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https://www.readbyqxmd.com/read/29342179/the-polymethoxy-flavonoid-sudachitin-suppresses-inflammatory-bone-destruction-by-directly-inhibiting-osteoclastogenesis-due-to-reduced-ros-production-and-mapk-activation-in-osteoclast-precursors
#1
Yoko Ohyama, Junta Ito, Victor J Kitano, Jun Shimada, Yoshiyuki Hakeda
Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS). Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells...
2018: PloS One
https://www.readbyqxmd.com/read/29340783/identification-of-bat-trypanosomes-from-minas-gerais-state-brazil-based-on-18s-rdna-and-cathepsin-l-like-targets
#2
Elaine Cristina Bento, César Gómez-Hernández, Lara Rocha Batista, Laís Anversa, André Luiz Pedrosa, Eliane Lages-Silva, Juan David Ramírez, Luis Eduardo Ramirez
Several bat species can be infected by trypanosomes, but there is not much information about which of these parasites infect bats from Triângulo Mineiro and Alto Paranaíba, Minas Gerais state, Brazil, a formerly endemic region for Trypanosoma cruzi, the causative agent of Chagas disease. The aim of this study was to describe, characterize, and identify the presence of trypanosomes in bats. The captured bats (448) belong to four families and to 19 different species. Of those, 37 bats were found to be positive for trypanosomes by microhematocrit, (infection rate 8...
January 16, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29337245/hepatic-alcohol-dehydrogenase-deficiency-induces-pancreatic-injury-in-chronic-ethanol-feeding-model-of-deer-mice
#3
Samir M Amer, Kamlesh K Bhopale, Ramu D Kakumanu, Vsevolod L Popov, Bill A Rampy, Inas H El-Mehallawi, Magdy M Ashmawy, G A Shakeel Ansari, Bhupendra S Kaphalia
The single most common cause of chronic pancreatitis (CP, a serious inflammatory disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase (ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH deficient (ADH-) vs. hepatic normal ADH (ADH+) deer mice fed 3.5g% ethanol via liquid diet daily for two months. Therefore, progression of ethanol-induced pancreatic injury was determined in ADH- deer mice fed ethanol for four months to delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis (ACP)...
January 11, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29334613/reduced-mir-144-3p-expression-in-serum-and-bone-mediates-osteoporosis-pathogenesis-by-targeting-rank
#4
Chunqing Wang, Hanliang He, Yu Jiang, Liang Wang, Youjia Xu
Osteoblasts and osteoclasts are responsible for the formation and resorption of bone, respectively. An imbalance between these two processes results in a disease called osteoporosis, in which a decreased level of bone strength increases the risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of 18-25 nucleotides that have been previously shown to control bone metabolism by regulating osteoblast and osteoclast differentiation. In the present study, we detected the expression pattern of 10 miRNAs in patient serum samples, and identified six miRNAs altered expression in patients with osteoporosis relative to non-osteoporosis...
January 15, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29333953/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-bcl-2-inhibitor-venetoclax-to-kill-mammary-cancer-cells
#5
Laurence Booth, Jane L Roberts, Francesca Avogadri-Connors, Richard E CutlerJr, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL-2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic fashion with venetoclax to kill HER2+ and TNBC mammary carcinoma cells. This was associated with the drug-combination: reducing the expression and phosphorylation of ERBB1/2/3; in an eIF2α-dependent fashion reducing the expression of MCL-1 and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the activity of the ATM-AMPKα-ULK1 S317 pathway which was causal in the formation of toxic autophagosomes...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333829/-galactosialidosis-a-new-de-novo-mutation-in-ctsa-gene-in-a-patient-with-late-infantile-galactosialidosis
#6
Lara García Hernández, Javier Sierra Sirvent, Laura Gort Mas, María J Coll Roseli
Galactosialidosis (OMIM #256540) is an autosomal recessive lysosomal storage disorder caused by mutations in the CTSA gene, which encodes the protective protein cathepsin A. The loss of function of this protein causes a secondarily deficiency of beta-galactosidase and N-acetyl-a-neuraminidase enzymes activities. We describe the clinical, biochemical and molecular analysis of a case report with a phenotype compatible with the late infantile form. The biochemical analysis reveled deficiencies of beta-galactosidase and neuraminidase activities in dried blood spot and fibroblasts and the molecular study showed two missense mutations in the CTSA gene: a previously reported mutation, p...
