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https://www.readbyqxmd.com/read/29352755/a-mos1-transposase-in-vivo-assay-to-screen-new-hiv-1-integrase-inhibitors
#1
Mariana Cancian, Elgion L S Loreto
The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28-32% when treated with dolutegravir...
January 19, 2018: Genetica
https://www.readbyqxmd.com/read/29352743/co-transplantation-of-adipose-tissue-derived-stromal-cells-and-olfactory-ensheathing-cells-for-spinal-cord-injury-repair
#2
Eduardo D Gomes, Sofia S Mendes, Rita C Assunção-Silva, Fábio G Teixeira, Ana O Pires, Sandra I Anjo, Bruno Manadas, Hugo Leite-Almeida, Jeffrey M Gimble, Nuno Sousa, Angelo C Lepore, Nuno A Silva, António J Salgado
Patients suffering from Spinal Cord Injury (SCI) still have a dismal prognosis. Despite all the efforts developed in this area, currently there are no effective treatments. Therefore, cell therapies have been proposed as a viable alternative to the current treatments employed. Adipose tissue-derived Stem Cells (ASCs) and Olfactory Ensheathing Cells (OECs) have been used with promising results in different models of SCI, namely due to the regenerative properties of the secretome of the first, and the guidance capability of the second...
January 20, 2018: Stem Cells
https://www.readbyqxmd.com/read/29352742/cambogin-suppresses-dextran-sulphate-sodium-induced-colitis-by-enhancing-treg-cell-stability-and-function
#3
Yue Lu, Na-Mi Kim, Yi-Wen Jiang, Hong Zhang, Dan Zheng, Fu-Xiang Zhu, Rui Liang, Bin Li, Hong-Xi Xu
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of gastrointestinal tract, and the dysfunction of immune regulation plays a critical role in IBD. Reflecting the limited use of current drugs and therapies for IBD treatment, it is necessary to explore novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin attenuates inflammation via Treg-cell-mediated immune modulation...
January 20, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29352731/induced-cumulus-expansion-of-poor-quality-buffalo-cumulus-oocyte-complexes-by-interleukin-1beta-improves-their-developmental-ability
#4
Gaurav Kumar Chaubey, Sandeep Kumar, Manish Kumar, Parul Sarwalia, Arumugam Kumaresan, Sachinandan De, Rakesh Kumar, Tirtha Kumar Datta
The present study was conceived with the aim of modulating the cumulus expansion characteristics of poor quality (BCB-) buffalo oocyte complexes (COCs) in order to improve their fertilization outcomes. BCB- COCs were subjected to in vitro maturation (IVM) in presence of Interleukin - 1 beta (IL-1β) along with BCB- (control) and good quality (BCB +) COCs. Results were assessed morphologically, by scanning electron microscopy (SEM) and by expression analysis of cumulus expansion related genes. Also, numbers of zona pellucida bound spermatozoa were counted and development rates of oocytes were monitored under different groups...
January 20, 2018: Journal of Cellular Biochemistry
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
#5
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/29352619/quantitative-evaluation-of-enzyme-induced-porcine-articular-cartilage-degeneration-based-on-observation-of-entire-cartilage-layer-using-ultrasound
#6
Jingchen Zhang, Liying Xiao, Lingying Tong, Chao Wan, Zhixiu Hao
Enzyme-induced articular cartilage degeneration resembling osteoarthritis was evaluated using a newly defined acoustic parameter, the "averaged magnitude ratio" (AMR), which has been suggested as an indicator of articular cartilage degeneration. In vitro experiments were conducted on porcine cartilage samples digested with trypsin for 2 h (n = 10) and 4 h (n = 13) and healthy control samples (n = 13). AMR was determined with 15- and 25-MHz ultrasound, and the integrated reflection coefficient (IRC) and apparent integrated backscattering coefficient (AIB) were also calculated for comparison...
January 15, 2018: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/29352520/ipragliflozin-improves-mitochondrial-abnormalities-in-renal-tubules-induced-by-a-high-fat-diet
#7
Susumu Takagi, Jinpeng Li, Yuta Takagaki, Munehiro Kitada, Kyoko Nitta, Toshiyuki Takasu, Keizo Kanasaki, Daisuke Koya
OBJECTIVE: Complete mechanisms of reno-protective effects of SGLT2 inhibitors have not been elucidated yet. Mitochondrial biogenesis is regulated by membrane GTPases, such as Opa1 and Mfn2. Here, we investigated whether SGLT2 inhibition in mice fed with a high-fat diet (HFD) improved mitochondrial morphology and restored mitochondrial biogenesis-related molecules. MATERIALS AND METHODS: Mice were fed in control diet or HFD with or without ipragliflozin treatment...
