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Drug resistant

Godwin U Ebiloma, Teresa Díaz Ayuga, Emmanuel O Balogun, Lucía Abad Gil, Anne Donachie, Marcel Kaiser, Tomás Herraiz, Daniel K Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs...
February 26, 2018: European Journal of Medicinal Chemistry
Yi-Lei Fan, Xiao-Hong Jin, Zhong-Ping Huang, Hai-Feng Yu, Zhi-Gang Zeng, Tao Gao, Lian-Shun Feng
Tuberculosis still remains one of the most common, communicable, and leading deadliest diseases known to mankind throughout the world. Drug-resistance in Mycobacterium tuberculosis which threatens to worsen the global tuberculosis epidemic has caused great concern in recent years. To overcome the resistance, the development of new drugs with novel mechanisms of actions is of great importance. Imidazole-containing derivatives endow with various biological properties, and some of them demonstrated excellent anti-tubercular activity...
March 7, 2018: European Journal of Medicinal Chemistry
Urmi Bajpai, Abhishek Kumar Mehta, Kandasamy Eniyan, Avni Sinha, Ankita Ray, Simran Virdi, Shazeb Ahmad, Aridni Shah, Deepanksha Arora, Devyani Marwaha, Gunjan Chauhan, Prarthna Saraswat, Punita Bathla, Ruchi Singh
Bacteriophages are being considered as a promising natural resource for the development of alternative strategies against mycobacterial diseases, especially in the context of the wide spread occurrence of drug-resistance amongst the clinical isolates of M. tuberculosis. However, there isn't much information documented on mycobacteriophages from India. Here, we report the isolation of 17 mycobacteriophages using M. smegmatis as the bacterial host where 9 phages also lyse M. tuberculosis H37Rv. We present detailed analysis of one of these mycobacteriophage (PDRPv)...
March 15, 2018: Canadian Journal of Microbiology
Zengli Zhang, Huiqian Wang, Qifeng Ding, Yufei Xing, Zhonghua Xu, Chun Lu, Dongdong Luo, Longjiang Xu, Wei Xia, Caicun Zhou, Minhua Shi
The prognosis of advanced non-small cell lung cancer (NSCLC) patients is poor. One of the reasons for this hampered progress has been a lack of in vitro models that would faithfully recapitulate the heterogeneity of tumors and response to treatment. In this study, surgically resected tumors were obtained from patients with stage I/II NSCLC during curative-intent surgery. Using a 3D patient-derived tumor spheroids culture system, our results demonstrate successful long-term expansion of primary NSCLC cells in vitro (> 120 days)...
2018: PloS One
Daniela Munro-Rojas, Esdras Fernandez-Morales, José Zarrabal-Meza, Ma Teresa Martínez-Cazares, Aurora Parissi-Crivelli, Javier Fuentes-Domínguez, Marie Nancy Séraphin, Michael Lauzardo, Jorge Alberto González-Y-Merchand, Sandra Rivera-Gutierrez, Roberto Zenteno-Cuevas
BACKGROUND: Mexico is one of the most important contributors of drug and multidrug-resistant tuberculosis in Latin America; however, knowledge of the genetic diversity of drug-resistant tuberculosis isolates is limited. METHODS: In this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs. FINDINGS: The results show eight major lineages, the most of which was T1 (24%), followed by LAM (16%) and H (15%)...
2018: PloS One
Nan Shwe Nwe Htun, Peter Odermatt, Ivan Müller, Peiling Yap, Peter Steinmann, Christian Schindler, Markus Gerber, Rosa Du Randt, Cheryl Walter, Uwe Pühse, Jürg Utzinger, Nicole Probst-Hensch
BACKGROUND: Low- and middle-income countries are facing a dual disease burden with infectious diseases (e.g., gastrointestinal tract infections) and non-communicable diseases (e.g., diabetes) being common. For instance, chronic parasite infections lead to altered immune regulatory networks, anemia, malnutrition, and diarrhea with an associated shift in the gut microbiome. These can all be pathways of potential relevance for insulin resistance and diabetes. The aim of this study was to investigate the association between common gastrointestinal tract infections and glycemia in children from non-fee paying schools in South Africa...
March 15, 2018: PLoS Neglected Tropical Diseases
Muyang Yang, Lixia Yu, Ruiwei Guo, Anjie Dong, Cunguo Lin, Jianhua Zhang
Synergistic combination therapy by integrating chemotherapeutics and chemosensitizers into nanoparticles has demonstrated great potential to reduce side effects, overcome multidrug resistance (MDR), and thus improve therapeutic efficacy. However, with regard to the nanocarriers for multidrug codelivery, it remains a strong challenge to maintain design simplicity, while incorporating the desirable multifunctionalities, such as coloaded high payloads, targeted delivery, hemodynamic stability, and also to ensure low drug leakage before reaching the tumor site, but simultaneously the corelease of drugs in the same cancer cell...
March 15, 2018: Nanomaterials
Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley
A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance...
March 15, 2018: Cancers
Norelle Sherry, Benjamin Howden
Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the "re-discovery" of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas Covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam...
March 15, 2018: Expert Review of Anti-infective Therapy
Xuejiao Song, Tiantao Gao, Qian Lei, Lidan Zhang, Yuqin Yao, Jingyuan Xiong
Malignant melanoma is a devastating skin cancer due to its severe drug resistance and prompt metastasis. Piperlongumine is an anti-inflammation and tumor-suppressing natural product with defined structure. While numerous studies revealed exceptional inhibitory effects of piperlongumine on several carcinomas, few investigations were performed on melanoma. Therefore, the present study investigated the anti-tumor effects of piperlongumine on human melanoma cells in vitro, and explored the mechanisms of action...
