Prostate cancer (PCa) is the second leading cause of death in men, and current studies have shown that circular RNAs (circRNAs) play important roles in its occurrence and development. Detection of circRNAs in PCa cells found that circ_KATNAL1 was down-regulated, mainly located in the cytoplasm and contained multiple binding sites of miR-145-3p, an anti-cancer miRNA. RIP detection with anti-AGO2 antibody, RNA pull down assay with biotin-labeled circ_KATNAL1 probe or miR-145-3p mimics, and dual luciferase reporter gene assay confirmed that circ_KATNAL1 directly bound to miR-145-3p in cells, and WISP1, which was highly expressed in many tumors, was an important target gene of miR-145-3p. Circ_KATNAL1 and miR-145-3p promoted each other's expression, and down-regulated the expression of target gene WISP1. Both circ_KATNAL1 and miR-145-3p inhibited cell proliferation, invasion, migration and the expression of MMP-2 and MMP-9, promoted cell apoptosis and the activation of Caspase-3, Caspase-8, Caspase-9 and PARP, while WISP1 had the opposite effects, and the above functions of circ_KATNAL1 were performed through the miR-145-3p/WISP1 pathway. Therefore, circ_KATNAL1 plays an anti-cancer role in PCa cells through the miR-145-3p/WISP1 pathway, which may be an important target for the diagnosis and treatment of PCa.
{"title":"Circ_KATNAL1 regulates prostate cancer cell growth and invasion through miR-145-3p/WISP1 pathway.","authors":"Yu Zheng, Chao-jiang Chen, Zhuoyuan Lin, Jianxin Li, Jie Liu, Fu-Jun Lin, Xing Zhou","doi":"10.1139/bcb-2019-0211","DOIUrl":"https://doi.org/10.1139/bcb-2019-0211","url":null,"abstract":"Prostate cancer (PCa) is the second leading cause of death in men, and current studies have shown that circular RNAs (circRNAs) play important roles in its occurrence and development. Detection of circRNAs in PCa cells found that circ_KATNAL1 was down-regulated, mainly located in the cytoplasm and contained multiple binding sites of miR-145-3p, an anti-cancer miRNA. RIP detection with anti-AGO2 antibody, RNA pull down assay with biotin-labeled circ_KATNAL1 probe or miR-145-3p mimics, and dual luciferase reporter gene assay confirmed that circ_KATNAL1 directly bound to miR-145-3p in cells, and WISP1, which was highly expressed in many tumors, was an important target gene of miR-145-3p. Circ_KATNAL1 and miR-145-3p promoted each other's expression, and down-regulated the expression of target gene WISP1. Both circ_KATNAL1 and miR-145-3p inhibited cell proliferation, invasion, migration and the expression of MMP-2 and MMP-9, promoted cell apoptosis and the activation of Caspase-3, Caspase-8, Caspase-9 and PARP, while WISP1 had the opposite effects, and the above functions of circ_KATNAL1 were performed through the miR-145-3p/WISP1 pathway. Therefore, circ_KATNAL1 plays an anti-cancer role in PCa cells through the miR-145-3p/WISP1 pathway, which may be an important target for the diagnosis and treatment of PCa.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80791754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chao Yang, Yu Chen, Liwu Zhong, Min You, Zhiling Yan, Maowen Luo, Bo Zhang, Benyanzi Yang, Qiang Chen
Mesenchymal stem cells (MSCs) have proven powerful potential for cell-based therapy both in regenerative medicine and disease treatment. Human umbilical cords and exfoliated deciduous teeth are the main sources to derive MSCs with nearly no donor injury and ethical issue. The goal of this study was to investigate the differences of biological characteristics in human umbilical cord mesenchymal stem cells (UCMSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). UCMSCs and SHEDs were identified by flow cytometry. The proliferation, differentiation, migration, chemotaxis, paracrine, immunomodulatory, neurite growth-promoting capabilities and acetaldehyde dehydrogenase (ALDH) activity were comparatively studied between these two MSCs in vitro. The results showed that both SHEDs and UCMSCs expressed cell surface markers characteristic of MSCs. Furthermore, SHEDs exhibited better capacities in proliferation, migration, promotion of neurite growth and chondrogenic differentiation. Meanwhile, UCMSCs showed more outstanding adipogenic differentiation and chemotaxis abilities. Additionally, there is no significant difference in osteogenic differentiation, immunomodulatory capacity, and the proportion of ALDH bright compartment. Our findings indicate that although both UCMSCs and SHEDs are mesenchymal stem cells and presented some similar biological characteristics, they also have differences in many aspects, which might be instructive to future clinical cellular therapeutics for different diseases.
