Search Results (13)

Antioxidants neutralize reactive oxygen species and free radicals, protecting cells from oxidative damage and maintaining cellular homeostasis. In cancer therapy, they play a complex dual role, serving as protective agents against oxidative stress while, under certain conditions, acting as pro-oxidants that may promote tumorigenesis and resistance to treatment. Redox regulation is governed by key antioxidant pathways, such as the BACH1 and NRF2 pathways, along with transcriptional factors that significantly affect cancer progression and immunotherapy response. In addition to their intracellular effects, antioxidants modulate the tumor microenvironment, including interactions with the extracellular matrix, which impact cancer cell behavior and therapeutic responses. This review also explores preclinical studies that investigate the roles of major antioxidants in cancer biology. While these studies present promising data, significant challenges persist, including the potential for antioxidants to interfere with standard cancer treatments or to inadvertently support tumor survival. We further highlight emerging strategies aimed at optimizing antioxidant therapy, including personalized medicine approaches, nanoparticle-based delivery systems, and combination treatments with immunotherapies and targeted therapies. By examining the therapeutic potential and associated risks of antioxidants, this review provides critical insights into their role in cancer treatment and offers a roadmap for advancing antioxidant-based strategies to improve clinical outcomes. Full article

Adipose tissue beiging refers to the process by which beige adipocytes emerge in classical white adipose tissue depots. Beige adipocytes dissipate chemical energy and secrete adipokines, such as classical brown adipocytes, to improve systemic metabolism, which is beneficial for people with obesity and metabolic diseases. Cold exposure and β3-adrenergic receptor (AR) agonist treatment are two commonly used stimuli for increasing beige adipocytes in mice; however, their underlying biological processes are different. Transcriptional analysis of inguinal white adipose tissue (iWAT) has revealed that changes in extracellular matrix (ECM) pathway genes are specific to cold exposure. Hyaluronic acid (HA), a non-sulfated linear polysaccharide produced by nearly all cells, is one of the most common components of ECM. We found that cold exposure significantly increased iWAT HA levels, whereas the β3-AR agonist CL316,243 did not. Increasing HA levels in iWAT by Has2 overexpression significantly increases cold-induced adipose tissue beiging; in contrast, decreasing HA by Spam1 overexpression, which encodes a hyaluronidase that digests HA, significantly decreases cold-induced iWAT beiging. All these data implicate a role of HA in promoting adipose tissue beiging, which is unique to cold exposure. Given the failure of β3-AR agonists in clinical trials for obesity and metabolic diseases, increasing HA could serve as a new approach for recruiting more beige adipocytes to combat metabolic diseases. Full article

Heat stress, as a negative factor, severely threatens the quality and production of bottle gourd, which prefers to grow in a warm environment. To understand which genes are involved in the resistance to heat stress in bottle gourd (Lagenaria siceraria (Mol.) Standl.), we analyzed the characteristics of two genetic bottle gourd varieties, “Mei feng”-MF (heat resistant) and “Lv long”-LL (heat sensitive). Under heat stress, MF plants exhibited a higher survival rate, lower relative electrolytic leakage, and decreased stomatal aperture compared with LL. In addition, RNA-Seq was carried out on the two varieties under normal conditions and heat stress. The results revealed a total of 1485 up-regulated and 946 down-regulated genes under normal conditions, while 602 genes were up-regulated and 1212 genes were down-regulated under heat stress. Among these genes, several differentially expressed genes (DEGs) involved in the MAPK (mitogen-activated protein kinase) signaling pathway and members of bHLH (basic helix-loop-helix) transcription factors showed significant up- or down-regulation after heat stress. Next, to validate these findings, we conducted quantitative real-time PCR (qRT-PCR) analysis, which confirmed the expression patterns of the genes detected through RNA-Seq. Collectively, the DEGs between the two contrasting cultivars identified in our study provide novel insight into excavating helpful candidate genes associated with heat tolerance in bottle gourd. Full article

Bile acids serve a vital function in lipid digestion and absorption; however, their accumulation can precipitate liver damage. In our study, we probed the effects of dimethyl sulfoxide (DMSO) on bile acid synthesis and the ensuing liver damage in mice induced by bile acids. Our findings indicate that DMSO efficaciously curbs bile acid synthesis by inhibiting key enzymes involved in the biosynthetic pathway, both in cultured primary hepatocytes and in vivo. Contrarily, we observed that DMSO treatment did not confer protection against bile-acid-induced liver damage in two distinct mouse models: one induced by a 0.1% DDC diet, leading to bile duct obstruction, and another induced by a CDA-HFD, resulting in non-alcoholic steatohepatitis (NASH). Histopathological and biochemical analyses unveiled a comparable extent of liver injury and fibrosis levels in DMSO-treated mice, characterized by similar levels of increase in Col1a1 and Acta2 expression and equivalent total liver collagen levels. These results suggest that, while DMSO can promptly inhibit bile acid synthesis in healthy mice, compensatory mechanisms might rapidly override this effect, negating any protective impact against bile-acid-induced liver damage in mice. Through these findings, our study underscores the need to reconsider treating DMSO as a mere inert solvent and prompts further exploration to identify more effective therapeutic strategies for the prevention and treatment of bile-acid-associated liver diseases. Full article

