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How does Hedgehog signaling participate in the cross-interaction of hormones and testis development?
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作者 JUN-JIE YU WAN-XI YANG 《BIOCELL》 2025年第1期93-107,共15页
Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The d... Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers. 展开更多
关键词 Hedgehog signaling HORMONE TESTIS Leydig cell Gonadal dysgenesis
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Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease
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作者 Milica Zeljkovic Jovanovic Jelena Stanojevic +4 位作者 Ivana Stevanovic Milica Ninkovic Tihomir V.Ilic Nadezda Nedeljkovic Milorad Dragic 《Neural Regeneration Research》 SCIE CAS 2025年第7期2053-2067,共15页
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog... An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control. 展开更多
关键词 A_(1)R A_(2A)R adenosine receptors ADENOSINE ecto-5′-nucleotidase intermittent theta burst stimulation non-invasive brain stimulation Parkinson's disease purinergic signalling
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Exploration of The Construction Path of Sports Injury and First Aid Course Systems for College Students
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作者 Xiaobo Zhan Haiyan Liu Dan Tan 《Journal of Clinical and Nursing Research》 2024年第4期105-109,共5页
By the requirements of the Ministry of Education on life safety education, colleges, and universities have set up a course on Sports Injury and First Aid to organize relevant knowledge and increase the student’s awar... By the requirements of the Ministry of Education on life safety education, colleges, and universities have set up a course on Sports Injury and First Aid to organize relevant knowledge and increase the student’s awareness of first aid knowledge so that they can use reasonable methods to address sport-related injuries. At the same time, they can cope with first-aid situations and assist rescuers in completing resuscitation activities. This paper is based on the study of three colleges in Chongqing. This paper selected students from 3 universities in Chongqing and evaluated the mastery of first aid knowledge of college students, pointing out the value of implementing the “Sports Injury and First Aid” course in colleges and universities. This can provide opportunities to improve the theoretical content of the discipline, actively carry out practical activities, reasonably set the assessment method, and provide basic protection to ensure that the “Sports Injury and First Aid” course can be carried out normally to improve the mastery level of students’ first aid knowledge. 展开更多
关键词 College students Sports injury and first aid course INFRASTRUCTURE Faculty strength
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Reform of the Comprehensive Practical Course System for Mechanical and Electronic Engineering Majors Under the Background of New Engineering
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作者 Yali Yu Keyi Wang Yong Yang 《Journal of Contemporary Educational Research》 2024年第2期85-90,共6页
Under the background of new engineering,the reform of the comprehensive practical course system for mechanical and electronic engineering majors actively responds to the challenges posed by the new round of technologi... Under the background of new engineering,the reform of the comprehensive practical course system for mechanical and electronic engineering majors actively responds to the challenges posed by the new round of technological revolution and industrial transformation to higher education,cultivating top-notch innovative intellectuals with comprehensive engineering qualities,meeting the requirements of being able to solve complex engineering problems rather than just cognitive capabilities,forming two core courses through reconstructing and reshaping the core courses of the major.The core courses include Drive,Measurement,and Control I and Drive,Measurement,and Control II,which highlight the comprehensive framework of mechanical and electronic engineering professional knowledge,continuing the comprehensive practical course system based on the unity of knowledge and practice,following the trend of new engineering,highlighting the practicality of professional innovation,assisting engineering education reform,and promoting high-quality development of new engineering professionals cultivation. 展开更多
关键词 Comprehensive engineering quality Mechanical and Electronic Engineering Practical course system New engineering
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Modeling and Comprehensive Review of Signaling Storms in 3GPP-Based Mobile Broadband Networks:Causes,Solutions,and Countermeasures
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作者 Muhammad Qasim Khan Fazal Malik +1 位作者 Fahad Alturise Noor Rahman 《Computer Modeling in Engineering & Sciences》 SCIE EI 2025年第1期123-153,共31页
