Huanhuan Wang, Qin Fan, Qian Liang, Yao Wu, Zhongming Ye, Haipeng Wu, Qian Sun, Huanwen Tang, Yungang Liu, Qizhan Liu, Yuting Chen
Aflatoxin B1 (AFB1) is the most toxic mycotoxin and a proven human carcinogen that requires metabolic activation, known by cytochrome P450 (CYP) 1A2 and 3A4. Previous evidence showed that AFB1 is activated by human recombinant CYP1A1 expressed in budding yeast. Yet, the toxicity, in particular the genotoxicity of the reactive metabolites formed from AFB1 remains unclear. Humans could be exposed to both AFB1 and benzo(a)pyrene (BaP) simultaneously, thus we were interested in their combined genotoxic effects subsequent to metabolic activation by CYP1A1...
February 19, 2024: Chemico-biological Interactions
Jana Kasparkova, Vojtech Novohradsky, José Ruiz, Viktor Brabec
Cyclometalated Ir(III) complex [Ir(L)2 (dppz)]PF6 (where L = 1-methyl-2-(thiophen-2-yl)-1H-benzo [d]imidazole and dppz = dipyrido [3,2-a:2',3'-c]phenazine) (Ir1) is potent anticancer agent whose potency can be significantly increased by irradiation with blue light. Structural features of the cyclometalated Ir(III) complex Ir1 investigated in this work, particularly the presence of dppz ligand possessing an extended planar area, suggest that this complex could interact with DNA. Here, we have shown that Ir1 accumulates predominantly in mitochondria of cancer cells where effectively and selectively binds mitochondrial (mt) DNA...
February 19, 2024: Chemico-biological Interactions
Anjali Mandava, Binhan Pham, Michelle Pedler, Biehuoy Shieh, Hari Gopalakrishnan, J Mark Petrash
Aldose reductase is a member of the 1B1 subfamily of aldo-keto reductase gene superfamily. The action of aldose reductase (AR) has been implicated in the pathogenesis of a variety of disease states, most notably complications of diabetes mellitus including neuropathy, retinopathy, nephropathy, and cataracts. To explore for mechanistic roles for AR in disease pathogenesis, we established mutant strains produced using Crispr-Cas9 to inactivate the AKR1B3 gene in C57BL6 mice. Phenotyping AR-knock out (ARKO) strains confirmed previous reports of reduced accumulation of tissue sorbitol levels...
February 17, 2024: Chemico-biological Interactions
Elena Navarro-Carrasco, Aurora Campos-Díaz, Eva Monte-Serrano, Frank Rolfs, Richard de Goeij-de Haas, Thang V Pham, Sander R Piersma, Connie R Jiménez, Pedro A Lazo
Dynamic chromatin remodeling requires regulatory mechanisms for its adaptation to different nuclear function, which are likely to be mediated by signaling proteins. In this context, VRK1 is a nuclear Ser-Thr kinase that regulates pathways associated with transcription, replication, recombination, and DNA repair. Therefore, VRK1 is a potential regulatory, or coordinator, molecule in these processes. In this work we studied the effect that VRK1 depletion has on the basal nuclear and chromatin phosphoproteome, and their associated pathways...
February 15, 2024: Chemico-biological Interactions
Rafael Arsuffi-Marcon, Lizandra Gomes Souza, Artur Santos-Miranda, Julliane V Joviano-Santos
Neurodegenerative diseases are associated with diverse symptoms, both motor and mental. Genetic and environmental factors can trigger neurodegenerative diseases. Chemicals as pesticides are constantly used in agriculture and also domestically. In this regard, pyrethroids (PY), are a class of insecticides in which its main mechanism of action is through disruption of voltage-dependent sodium channels function in insects. However, in mammals, they can also induce oxidative stress and enzyme dysfunction. This review investigates the association between PY and neurodegenerative diseases as Alzheimer's, Huntington's, Parkinson's, Amyotrophic Lateral Sclerosis, and Autism in animal models and humans...
