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https://www.readbyqxmd.com/read/29775899/hispidulin-alleviates-high-glucose-induced-podocyte-injury-by-regulating-protective-autophagy
#1
Fengbo Wu, Sijia Li, Nan Zhang, Wei Huang, Xiang Li, Manyi Wang, Ding Bai, Bo Han
OBJECTIVES: Diabetic nephropathy (DN) is one of the most common complications in patients with diabetes, and the discovery of novel targeted therapeutic approaches for DN treatment still faces severe challenges. In the current study, we aimed to discover a novel natural product for potential DN treatment and determine its molecular mechanisms. MATERIALS AND METHODS: Methylthiazoltetrazolium (MTT) assay was employed to evaluate cell viability. Transmission electron microscopy, GFP-LC3 fluorescence fusion plasmid, and Annexin V/PI apoptosis assay were carried out to determine cellular autophagy and apoptosis...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775812/virus-entry-and-its-inhibition-to-prevent-and-treat-hepatitis-b-and-hepatitis-d-virus-infections
#2
REVIEW
Thomas Tu, Stephan Urban
While chronic infection with the human hepatitis B virus (HBV) and hepatitis delta virus (HDV) inflict major health burdens worldwide, current therapies cannot cure patients. One possible novel approach is blocking virus entry to prevent the establishment of infection in naïve hepatocytes. As HBV and HDV use identical viral envelope proteins and the same entry mechanisms, such a strategy would target both viruses. Entry inhibitors (e.g. neutralizing antibodies) have been relegated to the limited role of prophylaxis...
May 15, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29775760/synthesis-of-axially-disubstituted-silicon-phthalocyanines-and-investigation-of-photodynamic-effects-on-hct-116-colorectal-cancer-cell-line
#3
Ceren Sarı, Figen Celep Eyüpoğlu, İsmail Değirmencioğlu, Rıza Bayrak
Photodynamic therapy is one of the hot topics in cancer studies recently. Basically, photosensitizing chemical substrates which are stimulated by light having a specific wavelength cause fatal effect on different kind of cells in photodynamic therapy. In this study, axially 4-{[(1E)-2-furylmethylene]amino}phenol, 4-{[(1E)-2-thienylmethylene]amino}phenol and 4-{[(1E)-(4-nitro-2-thienyl)methylene]amino}phenol disubstituted silicon phthalocyanines were synthesized as Photosensitizers for photodynamic therapy in cancer treatment for the first time...
May 15, 2018: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29775627/acquisition-of-tumorigenic-potential-and-therapeutic-resistance-in-cd133-subpopulation-of-prostate-cancer-cells-exhibiting-stem-cell-like-characteristics
#4
Rajnee Kanwal, Sanjeev Shukla, Ethan Walker, Sanjay Gupta
The role of CD133 (Prominin-1) as a cancer stem cell marker may be useful for therapeutic approaches and prognostication in prostate cancer patients. We investigated the stem-cell-related function and biological features of a subpopulation of CD133+ cells isolated from established primary human prostate cancer cell lines. The CD133+ cells sorted from human prostate cancer 22Rv1 exhibited high clonogenic and tumorigenic capabilities, sphere forming capacity and serially reinitiated transplantable tumors in NOD-SCID mice...
May 15, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29775610/monocarboxylate-transporters-in-breast-cancer-and-adipose-tissue-are-novel-biomarkers-and-potential-therapeutic-targets
#5
Zhiyu Li, Qi Wu, Si Sun, Juan Wu, Juanjuan Li, Yimin Zhang, Changhua Wang, Jingping Yuan, Shengrong Sun
Monocarboxylate transporters (MCTs) are transmembrane proteins that control the lactate metabolism and associated with poor prognosis in solid tumors including breast cancer (BC). This study aimed to evaluate the clinical and prognostic value of MCTs used by immunohistochemistry and quantum dots-based fluorescent imaging technique in BC and surrounding stroma with emphasis on the interaction between tumour and stroma. Moreover, the data from The Cancer Genome Atlas (TCGA) was analyzed to evaluate the association between MCTs mRNA expression and prognosis of breast cancer patients...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775441/-the-biological-function-and-significance-of-il-35-in-the-pathogenesis-of-atherosclerosis
#6
EDITORIAL
Mateusz Staciwa, Marlena Broncel
The imbalance of anti-inflammatory /pro- inflammatory cytokines plays an important role in the progression of atherosclerosis. Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBVinduced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immunesuppressive cytokine mainly produced by regulatory T cells. Accumulating evidence suggests that IL-35 may represent a target for antiatherosclerotic therapy based on its several anti-inflammatory features. This review provide a brief overview of IL-35 biology and the role of IL-35 in the atherosclerosis, autoimmune disease and cancers...
