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Cancer Communications (London, England) Feb 2024Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few... (Review)
Review
Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.
Topics: Humans; Neoplasms; Extracellular Vesicles; Antineoplastic Agents; Drug Resistance
PubMed: 38155418
DOI: 10.1002/cac2.12518 -
International Journal of Molecular... Nov 2023The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR)... (Review)
Review
The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.
Topics: Humans; Anti-Bacterial Agents; Liposomes; Phospholipids; Virosomes; Drug Resistance, Bacterial; Bacteria
PubMed: 37958915
DOI: 10.3390/ijms242115934 -
MBio Oct 2023Malaria is a devastating disease caused by parasites. The evolution of parasite drug resistance continues to hamper progress toward malaria elimination, and despite...
Malaria is a devastating disease caused by parasites. The evolution of parasite drug resistance continues to hamper progress toward malaria elimination, and despite extensive efforts to control malaria, it remains a leading cause of death in Mozambique and other countries in the region. The development of successful vaccines and identification of molecular markers to track drug efficacy are essential for managing the disease burden. We present an analysis of the parasite genome in Mozambique, a country with one of the highest malaria burdens globally and limited available genomic data, revealing current selection pressure. We contribute additional evidence to limited prior studies supporting the effectiveness of SWGA in producing reliable genomic data from complex clinical samples. Our results provide the identity of genomic loci that may be associated with current antimalarial drug use, including artemisinin and lumefantrine, and reveal selection pressure predicted to compromise the efficacy of current vaccine candidates.
Topics: Animals; Humans; Plasmodium falciparum; Mozambique; Antimalarials; Malaria; Parasites; Genomics; Drug Resistance; Malaria, Falciparum
PubMed: 37750720
DOI: 10.1128/mbio.01768-23 -
Journal of Controlled Release :... Nov 2023There is increasing evidence that malignant tumors are initiated and maintained by a sub-population of tumor cells that have similar biological properties to normal... (Review)
Review
There is increasing evidence that malignant tumors are initiated and maintained by a sub-population of tumor cells that have similar biological properties to normal adult stem cells. This very small population of Cancer Stem Cells (CSC) comprises tumor initiating cells responsible for cancer recurrence, drug resistance and metastasis. Conventional treatments such as chemotherapy, radiotherapy and surgery, in addition to being potentially toxic and non-specific, may paradoxically increase the population, spread and survival of CSCs. Next-generation sequencing and omics technologies are increasing our understanding of the pathways and factors involved in the development of CSCs, and can help to discover new therapeutic targets against CSCs. In addition, recent advances in nanomedicine have provided hope for the development of optimal specific therapies to eradicate CSCs. Moreover, the use of artificial intelligence and nano-informatics can elucidate new drug targets, and help to design drugs and nanoparticles (NPs) to deal with CSCs. In this review, we first summarize the properties of CSCs and describe the signaling pathways and molecular characteristics responsible for the emergence and survival of CSCs. Also, the location of CSCs within the tumor and the effect of host factors on the creation and maintenance of CSCs are discussed. Newly discovered molecular targets involved in cancer stemness and some novel therapeutic compounds to combat CSCs are highlighted. The optimum properties of anti-CSC NPs, including blood circulation and stability, tumor accumulation and penetration, cellular internalization, drug release, endosomal escape, and aptamers designed for specific targeting of CSCs are covered. Finally, some recent smart NPs designed for therapeutic and theranostic purposes to overcome CSCs are discussed.
Topics: Humans; Antineoplastic Agents; Drug Resistance, Neoplasm; Artificial Intelligence; Neoplasms; Neoplastic Stem Cells; Nanoparticles
PubMed: 37739017
DOI: 10.1016/j.jconrel.2023.09.029 -
Emerging Infectious Diseases Oct 2023Slaughterhouses are hotspots for the transmission of antimicrobial-resistant pathogens. We conducted stakeholder discussions on antimicrobial-resistant pathogens within...