February 15, 2024: Chemico-biological Interactions
Saad Fettach, Fatima Zahra Thari, Khalid Karrouchi, Laila Benbacer, Learn-Han Lee, Abdelhakim Bouyahya, Yahia Cherrah, Hassan Sefrioui, Khalid Bougrin, My El Abbes Faouzi
Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal...
February 15, 2024: Chemico-biological Interactions
Haiyan Zhu, Yenan Duan, Yijing Yang, Enqing Chen, Hanxin Huang, Xi Wang, Jie Zhou
Sodium aescinate (SA) is extracted from Aesculus wilsonii Rehd seeds and was first marketed as a medicament in German. With the wide application of SA in clinical practice, reports of adverse drug reactions and adverse events have gradually increased, including renal impairment. However, the pathogenic mechanisms of SA have not yet been fully elucidated. The toxic effects and underlying mechanisms of SA were explored in this study. Our data showed that SA significantly elevated the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and Kidney injury molecule 1 (Kim-1), accompanied by pathologically significant changes in renal tissue...
February 15, 2024: Chemico-biological Interactions
Cyrus Takahashi, Mikhail Chtcherbinine, Brandt C Huddle, Michael W Wilson, Timothy Emmel, Robert M Hohlman, Stacy McGonigal, Ronald J Buckanovich, Scott D Larsen, Thomas D Hurley
Aldehyde dehydrogenase 1A (ALDH1A) isoforms may be a useful target for overcoming chemotherapy resistance in high-grade serous ovarian cancer (HGSOC) and other solid tumor cancers. However, as different cancers express different ALDH1A isoforms, isoform selective inhibitors may have a limited therapeutic scope. Furthermore, resistance to an ALDH1A isoform selective inhibitor could arise via induction of expression of other ALDH1A isoforms. As such, we have focused on the development of pan-ALDH1A inhibitors, rather than on ALDH1A isoform selective compounds...
February 14, 2024: Chemico-biological Interactions
Wenhui Shen, Xianhui Zeng, Xiangchen Zeng, Baoshan Hu, Chong Ren, Zhiming Lin, Long Zhang, Gang Rui, Miersalijiang Yasen, Xiaohui Chen
Osteosarcoma is a prevalent kind of primary bone malignancy. Trifluoperazine, as an antipsychotic drug, has anti-tumor activity against a variety of cancers. Nevertheless, the impact of trifluoperazine on osteosarcoma is unclear. Our investigation aimed to explore the mechanism of trifluoperazine's effect on osteosarcoma. We found that trifluoperazine inhibited 143B and U2-OS osteosarcoma cell proliferation in a method based on the dose. Furthermore, it was shown that trifluoperazine induced the accumulation of reactive oxygen species (ROS) to cause mitochondrial damage and induced mitophagy in osteosarcoma cells...
February 13, 2024: Chemico-biological Interactions
Jie He, Jie Xu, Mucong Zheng, Kai Pan, Lilin Yang, Lina Ma, Chuyang Wang, Jie Yu
Thyroid disease has been rapidly increasing, but its causes remain unclear. At present, many studies have focused on the relationship between environmental endocrine disruptors (EEDs) and the pathogenesis of thyroid disease. Herein, we summarize such studies exploring the effects of exposure to common EEDs on thyrotoxicosis, finding that EEDs appear to contribute to the pathogenesis of thyroid-related diseases such as thyroid cancer, goiter, thyroiditis, hyperthyroidism, and hypothyroidism. To explore this causative effect in detail, we have analyzed the following three aspects of how EEDs are believed to exert their impacts on the occurrence and development of thyroid disease: (1) damage to the thyroid tissue structure, including disrupted mitochondria and the stratification of thyroid follicular epithelial cells; (2) disruption of thyroid hormone signaling, including thyroid hormone synthesis and secretion disorders, destruction of normal function of the hypothalamus-pituitary-thyroid axis, disturbed estrogen signaling in the body, alterations to the level of thyroid-stimulating hormone, inhibition of the release of thyroglobulin from thyroid cells, and reductions in the levels of sodium iodide co-transporters, thyroid peroxidase, deiodinase, and transthyretin; and (3) molecular mechanisms underlying the disruption of thyroid function, including competitive binding to T3 and T4 receptors, disturbance of the hypothalamic-pituitary-thyroid axis, activation of the ERK and Akt pathways, oxidative stress, regulation of the expression of the proto-oncogene k-Ras, tumor suppressor gene PTEN, and thyroid TSHR gene, and induction of autophagy in thyroid cells...
