المؤلفون: Pham, Hung, Rodriguez, C Ekaterina, Donald, Graham W, Hertzer, Kathleen M, Jung, Xiaoman S, Chang, Hui-Hua, Moro, Aune, Reber, Howard A, Hines, O Joe, Eibl, Guido

المصدر: Biochemical and Biophysical Research Communications. 439(1)

مصطلحات موضوعية: Medicinal and Biomolecular Chemistry, Chemical Sciences, Biotechnology, Genetics, Cancer, Pancreatic Cancer, Rare Diseases, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Butadienes, Cell Line, Tumor, Cell Proliferation, Cyclooxygenase 2, DNA-Binding Proteins, Dinoprostone, Enzyme Inhibitors, Flavonoids, Gene Expression Regulation, Neoplastic, Humans, MAP Kinase Kinase Kinases, MicroRNAs, Nitriles, Pancreatic Neoplasms, RNA Stability, RNA, Messenger, Signal Transduction, Time Factors, Transcription Factors, p38 Mitogen-Activated Protein Kinases, miR-143, Cyclooxygenase-2, MAPK, Prostaglandin E-2, Pancreatic cancer, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, COX-2, CREB, MAPK kinase, MEK, MTT, PGE(2), PKA, PaCa, Prostaglandin E(2), RREB1, cyclic AMP responsive element binding protein, cyclooxygenase-2, microRNA-143, mitogen-activated protein kinase, pancreatic cancer, prostaglandin E(2), protein kinase A, ras responsive element binding protein, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medicinal and biomolecular chemistry

الوصف: Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate the degradation of message RNA (mRNA) by targeting the 3'-untranslated region (3'-UTR) in regulating growth and survival through gene suppression. Deregulated miRNA expression contributes to disease progression in several cancers types, including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandin E2 (PGE2) resulting in increased cancer growth and metastases. Human PaCa cell lines were used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 ± 0.06 in AsPC-1, 0.20 ± 0.05 in Capan-2 and 0.10 ± 0.02 in MIA PaCa-2. miR-143 was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with 10 μM of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187 ± 18 and 152 ± 26-fold in BxPC-3 and 182 ± 7 and 136 ± 9-fold in HPAF-II. miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 ± 0.3-fold in BxPC-3 and 2.5 ± 0.2-fold in HPAF-II. COX-2 expression and cellular proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143. PGE2 levels decreased by 39.3 ± 5.0% in BxPC-3 and 48.0 ± 3.0% in HPAF-II transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX-2, PGE2, cellular proliferation and MEK/MAPK activation, implicating this pathway in regulating miR-143 expression.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8gw7g8zzTest

المؤلفون: Leefa, Isabelle, Prost, Gaëlle, Williams, Jennifer A., Moss, Stephen E., Nuber, Ulrike A.

المصدر: Biochemical and Biophysical Research Communications. 478(2):573-579

مصطلحات موضوعية: Annexin A2, Cell viability, MAPK pathway, Neural stem/progenitor cells, Podocalyxin, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Cell- och molekylärbiologi, Medical and Health Sciences, Basic Medicine, Cell and Molecular Biology

الوصف: Podocalyxin (PODXL) is a highly glycosylated and sialylated transmembrane protein that is up-regulated in various types of tumors and whose expression levels positively correlate with tumor grade. We previously found Podxl to be highly expressed in murine tumorigenic neural stem/progenitor cells (NSPs). Here we investigated the effects of elevated Podxl levels in these cells. NSPs overexpressing Podxl did not form brain tumors upon intracranial transplantations, indicating that high levels of this gene alone are not sufficient for tumor initiation. However, Podxl overexpression had a positive effect on cell number, sphere formation and cell viability, indicating that it might in this way contribute to the development and/or maintenance of tumors. Proteome analyses of Podxl-overexpressing and control NSPs revealed increased levels of Annexin A2 (ANXA2). We also found increased transcript levels, indicating that PODXL stimulates expression of the Anxa2 gene. Lack of Anxa2 in Podxl-overexpressing NSPs resulted in reduced viability of these cells, suggesting that PODXL-mediated pro-survival effects can at least in part be explained by increased ANXA2 levels. Finally, our data indicate that Podxl overexpression activates the MAP kinase (MAPK) pathway which in turn up-regulates Anxa2 expression. Our data indicate a novel molecular connection between PODXL and ANXA2: both exert pro-survival effects in NSPs, and PODXL positively regulates ANXA2 expression through the MAPK pathway.

