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Sheng Wu Gong Cheng Xue Bao = Chinese... Dec 2020The discovery of antibiotics is a big revolution in human history, and its clinical application has saved countless lives. However, with the widespread and abuse of... (Review)
Review
The discovery of antibiotics is a big revolution in human history, and its clinical application has saved countless lives. However, with the widespread and abuse of antibiotics, many pathogens have developed resistance, and even "Super Bacteria" resistance to multiple drugs have evolved. In the arms race between humans and pathogens, humans are about to face a situation where no medicine is available. Research on microbial antibiotic resistance genes, resistance mechanisms, and the spread of resistance has attracted the attention of many scientific researchers, and various antibiotic resistance gene databases and analysis tools have emerged. In this review, we collect the current databases that focus on antibiotics resistance genes, and discuss these databases in terms of database types, data characteristics, antibiotics resistance gene prediction models and the types of analyzable sequences. In addition, a few gene databases of anti-metal ions and anti-biocides are also involved. It is believed that this summary will provide a reference for how to select and use antibiotic resistance gene databases.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Drug Resistance, Microbial; Humans; Metals
PubMed: 33398956
DOI: 10.13345/j.cjb.200375 -
Science Signaling Oct 2018This Editorial discusses the state of research on drug resistance in the fields of cancer, infectious disease, and agriculture. Reaching across the aisle for a more...
This Editorial discusses the state of research on drug resistance in the fields of cancer, infectious disease, and agriculture. Reaching across the aisle for a more cross-collaborative approach may lead to exciting breakthroughs toward tackling the challenges of drug resistance in each field.
Topics: Agriculture; Communicable Diseases; Drug Resistance, Microbial; Drug Resistance, Neoplasm; Humans; Interdisciplinary Communication; Mutation; Neoplasms; Stochastic Processes
PubMed: 30352947
DOI: 10.1126/scisignal.aav0442 -
Drug Design, Development and Therapy 2017Leukemia is a clonal malignant hematopoietic stem cell disease. It is the sixth most lethal cancer and accounts for 4% of all cancers. The main form of treatment for... (Review)
Review
Leukemia is a clonal malignant hematopoietic stem cell disease. It is the sixth most lethal cancer and accounts for 4% of all cancers. The main form of treatment for leukemia is chemotherapy. While some cancer types with a higher incidence than leukemia, such as lung and gastric cancer, have shown a sharp decline in mortality rates in recent years, leukemia has not followed this trend. Drug resistance is often regarded as the main clinical obstacle to effective chemotherapy in patients diagnosed with leukemia. Many resistance mechanisms have now been identified, and multidrug resistance (MDR) is considered the most important and prevalent mechanism involved in the failure of chemotherapy in leukemia. In order to reverse MDR and improve leukemia prognosis, effective detection methods are needed to identify drug resistance genes at initial diagnosis. This article provides a comprehensive overview of published approaches for the detection of MDR in leukemia. Identification of relevant MDR genes and methods for early detection of these genes will be needed in order to treat leukemia more effectively.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Leukemia
PubMed: 28458519
DOI: 10.2147/DDDT.S134529 -
Journal of Exposure Science &... Jan 2020The indoor environment is an important source of microbial exposures for its human occupants. While we naturally want to favor positive health outcomes, built... (Review)
Review
The indoor environment is an important source of microbial exposures for its human occupants. While we naturally want to favor positive health outcomes, built environment design and operation may counter-intuitively favor negative health outcomes, particularly with regard to antibiotic resistance. Indoor environments contain microbes from both human and non-human origins, providing a unique venue for microbial interactions, including horizontal gene transfer. Furthermore, stressors present in the built environment could favor the exchange of genetic material in general and the retention of antibiotic resistance genes in particular. Intrinsic and acquired antibiotic resistance both pose a potential threat to human health; these phenomena need to be considered and controlled separately. The presence of both environmental and human-associated microbes, along with their associated antibiotic resistance genes, in the face of stressors, including antimicrobial chemicals, creates a unique opportunity for the undesirable spread of antibiotic resistance. In this review, we summarize studies and findings related to various interactions between human-associated bacteria, environmental bacteria, and built environment conditions, and particularly their relation to antibiotic resistance, aiming to guide "healthy" building design.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Ecology; Gene Transfer, Horizontal; Humans
PubMed: 31591493
DOI: 10.1038/s41370-019-0171-0 -
Pharmacological Research Apr 2024Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the... (Review)
Review
Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.
Topics: Humans; Antineoplastic Agents; Biological Products; Neoplasms; Drug Resistance, Multiple; Drug Resistance, Neoplasm
PubMed: 38342327
DOI: 10.1016/j.phrs.2024.107099 -
Malaria Journal Mar 2016Plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is... (Review)
Review
Plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is due to mutation of the PfK13 propeller domain and involves an unconventional mechanism based on a quiescence state leading to parasite recrudescence as soon as drug pressure is removed. The enhanced P. falciparum quiescence capacity of artemisinin-resistant parasites results from an increased ability to manage oxidative damage and an altered cell cycle gene regulation within a complex network involving the unfolded protein response, the PI3K/PI3P/AKT pathway, the PfPK4/eIF2α cascade and yet unidentified transcription factor(s), with minimal energetic requirements and fatty acid metabolism maintained in the mitochondrion and apicoplast. The detailed study of these mechanisms offers a way forward for identifying future intervention targets to fend off established artemisinin resistance.
