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Frontiers in Pharmacology 2023Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Platinum-based chemotherapy is standard-of-care but has limitations including...
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Platinum-based chemotherapy is standard-of-care but has limitations including toxicity and resistance. Metal complexes of gold, ruthenium, and other metals have emerged as promising alternatives. This review provides a comprehensive analysis of metallodrugs for NSCLC. Bibliometric analysis reveals growing interest in elucidating mechanisms, developing targeted therapies, and synergistic combinations. Classification of metallodrugs highlights platinum, gold, and ruthenium compounds, as well as emerging metals. Diverse mechanisms include DNA damage, redox modulation, and immunomodulation. Preclinical studies demonstrate cytotoxicity and antitumor effects and , providing proof-of-concept. Clinical trials indicate platinums have utility but resistance remains problematic. Non-platinum metallodrugs exhibit favorable safety but modest single agent efficacy to date. Drug delivery approaches like nanoparticles show potential to enhance therapeutic index. Future directions include optimization of metal-based complexes, elucidation of resistance mechanisms, biomarker development, and combination therapies to fully realize the promise of metallodrugs for NSCLC.
PubMed: 37727388
DOI: 10.3389/fphar.2023.1242488 -
PloS One 2023The microfluidic sperm selection (MFSS) device has emerged as a promising adjunct in assisted reproduction treatments (ART). It employs mechanisms of biomimicry based on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The microfluidic sperm selection (MFSS) device has emerged as a promising adjunct in assisted reproduction treatments (ART). It employs mechanisms of biomimicry based on the microanatomy of the female reproductive tract through strategies like chemotaxis and rheotaxis. Numerous studies assert improvements in ART outcomes with the use of MFSS, often attributed to the theoretical reduction in sperm DNA damage compared to other techniques. However, these attributed benefits lack validation through large-scale clinical trials, and there is no significant evidence of enhanced assisted reproductive treatments (ART) outcomes.
OBJECTIVE
To evaluate whether the utilization of MFSS enhances clinical pregnancy results and abortion outcomes in couples undergoing ART compared to standard sperm selection techniques for Intracytoplasmic Sperm Injection (ICSI). We also assessed laboratory outcomes as a supplementary analysis.
SEARCH METHODS
We conducted searches across databases including PubMed, NIH, LILACS, CENTRAL, Crossref, Scopus, and OpenAlex. A total of 1,255 records were identified. From these, 284 duplicate records were eliminated, and an additional 895 records were excluded due to their association with patent applications, diagnostic tests, forensic analyses, or irrelevance to the research focus. Among the initially eligible 76 studies, 63 were excluded, encompassing abstracts, studies lacking adequate control groups, and ongoing clinical trials. Ultimately, 13 studies were selected for inclusion in the ensuing meta-analysis.
RESULTS
Regarding clinical pregnancy, we assessed a total of 868 instances of clinical pregnancies out of 1,646 embryo transfers. Regarding miscarriage, we examined 95 cases of pregnancy loss among the 598 confirmed clinical pregnancies in these studies.
CONCLUSION
The utilization of MFSS demonstrates marginal positive outcomes compared to standard sperm selection techniques, without statistical significance in any of the analyses.
BROADER IMPLICATIONS
This study conducted the first meta-analysis to evaluate clinical pregnancy rates, miscarriage rates, and laboratory results associated with the use of MFSS compared to standard sperm selection techniques. We have also listed potentially eligible studies for future inclusion. It's important to emphasize the need for multicenter studies with standardized parameters to attain a more robust clarification of this issue.
Topics: Pregnancy; Male; Female; Humans; Abortion, Spontaneous; Microfluidics; Semen; Sperm Injections, Intracytoplasmic; Pregnancy Rate; Spermatozoa; Live Birth
PubMed: 37983267
DOI: 10.1371/journal.pone.0292891 -
Head & Neck Feb 2024The involvement of the KMT2 methyltransferase family in the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains elusive. (Review)
Review
BACKGROUND
The involvement of the KMT2 methyltransferase family in the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains elusive.
METHOD
This study adhered to the PRISMA guidelines, employing a search strategy in the LIVIVO, PubMed, Scopus, Embase, Web of Science, and Google Scholar databases. The methodological quality of the studies was assessed by the Joanna Briggs Institute.
RESULTS
A total of 33 studies involving 4294 individuals with HNSCC were included in this review. The most important alteration was the high mutational frequency in the KMT2C and KMT2D genes, with reported co-occurrence. The expression of the KMT2D gene exhibited considerable heterogeneity across the studies, while limited data was available for the remaining genes.