{"title":"Homogeneity and heterogeneity of biological characteristics in mesenchymal stem cells from human umbilical cords and exfoliated deciduous teeth.","authors":"Chao Yang, Yu Chen, Liwu Zhong, Min You, Zhiling Yan, Maowen Luo, Bo Zhang, Benyanzi Yang, Qiang Chen","doi":"10.1139/bcb-2019-0253","DOIUrl":"https://doi.org/10.1139/bcb-2019-0253","url":null,"abstract":"Mesenchymal stem cells (MSCs) have proven powerful potential for cell-based therapy both in regenerative medicine and disease treatment. Human umbilical cords and exfoliated deciduous teeth are the main sources to derive MSCs with nearly no donor injury and ethical issue. The goal of this study was to investigate the differences of biological characteristics in human umbilical cord mesenchymal stem cells (UCMSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). UCMSCs and SHEDs were identified by flow cytometry. The proliferation, differentiation, migration, chemotaxis, paracrine, immunomodulatory, neurite growth-promoting capabilities and acetaldehyde dehydrogenase (ALDH) activity were comparatively studied between these two MSCs in vitro. The results showed that both SHEDs and UCMSCs expressed cell surface markers characteristic of MSCs. Furthermore, SHEDs exhibited better capacities in proliferation, migration, promotion of neurite growth and chondrogenic differentiation. Meanwhile, UCMSCs showed more outstanding adipogenic differentiation and chemotaxis abilities. Additionally, there is no significant difference in osteogenic differentiation, immunomodulatory capacity, and the proportion of ALDH bright compartment. Our findings indicate that although both UCMSCs and SHEDs are mesenchymal stem cells and presented some similar biological characteristics, they also have differences in many aspects, which might be instructive to future clinical cellular therapeutics for different diseases.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78223887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aline Haas de Mello, R. Schraiber, M. Goldim, Khiany Mathias, Carolini Mendes, M. E. A. B. Corrêa, M. L. Gomes, P. C. Silveira, P. F. Schuck, F. Petronilho, G. Rezin
This study evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oxidative stress and energy metabolism parameters in the visceral fat of a high-fat-diet induced obesity model. Energy intake, body mass, and visceral fat mass were also evaluated. Male Swiss mice received either a control diet (control group) or a high-fat diet (obese group) for 6 weeks. After this period, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + omega-3, and to these groups 400 mg·(kg body mass)-1·day-1 of fish oil (or saline) was administered orally, for 4 weeks. Energy intake and body mass were monitored throughout the experiment. In the 10th week, the animals were euthanized and the visceral fat (mesenteric) was removed. Treatment with omega-3 PUFAs did not affect energy intake or body mass, but it did reduced visceral fat mass. In visceral fat, omega-3 PUFAs reduced oxidative damage and alleviated changes to the antioxidant defense system and the Krebs cycle. The mitochondrial respiratory chain was neither altered by obesity nor by omega-3 PUFAs. In conclusion, omega-3 PUFAs have beneficial effects on the visceral fat of obese mice because they mitigate changes caused by the consumption of a high-fat diet.