Background: Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are longer than 200 nucleotides and were initially believed to lack encoding capability. However, recent research has found open reading frames (ORFs) within lncRNAs, suggesting that they may have coding capacity. Despite this discovery, the mechanisms by which lncRNA-encoded products are involved in cancer are not well understood. The current study aims to investigate whether lncRNA HCP5-encoded products promote triple-negative breast cancer (TNBC) by regulating ferroptosis. Methods: We used bioinformatics to predict the coding capacity of lncRNA HCP5 and conducted molecular biology experiments and a xenograft assay in nude mice to investigate the mechanism of its encoded products. We also evaluated the expression of the HCP5-encoded products in a breast cancer tissue microarray. Results: Our analysis revealed that the ORF in lncRNA HCP5 can encode a protein with 132-amino acid (aa), which we named HCP5-132aa. Further experiments showed that HCP5-132aa promotes TNBC growth by regulating GPX4 expression and lipid ROS level through the ferroptosis pathway. Additionally, we found that the breast cancer patients with high levels of HCP5-132aa have poorer prognosis. Conclusions: Our study suggests that overexpression of lncRNA HCP5-encoded protein is a critical oncogenic event in TNBC, as it regulates ferroptosis. These findings could provide new therapeutic targets for the treatment of TNBC. Full article

This study aimed to construct an effective nomogram based on the clinical and oxidative stress-related characteristics to predict the prognosis of stage I lung adenocarcinoma (LUAD). A retrospective study was performed on 955 eligible patients with stage I LUAD after surgery at our hospital. The relationship between systematic-oxidative-stress biomarkers and the prognosis was analyzed. The systematic oxidative stress score (SOS) was established based on three biochemical indicators, including serum creatinine (CRE), lactate dehydrogenase (LDH), and uric acid (UA). SOS was an independent prognostic factor for stage I LUADs, and the nomogram based on SOS and clinical characteristics could accurately predict the prognosis of these patients. The nomogram had a high concordance index (C-index) (0.684, 95% CI, 0.656–0.712), and the calibration curves for recurrence-free survival (RFS) probabilities showed a strong agreement between the nomogram prediction and actual observation. Additionally, the patients were divided into two groups according to the cut-off value of risk points based on the nomogram, and a significant difference in RFS was observed between the high-risk and low-risk groups (p < 0.0001). SOS is an independent prognostic indicator for stage I LUAD. These things considered, the constructed nomogram based on SOS could accurately predict the survival of those patients. Full article

The eighth TNM staging system proposal classifies lung cancer with partial or complete atelectasis/obstructive pneumonia into the T2 category. We aimed to develop nomograms to predict the possibility of lymph node metastasis (LNM) and the prognosis for NSCLC based on atelectasis and obstructive pneumonitis. Methods: NSCLC patients over 20 years old diagnosed between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The nomograms were based on risk factors that were identified by Logistic regression. The area under the receiver operating characteristic (ROC) curve (AUC) was performed to confirm the predictive values of our nomograms. Cox proportional hazards analysis and Kaplan–Meier survival analysis were also used in this study. Results: A total of 470,283 patients were enrolled. Atelectasis/obstructive pneumonitis, age, gender, race, histologic types, grade, and tumor size were defined as independent predictive factors; then, these seven factors were integrated to establish nomograms of LNM. The AUC is 0.70 (95% CI: 0.694–0.704). Moreover, the Cox proportional hazards analysis and Kaplan–Meier survival analysis showed that the scores derived from the nomograms were significantly correlated with the survival of pathological N0 classification. Conclusion: Nomograms based on atelectasis/obstructive pneumonitis were developed and validated to predict LNM and the postoperative prognosis of NSCLC. Full article

Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD⁺, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept. Full article

Fusarium wilt results in undesirable effects on the quality and production of chieh-qua (Benincasa hispida Cogn. var. Chieh-qua How). Fusaric acid (FA), a secondary metabolite of biotin produced by pathogens of genus Fusarium, induced resistant responses in chieh-qua; however, the physiological and molecular mechanism(s) of FA resistance remains largely unknown. In our study, ‘A39’ (FA-resistant cultivar) exhibited decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) enzyme activity when exposed to FA compared with ‘H5’ (FA-susceptible cultivar). More apoptosis cells existed in ‘H5’ than ‘A39’ after 2 days of FA treatment. RNA-seq results revealed that a total of 2968 and 3931 differentially expressed genes (DEGs) were detected under normal conditions (1562 up-regulated and 1406 down-regulated) and FA treatment (2243 up-regulated and 1688 down-regulated), respectively. Interestingly, DEGs associated with pathogen-related protein and ethylene (ET) biosynthesis and signal pathways were most significantly changed during FA stress. Notably, several crucial genes encoding pathogenesis-related protein (CL4451.Contig2, CL2175.Contig4), peroxidase (Unigene49615 and CL11695.Contig2), and ET-responsive transcription factors (TFs) (CL9320.Contig1, CL9849.Contig3, CL6826.Contig2, CL919. Contig6, and CL518.Contig7) were specifically induced after FA treatment. Collectively, the study provides molecular data for isolating candidate genes involved in FA resistance, especially ET related genes in chieh-qua. Full article

