Abstract. Tremella fuciformis polysaccharide (TFPS), which is the extract of Tremella fuciformis Berk, has previously been demonstrated to exhibit potent anti-oxidative, anti-inflammatory and anti-aging effects. However, the mechanisms underlying these protective and therapeutic effects remain to be elucidated. The aim of the present study was to investigate the protective effects of TFPS on hydrogen peroxide-induced injury of human skin fibroblasts and to elucidate the aforementioned underlying mechanisms. A hydrogen peroxide-induced human skin fibroblast injury model was firstly established. MTT and reactive oxygen species (ROS) production assays, in addition to terminal deoxynucleotidyl transferase dUTP nick end labeling, reverse transcription-quantitative polymerase chain reaction and western blotting, were performed to investigate the protective effects of TFPS. Hydrogen peroxide decreased human skin fibroblast viability with a concurrent increase in ROS generation and cell apoptosis. Treatment with 0-400 µg/ml TFPS alone for up to 48 h did not result in alteration in cell viability. Notably, TFPS pre-treatment reduced oxidative stress and cell apoptosis in hydrogen peroxide-treated skin fibroblasts. In addition, there was profound inhibition of p16, p21, p53 and caspase-3 expression, and activation of extracellular-signal regulated kinase and Akt serine/threonine kinase 1, following TFPS pre-treatment. Furthermore, it was revealed that TFPS additionally protected fibroblasts via the upregulation of SIRT1 expression, and this was abrogated by the SIRT1 inhibitor niacinamide. These results indicated that TFPS alleviated hydrogen peroxide-induced oxidative stress and apoptosis in skin fibroblasts via upregulation of SIRT1 expression, indicating that TFPS may act as a potential therapeutic agent for oxidative-stress-associated skin diseases and aging. IntroductionOxidative stress induced by free radicals, which are produced in response to redox reactions, radiation and chemical reactions, can cause DNA and protein damage. Such stress is associated with the development of many diseases, such as atherosclerosis, diabetes mellitus, articular gout, and cancer (1,2). Hydrogen peroxide (H 2 O 2 ) is one of type of reactive oxygen species (ROS) produced in normal cells during cell respiration and metabolism (3). However, many studies have indicated that a high concentration of H 2 O 2 , present under pathological conditions, may induce various human degenerative diseases and aging. Furthermore, H 2 O 2 also interacts with intracellular ions such as iron and copper, leading to a chain reaction that produces more reactive radicals and amplifies the damage, thereby causing DNA and protein damage (4). Therefore, antioxidants are very important for the treatment of oxidative-stress-related diseases and aging.Antioxidants in food, including vitamin C, polyphenols, tocopherols and f lavonoids, may prevent free-radical-induced cell damage (5). They also may attenuate oxidative-stress-induced inflammatory reactions and apopto...
Ferroptosis is a type of regulated cell death caused by iron overload and lipid peroxidation, and its core is an imbalance of redox reactions. Recent studies showed that ferroptosis played a dual role in liver diseases, that was, as a therapeutic target and a pathogenic factor. Therefore, herein, we summarized the role of ferroptosis in liver diseases, reviewed the part of available targets, such as drugs, small molecules, and nanomaterials, that acted on ferroptosis in liver diseases, and discussed the current challenges and prospects.
Nanomedicine shows great potential in screening, diagnosing and treating diseases. However, given the limitations of current technology, detection of some smaller lesions and drugs’ dynamic monitoring still need to be improved. With the advancement of nanotechnology, researchers have produced various nanomaterials with imaging capabilities which have shown great potential in biomedical research. Here, we summarized the researches based on the characteristics of imageable nanomaterials, highlighted the advantages and biomedical applications of imageable nanomaterials in the diagnosis and treatment of diseases, and discussed current challenges and prospects.
Background: N6-methyladenosine (m6A) is the internal chemical modification of organism mRNA and participates in various biological processes in cancers. Studies have shown that m6A can be cleared by ALKBH5 (alkB homolog 5), indicating that it may play important functions. Therefore, we intend to conduct a comprehensive analysis of ALKBH5 from a pan-cancer perspective to clarify its role in cancers. Methods: Differently expression of ALKBH5 was performed by ‘edger’ package. Cox Univariate and log-rank analysis were used to evaluate the prognosis of ALKBH5. The correlation between ALKBH5 expression and immune cell infiltration, tumor microenvironment, copy number variations, tumor mutational burden, neoantigen, homologous recombination deficiency and microsatellite instability, methyltransferases and stemness scores were analyzed respectively via Pearson or Spearman analysis. ESTIMATE, stromal and immune scores were evaluated through ‘ESTIMATE’ package and tumor mutational burden was calculated by ‘maftools’ package.Results: We found that ALKBH5 was differentially expressed and important for prognosis in some cancers. Also, we found that the expression of ALKBH5 had a significant correlation with immune cell infiltration, tumor microenvironment, copy number variations, tumor mutational burden, neoantigen, homologous recombination deficiency and microsatellite instability in various common cancers. Further, the ALKBH5 expression significantly correlated with the expression of methyltransferases and stemness scores in various cancers.Conclusions: Our research showed that ALKBH5 plays a pivotal role in several cancers and can be a novel immunological and prognostic biomarker, indicating its role as a target of immunotherapy.
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