keyword
https://read.qxmd.com/read/38533178/genotoxicity-and-cytotoxicity-of-antineoplastic-drugs-at-environmentally-relevant-concentrations-after-long-term-exposure
#21
JOURNAL ARTICLE
P da Cunha de Medeiros, E A Nunes, G R M Barcelos, J E Perobelli
INTRODUCTION: 5-fluorouracil (5-FU) and methotrexate (MTX) are the antineoplastic drugs most commonly used worldwide. Considered cytotoxic, these pharmaceuticals exhibit low specificity, causing damage not only to cancer cells but also to healthy cells in organisms. After being consumed and metabolized, these drugs are excreted through urine and feces, followed by wastewater treatment. However, conventional treatments do not have the capacity to completely remove these substances, risking their introduction into freshwater systems...
April 2024: Toxicology Research
https://read.qxmd.com/read/38532930/targeting-of-lysosomal-bound-protein-meak-7-for-cancer-therapy
#22
REVIEW
Insoon Chang, Yi-Ling Loo, Jay Patel, Joe Truong Nguyen, Jin Koo Kim, Paul H Krebsbach
mEAK-7 (mammalian EAK-7 or MTOR-associated protein, eak-7 homolog), is an evolutionarily conserved lysosomal membrane protein that is highly expressed in several cancer cells. Multiple recent studies have identified mEAK-7 as a positive activator of mTOR (mammalian/mechanistic target of rapamycin) signaling via an alternative mTOR complex, implying that mEAK-7 plays an important role in the promotion of cancer proliferation and migration. In addition, structural analyses investigating interactions between mEAK-7 and V-ATPase, a protein complex responsible for regulating pH homeostasis in cellular compartments, have suggested that mEAK-7 may contribute to V-ATPase-mediated mTORC1 activation...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38532652/recent-progress-of-atmospheric-and-room-temperature-plasma-as-a-new-and-promising-mutagenesis-technology
#23
REVIEW
Dongao Li, Jie Shen, Qiang Ding, Jinyong Wu, Xiangsong Chen
At present, atmospheric and room-temperature plasma (ARTP) is regarded as a new and powerful mutagenesis technology with the advantages of environment-friendliness, operation under mild conditions, and fast mutagenesis speed. Compared with traditional mutagenesis strategies, ARTP is used mainly to change the structure of microbial DNA, enzymes, and proteins through a series of physical, chemical, and electromagnetic effects with the organisms, leading to nucleotide breakage, conversion or inversion, causing various DNA damages, so as to screen out the microbial mutants with better biological characteristics...
April 2024: Cell Biochemistry and Function
https://read.qxmd.com/read/38532477/gsdmd-induces-hepatocyte-pyroptosis-to-trigger-alcoholic-hepatitis-through-modulating-mitochondrial-dysfunction
#24
JOURNAL ARTICLE
Yandi Xie, Zilong Wang, Guangjun Song, Hui Ma, Bo Feng
BACKGROUND: Mechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces hepatocyte pyroptosis by regulating mitochondrial dysfunction in AH. RESULTS: Liver damage in AH mice was assessed by HE staining, serum levels of AST, ALT, TC, and TG. The levels of IL-1β, IL-18, LDH, inflammasome-associated proteins and hepatocyte death were assessed to determine pyroptosis...
March 26, 2024: Cell Division
https://read.qxmd.com/read/38532240/uncovering-cell-cycle-dysregulations-and-associated-mechanisms-in-cancer-and-neurodegenerative-disorders-a-glimpse-of-hope-for-repurposed-drugs
#25
REVIEW
Dia Advani, Pravir Kumar
The cell cycle is the sequence of events orchestrated by a complex network of cell cycle proteins. Unlike normal cells, mature neurons subsist in a quiescent state of the cell cycle, and aberrant cell cycle activation triggers neuronal death accompanied by neurodegeneration. The periodicity of cell cycle events is choreographed by various mechanisms, including DNA damage repair, oxidative stress, neurotrophin activity, and ubiquitin-mediated degradation. Given the relevance of cell cycle processes in cancer and neurodegeneration, this review delineates the overlapping cell cycle events, signaling pathways, and mechanisms associated with cell cycle aberrations in cancer and the major neurodegenerative disorders...
March 26, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38531964/extracellular-vesicle-mediated-transfer-of-mirna-1-from-primary-tumors-represses-the-growth-of-distant-metastases
#26
JOURNAL ARTICLE
Chae-Yi Kim, Kang-Hoon Lee, Keun Hong Son, Tae-Jin Shin, Je-Yoel Cho
Metastases originate from primary tumors and reach distant organs. Growing evidence suggests that metastases are under the control of primary tumors even outside the primary site; however, the mechanisms by which primary tumors remotely control metastases remain unclear. Here, we discovered a molecular mechanism by which primary tumors suppress metastatic growth. Interestingly, we found that extracellular vesicles (EVs) derived from the primary tumor can inhibit the growth of metastases both in vitro and in vivo...
