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https://www.readbyqxmd.com/read/29352647/ifn-%C3%AE-and-tnf-%C3%AE-pre-licensing-protects-mesenchymal-stromal-cells-from-the-pro-inflammatory-effects-of-palmitate
#1
Lauren Boland, Anthony J Burand, Alex J Brown, Devlin Boyt, Vitor A Lira, James A Ankrum
The use of mesenchymal stromal cell (MSC) therapy for the treatment of type 2 diabetes (T2D) and T2D complications is promising; however, the investigation of MSC function in the setting of T2D has not been thoroughly explored. In our current study, we investigated the phenotype and function of MSCs in a simulated in vitro T2D environment. We show that palmitate, but not glucose, exposure impairs MSC metabolic activity with moderate increases in apoptosis, while drastically affecting proliferation and morphology...
December 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29350904/nanoplatform-assembled-from-a-cd44-targeted-prodrug-and-smart-liposomes-for-dual-targeting-of-tumor-microenvironment-and-cancer-cells
#2
Yaqi Lv, Chaoran Xu, Xiangmei Zhao, Chenshi Lin, Xin Yang, Xiaofei Xin, Li Zhang, Chao Qin, Xiaopeng Han, Lei Yang, Wei He, Lifang Yin
The tumor microenvironment (TME) plays a critical role in tumor initiation, progression, invasion and metastasis. Therefore, a therapy that combines chemotherapeutic drugs with a TME modulator could be a promising route for cancer treatment. This paper reports a nanoplatform self-assembled from a hyaluronic acid (HA)-paclitaxel (PTX) (HA-PTX) prodrug and marimastat (MATT)-loaded thermosensitive liposomes (LTSLs) (MATT-LTSLs) for the dual targeting of the TME and cancer cells. Interestingly, the prodrug HA-PTX can self-assemble on both positively and negatively charged liposomes, forming hybrid nanoparticles (HNPs, 100 nm)...
January 19, 2018: ACS Nano
https://www.readbyqxmd.com/read/29350484/paraptosis-inducing-nanomedicine-overcomes-cancer-drug-resistance-for-a-potent-cancer-therapy
#3
Yongcun Zhou, Feiteng Huang, Ying Yang, Pingli Wang, Zhen Zhang, Yining Tang, Youqing Shen, Kai Wang
Most chemotherapeutic drugs and their nanomedicine formulations exert anticancer activity by inducing cancer cell apoptosis. However, cancer cells inherently have and acquire many antiapoptosis mechanisms, causing cancer drug resistance and poor prognoses in patients. Herein, a potent paraptosis-inducing nanomedicine is reported that causes quick nonapoptotic death of cancer cells, overcoming apoptosis-based resistance and effectively inhibiting drug-resistant tumor growth. The nanomedicine is composed of micelles made from an amphiphilic 8-hydroxyquinoline (HQ)-conjugate block copolymer with polyethylene glycol...
January 19, 2018: Small
https://www.readbyqxmd.com/read/29350067/soluble-neuregulin1-is-strongly-up-regulated-in-the-rat-model-of-charcot-marie-tooth-1a-disease
#4
Benedetta Elena Fornasari, Giulia Ronchi, Davide Pascal, Davide Visigalli, Giovanna Capodivento, Lucilla Nobbio, Isabelle Perroteau, Angelo Schenone, Stefano Geuna, Giovanna Gambarotta
Neuregulin1 (NRG1) is a growth factor playing a pivotal role in peripheral nerve development through the activation of the transmembrane co-receptors ErbB2-ErbB3. Soluble NRG1 isoforms, mainly secreted by Schwann cells, are strongly and transiently up-regulated after acute peripheral nerve injury, thus suggesting that they play a crucial role also in the response to nerve damage. Here we show that in the rat experimental model of the peripheral demyelinating neuropathy Charcot-Marie-Tooth 1A (CMT1A) the expression of the different NRG1 isoforms (soluble, type α and β, type a and b) is strongly up-regulated, as well as the expression of NRG1 co-receptors ErbB2-ErbB3, thus showing that CMT1A nerves have a gene expression pattern highly reminiscent of injured nerves...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29350055/therapeutic-strategies-and-nano-drug-delivery-applications-in-management-of-ageing-alzheimer-s-disease
#5
Govindarajan Karthivashan, Palanivel Ganesan, Shin-Young Park, Joon-Soo Kim, Dong-Kug Choi
In recent years, the incidental rate of neurodegenerative disorders has increased proportionately with the aging population. Alzheimer's disease (AD) is one of the most commonly reported neurodegenerative disorders, and it is estimated to increase by roughly 30% among the aged population. In spite of screening numerous drug candidates against various molecular targets of AD, only a few candidates - such as acetylcholinesterase inhibitors are currently utilized as an effective clinical therapy. However, targeted drug delivery of these drugs to the central nervous system (CNS) exhibits several limitations including meager solubility, low bioavailability, and reduced efficiency due to the impediments of the blood-brain barrier (BBB)...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29350016/biomarkers-of-treatment-efficacy-in-patients-with-chronic-spontaneous-urticaria
#6
M Sánchez-Borges, A Capriles-Hulett, F Caballero-Fonseca, L González-Aveledo
Background. Currently there are no biomarkers useful to predict the future evolution and the therapeutic response in patients with chronic spontaneous urticaria (CSU). Objective. To review the available information on biomarkers that might be applied for the follow up of the response to guideline recommended therapies for CSU. Methods. A review of the medical literature on CSU potential clinical and laboratory biomarkers in PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, chronic spontaneous urticaria, antihistamines (AHs), omalizumab (OMA), cyclosporine (CyA), and treatment...