الوصول الحر: https://lup.lub.lu.se/record/064a74ab-274d-4c05-a8ed-6a682db41163Test
http://dx.doi.org/10.1016/j.bbrc.2016.07.102Test

المؤلفون: Johanna Zerbib, Daniel Aberdam, Edward Pichinuk, Elie Frank, Léa Zennaro, Keren Oved, Orly Dorot, Lauriane N. Roux, Dominique Bremond-Gignac

المصدر: Biochemical and Biophysical Research Communications. 582:100-104

مصطلحات موضوعية: MAPK/ERK pathway, PAX6 Transcription Factor, Biophysics, Ritanserin, Haploinsufficiency, Limbus Corneae, Models, Biological, Biochemistry, Cell Line, Cell Movement, medicine, Humans, Receptor, Serotonin, 5-HT2A, Aniridia, Molecular Biology, Cell Proliferation, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, business.industry, Stem Cells, Drug Repositioning, Epithelium, Corneal, Cell migration, Cell Biology, medicine.disease, eye diseases, Hedgehog signaling pathway, HEK293 Cells, Gene Expression Regulation, Eye development, Cancer research, Serotonin Antagonists, sense organs, PAX6, Ophthalmic Solutions, business, Signal Transduction, medicine.drug

الوصف: Aniridia is a panocular inherited rare eye disease linked to heterozygous mutations on the PAX6 gene, which fail to properly produce sufficient protein essential for normal eye development and function. Most of the patients suffer from aniridia-related keratopathy, a progressive opacification of the cornea. There is no effective treatment for this blinding disease. Here we screen for small compounds and identified Ritanserin, a serotonin 2A receptor antagonist, that can rescue PAX6 haploinsufficiency of mutant limbal cells, defective cell migration and PAX6-target gene expression. We further demonstrated that Ritanserin activates PAX6 production through the selective inactivation of the MEK/ERK signaling pathway. Our data strongly suggest that repurposing this therapeutic molecule could be effective in preventing or treating existing blindness by restoring corneal transparency.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b1238d9cea94e57a0c2d98fb696fc82Test
https://doi.org/10.1016/j.bbrc.2021.10.036Test

المؤلفون: Ju Yeong Kim, Tai Soon Yong, Hun Hee Park, Soung Hoo Jeon

المصدر: Biochemical and Biophysical Research Communications. 581:74-80

مصطلحات موضوعية: inorganic chemicals, MAPK/ERK pathway, MAP Kinase Signaling System, Primary Cell Culture, Biophysics, Bone Marrow Cells, Biochemistry, Cell Movement, Epidermal growth factor, GSK-3, Cell Line, Tumor, Humans, Phosphorylation, Wnt Signaling Pathway, Molecular Biology, beta Catenin, Cell Proliferation, Cell Nucleus, Mitogen-Activated Protein Kinase 1, Glycogen Synthase Kinase 3 beta, Mitogen-Activated Protein Kinase 3, Osteoblasts, Epidermal Growth Factor, Chemistry, Cell growth, Wnt signaling pathway, Cell migration, Cell Biology, Cell biology, Gene Expression Regulation, Neoplastic, Protein Transport, Cancer cell, Diffusion Chambers, Culture, Cell fractionation, Lithium Chloride

الوصف: Lithium chloride (LiCl) is an important mood-stabilizing therapeutic agent for bipolar disorders, which has also been shown to inhibit cancer cell metastasis. Investigations of LiCl-induced signaling have focused mainly on extracellular signal regulated kinase 1/2 (ERK1/2) and glycogen synthase kinase 3 (GSK-3). However, little is known about the differences in cellular activities resulting from specific signaling via each of these pathways. In this study, we investigated the difference in responses between the Wnt/β-catenin and ERK pathways by LiCl or epidermal growth factor (EGF) treatment of osteosarcoma cells. In particular, we analyzed the mechanisms responsible for differences in cell mobility and cell proliferation when pERK or β-catenin is activated. In osteosarcoma cells treated with LiCl or EGF, active β-catenin and p-ERK protein levels were significantly increased compared to those in the control group. However, in wound healing and transwell invasion assays, U2OS and SaOS2 cell migration was significantly reduced by LiCl treatment but increased by EGF treatment. In addition, the proliferation of U2OS cells was reduced by LiCl treatment but increased by EGF treatment. Using immunofluorescence microscopy, we observed nuclear accumulation of phosphorylated ERK (pERK) with EGF treatment, but pERK was restricted to the perinuclear area with LiCl treatment. These results were confirmed using immunoblot assays after subcellular fractionation. Together, these data suggest that LiCl interferes with the translocation of pERK from the cytoplasm to the nucleus.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e8beb6e223b593524f8059875b14875Test
https://doi.org/10.1016/j.bbrc.2021.10.025Test