April 23, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29775223/curcumin-down-regulates-il-17a-mediated-p53-fibrinolytic-system-in-bleomycin-induced-acute-lung-injury-in-vivo
#7
Mahesh M Gouda, Yashodhar P Bhandary
Bleomycin (BLM) induced cellular damage causes inflammation in the alveolar compartment and impairment of fibrinolytic system leads to alveolar epithelial cell apoptosis. Here, we describe novel inflammatory pathway associated with p53-fibrinolytic system and apoptosis of alveolar epithelial cells and pharmacological efficiency of curcumin against this action. In the present study we used C57BL/6 mice. The specific dose and time interval of curcumin were analyzed to assess the intervention. Experiments were designed to investigate the IL-17A mediated modulation in the alveolar epithelial cell apoptosis and injury...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29774563/alternative-therapies-for-gerd-a-way-to-personalized-antireflux-surgery
#8
Erwin Rieder, Martin Riegler, Aleksandar P Simić, Ognjan M Skrobić, Luigi Bonavina, Richard Gurski, Matthias Paireder, Donald O Castell, Sebastian F Schoppmann
Gastroesophageal reflux disease (GERD) is a common disorder, known to affect about 20% of the Western population. Although conventional medical or surgical treatment has proven effective, there is certainly room for improvements. As only 10% of GERD patients are finally treated by antireflux surgery, a large therapeutic window exists. This treatment gap consists of patients who are not effectively treated with proton pump inhibitor but do not want to run the potential risks of conventional surgery. During the last two decades, several novel and intriguing options for the surgical treatment of GERD have been introduced and found their way into clinical use...
May 17, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29774543/human-monocyte-transciptional-profiling-identifies-interleukin-18-receptor-accessory-protein-and-lactoferrin-as-novel-immune-targets-in-hypertension
#9
Matthew R Alexander, Allison E Norlander, Fernando Elijovich, Ravi V Atreya, Amadou Gaye, Juan S Gnecco, Cheryl L Laffer, Cristi L Galindo, Meena S Madhur
BACKGROUND AND PURPOSE: Monocytes play a critical role in hypertension. The purpose of our study was to use an unbiased approach to determine whether hypertensive individuals on conventional therapy exhibit an altered monocyte gene expression profile and to perform validation studies of select genes to identify novel therapeutic targets for hypertension. EXPERIMENTAL APPROACH: Next-generation RNA sequencing identified differentially expressed genes in a small discovery cohort of normotensive and hypertensive individuals...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29774169/phase-2-study-of-everolimus-for-relapsed-or-refractory-classical-hodgkin-lymphoma
#10
Patrick B Johnston, Lauren C Pinter-Brown, Ghulam Warsi, Kristen White, Radhakrishnan Ramchandren
Background: The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29774123/the-association-of-human-endogenous-retrovirus-h-long-terminal-repeat-associating-protein-2-hhla2-expression-with-gastric-cancer-prognosis
#11
Masataka Shimonosono, Takaaki Arigami, Shigehiro Yanagita, Daisuke Matsushita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Yoshikazu Uenosono, Sumiya Ishigami, Shoji Natsugoe
Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#12
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774078/targeting-intracellular-mmps-efficiently-inhibits-tumor-metastasis-and-angiogenesis
#13
Yaqi Lv, Xiangmei Zhao, Lidan Zhu, Sijia Li, Qingqing Xiao, Wei He, Lifang Yin
Treatment for metastatic cancer is a great challenge throughout the world. Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis. Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/β-casein (CN) complexes was established to cure a 4T1 metastatic cancer model via targeting CD44 and intracellular, rather than extracellular, MMPs. Methods: HPMC NPs were prepared by assembling the complexes and prodrug under ultrasonic treatment, which the interaction between them was evaluated by förster resonance energy transfer, circular dichroism and fluorescence spectra...
2018: Theranostics
https://www.readbyqxmd.com/read/29774066/caveolae-mediated-mesenchymal-stem-cell-labelling-by-pss-coated-plga-pfob-nano-contrast-agent-for-mri
#14
Hieu Vu Quang, Chi-Chih Chang, Ping Song, Ellen-Margrethe Hauge, Jørgen Kjems
Rationale: Non-invasive tracking of transplanted cells is critical in evaluating delivery, migration and prognosis of cell therapies. Methods: We formulated a nano-contrast agent consisting of a perfluorooctylbromide (PFOB) core within a shell of poly (lactic-co-glycolic acid) (PLGA) followed by a coat of polystyrene sulfonate (PSS) for 19 F MRI. The nano-contrast agent (PSS-NP) was characterised by DLS and the uptake efficiency of the nano-contrast agent (PSS-NP) was tested using flow cytometry, in vitro MRI and confocal microscopy...
