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https://www.readbyqxmd.com/read/29150361/post-translational-mechanisms-of-host-subversion-by-bacterial-effectors
#1
REVIEW
Nichollas E Scott, Elizabeth L Hartland
Bacterial effector proteins are a specialized class of secreted proteins that are translocated directly into the host cytoplasm by bacterial pathogens. Effector proteins have diverse activities and targets, and many mediate post-translational modifications of host proteins. Effector proteins offer potential in novel biotechnological and medical applications as enzymes that may modify human proteins. Here, we discuss the mechanisms used by effectors to subvert the human host through blocking, blunting, or subverting immune mechanisms...
November 14, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29150301/is-subchondral-bone-cyst-formation-in-non-load-bearing-region-of-osteoarthritic-knee-a-vascular-problem
#2
Pok Man Boris Chan, Chunyi Wen, Wai Ching Yang, Chunhoi Yan, KwongYuen Chiu
Subchondral bone cyst is common in the progressive knee osteoarthritis yet its underlying mechanism remains unclear. In addition to the existing theories such as synovial fluid influx and mechanical contusion, we identified the potential link between vascular pathology and osteoarthritic bone pathologies including cystic lesion formation, particularly in the non-load-bearing region. This new hypothesis for SBC formation in non-load-bearing region for knee, which cannot be explained by the existing theories, will provide us a new angle to understand the pathomechanism and pathophysiology of subchondral bone disturbance in osteoarthritis in addition to the classical biomechanical overloading theories...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149835/forkhead-transcription-factors-formulating-a-foxo-target-for-cognitive-loss
#3
Kenneth Maiese
BACKGROUND: With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. METHODS: Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29149824/gene-therapy-and-retinal-diseases
#4
Claudio Campa, Carla Enrica Gallenga, Elena Bolletta, Paolo Perri
Background Gene therapy represents the therapeutic delivery of nucleic acid polymers into a patient's cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ...
November 16, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29149454/melatonin-alleviates-adipose-inflammation-through-elevating-%C3%AE-ketoglutarate-and-diverting-adipose-derived-exosomes-to-macrophages-in-mice
#5
Zhenjiang Liu, Lu Gan, Tiantian Zhang, Qian Ren, Chao Sun
Obesity is associated with macrophage infiltration and metabolic inflammation, both of which promote metabolic disease progression. Melatonin is reported to possess anti-inflammatory properties by inhibiting inflammatory response of adipocytes and macrophages activation. However, the effects of melatonin on the communication between adipocytes and macrophages during adipose inflammation remain elusive. Here, we demonstrated melatonin alleviated inflammation and elevated α-ketoglutarate (αKG) level in adipose tissue of obese mice...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29149420/blood-clearance-and-occupational-exposure-for-177-lu-dotatate-compared-to-177-lu-psma-radionuclide-therapy
#6
Mohammad Abuqbeitah, Mustafa Demir, Lebriz Uslu-Beşli, Nami Yeyin, Kerim Sönmezoğlu
The main target of this work is to examine blood clearance and external exposure for (177)Lu-DOTATATE compared with new emerging (177)Lu-PSMA therapy. Blood clearance and radiation exposure of 31 patients treated with 5.5 ± 1.1 GBq (177)Lu-DOTATATE were compared to those of 23 patients treated with 7.4 GBq (177)Lu-PSMA. Dose rates were measured at several distances and time points up to 120 h after treatment. Blood samples were collected conjunctively after infusion. Caregiver's cumulative dose was measured by means of an OSL (optically stimulated luminescence) dosimeter for 4-5 days and medical staff's dose was also estimated using electronic personal dosimeters...
November 17, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/29149413/tctp-has-a-crucial-role-in-the-different-stages-of-prostate-cancer-malignant-progression
#7
Virginie Baylot, Sara Karaki, Palma Rocchi
Prostate cancer (PC) is the second most common cause of cancer-related mortality in men in the western world after lung cancer. Many patients are not candidates for resection given the advanced stage of their cancer. The primary treatment for advanced PC is the castration therapy which supresses the production of androgens, hormone that promotes PC growth. Despite the efficiency of the castration therapy, most patients develop castration resistant disease which remains uncurable. Clearly, novel approaches are required to effectively treat castration resistant PC (CRPC)...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149067/the-hmgb1-rage-pro-inflammatory-axis-in-the-human-placenta-modulating-effect-of-low-molecular-weight-heparin
#8
Cristian Zenerino, Anna Maria Nuzzo, Domenica Giuffrida, Marilisa Biolcati, Alessandra Zicari, Tullia Todros, Alessandro Rolfo
We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR...