{"title":"Omega-3 polyunsaturated fatty acids have beneficial effects on visceral fat in diet-induced obesity model.","authors":"Aline Haas de Mello, R. Schraiber, M. Goldim, Khiany Mathias, Carolini Mendes, M. E. A. B. Corrêa, M. L. Gomes, P. C. Silveira, P. F. Schuck, F. Petronilho, G. Rezin","doi":"10.1139/bcb-2018-0361","DOIUrl":"https://doi.org/10.1139/bcb-2018-0361","url":null,"abstract":"This study evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oxidative stress and energy metabolism parameters in the visceral fat of a high-fat-diet induced obesity model. Energy intake, body mass, and visceral fat mass were also evaluated. Male Swiss mice received either a control diet (control group) or a high-fat diet (obese group) for 6 weeks. After this period, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + omega-3, and to these groups 400 mg·(kg body mass)-1·day-1 of fish oil (or saline) was administered orally, for 4 weeks. Energy intake and body mass were monitored throughout the experiment. In the 10th week, the animals were euthanized and the visceral fat (mesenteric) was removed. Treatment with omega-3 PUFAs did not affect energy intake or body mass, but it did reduced visceral fat mass. In visceral fat, omega-3 PUFAs reduced oxidative damage and alleviated changes to the antioxidant defense system and the Krebs cycle. The mitochondrial respiratory chain was neither altered by obesity nor by omega-3 PUFAs. In conclusion, omega-3 PUFAs have beneficial effects on the visceral fat of obese mice because they mitigate changes caused by the consumption of a high-fat diet.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"32 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86107308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tingting Wang, Yu Duan, Qiao Fu, Tao Liu, Jinbao Yu, Zhiyan Sui, Li Huang, Guoqiang Wen
Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt-β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood-brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of β-catenin and downstream proteins while suppressing the expression of GSK-3β. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt-β-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.
{"title":"IM-12 activates the Wnt-β-catenin signaling pathway and attenuates rtPA-induced hemorrhagic transformation in rats after acute ischemic stroke.","authors":"Tingting Wang, Yu Duan, Qiao Fu, Tao Liu, Jinbao Yu, Zhiyan Sui, Li Huang, Guoqiang Wen","doi":"10.1139/bcb-2018-0384","DOIUrl":"https://doi.org/10.1139/bcb-2018-0384","url":null,"abstract":"Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt-β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood-brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of β-catenin and downstream proteins while suppressing the expression of GSK-3β. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt-β-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"174 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2019-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86803872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biochemistry and Cell Biology celebrates its 90th anniversary.","authors":"James Davie, C. Nelson","doi":"10.1139/bcb-2019-0411","DOIUrl":"https://doi.org/10.1139/bcb-2019-0411","url":null,"abstract":"","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"39 1","pages":"i"},"PeriodicalIF":0.0,"publicationDate":"2019-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73467303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wen-bin Du, Ning Liu, Ya-feng Zhang, Xi Liu, Yuan-jun Yang, Wei Chen, Yi He
The purpose of the current study is to characterize the expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a membrane-bound homodimeric enzyme that specifically hydroxylates lysine in the telopeptide of procollagens, and assess the clinical significance of PLOD2 in colorectal cancer (CRC). Our results showed that PLOD2 was highly expressed in CRC tumor tissues samples and cell lines both in mRNA and protein level. Next, we found that PLOD2 was positively correlated with Grade (p=0.001), T stage (p=0.001), N stage (p<0.001) and an advanced TNM stage (p<0.001). PLOD2 knockdown attenuates CRC cell proliferation, migration and invasion in vitro. Mechanism analysis PLOD2 affected glycolysis by regulating HK2 expression. HK2 reverses the inhibiting effects of PLOD2 knockdown in CRC. Furthermore, the data suggest that PLOD2 could regulate the expression of HK2 via the STAT3 signaling pathway. Survival analysis reveals that high PLOD2 (HR = 3.800, p < 0.001) and HK2 expression (HR = 10.222, p < 0.001) were correlated with overall survival. After analyzing their expression and correlation, PLOD2 was positively correlated with HK2 (r=0.590, p < 0.001). Our findings have uncovered that PLOD2 is a novel regulatory factor of glucose metabolism via controlling HK2 expression in CRC cells, suggesting PLOD2 as a promising therapeutic target for CRC treatment.
