Open Life Sciences最新文献

Excessive intracellular copper accumulation triggers cuproptosis, a novel regulated cell death process with therapeutic potential. Analyzing 566 The Cancer Genome Atlas samples alongside lung adenocarcinoma (LUAD)-specific microarray and single-cell sequencing data, we identified 109 cuproptosis-associated genes, of which C1QBP and PFKP emerged as key prognostic markers. Four-gene risk model stratified patients into high- and low-risk groups with distinct survival outcomes, where high-risk scores correlated with advanced TNM stages. Clinical validation confirmed that elevated C1QBP/PFKP expression in LUAD tissues predicted shorter progression-free survival. Functional assays demonstrated that silencing C1QBP or PFKP increased intracellular copper concentration, suppressed proliferation, and inhibited invasion, mechanistically linking these genes to cuproptosis dysregulation. Our findings nominate C1QBP/PFKP as actionable targets for LUAD therapy, offering both prognostic biomarkers and copper-metabolism-directed treatment strategies.

Cell proliferation and epithelial-mesenchymal transition (EMT) are two common tumor phenotypes closely linked to malignant tumor progression. Genes regulating tumor progression often exhibit consistent regulatory trends in these phenotypes; however, certain genes may display inconsistent regulatory patterns in tumor proliferation and EMT. In this investigation, initial transcriptomic and tumor database analyses revealed that alcohol dehydrogenase 5 (ADH5) is downregulated in non-small cell lung cancer (NSCLC) tissues and correlates negatively with NSCLC prognosis. Subsequent experimental manipulation of ADH5 levels in tumor cells demonstrated that ADH5 overexpression decreased proliferation while enhancing migration and invasion capacities in NSCLC cells. Moreover, ADH5 overexpression hindered xenograft tumor growth in nude mice. However, ADH5 knockdown yielded contrasting outcomes by stimulating NSCLC cell proliferation while impeding migration and invasion abilities. Notably, ADH5 overexpression triggered EMT through Smad2/Smad3 activation, leading to the upregulation of SRY-Box Transcription Factor 9. TGFbetaR1/ALK5 inhibitor SB431542 was able to alleviate the effects of ADH5 overexpression on NSCLC cells. This study indicates a critical role of ADH5 in tumors associated with cancer cell growth inhibition but EMT activation. These findings underscore ADH5 as a potential regulator of NSCLC cell plasticity, emphasizing its promise as a therapeutic target for NSCLC management.

Clove, Syzygium aromaticum, is a medicinal plant from the Myrtaceae family with various applications in traditional medicine. The plant has been studied for its analgesic, anti-inflammatory, antiviral, and anticancer properties. This study focuses on the green synthesis of silver nanoparticles using clove leaf extract. The synthesized NPs were characterized using chemical methods and their anticancer activity was tested against a leukemia cell line, along with the signaling pathway that followed. The AgNPs were synthesized in a spherical shape and were less than 50 nm in size. The cytotoxic effects of the AgNPs on PCS-800-011 primary peripheral blood mononuclear cells and 32D-FLT3-ITD leukemia cells were evaluated over 48 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cancer cells showed reduced viability with an IC₅₀ value of 162 µg/mL after exposure to the AgNPs. Through a detailed examination of the mTOR pathway, it was observed that AgNPs can alter the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, affecting 32D-FLT3-ITD cell growth and death. This pathway may contribute to the inhibition of the cell cycle and induction of apoptosis by AgNPs. For this reason, AgNPs may be used as a natural anti-cancer treatment for leukemia.

Pathogenic co-infections in plants significantly impact microbial diversity and disease outcomes, yet their effects on microbial community structure and ecological processes remain unclear. Tobacco plants were co-infected with Ralstonia solanacearum and Neocosmospora falciformis. 16S ribosomal RNA and internal transcribed spacer amplicon sequencing were used to assess bacterial and fungal communities, respectively, in infected tobacco stems. The results were compared between co-infected and healthy control tobacco plants to assess the effects of infection. Co-infection reduced microbial diversity and shifted community structure, promoting ecological specialization. Network analysis revealed synergistic interactions between the pathogens, enhancing virulence through positive correlations with certain microbial taxa. Conversely, some taxa exhibited antagonistic effects, potentially limiting pathogen proliferation. Deterministic processes were found to dominate microbial community assembly under infection conditions, significantly reshaping the microbial landscape compared to healthy control plants. This study highlights the profound effects of co-infection on microbial diversity, community composition, microbial interactions, and community assembly processes in tobacco plants. These findings provide valuable insights for developing more targeted plant disease management strategies by manipulating microbial communities.