February 1, 2018: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/29332035/an-aspartyl-cathepsin-targeted-pet-agent-application-in-an-alzheimer-s-disease-mouse-model
#7
Jonatan A Snir, Mojmir Suchy, Geron A Bindseil, Michael Kovacs, Blaine A Chronik, Robert H E Hudson, Stephen H Pasternak, Robert Bartha
BACKGROUND: Early detection of Alzheimer's disease (AD) pathology is a serious challenge for both diagnosis and clinical trials. The aspartyl protease, Cathepsin D (CatD), is overexpressed in AD and could be a biomarker of disease. We have previously designed a unique contrast agent (CA) for dual-optical and magnetic resonance imaging of the activity of the CatD class of enzymes. OBJECTIVE: To compare the uptake and retention of a novel, more sensitive, and clinically-translatable 68Ga PET tracer targeting CatD activity in 5XFAD mice and non-Tg littermates...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331585/cathepsin-l-promotes-ionizing-radiation-induced-u251-glioma-cell-migration-and-invasion-through-regulating-the-gsk-3%C3%AE-cux1-pathway
#8
Yao Fei, Yajie Xiong, Xiao Shen, Yifan Zhao, Ying Zhu, Long Wang, Zhongqin Liang
Cathepsin L (CTSL) is a lysosomal cysteine protease overexpressed and secreted by tumor cells. Our previous study found that CTSL was involved in ionizing radiation (IR)-induced epithelial-mesenchymal transition (EMT) and the increase of glioma invasion and migration. However, the mechanisms by which CTSL promoted this IR-induced glioma migration and invasion remained unclear. In this study, we demonstrated that IR reduced glycogen synthase kinase-3β (GSK-3β) activity, via the CTSL-mediated phosphorylation of its serine-9 residue, in U251 cells...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29329618/vaccination-against-fasciola-hepatica-using-cathepsin-l3-and-b3-proteases-delivered-alone-or-in-combination
#9
Agnieszka Wesołowska, Katarzyna Basałaj, Luke J Norbury, Alicja Sielicka, Halina Wędrychowicz, Anna Zawistowska-Deniziak
No licensed vaccine is currently available for prevention of Fasciola hepatica infections. However, considering the alarming increase in drug resistance, there is an urgent need for a safe and fully effective vaccine against fasciolosis. Here, we tested if cathepsins L (FhCL3-1, FhCL3-2) and B (FhCB3) secreted by juvenile liver flukes are viable vaccine targets when delivered alone or in combination in a rat model. Since control over the early immune response is crucial for parasite's establishment in its host, it was hypothesised that targeting fluke juvenile stages may prove beneficial...
January 30, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29326439/lung-fibroblasts-promote-metastatic-colonization-through-upregulation-of-stearoyl-coa-desaturase-1-in-tumor-cells
#10
Guanghua Liu, Shi Feng, Lin Jia, Chunying Wang, Yan Fu, Yongzhang Luo
As a rate-limiting step in metastasis, metastatic colonization requires survival signals from supportive stroma. However, the mechanisms driving this process are incompletely understood. Here, we showed that the proliferation of B16F10 cells was promoted when cocultured with lung fibroblasts. Meanwhile, co-injection of B16F10 tumor cells with mouse lung fibroblasts significantly increased lung metastasis. Based on GEO database, we identified stearoyl-CoA desaturase 1 (SCD1) as a novel factor promoting metastatic colonization...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29325877/dmcatd-a-cathepsin-d-like-peptidase-of-the-hematophagous-insect-dipetalogaster-maxima-hemiptera-reduviidae-purification-bioinformatic-analyses-and-the-significance-of-its-interaction-with-lipophorin-in-the-internalization-by-developing-oocytes
#11
Jimena Leyria, Leonardo L Fruttero, Rodrigo Ligabue-Braun, Marina S Defferrari, Estela L Arrese, José L Soulages, Beatriz P Settembrini, Celia R Carlini, Lilián E Canavoso
DmCatD, a cathepsin D-like peptidase of the hematophagous insect Dipetalogaster maxima, is synthesized by the fat body and the ovary and functions as yolk protein precursor. Functionally, DmCatD is involved in vitellin proteolysis. In this work, we purified and sequenced DmCatD, performed bioinformatic analyses and investigated the events involved in its targeting and storage in developing oocytes. By ion exchange and gel filtration chromatography, DmCatD was purified from egg homogenates and its identity was confirmed by mass spectrometry...