本研究的目的是表征前胶原-赖氨酸，2-氧戊二酸5-双加氧酶2 (PLOD2)的表达，并评估PLOD2在结直肠癌(CRC)中的临床意义。PLOD2是一种膜结合的同质二聚体酶，在前胶原的端肽中特异性羟化赖氨酸。结果表明，PLOD2在CRC肿瘤组织样本和细胞系中mRNA和蛋白水平均有高表达。接下来，我们发现PLOD2与Grade (p=0.001)、T分期(p=0.001)、N分期(p<0.001)和TNM晚期(p<0.001)呈正相关。PLOD2敲低可减弱CRC细胞的增殖、迁移和侵袭。机制分析PLOD2通过调节HK2表达影响糖酵解。HK2逆转了PLOD2敲低在CRC中的抑制作用。此外，数据表明PLOD2可以通过STAT3信号通路调节HK2的表达。生存率分析显示，高PLOD2 (HR = 3.800, p < 0.001)和高HK2表达(HR = 10.222, p < 0.001)与总生存率相关。分析其表达及相关性，PLOD2与HK2呈正相关(r=0.590, p < 0.001)。我们的研究发现PLOD2是一种新的糖代谢调节因子，通过控制CRC细胞中HK2的表达，提示PLOD2是CRC治疗的一个有希望的治疗靶点。
{"title":"PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2.","authors":"Wen-bin Du, Ning Liu, Ya-feng Zhang, Xi Liu, Yuan-jun Yang, Wei Chen, Yi He","doi":"10.1139/bcb-2019-0256","DOIUrl":"https://doi.org/10.1139/bcb-2019-0256","url":null,"abstract":"The purpose of the current study is to characterize the expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a membrane-bound homodimeric enzyme that specifically hydroxylates lysine in the telopeptide of procollagens, and assess the clinical significance of PLOD2 in colorectal cancer (CRC). Our results showed that PLOD2 was highly expressed in CRC tumor tissues samples and cell lines both in mRNA and protein level. Next, we found that PLOD2 was positively correlated with Grade (p=0.001), T stage (p=0.001), N stage (p<0.001) and an advanced TNM stage (p<0.001). PLOD2 knockdown attenuates CRC cell proliferation, migration and invasion in vitro. Mechanism analysis PLOD2 affected glycolysis by regulating HK2 expression. HK2 reverses the inhibiting effects of PLOD2 knockdown in CRC. Furthermore, the data suggest that PLOD2 could regulate the expression of HK2 via the STAT3 signaling pathway. Survival analysis reveals that high PLOD2 (HR = 3.800, p < 0.001) and HK2 expression (HR = 10.222, p < 0.001) were correlated with overall survival. After analyzing their expression and correlation, PLOD2 was positively correlated with HK2 (r=0.590, p < 0.001). Our findings have uncovered that PLOD2 is a novel regulatory factor of glucose metabolism via controlling HK2 expression in CRC cells, suggesting PLOD2 as a promising therapeutic target for CRC treatment.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83443283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study investigated the potential effect of n-6/n-3 polyunsaturated fatty acids (PUFA) on inflammation and myocardial ischemic reperfusion injury (MIRI) in rats, together with the underlying protective mechanisms, and screen out most effective ratio of n-6/n-3 within limits. The rats with pre-infarct treatment were distributed among 5 groups according to the n-6/n-3 ratio (36:1; 1:1, 5:1, 10:1, 50:1); for the post-infarct treatment, the rats were distributed among 6 groups, including the control group (36:1) which was subjected to a sham procedure; the model group (36:1); and 4 test groups (n-6/n-3 ratio: 1:1, 5:1, 10:1, 50:1). All of the rats were fed a purple perilla seed oil and safflower oil-based fatty emulsion. The serum levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were determined using enzyme-linked immunosorbent assay. Staining with triphenyl tetrazolium chloride, hematoxylin and eosin, or Masson's trichrome was performed for histological examination. Cardiomyocyte apoptosis was examined by TUNEL assay. Western blotting was performed to examine the expression levels of apoptosis-related proteins and signaling pathway proteins. Our data indicate that in both the pre-infarct treatment and post-infarct treatment, low ratios of n-6/n-3 PUFAs significantly inhibited the levels of serum inflammatory factors, the infarct size of MIRI rats, number of cardiomyocytes undergoing apoptosis, and the expression levels of caspase-3, Bcl-2, and Bax in the MIRI group. Thus a low ratio of n-6/n-3 PUFAs ameliorates inflammation and myocardial ischemic reperfusion injury.