Control signaling is mandatory for the operation and management of all types of communication networks,including the Third Generation Partnership Project(3GPP)mobile broadband networks.However,they consume important a... Control signaling is mandatory for the operation and management of all types of communication networks,including the Third Generation Partnership Project(3GPP)mobile broadband networks.However,they consume important and scarce network resources such as bandwidth and processing power.There have been several reports of these control signaling turning into signaling storms halting network operations and causing the respective Telecom companies big financial losses.This paper draws its motivation from such real network disaster incidents attributed to signaling storms.In this paper,we present a thorough survey of the causes,of the signaling storm problems in 3GPP-based mobile broadband networks and discuss in detail their possible solutions and countermeasures.We provide relevant analytical models to help quantify the effect of the potential causes and benefits of their corresponding solutions.Another important contribution of this paper is the comparison of the possible causes and solutions/countermeasures,concerning their effect on several important network aspects such as architecture,additional signaling,fidelity,etc.,in the form of a table.This paper presents an update and an extension of our earlier conference publication.To our knowledge,no similar survey study exists on the subject. 展开更多
关键词 signaling storm problems control signaling load analytical modeling 3GPP networks smart devices diameter signaling mobile broadband data access data traffic mobility management signaling network architecture 5G mobile communication
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Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance
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作者 Theodora Ntetsika Sergiu-Bogdan Catrina Ioanna Markaki 《Neural Regeneration Research》 SCIE CAS 2025年第11期3113-3123,共11页
Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel... Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed. 展开更多
关键词 brain insulin resistance brain insulin signaling diabetes type 2 GLP-1 receptor agonists GLP-1 signaling insulin resistance insulin signaling NEURODEGENERATION Parkinson's disease targeted therapy
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Using Pearson’s System of Curves to Approximate the Distributions of the Difference between Two Correlated Estimates of Signal-to-Noise Ratios: The Cases of Bivariate Normal and Bivariate Lognormal Distributions
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作者 Mohamed M. Shoukri 《Open Journal of Statistics》 2024年第3期207-227,共21页
Background: The signal-to-noise ratio (SNR) is recognized as an index of measurements reproducibility. We derive the maximum likelihood estimators of SNR and discuss confidence interval construction on the difference ... Background: The signal-to-noise ratio (SNR) is recognized as an index of measurements reproducibility. We derive the maximum likelihood estimators of SNR and discuss confidence interval construction on the difference between two correlated SNRs when the readings are from bivariate normal and bivariate lognormal distribution. We use the Pearsons system of curves to approximate the difference between the two estimates and use the bootstrap methods to validate the approximate distributions of the statistic of interest. Methods: The paper uses the delta method to find the first four central moments, and hence the skewness and kurtosis which are important in the determination of the parameters of the Pearsons distribution. Results: The approach is illustrated in two examples;one from veterinary microbiology and food safety data and the other on data from clinical medicine. We derived the four central moments of the target statistics, together with the bootstrap method to evaluate the parameters of Pearsons distribution. The fitted Pearsons curves of Types I and II were recommended based on the available data. The R-codes are also provided to be readily used by the readers. 展开更多
关键词 signal-to-Noise Ratio Bivariate Distributions Bootstrap Methods Delta Method Pearson system of Curves
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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function
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作者 Chonglin Su Taiqi Huang +3 位作者 Meiyu Zhang Yanyu Zhang Yan Zeng Xingxing Chen 《Neural Regeneration Research》 SCIE CAS 2025年第9期2520-2537,共18页
The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an impo... The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders. 展开更多
关键词 brain-derived neurotrophic factor calcium signaling glucocorticoid receptor GLUCOCORTICOID glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders NEUROPLASTICITY stress
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Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases
