166 pubs · 9,479 cites · h-index 41
Randomized trial finds combined intervention improves cognitive function in frail older adults, suggesting effective strategies are needed.
Demonstrates efficient optical properties in engineered perovskite quantum dots, highlighting their potential in bioimaging applications.
BACKGROUND: Despite advancements in multimodal therapy, glioma remains a lethal brain tumor with limited prognostic biomarkers. Programmed cell death (PCD) pathways and long non-coding RNAs (lncRNAs) are emerging as therapeutic targets, but their combined prognostic potential in glioma remains underexplored. METHODS: RNA sequencing data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) cohorts were analyzed to identify PCD-related lncRNAs. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression and multivariate Cox proportional hazards regression analyses were applied to construct a prognostic signature, with external validation performed in an independent cohort. Tumor immune microenvironment characterization was subsequently conducted through the Tumor IMmune Estimation Resource (TIMER) database using the inverse fold product algorithm, which quantified six tumor-infiltrating immune cells (TIIC) subtypes across 10,897 pan-cancer samples. Immune checkpoint differential expression between risk strata was assessed via single-sample gene set enrichment analysis (ssGSEA). Drug sensitivity prediction was performed using the Cancer Genome Project (GCP) databases. RESULTS: A 4-lncRNA signature effectively stratified patients into high-risk and low-risk groups. The prognosis of the high-risk group is worse. In multivariate analysis, a risk score can independently predict the prognosis and has a robust prediction efficiency in the CGGA external verification set. The infiltration of immunosuppressive cells, such as M2 macrophages, increased the expression of immune checkpoints, such as PD-L1, increased, and the infiltration of CD8 + T cells decreased in high-risk patients. Computational screening identified elesclomol as a potential therapeutic agent showing subtype-specific efficacy. CONCLUSIONS: This study highlights the prognostic significance of lncRNAs associated with PCD in glioma and provides computational evidence for their potential as therapeutic targets. While the results suggest novel avenues for treatment development, they must be interpreted cautiously due to the lack of experimental validation. Future studies should aim to validate these results through controlled clinical trials and explore underlying molecular mechanisms.
Review highlights potential influence of fermented foods on colorectal cancer through diet and microorganisms.
Prosthetic loosening represents a catastrophic postoperative complication in artificial joint replacement, resulting in severe patient morbidity and substantial healthcare costs. This investigation aimed to develop a novel strategy for preventing prosthetic loosening. Two-dimensional MXene V 2 C nanosheets were synthesized and subsequently immobilized onto three-dimensional porous sulfonated polyetheretherketone (SPEEK) surfaces with polydopamine (PDA) to form V 2 C-PDA@SPEEK (Abbrev. V 2 C-PS). The biocompatibility was systematically evaluated using rat bone marrow mesenchymal stem cells (rBMSCs) and murine models. The osteogenic differentiation potential of V 2 C-PS was assessed through real-time PCR analysis, Alkaline phosphatase (ALP) staining, and Alizarin Red staining. The in vivo osteogenic capacity of V 2 C-PS surrounding the implant material was evaluated in rat femoral models using micro-CT analysis, biomechanical pull-out testing, sequential fluorescent labeling of newly formed bone, and Van Gieson staining. The molecular mechanisms underlying V 2 C-PS -mediated osteogenic differentiation of rBMSCs were investigated both in vitro and in vivo using chemical inhibitors, β-catenin shRNA lentiviral silencing, and β-catenin mRNA lentiviral overexpression. The results demonstrated that V 2 C-PS exhibited excellent biocompatibility. Quantitative analysis revealed substantial upregulation (p<0.05) of critical osteogenic markers, including RUNX2 (4.4-fold), COL-1 (5.7-fold), OCN (3.3-fold), BMP-2 (4.4-fold), OPN (3.1-fold), BSP (3.3-fold), ON (4.3-fold), and OSX (2.83-fold), in the 25V 2 C-PS treatment group compared to PS group. The bone parameters were also remarkably enhanced in the 25V 2 C-PS group (BMD increased by 241 %, bone-implant contact by 159 %, BV/TV by 225 %, Tb.N by 281 %, Tb.Th by 214 %, maximum pull-out force by 250 %, and Tp.Sp decreased by 33 %). Furthermore, V 2 C-PS were found to enhance rBMSC osteogenic differentiation through activation of the Wnt/β-catenin signaling pathway. This study presents a promising approach for preventing orthopedic prosthetic loosening and demonstrates significant potential for clinical translation.
