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PI3K/AKT

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https://www.readbyqxmd.com/read/29166568/camel-whey-protein-protects-lymphocytes-from-apoptosis-via-the-pi3k-akt-nf-%C3%AE%C2%BAb-atf-3-and-hsp-70-signaling-pathways-in-heat-stressed-male-mice
#1
Gamal Badr, Nancy K Ramadan, Hanem S Abdel-Tawab, Samia F Ahmed, Mohamed H Mahmoud
Heat stress (HS) is an environmental factor that depresses the immune systems mediating dysfunctional immune cells. Camel whey protein (CWP) can scavenge free radicals and enhance immunity. The present study investigated the impact of dietary supplementation with CWP on immune dysfunction induced by exposure to HS. Male mice (n = 45) were divided into three groups: control group; HS group; and HS mice that were orally administered CWP (HS+CWP group). The HS group exhibited elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) as well as a significant reduction in the IL-2 and IL-4 levels...
November 22, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29164984/salvianolic-acid-a-a-novel-pi3k-akt-inhibitor-induces-cell-apoptosis-and-suppresses-tumor-growth-in-acute-myeloid-leukemia
#2
Renzhi Pei, Ting Si, Ying Lu, Jeff Xiwu Zhou, Lei Jiang
Salvianolic acid A (SAA), one of the main derivatives of Salvia miltiorrhiza, has been shown to possess anti-inflammatory and anti-thrombotic activities. Its role in inhibiting tumor growth, however, remains elusive. The aim of this study was to investigate the effect of SAA on acute myeloid leukemia (AML). Here, SAA showed a dose-dependent cell viability inhibition and apoptosis induction in AML cells. At the molecular level, SAA increased the expression of Bak and decreased the expression of Bcl-xL, following by PARP cleavage and caspase-3 activation...
November 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29164980/role-of-flunarizine-hydrochloride-in-secondary-brain-injury-following-intracerebral-hemorrhage-in-rats
#3
Jianping Niu, Rui Hu
This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood-brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay...
November 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/29164058/delineation-of-the-hpv11e6-and-hpv18e6-pathways-in-initiating-cellular-transformation
#4
Lamech M Mwapagha, Nicki Tiffin, M Iqbal Parker
Although high-risk human papillomaviruses (HPVs) are the major risk factors for cervical cancer they have been associated with several other cancers, such as head and neck and oral cancers. Since integration of low-risk HPV11 DNA has been demonstrated in esophageal tumor genomes, this study compared the effects of low-risk HPV11E6 and high-risk HPV18E6 on cellular gene expression. The HPV11E6 and HPV18E6 genes were cloned into an adenoviral vector and expressed in human keratinocytes (HaCaT) in order to investigate early events and to eliminate possible artifacts introduced by selective survival of fast growing cells in stable transfection experiments...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29163854/interactions-between-tgf-%C3%AE-1-canonical-wnt-%C3%AE-catenin-pathway-and-ppar-%C3%AE-in-radiation-induced-fibrosis
#5
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Radiation therapy induces DNA damage and inflammation leading to fibrosis. Fibrosis can occur 4 to 12 months after radiation therapy. This process worsens with time and years. Radiation-induced fibrosis is characterized by fibroblasts proliferation, myofibroblast differentiation, and synthesis of collagen, proteoglycans and extracellular matrix. Myofibroblasts are non-muscle cells that can contract and relax. Myofibroblasts evolve towards irreversible retraction during fibrosis process. In this review, we discussed the interplays between transforming growth factor-β1 (TGF-β1), canonical WNT/β-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR γ) in regulating the molecular mechanisms underlying the radiation-induced fibrosis, and the potential role of PPAR γ agonists...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163781/synj2bp-promotes-the-degradation-of-pten-through-the-lysosome-pathway-and-enhances-breast-tumor-metastasis-via-pi3k-akt-snai1-signaling
#6
Miao Wang, Huijian Wu, Shujing Li, Zhaowei Xu, Xiahui Li, Yangyang Yang, Bowen Li, Yanan Li, Jing Guo, Huan Chen