2018: Theranostics
https://www.readbyqxmd.com/read/29774062/-in-vivo-imaging-biomarkers-of-neuroinflammation-in-the-development-and-assessment-of-stroke-therapies-towards-clinical-translation
#15
REVIEW
Bastian Zinnhardt, Maximilian Wiesmann, Lisa Honold, Cristina Barca, Michael Schäfers, Amanda J Kiliaan, Andreas H Jacobs
Modulation of the inflammatory microenvironment after stroke opens a new avenue for the development of novel neurorestorative therapies in stroke. Understanding the spatio-temporal profile of (neuro-)inflammatory imaging biomarkers in detail thereby represents a crucial factor in the development and application of immunomodulatory therapies. The early integration of quantitative molecular imaging biomarkers in stroke drug development may provide key information about (i) early diagnosis and follow-up, (ii) spatio-temporal drug-target engagement (pharmacodynamic biomarker), (iii) differentiation of responders and non-responders in the patient cohort (inclusion/exclusion criteria; predictive biomarkers), and (iv) the mechanism of action...
2018: Theranostics
https://www.readbyqxmd.com/read/29774059/inflammation-in-stroke-the-role-of-cholinergic-purinergic-and-glutamatergic-signaling
#16
REVIEW
Abraham Martín, María Domercq, Carlos Matute
The inflammatory response is a major factor in stroke pathophysiology and contributes to secondary neuronal damage in both acute and chronic stages of the ischemic injury. Recent work in experimental cerebral ischemia has demonstrated the involvement of neurotransmitter signaling in the modulation of neuroinflammation. The present review discusses recent findings on the therapeutic potential and diagnostic perspectives of cholinergic, purinergic and glutamatergic receptors and transporters in experimental stroke...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29774055/immunotherapy-of-experimental-and-human-stroke-with-agents-approved-for-multiple-sclerosis-a-systematic-review
#17
REVIEW
Mirjam Dreikorn, Zeljko Milacic, Vladimir Pavlovic, Sven G Meuth, Christoph Kleinschnitz, Peter Kraft
Background: 'Thromboinflammation' describes a novel concept in stroke pathophysiology that has opened up the possibility of immunotherapeutic approaches which could become promising strategies for targeted stroke therapies in the future. Methods: We reviewed current evidence for agents approved for multiple sclerosis in preclinical and clinical stroke studies. A systematic review was performed in accordance with the PRISMA statement, searching MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 16 October 2017...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29773864/igg-single-chain-trail-fusion-proteins-for-tumour-therapy
#18
Martin Siegemund, Felix Schneider, Meike Hutt, Oliver Seifert, Ines Müller, Dagmar Kulms, Klaus Pfizenmaier, Roland E Kontermann
Single-chain formats of TNF-related apoptosis inducing ligand (scTRAIL) can serve as effector components of tumour-associated antigen-targeted as well as non-targeted fusion proteins, being characterized by high tumour cell-specific induction of apoptosis through death receptor activation. We studied the suitability of immunoglobulin G as a scaffold for oligovalent and bispecific TRAIL fusion proteins. Thus, we developed novel targeted hexa- and dodecavalent IgG-scTRAIL molecules by fusing scTRAIL to the C-terminus of either light (LC-scTRAIL) or heavy immunoglobulin chain (HC-scTRAIL), or to both ends (LC/HC-scTRAIL) of the anti-EGFR IgG antibody hu225...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773803/a-novel-small-molecule-chaperone-of-rod-opsin-and-its-potential-therapy-for-retinal-degeneration
#19
Yuanyuan Chen, Yu Chen, Beata Jastrzebska, Marcin Golczak, Sahil Gulati, Hong Tang, William Seibel, Xiaoyu Li, Hui Jin, Yong Han, Songqi Gao, Jianye Zhang, Xujie Liu, Hossein Heidari-Torkabadi, Phoebe L Stewart, William E Harte, Gregory P Tochtrop, Krzysztof Palczewski
Rhodopsin homeostasis is tightly coupled to rod photoreceptor cell survival and vision. Mutations resulting in the misfolding of rhodopsin can lead to autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration that currently is untreatable. Using a cell-based high-throughput screen (HTS) to identify small molecules that can stabilize the P23H-opsin mutant, which causes most cases of adRP, we identified a novel pharmacological chaperone of rod photoreceptor opsin, YC-001. As a non-retinoid molecule, YC-001 demonstrates micromolar potency and efficacy greater than 9-cis-retinal with lower cytotoxicity...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773553/intratumoral-androgen-levels-are-linked-to-tmprss2-erg-fusion-in-prostate-cancer
#20
Matias Knuuttila, Arfa Mehmood, Jenni Mäki-Jouppila, Henrik Ryberg, Pekka Taimen, Juha Knaapila, Otto Ettala, Peter J Bostrom, Claes Ohlsson, Mikko S Venäläinen, Asta Laiho, Laura L Elo, Petra Sipilä, Sari Makela, Matti Poutanen
Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral DHT concentrations were significantly higher in the cancerous tissues compared to benign prostate (p<0...
May 17, 2018: Endocrine-related Cancer
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