March 27, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38531791/melatonin-s-protective-effects-on-neurons-in-an-in-vitro-cell-injury-model
#27
JOURNAL ARTICLE
Wei Gu, Mimi Wu, Shihe Cui, Jinhua Bo, Hao Wu
BACKGROUND: Currently, the role of melatonin (MT) in neuronal damage remains unclear and this study aimed to explore the protective effects of MT on neurons in an in vitro cell injury model. METHODS: The Sprague Dawley (SD) rat traumatic brain injury (TBI) model was prepared, and brain tissue extract (BTE) from the injured area were generated. To establish a cell injury model in vitro , the BTE was added to the culture medium during the neuron culture process. MT was introduced into the culture medium of the cell injury model to observe its protective effects on neurons...
March 2024: Discovery Medicine
https://read.qxmd.com/read/38531693/comprehensive-toxicity-assessment-of-nanodiamond-on-blaps-polychresta-implications-and-novel-findings
#28
JOURNAL ARTICLE
Marwa Saad, Nabila Selim, Lamia M El-Samad
With the increasing development of nanomaterials, the use of nanodiamonds (NDs) has been broadly manifested in many applications. However, their high penetration into the ecosystem indubitably poses remarkable toxicological risks. This paper investigates the toxic effects of NDs on the darkling beetle, Blaps polychresta Forskal, 1775 (Coleoptera: Tenebrionidae). Survival analysis was carried out by monitoring the beetles for 30 d after the injection of four different doses of NDs. A dose of 10.0 mg NDs/g body weight, causing less than 50% mortality effect, was assigned in the analysis of the different organs of studied beetles, including testis, ovary, and midgut...
March 26, 2024: Insect Science
https://read.qxmd.com/read/38531625/myeloperoxidase-inhibition-protects-bone-marrow-mononuclear-cells-from-dna-damage-induced-by-the-top2-poison-anti-cancer-drug-etoposide
#29
JOURNAL ARTICLE
Ian G Cowell, Caroline A Austin
Myeloperoxidase (MPO) is found almost exclusively in granulocytes and immature myeloid cells. It plays a key role in the innate immune system, catalysing the formation of reactive oxygen species that are important in anti-microbial action, but MPO also oxidatively transforms the topoisomerase II (TOP2) poison etoposide to chemical forms that have elevated DNA damaging properties. TOP2 poisons such as etoposide are widely used anti-cancer drugs, but they are linked to cases of secondary acute myeloid leukaemias through a mechanism that involves DNA damage and presumably erroneous repair leading to leukaemogenic chromosome translocations...
March 26, 2024: FEBS Open Bio
https://read.qxmd.com/read/38531501/effects-of-moderate-ethanol-exposure-on-risk-factors-for-cardiovascular-disease-and-colorectal-cancer-in-adult-wistar-rats
#30
JOURNAL ARTICLE
Anna J Kwon, Lani Morales, Louise Chatagnier, Jacqueline Quigley, Jeremy Pascua, Natalie Pinkowski, Susan M Brasser, Mee Young Hong
While past studies have provided evidence linking excessive alcohol consumption to increased risk for cardiovascular diseases (CVDs) and colorectal cancer (CRC), existing data on the effects of moderate alcohol use on these conditions have produced mixed results. The purpose of this study was to investigate the effects of moderate alcohol consumption on risk factors associated with the development of CVDs and CRC in adult rats. Twenty-four, 14-month-old, non-deprived male Wistar rats were randomly assigned to either an ethanol group, which consisted of voluntary access to a 20% (v/v) ethanol solution on alternate days, or a water control group (n = 12/group) for 13 weeks...
March 24, 2024: Alcohol
https://read.qxmd.com/read/38531387/unveiling-thioacetamide-induced-toxicity-multi-organ-damage-and-omitted-bone-toxicity
#31
JOURNAL ARTICLE
Haodong Zhang, Jian Xu
Thioacetamide (TAA), a widely employed hepatotoxic substance, has gained significant traction in the induction of liver failure disease models. Upon administration of TAA to experimental animals, the production of potent oxidative derivatives ensues, culminating in the activation of oxidative stress and subsequent infliction of severe damage upon multiple organs via dissemination through the bloodstream. This review summarized the various organ damages and corresponding mechanistic explanations observed in previous studies using TAA in toxicological animal experiments...