January 8, 2018: Journal of Insect Physiology
https://www.readbyqxmd.com/read/29325204/a-transformable-chimeric-peptide-for-cell-encapsulation-to-overcome-multidrug-resistance
#12
Chi Zhang, Li-Han Liu, Wen-Xiu Qiu, Yao-Hui Zhang, Wen Song, Lu Zhang, Shi-Bo Wang, Xian-Zheng Zhang
Multidrug resistance (MDR) remains one of the biggest obstacles in chemotherapy of tumor mainly due to P-glycoprotein (P-gp)-mediated drug efflux. Here, a transformable chimeric peptide is designed to target and self-assemble on cell membrane for encapsulating cells and overcoming tumor MDR. This chimeric peptide (C16 -K(TPE)-GGGH-GFLGK-PEG8 , denoted as CTGP) with cathepsin B-responsive and cell membrane-targeting abilities can self-assemble into nanomicelles and further encapsulate the therapeutic agent doxorubicin (termed as CTGP@DOX)...
January 11, 2018: Small
https://www.readbyqxmd.com/read/29322360/highly-conserved-arg-residue-of-erfnin-motif-of-pro-domain-is-important-for-ph-induced-zymogen-activation-process-in-cysteine-cathepsins-k-and-l
#13
Pulakesh Aich, Sampa Biswas
Pro-domain of a cysteine cathepsin contains a highly conserved Ex2Rx2Fx2Nx3Ix3N (ERFNIN) motif. The zymogen structure of cathepsins revealed that the Arg(R) residue of the motif is a central residue of a salt-bridge/H-bond network, stabilizing the scaffold of the pro-domain. Importance of the arginine is also demonstrated in studies where a single mutation (Arg → Trp) in human lysosomal cathepsin K (hCTSK) is linked to a bone-related genetic disorder "Pycnodysostosis". In the present study, we have characterized in vitro Arg → Trp mutant of hCTSK and the same mutant of hCTSL...
January 10, 2018: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29322325/histochemical-evidence-of-igf2-mrna-binding-protein-2-mediated-regulation-of-osteoclast-function-and-adhesive-ability
#14
Hongrui Liu, Dongfang Li, Shanshan Liu, Zhaopeng Liu, Minqi Li
Insulin-like growth factor 2 (IGF2) messenger RNA-binding proteins (IMPs) are a family of oncofetal RNA-binding proteins that play important roles in cell migration, renewal, and metabolism. IMP2 gene expression may be important in determining IGF2 levels and might, thereby, be central to bone metabolism. In our present study, IMP2-deficient mice exhibited more immature bone structures, characterized by abundant residual cartilage cores; growth plates containing more rich cartilage matrix, which was arranged irregularly; and a significantly thicker hypertrophic chondrocyte layer in the femoral metaphysis, compared with wild-type mice...
January 10, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29318549/targeting-the-expression-of-cathepsin-b-using-crispr-cas9-system-in-mammalian-cancer-cells
#15
Manu Gnanamony, Christopher S Gondi
Cathepsin B belongs to a family of cathepsins and plays an important role in normal physiological functions in the cell. However, overexpression of cathepsin B has been associated with different malignancies, and this has made it an attractive pharmacological target. The advent of CRISPR-Cas9 technology has allowed researchers to efficiently knock down genes with very less nonspecific activity compared to earlier methods. The protocol described below will enable investigators to develop cathepsin B knockdown stable cells and explains ways to study the knockdown...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29318303/synthesis-of-novel-5-n-boc-n-benzyl-2-aminoethyl-7-oxo-4-7-dihydropyrazolo-1-5-a-pyrimidin-3-carboxamides-and-their-inhibition-of-cathepsins-b-and-k
#16
Branislav Lukić, Uroš Grošelj, Marko Novinec, Jurij Svete
Eight novel 5-(N-Boc-N-benzyl-2-aminoethyl)-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-3-carboxamides were prepared in three steps from methyl 3-amino-1H-pyrazole-4-carboxylate and methyl 5-(benzyl(tert-butoxycarbonyl)amino)-3-oxopentanoate. The synthetic procedure comprises cyclocondensation of the above starting compounds, hydrolysis of the ester, and bis(pentafluorophenyl) carbonate (BPC)-mediated amidation. Title carboxamides were tested for inhibition of cathepsins K and B. The N-butylcarboxamide 5a exhibited appreciable inhibition of cathepsin K (IC50 ~ 25 μM), while the strongest inhibition of cathepsin B was achieved with N-(2-picolyl)carboxamide 5c (IC50 ~ 45 μM)...