Background Alzheimer’s disease (AD) is a common neurodegenerative disorder affecting older adults, characterized by progressive cognitive decline and pathological features such as amyloid plaque deposition, neuronal loss, and synaptic reduction. RNA N6-methyladenosine (m 6 A) methylation is prevalent in the brain and is intricately linked to synaptic plasticity, learning, and memory in AD. However, the precise mechanisms underlying these associations remain elusive. Methods This study employed the overexpression of methyltransferase-like protein 16 (METTL16), or overexpression of methionine adenosyltransferase 2A (MAT2A), or a combination of METTL16 overexpression with MAT2A knockdown to explore the influence of METTL16 on the regulation of MAT2A in cognitive function, hippocampal synaptic plasticity, and amyloid-beta (Aβ 1–42 ) metabolism in 5 × FAD mice. Results Our findings indicated a reduction in m 6 A methylation levels and the expression of METTL16 and MAT2A in the hippocampus of 5 × FAD mice. Overexpression of METTL16 led to an increase in overall m 6 A methylation levels, furthermore, overexpression of either METTL16 or MAT2A enhanced learning and memory in 5 × FAD mice, elevated the expression levels of postsynaptic density 95 (PSD95) and synaptophysin (Syp), increased dendritic spine density, and decreased the accumulation of Aβ 1–42 in the hippocampus. In the hippocampus of 5 × FAD mice, METTL16 was found to upregulate both the protein and mRNA levels of MAT2A, as well as enhance MAT2A mRNA m 6 A methylation levels. Concurrent, overexpression of METTL16 and knockdown of MAT2A in the hippocampus resulted in impaired learning and memory in 5 × FAD mice, alongside a reduction in synaptic protein expression and dendritic spine density, and an increase in Aβ 1–42 accumulation. Conclusion The present study demonstrated that METTL16 enhances learning and memory in 5 × FAD mice by regulating MAT2A mRNA m 6 A methylation, which leads to increased expression levels of PSD95 and Syp, greater dendritic spine density, and reduced Aβ 1–42 accumulation in the hippocampus. These findings reveal a novel approach for investigating the pathophysiological role of METTL16 in AD and offer new insights for developing of potential therapeutic targets for AD.
Epithelial ovarian cancer (EOC) is a gynecological tumor with high mortality. Despite aggressive treatment, survival rates for patients with advanced EOC are low, and more effective methods of diagnosis and treatment are urgently needed. Inflammation and cancer are strongly associated; however, the mechanisms that mediate this relationship are not fully understood. In this study, we found that the expression of interleukin-1β (IL-1β), a proinflammatory cytokine, increased in an ovarian cancer tissue microarray (TMA) and inhibited A2780 and SKOV3 cell viability and metastasis. Recombinant IL-1β protein and the overexpression of IL-1β decreased the proliferation and metastasis of ovarian cancer cells. IL-1β deficiency promoted proliferation and metastasis. Moreover, transcriptome sequencing revealed that IL-1β downregulates the expression of matrix metalloproteinase 12 (MMP12). The signaling pathway involving MAPK/AP-1/MMP12 is involved in IL-1β-regulated ovarian cancer progression. Overall, we found that the proinflammatory cytokine IL-1β inhibits ovarian cancer cell viability and metastasis. These findings provided deeper insights into inflammation and cancer progression.