2024: Human & Experimental Toxicology
https://read.qxmd.com/read/38531206/assessing-combined-effects-of-long-term-exposure-to-copper-and-marine-heatwaves-on-the-reef-forming-serpulid-ficopomatus-enigmaticus-through-a-biomarker-approach
#32
JOURNAL ARTICLE
Verdiana Vellani, Alessia Cuccaro, Matteo Oliva, Carlo Pretti, Monia Renzi
Sessile benthic organisms can be affected by global changes and local pressures, such as metal pollution, that can lead to damages at different levels of biological organization. Effects of exposure to marine heatwaves (MHWs) alone and in combination with environmentally relevant concentration of copper (Cu) were evaluated in the reef-forming tubeworm Ficopomatus enigmaticus using a multi-biomarker approach. Biomarkers of cell membrane damage, enzymatic antioxidant defences, metabolic activity, neurotoxicity, and DNA integrity were analyzed...
March 25, 2024: Marine Pollution Bulletin
https://read.qxmd.com/read/38531153/the-physiological-response-of-oriental-river-prawn-macrobrachium-nipponense-to-starvation-induced-stress
#33
JOURNAL ARTICLE
Fajun Li, Xiaocui Cui, Chunpeng Fu, Aili Wang
Environmental stresses play critical roles in the physiology of crustaceans. Food deprivation is an important environmental factor and a regular occurrence in both natural aquatic habitats and artificial ponds. However, the underlying physiological response mechanisms to starvation-caused stress in crustaceans are yet to be established. In the present study, the hepatopancreas tissue of Macrobrachium nipponense was transcriptome analyzed and examined for starvation effects on oxidative stress, DNA damage, autophagy, and apoptosis across four fasting stages (0 (control group), 7, 14, and 21 days)...
March 20, 2024: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://read.qxmd.com/read/38530880/glucosylceramide-accumulation-in-microglia-triggers-sting-dependent-neuroinflammation-and-neurodegeneration-in-mice
#34
JOURNAL ARTICLE
Rui Wang, Hongyang Sun, Yifan Cao, Zhixiong Zhang, Yajing Chen, Xiying Wang, Lele Liu, Jin Wu, Hao Xu, Dan Wu, Chenchen Mu, Zongbing Hao, Song Qin, Haigang Ren, Junhai Han, Ming Fang, Guanghui Wang
Mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GCase) are responsible for Gaucher disease (GD) and are considered the strongest genetic risk factor for Parkinson's disease (PD) and Lewy body dementia (LBD). GCase deficiency leads to extensive accumulation of glucosylceramides (GCs) in cells and contributes to the neuropathology of GD, PD, and LBD by triggering chronic neuroinflammation. Here, we investigated the mechanisms by which GC accumulation induces neuroinflammation. We found that GC accumulation within microglia induced by pharmacological inhibition of GCase triggered STING-dependent inflammation, which contributed to neuronal loss both in vitro and in vivo...
March 26, 2024: Science Signaling
https://read.qxmd.com/read/38530767/one-carbon-to-rule-them-all-formaldehyde-is-a-one-carbon-signal-connecting-one-carbon-metabolism-and-epigenetic-methylation
#35
Logan Tenney, Vanha N Pham, Christopher J Chang
Formaldehyde is commonly thought of as an environmental toxin or laboratory fixation reagent, but there is a growing appreciation for its broader physiological contributions as a naturally generated one-carbon metabolite across all kingdoms of life. In this In Focus article, we summarize emerging advances in the field that show how formaldehyde plays diverse roles as a one-carbon signal in DNA damage, one-carbon metabolism, and epigenetic regulation.
March 26, 2024: ACS Chemical Biology
https://read.qxmd.com/read/38530761/probiotics-supplementation-in-the-treatment-of-male-infertility-a-systematic-review
#36
REVIEW
Licia Cristina Silva de Lima Oliveira, Elton Carvalho Costa, Fernanda Domingues Gomes Martins, Alcenir Sales da Rocha, Girlandia Alexandre Brasil
Infertility is a widespread global issue that affects approximately 15% of sexually active and active couples, which contributes to about 50% of cases. Currently, the condition remains prevalent and often inadequately treated. This systematic review aims to evaluate existing studies investigating the effects of probiotic supplementation in men. A comprehensive search was conducted across major databases, including PubMed, Cochrane, Science Direct, and Scielo, using relevant keywords such as 'probiotic' OR 'Lactobacillus' OR 'Bifidobacterium' AND 'Male infertility' OR 'male fertility' OR 'sperm quality' OR 'sperm motility' OR 'oligoasthenoteratozoospermia' and their Portuguese equivalents...
