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autophagy AND pancreatitis

Wei Chen, Yue Zhou, Xiao Zhi, Tao Ma, Hao Liu, Brayant Wei Chen, Xiaoxiao Zheng, Shangzhi Xie, Bin Zhao, Xinhua Feng, Xiaowei Dang, Tingbo Liang
Pancreatic ductal adenocarcinoma (PDAC) is a destructive cancer with poor prognosis. Both novel therapeutic targets and approaches are needed to improve the overall survival of PDAC patients. MicroRNA-212 (miR-212) has been reported as a tumor suppressor in multiple cancers, but its definitive role and exact mechanism in the progression of pancreatic cancer is unclear. In this study, we developed a new chimeric peptide (PL-1) composed of plectin-1-targeted PDAC-specific and arginine-rich RNA-binding motifs which could condense miRNA to self-assemble supramolecular nanoparticles...
November 30, 2018: Biomaterials
Lihua Cui, Caixia Li, Ge Gao, Yuzhen Zhuo, Lei Yang, Naiqiang Cui, Shukun Zhang
AIMS: Pancreatic stellate cells (PSCs) play a critical role in the development of pancreatic fibrosis. Any agents that can affect PSC activation could become potential candidates for treating pancreatic fibrosis. FTY720 can attenuate chronic pancreatic fibrosis by suppressing T-cell infiltration, but its effect on PSCs remains unknown. This study was conducted to investigate the effects of FTY720 on PSC activation in cultured rat PSCs. MAIN METHODS: The viability of PSCs after FTY720 treatment was detected by MTT...
December 11, 2018: Life Sciences
Yifan Yang, Yang Sun, Huaitao Wang, Hansi Li, Mingjie Zhang, Lei Zhou, Xiangli Meng, Yunhao Wu, Peng Liu, Xin Liu, Jun Zhang, Xiaodong Tan
Pancreatic cancer is an aggressive type of cancer with a poor prognosis, short survival rate and high mortality. Therefore, understanding the molecular mechanism underlying the aggressive growth of pancreatic cancer is of importance. An increasing number of studies suggest that numerous microRNAs (miRNAs/miRs) are associated with the tumorigenesis, progression and prognosis of tumors. In a recent study by the present authors, it was revealed that the expression of miR-221 was significantly downregulated in highly aggressive pancreatic cancer cells compared with weakly aggressive pancreatic cancer cells...
December 2018: Oncology Letters
Qingcai Meng, Jin Xu, Chen Liang, Jiang Liu, Jie Hua, Yiyin Zhang, Quanxing Ni, Si Shi, Xianjun Yu
Given the dense stroma and poor vascularization, access to nutrients is limited in the microenvironment of pancreatic ductal adenocarcinoma (PDA). PDA cells can efficiently recycle various metabolic substrates through the activation of different rescuing pathways, including the autophagy pathway. However, the precise roles of autophagy in cancer metabolism are not yet fully understood. In the present study, we first monitored the effect of glucose deprivation on autophagy and on the expression of glutathione peroxidase-1 (GPx1) in PDA cells under the glucose-free environment...
December 11, 2018: Cell Death & Disease
Jordan Rowlands, Julian Heng, Philip Newsholme, Rodrigo Carlessi
The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions...
2018: Frontiers in Endocrinology
Ana Paula Courreges, Ana Clara Najenson, Marcelo S Vatta, Liliana G Bianciotti
Increasing evidence shows that the endoplasmic reticulum (ER) stress is an early event that injures pancreatic acinar cells and contributes to the pathogenesis of acute pancreatitis. In the present work we sought to establish whether atrial natriuretic peptide (ANP) alleviated ER stress in rats with cerulein-induced pancreatitis. The major components of the unfolded protein response (UPR) and their downstream effectors were assessed by immunoblotting or fluorimetry and the ultrastructure of ER evaluated by electron transmission microscopy...
December 7, 2018: Biochimica et biophysica acta. Molecular basis of disease
Chunli Wu, Liang Yang, Xun Qi, Taifang Wang, Meng Li, Ke Xu
Background: Resistance to radiation therapy is still a challenge for treatment of pancreatic cancer(PC). Long non-coding RNAs (lncRNA) HOTAIR has been found to play a oncogenic role in several cancers. However, the correlation between HOTAIR and radiotherapy in PC is still unclear. Methods: TCGA data was collected to analyze the expression of HOTAIR and its relationship with PC progression. A series of functional experiments were conducted to explore the role of HOTAIR in PC radiosensitivity and its underlying molecular mechanisms...