March 15, 2018: Nutrition and Cancer
Bo Zhang, Shuyuan Wang, Jie Qian, Wenjia Yang, Fangfei Qian, Jun Lu, Yanwei Zhang, Rong Qiao, Baohui Han
BACKGROUND: Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown. METHODS: From January 2011 to January 2017, patients diagnosed with EGFR mutations were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed...
March 15, 2018: Cancer
Ahmed A Aljohaney
OBJECTIVES: To determine the mortality rates and predictors among patients hospitalized with active tuberculosis (TB) at King Abdulaziz University Hospital (KAUH) in Jeddah. METHODS: A retrospective study was performed on 291 active TB patients hospitalized in KAUH, Jeddah, Saudi Arabia from December 2011 to December 2016. Medical records were collected and evaluated using a dedicated data extraction sheet. The records included demographics, clinical, radiological, laboratory, and drug resistance data...
March 2018: Saudi Medical Journal
Jing Ruan, Ying Wang, Fang Li, Renbing Jia, Guangming Zhou, Chunlin Shao, Liqi Zhu, Malin Cui, Da-Peng Yang, Shengfang Ge
Combination of drug chemotherapy and ray radiation is the main solution for treating patients with advanced colorectal carcinoma, but the toxicity and adverse effects caused in the surrounding normal tissues and the radio resistance in tumor site will severely influence its therapeutic effect. Nano radiosensitizer is an ideal choice for improving the tumor radiotherapy effects thanks to its high degree of tumor tissue uptake and secondary electrons productivity. Graphene quantum dots (GQDs) have good oxidative stress response and significantly high phototoxicity, and are regarded as a potential nano radiosensitizer...
March 15, 2018: ACS Applied Materials & Interfaces
Liwen Feng, Don Antoine Lanfranchi, Leandro Cotos, Elena Cesar-Rodo, Katharina Ehrhardt, Alice-Anne Goetz, Herbert Zimmermann, François Fenaille, Stephanie A Blandin, Elisabeth Davioud-Charvet
Malaria is a tropical parasitic disease threatening populations in tropical and sub-tropical areas. Resistance to antimalarial drugs has spread all over the world in the past 50 years, thus new drugs are urgently needed. Plasmodione (benzylmenadione series) has been identified as a potent antimalarial early lead drug, acting through a redox bioactivation on asexual and young sexual blood stages. To investigate its metabolism, a series of plasmodione-based tools, including a fully13 C-labelled lead drug and putative metabolites, have been designed and synthesized for drug metabolism investigation...
March 15, 2018: Organic & Biomolecular Chemistry
Ling Gui Ning, En-Tang Kang, Yun Bing Wang, Xue Feng Hu, Li Qun Xu
Traditional use of antibiotics through injection or oral ingestion has many disadvantages, such as detrimental side effects in the host, less effectiveness, high and repeated doses, and development of drug resistance. For prevention and treatment of implant-associated infections, the continuous local delivery of antibiotics is required. Thus, there is a strong demand for the development of drug carrier systems to control the release of antibiotics in a moderate manner over an appropriate timescale. This review summarizes the carrier platforms used for the loading of antibiotics, and highlights their drug release behaviors as well as in vitro and in vivo antibacterial properties...
March 14, 2018: Current Pharmaceutical Design
Jian Yin, Xudong Deng, Jie Zhang, Jun Lin
Adenosine triphosphate-binding cassette (ABC) transporters-mediated multidrug resistance (MDR) remains as a obstacle for effective cancer therapy. Nanoparticles (NPs)-based delivery systems are promising to overcome MDR, but only a few of them have been accepted for clinical treatment, due to characteristics such as insufficient transportation and potential toxicity. In this respect, mounting attention has been attracted towards interactions between NPs and ABC transporters, which hold a key role in the treatment of multidrug-resistant cancer and NP toxicity...
March 14, 2018: Current Medicinal Chemistry
Verònica Gálvez, Adrienne Li, Christina Huggins, Paul Glue, Donel Martin, Andrew A Somogyi, Angelo Alonzo, Anthony Rodgers, Philip B Mitchell, Colleen K Loo
BACKGROUND: Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. METHODS: This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam...
March 1, 2018: Journal of Psychopharmacology
Alexander V Kulikov, Raul R Gainetdinov, Evgeni Ponimaskin, Allan V Kalueff, Vladimir S Naumenko, Nina K Popova
Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3-4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs. Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance...
March 15, 2018: Expert Opinion on Therapeutic Targets
Pamela Orjuela-Sanchez, Zaira Hellen Villa, Marta Moreno, Carlos Tong-Rios, Stephan Meister, Gregory M LaMonte, Brice Campo, Joseph M Vinetz, Elizabeth A Winzeler
To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against Plasmodium vivax exoerythrocytic forms. However, a robust in vitro culture system for P. vivax is still lacking. Thus, to study exoerythrocytic forms, researchers must have simultaneous access to fresh, temperature-controlled patient blood samples, as well as an anopheline mosquito colony. In addition, researchers must rely on native mosquito species to avoid introducing a potentially dangerous invasive species into a malaria-endemic region...
March 15, 2018: ACS Infectious Diseases
Lin Cao, Jizheng Chen, Yaxin Wang, Yuting Yang, Jie Qing, Zihe Rao, Xinwen Chen, Zhiyong Lou
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry is an essential target step for antiviral development, but FDA-approved HCV entry inhibitor remains exclusive. Here we identify serotonin 2A receptor (5-HT2A R) is a HCV entry factor amendable to therapeutic intervention by a chemical biology strategy...
March 14, 2018: Protein & Cell
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