To cope with the increasingly complex electromagnetic environment, multistatic radar systems, especially the passive multistatic radar, are becoming a trend of future radar development due to their advantages in anti-electronic jam, anti-destruction properties, and no electromagnetic pollution. However, one problem with this multi-source network is that it brings a huge amount of information and leads to considerable computational load. Aiming at the problem, this paper introduces the idea of selecting external illuminators in the multistatic passive radar system. Its essence is to optimize the configuration of multistatic T/R pairs. Based on this, this paper respectively proposes two multi-source optimization algorithms from the perspective of resolution unit and resolution capability, the Covariance Matrix Fusion Method and Convex Hull Optimization Method, and then uses a Global Navigation Satellite System (GNSS) as an external illuminator to verify the algorithms. The experimental results show that the two optimization methods significantly improve the accuracy of multistatic positioning, and obtain a more reasonable use of system resources. To evaluate the algorithm performance under large number of transmitting/receiving stations, further simulation was conducted, in which a combination of the two algorithms were applied and the combined algorithm has shown its effectiveness in minimize the computational load and retain the target localization precision at the same time. Full article

Underwater object identification by optical sensors is usually difficult in turbid or dark environments. The objective of this paper was to identify different underwater materials using active electrolocation technology. We proposed a bionic sensor inspired by the weakly electric fish. The material identification was completed by analyzing electric signal images, since the electric signal changes when different materials are identified. Firstly, the effective lift-off distance for identification was researched. The materials used in this paper can be effectively identified by the sensor at a lift-off distance of 10 mm. Furthermore, the performance of the sensor for identifying and locating was studied in the presence of multiple materials. The results indicated that the sensor can effectively identify and locate the objects when the distance between objects is greater than 30 mm, while the location error is less than 5% in most cases. Our research proves that the bionic sensor we made can effectively recognize different materials underwater in short-range, which is about 10 mm. Therefore, we expect that the bionic sensor we made can be utilized as a useful tool for underwater object identification. Full article

Temperature rising caused by global warming has imposed significant negative effects on crop qualities and yields. To get the well-known molecular mechanism upon the higher temperature, we carefully analyzed the RNA sequencing-based transcriptomic responses of two contrasting chieh-qua genotypes: A39 (heat-tolerant) and H5 (heat-sensitive). In this study, twelve cDNA libraries generated from A39 and H5 were performed with a transcriptome assay under normal and heat stress conditions, respectively. A total of 8705 differentially expressed genes (DEGs) were detected under normal conditions (3676 up-regulated and 5029 down-regulated) and 1505 genes under heat stress (914 up-regulated and 591 down-regulated), respectively. A significant positive correlation between RNA-Seq data and qRT-PCR results was identified. DEGs related to heat shock proteins (HSPs), ubiquitin-protein ligase, transcriptional factors, and pentatricopeptide repeat-containing proteins were significantly changed after heat stress. Several genes, which encoded HSPs (CL2311.Contig3 and CL6612.Contig2), cytochrome P450 (CL4517.Contig4 and CL683.Contig7), and bHLH TFs (CL914.Contig2 and CL8321.Contig1) were specifically induced after four days of heat stress. DEGs detected in our study between these two contrasting cultivars would provide a novel basis for isolating useful candidate genes of heat stress responses in chieh-qua. Full article

Drought stress is one of the most serious threats to cucumber quality and yield. To gain a good understanding of the molecular mechanism upon water deficiency, we compared and analyzed the RNA sequencing-based transcriptomic responses of two contrasting cucumber genotypes, L-9 (drought-tolerant) and A-16 (drought-sensitive). In our present study, combining the analysis of phenotype, twelve samples of cucumber were carried out a transcriptomic profile by RNA-Seq under normal and water-deficiency conditions, respectively. A total of 1008 transcripts were differentially expressed under normal conditions (466 up-regulated and 542 down-regulated) and 2265 transcripts under drought stress (979 up-regulated and 1286 down-regulated). The significant positive correlation between RNA sequencing data and a qRT-PCR analysis supported the results found. Differentially expressed genes (DEGs) involved in metabolic pathway and biosynthesis of secondary metabolism were significantly changed after drought stress. Several genes, which were related to sucrose biosynthesis (Csa3G784370 and Csa3G149890) and abscisic acid (ABA) signal transduction (Csa4M361820 and Csa6M382950), were specifically induced after 4 days of drought stress. DEGs between the two contrasting cultivars identified in our study provide a novel insight into isolating helpful candidate genes for drought tolerance in cucumber. Full article