المؤلفون: Rui Su, Chuting Li, Xiuyuan Wang, Zhendong Li, Ziqi Wen, Zhao Yin, Guiping Huang, Yanjun Liu, Juhua Yang, Haiyan Hu, Hong Nie, Keda Zhang, Jia Fei

المصدر: Molecular Therapy: Nucleic Acids, Vol 32, Iss , Pp 729-742 (2023)

مصطلحات موضوعية: MT: Non-coding RNAs, chronic myeloid leukemia, BCR-ABL1-independent imatinib resistance, drug resistance, small activating RNA (saRNA), mir-181a, Therapeutics. Pharmacology, RM1-950

الوصف: A large proportion of patients with chronic myeloid leukemia (CML; 20%–50%) develop resistance to imatinib in a BCR-ABL1-independent manner. Therefore, new therapeutic strategies for use in this subset of imatinib-resistant CML patients are urgently needed. In this study, we used a multi-omics approach to show that PPFIA1 was targeted by miR-181a. We demonstrate that both miR-181a and PPFIA1-siRNA reduced the cell viability and proliferative capacity of CML cells in vitro, as well as prolonged the survival of B-NDG mice harboring human BCR-ABL1-independent imatinib-resistant CML cells. Furthermore, treatment with miR-181a mimic and PPFIA1-siRNA inhibited the self-renewal of c-kit+ and CD34+ leukemic stem cells and promoted their apoptosis. Small activating (sa)RNAs targeting the promoter of miR-181a increased the expression of endogenous primitive miR-181a (pri-miR-181a). Transfection with saRNA 1–3 inhibited the proliferation of imatinib-sensitive and -resistant CML cells. However, only saRNA-3 showed a stronger and more sustained inhibitory effect than the miR-181a mimic. Collectively, these results show that miR-181a and PPFIA1-siRNA may overcome the imatinib resistance of BCR-ABL1-independent CML, partially by inhibiting the self-renewal of leukemia stem cells and promoting their apoptosis. Moreover, exogenous saRNAs represent promising therapeutic agents in the treatment of imatinib-resistant BCR-ABL1-independent CML.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2162253123001129Test; https://doaj.org/toc/2162-2531Test

الوصول الحر: https://doaj.org/article/d06e377d9f1e4c018fd25423ef6dd82eTest

المؤلفون: Zeyuan Lin, Shanshan Li, Haiming Xiao, Zhanchi Xu, Chuting Li, Jingran Zeng, Shaogui Wang, Zhongqiu Liu, Heqing Huang

المصدر: Cell Reports, Vol 42, Iss 8, Pp 112851- (2023)

مصطلحات موضوعية: CP: Molecular biology, CP: Metabolism, Biology (General), QH301-705.5

الوصف: Summary: The multiple roles of TGR5 in the regulation of glucose metabolism, inflammation, and oxidative stress have drawn attention as therapeutic candidates for diabetes-related kidney disease. However, diabetes induces downregulation of renal TGR5 protein expression, and the regulatory mechanisms have not been clarified. Here, we identify that Smurf1, an E3 ubiquitin ligase, is a critical interactor of TGR5 and mediates the ubiquitination and proteasomal degradation of TGR5 under high glucose stimulation in glomerular mesangial cells. Genetic deficiency of Smurf1 restores TGR5 protein expression and attenuates renal injuries in diabetic mice. Mechanistically, Smurf1 interacts with the TGR5 ICL2 region by its HECT domain and induces K11/K48-linked polyubiquitination of TGR5 at K306 residue. Moreover, restoration of TGR5 protects db/db mice from diabetic nephropathy. These observations elucidate the critical role of Smurf1 in regulating TGR5 stability, suggesting that pharmacological targeting of the interaction between Smurf1 and TGR5 could serve as a promising therapeutic strategy against diabetic nephropathy.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2211124723008628Test; https://doaj.org/toc/2211-1247Test

الوصول الحر: https://doaj.org/article/ae59bc07476d47bb9a8e28b84fff1701Test

المؤلفون: Yanjun Liu, Chuting Li, Rui Su, Zhao Yin, Guiping Huang, Juhua Yang, Zhendong Li, Keda Zhang, Jia Fei

