Search Results (21,904)

Using sunscreens is one of the most widespread measures to protect human skin from sun ultraviolet radiation (UVR) damage. However, several studies have highlighted the toxicity of certain inorganic and organic UV filters used in sunscreens for the marine environment and human health. An alternative strategy may involve the use of natural products of marine origin to counteract UVR-mediated damage. Ovothiols are sulfur-containing amino acids produced by marine invertebrates, microalgae, and bacteria, endowed with unique antioxidant and UV-absorption properties. This study aimed to evaluate the protective effect of synthetic L-5-sulfanyl histidine derivatives, inspired by natural ovothiols, on human dermal fibroblasts (HDFs) upon UVA exposure. By using a custom-made experimental set-up to assess the UV screening ability, we measured the levels of cytosolic and mitochondrial reactive oxygen species (ROS), as well as cell viability and apoptosis in HDFs, in the presence of tested compounds, after UVA exposure, using flow cytometry assays with specific fluorescent probes. The results show that L-5-sulfanyl histidine derivatives display a UV screening capacity and prevent loss in cell viability, the production of cytosolic and mitochondrial ROS induced by UVA exposure in HDFs, and subsequent apoptosis. Overall, this study sheds light on the potential applications of marine-inspired sulfur-containing amino acids in developing alternative eco-safe sunscreens for UVR skin protection. Full article

Prolonged excessive intake of fluoride (F) can result in fluorosis, leading to a range of tissue oxidative damages. Therefore, mitigating the oxidative stress induced by fluorosis has become a significant research concern. Consequently, how to relieve oxidative stress caused by fluorosis is an urgent matter. In the present study, intestinal porcine epithelial (IPEC-J2) cells were chosen to explore the underlying mechanism of tea polyphenols (TPs) on F-induced oxidative stress. The results show that the cytotoxicity of IPEC-J2 cells induced by F presented a dose-dependent manner according to cell viability. Additionally, F treatment inhibited the activity of T-SOD, CAT, and GSH-Px as well as their transcription levels, increased the reactive oxygen (ROS) formation and cell damage rates, and then promoted cell apoptosis through the results of TUNEL and mitochondrial membrane potential detection when compared with the IPEC-J2 cells from the control group. As the main antioxidant ingredient in tea, TPs alleviated F-induced cell oxidation and apoptosis via blocking F-induced ROS generation and LDH’s release, as well as promoting the transcription of tight junction (TJ) proteins and the activities of antioxidant enzymes in IPEC-J2 cells. These results provide a new treatment strategy for F-induced intestinal oxidative impairment. Full article

Microplastics pose a great challenge to human health and could prove to be the most dangerous environmental contaminant of the 21st century. The study presented here is an attempt at proposing a new methodology for studying the interaction of microplastics with adherent mammalian cells using aides. The disposable holders proposed here provide direct contact between microplastics (with a density lower than that of water) and cells in the course of culturing, which is necessary as we postulate the existence of an interaction. Using several microscopic methods (confocal fluorescence microscopy and scanning electron microscopy (SEM)), we have observed that this interaction causes a non-destructive penetration of the cell monolayer and adhesion of microplastics to the cell surface. The Caco-2 cells were used for the experiments. The said cells are the approximation of the digestive system, which, due to the presence of plastics in drinking water, is particularly vulnerable to direct interactions with these contaminants. Model microplastics were obtained by grinding pellets of chemically pure polypropylene. The imaging of cells in both space and on the surface was supplemented by an assay to determine the cell welfare in the studied microplastic-exposed models, which did not show the occurrence of apoptosis or necrosis after a 24 h exposure. Full article

Periodontal diseases, including gingivitis and periodontitis, are chronic inflammatory conditions of the teeth’ supporting structures that can lead to progressive tissue destruction and loss if left untreated. Basic treatments like scaling and root planing, alone or combined with antimicrobial agents, are the standard of care. However, with the increasing prevalence of antibiotic resistance and the need for new ideas in therapy, adjunctive treatments like ozone therapy have gained attention. Ozone (O₃), a triatomic oxygen molecule, is used because of its strong antimicrobial, anti-inflammatory, and regenerative activity and, hence, as a potential tool in periodontal therapy. This review of the use of ozone therapy in periodontal disease breaks down the multifaceted mechanism of ozone therapy, which includes the selective antimicrobial action against biofilm-associated pathogens, immunomodulatory effects on host cells, and stimulation of tissue repair. O₃ therapy disrupts microbial biofilms, enhances immune cell function, and promotes healing by activating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways that regulate oxidative stress, inflammation, and apoptosis. Additional findings include its ability to upregulate growth factors and extracellular matrix proteins, which is significant for periodontal tissue regeneration. This review also discusses the application of O₃ therapy in periodontal cell lines, emphasizing its impact on cell viability, proliferation, and differentiation. Advances in periodontal regenerative techniques, combined with the antimicrobial and healing properties of O₃, have demonstrated significant clinical benefits. Challenges, including the need for standardized dosages, effective delivery systems, and long-term studies, are also addressed to ensure safe and effective clinical integration. O₃ therapy, with its dual antimicrobial and regenerative capabilities, offers an innovative adjunctive approach to periodontal treatment. Future research focusing on optimized protocols and evidence-based guidelines is essential to fully realize its potential in enhancing periodontal health and improving patient outcomes. Full article

