A systematic literature search was conducted based on appropriate keywords, using the Embase, Cochrane library, as well as PubMed. Our studiers also reviewed the key pertinent sources among the publications and included associated literatures published by June 2021. Odds ratios (ORs), mean difference (MD), as well as 95% confidence interval (95% CI) for each study were measured for further assessment and synthesis of outcomes. RESULTS: Thirty studies involving a total of 12,025 patients were eventually included in the current meta-analysis. Compared with LPS, RS could significantly decrease the estimated blood loss, the incidence of intraoperative complications, the length of hospital stay, and the rate of conversion, and increased the rate of readmission. Compared with LT, RS significantly decreased the estimated blood loss, blood transfusion volume, the length of hospital stay, the rate of total, intraoperative and postoperative complications, and the rate of readmission and re-operation, and increased the operative time. CONCLUSION: Considering the effects and safety profile of RS in terms of treating endometrial cancer, our study suggest that RS exerts superior outcomes than that of LPS and LT.
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Neoplasias Endometriales , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Neoplasias Endometriales/etiología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Laparoscopía/efectos adversos , Laparotomía/efectos adversos , Tiempo de Internación , Tempo Operativo , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Robotizados/efectos adversosRESUMEN
BACKGROUND: Extensor apparatus rupture is a severe complication after knee arthroplasty, but there have not been many reports on how to perform knee arthroplasty after chronic patellar ligament rupture. We reported a case of total knee arthroplasty (TKA) in a patient with severe osteoarthritis (OA) complicated by chronic patellar ligament rupture. CASE PRESENTATION: In this case, a 67-year-old male patient suffered from patellar ligament rupture due to trauma more than 20 years ago and did not undergo any formal treatment. Physical examination revealed a small amount of fluid and extension lag, and the patella was displaced upward by approximately 5.5 cm. The quadriceps were atrophic and weak. There was significant tenderness on the medial side of the left knee joint. Passive motion of the left knee joint ranged from full extension to 120° of flexion with discomfort during excessive flexion. Active flexion of the knee joint to 120°, and extensor lag was approximately 90°. We reconstructed the extensor apparatus through a quadriceps tendon V-Y quadricepsplasty and Krackow suture technique of the patellar ligament, and osteoarthritis was resolved with TKA. The visual analogue scale (VAS) score decreased from 5 points to 1 point after surgery. Six weeks later, the patient was able to walk normally without a walking stick, and the knee joint could stretch actively to approximately 30°. However, he had obvious extension lag. This problem improved 10 months after surgery. The AKS score increased from 35 to 95 10 months after surgery. The HSS score increased from 43 to 93. CONCLUSIONS: TKA and ligament reconstruction are options for the treatment of knee OA with chronic patellar ligament rupture. V-Y lengthening of the quadriceps femoris tendon after the Krackow suture technique of the patellar ligament with transpatellar tunnels may be a reasonable choice during TKA.
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Artroplastia de Reemplazo de Rodilla , Traumatismos de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Ligamento Rotuliano/lesiones , Rotura/cirugía , Traumatismos de los Tendones/cirugía , Anciano , Humanos , Traumatismos de la Rodilla/etiología , Masculino , Ligamento Rotuliano/cirugía , Músculo Cuádriceps/cirugía , Radiografía , Rango del Movimiento Articular , Rotura/etiología , Técnicas de Sutura , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study is to assess the clinical effectiveness and safety of hyaluronic acid gel for the prevention of postoperative intrauterine adhesions (IUAs). METHODS: PubMed, Cochrane Library, Embase and ClinicalTrials.gov databases were searched for randomized controlled trials. RESULTS: Six RCTs with a total of 564 patients met the inclusion criteria. The meta-analysis showed that, compared to no other treatment method, hyaluronic acid gel significantly reduced the rate of any IUA (risk ratio [RR] 0.68; 95% CI 0.53-0.86; p = 0.03; I2 = 64%) and adhesion score (standard mean difference = -2.90; 95% CI -4.61 to -1.49; p < 0.00001; I2 = 98%) following intraperitoneal or intrauterine surgery. Treatment lowered the rate of IUAs classified as moderate (RR 0.26; 95% CI 0.13-0.52; p = 0.13; I2 = 0%), but not those deemed mild (RR 0.86; 95% CI 0.62-1.21; p = 0.39; I2 = 3%) or severe (RR 0.33; 95% CI 0.03-3.09; p = 0.33; I2 = 0). Compliance with hyaluronic acid gel treatment was low. CONCLUSION: Hyaluronic acid gel can prevent IUAs, particularly those with moderate severity and a lower adhesion score.