المصدر: Molecular Therapy: Oncolytics, Vol 23, Iss , Pp 560-570 (2021)

مصطلحات موضوعية: SOS1, imatinib sensitivity, resistance with BCR-ABL independence, CML, SLC22A4, RNA-seq, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Resistance to the BCR-ABL inhibitor imatinib mesylate poses a major problem for the treatment of chronic myeloid leukemia. Imatinib resistance often results from a secondary mutation in BCR-ABL that interferes with drug binding. However, sometimes there is no mutation in BCR-ABL, and the basis of such BCR-ABL-independent imatinib mesylate resistance remains to be elucidated. SOS1, a guanine nucleotide exchange factor for Ras protein, affects drug sensitivity and resistance to imatinib. The depletion of SOS1 markedly inhibits cell growth either in vitro or in vivo and significantly increases the sensitivity of chronic myeloid leukemia cells to imatinib. Furthermore, LC-MS/MS and RNA-seq assays reveal that SOS1 negatively regulates the expression of SLC22A4, a member of the carnitine/organic cation transporter family, which mediates the active uptake of imatinib into chronic myeloid leukemia cells. HPLC assay confirms that intracellular accumulation of imatinib is accompanied by upregulation of SLC22A4 through SOS1 inhibition in both sensitive and resistant chronic myeloid leukemia cells. BAY-293, an inhibitor of SOS1/Ras, was found to depress proliferation and colony formation in chronic myeloid leukemia cells with resistance and BCR-ABL independence. Altogether these findings indicate that targeting SOS1 inhibition promotes imatinib sensitivity and overcomes resistance with BCR-ABL independence by SLC22A4-mediated uptake transport.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2372770521001595Test; https://doaj.org/toc/2372-7705Test

الوصول الحر: https://doaj.org/article/bdf5d9c72c494d8ba975006ae84f5c9cTest

المؤلفون: Rui Chen, Jingran Zeng, Chuting Li, Haiming Xiao, Shanshan Li, Zeyuan Lin, Kaipeng Huang, Juan Shen, Heqing Huang

المصدر: Frontiers in Pharmacology, Vol 13 (2022)

مصطلحات موضوعية: fraxin, diabetic nephropathy, oxidative stress, Connecxin43, AKT, Nrf2/ARE pathway, Therapeutics. Pharmacology, RM1-950

الوصف: Diabetic nephropathy (DN) is quickly becoming the largest cause of end-stage renal disease (ESRD) in diabetic patients, as well as a major source of morbidity and mortality. Our previous studies indicated that the activation of Nrf2/ARE pathway via Connexin43 (Cx43) considerably contribute to the prevention of oxidative stress in the procession of DN. Fraxin (Fr), the main active glycoside of Fraxinus rhynchophylla Hance, has been demonstrated to possess many potential pharmacological activities. Whereas, whether Fr could alleviate renal fibrosis through regulating Cx43 and consequently facilitating the activation of Nrf2/ARE pathway needs further investigation. The in vitro results showed that: 1) Fr increased the expression of antioxidant enzymes including SOD1 and HO-1 to inhibit high glucose (HG)-induced fibronectin (FN) and inflammatory cell adhesion molecule (ICAM-1) overexpression; 2) Fr exerted antioxidant effect through activating the Nrf2/ARE pathway; 3) Fr significantly up-regulated the expression of Cx43 in HG-induced glomerular mesangial cells (GMCs), while the knock down of Cx43 largely impaired the activation of Nrf2/ARE pathway induced by Fr; 4) Fr promoted the activation of Nrf2/ARE pathway via regulating the interaction between Cx43 and AKT. Moreover, in accordance with the results in vitro, elevated levels of Cx43, phosphorylated-AKT, Nrf2 and downstream antioxidant enzymes related to Nrf2 were observed in the kidneys of Fr-treated group compared with model group. Importantly, Fr significantly improved renal dysfunction pathological changes of renal fibrosis in diabetic db/db mice. Collectively, Fr could increase the Cx43-AKT-Nrf2/ARE pathway activation to postpone the diabetic renal fibrosis and the up-regulation of Cx43 is probably a novel mechanism in this process.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphar.2022.853383/fullTest; https://doaj.org/toc/1663-9812Test