February 8, 2024: Chemico-biological Interactions
Siqi Huang, Wei Song, Shuangmiao Jiang, Yuanchen Li, Min Wang, Na Yang, Huaijun Zhu
Wuzhi capsule (WZC), a commonly used Chinese patent medicine to treat various types of liver dysfunction in China, increases the exposure of tacrolimus (TAC) in liver transplant recipients. However, this interaction has inter-individual variability, and the underlying mechanism remains unclear. Current research indicates that CYP3A4/5 and drug transporters influence the disposal of both drugs. This study aims to evaluate the association between TAC dose-adjusted trough concentration (C/D) and specific genetic polymorphisms of CYP3A4/5, drug transporters and pregnane x receptor (PXR), and plasma levels of major WZC components, deoxyschisandrin and γ-schisandrin, in liver transplant patients receiving both TAC and WZC...
February 8, 2024: Chemico-biological Interactions
Liang Kun Huang, Xiao Shuang Zeng, Ze Wen Jiang, Hao Peng, Fei Sun
Steroid-induced osteonecrosis of the femoral head (SONFH), caused by glucocorticoid (GC) administration, is known to exhibit a high incidence worldwide. Although osteoblast apoptosis has been reported as an important cytological basis of SONFH, the precise mechanism remains elusive. Echinacoside (Ech), a natural phenylethanoid glycoside, exerts multiple beneficial effects, such as facilitation of cell proliferation and anti-inflammatory and anticancer activities. Herein, we aimed to explore the regulatory mechanism underlying glucocorticoid-induced osteoblast apoptosis and determine the protective efficacy of Ech against SONFH...
February 7, 2024: Chemico-biological Interactions
Jang Su Jeon, Hyemin Kim, Seongyea Jo, Jaehoon Sim, Sang Kyum Kim
This study delves into the intricate mechanisms underlying drug-induced liver injury (DILI) with a specific focus on bromfenac, the withdrawn nonsteroidal anti-inflammatory drug. DILI is a pervasive concern in drug development, prompting market withdrawals and posing significant challenges to healthcare. Despite the withdrawal of bromfenac due to DILI, the exact role of its microsomal metabolism in inducing hepatotoxicity remains unclear. Herein, employing HepG2 cells with human liver microsomes and UDP-glucuronic acid (UDPGA), our investigation revealed a substantial increase in bromfenac-induced cytotoxicity in the presence of UDPGA, pointing to the significance of UDP-glucuronosyltransferase (UGT)-dependent metabolism in augmenting toxicity...
February 6, 2024: Chemico-biological Interactions
Katarina Tomović Pavlović, Gordana Kocić, Andrija Šmelcerović
The cell cycle includes two checkpoint arrests allowing to repair of damaged DNA. Many cancer cell lines exhibit weak G1 checkpoint mechanisms relying significantly more on the G2 checkpoint than do healthy cells. Inhibition of Myt1 kinase (PKMYT1), a forgotten member of the Wee family, cyclin-dependent kinase 1 (Cdk1) inhibitory kinase, target for G2 checkpoint abrogation, whose inhibition forces cells into premature unchecked mitosis resulting in cell death, is a promising concept for anticancer therapy. There are not many inhibitors of this emerging, potentially clinically important kinase...
February 6, 2024: Chemico-biological Interactions
Ji Won Lee, Hwanhui Lee, Soon-Wook Noh, Hyung-Kyoon Choi
No abstract text is available yet for this article.