January 2018: European Annals of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29349894/assessment-of-the-potential-of-temporin-peptides-from-the-frog-rana-temporaria-ranidae-as-anti-diabetic-agents
#7
Vishal Musale, Bruno Casciaro, Maria Luisa Mangoni, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon
Temporin A (FLPLIGRVLSGIL-NH2 ), temporin F (FLPLIGKVLSGIL-NH2 ), and temporin G (FFPVIGRILNGIL-NH2 ), first identified in skin secretions of the frog Rana temporaria, produced concentration-dependent stimulation of insulin release from BRIN-BD11 rat clonal β-cells at concentrations ≥1 nM, without cytotoxicity at concentrations up to 3 μM. Temporin A was the most effective. The mechanism of insulinotropic action did not involve an increase in intracellular Ca2+ concentrations. Temporins B, C, E, H, and K were either inactive or only weakly active...
January 19, 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29349573/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-elevates-stimulus-evoked-release-of-dopamine-in-freely-moving-rats
#8
Juho-Matti Renko, Susanne Bäck, Merja H Voutilainen, T Petteri Piepponen, Ilkka Reenilä, Mart Saarma, Raimo K Tuominen
Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for neurodegenerative disorders like Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown neuroprotective and restorative effects on nigral dopaminergic neurons in various animal models of Parkinson's disease. To date, however, their effects on brain neurochemistry have not been compared using in vivo microdialysis...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348806/therapeutic-nanosystem-consisting-of-singlet-oxygen-responsive-prodrug-and-photosensitizer-excited-by-two-photon-light
#9
Yi Lin, Xiao-Fang Jiang, Xiangyan Duan, Fang Zeng, Bo Wu, Shuizhu Wu
Using light as the sole stimulus and employing the generated singlet oxygen as a therapeutic agent and the trigger to activate chemo-drug release could serve as an elegant way to bring into full play the advantageous features of light and enhance therapeutic efficacy through a combination of chemotherapy and photodynamic therapy. Herein a liposomal drug system has been developed by embedding a fluorescent photosensitizer and a prodrug into phospholipid vesicles. Upon one- or two-photon light irradiation, the photosensitizer generates singlet oxygen, which removes the protecting group of the prodrug and subsequently causes the release of the active drug chlorambucil...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29346736/light-activatable-red-blood-cell-membrane-camouflaged-dimeric-prodrug-nanoparticles-for-synergistic-photodynamic-chemotherapy
#10
Qing Pei, Xiuli Hu, Xiaohua Zheng, Shi Liu, Yawei Li, Xiabin Jing, Zhigang Xie
Biomimetic approach offers numerous opportunities to design therapeutic platforms with enhanced antitumor performance and biocompatibility. Herein we report a novel red blood cell membrane-camouflaged nanoparticle (RBC(M(TPC-PTX))) for synergistic chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX2-TK) and photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). In vitro experiments show that the prepared RBC(M(TPC-PTX)) is readily taken up into endosomes...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#11
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29344592/ph-responsible-fluorescent-carbon-nanoparticles-for-tumor-selective-theranostics-via-ph-turn-on-off-fluorescence-and-photothermal-effect-in-vivo-and-in-vitro
#12
Eun Bi Kang, Jung Eun Lee, Zihnil Adha Islamy Mazrad, Insik In, Ji Hoon Jeong, Sung Young Park
We developed nanoparticles comprising a photothermal dye (IR825)-loaded carbonized zwitterionic polymer [FNP-I] as "switch-on" pH-responsive fluorescence probes to sense intracellular cancer cells and for near-infrared (NIR) controllable photothermal therapy (PTT) in vivo and in vitro. The fluorescent "off" of FNP-I was activated after reaching the cancer cell environment, where the zwitterionic compartment of FNP lost its hydrophobicity to induce PTT-mediated heat release of IR825 under NIR irradiation in the tumor...