الوصول الحر: https://doaj.org/article/54e4f4580925414182cc63a5ca820762Test

المؤلفون: Ge Xiong, Daifeng Dong, Chang Cheng, Yali Jiang, Xiaoqiang Sun, Jiayue He, Chuting Li, Yidian Gao, Xue Zhong, Haofei Zhao, Xiang Wang, Shuqiao Yao

المصدر: NeuroImage: Clinical, Vol 32, Iss , Pp 102871- (2021)

مصطلحات موضوعية: Major depressive disorder, Remitted depression, Subcortical volume, Structural covariance network, State-independent alteration, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429

الوصف: It has been proposed recently that major depressive disorder (MDD) could represent an adaptation to conserve energy after the perceived loss of an investment in a vital source, such as group identity, personal assets, or relationships. Energy conserving behaviors associated with MDD may form a persistent marker in brain regions and networks involved in cognition and emotion regulation. In this study, we examined whether subcortical regions and volume-based structural covariance networks (SCNs) have state-independent alterations (trait markers).First-episode drug-naïve currently depressed (cMDD) patients (N = 131), remitted MDD (RD) patients (N = 67), and healthy controls (HCs, N = 235) underwent structural magnetic resonance imaging (MRI). Subcortical gray matter volumes (GMVs) were calculated in FreeSurfer software, and group differences in GMVs and SCN were analyzed.Compared to HCs, major findings were decreased GMVs of left pallidum and pulvinar anterior of thalamus in the cMDD and RD groups, indicative of a trait marker. Relative to HCs, subcortical SCNs of both cMDD and RD patients were found to have reduced small-world-ness and path length, which together may represent a trait-like topological feature of depression.In sum, the left pallidum, left pulvinar anterior of thalamus volumetric alterations may represent trait marker and reduced small-world-ness, path length may represent trait-like topological feature of MDD.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2213158221003156Test; https://doaj.org/toc/2213-1582Test

الوصول الحر: https://doaj.org/article/d576f7fd064345039d0ae9d3a5b4fbf8Test

المؤلفون: Xiaoqiang Sun, Qingsen Ming, Xue Zhong, Daifeng Dong, Chuting Li, Ge Xiong, Chang Cheng, Wanyi Cao, Jiayue He, Xiang Wang, Jinyao Yi, Shuqiao Yao

المصدر: Frontiers in Behavioral Neuroscience, Vol 14 (2020)

مصطلحات موضوعية: stress, functional magnetic resonance imaging, monoamine oxidase A, cortisol, hippocampus, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: The stress response is regulated by many mechanisms. Monoamine oxidase A (MAOA) has been related to many mental illnesses. However, few studies have explored the relationship between MAOA and acute laboratory-induced psychosocial stress with functional magnetic resonance imaging (fMRI). In the current study, the Montreal Imaging Stress Task (MIST) and fMRI were used to investigate how MAOA influences the stress response. Increased cortisol concentrations were observed after the task; functional connectivity between the bilateral anterior hippocampus and other brain regions was reduced during stress. MAOA-H allele carriers showed greater deactivation of the right anterior hippocampus and greater cortisol response after stress than did MAOH-L allele carriers. Hippocampal deactivation may lead to disinhibition of the hypothalamic-pituitary-adrenal (HPA) axis and the initiation of stress hormone release under stress. Our results suggest that the MAOA gene regulates the stress response by influencing the right anterior hippocampus.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fnbeh.2020.00065/fullTest; https://doaj.org/toc/1662-5153Test

الوصول الحر: https://doaj.org/article/957824273a5849e182654534bfa69317Test

المؤلفون: Xue Zhong, Qingsen Ming, Daifeng Dong, Xiaoqiang Sun, Chang Cheng, Ge Xiong, Chuting Li, Xiaocui Zhang, Shuqiao Yao

