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treating to new targets

Ramnath Subbaraman, Ruvandhi R Nathavitharana, Srinath Satyanarayana, Madhukar Pai, Beena E Thomas, Vineet K Chadha, Kiran Rade, Soumya Swaminathan, Kenneth H Mayer
BACKGROUND: India has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world's "missing" patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The "cascade of care" is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions. METHODS AND FINDINGS: The care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India's TB patients...
October 2016: PLoS Medicine
Alexander Arlt, Niels Böhnke, Sebastian Horstmann, Arnoldus W P Vermeer, Stefan Werner, Robert Velten
During our continuous search for new resistance-breaking insecticides applicable to malaria vector control, a new class of α,β-unsaturated imines was identified by applying the principle of conformational rigidification as a powerful tool for compound optimisation. Herein we describe the successful synthesis of these compounds and their biological test results. Our lead compound 16 from this insecticidal class outperforms market standards, notably for the control of mosquito strains that exhibit either metabolic or target-site resistance to these established insecticides...
October 2016: Chimia
Weizhong Sheng, Yusheng Chen, Yuda Gong, Tiangeng Dong, Bo Zhang, Weidong Gao
Anaplastic thyroid carcinoma (ATC) is aggressive and lethal with extrathyroidal invasion, distant metastasis, and resistance to conventional therapies. Cancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in ATC. MicroRNAs (miRNAs) have recently been found as an important class of cellular regulators of ATC carcinogenesis. Identification of CSC-related miRNAs and targets is therefore a priority for the development of new therapeutic paradigms. Patient-derived ATC cells were cultured in conditional media on poly-hema-treated dish...
October 25, 2016: Oncology Reports
Wei Zhao, Xiaohui Zhang, Jia Liu, Bei Sun, Hua Tang, Hong Zhang
Metformin was demonstrated to have effects on breast cancer, and microRNA-27a (miR-27a) is a prognostic marker for breast cancer progression and patient survival. AMPKα2 was found to be a suppressor in breast cancer MCF-7 cells. Therefore, the present study aimed to explain this phenomenon in regards to the relationship between microRNAs (miRNAs) and their target genes and to predict how AMPKα2 may be a downstream target gene of miR-27a, thus exploring the new mechanism of metformin in the treatment of breast cancer regarding miRNAs...
October 24, 2016: Oncology Reports
Magali Hernandez, Bérengère Phulpin, Ludovic Mansuy, Dominique Droz
New targeted cancer therapies such as bisphosphonates, denosumab and bevacizumab are routinely used in adult for the past decades. Their introduction into pediatric medicine is more recent that means there is a paucity of data on long-term effects on dental development and on the risk of osteonecrosis of jaw. This paper aims to outline adverse effects of new targeted cancer therapies on oral cavity including dental abnormalities observed in pediatric population treated with these molecules and the risk of osteonecrosis of the jaw (ONJ)...
October 25, 2016: Journal of Oral Pathology & Medicine
Ethan B Fram, Matthew D Sorensen, Vincent G Bird, Joshua M Stern
Some regions are known to have an increased burden of urolithiasis. Urolithiasis is known to be affected by weather patterns, particularly high ambient temperatures. To identify geographic differences in risk factors, we compared metabolic information for 1254 patients in two geographically distinct regions, New York and Florida, with per sample adjustment for ambient weather. We observed that patients in New York were more likely to have low urine volume, but also lower total urinary calcium (168 vs 216 mg, p = 0...
October 24, 2016: Urolithiasis
Jiangao Zhu, Huiyao Chen, Xiaopei Huang, Songfu Jiang, Yiping Yang
Viral hepatitis remains a global health challenge despite recent progress in the development of more effective therapies. Although virus-specific CD8(+) and CD4(+) T cell responses are essential for viral clearance, it remains largely unknown what regulates T cell-mediated viral clearance. Thus, a better understanding of the regulation of anti-viral T cell immunity would be critical for the design of more effective therapies for viral hepatitis. Using a model of adenovirus-induced hepatitis, here we showed that adenoviral infection induced recruitment of Ly6C(hi) monocytes to the liver in a CCR2-dependent manner...