To develop a health education program for home enteral nutrition (HEN) after Esophageal cancer (EC) surgery based on Delphi method, providing reference opinions for clinical nursing education and patient home care. The health education program for HEN after EC surgery was constructed through literature research, theoretical analysis and group discussion. From February to June 2024, experts in clinical nursing, clinical medicine, and nutrition of EC were invited to conduct 2 rounds of Delphi expert consultation to initially determine the items of the program. The weight and assignment of each items were determined through analytic hierarchy process (AHP), and then the final health education program for HEN after EC surgery was established. The authoritative coefficients of the 2 rounds consulting experts were 0.918 and 0.929 and the positive coefficients were 100% and 95%, respectively; The mean range of importance assignment for the second round of consultation indicators was 4.26 to 5.00 points, with a full score range of 40.90% to 95.45%. The mean harmony coefficients for expert opinions from 2 rounds were 0.206 and 0.218 (P < .01), respectively. The final health education program for postoperative HEN in EC includes 6 primary items, 27 secondary items, and 18 tertiary items. The results of the AHP showed that the consistency coefficients (CR values) of each matrix for the tertiary items were all < 0.1, meeting the requirements of consistency testing. The constructed health education program for postoperative HEN patients with EC in this study has high scientific and practical value, and can provide reference for the health education of postoperative HEN patients with EC.
BACKGROUND: Angiogenesis is indispensable for the sustained survival and progression of both embryonic development and tumorigenesis. This intricate process is tightly regulated by a multitude of pro-angiogenic genes. The presence of gene modules facilitating angiogenesis has been substantiated in both embryonic development and the context of tumor proliferation. However, it remains unresolved whether the pro-angiogenic gene modules expressed during embryonic development also exist in tumors. METHODS: This study performed a pan-cancer single-cell RNA sequencing (scRNA-seq) analysis on samples from 332 patients across seven cancer types: thyroid carcinoma, lung cancer, breast cancer, hepatocellular carcinoma, colorectal cancer, ovarian carcinoma, and prostate adenocarcinoma. Data processing was carried out using the Seurat R package, with rigorous quality control to filter high-quality cells and mitigate batch effects across datasets. We used principal component analysis (PCA), shared nearest neighbor graph-based clustering, and Uniform Manifold Approximation and Projection (UMAP) to visualize cell types and identify distinct cell clusters. Myeloid cell subpopulations were further analyzed for the expression of embryonic pro-angiogenic gene modules (EPGM) and tumor pro-angiogenic gene modules (TPGM). RESULTS: The analysis identified nine major cell types within the tumor microenvironment, with myeloid cells consistently exhibiting elevated expression of both tumor pro-angiogenic gene modules (TPGM) and EPGM across all tumor types. In particular, myeloid cells, including macrophages and monocytes, showed high EPGM expression, indicating an active role of embryonic pro-angiogenesis pathways in tumors. A subset analysis revealed 20 distinct myeloid subtypes with varying EPGM and TPGM expression across different cancers. Treatment and disease stage influenced these gene expressions, with certain subtypes, such as HSPAhi/STAT1+ macrophages in breast cancer, displaying reduced pro-angiogenic gene activity post-treatment. CONCLUSION: This study provides evidence that tumors may exploit EPGM to enhance vascularization and support sustained growth, as evidenced by the elevated EPGM expression in tumor-associated myeloid cells. The consistent presence of EPGM in TAMs across multiple cancer types suggests a conserved mechanism wherein tumors harness embryonic angiogenic pathways to facilitate their progression. Distinct EPGM expression patterns in specific myeloid cell subsets indicate potential therapeutic targets, particularly in cases where EPGM activation contributes to resistance against anti-angiogenic therapies. These findings shed new light on the molecular mechanisms underlying tumor angiogenesis and highlight the prognostic relevance of EPGM expression in cancer, underscoring its potential as a biomarker for clinical applications.
