Journal of Receptors and Signal Transduction最新文献_第6页

In silico screening of c-Met tyrosine kinase inhibitors targeting nucleotide and drug-substrate binding sites of ABCB1 as potential MDR reversal agents. 以ABCB1的核苷酸和药物-底物结合位点为靶点的c-Met酪氨酸激酶抑制剂作为潜在的MDR逆转剂的硅学筛选。

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-12-01 Epub Date: 2022-06-15 DOI: 10.1080/10799893.2022.2086988

Fatemeh Moosavi, Tahereh Damghani, Somayeh Ghazi, Somayeh Pirhadi

{"title":"In silico screening of c-Met tyrosine kinase inhibitors targeting nucleotide and drug-substrate binding sites of ABCB1 as potential MDR reversal agents.","authors":"Fatemeh Moosavi, Tahereh Damghani, Somayeh Ghazi, Somayeh Pirhadi","doi":"10.1080/10799893.2022.2086988","DOIUrl":"10.1080/10799893.2022.2086988","url":null,"abstract":"Purpose: Cancer is a significant public health problem and ranks as a leading cause of death globally. Multidrug resistance (MDR) affects the therapeutic potential of conventional chemotherapeutic agents in cancer chemotherapy. Receptor tyrosine kinases (RTKs) are enzymes whose aberrant activation contributes to the tumorigenesis of various types of cancers. The ability of several RTKs, such as c-Met, to reverse ABC transporters mediated MDR was shown before. We aimed to explore the ability of c-Met inhibitors to circumvent MDR in cancer by inhibiting the ABCB1 transporter using in silico studies.Methods: Docking virtual screening of several potent and structurally diverse c-Met inhibitors were applied to find repurposed candidates to target the ATP binding sites and drug-substrate binding pockets of the ABCB1 transporter. The selected candidate was subjected to molecular dynamics simulations.Results: Based on docking findings, among 19 clinical c-Met inhibitors, several drugs, particularly golvatinib, exerted the affinity to both ATP binding sites in the nucleotide-binding domains (NBDs) as well as the drug-substrate binding site in the transmembrane domains (TMDs). Moreover, several non-clinical c-Met inhibitors obtained from the ChEMBL database had strong interactions with TMDs and NBDs, among which CHEMBL1950194 and CHEMBL2385194 compounds showed the highest binding affinity, respectively. Additionally, as a potential repositioning drug, MD simulation studies of golvatinib, corroborated the docking results.Conclusion: We applied docking and molecular dynamics simulations to screen the potential c-Met inhibitors as the MDR reversing agents targeting ATP and drug-substrate binding sites, and the results suggested several repurposed candidate drugs.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"549-561"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10702327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Gαs and Gαq/11 protein coupling bias of two AVPR2 mutants (R68W and V162A) that cause nephrogenic diabetes insipidus. 导致肾源性尿崩症的两个AVPR2突变体(R68W和V162A)的Gαs和Gαq/11蛋白偶联偏倚

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-12-01 DOI: 10.1080/10799893.2022.2102651

Beril Erdem Tuncdemir

{"title":"Gαs and Gαq/11 protein coupling bias of two AVPR2 mutants (R68W and V162A) that cause nephrogenic diabetes insipidus.","authors":"Beril Erdem Tuncdemir","doi":"10.1080/10799893.2022.2102651","DOIUrl":"https://doi.org/10.1080/10799893.2022.2102651","url":null,"abstract":"Loss-of-function mutations of the arginine vasopressin receptor 2 gene (AVPR2) cause Nephrogenic diabetes insipidus (NDI). AVPR2 is a kind of G protein coupled receptor (GPCR) and mainly couples with Gαs protein leading to cAMP accumulation in the cell as a secondary messenger. Recent studies showed that some AVPR2 mutations could cause biased Gαq/11 protein coupling rather than Gαs. Investigation into the characterization of biased receptors may give insights into the relationship between the conformational change of the receptor because of the mutation and related downstream signaling. In this study, R68W and V162A were analyzed to whether they show a bias to Gαs or Gαq/11 proteins. Their functionality in terms of cAMP production via Gαs protein coupling was decreased compared to the wild-type receptor. On the other hand, they showed the ability to couple with Gαq/11 protein and make Ca2+ mobilization at different levels in the cell. R68W showed bias to coupling with Gαq/11 protein rather than V162A and wild-type receptor. Studies about the Gα protein coupling bias of mutant AVPR2s may broaden our understanding of the relationship between the changed conformation of the receptor and consequently activated signaling pathways, and also may shed light on the development of more effective new therapeutics.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"573-579"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10359783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of novel mycocompounds as inhibitors of PI3K/AKT/mTOR pathway against RCC. 新型真菌化合物作为抗RCC PI3K/AKT/mTOR通路抑制剂的鉴定。

