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Reishi Toshiyama, Masamitsu Konno, Hidetoshi Eguchi, Hiroyasu Takemoto, Takehiro Noda, Ayumu Asai, Jun Koseki, Naotsugu Haraguchi, Yuji Ueda, Katsunori Matsushita, Kei Asukai, Tomofumi Ohashi, Yoshifumi Iwagami, Daisaku Yamada, Daisuke Sakai, Tadafumi Asaoka, Toshihiro Kudo, Koichi Kawamoto, Kunihito Gotoh, Shogo Kobayashi, Taroh Satoh, Yuichiro Doki, Nobuhiro Nishiyama, Masaki Mori, Hideshi Ishii
Previous studies highlighted that aminopeptidase N (APN)/CD13 acts as a scavenger in the survival of hepatocellular carcinoma (HCC) stem cells by reducing reactive oxygen species (ROS) levels. Hence, it has been proposed that APN/CD13 inhibition can increase cellular ROS levels and sensitize cells to chemotherapeutic agents. Although ubenimex, also known as bestatin, competitively inhibits proteases such as APN/CD13 on the cellular membrane and it is clinically used for patients with acute myeloid leukemia and lymphedema, research has demonstrated that higher concentrations of the agent induce the death of APN/CD13+ HCC stem cells...
August 8, 2018: Oncogene
Rie Watanabe, Christina Eckstrand, Hongwei Liu, Niels C Pedersen
Laboratory cats were infected with a serotype I cat-passaged field strain of FIP virus (FIPV) and peritoneal cells harvested 2-3 weeks later at onset of lymphopenia, fever and serositis. Comparison peritoneal cells were collected from four healthy laboratory cats by peritoneal lavage and macrophages predominated in both populations. Differential mRNA expression analysis identified 5621 genes as deregulated in peritoneal cells from FIPV infected versus normal cats; 956 genes showed > 2.0 Log2 Fold Change (Log2 FC) and 1589 genes showed < -2...
August 7, 2018: Veterinary Research
Cynthia L Schreiber, Bradley D Smith
This review focuses on recent advances in the molecular imaging of aminopeptidase N (APN, also known as CD13), a zinc metalloenzyme that cleaves N -terminal neutral amino acids. It is overexpressed in multiple cancer types and also on the surface of vasculature undergoing angiogenesis, making it a promising target for molecular imaging and targeted therapy. Molecular imaging probes for APN are divided into two large subgroups: reactive and nonreactive. The structures of the reactive probes (substrates) contain a reporter group that is cleaved and released by the APN enzyme...
2018: Contrast Media & Molecular Imaging
Miho Akimoto, Riruke Maruyama, Yasunari Kawabata, Yoshitsugu Tajima, Keizo Takenaga
The association between lower circulating adiponectin (APN) levels and the development of pancreatic cancer has been reported. However, the effect of APN on the growth and survival of pancreatic cancer cells remains elusive. Here, we investigate the effects of the anti-diabetic APN receptor (AdipoR) agonist AdipoRon and APN on human pancreatic cancer cells. We found that AdipoRon, but not APN, induces MIAPaCa-2 cell death, mainly through necroptosis. Mechanistically, although both AdipoRon and APN activate AMPK and p38 MAPK in an AdipoR-dependent manner that elicits survival signals, only AdipoRon induces rapid mitochondrial dysfunction through mitochondrial Ca2+ overload, followed by superoxide production via RIPK1 and ERK1/2 activation...
July 23, 2018: Cell Death & Disease
Amber Thomassen
Newly graduated advanced practice nurses (APNs) often accept positions equipped only with brief, limited training and are expected to primarily learn on the job. APN fellowship programs, such as the oncology fellowship program at Sylvester Comprehensive Cancer Center (SCCC) in Florida, may be a solution to this problem; they provide in-depth training to APNs, offer support through open communication with preceptors, grant APNs opportunities to develop skills and confidence, and allow APNs the time to earn the trust of others at the institution and take on additional responsibilities...
August 1, 2018: Clinical Journal of Oncology Nursing
Ewelina Węglarz-Tomczak, Michał Talma, Mirosław Giurg, Hans V Westerhoff, Robert Janowski, Artur Mucha
The potent transcription inhibitor Actinomycin D is used with several cancers. Here, we report the discovery that this naturally occurring antibiotic inhibits two human neutral aminopeptidases, the cell-surface alanine aminopeptidase and intracellular methionine aminopeptidase type 2. These metallo-containing exopeptidases participate in tumor cell expansion and motility and are targets for anticancer therapies. We show that the peptide portions of Actinomycin D and Actinomycin X2 are not required for effective inhibition, but the loss of these regions changes the mechanism of interaction...
