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Susumu Ishiguro, Nabil A Alhakamy, Deepthi Uppalapati, Jennifer Delzeit, Cory J Berkland, Masaaki Tamura
To evaluate the potential of cell-penetrating peptide-based delivery of apoptosis-inducer gene in cancer therapy, a modified HIV-1 TAT peptide (dimerized TAT peptide, dTAT) was studied. The dTAT and plasmid DNA (pDNA) complexes (dTAT-pDNA) were condensed using calcium chloride (dTAT-pDNA-Ca(2+)). This simple nonviral formulation approach showed high levels of gene expression in vitro without any cytotoxicity. In mouse studies, a single intratracheal (IT) aerosol spray or 2 intravenous (IV) injections of the dTAT, apoptosis-inducer gene, angiotensin II type 2 receptor (AT2R), and Ca(2+) complexes (dTAT-pAT2R-Ca(2+)) significantly attenuated the acutely growing mouse Lewis lung carcinoma allografts in mouse lungs...
October 18, 2016: Journal of Pharmaceutical Sciences
Angelos Hatzakis, Helen Papachristou, Sangeetha J Nair, Jacqueline Fortunko, Tracy Foote, HeeCheol Kim, Tashi L Peling, Andrew J Worlock
BACKGROUND: Quantitation of HIV-RNA is critically important for diagnosis, prognosis, treatment, monitoring and assessment of infectivity in HIV-1 infection. The objective of this study was to assess performance characteristics of the Aptima HIV-1 Quant Dx assay (Aptima), a new transcription mediated amplification (TMA), fully integrated and automated assay from Hologic Inc., San Diego, CA, USA. The analytical sensitivity, analytical specificity, precision and detection of HIV-1 subtypes were tested based on commercially available international standards or panels...
October 21, 2016: Virology Journal
Tshifhiwa Magoro, George Gachara, Lufuno Mavhandu, Emmaculate Lum, Helen K Kimbi, Roland N Ndip, Pascal Bessong
BACKGROUND: HBV and HIV share similar transmission routes. Concurrent infection with the two viruses usually results in more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Further, this co-infection may lead to cross-resistance between HIV and HBV drugs and increased liver injury, either due to direct hepatotoxicity or drug-related immune-reconstitution hepatitis. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to guide patient management...
October 21, 2016: Virology Journal
Zhujun Ao, Rong Zhu, Xiaoli Tan, Lisa Liu, Liyu Chen, Shuiping Liu, XiaoJian Yao
BACKGROUND: HIV-1 latency is a major obstacle for HIV-1 eradication. Extensive efforts are being directed toward the reactivation of latent HIV reservoirs with the aim of eliminating latently infected cells via the host immune system and/or virus-mediated cell lysis. RESULTS: We screened over 1,500 small molecules and kinase inhibitors and found that a small molecule, PKC412 (midostaurin, a broad-spectrum kinase inhibitor), can stimulate viral transcription and expression from the HIV-1 latently infected ACH2 cell line and primary resting CD4+ T cells...
October 21, 2016: Virology Journal
Meng Wang, Ian Tietjen, Min Chen, David E Williams, Julie Daoust, Mark A Brockman, Raymond J Andersen
Eight new sesterterpenoids, alotaketals D (8) and E (9), ansellones D (10), E (11), F (12), and G (13), anvilones A (14), and B (15), have been isolated from extracts of the marine sponge Phorbas sp. collected in Howe Sound British Columbia and their structures have been elucidated by analysis of NMR and MS data. Ansellone F (12) contains a rare 1,2-3,4 bis epoxy decalin substructure. Anvilones A (14) and B (15) have the unprecedented tetracylic anvilane terpenoid carbon skeleton. Using a cell culture model of latent HIV-1 infection, ansellone A (3), alotaketal D (8), and anvilone A (14) were found to induce HIV proviral gene expression similar to a control compound prostratin (1), while the known sesterterpenoid alotaketal C (2), isolated from the same extract, was more potent and gave a stronger response than prostratin (1)...
October 21, 2016: Journal of Organic Chemistry
Rita Meleddu, Simona Distinto, Angela Corona, Enzo Tramontano, Giulia Bianco, Claudia Melis, Filippo Cottiglia, Elias Maccioni
A series of 3-3-{2-[2-3-methyl-4-phenyl-2,3-dihydro-1,3-thiazol-2-ylidene]hydrazin-1-ylidene-2,3-dihydro-1H-indol-2-one derivatives has been designed and synthesized to study their activity on both HIV-1 (Human Immunodeficiency Virus type 1) RT (Reverse Transcriptase) associated functions. These derivatives are analogs of previously reported series whose biological activity and mode of action have been investigated. In this work we investigated the influence of the introduction of a methyl group in the position 3 of the dihydrothiazole ring and of a chlorine atom in the position 5 of the isatin nucleus...