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-12-01 DOI: 10.1080/10799893.2022.2123515

Ravi Prakash Yadav, Srilagna Chatterjee, Arindam Chatterjee, Dilip Kumar Pal, Sudakshina Ghosh, Krishnendu Acharya, Madhusudan Das

{"title":"Identification of novel mycocompounds as inhibitors of PI3K/AKT/mTOR pathway against RCC.","authors":"Ravi Prakash Yadav, Srilagna Chatterjee, Arindam Chatterjee, Dilip Kumar Pal, Sudakshina Ghosh, Krishnendu Acharya, Madhusudan Das","doi":"10.1080/10799893.2022.2123515","DOIUrl":"https://doi.org/10.1080/10799893.2022.2123515","url":null,"abstract":"PI3K/AKT/mTOR pathway is one of the frequently disrupted signaling pathways in renal cell carcinoma (RCC) that plays a significant role in tumor formation, disease progression and therapeutic resistance. Therefore, novel natural molecules targeting the critical proteins of this pathway will provide the best alternative to existing drugs, which are toxic and develops resistance. Recent studies have recognized the anti-cancer therapeutic potential of mycocompounds. The current study is focused on screening various mycocompounds from Astraeus hygrometricus against key cancer signaling proteins phosphoinositide 3-kinase (PI3K), protein kinase B, PKB (AKT1) and mammalian target of rapamycin (mTOR). We also studied in-silico cancer cells cytotoxicity and ADMET (absorption, distribution, metabolism, excretion and toxicity) profiles to elucidate the molecular mechanism against RCC and also to uncover the pharmacokinetic profile of these compounds. Astrakurkurone and Ergosta-4,6, 8-(14) 22-tetraene-3-one were the two most efficacious compounds with highest interaction scores and bonding. These compounds were both active against RCC4 and VMRC-RCZ cell lines of RCC. The ADME profiles of both were satisfactory based on druglikeness and bioavailability score criteria. Thus, this proposed study identified astrakurkurone and ergosta-4,6, 8-(14) 22-tetraene-3-one as potential anticancer drug candidates, and provides comparative structural insight into their binding to the 3 protein kinases.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"599-607"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10411097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ozone protects cardiomyocytes from myocardial ischemia-reperfusion injury through miR-200c/FOXO3 axis. 臭氧通过miR-200c/FOXO3轴保护心肌细胞免受心肌缺血再灌注损伤。

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-12-01 DOI: 10.1080/10799893.2022.2060259

Lian Zhang, Xingping Men, Shenglong Yu, Huizhuang Guo, Yi Luo, Hanwei Chen, Shaohua Mi