2018: Cancer Management and Research
Hua Chen, Chunle Zhao, Ruizhi He, Min Zhou, Yuhui Liu, Xingjun Guo, Min Wang, Feng Zhu, Renyi Qin, Xu Li
In contrast to the steady increase in survival observed for most cancer types, advances have been slow for pancreatic cancers. Current chemotherapy has limited benefits for patients with pancreatic cancer. Therefore, there is an urgent need for effective pancreatic cancer treatment strategies. At present, targeting the autophagic pathway is regarded as a promising new strategy for cancer treatment. Danthron (1,8-dihydroxyanthrquinone), a component from Rheum palmatum L. (polygonaceae), has several biological activities...
October 31, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Carlos Guillén, Manuel Benito
Type 2 Diabetes Mellitus (T2DM), a worldwide epidemics, is a progressive disease initially developing an insulin resistant state, with manifest pancreatic beta islet overwork and hyperinsulinemia. As the disease progresses, pancreatic β cells are overwhelmed and fails in their capacity to compensate insulin resistance. In addition, it is usually associated with other metabolic diseases such as hyperlipidemia, obesity and the metabolic syndrome. During the progression to T2DM there is a chronic activation of mTORC1 signaling pathway, which induces aging and acts as an endogenous inhibitor of autophagy...
2018: Frontiers in Endocrinology
Yi Zang, Lei Zhu, Tong Li, Qi Wang, Juanjuan Li, Yuting Qian, Lumin Wei, Mingping Xie, Wen-Hao Tang, Xu Liu, Ying Zhu, Lifu Wang
The EI24 autophagy-associated transmembrane protein is frequently associated with tumor growth and patient survival. In the present study, we found that EI24 was downregulated in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues and was associated with cancer cell differentiation. Overexpression of EI24 suppressed cancer cell growth in vitro and in vivo and induced cell cycle S phase arrest, with no impact on caspase-dependent apoptosis. EI24 overexpression also resulted in reduced c-Myc expression, an oncogene in PDAC, accompanied with increased LC3B-II formation, increased Beclin-1, and diminished p62...
2018: Gastroenterology Research and Practice
Stephen L Abrams, Matilde Y Follo, Linda S Steelman, Kvin Lertpiriyapong, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Saverio Candido, Massimo Libra, Ramiro M Murata, Pedro L Rosalen, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Weifeng Mao, Paolo Lombardi, James A McCubrey
Berberine (BBR) is a common nutraceutical consumed by millions worldwide. BBR has many different effects on human health, e.g., diabetes, diarrhea, inflammation and now more recently it has been proposed to have potent anti-cancer effects. BBR has been shown to suppress the growth of cancer cells more than normal cells. BBR has been proposed to exert its growth-inhibitory effects by many different biochemical mechanisms including: suppression of cell cycle progression, induction of reactive oxygen species, induction of apoptosis and autophagy and interactions with DNA potentially leading to DNA damage, and altered gene expression...
October 17, 2018: Advances in Biological Regulation
Cheng Xu, Yunfei Wang, Qiu Tu, Zhiye Zhang, Mengrou Chen, James Mwangi, Yaxiong Li, Yang Jin, Xudong Zhao, Ren Lai
Pancreatic cancer remains one of the deadliest human cancers despite current advances in conventional therapeutics including surgery and adjuvant therapies. Here, we showed that LZ1, a peptide derived from a snake venom cathelicidin, significantly inhibited growth of pancreatic cancer cells by inducing autophagy-dependent cell death both in vitro and in vivo. The LZ1-induced cell death was blocked by pharmacological or genetic inhibition of autophagy. In orthotopic model of pancreatic cancer, systemic administration of LZ1 (1-4 mg/kg) exhibited remarkable antitumor efficacy, significantly prolonged mice survival, and showed negligible adverse effects by comparison with gemcitabine (20 mg/kg)...
October 24, 2018: Oncogene
Wu Lv, Jialin Zhang, Ao Jiao, Bowen Wang, Baomin Chen, Jie Lin
It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors which can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP...
October 12, 2018: Canadian Journal of Physiology and Pharmacology
Suresh Awale, Dya Fita Dibwe, Chandrasekar Balachandran, Shaimaa Fayez, Doris Feineis, Blaise Kimbadi Lombe, Gerhard Bringmann
PANC-1 human pancreatic cancer cells are characterized by their ability to proliferate aggressively under hypovascular and hypoxic conditions in the tumor microenvironment, displaying a remarkable tolerance to nutrition starvation. The antiausterity strategy is a new approach in anticancer drug discovery aiming at the identification of potent agents that inhibit preferentially the survival of tumor cells during a limited supply of nutrients and oxygen. The new 5,8'-coupled naphthyldihydroisoquinoline alkaloid ancistrolikokine E3 (4), isolated from the Congolese liana Ancistrocladus likoko, showed potent preferential cytotoxicity against PANC-1 cells under nutrient-deprived conditions, with a PC50 value of 2...