October 21, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Aditya H Gaur, Hilda Kizito, Wasana Prasitsueubsai, Natella Rakhmanina, Mohammed Rassool, Rana Chakraborty, Jagmohan Batra, Pope Kosalaraksa, Wicharn Luesomboon, Danielle Porter, Yongwu Shao, Michael Myers, Lillian Ting, Devi SenGupta, Erin Quirk, Martin S Rhee
BACKGROUND: The prodrug tenofovir alafenamide is associated with improved renal and bone safety compared with tenofovir disoproxil fumarate. We aimed to assess safety, pharmacokinetics, and efficacy of this single-tablet, fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-infected, treatment-naive adolescents. METHODS: We did a 48 week, single-arm, open-label trial in treatment-naive adolescents with HIV from ten hospital clinics in South Africa, Thailand, Uganda, and the USA...
October 17, 2016: Lancet HIV
N Masdoua, L Boublenza, H Hassaine, J Ngou, A Nahet, M Segondy, F Razik, D Regagba, N Sadouki, D Mouhammedi
OBJECTIVES: We aimed to characterize HPV infections and cervical lesions in Western Algeria. PATIENTS AND METHODS: A total of 96 cervical samples obtained from women at risk of HPV infection (HIV-1-infected or presenting with a gynecological disease) were analyzed to characterize this infection and search for cytological abnormalities. RESULTS: A total of 60% of women at risk had an HPV infection. The rate of high-risk HPV (HR-HPV) infection among these women was 84...
October 17, 2016: Médecine et Maladies Infectieuses
Francesca Esposito, Ilaria Carli, Claudia Del Vecchio, Lijia Xu, Angela Corona, Nicole Grandi, Dario Piano, Elias Maccioni, Simona Distinto, Cristina Parolin, Enzo Tramontano
BACKGROUND: Despite the availability of effective antiretroviral therapies, drugs for HIV-1 treatment with new mode of action are still needed. An innovative approach is aimed to identify dual HIV-1 inhibitors, small molecules that can inhibit two viral functions at the same time. Rhubarb, originated from Rheum palmatum L. and Rheum officinale Baill., is one of the earliest and most commonly used medicinal plants in Traditional Chinese Medicine (TCM) practice. We wanted to explore TCM for the identification of new chemical scaffolds with dual action abilities against HIV-1...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I Bukrinsky, Paul J Brindley
Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein...
October 2016: PLoS Pathogens
Simnikiwe H Mayaphi, Desmond J Martin, Thomas C Quinn, Oliver Laeyendecker, Steve A S Olorunju, Gregory R Tintinger, Anton C Stoltz
BACKGROUND: Two thirds of the world's new HIV infections are in sub-Saharan Africa. Acute HIV infection (AHI) is the time of virus acquisition until the appearance of HIV antibodies. Early HIV infection, which includes AHI, is the interval between virus acquisition and establishment of viral load set-point. This study aimed to detect acute and early HIV infections in a hyper-endemic setting. METHODS: This was a cross-sectional diagnostic study that enrolled individuals who had negative rapid HIV results in five clinics in South Africa...
2016: PloS One
Herman G Sprenger, Wouter F Bierman, Melanie I Martes, Reindert Graaff, Tjip S Van Der Werf, Andries J Smit
OBJECTIVE: HIV-1 infection is associated with an increased cardiovascular disease (CVD) risk. Advanced glycation end products (AGEs) are formed as stable markers of glycemic and oxidative stress. Skin autofluorescence (SAF) as marker of accumulated AGEs is increased and predictive of CVD events in diabetes mellitus, chronic kidney disease (CKD) and pre-existing CVD. We determined SAF levels in HIV-1 infected patients, testing the hypothesis that SAF predicts CVD events in HIV infection...
October 18, 2016: AIDS
Rob Stenstrom, Daphne Ling, Eric Grafstein, Rolando Barrios, Chris Sherlock, Reka Gustafson, Farzaneh Osati, Iraj Poureslami, Aslam Anis
OBJECTIVES: The objective of this study was to estimate the seroprevalence of HIV infection and the acceptability of point-of-care HIV testing in an innercity Canadian emergency department. METHODS: We conducted a prospective cohort study in an urban tertiary care emergency department between August 2009 and January 2011. Randomly selected patients were enrolled using probabilistic sampling based on patient volumes. Inclusion criteria were age 19-75 years and ability to provide informed consent...
October 20, 2016: Canadian Journal of Public Health. Revue Canadienne de Santé Publique
Maria Prokofjeva, Vladimir Tsvetkov, Dmitry Basmanov, Anna Varizhuk, Maria Lagarkova, Igor Smirnov, Kirill Prusakov, Dmitry Klinov, Vladimir Prassolov, Galina Pozmogova, Sergey N Mikhailov
New natural and chemically modified DNA aptamers that inhibit HIV-1 activity at submicromolar concentrations (presumably via preventing viral entry into target cells) are reported. The new DNA aptamers were developed based on known intramolecular G-quadruplexes (G4s) that were functionally unrelated to HIV inhibition [the thrombin-binding aptamer and the fragment of the human oncogene promoter (Bcl2)]. The majority of previously described DNA inhibitors of HIV infection adopt intermolecular structures, and thus their folding variability represents an obvious disadvantage...