{"title":"Low n-6/n-3 PUFA ratio improves inflammation and myocardial ischemic reperfusion injury.","authors":"Cai-yun Ma, Zehang Xu, Heng Lv","doi":"10.1139/bcb-2018-0342","DOIUrl":"https://doi.org/10.1139/bcb-2018-0342","url":null,"abstract":"This study investigated the potential effect of n-6/n-3 polyunsaturated fatty acids (PUFA) on inflammation and myocardial ischemic reperfusion injury (MIRI) in rats, together with the underlying protective mechanisms, and screen out most effective ratio of n-6/n-3 within limits. The rats with pre-infarct treatment were distributed among 5 groups according to the n-6/n-3 ratio (36:1; 1:1, 5:1, 10:1, 50:1); for the post-infarct treatment, the rats were distributed among 6 groups, including the control group (36:1) which was subjected to a sham procedure; the model group (36:1); and 4 test groups (n-6/n-3 ratio: 1:1, 5:1, 10:1, 50:1). All of the rats were fed a purple perilla seed oil and safflower oil-based fatty emulsion. The serum levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were determined using enzyme-linked immunosorbent assay. Staining with triphenyl tetrazolium chloride, hematoxylin and eosin, or Masson's trichrome was performed for histological examination. Cardiomyocyte apoptosis was examined by TUNEL assay. Western blotting was performed to examine the expression levels of apoptosis-related proteins and signaling pathway proteins. Our data indicate that in both the pre-infarct treatment and post-infarct treatment, low ratios of n-6/n-3 PUFAs significantly inhibited the levels of serum inflammatory factors, the infarct size of MIRI rats, number of cardiomyocytes undergoing apoptosis, and the expression levels of caspase-3, Bcl-2, and Bax in the MIRI group. Thus a low ratio of n-6/n-3 PUFAs ameliorates inflammation and myocardial ischemic reperfusion injury.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"1 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2019-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76299976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PRPS1 (phosphoribosyl pyrophosphate synthetase 1), which drives the nucleotide biosynthesis pathway, modulates a variety of functions by providing central building blocks and cofactors for cell homeostasis. As tumor cells often display abnormal nucleotide metabolism, dysregulated de-novo nucleotide synthesis has potential impacts in cancers. We now report that PRPS1 is specifically and highly expressed in chemoresistant (CR) cancer cells derived from cisplatin-resistant human breast cancer cell lines SK-BR-3 and MCF-7. The inhibition of PRPS1 activity in CR cells by genetic silencing reduces cell viability and increases apoptosis in vitro, both of which can be further potentiated by cisplatin treatment. Significantly, such down-regulation of PRPS1 in CR cells when administered to nude mice enhanced the survival of those animals, as demonstrated by decreased tumor growth. Knockdown of PRPSI may cause these effects by potently inducing autonomous activation of caspase-3 and inhibiting the proliferation in the engrafted CR tumors. As a result, cisplatin sensitivity in a xenograft model of CR cancer cells can be restored by the down-regulation of PRPS1. Thus, PRPS1 inhibition may afford a therapeutic approach to relapsed patients with breast cancer, resistant to chemotherapy.