October 26, 2018: Journal of Natural Products
Sumate Ampawong, Duangnate Isarangkul, Onrapak Reamtong, Pornanong Aramwit
We recently demonstrated that in addition to its protective effect on pancreatic and adrenal biosynthesis, antioxidant properties of sericin decrease blood cholesterol levels and improve the liver mitochondrial architecture. However, little is known about the detailed mechanisms underlying these effects. Using proteomics and electron microscopy, we identified mitochondrial proteins that play important roles in the preservation of the mitochondrial ultrastructure and cholesterol-lowering properties of sericin...
October 8, 2018: Scientific Reports
Katarzyna Kornicka, Agnieszka Śmieszek, Jolanta Szłapka-Kosarzewska, Jennifer M Irwin Houston, Michael Roecken, Krzysztof Marycz
Endocrine disorders are becoming an increasing problem in both human and veterinary medicine. In recent years, more and more horses worldwide have been suffering from equine metabolic syndrome (EMS). This metabolic disorder is characterized by pathological obesity, hyperinsulinaemia, hyperglycaemia and insulin resistance. Although metabolic disorders, including diabetes, have been extensively studied, there are still no data on the molecular effects of EMS in horses. Thus, the aim of this study was to evaluate apoptosis, oxidative stress, autophagy and microRNA (miR) expression in multipotent intestinal epithelial stem cells (IECs) and pancreatic islets (PIs) isolated post mortem form healthy and EMS diagnosed horses...
October 8, 2018: International Journal of Molecular Sciences
Kivanc Görgülü, Kalliope N Diakopoulos, Jiaoyu Ai, Benjamin Schoeps, Derya Kabacaoglu, Angeliki-Faidra Karpathaki, Katrin J Ciecielski, Ezgi Kaya-Aksoy, Dietrich A Ruess, Alexandra Berninger, Marlena Kowalska, Marija Stevanovic, Sonja M Wörmann, Thomas Wartmann, Yue Zhao, Walter Halangk, Svetlana Voronina, Alexey Tepikin, Anna Melissa Schlitter, Katja Steiger, Anna Artati, Jerzy Adamski, Michaela Aichler, Axel Walch, Martin Jastroch, Götz Hartleben, Christos S Mantzoros, Wilko Weichert, Roland M Schmid, Stephan Herzig, Achim Krüger, Bruno Sainz, Marina Lesina, Hana Algül
BACKGROUND AND AIMS: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy-related 5 (Atg5) protein on pancreatic tumor formation and progression. METHODS: We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5+/- ;Kras), and compared them with mice with only oncogenic Kras (controls)...
October 6, 2018: Gastroenterology
Ben C King, Klaudia Kulak, Ulrika Krus, Rebecca Rosberg, Ewelina Golec, Katarzyna Wozniak, Maria F Gomez, Enming Zhang, David J O'Connell, Erik Renström, Anna M Blom
We show here that human pancreatic islets highly express C3, which is both secreted and present in the cytosol. Within isolated human islets, C3 expression correlates with type 2 diabetes (T2D) donor status, HbA1c, and inflammation. Islet C3 expression is also upregulated in several rodent diabetes models. C3 interacts with ATG16L1, which is essential for autophagy. Autophagy relieves cellular stresses faced by β cells during T2D and maintains cellular homeostasis. C3 knockout in clonal β cells impaired autophagy and led to increased apoptosis after exposure of cells to palmitic acid and IAPP...
October 1, 2018: Cell Metabolism
Kaylene Barrera, Albert Stanek, Kei Okochi, Zuzanna Niewiadomska, Cathy Mueller, Peiqi Ou, Devon John, Antonio E Alfonso, Scott Tenner, Chongmin Huan
Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP...
September 29, 2018: World Journal of Gastrointestinal Pathophysiology
Xinqun Li, Yeonju Lee, Ya'an Kang, Bingbing Dai, Mayrim Rios Perez, Michael Pratt, Eugene J Koay, Michael Kim, Rolf A Brekken, Jason B Fleming
Lumican is secreted by pancreatic stellate cells and inhibits cancer progression. Extracellular lumican inhibits cancer cell replication and restrains growth of early-stage pancreatic adenocarcinoma (PDAC) such that patients with tumors containing stromal lumican experience a three-fold longer survival after treatment. In the present study, patient tumor tissues, ex-vivo cultures of patient-derived xenografts (PDX), PDAC stellate and tumor cells were used to investigate whether hypoxia (1% O2 ) within the tumor microenvironment influences stromal lumican expression and secretion...
October 3, 2018: Cell Death and Differentiation
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