June 29, 2018: Oncotarget
Andrea Serena, Andrew A Dwyer, Solange Peters, Manuela Eicher
PURPOSE: The purpose of this study was to explore the acceptance of a novel role, the advanced practice nurse in lung cancer (APNLC), from the perspective of patients and healthcare professionals in a country lacking a regulatory oversight for advanced practice nursing (APN) roles. METHODS AND DESIGN: This study utilized a qualitative methodology using focus groups and semistructured interviews. Participants were purposively sampled in a Swiss academic medical center...
July 22, 2018: Journal of Nursing Scholarship
Yuan Lin Zhang, Xiu E Feng, Rong Rong Chang, Le Hua Zhang, Bao Guo Xiao, Qing Shan Li, Xu Liang Hao
Antibiotics are still the primary therapy for acute pyelonephritis (APN); rarely, natural polyphenols are also used. LM49 is a novel marine bromophenol derivative displaying strong anti-inflammatory effects. We investigated the therapeutic efficacy of LM49 in an experimental rat model of APN. The model was established by injecting 0.5 mL Escherichia coli (ATCC 25922, 108  CFU/mL) into the urinary bladders of Sprague Dawley rats. This model showed increased kidney viscera indices and renal bacterial growth scores, as well as pathological changes in kidneys...
July 11, 2018: International Immunopharmacology
Sara Swenson, Justin Bull, Iris B Chen, Dency Joseph, Jolly Joseph, Molly Varghese, Rita A Dellostritto
BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM), first reported by Japanese doctors, has gained an overall acknowledgment as an independent malady of international attention. It resembles the presentation of an acute myocardial infarction but lacks ischemic myocardial tissue. The objective of this article is to review the physiology, diagnostics, treatment, and complications of TCM and report a case study of a patient who developed TCM. METHODS: Observation through direct patient care allowed for data collection of this unique medical phenomenon...
July 2018: Journal of the American Association of Nurse Practitioners
Ping Chen, Jason Liwen Huang, Xiaoqin Yuan, Junjie Huang, Harry Haoxiang Wang, Gary Tse, Martin C S Wong, Yunlin Wu
BACKGROUND AND AIM: A proper colonoscopy referral criterion is essential for flexible sigmoidoscopy-based colorectal cancer screening. We aimed to compare the predictive capability of four existing criteria to detect proximal neoplasia (PN) and advanced proximal neoplasia (APN) in a Chinese population. METHODS: Asymptomatic Chinese participants aged 50-75 years, who received screening colonoscopy, were consecutively recruited. The four criteria included (i) UK flexible sigmoidoscopy; (ii) Italian Screening for COlon REctum; (iii) NORwegian Colorectal Cancer Prevention trial; and (iv) US clinical index...
July 3, 2018: Journal of Gastroenterology and Hepatology
Isabel Gómez, Daniel E Rodríguez-Chamorro, Gabriela Flores-Ramírez, Ricardo Grande, Fernando Zúñiga, Francisco J Portugal, Jorge Sánchez, Sabino Pacheco, Alejandra Bravo, Mario Soberón
Bacillus thuringiensis Cry1Ca is toxic to different Spodoptera species. The aim of this work was to identify the Cry1Ca binding proteins in S. frugiperda, to provide evidence on their participation in toxicity and to identify the Cry1Ca amino acid residues involved in receptor binding. Pull down assays using S. frugiperda brush border membrane vesicles (BBMV) identified aminopeptidase N (APN), APN1 and APN2 isoforms as Cry1Ca-binding proteins. Cry1Ca alanine substitutions in all residues of domain III β16 were characterized...
June 29, 2018: Applied and Environmental Microbiology
Bodong Wang, Hao Guo, Xia Li, Liang Yue, Haixiao Liu, Lei Zhao, Hao Bai, Xunyuan Liu, Xun Wu, Yan Qu
Ischemic stroke is among the leading causes of morbidity and mortality worldwide. Improving the tolerance of neurons to ischemia and reperfusion injury could be a feasible strategy against ischemia. Adiponectin (APN) is a major adipokine that regulates glucose and lipid metabolism and plays an important role in the protection of the cerebral nervous system. We aimed to investigate the effects of APN on oxygen and glucose deprivation (OGD)-induced neuronal injury in hippocampal neuronal HT22 cells. APN displayed neuroprotective effects against OGD, evidenced by increased cell viability and decreased lactate dehydrogenase release and apoptotic rate...
January 1, 2018: Cell Transplantation
Amena Khatun, Kyu-Ho Kang, Do-Yeal Ryu, Md Saidur Rahman, Woo-Sung Kwon, Myung-Geol Pang
Aminopeptidase N (APN) is defined as a multifunctional enzyme, which regulate cellular physiology of a wide variety of cells in human. Earlier studies reported that mammalian semen shares this common enzyme as a major protein of seminal plasma that has correlation with male fertility, while the regulatory mechanisms of APN in spermatozoa are still far from being well understood. Present study was designed to investigate the role of APN in biological and chemical functions of spermatozoa using an in vitro antagonistic approach...