المؤلفون: Deqiang Dou, Bai-chen Mu, Ting-Guo Kang, Dongwei Li, Xiao-Tong Wang

المصدر: Biochemical and Biophysical Research Communications. 570:26-34

مصطلحات موضوعية: Male, MAPK/ERK pathway, Antioxidant, MAP Kinase Signaling System, medicine.medical_treatment, Biophysics, Nitric Oxide Synthase Type II, Arthritis, Inflammation, Pharmacology, medicine.disease_cause, Biochemistry, Chalcone, medicine, Extracellular, Animals, Rats, Wistar, Molecular Biology, Chemistry, Kinase, Synovial Membrane, Quinones, Cell Biology, medicine.disease, Arthritis, Experimental, Cyclooxygenase 2, Organ Specificity, Rheumatoid arthritis, Cytokines, Cattle, medicine.symptom, Oxidation-Reduction, Oxidative stress

الوصف: Hydroxysafflor yellow A (HSYA) from safflower (Carthamus tinctorius L.) possesses several medicinal properties. However, it is unknown whether HSYA is effective in the treatment of rheumatoid arthritis (RA). Hence, we investigated the effects of HSYA on the inflammation and synovial damage in rats with collagen-induced arthritis (CIA) by subjecting them to treatment with different doses of HSYA. Our results revealed that HSYA could significantly reduce paw swelling, pathological manifestations, and serum cytokine levels in rats with CIA. The HSYA-treated groups showed increased antioxidant enzyme activity in the serum and decreased expression of inflammatory mediators in the synovial tissues. Furthermore, HSYA treatment inhibited extracellular signal-regulated kinase (ERK) signalling pathway activation. Notably, the highest dose of HSYA (20 mg/kg) exhibited the best effects against RA symptoms. Therefore, our findings suggest that HSYA alleviates the inflammatory response and synovial damage in rats with CIA by inhibiting the ERK signalling pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::15ed0d14e2f6c7dad5f4e7ff7a966b6eTest
https://doi.org/10.1016/j.bbrc.2021.07.026Test

المؤلفون: Qiqian Huang, Kai Tu, Feiyan Liu, Yuelin Guan

المصدر: Biochemical and Biophysical Research Communications. 567:22-28

مصطلحات موضوعية: 0301 basic medicine, MAPK/ERK pathway, Programmed cell death, Colorectal cancer, Chemistry, MEK inhibitor, Biophysics, Cell Biology, medicine.disease, Biochemistry, Small molecule, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Apoptosis, 030220 oncology & carcinogenesis, medicine, Verticillin, Cancer research, MEK-ERK Pathway, Molecular Biology

الوصف: ABT-737, a small molecule BH-3 mimetic, is less effective against human colon cancers due to its resistance. Verticillin A is a natural compound, which was previously purified from verticillium-infected mushrooms. Hence, we aimed at overcoming the ABT737 resistance observed in CRC tumors by combining Verticillin A with ABT-737 and figuring out the potential mechanism. In this study, we observed that Verticillin A could sensitize colon cancer to ABT-737-induced cell death through induction of mitochondrial-dependent apoptosis. Verticillin A could significantly increase the BIMEL/MCL-1 ratio to overcome ABT737 resistance through the suppression of the MEK/ERK pathway. In addition, up-regulation of BIM protein levels to activate BAX translocation results in apoptosis induction. Altogether, our work suggested the potential application of Verticillin A as a MEK inhibitor in BH3-mimetic-based therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::64d9c63647a1311b15c7c9a36f3ab1a2Test
https://doi.org/10.1016/j.bbrc.2021.05.103Test

المؤلفون: Qi Zhang, Dong-Hao Wu, Xiang-Yuan Wu, Ying-fen Hong, Hui-qiang Huang, Zhan-Hong Chen, Chang-Chang Jia, Tian-Tian Wang, Yang Li