Topics: Antimalarials; Artemisinins; Drug Resistance; Humans; Malaria, Falciparum; Models, Biological; Plasmodium falciparum
PubMed: 26955948
DOI: 10.1186/s12936-016-1206-9 -
PLoS Medicine Nov 2017Resistance to first-line treatments for Plasmodium falciparum malaria and the insecticides used for Anopheles vector control are threatening malaria elimination efforts.... (Review)
Review
Resistance to first-line treatments for Plasmodium falciparum malaria and the insecticides used for Anopheles vector control are threatening malaria elimination efforts. Suboptimal responses to drugs and insecticides are both spreading geographically and emerging independently and are being seen at increasing intensities. Whilst resistance is unavoidable, its effects can be mitigated through resistance management practices, such as exposing the parasite or vector to more than one selective agent. Resistance contributed to the failure of the 20th century Global Malaria Eradication Programme, and yet the global response to this issue continues to be slow and poorly coordinated-too often, too little, too late. The Malaria Eradication Research Agenda (malERA) Refresh process convened a panel on resistance of both insecticides and antimalarial drugs. This paper outlines developments in the field over the past 5 years, highlights gaps in knowledge, and proposes a research agenda focused on managing resistance. A deeper understanding of the complex biological processes involved and how resistance is selected is needed, together with evidence of its public health impact. Resistance management will require improved use of entomological and parasitological data in decision making, and optimisation of the useful life of new and existing products through careful implementation, combination, and evaluation. A proactive, collaborative approach is needed from basic science and the development of new tools to programme and policy interventions that will ensure that the armamentarium of drugs and insecticides is sufficient to deal with the challenges of malaria control and its elimination.
Topics: Animals; Antimalarials; Disease Eradication; Drug Resistance; Humans; Insecticide Resistance; Insecticides; Malaria; Mosquito Control
PubMed: 29190671
DOI: 10.1371/journal.pmed.1002450 -
Journal of Experimental & Clinical... Jul 2019Drug resistance represents the major reason of pharmacological treatment failure. It is supported by a broad spectrum of mechanisms, whose molecular bases have been... (Review)
Review
Drug resistance represents the major reason of pharmacological treatment failure. It is supported by a broad spectrum of mechanisms, whose molecular bases have been frequently correlated to aberrant protein phosphorylation. CK2 is a constitutively active protein kinase which phosphorylates hundreds of substrates; it is expressed in all cells, but its level is commonly found higher in cancer cells, where it plays anti-apoptotic, pro-migration and pro-proliferation functions. Several evidences support a role for CK2 in processes directly responsible of drug resistance, such as drug efflux and DNA repair; moreover, CK2 intervenes in signaling pathways which are crucial to evade drug response (as PI3K/AKT/PTEN, NF-κB, β-catenin, hedgehog signaling, p53), and controls the activity of chaperone machineries fundamental in resistant cells. Interestingly, a panel of specific and effective inhibitors of CK2 is available, and several examples are known of their efficacy in resistant cells, with synergistic effect when used in combination with conventional drugs, also in vivo. Here we analyze and discuss evidences supporting the hypothesis that CK2 targeting represents a valuable strategy to overcome drug resistance.
Topics: Casein Kinase II; Drug Resistance; Humans; Protein Isoforms
PubMed: 31277672
DOI: 10.1186/s13046-019-1292-y -
Journal of Theoretical Biology Jan 2021Combination therapies have shown remarkable success in preventing the evolution of resistance to multiple drugs, including HIV, tuberculosis, and cancer. Nevertheless,...
Combination therapies have shown remarkable success in preventing the evolution of resistance to multiple drugs, including HIV, tuberculosis, and cancer. Nevertheless, the rise in drug resistance still remains an important challenge. The capability to accurately predict the emergence of resistance, either to one or multiple drugs, may help to improve treatment options. Existing theoretical approaches often focus on exponential growth laws, which may not be realistic when scarce resources and competition limit growth. In this work, we study the emergence of single and double drug resistance in a model of combination therapy of two drugs. The model describes a sensitive strain, two types of single-resistant strains, and a double-resistant strain. We compare the probability that resistance emerges for three growth laws: exponential growth, logistic growth without competition between strains, and logistic growth with competition between strains. Using mathematical estimates and numerical simulations, we show that between-strain competition only affects the emergence of single resistance when resources are scarce. In contrast, the probability of double resistance is affected by between-strain competition over a wider space of resource availability. This indicates that competition between different resistant strains may be pertinent to identifying strategies for suppressing drug resistance, and that exponential models may overestimate the emergence of resistance to multiple drugs. A by-product of our work is an efficient strategy to evaluate probabilities of single and double resistance in models with multiple sequential mutations. This may be useful for a range of other problems in which the probability of resistance is of interest.
Topics: Combined Modality Therapy; Drug Resistance; Drug Resistance, Multiple; Humans; Probability; Tuberculosis
PubMed: 33049229
DOI: 10.1016/j.jtbi.2020.110524 -
Progress in Biophysics and Molecular... Jan 2019Efflux pumps play a major role in the increasing antimicrobial resistance rendering a large number of drugs of no use. Large numbers of pathogens are becoming multidrug... (Review)
Review
Efflux pumps play a major role in the increasing antimicrobial resistance rendering a large number of drugs of no use. Large numbers of pathogens are becoming multidrug resistant due to inadequate dosage and use of the existing antimicrobials. This leads to the need for identifying new efflux pump inhibitors. Design of novel targeted therapies using inherent complexity involved in the biological network modeling has gained increasing importance in recent times. The predictive approaches should be used to determine antimicrobial activities with high pathogen specificity and microbicidal potency. Antimicrobial peptides, which are part of our innate immune system, have the ability to respond to infections and have gained much attention in making resistant strain sensitive to existing drugs. In this review paper, we outline evidences linking host-directed therapy with the efflux pump activity to infectious disease.
Topics: Anti-Infective Agents; Drug Resistance; Genomics
PubMed: 30031023
DOI: 10.1016/j.pbiomolbio.2018.07.008