January 20, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29352512/trpv1-antagonists-that-cause-hypothermia-instead-of-hyperthermia-in-rodents-compounds-pharmacological-profiles-in-vivo-targets-thermoeffectors-recruited-and-implications-for-drug-development
#8
Andras Garami, Eszter Pakai, Heath A McDonald, Regina M Reilly, Arthur Gomtsyan, Joshua J Corrigan, Erika Pinter, Dawn X D Zhu, Sonya G Lehto, Narender R Gavva, Philip R Kym, Andrej A Romanovsky
AIM: Thermoregulatory side effects hinder the development of transient receptor potential vanilloid-1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well-studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein. METHODS: Two hypothermia-inducing TRPV1 antagonists, the newly synthesized A-1165901 and the known AMG7905, were used in physiological experiments in rats and mice...
January 20, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29352508/inhibition-of-brd4-attenuates-cardiomyocyte-apoptosis-via-nf-%C3%AE%C2%BAb-pathway-in-a-rat-model-of-myocardial-infarction
#9
Yiping Sun, Ying Xie, Luping Du, Jingwu Sun, Zhiqiang Liu
Myocardial infarction (MI) remains the most common cause of heart failure (HF) worldwide. For almost 50 years, HF has been recognized as a determinant of adverse prognosis after MI, but efforts to promote myocardial repair have failed to be translated into clinical therapies. In the present study, we investigated the effects of BRD4 on cardiac function and the underlying mechanism. We found that BRD4 protein expression was significantly increased in cardiomyocytes of MI rat model and cardiomyocytes under hypoxia, accompanied by the expression of natriuretic peptide A (NPPA) and natriuretic peptide B (NPPB)...
January 20, 2018: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29352446/mycobacterium-marinum-infection-in-zebrafish-and-microglia-imitates-the-early-stage-of-tuberculous-meningitis
#10
Zhan Chen, Xiao-Yi Shao, Chao Wang, Min-Hui Hua, Cheng-Niu Wang, Xin Wang, Qian-Jin Wang, Jin-Yi Yao, Yi-Hui Fan, Yong-Wei Qin
Mycobacterium tuberculosis (M. tuberculosis) invading and activating microglia causes the most serious subtypes of tuberculosis called tubercular meningitis. However, the developmental process of tubercular meningitis, especially the early phase, is poorly understood due to lacking well-established and well-accepted visible models in vitro and in vivo. Here, consistent with one recent report, we found Mycobacterium marinum (M. marinum) invade the zebrafish brain and subsequently cause granuloma-like structures...
January 20, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352443/baculovirus-based-gene-silencing-of-humanin-for-the-treatment-of-pituitary-tumors
#11
María Florencia Gottardo, Matías L Pidre, Camila Zuccato, Antonela S Asad, Mercedes Imsen, Gabriela Jaita, Marianela Candolfi, Víctor Romanowski, Adriana Seilicovich
Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells...
January 19, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29352427/preserved-in-vitro-immunoreactivity-in-children-receiving-long-term-immunosuppressive-therapy-due-to-inflammatory-bowel-disease-or-autoimmune-hepatitis
#12
Teresa Schleker, Eva-Maria Jacobsen, Benjamin Mayer, Gudrun Strauss, Klaus-Michael Debatin, Carsten Posovszky
BACKGROUND: Children with inflammatory bowel disease (IBD) or autoimmune hepatitis (AIH) are at risk for severe infections. This is partially a result of their chronic disease condition but, moreover, a side effect of their immunosuppressive therapy. Currently, vaccinations with live vaccines are regarded as contraindicated under immunosuppressive therapy, mainly because of concerns about side effects and a lack of data showing an adequate immune reaction. As there is no systematic study on the individual immunoreactivity under immunosuppressive therapy in this patient group, we analyzed the lymphocyte subgroups and immunoreactivity of lymphocytes in children with IBD or AIH with and without immunosuppressive therapy in vitro...
