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https://www.readbyqxmd.com/read/29775632/controlled-delivery-of-a-focal-adhesion-kinase-inhibitor-results-in-accelerated-wound-closure-with-decreased-scar-formation
#1
Kun Ma, Sun Hyung Kwon, Jagannath Padmanabhan, Dominik Duscher, Artem A Trotsyuk, Yixiao Dong, Mohammed Inayathullah, Jayakumar Rajadas, Geoffrey C Gurtner
Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries...
May 15, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29774078/targeting-intracellular-mmps-efficiently-inhibits-tumor-metastasis-and-angiogenesis
#2
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/29774064/tumour-homing-chimeric-polypeptide-conjugated-polypyrrole-nanoparticles-for-imaging-guided-synergistic-photothermal-and-chemical-therapy-of-cancer
#3
Mengmeng Sun, Jianwen Guo, Hanjun Hao, Tong Tong, Kun Wang, Weiping Gao
Near-infrared (NIR)-absorbing conjugated polymer nanoparticles are interesting for imaging-guided combination therapy, especially for synergistic photothermal therapy and chemotherapy; however, most of them target tumours passively through the enhanced permeability and retention (EPR) effect, leading to low utilization efficiency. To address this problem, we report an active tumour-targeting strategy of tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles as a new class of drug nanocarriers for imaging-guided combination therapy of cancer...
2018: Theranostics
https://www.readbyqxmd.com/read/29773871/the-somatostatin-secreting-pancreatic-%C3%AE-cell-in-health-and-disease
#4
REVIEW
Patrik Rorsman, Mark O Huising
The somatostatin-secreting δ-cells comprise ~5% of the cells of the pancreatic islets. The δ-cells have complex morphology and might interact with many more islet cells than suggested by their low numbers. δ-Cells contain ATP-sensitive potassium channels, which open at low levels of glucose but close when glucose is elevated. This closure initiates membrane depolarization and electrical activity and increased somatostatin secretion. Factors released by neighbouring α-cells or β-cells amplify the glucose-induced effects on somatostatin secretion from δ-cells, which act locally within the islets as paracrine or autocrine inhibitors of insulin, glucagon and somatostatin secretion...
May 17, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29773592/investigating-chemoresistance-to-improve-sensitivity-of-childhood-t-cell-acute-lymphoblastic-leukemia-to-parthenolide
#5
Benjamin C Ede, Rafal R Asmaro, John P Moppett, Paraskevi Diamanti, Allison Blair
Current therapies for childhood T cell acute lymphoblastic leukemia have increased survival rates to above 85% in developed countries. Unfortunately, some patients fail to respond to therapy and many suffer from serious side effects, highlighting the need to investigate other agents to treat this disease. Parthenolide, a nuclear factor kappa B inhibitor and reactive oxygen species inducer, has been shown to have excellent anti-cancer activity in pediatric leukemia xenografts, with minimal effects on normal hemopoietic cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773367/reduction-active-polymeric-prodrug-micelles-based-on-%C3%AE-cyclodextrin-polyrotaxanes-for-triggered-drug-release-and-enhanced-cancer-therapy
#6
Shuang Bai, Meili Hou, Xiaoxiao Shi, Jiucun Chen, Xiaoqian Ma, Yong-E Gao, Yajun Wang, Peng Xue, Yuejun Kang, Zhigang Xu
As one of the medical polymers approved by US Food and Drug Administration (FDA), poly(ethylene glycol) has low toxicity, high stability, good biocompatibility, unique physical and chemical properties. Cyclodextrin is an ideal candidate as a drug carrier due to its special structures and characteristics. These two materials were successfully assembled through chemosynthesis in combination with the hydrophilic poly(ethylene glycol) methyl ether methacrylate (OEGMA) chain and hydrophobic polymeric camptothecin (CPT) chain by atom transfer radical polymerization (ATRP)...