Ovarian cancer (OC) is known for its high mortality rate. Although sodium citrate has anti-tumor effects in various cancers, its effect and mechanism in OC remain unclear. To analyze the inhibitory effect of sodium citrate on ovarian cancer cells and the underlying mechanism. Cell apoptosis was examined by TUNEL staining, flow cytometry and ferroptosis was examined intracellular Fe2+, MDA, LPO assays respectively. Cell metabolism was examined by OCR and ECAR measurements. Immunoblotting and immunoprecipitation were used to elucidate the mechanism. This study suggested that sodium citrate not only promoted ovarian cancer cell apoptosis but also triggered ferroptosis, manifested as elevated levels of Fe2+, LPO, MDA and lipid ROS production. On one hand, sodium citrate treatment led to a decrease of Ca2+ content in the cytosol by chelating Ca2+, which further inhibited the Ca2+/CAMKK2/AKT/mTOR signaling, thereby suppressing HIF1α-dependent glycolysis pathway and inducing cell apoptosis. On the other hand, the chelation of Ca2+ by sodium citrate resulted in inactivation of CAMKK2 and AMPK, leading to increase of NCOA4-mediated ferritinophagy, causing increased intracellular Fe2+ levels. More importantly, the inhibition of Ca2+/CAMKK2/AMPK signaling pathway reduced the activity of the MCU and Ca2+ concentration within the mitochondria, resulting in an increase in mitochondrial ROS. Additionally, metabolomic analysis indicated that sodium citrate treatment significantly increased de novo lipid synthesis. Altogether, these factors contributed to ferroptosis. As expected, Ca2+ supplementation successfully reversed the cell death and decreased tumor growth induced by sodium citrate. Inspiringly, it was found that coadministration of sodium citrate increased the sensitivity of OC cells to chemo-drugs. These results revealed that the sodium citrate exerted its anti-cancer activity by inhibiting Ca2+/CAMKK2-dependent cell apoptosis and ferroptosis. Sodium citrate will hopefully serve as a prospective compound for OC treatment and for improving the efficacy of chemo-drugs.
Experimental study reveals that niche Tet acts as a non-enzymatic scaffold to sustain germline stem cells in fruit flies, indicating a conserved role in stem cell self-renewal.
Coactivator-associated arginine methyltransferase 1 (CARM1) promotes the development and metastasis of estrogen receptor alpha (ERα)-positive breast cancer. The function of CARM1 in triple-negative breast cancer (TNBC) is still unclear and requires further exploration. Here, we report that CARM1 promotes proliferation, epithelial-mesenchymal transition, and stemness in TNBC. CARM1 is upregulated in multiple cancers and its expression correlates with breast cancer progression. Genome-wide analysis of CARM1 showed that CARM1 is recruited by hypoxia-inducible factor-1 subunit alpha (HIF1A) and occupy the promoters of CDK4, Cyclin D1, β-Catenin, HIF1A, MALAT1, and SIX1 critically involved in cell cycle, HIF-1 signaling pathway, Wnt signaling pathway, VEGF signaling pathway, thereby modulating the proliferation and invasion of TNBC cells. We demonstrated that CARM1 is physically associated with and directly interacts with HIF1A. Moreover, we found that ellagic acid, an inhibitor of CARM1, can suppress the proliferation and invasion of TNBC by directly inhibiting CDK4 expression. Our research has determined the molecular basis of CARM1 carcinogenesis in TNBC and its effective natural inhibitor, which may provide new ideas and drugs for cancer therapy.