November 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29148294/synthesis-physiochemical-property-and-antimicrobial-activity-of-novel-quaternary-ammonium-salts
#9
Xianrui Xie, Wei Cong, Feng Zhao, Hongjuan Li, Wenyu Xin, Guige Hou, Chunhua Wang
Twenty-four novel 5-phenyl-1,3,4-oxadiazole-2-thiol (POT) analogues, benzo[d]oxazole-2-thiol, benzo[d]thiazole-2-thiol and 5-methyl-1,3,4-thiadiazole-2-thiol-substituted N,N-bis(2-hydroxyethyl) quaternary ammonium salts (QAS) (5a-d, 6a-d, 7a-d, 10a-d, 13a-d, 16a-d) were prepared and characterised by FTIR, NMR and elemental analysis. Part of target compounds (5d, 6d, 7d, 10d, 13d, 16d) displayed potent antimicrobial effect against ten common pathogens (S. aureus, α-H-tococcus, β-H-tococcus, E. coli, P. aeruginosa, Proteus vulgaris, Canidia Albicans, Cytospora mandshurica, Physalospora piricola, Aspergillus niger) and had relatively low cytotoxity against two human cell lines (HaCat and LO2)...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29147793/pharmacophoric-characteristics-of-dengue-virus-ns2b-ns3pro-inhibitors-a-systematic-review-of-the-most-promising-compounds
#10
REVIEW
Camyla Alves Leonel, William Gustavo Lima, Michelli Dos Santos, Ariane Coelho Ferraz, Alex Gutterres Taranto, José Carlos de Magalhães, Luciana Lara Dos Santos, Jaqueline Maria Siqueira Ferreira
Dengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease due to the lack of specific immunotherapies and antiviral drugs. That said, the DENV NS2B/NS3pro protease complex is essential in both the viral multiplication cycle and in disease pathogenesis, and is considered a promising target for new antiviral therapies. Here, we performed a systematic review to evaluate the pharmacophoric characteristics of promising compounds against NS2B/NS3pro reported in the past 10 years...
November 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#11
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146540/temperature-sensitive-copolymer-coated-fluorescent-mesoporous-silica-nanoparticles-as-a-reactive-oxygen-species-activated-drug-delivery-system
#12
Feng Yu, Huijing Wu, Yao Tang, Yufang Xu, Xuhong Qian, Weiping Zhu
In this study, a temperature and ROS-responsive drug delivery system ROSP@MSN based on mesoporous silica nanoparticles has been designed and synthesized by taking advantage of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate modified polymers (ROSP) as "nano-valve", which can respond selectively to cancer exclusive microenvironment and implement targeted drug release. Due to the superior temperature-sensitive properties of ROSP, ROSP@MSN could achieve cargo loading in cold water, and subsequently close the pore by raising temperature to obtain ROSP@MSN@DOX...
November 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29145972/cancer-immunotherapy-getting-brainy-visualizing-the-distinctive-cns-metastatic-niche-to-illuminate-therapeutic-resistance
#13
Mark Owyong, Niloufar Hosseini-Nassab, Gizem Efe, Alexander Honkala, Renske J E van den Bijgaart, Vicki Plaks, Bryan Ronain Smith
The advent of cancer immunotherapy (CIT) and its success in treating primary and metastatic cancer may offer substantially improved outcomes for patients. Despite recent advancements, many malignancies remain resistant to CIT, among which are brain metastases, a particularly virulent disease with no apparent cure. The immunologically unique niche of the brain has prompted compelling new questions in immuno-oncology such as the effects of tissue-specific differences in immune response, heterogeneity between primary tumors and distant metastases, and the role of spatiotemporal dynamics in shaping an effective anti-tumor immune response...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145462/circulating-soluble-endoglin-modifies-the-inflammatory-response-in-mice
#14
Laura Ruiz-Remolina, Claudia Ollauri-Ibáñez, Lucía Pérez-Roque, Elena Núñez-Gómez, Fernando Pérez-Barriocanal, José Miguel López-Novoa, Miguel Pericacho, Alicia Rodríguez-Barbero
Inflammation is associated with every health condition, and is an important component of many pathologies such as cardiovascular diseases. Circulating levels of soluble endoglin have been shown to be higher in the serum of patients with cardiovascular diseases with a significant inflammatory component. The aim of this study was to evaluate the implication of circulating soluble endoglin in the inflammatory response. For this purpose, a transgenic mouse expressing human soluble endoglin (sEng+) was employed, and three different inflammatory approaches were used to mimic inflammatory conditions in different tissues...
