Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.2 (PDK1)
 2,238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND This study aimed to identify the potential key long non-coding RNAs (lncRNAs) and target genes associated with pneumonia using lncRNA sequencing (lncRNA-seq). MATERIAL AND METHODS A total of 9 peripheral blood samples from patients with mild pneumonia (n=3) and severe pneumonia (n=3), as well as volunteers without pneumonia (n=3), were received for lncRNA-seq. Based on the sequencing data, differentially expressed lncRNAs (DE-lncRNAs) were identified by the limma package. After the functional enrichment analysis, target genes of DE-lncRNAs were predicted, and the regulatory network was constructed. RESULTS In total, 99 DE-lncRNAs (14 upregulated and 85 downregulated ones) were identified in the mild pneumonia group and 85 (72 upregulated and 13 downregulated ones) in the severe pneumonia group, compared with the control group. Among these DE-lncRNAs, 9 lncRNAs were upregulated in both the mild and severe pneumonia groups. A set of 868 genes were predicted to be targeted by these 9 DE-lncRNAs. In the network, RP11-248E9.5 and RP11-456D7.1 targeted the majority of genes. RP11-248E9.5 regulated several genes together with CTD-2300H10.2, such as QRFP and EPS8. Both upregulated RP11-456D7.1 and RP11-96C23.9 regulated several genes, such as PDK2. RP11-456D7.1 also positively regulated CCL21. CONCLUSIONS These novel lncRNAs and their target genes may be closely associated with the progression of pneumonia.
Med Sci Monit 2016 Sep 24
PMID:Identification of Potential Key Long Non-Coding RNAs and Target Genes Associated with Pneumonia Using Long Non-Coding RNA Sequencing (lncRNA-Seq): A Preliminary Study. 2766 62

BACKGROUND Alzheimer's disease (AD) is an age-associated neurodegenerative disorder. This study aimed to investigate effects of acupuncture administration on cognitive function and associated mechanisms. MATERIAL AND METHODS Senescence-accelerated prone 8 (SAM-P8) mice were randomly divided into 3 groups: the SAM-P8 group (P8-CN), the SAM-P8 administrating with acupuncture (P8-Acup) group, and the SAM-P8 administrating without acupuncture (P8-Sham) group. Morris water maze test was conducted to evaluate cognitive functions (memory and learning ability). PDK1, nPKC, and Rac1 inhibitors were used to treat SAM-P8 mice. Transmission electron microscope analysis was used to examine nuclear damage hippocampal tissues. Hematoxylin and eosin (H&E) staining was employed to evaluate inflammation. Western blot was used to detect PI3K, PDK1, nPKC, and Rac 1 expression in hippocampal tissues. RESULTS Acupuncture administration significantly reduced PI3K, PDK1, nPKC, and Rac 1 levels compared to P8-CN group (P<0.05). Both acupuncture and enzyme inhibitors (NSC23766, Rottlerin, OSU03012) significantly improved cognitive functions, reduced inflammation, and alleviated nuclear damages of SAM-P8 mice compared to P8-CN group (P<0.05). Acupuncture significantly enhanced effects of inhibitors on inflammation and nuclear damages compared to inhibitor treatment single (P<0.05). Acupuncture significantly enhanced down-regulative effects of OSU03012 on PI3K and PDK1 levels, increased down-regulative effects of Rottlerin on nPKC and Rac 1 levels and enhanced effects of Rottlerin on Rac 1 compared to P8-CN group (P<0.05). CONCLUSIONS Acupuncture administration improved cognitive functions and alleviated inflammatory response and nuclear damage of SAM-P8 mice, by downregulating PI3K/PDK1/nPKC/Rac 1 signaling pathway. This study could provide potential insight for treating cognitive dysfunction and aging of AD patients.
Med Sci Monit 2019 Jun 01
PMID:Acupuncture Administration Improves Cognitive Functions and Alleviates Inflammation and Nuclear Damage by Regulating Phosphatidylinositol 3 Kinase (PI3K)/Phosphoinositol-Dependent Kinase 1 (PDK1)/Novel Protein Kinase C (nPKC)/Rac 1 Signaling Pathway in Senescence-Accelerated Prone 8 (SAM-P8) Mice. 3115 45

BACKGROUND Doxorubicin-induced myocardial toxicity is associated with oxidative stress, cardiomyocyte, apoptosis, and loss of contractile function. Previous studies showed that microRNA-375 (miR-375) expression was increased in mouse models of heart failure and clinically, and that inhibition of miR-375 reduced inflammation and increased survival of cardiomyocytes. This study aimed to investigate the effects and mechanisms of inhibition of miR-375 in a mouse model of doxorubicin-induced cardiac toxicity in vivo and in doxorubicin-treated rat and mouse cardiomyocytes in vitro. MATERIAL AND METHODS The mouse model of doxorubicin-induced cardiac toxicity was developed using an intraperitoneal injection of doxorubicin (15 mg/kg diluted in 0.9% saline) for eight days. Treatment was followed by a single subcutaneous injection of miR-375 inhibitor. H9c2 rat cardiac myocytes and adult murine cardiomyocytes (AMCs) were cultured in vitro and treated with doxorubicin, with and without pretreatment with miR-375 inhibitor. RESULTS Doxorubicin significantly upregulated miR-375 expression in vitro and in vivo, and inhibition of miR-375 re-established myocardial redox homeostasis, prevented doxorubicin-induced oxidative stress and cardiomyocyte apoptosis, and activated the PDK1/AKT axis by reducing the direct binding of miR-375 to 3' UTR of the PDK1 gene. Inhibition of PDK1 and AKT abolished the protective role of miR-375 inhibition on doxorubicin-induced oxidative damage. CONCLUSIONS Inhibition of miR-375 prevented oxidative damage in a mouse model of doxorubicin-induced cardiac toxicity in vivo and in doxorubicin-treated rat and mouse cardiomyocytes in vitro through the PDK1/AKT signaling pathway.
Med Sci Monit 2020 Mar 18
PMID:The Effects of Inhibition of MicroRNA-375 in a Mouse Model of Doxorubicin-Induced Cardiac Toxicity. 3218 83