CONCLUSIONS
KMT2C and KMT2D genes seem to have tumor suppressor activities, with involvement of cell cycle inhibitors, regulating different pathways that can lead to tumor progression, disease aggressiveness, and DNA damage accumulation.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Methyltransferases; Head and Neck Neoplasms; Genes, Tumor Suppressor
PubMed: 38102754
DOI: 10.1002/hed.27597 -
IET Nanobiotechnology 2024Foodborne disease outbreaks due to bacterial pathogens and their toxins have become a serious concern for global public health and security. Finding novel antibacterial... (Review)
Review
Foodborne disease outbreaks due to bacterial pathogens and their toxins have become a serious concern for global public health and security. Finding novel antibacterial agents with unique mechanisms of action against the current spoilage and foodborne bacterial pathogens is a central strategy to overcome antibiotic resistance. This study examined the antibacterial activities and mechanisms of action of inorganic nanoparticles (NPs) against foodborne bacterial pathogens. The articles written in English were recovered from registers and databases (PubMed, ScienceDirect, Web of Science, Google Scholar, and Directory of Open Access Journals) and other sources (websites, organizations, and citation searching). "Nanoparticles," "Inorganic Nanoparticles," "Metal Nanoparticles," "Metal-Oxide Nanoparticles," "Antimicrobial Activity," "Antibacterial Activity," "Foodborne Bacterial Pathogens," "Mechanisms of Action," and "Foodborne Diseases" were the search terms used to retrieve the articles. The PRISMA-2020 checklist was applied for the article search strategy, article selection, data extraction, and result reporting for the review process. A total of 27 original research articles were included from a total of 3,575 articles obtained from the different search strategies. All studies demonstrated the antibacterial effectiveness of inorganic NPs and highlighted their different mechanisms of action against foodborne bacterial pathogens. In the present study, small-sized, spherical-shaped, engineered, capped, low-dissolution with water, high-concentration NPs, and in Gram-negative bacterial types had high antibacterial activity as compared to their counterparts. Cell wall interaction and membrane penetration, reactive oxygen species production, DNA damage, and protein synthesis inhibition were some of the generalized mechanisms recognized in the current study. Therefore, this study recommends the proper use of nontoxic inorganic nanoparticle products for food processing industries to ensure the quality and safety of food while minimizing antibiotic resistance among foodborne bacterial pathogens.
Topics: Anti-Bacterial Agents; Foodborne Diseases; Nanoparticles; Food Microbiology; Microbial Sensitivity Tests; Metal Nanoparticles; Bacteria; Humans
PubMed: 38863967
DOI: 10.1049/2024/5417924 -
Radiation Research Jun 2024This study offers a review of published data on DNA double strand break (DSB) repair kinetics after exposure to ionizing radiation. By compiling a database, which...
This study offers a review of published data on DNA double strand break (DSB) repair kinetics after exposure to ionizing radiation. By compiling a database, which currently includes 285 DNA DSB repair experiments utilizing both photons and ions, we investigate the impact of distinct experimental parameters on the kinetics of DNA DSB repair. Methodological differences and inconsistencies in reporting make the comparison of data generated by different research groups challenging. Nevertheless, by implementing filtering criteria, we can compare repair kinetics obtained with normal and tumor cells derived from human or animal tissues, as well as cells exposed to photons or ions ranging from hydrogen to iron ions. In addition, several repair curves of repair deficient cell lines were included. The study aims to provide researchers with a comprehensive overview of experimental factors that may confound results and emphasize the importance of precise reporting of experimental parameters. Moreover, we identify gaps in the literature that require attention in future studies, aiming to address clinically relevant questions related to radiotherapy. The database can be freely accessed at: https://github.com/weradstake/DRDNA.
Topics: DNA Breaks, Double-Stranded; Humans; Photons; DNA Repair; Kinetics; Animals; Ions
PubMed: 38376467
DOI: 10.1667/RADE-23-00190.1 -
Journal of Neurochemistry Jun 2024Alzheimer's disease (AD) is the most common type and accounts for 60%-70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non-coding RNAs that play a...
Alzheimer's disease (AD) is the most common type and accounts for 60%-70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in gene expression regulation. Although the diagnosis of AD is primarily clinical, several miRNAs have been associated with AD and considered as potential markers for diagnosis and progression of AD. We sought to match AD-related miRNAs in cerebrospinal fluid (CSF) found in the GeoDataSets, evaluated by machine learning, with miRNAs listed in a systematic review, and a pathway analysis. Using machine learning approaches, we identified most differentially expressed miRNAs in Gene Expression Omnibus (GEO), which were validated by the systematic review, using the acronym PECO-Population (P): Patients with AD, Exposure (E): expression of miRNAs, Comparison (C): Healthy individuals, and Objective (O): miRNAs differentially expressed in CSF. Additionally, pathway enrichment analysis was performed to identify the main pathways involving at least four miRNAs selected. Four miRNAs were identified for differentiating between patients with and without AD in machine learning combined to systematic review, and followed the pathways analysis: miRNA-30a-3p, miRNA-193a-5p, miRNA-143-3p, miRNA-145-5p. The pathways epidermal growth factor, MAPK, TGF-beta and ATM-dependent DNA damage response, were regulated by these miRNAs, but only the MAPK pathway presented higher relevance after a randomic pathway analysis. These findings have the potential to assist in the development of diagnostic tests for AD using miRNAs as biomarkers, as well as provide understanding of the relationship between different pathophysiological mechanisms of AD.