{"title":"Ozone protects cardiomyocytes from myocardial ischemia-reperfusion injury through miR-200c/FOXO3 axis.","authors":"Lian Zhang, Xingping Men, Shenglong Yu, Huizhuang Guo, Yi Luo, Hanwei Chen, Shaohua Mi","doi":"10.1080/10799893.2022.2060259","DOIUrl":"https://doi.org/10.1080/10799893.2022.2060259","url":null,"abstract":"Purpose: Myocardial ischemia-reperfusion injury (I/R) is a detrimental process contributing to the pathological progression of coronary artery diseases. Studies indicate that miRNAs are implicated in ischemic heart disease, and ozone therapy could protect the heart from ischemic heart disease. In this study, we investigated the effect of ozone on miR-200c expression and the potential role of miR-200c in an I/R myocardial injury model.Methods: A myocardial cellular model of I/R was established to detect the expression of miR-200c. Cardiomyocytes with I/R induction were treated with ozone as a cellular model to detect miR-200 expression and investigate its functional roles. The downstream target of miR-200c was predicted with Starbase online tools and validated by dual luciferase reporter assay. The function of miR-200c/FOXO3 axis in I/R was examined by CCK-8 proliferation and apoptotic assays.Results: miR-200c was upregulated in primary cardiomyocytes of the I/R model. In cardiomyocyte cells, cell proliferation in the I/R group was significantly impaired, which could be partially rescued by miR-200c inhibitor or ozone treatment. Cell death detected by LDH release and apoptosis assay in the I/R model could also be inhibited by miR-200c inhibitor or ozone treatment. FOXO3 was identified as a downstream target of miR-200c, which was induced by ozone treatment and suppressed by miR-200c. Silencing FOXO3 abrogated the protective effect of ozone treatment on the I/R cell model.Conclusion: Overall, our results suggest that ozone plays a cardio-protective role in I/R through regulating miR-200/FOXO3 axis, and indicate that targeting miR-200/FOXO3 axis could potentially alleviate I/R.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"531-539"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10817490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Methylglyoxal enhances the proliferation of vascular smooth muscle cells via Akt phosphorylation. 甲基乙二醛通过Akt磷酸化促进血管平滑肌细胞的增殖。

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-12-01 DOI: 10.1080/10799893.2022.2098328

Mustafa Kırça

{"title":"Methylglyoxal enhances the proliferation of vascular smooth muscle cells via Akt phosphorylation.","authors":"Mustafa Kırça","doi":"10.1080/10799893.2022.2098328","DOIUrl":"https://doi.org/10.1080/10799893.2022.2098328","url":null,"abstract":"Methylglyoxal (MGO) is predominantly produced as a by-product of the glycolysis pathway. The glyoxalase system effectively removes it in a healthy organism. However, this process is impaired, and MGO level is elevated in people with diabetes. MGO's effects on proliferation were mostly studied in cancer cells, and the data in other cell types are limited. This study inspected the proliferative capacity of MGO in vascular smooth muscle cells (VSMCs), which have a crucial role in atherosclerosis and restenosis. The roles of ERK1/2 MAPK and Akt phosphorylations in proliferation were determined. Telmisartan, irbesartan, and NF-κB inhibitor JSH-23's roles in protecting the cells from MGO-induced proliferation were also investigated. Primary VSMCs were isolated from the rat aorta. The proliferation was spectrophotometrically measured by using a tetrazolium salt (Wst-1). The cells were cultured in standard media (SM, glucose conc. 5.5 mM) or high glucose media (HGM, glucose conc. 25 mM; an in vitro model of hyperglycemia). ERK1/2 MAPK and Akt phosphorylations were determined by the western blot method. MGO triggered the proliferation at 24, 48, and 72 hrs in SM and 48 and 72 hrs in HGM. Low doses of MGO such as 1-10 µM can induce proliferation. The phosphorylated ERK1/2 MAPK and Akt participated in MGO-induced proliferation. Telmisartan, irbesartan, and JSH-23 effectively alleviated the proliferation and Akt phosphorylation. MGO could proliferate VSMCs even at low doses. Moreover, hypertensive diabetic patients might benefit from a sartan family drug to protect VSMCs from MGO-induced proliferation.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"567-572"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10335788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crosstalk between kisspeptin and gonadotropin-inhibitory hormone in the silence of puberty: preclinical evidence from a calcium signaling study. kisspeptin和促性腺激素抑制激素在青春期沉默中的串扰:来自钙信号研究的临床前证据。