SYNJ2BP plays an important role in breast cancer metastasis. However, the molecular mechanism associated with the function of SYNJ2BP in metastasis remains unclear. In this study, we investigated the role of SYNJ2BP in tumor metastasis and established the associated underlying mechanism. Over-expression of SYNJ2BP promoted both cell migration and invasion. In contrast, silencing SYNJ2BP caused the suppression of cell migration and invasion. SYNJ2BP increased the levels of phosphorylation for AKT and GSK3β, which could be inhibited by the PI3K inhibitor, LY294002, and the GSK3β inhibitor, LiCl, and regulated the accumulation of SNAI1 in the nucleus and the expression of the SNAI1 target gene, E-cadherin (EMT marker)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163776/mir-1268b-confers-chemosensitivity-in-breast-cancer-by-targeting-erbb2-mediated-pi3k-akt-pathway
#7
Wen-Jie Zhu, Xu Chen, Ya-Wen Wang, Hai-Ting Liu, Ran-Ran Ma, Peng Gao
Chemoresistance represents a major obstacle to effective therapy for breast cancer. Emerging evidences associated aberrantly expressed miRNAs with tumor development and chemoresistance. MiR-1268b has never been studied in any cancers before, and its roles in mediating tumor progression and drug resistance are still unclear. Selected from miRNA microarray and confirmed by real-time quantitative PCR (RT-qPCR), miR-1268b was found to be significantly upregulated in drug sensitive and ERBB2 negative tissues, as well as in breast cancer patients with low clinical stage...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163683/knockdown-of-hmgn5-increases-the-chemosensitivity-of-human-urothelial-bladder-cancer-cells-to-cisplatin-by-targeting-pi3k-akt-signaling
#8
Yu Gan, Leye He, Kun Yao, Jing Tan, Qing Zeng, Yingbo Dai, Jianye Liu, Yuxin Tang
High-mobility group nucleosome-binding domain 5 (HMGN5) is the latest member of the HMGN family of proteins. Numerous studies have confirmed the carcinogenic role of HMGN5 in cancer, but its function in the regulation of chemosensitivity is largely unknown and controversial. A previous study by the authors of the present study demonstrated that HMGN5 contributes to the progression of urothelial bladder cancer (UBC) through regulating the expression of E-cadherin and vascular endothelial growth factor (VEGF)-C, which are associated with the sensitivity of tumor cells to cisplatin...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29163427/antimycobacterial-and-anti-inflammatory-mechanisms-of-baicalin-via-induced-autophagy-in-macrophages-infected-with-mycobacterium-tuberculosis
#9
Qingwen Zhang, Jinxia Sun, Yuli Wang, Weigang He, Lixin Wang, Yuejuan Zheng, Jing Wu, Ying Zhang, Xin Jiang
Tuberculosis (TB) remains a leading killer worldwide among infectious diseases and the effective control of TB is still challenging. Autophagy is an intracellular self-digestion process which has been increasingly recognized as a major host immune defense mechanism against intracellular microorganisms like Mycobacterium tuberculosis (Mtb) and serves as a key negative regulator of inflammation. Clinically, chronic inflammation surrounding Mtb can persist for decades leading to lung injury that can remain even after successful treatment...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29163176/jiang-tang-xiao-ke-granule-play-an-anti-diabetic-role-in-diabetic-mice-pancreatic-tissue-by-regulating-the-mrnas-and-micrornas-associated-with-pi3k-akt-signaling-pathway
#10
Fang-Fang Mo, Tian An, Zi-Jian Zhang, Yu-Fei Liu, Hai-Xia Liu, Yan-Yun Pan, Jia-Nan Miao, Dan-Dan Zhao, Xiu-Yan Yang, Dong-Wei Zhang, Guang-Jian Jiang, Si-Hua Gao
Purpose: To investigate the effect of JTXK granule on the expression pattern of miRNA in pancreatic tissue of KKAy diabetic mice, and to explore the molecular mechanism and pathways of JTXK granule in anti-diabetic effect. Methods: We used high fat diet (HFD) to induce the KKAy diabetic mice and screened the differentially expressed miRNAs (DEMs) between JTXK-treated group (n = 6) and the diabetic group (n = 6) using MicroRNA (miRNA) Microarray. C57BL/6J mice were given a normal diet as the control group (n = 6)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163163/guanxin-danshen-formulation-protects-against-myocardial-ischemia-reperfusion-injury-induced-left-ventricular-remodeling-by-upregulating-estrogen-receptor-%C3%AE
#11
Xuehong Deng, Xiaoyan Xing, Guibo Sun, Xudong Xu, Haifeng Wu, Guang Li, Xiaobo Sun