The glucose metabolism homeostasis in the follicular fluid microenvironment plays an important role in follicular maturation and ovulation, and excessively high or low glucose concentrations have adverse effects on the differentiation of follicular granulosa cells (GCs). However, a limited number of microRNAs (miRNA) have been reported to be involved in glucose-stimulated GCs differentiation. In this study, we characterized the miRNA expression profiles of sheep ovarian GCs cultured in high-glucose and optimal glucose concentrations and focused on a differentially expressed miRNA: miR-17-5p, which may be involved in regulating high-glucose-induced GC apoptosis by targeting KPNA2. We found that overexpression of miR-17-5p significantly promoted GCs proliferation and inhibited cell apoptosis, while downregulated the mRNA and protein expression of apoptosis-related makers (Bax, Caspase-3, Caspase-9, and Bcl-2). In contrast to the classical mechanism of miRNA silencing target gene expression, miR-17-5p overexpression significantly upregulated the expression of target gene KPNA2. A dual luciferase reporter gene assay verified the targeted binding relationship between miR-17-5p and KPNA2 promoter. Meanwhile, overexpression of KPNA2 further promoted the downregulation of apoptosis-related genes driven by miR-17-5p mimics. Knockdown of KPNA2 blocked the inhibitory effect of miR-17-5p mimics on the expression of apoptosis-related genes. Our results demonstrated that miR-17-5p activated the KPNA2 promoter region and upregulated KPNA2 expression, thereby inhibiting GCs apoptosis under high glucose. Full article

Klotho, initially identified as an anti-aging gene, has been shown to play significant roles in cancer biology. Alongside α-Klotho, the β-Klotho and γ-Klotho isoforms have also been studied; these studies showed that Klotho functions as a potential tumor suppressor in many different cancers by inhibiting cancer cell proliferation, inducing apoptosis and modulating critical signaling pathways such as the Wnt/β-catenin and PI3K/Akt pathways. In cancers such as breast cancer, colorectal cancer, hepatocellular carcinoma, ovarian cancer, and renal cell carcinoma, reduced Klotho expression often correlates with a poor prognosis. In addition, Klotho’s role in enhancing chemotherapy sensitivity and its epigenetic regulation further underscores its potential as a target for cancer treatments. This review details Klotho’s multifaceted contributions to cancer suppression and its potential as a therapeutic target, enhancing the understanding of its significance in cancer treatment and prognoses. Full article

Zearalenone (ZEA) is one of the common mycotoxins in feeds. ZEA and its metabolites have estrogen-like activity and can competitively bind to estrogen receptors, causing reproductive dysfunction and damage to reproductive organs. The toxicity mechanism of ZEA mainly inhibits the antioxidant pathway and antioxidant enzyme activity, induces cell cycle arrest and DNA damage, and blocks the process of cellular autophagy to produce toxic effects. In animal husbandry practice, when animals ingest ZEA-contaminated feed, it is likely to lead to abortion in females, abnormal sperm viability in males with inflammatory reactions in various organs, and cancerous changes in the reproductive organs of humans when they ingest contaminated animal products. In this paper, we reviewed in detail how ZEA induces oxidative damage by inducing the generation of reactive oxygen species (ROS) and regulating the expression of genes related to oxidative pathways, induces germ cell apoptosis through the mitochondrial and death receptor pathways, and activates the expression of genes related to autophagy in order to induce cellular autophagy. In addition, the molecular detoxification mechanism of ZEA is also explored in this paper, aiming to provide a new direction and theoretical basis for the development of new ZEA detoxification methods to better reduce the global pollution and harm caused by ZEA. Full article

The evergreen coniferous tree Thuja occidentalis is a member of the Cupressaceae family. This study included biological, cytotoxic, and in silico docking analyses in addition to a phytochemical composition analysis of the plant leaves and stem ethanolic extracts. The extracts’ in vitro cytotoxicity efficacy against various cancer cell lines was examined. Additionally, certain phytochemical compounds were identified by gas chromatographic analysis and subsequently assessed in silico against anticancer molecular targets. Also, their antiviral effect was assessed. Good cytotoxic activity was demonstrated by plant extracts against the lung and colorectal cancer cell lines. With half-maximal inhibitory concentration values of 18.45 μg/mL for the leaf extract and 33.61 μg/mL for the stem extract, apoptosis and S-phase arrest was observed in the lung cancer cell line. In addition, the leaf extract demonstrated effective antiviral activity, with suppression rates of 17.7 and 16.2% for the herpes simplex and influenza viruses, respectively. Gas chromatographic analysis revealed the presence of relevant bioactive components such as Podocarp-7-en-3β-ol, 13β-methyl-13-vinyl, Megastigmatrienone, and Cedrol, which were tested in silico against anticancer molecular targets. Our findings suggest that plant ethanolic extracts may have potential therapeutic uses as anticancer drugs against lung cancer in addition to their antiviral properties, which opens up further avenues for more investigation and applications. Full article