January 18, 2018: Nanoscale
https://www.readbyqxmd.com/read/29344350/the-sensitivity-of-the-human-thirst-response-to-changes-in-plasma-osmolality-a-systematic-review
#13
REVIEW
Fintan Hughes, Monty Mythen, Hugh Montgomery
Background: Dehydration is highly prevalent and is associated with adverse cardiovascular and renal events. Clinical assessment of dehydration lacks sensitivity. Perhaps a patient's thirst can provide an accurate guide to fluid therapy. This systematic review examines the sensitivity of thirst in responding to changes in plasma osmolality in participants of any age with no condition directly effecting their sense of thirst. Methods: Medline and EMBASE were searched up to June 2017...
2018: Perioperative Medicine
https://www.readbyqxmd.com/read/29342359/semiconducting-photothermal-nanoagonist-for-remote-controlled-specific-cancer-therapy
#14
Xu Zhen, Chen Xie, Yuyan Jiang, Xiangzhao Ai, Bengang Xing, Kanyi Pu
Nanomedicines have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally-responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively...
January 17, 2018: Nano Letters
https://www.readbyqxmd.com/read/29341292/amniotic-fluid-stem-cell-exosomes-therapeutic-perspective
#15
Francesca Beretti, Manuela Zavatti, Francesca Casciaro, Giuseppina Comitini, Fabrizia Franchi, Veronica Barbieri, Giovanni B La Sala, Tullia Maraldi
It is widely accepted that the therapeutic potential of stem cells can be largely mediated by paracrine factors, also included into exosomes. Thus, stem cell-derived exosomes represent a major therapeutic option in regenerative medicine avoiding, if compared to stem cells graft, abnormal differentiation and tumor formation. Exosomes derived from mesenchymal stem cells (MSC) induce damaged tissue repair, and can also exert immunomodulatory effects on the differentiation, activation and function of different lymphocytes...
January 16, 2018: BioFactors
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#16
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339024/nrf2-are-pathway-attenuates-oxidative-and-apoptotic-response-in-human-osteoarthritis-chondrocytes-by-activating-erk1-2-elk1-p70s6k-p90rsk-signaling-axis
#17
Nazir M Khan, Imran Ahmad, Tariq M Haqqi
Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1β stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient...
January 12, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29338453/proteomic-serum-biomarkers-for-neuromuscular-diseases
#18
Sandra Murphy, Margit Zweyer, Rustam R Mundegar, Dieter Swandulla, Kay Ohlendieck
The clinical evaluation of neuromuscular symptoms often includes the assessment of altered blood proteins or changed enzyme activities. However, the blood concentration of many muscle-derived serum markers is not specific for different neuromuscular disorders and also shows alterations in the course of these diseases. Thus, the establishment of more reliable biomarker signatures for improved muscle diagnostics is required. Areas covered: To address the lack of muscle disease-specific marker molecules, mass spectrometry-based proteomics was applied to the systematic identification and biochemical characterization of new serum biomarker candidates...
January 17, 2018: Expert Review of Proteomics
https://www.readbyqxmd.com/read/29337311/dinaciclib-induces-immunogenic-cell-death-and-enhances-anti-pd-1-mediated-tumor-suppression
#19
Dewan Md Sakib Hossain, Sarah Javaid, Mingmei Cai, Chunsheng Zhang, Anandi Sawant, Marlene Hinton, Manjiri Sathe, Jeff Grein, Wendy Blumenschein, Elaine M Pinheiro, Alissa Chackerian
Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337110/muc16-c-terminal-induced-secretion-of-tumor-derived-il-6-contributes-to-tumor-associated-treg-enrichment-in-pancreatic-cancer
#20
Kun Fan, Chao Yang, Zhiyao Fan, Qiuyi Huang, Yiyin Zhang, He Cheng, Kaizhou Jin, Yu Lu, Zhengshi Wang, Guopei Luo, Xianjun Yu, Chen Liu
Pancreatic cancer is the most lethal tumor. CA125 (gene symbol MUC16) is an important serum marker for pancreatic cancer diagnosis and treatment. High serum CA125 is related to metabolic tumor burden and poor prognosis. The circulating Treg subset is another independent prognostic factor for pancreatic cancer. Our unpublished data indicated that the circulating Treg proportion might be related to the serum CA125 level. However, the potential relationship and underlying mechanism of MUC16 and Treg in pancreatic cancer tissues remain unclear...
January 11, 2018: Cancer Letters
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