المصدر: Biochemical and Biophysical Research Communications. 558:14-21

مصطلحات موضوعية: Male, 0301 basic medicine, MAPK/ERK pathway, Gene Expression, Apoptosis, Biochemistry, Mice, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, RNA-Seq, Cytotoxicity, Mice, Inbred BALB C, TOR Serine-Threonine Kinases, Liver Neoplasms, Drug Synergism, Sorafenib, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, medicine.drug, Carcinoma, Hepatocellular, Combination therapy, MAP Kinase Signaling System, Ubiquitin-Protein Ligases, Xanthones, Biophysics, Mice, Nude, Antineoplastic Agents, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Humans, Protein Kinase Inhibitors, neoplasms, Molecular Biology, PI3K/AKT/mTOR pathway, Cell Proliferation, Cell growth, business.industry, Membrane Proteins, Cell Biology, medicine.disease, Antineoplastic Agents, Phytogenic, Xenograft Model Antitumor Assays, digestive system diseases, 030104 developmental biology, Cancer research, business

الوصف: Sorafenib remains the standard first-line treatment for advanced hepatocellular carcinoma (HCC), although other clinical trials are currently underway for treatments that show better curative effects. However, some patients are not sensitive to sorafenib. α-Mangostin, extracted from the pericarp of the mangosteen, which is widely used as a traditional medicine, has anticancer and anti-proliferative properties in various types of cancers, including HCC. In the present study, we found that combining sorafenib and α-Mangostin could be synergistically toxic to HCC both in vitro and in vivo. We then demonstrated that the combination of sorafenib and α-Mangostin enhances the inhibition of cell proliferation in HCC cell lines. Combination therapy leads directly to apoptosis. In xenograft mouse models, the in vivo safety and effectivity was confirmed by a reduction in tumor size after combination treatment. RNA sequencing and protein testing showed that the expression of LRRC8A and RNF181 genes and mTOR and MAPK pathways may be associated with the synergistic effect of the two drugs. In conclusion, our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b06422124bd937a6545abfeaa0a42e81Test
https://doi.org/10.1016/j.bbrc.2021.04.047Test

المؤلفون: Masahiro Shiihara, Taiki Kajiwara, Hideaki Karasawa, Kazuki Kumada, Muneaki Shimada, Minoru Kobayashi, Mizuki Sato, Li Bin, Akihiro Yamamura, Shinobu Ohnuma, Hideyuki Suzuki, Toru Furukawa, Fumiki Katsuoka, Yuuri Hatsuzawa, Shigehiro Ito, Hodaka Tayama, Yasunobu Okamura, Takashi Kamei, Michiaki Unno, Yeashin Gazi

المصدر: Biochemical and Biophysical Research Communications. 560:59-65

مصطلحات موضوعية: Proto-Oncogene Proteins B-raf, 0301 basic medicine, MAPK/ERK pathway, Indazoles, endocrine system diseases, Colorectal cancer, Biophysics, Gene mutation, Biology, medicine.disease_cause, Biochemistry, Piperazines, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Exome Sequencing, medicine, Humans, Enzyme Inhibitors, Extracellular Signal-Regulated MAP Kinases, Protein kinase A, neoplasms, Molecular Biology, Mutation, Kinase, High-Throughput Nucleotide Sequencing, Cancer, Cell Biology, medicine.disease, digestive system diseases, Organoids, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, KRAS, Colorectal Neoplasms

الوصف: The mitogen-activated protein kinase (MAPK) pathway plays an important role in the colorectal cancer (CRC) progression, being supposed to be activated by the gene mutations, such as BRAF or KRAS. Although the inhibitors of extracellular signal-regulated kinase (ERK) have demonstrated efficacy in the cells with the BRAF or KRAS mutations, a clinical response is not always associated with the molecular signature. The patient-derived organoids (PDO) have emerged as a powerful in vitro model system to study cancer, and it has been widely applied for the drug screening. The present study aims to analyze the association between the molecular characteristics which analyzed by next-generation sequencing (NGS) and sensitivity to the ERK inhibitor (i.e., SCH772984) in PDO derived from CRC specimens. A drug sensitivity test for the SCH772984 was conducted using 14 CRC cell lines, and the results demonstrated that the sensitivity was in agreement with the BRAF mutation, but was not completely consistent with the KRAS status. In the drug sensitivity test for PDO, 6 out of 7 cases with either BRAF or KRAS mutations showed sensitivity to the SCH772984, while 5 out of 6 cases of both BRAF and KRAS wild-types were resistant. The results of this study suggested that the molecular status of the clinical specimens are likely to represent the sensitivity in the PDOs but is not necessarily absolutely overlapping. PDO might be able to complement the limitations of the gene panel and have the potential to provide a novel precision medicine.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::324cdca03241bc906f9fa89aecb88193Test
https://doi.org/10.1016/j.bbrc.2021.04.130Test