Extracellular vesicles (EVs) are key mediators in the communication between cancer cells and their microenvironment, significantly influencing drug resistance. This review provides a comprehensive analysis of the roles of EVs in promoting drug resistance through mechanisms such as drug efflux, apoptosis resistance, autophagy imbalance, and tumor microenvironment modulation. Despite extensive research, details of EVs biogenesis, cargo selection, and specific pathways in EVs-mediated drug resistance are not fully understood. This review critically examines recent advancements, highlighting key studies that elucidate the molecular mechanisms of EVs functions. Additionally, innovative therapeutic strategies targeting EVs are explored, including inhibiting EVs biogenesis, engineering EVs for drug delivery, and identifying resistance-inhibiting molecules within EVs. By integrating insights from primary research and proposing new directions for future studies, this review aims to advance the understanding of EVs in cancer biology and foster effective interventions to mitigate drug resistance in cancer therapy. Full article

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and has a poor prognosis. Ataxia telangiectasia mutated and Rad3 related (ATR) is a key regulator for the DNA damage response and a potential target to treat cancer. Methods: We assessed the efficacy of BAY 1895344, an ATR inhibitor, in three ATC cell lines. Results: BAY 1895344 caused dose–response cytotoxicity in three ATC cell lines. BAY 1895344 induced S-phase and G2-phase arrest, activated caspase-3 activity and induced apoptosis in ATC cells. BAY 1895344 meaningfully retarded the tumor growth of an ATC xenograft model. BAY 1895344 therapy, combined with dabrafenib and trametinib, had synergism in vitro and revealed robust tumor growth suppression in vivo in two xenograft models of ATC harboring mutant BRAF^V600E. Furthermore, the combination of BAY 1895344 with lenvatinib was more effective than either agent alone in a xenograft model of ATC. Conclusions: These results reveal that BAY 1895344 has potential in treating ATC. Full article

Bladder cancer is a globally prevalent urological malignancy, with transitional carcinoma (TCC) representing the majority of cases. Cisplatin is the primary drug for metastatic bladder cancer chemotherapy; however, its application is limited by nephrotoxicity and resistance. Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogenic transcription factor often overactivated in various cancers, making it an appealing drug target. Fucoxanthin, a marine carotenoid, has significant anticancer properties. This study explored Fucoxanthin’s cytotoxic effects and its potential to potentiate the efficacy of Cisplatin, along with the mechanisms underlying these effects, on human bladder TCC cells. We demonstrated that Fucoxanthin is cytotoxic to bladder TCC cells by inducing apoptosis, evidenced by z-VAD-fmk-mediated annulment of Fucoxanthin’s cytotoxicity. Furthermore, Fucoxanthin reduced the levels of inherent or interleukin-6-induced tyrosine 705-phosphorylated STAT3 accompanied by downregulating BCL-xL, a well-established STAT3 target. Notably, ectopic expression of STAT3-C, a dominant-active STAT3 mutant, or BCL-xL thwarted Fucoxanthin’s proapoptotic and cytotoxic actions. Moreover, Fucoxanthin at subtoxic dosages enhanced the susceptibility to Cisplatin-induced apoptosis of bladder TCC cells initially resistant to Cisplatin. Remarkably, this Cisplatin-sensitizing effect of Fucoxanthin was abrogated when cells ectopically expressed STAT3-C or BCL-xL. Overall, for the first time, we proved that the proapoptotic, cytotoxic, and Cisplatin-sensitizing effects of Fucoxanthin on human bladder TCC cells are attributed to the blockade of the STAT3/BCL-xL axis. Our findings highlight that targeting the STAT3/BCL-xL axis is a promising strategy to eliminate bladder TCC cells and facilitate Cisplatin sensitization, and further support the potential of incorporating Fucoxanthin into Cisplatin-based chemotherapy for treating bladder cancer. Full article