December 2017: Acta Chimica Slovenica
https://www.readbyqxmd.com/read/29317587/-progress-in-the-study-on-roles-of-cathepsin-in-hypertension
#17
Zhouyangfan Peng, Yapei Li, Pingyu Zeng, Xiaohui Li
Cardiovascular remodeling or dysfunction-induced abnormal cardiac output, blood volume and peripheral vascular resistance is an important pathophysiological mechanism for the occurrence and development of hypertension. Cathepsins are widely expressed in human various tissue and cells and they are involved in the pathogenesis of hypertension through activation of renin - angiotensin system, degradation of cytoplasmic matrix, proliferation of smooth muscle cell and hypertrophy of myocyte. The clinical studies have found that cathepsins can be used as a biomarker for hypertension...
December 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29317302/bu-shen-tong-luo-decoction-prevents-bone-loss-via-inhibition-of-bone-resorption-and-enhancement-of-angiogenesis-in-ovariectomy-induced-osteoporosis-of-rats
#18
Han Yuan, Linyan Xiao, Wen Min, Wenchao Yuan, Shengfeng Lu, Guicheng Huang
ETHNOPHARMACOLOGICAL RELEVANCE: Gathering three ancient formulas, traditional Chinese medicine Bu-Shen-Tong-Luo decoction (BSTLD) has been used to treat postmenopausal osteoporosis (PMO) at the Jiangsu Province Hospital of Chinese Medicine for decades. However, the effect of BSTLD on angiogenesis and bone resorption as well as its possible mechanism are still unknown. AIM OF THE STUDY: This study was aimed to evaluate the preventive effect of BSTLD on ovariectomy-induced bone loss and vasculature disorder, and to investigate the possible bone protection mechanism of BSTLD in inhibiting bone resorption by enhancing angiogenesis signaling in ovariectomy-induced osteoporosis of rats...
January 6, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29316692/3-3-diindolylmethane-suppressed-cyprodinil-induced-epithelial-mesenchymal-transition-and-metastatic-related-behaviors-of-human-endometrial-ishikawa-cells-via-an-estrogen-receptor-dependent-pathway
#19
Bo-Gyoung Kim, Jin-Wook Kim, Soo-Min Kim, Ryeo-Eun Go, Kyung-A Hwang, Kyung-Chul Choi
Cyprodinil (CYP) is a pyrimidine amine fungicide that has been extensively used in agricultural areas. 3,3'-Diindolylmethane (DIM) is a derivative of the dietary phytoestrogen, indole-3-carbinol (I3C), which is derived from cruciferous vegetables and considered to be a cancer-preventive phytonutrient agent. In this study, the effects of CYP and DIM were examined on the cell viability, invasion, and metastasis of human endometrial cancer cells, Ishikawa, via epithelial mesenchymal transition (EMT). CYP increased the level of cell viability of Ishikawa cells compared to DMSO as a control, as did E2...
January 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29316513/the-biology-of-male-breast-cancer
#20
REVIEW
Ian S Fentiman
Important differences have begun to emerge concerning the molecular profile of female and male breast cancer which may prove to be of therapeutic value. This review examined all the available data on the genomics of MBC. Most male cancers are ER+ve but without a corresponding increase in PR positivity and only a weaker association with estrogen-controlled markers such as PS2, HSP27 and Cathepsin-D. HER2 +ve cancers are rare in males and the role of androgen receptor is controversial. Although the Luminal A phenotype was the most frequent in both MBC and FBC, no Luminal B or HER2 phenotypes were found in males and the basal phenotype was very rare...
January 6, 2018: Breast: Official Journal of the European Society of Mastology
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