{"title":"PRPS1 silencing reverses cisplatin resistance in human breast cancer cells.","authors":"M. He, L. Chao, Yi-Ping You","doi":"10.1139/bcb-2016-0106","DOIUrl":"https://doi.org/10.1139/bcb-2016-0106","url":null,"abstract":"PRPS1 (phosphoribosyl pyrophosphate synthetase 1), which drives the nucleotide biosynthesis pathway, modulates a variety of functions by providing central building blocks and cofactors for cell homeostasis. As tumor cells often display abnormal nucleotide metabolism, dysregulated de-novo nucleotide synthesis has potential impacts in cancers. We now report that PRPS1 is specifically and highly expressed in chemoresistant (CR) cancer cells derived from cisplatin-resistant human breast cancer cell lines SK-BR-3 and MCF-7. The inhibition of PRPS1 activity in CR cells by genetic silencing reduces cell viability and increases apoptosis in vitro, both of which can be further potentiated by cisplatin treatment. Significantly, such down-regulation of PRPS1 in CR cells when administered to nude mice enhanced the survival of those animals, as demonstrated by decreased tumor growth. Knockdown of PRPSI may cause these effects by potently inducing autonomous activation of caspase-3 and inhibiting the proliferation in the engrafted CR tumors. As a result, cisplatin sensitivity in a xenograft model of CR cancer cells can be restored by the down-regulation of PRPS1. Thus, PRPS1 inhibition may afford a therapeutic approach to relapsed patients with breast cancer, resistant to chemotherapy.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"1 1","pages":"385-393"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91107357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND Liver fibrosis is one of the major complications from upper right quadrant radiotherapy. MicroRNA-17-5p (miR-17-5p) is hypothesized to act as a regulator of hepatic stellate cell (HSCs) activation by activation of the canonical Wnt-β-catenin pathway. Diosmin (Dios), a citrus bioflavonoid, is known to possess potent antioxidant, anti-inflammatory, and anti-apoptotic properties. PURPOSE To explore the molecular mechanisms that underlie radiation-induced liver fibrosis, and to evaluate the possible influence of Dios on the miR-17-5p-Wnt-β-catenin signaling axis during fibrogenesis provoked by irradiation (IRR) in rats. Also, the effect of Dios on hepatic peroxisome proliferator activated receptor-γ (PPAR-γ) expression as a regulator for HSC activation was considered. METHODS We administered 100 mg·(kg body mass)-1·day-1 (per oral) of Dios were administered to IRR-exposed rats (overall dose of 12 Gy on 6 fractions of 2 Gy each) for 6 successive weeks. RESULTS Data analysis revealed that Dios treatment mitigated oxidative stress, enhanced antioxidant defenses, alleviated hepatic inflammatory responses, abrogated pro-fibrogenic cytokines, and stimulated PPAR-γ expression. Dios treatment repressed the miR-17-5p activated Wnt-β-catenin signaling induced by IRR. Moreover, Dios treatment restored the normal hepatic architecture and reversed pathological alterations induced by IRR. CONCLUSION We hypothesize that the stimulation of PPAR-γ expression and interference with miR-17-5p activated Wnt-β-catenin signaling mediates the antifibrotic properties of Dios.