المؤلفون: Zhi Zhang, Po Gao, Suqing Yin, Bao-Shan Wang, Weifeng Yu, Liqun Yang, Yan-Yu Zhou, Yu-Ling Wu, Dong-Dong Lv, Meng-Han Mao, Ling Zhu, Yingfu Jiao

المصدر: Biochemical and Biophysical Research Communications. 557:69-76

مصطلحات موضوعية: Male, 0301 basic medicine, MAPK/ERK pathway, MAP Kinase Signaling System, medicine.medical_treatment, Biophysics, Remifentanil, Mice, Transgenic, Pharmacology, Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, Cyclin D1, Downregulation and upregulation, medicine, Animals, Hepatectomy, Molecular Biology, Cells, Cultured, Cell Proliferation, Mice, Knockout, Chemistry, Regeneration (biology), Cell Biology, beta-Arrestin 2, Liver regeneration, Liver Regeneration, Up-Regulation, Analgesics, Opioid, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Reperfusion Injury, 030220 oncology & carcinogenesis, Hepatocyte, Hepatocytes, medicine.drug

الوصف: Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 μg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of β-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific β-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a β-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::746f5820c38f2a382cba85ba9b650dc1Test
https://doi.org/10.1016/j.bbrc.2021.04.008Test

المؤلفون: Chunqiu Li, Qiao-Yun Yang, Wuyang He, Li Wang, Qingwei Chen, Yi-Pin Zhao, Chun-Rong Wu

المصدر: Biochemical and Biophysical Research Communications. 552:37-43

مصطلحات موضوعية: Male, 0301 basic medicine, MAPK/ERK pathway, medicine.medical_specialty, MAP Kinase Kinase 4, p38 mitogen-activated protein kinases, Biophysics, Apoptosis, Inflammation, Diet, High-Fat, p38 Mitogen-Activated Protein Kinases, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Protein kinase A, Molecular Biology, Cells, Cultured, Mice, Knockout, Chemistry, Kinase, digestive, oral, and skin physiology, Cell Biology, Atherosclerosis, Ghrelin, Lipoproteins, LDL, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Cerebrovascular Circulation, 030220 oncology & carcinogenesis, Pericyte, Signal transduction, medicine.symptom, Pericytes, Injections, Intraperitoneal, Signal Transduction

الوصف: Ghrelin is a peptide hormone with strong anti-inflammatory properties. In fact, Ghrelin was reported to improve endothelial dysfunction caused by excessive fat. However, its role in preserving the integrity of brain microvascular, under conditions of lipid dysregulation and inflammation, is not known. The objective of this study is to characterize the role of Ghrelin in the protection of cerebral microvascular integrity, during atherosclerosis, and uncover its underlying molecular mechanism. Our results demonstrated that an atherosclerotic condition, brought on by a high fat diet (HFD), can produce massive increases in serum inflammatory factors, blood lipids, cerebral microvascular leakage, and activation of the p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK-JNK) pathway. It also produced significantly damaged pericytes morphology, resulting in pericyte decrease. Ghrelin treatment, on the other hand, protected against cerebral microvascular leakage and pericytes damage. Ghrelin effectively downregulated the expression of pro-inflammatory cytokines, and it also suppressed the p38 MAPK-JNK signaling pathway. Additionally, in isolated mouse cerebral microvascular pericytes, ox-LDL lead to increased apoptosis and secretion of inflammatory factors, along with an elevation in phosphorylated p38 MAPK-JNK proteins. Alternately, Ghrelin administration markedly lowered expression of inflammatory factors, suppressed the p38 MAPK-JNK signaling path, and halted cell apoptosis. However, pretreatment of Hesperetin, a p38 MAPK-JNK agonist, abrogated the Ghrelin-mediated suppression of inflammation and apoptosis in pericytes. Taken together, these results suggest that Ghrelin restored cerebral microvascular integrity and reduced vascular leakage in atherosclerosis mice, in part, by its regulation of inflammatory and apoptotic signaling pathways in pericytes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88d1b5a5d9a1c3a1fca56b9b66bd7f6eTest
https://doi.org/10.1016/j.bbrc.2021.03.032Test