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作者 Fengcheng Deng Dan Yang +6 位作者 Lingxi Qing Yifei Chen Jilian Zou Meiling Jia Qian Wang Runda Jiang Lihua Huang 《Neural Regeneration Research》 SCIE CAS 2025年第11期3095-3112,共18页
The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enh... The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases. 展开更多
关键词 cyclic adenosine monophosphate emotional disorders gut microbiota neurodegenerative diseases neurological diseases protein kinase A reciprocal regulation signaling pathway STRATEGY theRAPIES
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The dopaminergic system and Alzheimer's disease
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作者 Yuhan Zhang Yuan Liang Yixue Gu 《Neural Regeneration Research》 SCIE CAS 2025年第9期2495-2512,共18页
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b... Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options. 展开更多
关键词 adverse drug reaction Alzheimer's disease CATECHOLAMINE dopamine receptor dopamine receptor heterodimers dopaminergic system neurodegenerative disease NEUROTRANSMITTER signaling pathways traditional Chinese medicine TREATMENT
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Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease
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作者 Mackenzie M.Spicer Jianqi Yang +5 位作者 Daniel Fu Alison N.DeVore Marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher 《Neural Regeneration Research》 SCIE CAS 2025年第10期2969-2981,共13页
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode... Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease. 展开更多
关键词 adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus EXERCISE learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)
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Mesalazine alleviated the symptoms of spontaneous colitis in interleukin-10 knockout mice by regulating the STAT3/NF-κB signaling pathway
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作者 Qian Chen Ya-Li Zhang +1 位作者 Yong-Quan Shi Lie Zheng 《World Journal of Gastroenterology》 2025年第7期88-97,共10页
BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear f... BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway. 展开更多
关键词 MESALAZINE Ulcerative colitis Interleukin-10-/-mice signal transducer and activator of transcription 3/nuclear factor kappa B signaling pathway Endoplasmic reticulum stress Inflammatory bowel disease
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Dapagliflozin exerts anti-apoptotic effects by mitigating macrophage polarization via modulation of the phosphoinositide 3-kinase/protein kinase B signaling pathway
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作者 Sheng-Xi Xiong Lin-Juan Huang +5 位作者 Han-Shuang Liu Xiao-Xiao Zhang Min Li Yu-Bing Cui Chen Shao Xiao-Lei Hu 《World Journal of Diabetes》 2025年第2期163-174,共12页
BACKGROUND Macrophages are central to the orchestration of immune responses,inflammatory processes,and the pathogenesis of diabetic complications.The dynamic polarization of macrophages into M1 and M2 phenotypes criti... BACKGROUND Macrophages are central to the orchestration of immune responses,inflammatory processes,and the pathogenesis of diabetic complications.The dynamic polarization of macrophages into M1 and M2 phenotypes critically modulates inflammation and contributes to the progression of diabetic nephropathy.Sodiumglucose cotransporter 2 inhibitors such as dapagliflozin,which are acclaimed for their efficacy in diabetes management,may influence macrophage polarization,thereby ameliorating diabetic nephropathy.This investigation delves into these mechanistic pathways,aiming to elucidate novel therapeutic strategies for diabetes.AIM To investigate the inhibitory effect of dapagliflozin on macrophage M1 polarization and apoptosis and to explore its mechanism of action.METHODS We established a murine model of type 2 diabetes mellitus and harvested peritoneal macrophages following treatment with dapagliflozin.Concurrently,the human monocyte cell line cells were used for in vitro studies.Macrophage viability was assessed in a cell counting kit 8 assay,whereas apoptosis was evaluated by Annexin V/propidium iodide staining.Protein expression was examined through western blotting,and the expression levels of macrophage M1 surface immunosorbent assay,and quantitative real-time polymerase chain reaction analyses.RESULTS Dapagliflozin attenuated M1 macrophage polarization and mitigated apoptosis in the abdominal macrophages of diabetic mice,evidenced by the downregulation of proapoptotic genes(Caspase 3),inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-α,and IL-1β],and M1 surface markers(inducible nitric oxide synthase,and cluster of differentiation 86),as well as the upregulation of the antiapoptotic gene BCL2.Moreover,dapagliflozin suppressed the expression of proteins associated with the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway(PI3K,AKT,phosphorylated protein kinase B).These observations were corroborated in vitro,where we found that the modulatory effects of dapagliflozin were abrogated by 740Y-P,an activator of the PI3K/AKT signaling pathway.CONCLUSION Dapagliflozin attenuates the polarization of macrophages toward the M1 phenotype,thereby mitigating inflammation and promoting macrophage apoptosis.These effects are likely mediated through the inhibition of the PI3K/AKT signaling pathway. 展开更多