Background: Guanxin Danshen formulation (GXDSF) is a traditional Chinese herbal recipe recorded in the Chinese Pharmacopeia since 1995 edition, which consists of Salviae miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and Dalbergiae odoriferae Lignum. Our previous research suggested GXDSF had positive effect on cardiovascular disease. Therefore, the aim of this study was to elucidate the effects of GXDSF on myocardial ischemia reperfusion injury-induced left ventricular remodelling (MIRI-LVR). Methods: The effects of GXDSF on cardiac function were detected by haemodynamics and echocardiograms...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163047/biphasic-regulation-of-caveolin-1-gene-expression-by-fluoxetine-in-astrocytes-opposite-effects-of-pi3k-akt-and-mapk-erk-signaling-pathways-on-c-fos
#12
Baoman Li, Shu Jia, Tingting Yue, Li Yang, Chen Huang, Alexej Verkhratsky, Liang Peng
Previously, we reported that fluoxetine acts on 5-HT2B receptor and induces epidermal growth factor receptor (EGFR) transactivation in astrocytes. Recently, we have found that chronic treatment with fluoxetine regulates Caveolin-1 (Cav-1)/PTEN/PI3K/AKT/glycogen synthase kinase 3β (GSK-3β) signaling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence. At low concentrations fluoxetine down-regulates Cav-1 gene expression, decreases membrane content of PTEN, increases PI3K activity and increases phosphorylation of GSK-3β and increases its activity; at high concentrations fluoxetine acts on PTEN/PI3K/AKT/GSK-3β in an inverse fashion...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29161771/tetramethylpyrazine-nitrone-activates-akt-creb-through-increasing-bdnf-expression-to-promote-post-ischemic-neuroregeneration-and-recovery-of-neurological-functions-in-rats
#13
Gaoxiao Zhang, Tao Zhang, Ning Li, Liangmiao Wu, Jianbo Gu, Cuimei Li, Chen Zhao, Wei Liu, Luchen Shan, Pei Yu, Xifei Yang, Yaohui Tang, Guo-Yuan Yang, Yuqiang Wang, Yewei Sun, Zaijun Zhang
BACKGROUND AND PURPOSE: Neuronal regeneration from endogenous precursors is an attractive strategy for the treatment of ischemic stroke; however, most stroke-generated new born neurons die over time. Therefore, a drug that is both neuroprotective and pro-neurogenic may be promising. In this study, we assessed the neurogenic and oligodendrogenic effects of tetramethylpyrazine nitrone (TBN), a neuroprotective drug candidate for stroke, in a rat model of ischemic stroke. EXPERIMENTAL APPROACH: Sprague Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO)...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29160133/inhibition-of-metastasis-and-angiogenesis-in-hep-2-cells-by-wheatgrass-extract-an-in-vitro-and-in-silico-approach
#14
Garima Shakya, Sangeetha Balasubramanian, Muddasarul Hoda, Rukkumani Rajagopalan
Metastasis is the major hindrance in the treatment of all cancers, including laryngeal squamous cell carcinoma. Intensive researches are under way to identify the effective natural polyphenols with anti-metastatic ability for cancer treatment. Wheatgrass, an herbal plant has been reported to show anticancer effects. Hence, in this study, we aimed to analyze the anti-metastatic effect of methanol extract of wheatgrass (MEWG). The levels of metastatic marker proteins were determined by western blot. PI3K and AKT levels were determined by real time (RT)-PCR analysis...
November 21, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/29160061/a-dual-macrophage-targeting-nanovector-for-delivery-of-oligodeoxynucleotides-to-overcome-cancer-associated-immunosuppression
#15
Xiao-Yan He, Bo-Ya Liu, Jin-Long Wu, Shu-Lun Ai, Ren-Xi Zhuo, Si-Xue Cheng
To overcome cancer-associated immunosuppression, we prepared a dual-targeting vector to deliver CpG oligodeoxynucleotides (ODN) to macrophages. The dual-targeting system composed of mannosylated carboxymethyl chitosan (MCMC)/hyaluronan (HA) for macrophage targeting and protamine sulfate (PS) for ODN complexation was prepared by self-assembly. The effects of ODN delivery on immune cells was studied in J774A.1 cells. Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibits a higher immune stimulatory activity compared with the mono-targeting delivery system containing either MCMC or HA, resulting in dramatically enhanced secretion of pro-inflammatory cytokines and a successful shift to activated macrophages (M1)...