المصدر: Frontiers in Psychology, Vol 10 (2020)

مصطلحات موضوعية: childhood maltreatment, stress, cortisol, fMRI, sensitization, Psychology, BF1-990

الوصف: BackgroundChildhood maltreatment is a strong risk factor for the development of depression in later life. However, the neurobiological mechanisms underlying this vulnerability are not well understood. As depression has been associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and increased responsiveness to psychosocial stressors, we speculated that childhood maltreatment may lead to lasting alteration of the stress response system, thereby increasing the risk of depression. This study investigated the effects of childhood maltreatment on the stress response in healthy subjects while controlling for psychiatric condition.MethodsForty-eight healthy young adults (24 females) with childhood maltreatment experience and 48 healthy controls (33 females) without such experience were administered the Montreal Imaging Stress Task during functional magnetic resonance imaging. Childhood maltreatment experience was assessed using the 28-item Childhood Trauma Questionnaire (CTQ). Between-group differences in subjective stress levels, whole brain activations and cortisol levels were assessed.ResultsRelative to healthy control subjects, individuals exposed to childhood maltreatment exhibited higher subjective stress and cortisol levels. Neurofunctionally, participants with histories of childhood maltreatment displayed significantly increased activation in the dorsolateral prefrontal cortex (dlPFC), insula and precuneus, and decreased activation in ventromedial prefrontal cortex (vmPFC) relative to healthy controls during the psychosocial stress task. Activations in dlPFC and insula correlated with CTQ scores in the childhood maltreatment group.ConclusionThe results of this study show that childhood maltreatment induces lasting changes in brain function and HPA-axis responsiveness to stress. The observed abnormal activation in the dlPFC, insula and vmPFC and enhanced cortisol response are similar to those seen in individuals with depression. This dysfunction might serve as a diathesis that embeds latent vulnerability to psychiatric disorders, and this mechanism provides evidence supporting the stress sensitization model.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fpsyg.2019.02961/fullTest; https://doaj.org/toc/1664-1078Test

الوصول الحر: https://doaj.org/article/53cea755aeab4fd8ad98c6e1370db582Test

المؤلفون: Wanyi Cao, Chuting Li, Jing Zhang, Daifeng Dong, Xiaoqiang Sun, Shuqiao Yao, Bingsheng Huang, Jun Liu

المصدر: Frontiers in Human Neuroscience, Vol 13 (2019)

مصطلحات موضوعية: early-onset conduct disorder, adolescent-onset conduct disorder, regional homogeneity, resting-state functional magnetic resonance imaging, developmental taxonomic theory, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Purpose: Developmental taxonomic theory posits that formation of early-onset conduct disorder (EO-CD), is considered to have a neurodevelopmental etiology and have more severe psychosocial and neuropsychological dysfunction than adolescent-onset CD (AO-CD), which is thought to stem largely from social mimicry of deviant peers. The purpose of the current study was to investigate whether regional homogeneity (ReHo), denoting the spontaneous brain activity, supports developmental taxonomic theory in a resting state (rs).Materials and Methods: Rs-functional magnetic resonance imaging (fMRI) examinations were administered to 36 EO-CD patients, 32 AO-CD patients, and 30 healthy controls (HCs). All participants were male adolescents, aged between 12 and 17 years old. A one-way analysis of covariance (ANCOVA), with age and IQ as covariates, was performed to identify regions with significant group differences in ReHo values, followed by a post hoc analyses.Results: Compared with the AO-CD groups, EO-CD had higher ReHo values in the right middle/inferior frontal gyrus. Compared with the HCs, the EO-CD group exhibited lower ReHo values in the left precuneus, left middle occipital gyrus, left cerebellum posterior lobe and the right inferior parietal lobule, as well as higher ReHo values in the right middle frontal gyrus, left insula/inferior frontal gyrus, right postcentral gyrus, and the left anterior cingulate gyrus. Compared with the HCs, the AO-CD group showed lower ReHo values in the bilateral precuneus, left cerebellum posterior lobe, and the right inferior parietal lobule.Conclusion: Significant differences in ReHo were observed between the EO-CD and AO-CD groups, implying distinct neuropathological mechanisms of the two CD subtypes, consistent with developmental taxonomic theory. CD-associated abnormalities in ReHo may be related to high-order cognitive and low-level perceptual system impairments in CD.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fnhum.2019.00026/fullTest; https://doaj.org/toc/1662-5161Test