关键词 DAPAGLIFLOZIN Macrophage polarization INFLAMMATION Macrophage apoptosis Phosphoinositide 3-kinase/protein kinase B signaling pathway
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Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) via dephosphorylation of the EGFR signaling pathway 被引量:1
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作者 Muhammad Zubair Hafiz Jie Pan +4 位作者 Zhiwei Gao Ying Huo Haobin Wang Wei Liu Jian Yang 《Journal of Biomedical Research》 CAS CSCD 2024年第4期382-396,共15页
The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administratio... The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway. 展开更多
关键词 timosaponin AⅢ CAR metabolism enzyme ERK1/2 signaling pathway EGFR signaling pathway
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Hypoglycemic mechanism of Tegillarca granosa polysaccharides on type 2 diabetic mice by altering gut microbiota and regulating the PI3K-akt signaling pathwaye 被引量:2
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作者 Qihong Jiang Lin Chen +5 位作者 Rui Wang Yin Chen Shanggui Deng Guoxin Shen Shulai Liu Xingwei Xiang 《Food Science and Human Wellness》 SCIE CSCD 2024年第2期842-855,共14页
Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2... Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical. 展开更多
关键词 Tegillarca granosa polysaccharide Type 2 diabetes mellitus Glycolipid metabolism PI3K/Akt signaling pathway
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Design and implementation of the simulation system for GPS new civil signals
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作者 祝雪芬 陈熙源 陈建锋 《Journal of Southeast University(English Edition)》 EI CAS 2012年第3期305-309,共5页
In order to research on the design and implementation of a modernized GPS civil signals simulation system,a brief review of the modernized GPS signals is introduced,including the signal structure and characteristics o... In order to research on the design and implementation of a modernized GPS civil signals simulation system,a brief review of the modernized GPS signals is introduced,including the signal structure and characteristics of L2C,L5 and L1C signals.The design and implementation of the main modules of the simulation system is described in detail.The simulation system is mainly composed of parameter setting,system initialization,signal generator,noise generator,disturbance generator,signal synthesis,low-pass filter,A/D conversion and storage.The simulation results based on Matlab are then presented,and the power spectral density(PSD) of all navigation signals is analyzed.The simulation system completes the physical layer simulation of a modernized GPS new civil signal and can provide a controllable signal source for designing and testing of modernized GPS civil receivers,especially for the signal processing algorithm design of the GPS software receiver. 展开更多
关键词 modernized GPS L2 civil signal L1 civil signal L5 signal simulation system
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Comparison of displacement damage effects on the dark signal in CMOS image sensors induced by CSNS back-n and XAPR neutrons 被引量:1
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作者 Yuan-Yuan Xue Zu-Jun Wang +3 位作者 Wu-Ying Ma Min-Bo Liu Bao-Ping He Shi-Long Gou 《Nuclear Science and Techniques》 SCIE EI CAS CSCD 2024年第10期29-40,共12页
This study investigates the effects of displacement damage on the dark signal of a pinned photodiode CMOS image sensor(CIS)following irradiation with back-streaming white neutrons from white neutron sources at the Chi... This study investigates the effects of displacement damage on the dark signal of a pinned photodiode CMOS image sensor(CIS)following irradiation with back-streaming white neutrons from white neutron sources at the China spallation neutron source(CSNS)and Xi'an pulsed reactor(XAPR).The mean dark signal,dark signal non-uniformity(DSNU),dark signal distribution,and hot pixels of the CIS were compared between the CSNS back-n and XAPR neutron irradiations.The nonionizing energy loss and energy distribution of primary knock-on atoms in silicon,induced by neutrons,were calculated using the open-source package Geant4.An analysis combining experimental and simulation results showed a noticeable proportionality between the increase in the mean dark signal and the displacement damage dose(DDD).Additionally,neutron energies influence DSNU,dark signal distribution,and hot pixels.High neutron energies at the same DDD level may lead to pronounced dark signal non-uniformity and elevated hot pixel values. 展开更多