March 26, 2024: JBRA Assisted Reproduction
https://read.qxmd.com/read/38530541/ginsenoside-rb1-deters-cell-proliferation-induces-apoptosis-alleviates-oxidative-stress-and-antimetastasis-in-oral-squamous-carcinoma-cells
#37
JOURNAL ARTICLE
Le An, Yang Yu, Long He, Xu Xiao, Pengcheng Li
There are numerous therapeutic applications for ginsenoside Rb1 (GRb1), the primary saponin derived from ginseng root. According to earlier research, ginsenoside Rb1 causes apoptosis and reduces the cell cycle. Its adverse effects, especially those on the development of the embryo, still need to be thoroughly studied. A host's lifestyle choices, including smoking, drinking too much alcohol, using tobacco products, and having an HPV infection, can increase the risk of oral squamous cell carcinoma (OSCC), one of the most prevalent malignancies of the oral cavity...
March 26, 2024: Applied Biochemistry and Biotechnology
https://read.qxmd.com/read/38530432/chemotherapy-initiated-cysteine-rich-protein-61-decreases-acute-b-lymphoblastic-leukemia-chemosensitivity
#38
JOURNAL ARTICLE
Pengchong Shi, Zhen Lin, Yanfang Song, Zhaozhong Li, Menglu Zeng, Li Luo, Yingping Cao, Xianjin Zhu
PURPOSE: Chemoresistance is a major challenge for acute lymphoblastic leukemia (ALL) treatment. Cysteine-rich protein 61 (Cyr61) plays an important role in drug resistance modulation of tumor cells, and Cyr61 levels are increased in the bone marrow of patients with ALL and contribute to ALL cell survival. However, the effect of Cyr61 on B cell acute lymphoblastic leukemia (B-ALL) cell chemosensitivity and the regulatory mechanisms underlying Cyr61 production in bone marrow remain unknown...
March 26, 2024: Journal of Cancer Research and Clinical Oncology
https://read.qxmd.com/read/38530366/oncogenic-ets-fusions-promote-dna-damage-and-proinflammatory-responses-via-pericentromeric-rnas-in-extracellular-vesicles
#39
JOURNAL ARTICLE
Peter Ruzanov, Valentina Evdokimova, Manideep C Pachva, Alon Minkovich, Zhenbo Zhang, Sofya Langman, Hendrik Gassmann, Uwe Thiel, Marija Orlic-Milacic, Syed H Zaidi, Vanya Peltekova, Lawrence E Heisler, Manju Sharma, Michael E Cox, Trevor D McKee, Mark Zaidi, Eve Lapouble, John D McPherson, Olivier Delattre, Laszlo Radvanyi, Stefan Eg Burdach, Lincoln D Stein, Poul H Sorensen
Aberrant expression of ETS transcription factors characterizes numerous human malignancies. Many of these proteins, including EWS::FLI1 and EWS::ERG fusions in Ewing sarcoma (EwS) and TMPRSS2::ERG in prostate cancer (PCa), drive oncogenic programs via binding to GGAA repeats. We report here that both EWS::FLI1 and ERG bind and transcriptionally activate GGAA-rich pericentromeric heterochromatin. The respective pathogen-like HSAT2 and HSAT3 RNAs, together with LINE, SINE, ERV and other repeat transcripts, are expressed in EwS and PCa tumors, secreted in extracellular vesicles (EVs) and are highly elevated in plasma of EwS patients with metastatic disease...
March 26, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38530160/a-phase-0-1-pharmacokinetic-and-pharmacodynamics-and-safety-and-tolerability-study-of-letrozole-in-combination-with-standard-therapy-in-recurrent-high-grade-gliomas
#40
JOURNAL ARTICLE
Pankaj B Desai, Aniruddha Karve, Misam Zawit, Priyanka Arora, Nimita Dave, Joy Awosika, Ningjing Li, Bethany Fuhrman, Mario Medvedovic, Larry Sallans, Ady Kendler, Biplab DasGupta, David Plas, Richard Curry, Mario Zuccarello, Rekha Chaudhary, Soma Sengupta, Trisha M Wise-Draper
PURPOSE: High grade gliomas (HGGs) carry a poor prognosis, with glioblastoma accounting for almost 50% of primary brain malignancies in the elderly. Unfortunately, despite the use of multiple treatment modalities, the prognosis remains poor in this population. Our pre-clinical studies suggest that the presence of aromatase expression, encoded by CYP19A1, is significantly upregulated in HGGs. Remarkably, we find that letrozole (LTZ), an FDA approved aromatase inhibitor, has marked activity against HGGs...
March 26, 2024: Clinical Cancer Research
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