COPYRIGHT © 2023 Zhang, Liu, Bai and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Virtual reality technology in the rehabilitation of post-stroke cognitive impairment: an opinion article on recent findings
N 6 -methyladenosine (m 6 A) RNA modification controls numerous cellular processes. To what extent these post-transcriptional regulatory mechanisms play a role in hematopoiesis has not been fully elucidated. We here show that the m 6 A demethylase alkB homolog 5 (ALKBH5) controls mitochondrial ATP production and modulates hematopoietic stem and progenitor cell (HSPC) fitness in an m 6 A-dependent manner. Loss of ALKBH5 results in increased RNA methylation and instability of oxoglutarate-dehydrogenase ( Ogdh ) messenger RNA and reduction of OGDH protein levels. Limited OGDH availability slows the tricarboxylic acid (TCA) cycle with accumulation of α-ketoglutarate (α-KG) and conversion of α-KG into L-2-hydroxyglutarate (L-2-HG). L-2-HG inhibits energy production in both murine and human hematopoietic cells in vitro . Impaired mitochondrial energy production confers competitive disadvantage to HSPCs and limits clonogenicity of Mll-AF9 -induced leukemia. Our study uncovers a mechanism whereby the RNA m 6 A demethylase ALKBH5 regulates the stability of metabolic enzyme transcripts, thereby controlling energy metabolism in hematopoiesis and leukemia.
BACKGROUND: Proteins containing the Jumonji C (JmjC) domain participated in tumorigenesis and cancer progression. However, the mechanisms underlying this effect are still poorly understood. Our objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2 (JARID2) - a JmjC family protein - in breast cancer, as well as its latent association with obesity. METHODS: Immunohistochemistry, The Cancer Genome Atlas, Gene Expression Omnibus, and other databases were used to analyze the expression of JARID2 in breast cancer cells. Growth curve, 5-ethynyl-2-deoxyuridine (EdU), colony formation, and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and invasion. Spheroidization-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer stemness. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 participates. Immunoaffinity purification and silver staining mass spectrometry were conducted to search for proteins that might interact with JARID2. The results were further verified using co-immunoprecipitation and glutathione S-transferase (GST) pull-down experiments. Using chromatin immunoprecipitation (ChIP) sequencing, we sought the target genes that JARID2 and metastasis-associated protein 1 (MTA1) jointly regulated; the results were validated by ChIP-PCR, quantitative ChIP (qChIP) and ChIP-reChIP assays. A coculture experiment was used to explore the interactions between breast cancer cells and adipocytes. RESULTS: In this study, we found that JARID2 was highly expressed in multiple types of cancer including breast cancer. JARID2 promoted glycolysis, lipid metabolism, proliferation, invasion, and stemness of breast cancer cells. Furthermore, JARID2 physically interacted with the nucleosome remodeling and deacetylase (NuRD) complex, transcriptionally repressing a series of tumor suppressor genes such as BRCA2 DNA repair associated (BRCA2), RB transcriptional corepressor 1 (RB1), and inositol polyphosphate-4-phosphatase type II B (INPP4B). Additionally, JARID2 expression was regulated by the obesity-associated adipokine leptin via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in the breast cancer microenvironment. Analysis of various online databases also indicated that JARID2/MTA1 was associated with a poor prognosis of breast cancer. CONCLUSION: Our data indicated that JARID2 promoted breast tumorigenesis and development, confirming JARID2 as a target for cancer treatment.
BACKGROUND: The discovery of new anti-melanoma drugs with low side effect is urgently required in the clinic. Recent studies showed that morusin, a flavonoid compound isolated from the root bark of Morus Alba, has the potential to treat multiple types of cancers, including breast cancer, gastric cancer, and prostate cancer. However, the anti-cancer effect of morusin on melanoma cells has not been investigated. METHODS: We analyzed the effects of morusin on the proliferation, cell cycle, apoptosis, cell migration and invasion ability of melanoma cells A375 and MV3, and further explored the effects of morusin on tumor formation of melanoma cell. Finally, the effects of morusin on the proliferation, cycle, apoptosis, migration and invasion of A375 cells after knockdown of p53 were detected. RESULTS: Morusin effectively inhibits the proliferation of melanoma cells and induces cell cycle arrest in the G2/M phase. Consistently, CyclinB1 and CDK1 that involved in the G2/M phase transition were down-regulated upon morusin treatment, which may be caused by the up-regulation of p53 and p21. In addition, morusin induces cell apoptosis and inhibits migration of melanoma cells, which correlated with the changes in the expression of the associated molecules including PARP, Caspase3, E-Cadherin and Vimentin. Moreover, morusin inhibits tumor growth in vivo with little side effect on the tumor-burden mice. Finally, p53 knockdown partially reversed morusin-mediated cell proliferation inhibition, cell cycle arrest, apoptosis, and metastasis. CONCLUSION: Collectively, our study expanded the spectrum of the anti-cancer activity of morusin and guaranteed the clinical use of the drug for melanoma treatment.