2017: PloS One
https://www.readbyqxmd.com/read/29145426/buserelin-alleviates-chloride-transport-defect-in-human-cystic-fibrosis-nasal-epithelial-cells
#15
Marie-Laure Calvez, Nathalie Benz, Florentin Huguet, Aude Saint-Pierre, Elise Rouillé, Christelle Coraux, Claude Férec, Mathieu Kerbiriou, Pascal Trouvé
Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride (Cl-) channel regulated by protein kinases, phosphatases, divalent cations and by protein-protein interactions. Among protein-protein interactions, we previously showed that Annexin A5 (AnxA5) binds to CFTR and is involved in the channel localization within membranes and in its Cl- channel function. The deletion of phenylalanine at position 508 (F508del) is the most common mutation in CF which leads to an altered protein (F508del-CFTR) folding with a nascent protein retained within the ER and is quickly degraded...
2017: PloS One
https://www.readbyqxmd.com/read/29145036/liver-immunotolerance-and-hepatocellular-carcinoma-patho-physiological-mechanisms-and-therapeutic-perspectives
#16
REVIEW
Gaël S Roth, Thomas Decaens
At the moment of the diagnosis of hepatocellular carcinoma (HCC), 70% of patients have only access to palliative treatments, with very few therapeutic options. Liver immunology is very specific, and liver immunotolerance is particularly developed because of the constant and massive influx of antigens. Deregulation of hepatic immunotolerance is implicated in chronic liver diseases development and particularly in liver carcinogenesis. For these reasons, HCC may be an excellent candidate for anticancer immunotherapies such as immune checkpoint inhibitors targeting CTLA-4 and PD-L1/PD-1...
November 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#17
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29143669/considerations-for-using-minocycline-vs-doxycycline-for-treatment-of-canine-heartworm-disease
#18
Mark G Papich
BACKGROUND: Doxycycline has been considered the first drug of choice for treating Wolbachia, a member of the Rickettsiaceae, which has a symbiotic relationship with filarial worms, including heartworms. Wolbachia, is susceptible to tetracyclines, which have been used as adjunctive treatments for heartworm disease. Treatment with doxycycline reduces Wolbachia numbers in all stages of heartworms and improves outcomes and decreased microfilaremia in dogs treated for heartworm disease. The American Heartworm Society recommends treatment with doxycycline in dogs diagnosed with heartworm disease at a dose of 10 mg/kg twice daily for 28 days...
November 9, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29142786/extraordinary-clinical-benefit-to-sequential-treatment-with-targeted-therapy-and-immunotherapy-of-a-braf-v600e-and-pd-l1-positive-metastatic-lung-adenocarcinoma
#19
Shuyu D Li, Annia Martial, Alexa B Schrock, Jane J Liu
Background: The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29142420/exploring-the-cytotoxic-potential-of-triterpenoids-enriched-fraction-of-bacopa-monnieri-by-implementing-in-vitro-in-vivo-and-in-silico-approaches
#20
Md Nasar Mallick, Washim Khan, Rabea Parveen, Sayeed Ahmad, Sadaf, Mohammad Zeeshan Najm, Istaq Ahmad, Syed Akhtar Husain
Background: Bacopa monnieri (BM) is a herbaceous plant traditionally used from time immemorial in Ayurvedic and folklore medicines. We hypothesized that the extract of the whole plant might contain numerous molecules with having antitumor activities that could be very effective in killing of human cancer cells. Objectives: This work investigated anticancer activity of bioactive fraction of BM. Materials and Methods: The hydroalcoholic extract of BM was fractionated with different solvent, namely, hexane, dichloromethane (DCM), acetone, methanol, and water...
October 2017: Pharmacognosy Magazine
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