Slaughterhouses are hotspots for the transmission of antimicrobial-resistant pathogens. We conducted stakeholder discussions on antimicrobial-resistant pathogens within the slaughterhouse setting. Butchers were described as powerful stakeholders; challenges included limited funding and staff, inadequate infrastructure, and limited laboratory capacity. Slaughterhouse workers understood that their work increased their risk for exposure.
Topics: Humans; Kenya; Abattoirs; Anti-Bacterial Agents; Drug Resistance, Bacterial; Laboratories
PubMed: 37735786
DOI: 10.3201/eid2910.230017 -
Journal of Hazardous Materials Jun 2024Aquatic microplastics (MPs) act as reservoirs for microbial communities, fostering the formation of a mobile resistome encompassing diverse antibiotic (ARGs) and...
Aquatic microplastics (MPs) act as reservoirs for microbial communities, fostering the formation of a mobile resistome encompassing diverse antibiotic (ARGs) and biocide/metal resistance genes (BMRGs), and mobile genetic elements (MGEs). This collective genetic repertoire, referred to as the "plastiome," can potentially perpetuate environmental antimicrobial resistance (AMR). Our study examining two Japanese rivers near Tokyo revealed that waterborne MPs are primarily composed of polyethylene and polypropylene fibers and sheets of diverse origin. Clinically important genera like Exiguobacterium and Eubacterium were notably enriched on MPs. Metagenomic analysis uncovered a 3.46-fold higher enrichment of ARGs on MPs than those in water, with multidrug resistance genes (MDRGs) and BMRGs prevailing, particularly within MPs. Specific ARG and BMRG subtypes linked to resistance to vancomycin, beta-lactams, biocides, arsenic, and mercury showed selective enrichment on MPs. Network analysis revealed intense associations between host genera with ARGs, BMRGs, and MGEs on MPs, emphasizing their role in coselection. In contrast, river water exhibited weaker associations. This study underscores the complex interactions shaping the mobile plastiome in aquatic environments and emphasizes the global imperative for research to comprehend and effectively control AMR within the One Health framework.
Topics: Rivers; Microplastics; Anti-Bacterial Agents; Water Pollutants, Chemical; Bacteria; Water Microbiology; Interspersed Repetitive Sequences; Genes, Bacterial; Drug Resistance, Bacterial; Disinfectants; Microbiota; Drug Resistance, Microbial
PubMed: 38678707
DOI: 10.1016/j.jhazmat.2024.134353 -
MBio Oct 2023is an opportunistic fungal pathogen with increasing incidence in hospital settings worldwide; however, we lack a comprehensive understanding of the mechanisms promoting...
is an opportunistic fungal pathogen with increasing incidence in hospital settings worldwide; however, we lack a comprehensive understanding of the mechanisms promoting its virulence and drug resistance. Bergin et al. systematically quantify the frequency and effect of copy number variation (CNV) across 170 diverse clinical and environmental isolates of (Bergin SA, Zhao F, Ryan AP, Müller CA, Nieduszynski CA, Zhai B, Rolling T, Hohl TM, Morio F, Scully J, Wolfe KH, Butler G, 2022, mBio, https://doi.org/10.1128/mbio.01777-22). Using a combination of both short- and long-read whole genome sequencing techniques, they determine the structure and copy number of two CNVs that arose recurrently throughout the evolution of these isolates. Each CNV predominantly amplifies one coding sequence ( or ); however, the amplitude and recombination breakpoints are variable across the isolates. Amplification of correlates with drug resistance and deletion causes drug susceptibility. This study highlights the need for further research into the mechanisms and dynamics of CNV formation and the impact of these CNVs on virulence and drug resistance across diverse fungal pathogens.