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-12-01 DOI: 10.1080/10799893.2022.2125014

Ferah Bulut, Emine Kacar, Batuhan Bilgin, Munevver Gizem Hekim, Muhammed Mirac Keleştemur, Zafer Sahin, Ahmet Ayar, Mete Ozcan

{"title":"Crosstalk between kisspeptin and gonadotropin-inhibitory hormone in the silence of puberty: preclinical evidence from a calcium signaling study.","authors":"Ferah Bulut, Emine Kacar, Batuhan Bilgin, Munevver Gizem Hekim, Muhammed Mirac Keleştemur, Zafer Sahin, Ahmet Ayar, Mete Ozcan","doi":"10.1080/10799893.2022.2125014","DOIUrl":"https://doi.org/10.1080/10799893.2022.2125014","url":null,"abstract":"Kisspeptin and gonadotropin-inhibitory hormone (GnIH) are among suggested neuroendocrine modulators of reproductive function. Intracellular calcium signaling is a critical component in the regulation of a variety of physiological and pathological processes including neurotransmitter release, and, therefore, can be used as signaling indicator for investigating the involvement of kisspeptin, GnIH, and gonadotropin-releasing hormone (GnRH) release. Hence, this study investigated the effects of kisspeptin and GnIH on calcium signaling using immortalized hypothalamic cells (rHypoE-8) as a model. Kisspeptin neurons were loaded with the ratiometric calcium dye (Fura-2 AM, 1 μmol) and intracellular free calcium ([Ca2+]i) responses were quantified using digital fluorescence imaging system. Kisspeptin-10 (100, 300, and 1000 nM) caused a significant increase in [Ca2+]i in rHypoE-8 cells (n = 58, n = 64, and n = 49, respectively, p < 0.001). The kisspeptin receptor antagonist, P234, inhibited the calcium responses to kisspeptin (p < 0.001, n = 32). GnIH (100 and 1000 nM), alone, did not cause any significant change in the mean basal [Ca2+]i levels in kisspeptin cells, but GnIH attenuated the kisspeptin-evoked [Ca2+]i transients (n = 47, p < 0.001). This novel findings of [Ca2+]i signaling in in vitro setting implicate that kisspeptin and GnIH may exert their effects on hypothalamus-pituitary-gonadal (HPG) axis by modulating kisspeptin neurons. These results also implicate that kisspeptin neurons may have an autocrine regulation.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"608-613"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10336587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Pharmacological characterization of the α_2A-adrenergic receptor inhibiting rat hippocampal CA3 epileptiform activity: comparison of ligand efficacy and potency. 抑制大鼠海马 CA3 癫痫样活动的 α2A-肾上腺素能受体的药理学特征：配体功效和效力的比较。

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-12-01 Epub Date: 2022-08-19 DOI: 10.1080/10799893.2022.2110896

Joseph P Biggane, Ke Xu, Brianna L Goldenstein, Kylie L Davis, Elizabeth J Luger, Bethany A Davis, Chris W D Jurgens, Dianne M Perez, James E Porter, Van A Doze