February 5, 2024: Chemico-biological Interactions
Xuan Xia, Kaiqi Chen, Yawen Chen
With the improvement of living quality, people pay more and more attention to vitamin supplements. The vitamins in the daily diet can meet the needs of the body. Whether additional vitamin supplementation is necessary still needs to be further explored. Many studies have reported that vitamin deficiency and excessive vitamin supplementation could lead to abnormal development in the body or increase the risk of diseases. Here, we summarize the abnormal levels of vitamins can cause the homeostasis imbalance of hypothalamus-pituitary-adrenal (HPA) axis by affecting its development and function...
February 5, 2024: Chemico-biological Interactions
Jing-Yu Sun, Jun Zha, Yue Qiu, Ting-Jun Fan
Betaxolol is commonly used to manage glaucoma in clinical practice. However, its long-term use may damage the cornea. Thus, the cytotoxicity and mechanisms of betaxolol in human corneal stromal cells (HCSCs) warrant further study. In this study, we used in vitro HCSCs and in vivo rabbit corneal models to investigate betaxolol cytotoxic effects and mechanism of action. At near-clinical concentrations (0.28% and 0.14%), betaxolol inhibited caspase-8 activity, activated receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed-spectrum kinase-like domain (MLKL), and phosphorylated MLKL to induce necroptosis in HCSCs...
February 5, 2024: Chemico-biological Interactions
Mykaella Andrade de Araújo, Erivaldo Davi Dos Santos Júnior, Bruna Priscila Dos Santos, Ygor Daniel Ramos Dos Santos, Pedro Augusto Tibúrcio Paulino, Elane Conceição Dos Santos, Tayhana Priscila Medeiros Souza, Lucas Anhezini, Ênio José Bassi, Marcelo Duzzioni, Olagide Wagner Castro, Tiago Gomes de Andrade, Camila Braga Dornelas, Daniel Leite Góes Gitaí
Layered double hydroxides (LDHs) have been employed as nano-sized carriers for therapeutic/bio-active molecules, including small interfering RNAs (siRNAs). However, the potential of LDHs nanoparticles for an efficient and safe antisense oligonucleotide (AMO) delivery still requires studies. In this research, we have tested the suitability of a Mg-Al-LDH-based nanocarrier loaded with a miRNA-196b-5p inhibitor. LDHs (and LDH-Oligo complex) were synthesized by the coprecipitation method followed by physicochemical characterization as hydrodynamic size, surface charge, crystallinity, and chemical groups...
February 2, 2024: Chemico-biological Interactions
Deren Liu, Wei Mei, Junfeng Kang, Taiyang Liao, Yibao Wei, Lishi Jie, Lei Shi, Peimin Wang, Jun Mao, Peng Wu
Knee osteoarthritis (KOA) is a chronic, disabling knee joint lesion in which degeneration and defects in articular cartilage are the most important features. Casticin (CAS) is a flavonoid extracted from the Chinese herb Vitex species that has anti-inflammatory and antitumor effects. The aim of this study was to investigate the therapeutic and mechanistic effects of CAS on cartilage damage in KOA. A KOA rat model was established by anterior cruciate ligament transection (ACLT), and cartilage morphological changes were assessed by histological analysis and micro-CT scans...
February 1, 2024: Chemico-biological Interactions
Sonia Fantone, Giovanni Tossetta, Laura Cianfruglia, Andrea Frontini, Tatiana Armeni, Antonio D Procopio, Armanda Pugnaloni, Alessandro F Gualtieri, Daniela Marzioni
Asbestos has been widely used due to its unique characteristics. It is known that exposure to asbestos causes serious damage to health but one species, chrysolite, is still used because it is considered less toxic and not biopersistent in some countries. The aim of our study was to investigate if cellular process underlying the proliferation, differentiation and cell death of placental tissues could be modify in presence of asbestos fibres (50 μg/ml final concentration), long chrysolite fibres (CHR-L) and short chrysolite fibres (CHR-S), using BeWo cell line, an in vitro model that mimics the syncytiotrophoblast (STB), the outer layer of placental villi...
January 30, 2024: Chemico-biological Interactions
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