关键词 Displacement damage effects CMOS image sensor(CIS) CSNS back-n XAPR neutrons Geant4 Dark signal non-uniformity(DSNU)
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Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside
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作者 Meijing Zhang Gaoshuai Zhang +10 位作者 Xiangxing Meng Xinxin Wang Jiao Xie Shaoshu Wang Biao Wang Jilite Wang Suwen Liu Qun Huang Xu Yang Jing Li Hao Wang 《Food Science and Human Wellness》 SCIE CAS CSCD 2024年第4期1864-1876,共13页
Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pat... Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside. 展开更多
关键词 HYPEROSIDE QUERCETIN HepG2 cell Oxidative damage Nrf2 signalling pathway
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Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions
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作者 Yi-Mei Wang Zheng-Wei Luo +5 位作者 Yu-Lin Shu Xiu Zhou Lin-Qing Wang Chun-Hong Liang Chao-Qun Wu Chang-Ping Li 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第3期979-990,共12页
BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and th... BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to GC.Therefore,it is necessary to find a novel drug that is inexpensive and preventive to against GC.AIM To explore the effects of H.pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),H.pylori+MNU,and Moluodan groups.We first created an H.pylori infection model in the H.pylori+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control group.Moluodan was fed to mice in the Moloudan group ad libitum.The general condition of mice were observed during the whole experiment period.Gastric tissues of mice were grossly and microscopically examined.Through quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were detected.RESULTS Mice in the H.pylori+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control group.QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the H.pylori+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control group.CONCLUSION H.pylori can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of PLGC.Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC. 展开更多
关键词 Helicobacter pylori Gastric cancer Wnt/β-catenin signaling pathway Moluodan
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Granulometric and Mineralogical Characterization of the Sands of the Middle Course of the Kasai River (Territory of Ilebo, Province of Kasai/DR Congo)
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作者 Lowny Trésor Madienga Kitshabi Ivon Ndala Tshiwisa +4 位作者 Modeste Kisangala Muke Thomas Kanika Mamena Dominique Wetshondo Osomba Emmanuel Cibambula Musau Adalbert-Jules Makutu Ma Ngwayaya 《Journal of Geoscience and Environment Protection》 2024年第7期50-71,共22页
The sand bars, in perpetual transformation, observable in the middle course of the Kasai river on the section between the city of Ilebo (pk605) to the confluence of the Loange river (pk525), pose enormous navigability... The sand bars, in perpetual transformation, observable in the middle course of the Kasai river on the section between the city of Ilebo (pk605) to the confluence of the Loange river (pk525), pose enormous navigability problems. This may be dependent on hydrosedimentological characteristics of the Kasai River. This abundance of sand thus conditions the morphology of the middle course of the Kasai River in the section under our study. It therefore constitutes sedimentary navigation obstacles. The objective of this study is the granulometric and mineralogical characterization of the bar sands of the Kasai River in this study section. Particle size analyzes reveal these are moderately well classified to well classified unimodal sands (Classification coefficient between 1.29 to 1.742) largely presenting grain size symmetry and rarely fine asymmetry (Asymmetry coefficient—Skewness between −0.197 to 0.069) with mesorkurtic and rarely leptokurtic and platykurtic acuity (Angulosity coefficient—Kurtosis between 0.814 to 1.323). All these parameters evolve in sawtooth patterns from upstream to downstream. And then, an automated mineralogical analysis of the sands of the Kasaï River using a Qemscan FEG Quanta 650 made it possible to determine a very varied mineralogical procession with a sawtooth evolution. It is largely dominated by quartz (between 93.73% and 99.07%), followed by calcite (0.01% - 2.66%), iron oxides (0.01% - 1.88%), orthoclase (0.04% - 0.99%), plagioclase (0.01% - 0.75%) and Kaolinite (0.18% - 0.71%). Finally, this mineralogical procession is characterized by a group of minerals which do not reach the threshold of 0.55% such as: illite, apatite, ilmenite, muscovite, chlorite, biotite, montmorillonite, rutile, pyrophyllite, siderite, zircon and dolomite. The evolution of the mineralogical procession of the sands of the bars is not as clear as in the case of particle size parameters. 展开更多
关键词 Characterization Granulometric MINERALOGICAL SandS Middle course Kasai River
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