{"title":"Pharmacological characterization of the α2A-adrenergic receptor inhibiting rat hippocampal CA3 epileptiform activity: comparison of ligand efficacy and potency.","authors":"Joseph P Biggane, Ke Xu, Brianna L Goldenstein, Kylie L Davis, Elizabeth J Luger, Bethany A Davis, Chris W D Jurgens, Dianne M Perez, James E Porter, Van A Doze","doi":"10.1080/10799893.2022.2110896","DOIUrl":"10.1080/10799893.2022.2110896","url":null,"abstract":"The mechanism underlying the antiepileptic actions of norepinephrine (NE) is unclear with conflicting results. Our objectives are to conclusively delineate the specific adrenergic receptor (AR) involved in attenuating hippocampal CA3 epileptiform activity and assess compounds for lead drug development. We utilized the picrotoxin model of seizure generation in rat brain slices using electrophysiological recordings. Epinephrine (EPI) reduced epileptiform burst frequency in a concentration-dependent manner. To identify the specific receptor involved in this response, the equilibrium dissociation constants were determined for a panel of ligands and compared with established binding values for α1, α2, and other receptor subtypes. Correlation and slope of unity were found for the α2A-AR, but not other receptors. Effects of different chemical classes of α-AR agonists at inhibiting epileptiform activity by potency (pEC50) and relative efficacy (RE) were determined. Compared with NE (pEC50, 6.20; RE, 100%), dexmedetomidine, an imidazoline (pEC50, 8.59; RE, 67.1%), and guanabenz, a guanidine (pEC50, 7.94; RE, 37.9%), exhibited the highest potency (pEC50). In contrast, the catecholamines, EPI (pEC50, 6.95; RE, 120%) and α-methyl-NE (pEC50, 6.38; RE, 116%) were the most efficacious. These findings confirm that CA3 epileptiform activity is mediated solely by α2A-ARs without activation of other receptor systems. These findings suggest a pharmacotherapeutic target for treating epilepsy and highlight the need for selective and efficacious α2A-AR agonists that can cross the blood-brain barrier.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"580-587"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10607954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Can calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX-3) be useful in diagnosing acute migraine attack? 降钙素基因相关肽(CGRP)和戊素-3 (PTX-3)在诊断急性偏头痛发作中有用吗?

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-12-01 DOI: 10.1080/10799893.2022.2097264

Sevilay Vural, Levent Albayrak

{"title":"Can calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX-3) be useful in diagnosing acute migraine attack?","authors":"Sevilay Vural, Levent Albayrak","doi":"10.1080/10799893.2022.2097264","DOIUrl":"https://doi.org/10.1080/10799893.2022.2097264","url":null,"abstract":"Purpose: Even if migraine is not fatal, it is a common and challenging disease with adverse effects on individuals' lives. The lack of objective diagnostic tools causes delays in diagnosis and treatment initiation. The primary aim of this study is to reveal the diagnostic value of Calcitonin Gene-Related Peptide (CGRP) and Pentraxin-3 (PTX-3) in acute migraine. To this aim, we compared the serum CGRP and PTX-3 levels of migraine patients with acute attacks to those in healthy individuals.Material and method: A total of 135 individuals (85 patients with migraine attacks with or without aura and 50 healthy controls) participated in the study. Serum CGRP and PTX-3 levels were measured with ELISA analysis. A p value less than 0.05 was considered significant.Results: Serum CGRP [146.70 (21.52-413.67) vs. 65.90 (3.80-256.60) pg/mL] and PTX-3 levels [12.71 (0.62-33.97) vs. 1.01 (0.06-9.48) ng/mL] were higher in patients with migraine attack than the control group (p < 0.01 and p < 0.01, respectively). ROC analysis showed that the cutoff value for serum CGRP was 121.39 pg/mL (AUC: 0.751, Sen:%61, Spe:%64) whereas the cutoff value for PTX-3 was 4,06 ng/mL (AUC:0.876, Sen:%73, Spe:%76). Serum CGRP levels were positively correlated with pain intensity. Serum CGRP and PTX-3 levels did not differ across gender groups and presence of aura in subgroup analysis.Conclusion: Patients with acute migraine attacks have higher serum CGRP and PTX-3 levels than controls. Both biomarkers show high potential for the diagnosis of a migraine attack.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 6","pages":"562-566"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10359779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Endothelial progenitor cells promote neural stem cell proliferation in hypoxic conditions through VEGF via the PI3K/AKT pathway. 内皮祖细胞通过PI3K/AKT通路通过VEGF促进缺氧条件下神经干细胞的增殖。

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-10-01 DOI: 10.1080/10799893.2021.2019275