{"title":"Diosmin attenuates radiation-induced hepatic fibrosis by boosting PPAR-γ expression and hampering miR-17-5p-activated canonical Wnt-β-catenin signaling.","authors":"H. Hasan, M. Abdel-Rafei, S. Galal","doi":"10.1139/bcb-2016-0142","DOIUrl":"https://doi.org/10.1139/bcb-2016-0142","url":null,"abstract":"BACKGROUND\u0000Liver fibrosis is one of the major complications from upper right quadrant radiotherapy. MicroRNA-17-5p (miR-17-5p) is hypothesized to act as a regulator of hepatic stellate cell (HSCs) activation by activation of the canonical Wnt-β-catenin pathway. Diosmin (Dios), a citrus bioflavonoid, is known to possess potent antioxidant, anti-inflammatory, and anti-apoptotic properties.\u0000\u0000\u0000PURPOSE\u0000To explore the molecular mechanisms that underlie radiation-induced liver fibrosis, and to evaluate the possible influence of Dios on the miR-17-5p-Wnt-β-catenin signaling axis during fibrogenesis provoked by irradiation (IRR) in rats. Also, the effect of Dios on hepatic peroxisome proliferator activated receptor-γ (PPAR-γ) expression as a regulator for HSC activation was considered.\u0000\u0000\u0000METHODS\u0000We administered 100 mg·(kg body mass)-1·day-1 (per oral) of Dios were administered to IRR-exposed rats (overall dose of 12 Gy on 6 fractions of 2 Gy each) for 6 successive weeks.\u0000\u0000\u0000RESULTS\u0000Data analysis revealed that Dios treatment mitigated oxidative stress, enhanced antioxidant defenses, alleviated hepatic inflammatory responses, abrogated pro-fibrogenic cytokines, and stimulated PPAR-γ expression. Dios treatment repressed the miR-17-5p activated Wnt-β-catenin signaling induced by IRR. Moreover, Dios treatment restored the normal hepatic architecture and reversed pathological alterations induced by IRR.\u0000\u0000\u0000CONCLUSION\u0000We hypothesize that the stimulation of PPAR-γ expression and interference with miR-17-5p activated Wnt-β-catenin signaling mediates the antifibrotic properties of Dios.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"17 1","pages":"400-414"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75656103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The two membrane transporters Slc23a1 and Slc23a2 mediate ascorbic acid uptake into cells. We recently determined the key role of Slc23a1 in renal re-absorption of ascorbic acid in a knockout mouse model. However, the renal spatial and temporal expression patterns of murine Slc23a1 and Slc23a2 are not defined. This study utilizes database evidence combined with experimental confirmation via in-situ hybridization to define the spatial and temporal expression of Slc23a1 in the murine kidney. Slc23a1 is expressed in the early proximal tubule, but not in its precursors during embryonic development, and exclusive proximal tubular expression persists throughout the animal's lifetime. In contrast, Slc23a2 is uniformly expressed in metabolic cell types such as stromal cells. The expression patterns appear to be conserved from rodent lineages to humans.
{"title":"Temporo-spacial microanatomical distribution of the murine sodium-dependent ascorbic acid transporters Slc23a1 and Slc23a2 in the kidney throughout development.","authors":"P. Eck, C. Corpe, M. Levine","doi":"10.1139/bcb-2015-0090","DOIUrl":"https://doi.org/10.1139/bcb-2015-0090","url":null,"abstract":"The two membrane transporters Slc23a1 and Slc23a2 mediate ascorbic acid uptake into cells. We recently determined the key role of Slc23a1 in renal re-absorption of ascorbic acid in a knockout mouse model. However, the renal spatial and temporal expression patterns of murine Slc23a1 and Slc23a2 are not defined. This study utilizes database evidence combined with experimental confirmation via in-situ hybridization to define the spatial and temporal expression of Slc23a1 in the murine kidney. Slc23a1 is expressed in the early proximal tubule, but not in its precursors during embryonic development, and exclusive proximal tubular expression persists throughout the animal's lifetime. In contrast, Slc23a2 is uniformly expressed in metabolic cell types such as stromal cells. The expression patterns appear to be conserved from rodent lineages to humans.","PeriodicalId":9524,"journal":{"name":"Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire","volume":"28 1","pages":"421-427"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83683568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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