The p21-activated kinases (PAKs) are a conserved family of serine/threonine protein kinases, which are effectors for the Rho family GTPases, namely, Rac/Cdc42. PAKs are divided into two groups: group I (PAK1–3) and group II (PAK4–6). Both groups of PAKs have been well studied in apoptosis, protein synthesis, glucose homeostasis, growth (proliferation and survival) and cytoskeletal regulation, as well as in cell motility, proliferation and cycle control. However, little is known about the role of PAKs in the secretory tissues, including in exocrine tissue, such as the exocrine pancreas (except for islet function and pancreatic cancer growth). Recent studies have provided insights supporting the importance of PAKs in exocrine pancreas. This review summarizes the recent insights into the importance of PAKs in the exocrine pancreas by reviewing their presence and activation; the ability of GI hormones/neurotransmitters/GFs/post-receptor activators to activate them; the kinetics of their activation; the participation of exocrine-tissue PAKs in activating the main growth-signaling cascade; their roles in the stimulation of enzyme secretion; finally, their roles in pancreatitis. These insights suggest that PAKs could be more important in exocrine/secretory tissues than currently appreciated and that their roles should be explored in more detail in the future. Full article

Background: Diffuse intrinsic pontine glioma [DIPG] is a fatal pediatric disease characterized by a post-translational modification, a replacement of lysine by methionine in position 27 of the N-terminal [H3K27M] tail of histone 3 isoform-1 [H3.1] or histone 3 isoform-3 [H3.3], respectively, expressed in the DIPG-36 and DIPG-50 cells. We investigated the role of cation channels in DIPG cells for the first time and the effects of ATP-sensitive K⁺[KATP] and TRPV1 channel modulators. Methods: Experiments were performed using “in vitro” cytotoxic assays combined with the patch clamp technique, RT-PCR, Western blot, and flow cytometry assays. Results: The most effective anti-proliferative drugs were repaglinide and glibenclamide after short and long-term incubation [6–96 h]. These drugs reduced macroscopic currents of the DIPG cells recorded in whole-cell patch clamp. Repaglinide concentration dependently enhanced the target protein H3K27ac in Western blotting after 48 h of incubation. This drug reduced cell diameter and enhanced cleaved caspase-3 in DIPG cells; total AKT/mTOR levels and phospho-mTOR were downregulated in DIPG-36. Conclusions: KATP and TRPV1 channels are functionally expressed, and sulphonylureas are effective antiproliferative upregulating H3K27ac with apoptosis in DIPG cells and the sub-micromolar concentrations in DIPG-50. Full article

Exposure to air pollution, especially fine particulate matter (PM2.5), is closely linked to various adverse health effects, particularly in the respiratory system. The present study was designed to investigate the lncRNA–mRNA interactions in PM2.5-induced lung cell injury using weighted gene co-expression network analysis (WGCNA). We downloaded the gene expression data of GSE138870 from the Gene Expression Omnibus (GEO) database and screened for differentially expressed lncRNAs and mRNAs. We constructed co-expression modules with WGCNA. Furthermore, functional enrichment analysis was also performed. We also constructed lncRNA–mRNA co-expression networks and lncRNA–mRNA-pathway networks to identify key regulatory relationships. The results revealed several modules significantly correlated with PM2.5-induced lung injury, such as the turquoise and blue modules. Genes within these modules were enriched in pathways related to signal transduction, metabolism, and cancer. Hub lncRNAs in the turquoise module, including LOC100129034 and CROCCP2, were found to be co-expressed with mRNAs involved in apoptosis and proliferation regulation. In the blue module, lnc-CLVS2-2 and GARS1-DT were connected to genes related to cell migration, invasion, and lung injury. These findings contribute novel perspectives to the molecular mechanisms involved in PM2.5-induced lung injury and suggest that WGCNA could be a valuable tool for predicting and understanding this disease process. Full article

Citrinin (CIT), a mycotoxin commonly found in cereals, is produced by fungi from the Aspergillus, Penicillium, and Monascus genera. While its nephrotoxic effects are well studied, its impact on neurons is less understood. This study investigates CIT-induced toxicity in human neuroblastoma cells (SH-SY5Y). The IC₅₀ values for cells treated with CIT were 77.1 μM at 24 h and 74.7 μM at 48 h using MTT assay, and 101.0 μM at 24 h and 54.7 μM at 48 h using neutral red assay. CIT exposure caused G2/M phase arrest, with cells in this phase increasing from 11.83% (control) to 33.10% at 50 μM CIT. At 50 μM, the percentage of cells in the S phase also increased, which may suggest that cellular stress pathways were activated. Moreover, an increase in late apoptosis process was noted in cells exposed to CIT for 24 h, particularly at the highest concentrations (38.75 and 50 µM). Western blot analysis confirmed a rapid change in the anti-apoptotic protein Bcl-2, but no significant changes in Bax. In conclusion, CIT induces apoptosis and cell cycle arrest in SH-SY5Y cells. However, further transcriptomic studies in specific proteins involved in different pathways described in this work are needed to gain a comprehensive understanding of the specific mechanisms underlying CIT’s toxicity in SH-SY5Y cells. Full article