Topics: Alzheimer Disease; Humans; Machine Learning; MicroRNAs; Data Mining; Biomarkers
PubMed: 38390627
DOI: 10.1111/jnc.16060 -
Medical Oncology (Northwood, London,... Apr 2024Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell... (Review)
Review
Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell (HSC) self-renewal and the generation of specialized cells. Cytokines and chemokines, two important components of the inflammatory process, also influence hematological differentiation. In this scenario, immunological dysregulation plays a pivotal role in the pathogenesis of bone marrow neoplasms. The STING pathway recognizes DNA fragments in the cell cytoplasm and triggers an immune response by type I interferons. The role of STING in cancer has not yet been established; however, both actions, as an oncogene or tumor suppressor, have been documented in other types of cancer. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42023407512) to discuss the role of STING pathway in the advancement of pathogenesis and/or prognosis for different myeloid neoplasms. In brief, scientific evidence supports investigations that primarily use cell lines from myeloid neoplasms, such as leukemia. More high-quality research and clinical trials are needed to understand the role of the STING pathway in the pathology of hematological malignancies. Finally, the STING pathway suggests being a promising therapeutic molecular target, particularly when combined with current drug therapies.
Topics: Humans; Hematologic Neoplasms; Membrane Proteins; Myeloproliferative Disorders; Signal Transduction
PubMed: 38656461
DOI: 10.1007/s12032-024-02376-8 -
Journal of Applied Toxicology : JAT Jan 2024The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A... (Review)
Review
The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA-directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA-induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA-directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.
PubMed: 38212177
DOI: 10.1002/jat.4574 -
Nutrients Jan 2024The PHYTOME study investigated the effect of consuming processed meat products on outcomes related to colorectal cancer risk without testing the impact of genetic...
Genetic Variability Impacts Genotoxic and Transcriptome Responses in the Human Colon after the Consumption of Processed Red Meat Products and Those with Added Phytochemical Extracts.
The PHYTOME study investigated the effect of consuming processed meat products on outcomes related to colorectal cancer risk without testing the impact of genetic variability on these responses. This research aims to elucidate the genetic impact on apparent total N-nitroso compound (ATNC) excretion, colonic DNA adduct formation, ex vivo-induced DNA damage, and gene expression changes in colon biopsies of healthy participants. Through a systematic literature review, candidate polymorphisms were selected and then detected using TaqMan and PCR analysis. The effect of genotype on study outcomes was determined via a linear mixed model and analysis of variance. Machine learning was used to evaluate relative allele importance concerning genotoxic responses, which established a ranking of the most protective alleles and a combination of genotypes (gene scores). Participants were grouped by GSTM1 genotype and differentially expressed genes (DEGs), and overrepresented biological pathways were compared between groups. Stratifying participants by ten relevant genes revealed significant variations in outcome responses. After consumption of processed red meat, variations in NQO1 and COMT impacted responses in ATNC levels (µmol/L) (+9.56 for wildtype vs. heterozygous) and DNA adduct levels (pg/µg DNA) (+1.26 for variant vs. wildtype and +0.43 for variant vs. heterozygous), respectively. After phytochemicals were added to the meat, GSTM1 variation impacted changes in DNA adduct levels (-6.12 for deletion vs. wildtype). The gene scores correlated with these responses and DEGs were identified by GSTM1 genotype. The altered pathways specific to the GSTM1 wildtype group included 'metabolism', 'cell cycle', 'vitamin D receptor', and 'metabolism of water-soluble vitamins and co-factors'. Genotype impacted both the potential genotoxicity of processed red meat and the efficacy of protective phytochemical extracts.
Topics: Humans; Meat Products; DNA Adducts; Transcriptome; DNA Damage; Meat; Red Meat; Nitroso Compounds; Colon
PubMed: 38337709
DOI: 10.3390/nu16030425 -
International Journal of Environmental... Mar 2024This study aimed to evaluate the scientific literature on the micronucleus assay in nasal mucosa as an appropriate method for evaluating genotoxicity caused by chemical... (Review)
Review
This study aimed to evaluate the scientific literature on the micronucleus assay in nasal mucosa as an appropriate method for evaluating genotoxicity caused by chemical agents. According to the PRISMA guidelines, only in vivo human studies with micronucleus assays using nasal cells were considered. Reviews, case reports, editorials, letters to the editor, and articles not written in English were excluded. The following scientific databases/search engines were used: PubMed/MEDLINE, Scopus, and Web of Science. Results: This review included 13 studies. Four articles detected no statistical significance regarding the frequency of micronuclei while nine articles showed an increase in micronuclei in nasal cells. In the qualitative analysis, two articles were considered strong, eight were moderate and three were weak. The micronucleus assay using nasal mucosa cells is a sensitive and effective technique for assessing DNA damage and an appropriate method for monitoring humans continuously exposed to chemicals.
Topics: Humans; Micronucleus Tests; Mutagens; Nasal Mucosa; DNA Damage
PubMed: 37442547
DOI: 10.1080/09603123.2023.2234300