الوصول الحر: https://doaj.org/article/1cf68acc99974519af4a5a85fb549fbbTest

المؤلفون: Yi Zhang, Lei Wang, Xin Wang, Yuting Wang, Chuting Li, Xiongzhao Zhu

المصدر: Frontiers in Psychiatry, Vol 9 (2019)

مصطلحات موضوعية: maternal deprivation, depression, GDNF, DNA methylation, ventral regimental area, Psychiatry, RC435-571

الوصف: Objective: To study the expression and DNA methylation of the Glial cell line-derived neurotrophic factor (GDNF) gene in the development of depression-like behaviors in rats experiencing maternal deprivation stress in early life.Methods: Newborn SD rats were randomly assigned to a normal control group (NOR) or maternal deprivation group (MD). An open field test (OPT), sucrose preference test (SPT), and a forced swimming test (FST) were used to evaluate rats' behaviors. Protein, mRNA, and methylation levels were measured by ELISA/Western blot, real-time PCR, and BiSulfte Amplicon sequencing PCR, respectively.Results: MD rats had significantly shorter total distance and more fecal pellets in OPT, a lower sucrose preference rate in SPT, and a longer immobility time in FST than NOR rats. Compared with NOR rats, MD rats showed a significantly higher plasma corticosterone (CORT) level. The levels of plasma dopamine (DA) and the GDNF were significantly lower in the MD rats than in NOR rats. In the ventral tegmental area (VTA) tissues, MD rats had a significantly higher level of methylation at the GDNF gene promoter than NOR rats. The expression of the GDNF mRNA and protein were significantly lower in MD rats than in NOR rats. The total distance was significantly correlated with plasma DA and GDNF, the DNA methylation level at the GDNF promoter and the GDNF mRNA level in the VTA. Fecal pellets showed a significant correlation with plasma CORT. The sucrose preference rate was significantly correlated with plasma DA, the DNA methylation level at the GDNF promoter and the GDNF mRNA level in the VTA. Immobility time showed a significant correlation with the plasma DA, the plasma GDNF and the GDNF mRNA level in the VTA.Conclusion: up-regulation of DNA methylation at the GDNF gene promotor and the subsequent down-regulation of the GDNF gene expression in the VTA, may be involved in the development of depression-like behaviors in rats experiencing MD in early life.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fpsyt.2018.00732/fullTest; https://doaj.org/toc/1664-0640Test

الوصول الحر: https://doaj.org/article/91249701e07c40d897584c8ccccf3360Test

المؤلفون: Chuting Li, Yuan Liu, Dexiang Liu, Hong Jiang, Fang Pan

المصدر: Neural Plasticity, Vol 2016 (2016)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Several types of microRNA (miRNA) overexpression in the brain are associated with stress. One of the targets of miR-34c is the stress-related corticotrophin releasing factor receptor 1 mRNA (CRFR1 mRNA). Here we will probe into the short-term effect and long-term effect of early adolescent traumatic stress on the expression of miR-34c and CRFR1 mRNA. Traumatic stress was established by electric foot shock for six consecutive days using 28-day rats. The anxiety-like behaviors, memory damage, CRFR1 protein, CRFR1 mRNA, and miR-34c expression were detected in our study. The results of our study proved that exposure to acute traumatic stress in early adolescent can cause permanent changes in neural network, resulting in dysregulation of CRFR1 expression and CRFR1 mRNA and miR-34c expression in hypothalamus, anxiety-like behavior, and memory impairment, suggesting that the miR-34c expression in hypothalamus may be an important factor involved in susceptibility to PTSD.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2090-5904Test; https://doaj.org/toc/1687-5443Test

الوصول الحر: https://doaj.org/article/9b32f1d684be4a3f86e0f7d7b1edd3a4Test