August 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29772664/the-cholinergic-anti-inflammatory-response-and-the-role-of-macrophages-in-hiv-induced-inflammation
#7
REVIEW
Manuel Delgado-Vélez, José A Lasalde-Dominicci
Macrophages are phagocytic immune cells that protect the body from foreign invaders and actively support the immune response by releasing anti- and proinflammatory cytokines. A seminal finding revolutionized the way macrophages are seen. The expression of the neuronal alpha7 nicotinic acetylcholine receptor (α7-nAChR) in macrophages led to the establishment of the cholinergic anti-inflammatory response (CAR) in which the activation of this receptor inactivates macrophage production of proinflammatory cytokines...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29771149/preparation-and-evaluation-of-tumour-microenvironment-response-multistage-nanoparticles-for-epirubicin-delivery-and-deep-tumour-penetration
#8
Jialing Dai, Shangcong Han, Fang Ju, Mei Han, Lisa Xu, Ruoyu Zhang, Yong Sun
Poor tumour penetration became a major challenge for the use of nanoparticles in anticancer therapy. To further enhance the tumour penetration efficiency, we developed a tumour-microenvironment-responsive multistage drug delivery system which was formed layer by layer via electrostatic interaction with cationic drug-loaded nanoparticles, hyaluronidase (HAase) and iRGD-modified gelatin (G-iRGD). The drug-loaded nanoparticles were formed by self-assembling mPEG-PDPA-PG and encapsulation with epirubicin (EPI)...
May 17, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29769377/-ex-vivo-cytokine-release-determined-by-a-multiplex-cytokine-assay-in-response-to-coccidioidal-antigen-stimulation-of-whole-blood-among-subjects-with-recently-diagnosed-primary-pulmonary-coccidioidomycosis
#9
Neil M Ampel, Ian Robey, Chinh T Nguyen, Brentin Roller, Jessica August, Kenneth S Knox, Demosthenes Pappagianis
The elements of the cellular immune response in human coccidioidomycosis remain undefined. We examined the ex vivo release of an array of inflammatory proteins in response to incubation with a coccidioidal antigen preparation to ascertain which of these might be associated with diagnosis and outcome. Patients with a recent diagnosis of primary pulmonary coccidioidomycosis and a control group of healthy subjects were studied. Blood samples were incubated for 18 h with T27K, a soluble coccidioidal preparation containing multiple glycosylated antigens, and the supernatant was assayed for inflammatory proteins using the multiplex Luminex system...
June 27, 2018: MSphere
https://www.readbyqxmd.com/read/29768228/facile-synthesis-by-a-covalent-binding-reaction-for-ph-responsive-drug-release-of-carboxylated-chitosan-coated-hollow-mesoporous-silica-nanoparticles
#10
Qiang Liu, Jiao Wang, Linnan Yang, Xiaofei Xia, Mei Wang, Shengguang Chen, Rongrong Zhu, Qingxiu Wang, Xianzheng Wu, Shilong Wang
In this study, a promising drug nano-carrier system consisting of mono-dispersed and pH sensitive carboxylated chitosan-hollow mesoporous silica nanoparticles (Ccs-HMSNs) suitable for the treatment of malignant cells was synthesised and investigated. At neutral pH, the Ccs molecules are orderly aggregated state, which could effectively hinder the release of loaded drug molecules. However, in slightly acidic environment, Ccs chains are heavily and flexibly entangled in gel state, which would enhance the subsequent controlled release of the loaded drug...
June 2018: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29768179/intestinal-epithelial-wnt-signaling-mediates-acetylcholine-triggered-host-defense-against-infection
#11
Sid Ahmed Labed, Khursheed A Wani, Sakthimala Jagadeesan, Abdul Hakkim, Mehran Najibi, Javier Elbio Irazoqui
Regulated antimicrobial peptide expression in the intestinal epithelium is key to defense against infection and to microbiota homeostasis. Understanding the mechanisms that regulate such expression is necessary for understanding immune homeostasis and inflammatory disease and for developing safe and effective therapies. We used Caenorhabditis elegans in a preclinical approach to discover mechanisms of antimicrobial gene expression control in the intestinal epithelium. We found an unexpected role for the cholinergic nervous system...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29767951/nanogel-incorporated-injectable-hydrogel-for-synergistic-therapy-based-on-sequential-local-delivery-of-combretastatin-a4-phosphate-ca4p-and-doxorubicin-dox
#12
Wen Jing Yang, Peng Zhou, Lijun Liang, Yanpeng Cao, Junqin Qiao, Xiaohui Li, Zhaogang Teng, Lianhui Wang
Drug combination therapies employing dual drug delivery systems offer an effective approach to reduce disadvantages of single drug therapy, such as high dose and easy generation of drug resistance. Herein, a dual drug delivery system based on nanogel-incorporated injectable hydrogel (NHG) was designed for sequentially local delivery of combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) for antiangiogensis and anticancer combination therapy. The injectable hydrogel was prepared for loading and quick release of hydrophilic drug CA4P, while the pH and redox stimuli-responsive nanohydrogels were incorporated into the injectable hydrogel by pH-responsive boronate ester bond for sustained long-term DOX delivery...