Topics: Humans; Candida parapsilosis; Antifungal Agents; DNA Copy Number Variations; Saccharomyces cerevisiae; Gene Amplification; Drug Resistance
PubMed: 37787545
DOI: 10.1128/mbio.00713-23 -
Biomedicine & Pharmacotherapy =... Jan 2024The resistance of cancer cells to chemotherapy, also known as chemo-resistance, poses a significant obstacle to cancer treatment and can ultimately result in patient... (Review)
Review
The resistance of cancer cells to chemotherapy, also known as chemo-resistance, poses a significant obstacle to cancer treatment and can ultimately result in patient mortality. Epithelial-mesenchymal transition (EMT) is one of the many factors and processes responsible for chemo-resistance. Studies have shown that targeting EMT can help overcome chemo-resistance, and nanotechnology and nanomedicine have emerged as promising approaches to achieve this goal. This article discusses the potential of nanotechnology in inhibiting EMT and proposes a viable strategy to combat chemo-resistance in various solid tumors, including breast cancer, lung cancer, pancreatic cancer, glioblastoma, ovarian cancer, gastric cancer, and hepatocellular carcinoma. While nanotechnology has shown promising results in targeting EMT, further research is necessary to explore its full potential in overcoming chemo-resistance and discovering more effective methods in the future.
Topics: Humans; Female; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Breast Neoplasms; Liver Neoplasms; Nanotechnology; Cell Line, Tumor
PubMed: 38064969
DOI: 10.1016/j.biopha.2023.115973 -
The Lancet. Microbe May 2024Antimicrobial resistance (AMR) threatens human, animal, and environmental health. Acknowledging the urgency of addressing AMR, an opportunity exists to extend AMR... (Review)
Review
Antimicrobial resistance (AMR) threatens human, animal, and environmental health. Acknowledging the urgency of addressing AMR, an opportunity exists to extend AMR action-focused research beyond the confines of an isolated biomedical paradigm. An AMR learning system, AMR-X, envisions a national network of health systems creating and applying optimal use of antimicrobials on the basis of their data collected from the delivery of routine clinical care. AMR-X integrates traditional AMR discovery, experimental research, and applied research with continuous analysis of pathogens, antimicrobial uses, and clinical outcomes that are routinely disseminated to practitioners, policy makers, patients, and the public to drive changes in practice and outcomes. AMR-X uses connected data-to-action systems to underpin an evaluation framework embedded in routine care, continuously driving implementation of improvements in patient and population health, targeting investment, and incentivising innovation. All stakeholders co-create AMR-X, protecting the public from AMR by adapting to continuously evolving AMR threats and generating the information needed for precision patient and population care.
Topics: Humans; United Kingdom; Anti-Bacterial Agents; Drug Resistance, Bacterial; Antimicrobial Stewardship; Anti-Infective Agents; Drug Resistance, Microbial; Animals
PubMed: 38461831
DOI: 10.1016/S2666-5247(24)00003-X -
Computers in Biology and Medicine Nov 2023The progressive emergence of antimicrobial resistance has become a global health problem in need of rapid solution. Research into new antimicrobial drugs is imperative....
The progressive emergence of antimicrobial resistance has become a global health problem in need of rapid solution. Research into new antimicrobial drugs is imperative. Drug repositioning, together with computational mathematical prediction models, could be a fast and efficient method of searching for new antibiotics. The aim of this study was to identify compounds with potential antimicrobial capacity against Escherichia coli from US Food and Drug Administration-approved drugs, and the similarity between known drug targets and E. coli proteins using a topological structure-activity data analysis model. This model has been shown to identify molecules with known antibiotic capacity, such as carbapenems and cephalosporins, as well as new molecules that could act as antimicrobials. Topological similarities were also found between E. coli proteins and proteins from different bacterial species such as Mycobacterium tuberculosis, Pseudomonas aeruginosa and Salmonella Typhimurium, which could imply that the selected molecules have a broader spectrum than expected. These molecules include antitumor drugs, antihistamines, lipid-lowering agents, hypoglycemic agents, antidepressants, nucleotides, and nucleosides, among others. The results presented in this study prove the ability of computational mathematical prediction models to predict molecules with potential antimicrobial capacity and/or possible new pharmacological targets of interest in the design of new antibiotics and in the better understanding of antimicrobial resistance.
Topics: Drug Repositioning; Anti-Bacterial Agents; Escherichia coli; Drug Resistance, Bacterial; Humans
PubMed: 37793206
DOI: 10.1016/j.compbiomed.2023.107496