October 20, 2016: JCI Insight
Cristina Prat, Alicia Lacoma
BACKGROUND: Acute and chronic respiratory tract infections are a common cause of inappropriate antimicrobial prescription. Antimicrobial therapy leads to the development of resistance and the emergence of opportunistic pathogens that substitute the indigenous microbiota. METHODS: This review explores the major challenges and lines of research to adequately establish the clinical role of bacteria and the indications for antimicrobial treatment, and reviews novel therapeutic approaches...
October 2016: International Journal of Infectious Diseases: IJID
Guang-Hui Ma, Yan Ye, Dan Zhang, Xin Xu, Pei Si, Jian-Long Peng, Yong-Long Xiao, Rui-Yuan Cao, Yu-Ling Yin, Jing Chen, Lin-Xiang Zhao, Yu Zhou, Wu Zhong, Hong Liu, Xiao-Min Luo, Li-Li Chen, Xu Shen
Hand, foot and mouth disease (HFMD) is a serious, highly contagious disease. HFMD caused by Enterovirus 71 (EV71), results in severe complications and even death. The pivotal role of EV71 3C(pro) in the viral life cycle makes it an attractive target for drug discovery and development to treat HFMD. In this study, we identified novel EV71 3C(pro) inhibitors by docking-based virtual screening. Totally 50 compounds were selected to test their inhibitory activity against EV71 3C(pro). The best inhibitor DC07090 exhibited the inhibition potency with an IC50 value of 21...
October 11, 2016: European Journal of Medicinal Chemistry
Penelope Anne Lynch, Mike Boots
Evolution persistently undermines vector control programs through insecticide resistance. Here we propose a novel strategy which instead exploits evolution to generate and sustain new control tools. Effective spatial repellents are needed to keep vectors out of houses. Our approach generates such new repellents by combining a high-toxicity insecticide with a candidate repellent initially effective against only part of the vector population. By killing mosquitoes that enter treated properties the insecticide selects for vector phenotypes deflected by the repellent, increasing efficacy of the repellent against the target vector population and in turn protecting the insecticide against the spread of insecticide resistance...
October 25, 2016: ELife
Bharathkumar Inturi, Gurubasavaraj V Pujar, Madhusudhan N Purohit
Mycobacterium tuberculosis enoyl-ACP reductase (InhA) has been validated as a promising target for antitubercular agents. Isoniazid (INH), the most prescribed drug to treat tuberculosis (TB), inhibits a NADH-dependent InhA that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. It is a pro-drug that needs activation to form the inhibitory INH-NAD adduct by KatG coding for catalase-peroxidase. The INH resistance of M. tuberculosis is caused by mutations in KatG, which may lead to multidrug-resistant TB (MDR-TB)...
October 24, 2016: Archiv der Pharmazie
Jin Young Ahn, David Boettiger, Sasisopin Kiertiburanakul, Tuti Parwati Merati, Bui Vu Huy, Wing Wai Wong, Rossana Ditangco, Man Po Lee, Shinichi Oka, Nicolas Durier, Jun Yong Choi
INTRODUCTION: Outbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries. METHODS: Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed...
2016: Journal of the International AIDS Society
Yung-Hao Wong, Chia-Chiun Chiu, Chih-Lung Lin, Ting-Shou Chen, Bo-Ren Jheng, Yu-Ching Lee, Jeremy Chen, Bor-Sen Chen
In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases...
October 19, 2016: Current Pharmaceutical Biotechnology
Mario Maggi, Frederick C W Wu, Thomas H Jones, Graham Jackson, Hermann M Behre, Geoffrey Hackett, Antonio Martin-Morales, Giancarlo Balercia, Adrian S Dobs, Stefan T E Arver, Marcello Maggio, Glenn R Cunningham, Andrea M Isidori, Richard Quinton, Olivia A Wheaton, Flora S Siami, Raymond C Rosen
AIMS: The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). METHODS: The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3 years...