May 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29766488/nanoemulsions-and-dermatological-diseases-contributions-and-therapeutic-advances
#13
REVIEW
Myla Lôbo de Souza, Douglas Dourado Oliveira, Neila de Paula Pereira, Denis Melo Soares
Skin disease is one of the most common human diseases and affects between 30% and 70% of individuals, which requires a lot of attention to their treatments. The delivery of active pharmacological ingredients at the topical level is a challenge because of the difficulties in overcoming the mechanical barrier created by the skin and reaching greater depths, since delivery specificities are decisive for the degree of effectiveness. In this way, the nanoemulsions emerge as a potential system for the incorporation of active substances in the cells and for the controlled release of active principles...
May 15, 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/29764192/simvastatin-suppresses-interleukin-i%C3%AE-release-in-human-peripheral-blood-mononuclear-cells-stimulated-with-cholesterol-crystals
#14
Anna J Boland, Nisha Gangadharan, Pierce Kavanagh, Linda Hemeryck, Jennifer Kieran, Michael Barry, Patrick T Walsh, Margaret Lucitt
Statins are mainstream therapy in the treatment and prevention of cardiovascular disease through inhibitory effects on cholesterol synthesis. However, statins' beneficial effects in cardiovascular disease may also be attributable to their role as anti-inflammatory mediators. Here, we investigated the effects of simvastatin treatment on expression levels of interleukin (IL) 1β in both patient with hyperlipidemia and healthy human peripheral blood mononuclear cells (PBMCs) using cholesterol crystals (CC), a cardiovascular pathogenic stimulus for activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29763901/5-aminolevulinic-acid-mediated-sonodynamic-therapy-alleviates-atherosclerosis-via-enhancing-efferocytosis-and-facilitating-a-shift-in-the-th1-th2-balance-toward-th2-polarization
#15
Yang Yang, Yuanyuan Liu, Xi Chen, Jie Gong, Zhen Huang, Wei Wang, Yuanqi Shi, Yu Wang, Jianting Yao, Zhaoqian Shen, Zhen Tian, Hong Jin, Ye Tian
BACKGROUND/AIMS: We and other groups have demonstrated that 5-aminolevulinic acid (ALA)-mediated sonodynamic therapy (ALA-SDT) induces macrophage and foam cell apoptosis and stabilizes atherosclerosis (AS) plaques in animal models. Lymphocytes also play vital roles in the development of AS. The primary purpose of the present study was to investigate the effects of ALA-SDT on T helper (Th) cell fate and function, Th subset differentiation, and atherosclerotic lesion stability. METHODS: We utilized ALA-SDT on Western diet-fed apoE-/-mice in vivo and human Jurkat cells in vitro...