November 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29159980/role-of-pi3k-in-myocardial-ischaemic-preconditioning-mapping-pro-survival-cascades-at-the-trigger-phase-and-at-reperfusion
#16
Xavier Rossello, Jaime A Riquelme, Sean M Davidson, Derek M Yellon
The Reperfusion Injury Salvage Kinase (RISK) pathway is considered the main pro-survival kinase cascade mediating the ischaemic preconditioning (IPC) cardioprotective effect. To assess the role of PI3K-Akt, its negative regulator PTEN and other pro-survival proteins such as ERK and STAT3 in the context of IPC, C57BL/6 mouse hearts were retrogradely perfused in a Langendorff system and subjected to 4 cycles of 5 min. ischaemia and 5 min. reperfusion prior to 35 min. of global ischaemia and 120 min. of reperfusion...
November 20, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29159601/activating-fgfr1-mutations-in-sporadic-pheochromocytomas
#17
Jenny Welander, Małgorzata Łysiak, Michael Brauckhoff, Laurent Brunaud, Peter Söderkvist, Oliver Gimm
INTRODUCTION: Pheochromocytomas are neuroendocrine tumors of the adrenal glands. Up to 40% of the cases are caused by germline mutations in one of at least 15 susceptibility genes, making them the human neoplasms with the highest degree of heritability. Recurrent somatic alterations are found in about 50% of the more common sporadic tumors with NF1 being the most common mutated gene (20-25%). In many sporadic tumors, however, a genetic explanation is still lacking. MATERIALS AND METHODS: We investigated the genomic landscape of sporadic pheochromocytomas with whole-exome sequencing of 16 paired tumor and normal DNA samples and extended confirmation analysis in 2 additional cohorts comprising a total of 80 sporadic pheochromocytomas...
November 20, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/29158991/ndufa4l2-is-associated-with-clear-cell-renal-cell-carcinoma-malignancy-and-is-regulated-by-elk1
#18
Lei Wang, Zhiqiang Peng, Kaizhen Wang, Yijun Qi, Ying Yang, Yue Zhang, Xinyuan An, Shudong Luo, Junfang Zheng
Background: Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. However, its pathogenesis has not been fully understood till now, which hinders the therapeutic development of ccRCC. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) was found to be upregulated and play an important role in ccRCC. We aimed to further investigate the underlying mechanisms by which NDUFA4L2 exerted function and its expression level was upregulated...
2017: PeerJ
https://www.readbyqxmd.com/read/29158820/ph-sensitive-nano-complexes-overcome-drug-resistance-and-inhibit-metastasis-of-breast-cancer-by-silencing-akt-expression
#19
Jieying Yin, Tianqun Lang, Dongmei Cun, Zhong Zheng, Yan Huang, Qi Yin, Haijun Yu, Yaping Li
The therapy of breast cancer is encumbered by drug resistance and metastasis, which can be due to a defective PI3K/AKT/mTOR signaling pathway. This study was aimed at improving the anti-cancer effect of the chemotherapeutic agent paclitaxel (PTX) on the drug resistant and metastatic breast cancer by co-delivering PTX and a siRNA, siAkt, directed at silencing the Akt expression. Methods: The pH-sensitive amphiphilic polymer, poly [(1,4-butanediol)-diacrylate-β-N, N-diisopropylethylenediamine]-polyethyleneimine (BDP) was synthesized...
2017: Theranostics
https://www.readbyqxmd.com/read/29158773/construction-of-an-mirna-regulated-pathway-network-reveals-candidate-biomarkers-for-postmenopausal-osteoporosis
#20
Min Shao
We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP) via establishing an microRNAs- (miRNA-) regulated pathway network (MRPN). Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS). Significant pathways based on differentially expressed genes (DEGs) using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods...
2017: Computational and Mathematical Methods in Medicine
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