Atmospheric nitrogen (N) deposition is recognized as a pivotal nutrient input in forest ecosystems. However, significant gaps persist in our comprehension of the global-scale fate of N in forest ecosystems. In a pioneering effort, this study analyzed the fluxes and determinants of deposited N by 234 observations from 52 published articles. Our findings indicated that plant uptake, soil retention, and N losses, respectively, accounted for 27.4, 57.9, and 14.6% of the total deposited N. The fate of deposited N was significantly influenced by a suite of factors, including forest type, climatic parameters such as mean annual temperature (MAT) and precipitation (MAP), edaphic characteristics such as soil pH and the carbon to nitrogen ratio (C/N), and experimental factors like nitrogen addition rate (NR), nitrogen forms (NF), plot size (PS) for ¹⁵N studies, and the duration of study. For the uptake of deposited N, MAP emerged as the predominant positive factors, whereas NR was the dominant negative factors; for deposited N soil retention, NR was the key positive factors, while MAT was the key negative factors; for N losses, MAP was the predominant positive factors, with the C/N ratio serving as a significant negative factor. Thus, for a given forest ecosystem with relatively stable climate and soil conditions, NR, NF, and the soil C/N were the main controlling factors regulating the fate of deposited N. These insights significantly advance our grasp of the N cycle in forest ecosystems. Consecutive monitoring of the impact of deposited N on soil N transformations and carbon sequestration is needed in future studies.

A chronic inflammatory skin disorder, psoriasis, affects 2-3% of people worldwide. A bioactive substance, glycitein (GCN), has several pharmacological characteristics. This work aims to evaluate the effects of GCN on the in vitro proliferation and death of human HaCaT keratinocytes. An in vitro model was created to simulate psoriatic features utilizing HaCaT keratinocytes activated by M5 cytokines. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide test was used to quantify cell viability, whereas the BrdU assay was used to assess the proliferation rate. Using a DCFH-DA probe and an Annexin V-FITC/propidium iodide detection kit, flow cytometry was used to examine the generation of reactive oxygen species (ROS) and apoptosis, respectively. Western blot and quantitative polymerase chain reaction were employed to determine the amounts of phosphorylated Akt (p-Akt) and Akt proteins. GCN dramatically decreased the inflammation and hyperproliferation that cytokines caused in HaCaT keratinocytes. The alteration of mitochondrial membrane potential promoted apoptosis and caused cell cycle arrest at the sub-G1 phase, which indicates apoptotic DNA fragmentation. The suppression of the PI3K/Akt signalling pathway was linked to increased intracellular ROS levels brought on by GCN therapy. These results imply that GCN reduces inflammation and keratinocyte hyperproliferation by controlling cell cycle progression and apoptosis via ROS-associated inhibition of the PI3K/Akt pathway.