May 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29763898/fgfr4-links-glucose-metabolism-and-chemotherapy-resistance-in-breast-cancer
#16
Min Xu, Shuzheng Chen, Weibin Yang, Xue Cheng, Yani Ye, Jianting Mao, Xulu Wu, Li Huang, Jiansong Ji
BACKGROUND/AIMS: Poor response to chemotherapy leads to the relapse and metastatic progression of tumors. Reprogrammed glucose metabolism is one of the important hallmarks of cancer that facilitates cancer cell survival, proliferation and chemoresistance. However, the precise fate of glucose metabolism and its role in therapy responsiveness in cancers remains largely unexplored. METHODS: The glycolytic phenotype of doxorubicin (ADR)-resistant breast cancer cells and their parental cells was assessed by measuring glucose uptake, lactate release, and extracellular acidification rate (ECAR)...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29763756/tobramycin-mediated-silver-nanospheres-graphene-oxide-composite-for-synergistic-therapy-of-bacterial-infection
#17
Sadeeq Ullah, Aftab Ahmad, Fazli Subhan, Aminullah Jan, Muslim Raza, Arif Ullah Khan, Aziz-Ur Rahman, Usman Ali Khan, Muhammad Tariq, Qipeng Yuan
Graphene-based materials have attracted a significant attention in constructing hybrid systems for drug delivery with enhanced antimicrobial activities. In our work, we demonstrated the formation of silver nanoparticles (AgNPs) on graphene oxide (GO) using tobramycin (TOB), an aminoglycoside antibiotic, as reducing and decorating agent. The TOB decorated GO AgNPs (TOB-GO-Ag) composite was used as an antibacterial agent against multi-drug resistant Gram-negative E-coli (BL21 DE3). The reversal of surface potential from -30 mV (GO) to +20 mV confirms the successful reduction of GO by TOB...
May 7, 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29763715/near-infrared-light-activated-red-emitting-upconverting-nanoplatform-for-t-1-weighted-magnetic-resonance-imaging-and-photodynamic-therapy
#18
Xiang-Long Tang, Jun Wu, Ben-Lan Lin, Sheng Cui, Hong-Mei Liu, Ru-Tong Yu, Xiao-Dong Shen, Ting-Wei Wang, Wei Xia
Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF4 : 40% Yb, 2% Er@CaF2 upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn2+ , is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs...
May 12, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29760725/the-effects-of-hyperacute-serum-on-the-elements-of-the-human-subchondral-bone-marrow-niche
#19
Melinda Simon, Bálint Major, Gabriella Vácz, Olga Kuten, István Hornyák, Adél Hinsenkamp, Dorottya Kardos, Marcell Bagó, Domonkos Cseh, Adrienn Sárközi, Denes Horvathy, Stefan Nehrer, Zsombor Lacza
Mesenchymal stem cells (MSCs) are widely used in laboratory experiments as well as in human cell therapy. Their culture requires animal sera like fetal calf serum (FCS) as essential supplementation; however, animal sera pose a risk for clinical applications. Human blood derivatives, for example, platelet-rich plasma (PRP) releasates, are potential replacements of FCS; however, it is unclear which serum variant has the best effect on the given cell or tissue type. Additionally, blood derivatives are commonly used in musculoskeletal diseases like osteoarthritis (OA) or osteonecrosis as "proliferative agents" for the topical MSC pool...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29760707/the-yin-and-yang-of-tyrosine-kinase-inhibition-during-experimental-polymicrobial-sepsis
#20
Cassiano Felippe Gonçalves-de-Albuquerque, Ina Rohwedder, Adriana Ribeiro Silva, Alessandra Silveira Ferreira, Angela R M Kurz, Céline Cougoule, Sarah Klapproth, Tanja Eggersmann, Johnatas D Silva, Gisele Pena de Oliveira, Vera Luiza Capelozzi, Gabriel Gutfilen Schlesinger, Edlaine Rijo Costa, Rita de Cassia Elias Estrela Marins, Attila Mócsai, Isabelle Maridonneau-Parini, Barbara Walzog, Patricia Rieken Macedo Rocco, Markus Sperandio, Hugo Caire de Castro-Faria-Neto
Neutrophils are the first cells of our immune system to arrive at the site of inflammation. They release cytokines, e.g., chemokines, to attract further immune cells, but also actively start to phagocytose and kill pathogens. In the case of sepsis, this tightly regulated host defense mechanism can become uncontrolled and hyperactive resulting in severe organ damage. Currently, no effective therapy is available to fight sepsis; therefore, novel treatment targets that could prevent excessive inflammatory responses are warranted...
2018: Frontiers in Immunology
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