January 19, 2018: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/29352403/micronized-zaleplon-delivery-via-orodispersible-film-and-orodispersible-tablets
#13
Prashanth Manda, Carmen Popescu, Abhishek Juluri, Karthik Janga, Praneeth Rao Kakulamarri, Sushmitha Narishetty, S Narasimha Murthy, Michael A Repka
The following research study focuses on improving the solubility of zaleplon (BCS class II drug) via micronization technique in order to enhance its oral delivery in orodispersible formulations. Zaleplon along with a surfactant solution was micronized by ultrasonication. The micronization process reduced the particle size of the crystalline drug about six-fold from its original size of 155.5 μm. The micronized zalepon dispersion was lyophilized to allow for a change in the state of matter (to a powder). The superior dissolution parameters (Q5, Q30, IDR, MDR, MDT, DE, and RDR) of zaleplon in microcrystalline form over the original crystalline form in in vitro dissolution studies had unraveled that micronization technique is an efficient tool in enhancing drug solubility...
January 19, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29352397/bio-prospectus-of-cadmium-bioadsorption-by-lactic-acid-bacteria-to-mitigate-health-and-environmental-impacts
#14
REVIEW
Narendra Kumar, Vandna Kumari, Chand Ram, Kiran Thakur, Sudhir Kumar Tomar
Foodstuffs and water are the key sources of cadmium biomagnifiaction. The available strategies to mitigate this problem are unproductive and expensive for practical large-scale use. Biological decontamination of metals through environmental microbes has been known since long time, whereas lactic acid bacteria (LAB) have not been extensively studied for this purpose. The LAB are known for maintaining homeostasis and suppression of pathogens in humans and animals. They also play a vital role in bioremediation of certain heavy metals...
January 19, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29352392/impact-of-dexamethasone-concentration-on-cartilage-tissue-formation-from-human-synovial-derived-stem-cells-in-vitro
#15
Ryota Chijimatsu, Masato Kobayashi, Kosuke Ebina, Toru Iwahashi, Yosuke Okuno, Makoto Hirao, Atsunori Fukuhara, Norimasa Nakamura, Hideki Yoshikawa
Human synovial mesenchymal stem cells (hSMSCs) are a promising cell source for cartilage regeneration because of their superior chondrogenic potential in vitro. This study aimed to further optimize the conditions for inducing chondrogenesis of hSMSCs, focusing on the dose of dexamethasone in combination with transforming growth factor-β3 (TGFβ3) and/or bone morphogenetic protein-2 (BMP2). When hSMSCs-derived aggregates were cultured with TGFβ3, dexamethasone up to 10 nM promoted chondrogenesis, but attenuated it with heterogeneous tissue formation when used at concentrations over than 100 nM...
January 19, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29352347/autologous-cell-based-therapy-for-treatment-of-large-bone-defects-from-bench-to-bedside
#16
REVIEW
R Verboket, M Leiblein, C Seebach, C Nau, M Janko, M Bellen, H Bönig, D Henrich, I Marzi
OBJECTIVES: Reconstruction of long segmental bone defects is demanding for patients and surgeons, and associated with long-term treatment periods and substantial complication rates in addition to high costs. While defects up to 4-5 cm length might be filled up with autologous bone graft, heterologous bone from cadavers, or artificial bone graft substitutes, current options to reconstruct bone defects greater than 5 cm consist of either vascularized free bone transfers, the Masquelet technique or the Ilizarov distraction osteogenesis...
January 19, 2018: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/29352318/temozolomide-induced-increase-of-tumorigenicity-can-be-diminished-by-targeting-of-mitochondria-in-in-vitro-models-of-patient-individual-glioblastoma
#17
Doreen William, Madlin Walther, Björn Schneider, Michael Linnebacher, Carl Friedrich Classen
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29352310/leishmania-proteophosphoglycans-regurgitated-from-infected-sand-flies-accelerate-dermal-wound-repair-and-exacerbate-leishmaniasis-via-insulin-like-growth-factor-1-dependent-signalling
#18
Emilie Giraud, Tereza Lěstinová, Tamsyn Derrick, Oihane Martin, Rod J Dillon, Petr Volf, Ingrid Műller, Paul A Bates, Matthew E Rogers
Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352298/hexokinase-ii-may-be-dispensable-for-cd4-t-cell-responses-against-a-virus-infection
#19
Siva Karthik Varanasi, Ujjaldeep Jaggi, Nissim Hay, Barry T Rouse
Activation of CD4 T cells leads to their metabolic reprogramming which includes enhanced glycolysis, catalyzed through hexokinase enzymes. Studies in some systems indicate that the HK2 isoform is the most up regulated isoform in activated T cells and in this report the relevance of this finding is evaluated in an infectious disease model. Genetic ablation of HK2 was achieved in only T cells and the outcome was evaluated by measures of T cell function. Our results show that CD4 T cells from both HK2 depleted and WT animals displayed similar responses to in vitro stimulation and yielded similar levels of Th1, Treg or Th17 subsets when differentiated in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#20
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
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