October 2016: International Journal of Clinical Practice
Gil Benedek, Arthur A Vandenbark, Nabil J Alkayed, Halina Offner
The worldwide prevalence of stroke continues to rise despite recent successes in treating acute ischemic stroke. With limited patient eligibility and associated risk of tPA and mechanical thrombectomy, new preventive and therapeutic modalities are needed to stave the rising wave of stroke. Inflammation plays a key role in brain damage after cerebral ischemia, and novel therapies that target pro-inflammatory cells have demonstrated promise for treatment for stroke. Partial MHC class II constructs have been shown to prevent and/or reverse clinical signs of various inflammatory diseases such as experimental autoimmune encephalomyelitis, collagen-induced arthritis and experimental autoimmune uveitis, by reducing the number and frequency of activated cells in the damaged CNS...
October 20, 2016: Neurochemistry International
M Tampellini, A La Salvia, G V Scagliotti
Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising from bile ducts and/or peribiliary glands. Even though it is considered as a rare neoplasm, its incidence is raising, particularly in developed countries. Prognosis is generally poor with few patients who present the inclusion criteria for surgery (the mainstay treatment for this tumour). Several genetic alterations potentially driving tumour progression have been described, representing a possible target for new compounds. Areas covered: A clinical trial search in Clinicaltrials...
October 22, 2016: Expert Opinion on Investigational Drugs
Masafumi Yamabe, Takashi Kumagai, Rieko Shimogawara, Emmanuel Awusah Blay, Akina Hino, Koichiro Ichimura, Akira Sato, Hye-Sook Kim, Nobuo Ohta
The new synthetic compound 1,2,6,7-tetraoxaspiro[7.11]nonadecan (N-89), a novel anti-malaria drug candidate, is also a promising drug candidate against schistosomiasis with killing effects against juvenile stage of S. mansoni. In order to investigate how N-89 kills schistosomes, we used a derivative of N-89, 6-(1,2,6,7-tetraoxaspiro[7.11] nonadec-4-yl)hexan-1-ol (N-251), which enables us to conjugate with fluorescent reagents. Firstly, N-251 showed strong killing effects to larvae of S. mansoni in vitro. Ultrastructural analysis showed the disruptions of the lysosome-like organelles or the acetabular glands, followed by cytoplasmic lysis inside the worm body in N-251-treated group under electron microscopy...
October 19, 2016: Parasitology International
Aimy Sebastian, Gabriela G Loots
Sclerostin is an osteocyte derived negative regulator of bone formation. A highly specific expression pattern and the exclusive bone phenotype have made Sclerostin an attractive target for therapeutic intervention in treating metabolic bone diseases such as osteoporosis and in facilitating fracture repair. Understanding the molecular mechanisms that regulate Sclerostin transcription is of great interest as it may unveil new avenues for therapeutic approaches. Such studies may also elucidate how various signaling pathways intersect to modulate bone metabolism...
October 19, 2016: Bone
Jack J Olney, Paula Braitstein, Jeffrey W Eaton, Edwin Sang, Monicah Nyambura, Sylvester Kimaiyo, Ellen McRobie, Joseph W Hogan, Timothy B Hallett
BACKGROUND: With expanded access to antiretroviral therapy (ART) in sub-Saharan Africa, HIV mortality has decreased, yet life-years are still lost to AIDS. Strengthening of treatment programmes is a priority. We examined the state of an HIV care programme in Kenya and assessed interventions to improve the impact of ART programmes on population health. METHODS: We created an individual-based mathematical model to describe the HIV epidemic and the experiences of care among adults infected with HIV in Kenya...
October 19, 2016: Lancet HIV
Andreas Keil, Sean R Hall, Meike Körner, Martin Herrmann, Ralph A Schmid, Steffen Frese
BACKGROUND: Since the precise mechanism for the pathogenesis of systemic lupus erythematosus (SLE) is unknown, no targeted therapies in addition to immunosuppression are available so far. We recently demonstrated that administration of the topoisomerase I (topo I) inhibitor irinotecan at extremely low concentrations reversed established lupus nephritis in NZB/NZW mice. While profound immunosuppression was absent, we proposed changes in DNA relaxation and anti-double-stranded (ds)DNA antibody binding as the underlying mechanism...
October 22, 2016: Arthritis Research & Therapy
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