October 20, 2016: Nucleic Acid Therapeutics
Lu Cao, Mingui Fu, Santosh Kumar, Anil Kumar
Methamphetamine (METH), a commonly used controlled substance, is known to exacerbate neuropathological dysfunction in HIV-infected individuals. The neuropathological manifestation results from cell death or dysfunction in the central nervous system (CNS) wherein autophagy is expected to have an important role. Autophagy is generally considered protective during deprivation/stress. However, excessive autophagy can be destructive, leading to autophagic cell death. This study was designed to investigate if METH and HIV-1 gp120 interact to induce autophagy in SVGA astrocytes, and whether autophagy is epiphenomenal or it has a role in METH- and gp120-induced cytotoxicity...
October 20, 2016: Cell Death & Disease
Mary Norval, Anna K Coussens, Robert J Wilkinson, Liza Bornman, Robyn M Lucas, Caradee Y Wright
In this review, reports were retrieved in which vitamin D status, as assessed by serum 25-hydroxyvitamin D [25(OH)D] levels, was measured in South African population groups with varied skin colours and ethnicities. Healthy children and adults were generally vitamin D-sufficient [25(OH)D level >50 nmol/L] but the majority of those aged above 65 years were deficient. A major role for exposure to solar ultraviolet radiation (UVR) in determining 25(OH)D levels was apparent, with the dietary contribution being minor...
October 18, 2016: International Journal of Environmental Research and Public Health
Wenjun Zhang, Junfang Chen, Xiao Hong Pan, Jiafeng Zhang, Zhihong Guo, Yan Luo, Jiezhe Yang, Yan Xia, Lin He, Yun Xu, Ke Xu, Xiaobei Ding
OBJECTIVE: To investigate the HIV-1 molecular epidemiology among young people (18 to 25 years old) in Hangzhou. METHODS: Plasma samples from 262 newly diagnosed HIV-1 infected patients were collected between 2009 and 2013 from Hangzhou of Zhejiang province. HIV-1 nucleotide sequences of pol gene regions were amplified using a nested PCR method and sequenced. Phylogenetic and recombination analyses were used to determine the HIV-1 genotypes. RESULTS: Based on all sequences generated, the subtype/circulating recombinant forms (CRF) distribution was as follows: CRF01_AE (68...
October 20, 2016: AIDS Research and Human Retroviruses
Yihong Hu, Zhenzhou Wan, Yan-Heng Zhou, Davey M Smith, Yong-Tang Zheng, Chiyu Zhang
The on-going generation of HIV-1 inter-subtype recombination has led to new circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in Asia. Here, we evaluated whether previously reported URFs were actually CRFs. All available complete or near full-length HIV-1 URFs sequences from Asia were retrieved from the HIV Los Alamos National Laboratory Sequence database, and phylogenetic, transmission cluster and bootscan analyses were performed using MEGA 6.0, Cluster Picker 1.2.1, and SimPlot3.5.1...
October 20, 2016: AIDS Research and Human Retroviruses
Elizabeth Wolf, Joshua Herbeck, Stephen Van Rompaey, Mari M Kitahata, Katherine K Thomas, Gregory Pepper, Lisa Frenkel
HIV-1 incidence among youth, especially men who have sex with men (MSM), is increasing in the US. We aimed to better understand the patterns of adolescent HIV-1 acquisition, in order to help guide future prevention interventions. We conducted a study combining epidemiologic and HIV-1 pol sequence data from a retrospective cohort of HIV-infected adults and adolescents in Seattle, WA between 2000 and 2013. Adolescents were defined as 13-24 years of age at the time of first HIV-1 care. Maximum-likelihood phylogenetic trees were reconstructed to identify putative viral transmission clusters of two or more individuals, followed by multivariable regression tests of associations between clustering and demographic and clinical parameters...
October 20, 2016: AIDS Research and Human Retroviruses
Mahar Fatima, Bharat Prajapati, Kanza Saleem, Rina Kumari, Chitra Mohindar Singh Singal, Pankaj Seth
Astroglia are indispensable component of the tripartite synapse ensheathing innumerous soma and synapses. Its proximity to neurons aids the regulation of neuronal functions, health and survival through dynamic neuroglia crosstalk. Susceptibility of astrocyte to HIV-1 infection and subsequent latency culminates in compromised neuronal health. The viral protein HIV-1 transactivator of transcription (Tat) is neurotoxic. HIV-1 Tat is detected in brain of AIDS patients even in cases where viral load is non-detectable due to successful HAART therapy...
October 20, 2016: Glia
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