June 12, 2018: Theriogenology
Sarah Nicolas, Joëlle Chabry, Alice Guyon, Hadi Zarif, Catherine Heurteaux, Agnès Petit-Paitel
Adiponectin (ApN) is a hormone produced by adipose tissue, yet the plasma level of ApN is decreased in overweight and obese people, as well as in people with diabetes. In the periphery, this decrease in circulating levels of ApN induces the establishment of a chronic low-grade inflammatory state and is involved in the development of insulin resistance and atheromas. Conversely, "favorable" living conditions, weight loss and regular physical exercise increase ApN blood concentration. Some forms of ApN can reach the brain parenchyma through the cerebrospinal fluid...
May 2018: Médecine Sciences: M/S
Victor L Villemagne, Vincent Doré, Samantha C Burnham, Colin L Masters, Christopher C Rowe
In Figure 1 of this article as originally published, the chemical structure at bottom right was incorrectly labelled 18 F-PM-PBB3. The text label has been corrected to 18 F-PBB3 in the PDF and HTML versions of the article. As of this date, the structure of PM-PBB3 (also known as APN-1607) has not yet been published.
June 7, 2018: Nature Reviews. Neurology
Weiwei Hu, Shuai Zhang, Yumeng Shen, Qian Yang
Transmissible gastroenteritis virus (TGEV) causes severe diarrhea and high mortality in newborn piglets. It is well established that porcine intestinal epithelium is the target of the TGEV infection, however the mechanism that TGEV invades the host epithelium remains largely unknown. Aminopeptidase N (APN) is a known receptor of TGEV. This study discovered that the extracellular receptor binding domain 1 pertaining to epidermal growth receptor (EGFR) interact with TGEV spike protein. APN and EGFR synergistically promote TGEV invasion...
June 4, 2018: Virology
Mi Tian, Li Tang, Yuanyuan Wu, Srinivasan Beddhu, Yufeng Huang
Adiponectin (ApN) is a multifunctional adipokine. However high, rather than low, concentrations of ApN are unexpectedly found in patients with chronic kidney disease (CKD) via an as yet unknown mechanism and the role of ApN in CKD is unclear. We, herein, investigated the effect of ApN overexpression on the progressive renal injury resulted from deoxycorticosterone acetate-salt (DOCA) and angiotensin II (Ang-II) infusion using a transgenic, inducible ApN-overexpressing mouse model. Three groups of mice (wild type receiving no infusion (WT), WT and cyp1a1 ApN transgenic mice (ApN-Tg) receiving DOCA+Ang-II infusion (WT/DOCA+Ang-II and ApN-Tg/DOCA+Ang-II)) were assigned to receive a normal food containing 0...
June 6, 2018: American Journal of Physiology. Renal Physiology
Shaohua Wang, Dan Li, Conggai Huang, Yu Wan, Jieqiong Wang, Xiao Zan, Bo Yang
Oxidative stress and blood-brain barrier (BBB) dysfunction contribute to brain injury after intracerebral hemorrhage (ICH). Adiponectin (APN) inhibits oxidative stress in the CNS, but the role of APN in ICH is not clear. Thus, we elucidated the possible neuroprotective effect of APN in ICH-induced brain injury in rats and investigated the neuroprotective mechanisms. A lentivirus-carrying APN gene was injected into rats 14 days before ICH induced via intracerebral injection of autologous blood. The effects of lentiviral overexpression of APN on brain injury were evaluated 24 h after ICH...
June 2, 2018: Neuroscience Letters
Limei Piao, Chenglin Yu, Wenhu Xu, Aiko Inoue, Rei Shibata, Xiang Li, Yongshan Nan, Guangxian Zhao, Hailong Wang, Xiangkun Meng, Yanna Lei, Hiroki Goto, Noriyuki Ouchi, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: The mechanism by which angiogenesis declines with aging remains largely unknown. Given that the plasma levels of adiponectin (APN) are decreased in the presence of ischemic cardiovascular disease, we explore the possible mechanisms by which APN/adiponectin receptor1 (AdipoR1) axis inactivation contributes to the decline in vascular regeneration capacity in elderly animals. METHODS AND RESULTS: To study aging-related changes in the APN/AdipoR1 axis and its impact on ischemia-induced angiogenesis, a hindlimb ischemia model was applied to young and aged mice...
September 15, 2018: International Journal of Cardiology
Jiangying Cao, Chunhua Ma, Jie Zang, Shuai Gao, Qianwen Gao, Xiujie Kong, Yugang Yan, Xuewu Liang, Qin'ge Ding, Chunlong Zhao, Binghe Wang, Wenfang Xu, Yingjie Zhang
The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50  = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities...
July 23, 2018: Bioorganic & Medicinal Chemistry
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