Jingti Jing, Haoming Jiang, Lin Zhang

{"title":"Endothelial progenitor cells promote neural stem cell proliferation in hypoxic conditions through VEGF via the PI3K/AKT pathway.","authors":"Jingti Jing, Haoming Jiang, Lin Zhang","doi":"10.1080/10799893.2021.2019275","DOIUrl":"https://doi.org/10.1080/10799893.2021.2019275","url":null,"abstract":"Neurons and vascular cells compose neurovascular niches in the central nervous system where endothelial cells can promote neurogenesis via direct and indirect effects. Neurocytes and vascular cells are gravely destroyed upon spinal cord injury, which severely affects spinal motor functions. Neurogenesis originates from neural stem cells (NSCs) and endothelial cells derived from endothelial progenitor cells (EPCs) in the spinal cord. To demonstrate whether EPCs promote NSC proliferation, we cultured NSCs with EPC-conditioned medium from hypoxic conditions (CM) and EPC-unconditioned medium (UCM), i.e. endothelial cell basal medium-2, as a control. The number of S-phase cells in CM were 54.73 ± 0.67 whereas those in UCM were 26.30 ± 0.43, and the number of cells in CM was higher than that in UCM (0.32 ± 0.0019 vs. 0.55 ± 0.0029). We hypothesized that the cell proliferation was promoted by vascular endothelial growth factor A (VEGFA), which is secreted by EPCs in hypoxic conditions. We then used VEGF shRNA to decrease VEGFA secretion by EPCs. NSCs were cultured in conditioned medium from shRNA transfected EPCs under hypoxia (shRNA-CM) and EPC-conditioned medium under hypoxia (CM). The number of S-phase cells in the shRNA-CM was 36.86 ± 0.49 whereas that in CM was 53.61 ± 0.89, and the number of cells in the shRNA-CM was lower than that in CM (0.55 ± 0.0032 vs. 0.34 ± 0.0029). These data indicate that EPCs could promote NSC proliferation in hypoxic condition through VEGFA secretion.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 5","pages":"479-485"},"PeriodicalIF":2.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9199229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

SMILES-based QSAR and molecular docking study of xanthone derivatives as α-glucosidase inhibitors. 基于smiles的山酮类α-葡萄糖苷酶抑制剂QSAR与分子对接研究。

IF 2.8 4区生物学

Journal of Receptors and Signal Transduction Pub Date : 2022-08-01 Epub Date: 2021-08-12 DOI: 10.1080/10799893.2021.1957932

Shahin Ahmadi, Zohreh Moradi, Ashwani Kumar, Ali Almasirad

{"title":"SMILES-based QSAR and molecular docking study of xanthone derivatives as α-glucosidase inhibitors.","authors":"Shahin Ahmadi, Zohreh Moradi, Ashwani Kumar, Ali Almasirad","doi":"10.1080/10799893.2021.1957932","DOIUrl":"https://doi.org/10.1080/10799893.2021.1957932","url":null,"abstract":"Increasing diabetic population is one of the major health concerns all over the world. Inhibition of α-glucosidase is a clinically proved and attractive strategy to manage diabetes. In this study, robust and reliable QSAR models to predict α-glucosidase inhibitory potential of xanthone derivatives are developed by the Monte Carlo technique. The chemical structures are represented by SMILES notation without any 3D-optimization. The significance of the index of ideality correlation (IIC) with applicability domain (AD) is also studied in depth. The models developed using CORAL software by considering IIC criteria are found to be statistically more significant and robust than simple balance of correlation. The QSAR models are validated by both internal and external validation methods. The promoters of increase and decrease of activity are also extracted and interpreted in detail. The interpretation of developed models explains the role of different structural attributes in predicting the pIC50 of xanthone derivatives as α-glucosidase inhibitors. Based on the results of model interpretation, modifications are done on some xanthone derivatives and 15 new molecules are designed. The α-glucosidase inhibitory activity of novel molecules is further supported by docking studies.","PeriodicalId":16962,"journal":{"name":"Journal of Receptors and Signal Transduction","volume":"42 4","pages":"361-372"},"PeriodicalIF":2.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39304983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8