Descurainia sophia (L.) Webb ex Pran known as Flixweed is recognized as an ethnomedicinal plant in Chinese traditional medicine, offering numerous therapeutic benefits. Antioxidant chemicals found in this medicinal plant protect cellular integrity from various sources of damage and may help prevent cancer. In this study, we investigated copper/nickel nanoparticles (Cu/NiBMNPs@Flixweed) that were green-mediated following principles of green chemistry, utilizing the aqueous extract of D. sophia seeds for the treatment of lung carcinoma. The effectiveness of these Cu/Ni nanoparticles' effectiveness was tested against three common human lung cancer cell lines. Methods such as X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), Fourier transform-infrared spectroscopy, and energy dispersive X-ray were used to analyze the Cu/Ni nanoparticles produced through environmentally friendly methods. The XRD pattern revealed that the crystalline structure of the generated NPs is seen in the XRD pattern. According to the FE-SEM results, the nanoparticles had an average size of 68.52 nm and a semi-spherical shape. The IC₅₀ values of Cu/NiBMNPs@Flixweed against HLC-1, LC-2/ad, and PC-14 cells were found to be 170, 98, and 57 μg/mL, respectively. The IC₅₀ values of Cu/NiBMNPs@Flixweed against 2,2-diphenyl-1-picrylhydrazyl free radicals was 30 μg/mL. Recent research indicates that Cu/NiBMNPs@Flixweed may be a promising option to assist in the treatment various types of lung cancer.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. A key pathological feature of AF is atrial fibrosis, which promotes arrhythmogenic remodeling. While myocardial fibrosis has been widely observed in AF models, the underlying molecular mechanisms driving fibrotic progression remain incompletely understood. AF rats were modeled using acetylcholine, followed by treatment with different concentrations of dapagliflozin (DAPA) or positive control amiodarone. To elucidate the role of the high-mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) pathway in AF, lipopolysaccharide (LPS; an HMGB1/RAGE pathway activator) and FPS-ZM1 (a RAGE inhibitor) were employed. Cardiac function, myocardial fibrosis, and inflammation-related proteins were assessed using echocardiography, enzyme-linked immunosorbent assay, histological staining, Western blotting, and reverse transcription quantitative polymerase chain reaction. AF rats exhibited marked cardiac dysfunction, fibrosis, and increased expression of inflammatory markers. DAPA restored cardiac function, attenuating fibrosis and inflammation. LPS aggravated cardiac injury, while DAPA attenuated the damage, with the greatest protective effects observed in the LPS + DAPA + FPS-ZM1 group. DAPA attenuates atrial fibrosis and cardiac dysfunction in AF rats by inhibiting the HMGB1/RAGE pathway. This study suggests the potential of DAPA as a therapeutic option for AF.

The Latin scientific name of turmeric is Curcuma longa L., and it belongs to the Zingiberaceae plant family. Curcumin is a yellow compound extracted from the rhizomes of turmeric, known for its various biological activities, including antioxidant, anti-inflammatory, and anticancer properties. This study presents a comprehensive review of the relationship between curcumin and the immune response in breast cancer (BC). Specific therapeutic approaches of curcumin for BC treatment are summarized. The anti-tumor activity of curcumin has garnered significant attention, with unique immunomodulatory effects on inhibiting cancer cell proliferation, inducing autophagy, affecting the cell cycle, and regulating cell apoptosis. Curcumin enhances immune cell-mediated actions against cancer cells through modulation of immune response pathways, alteration of the tumor microenvironment, and influencing immune cell function. Curcumin, via multiple pathways such as anti-inflammatory, antioxidant, apoptosis-inducing, and immunomodulatory effects, holds important clinical value in BC therapy.

The legalization of cannabis for industrial and medicinal purposes has significantly expanded worldwide. This study delves into the analgesic potential toxicity study of chloroformic extract from the Moroccan Cannabis sativa L. (C. sativa) cultivar, Khardala (KH extract). Our findings reveal that the lethal dose of KH extract is ≥5,000 mg/kg, with mice given 2,000 mg/kg exhibiting neurotoxic symptoms, including piloerection, aggressiveness, and fear, along with marked hepato-renal toxicity indicated by elevated levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and creatinine in both male and female subjects. Importantly, no toxicity was observed at 250 mg/kg and 500 mg/kg doses. Remarkably, at a dose of 500 mg/kg, the KH extract demonstrated a potent analgesic effect superior to cannabidiol (CBD), suggesting a synergistic interaction among the extract's bioactive compounds, such as CBD, cannabidivarin (CBDV), Delta 9 tetrahydrocannabinol (THC), cannabigerol (CBG), Delta 9 tetrahydrocannabivarin (THCV), and β-caryophyllene. In silico analysis supports these findings, showing the strong binding potential of THC, THCV, CBG, and CBDV to delta opioid receptors, with G-scores >-5.0 kcal/mol, highlighting the promising analgesic efficacy of this cannabis cultivar extract. This study underscores the therapeutic potential of the KH cultivar, positioning it as a promising candidate for pain management therapies.