Background: Osteosarcoma is a malignant bone tumor with a high rate of lung metastasis and mortality. It has been demonstrated that resveratrol can inhibit tumor proliferation and metastasis, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare folate-modified liposomes loaded with resveratrol to investigate its anti-osteosarcoma effect in vitro and in vivo. Methods: We prepared and characterized resveratrol liposomes modified with folate (denoted as, FA-Res/Lps). The effects of FA-Res/Lps on human osteosarcoma cell 143B proliferation, apoptosis, and migration were investigated by MTT, cell cloning, wound-healing assay, transwell, and flow cytometry. A xenograft tumor and lung metastasis model of osteosarcoma was constructed to study the therapeutic effects of FA-Res/Lps on the growth and metastasis of osteosarcoma in vivo. Results: The FA-Res/Lps were prepared with a particle size of 118.5 ± 0.71 and a small dispersion coefficient of 0.154 ± 0.005. We found that FA-modified liposomes significantly increased resveratrol uptake by osteosarcoma cells 143B in flow cytometric assay, resulting in FA-Res/Lps, which inhibit tumor proliferation, migration and induce apoptosis more effectively than free Res and Res/Lps. The mechanism of action may be associated with the inhibition of JAK2/STAT3 signaling. In vivo imaging demonstrated that FA-modified DiR-modified liposomes significantly increased the distribution of drugs at the tumor site, leading to significant inhibition of osteosarcoma growth and metastasis by FA-Res/Lps. Furthermore, we found that FA-Res/Lps did not cause any adverse effects on mice body weight, liver, or kidney tissues. Conclusion: Taken together, the anti-osteosarcoma effect of resveratrol is significantly enhanced when it is loaded into FA-modified liposomes. FA-Res/Lps is a promising strategy for the treatment of osteosarcoma.
Circadian rhythms, as physiological systems with self-regulatory functions in living organisms, are controlled by core clock genes and are involved in tumor development. The protein arginine methyltransferase 6 (PRMT6) serves as an oncogene in a myriad of solid tumors, including breast cancer. Hence, the primary aim of the current study is to investigate the molecular mechanisms by which the PRMT6 complex promotes breast cancer progression. The results show that PRMT6, poly(ADP-ribose) polymerase 1 (PARP1), and the cullin 4 B (CUL4B)-Ring E3 ligase (CRL4B) complex interact to form a transcription-repressive complex that co-occupies the core clock gene PER3 promoter. Moreover, genome-wide analysis of PRMT6/PARP1/CUL4B targets identifies a cohort of genes that is principally involved in circadian rhythms. This transcriptional-repression complex promotes the proliferation and metastasis of breast cancer by interfering with circadian rhythm oscillation. Meanwhile, the PARP1 inhibitor Olaparib enhances clock gene expression, thus, reducing breast carcinogenesis, indicating that PARP1 inhibitors have potential antitumor effects in high-PRMT6 expression breast cancer.
Frailty causes emerging global health burden due to its high prevalence and mortality. In this study, we used Mendelian randomization (MR) approach to examine the potential causal relationship between smoking and frailty in ageing. Using inverse-variance weighted (IVW) method, genetically predicted smoking initiation was associated with an increased risk of frailty in ageing (odd ratio (OR) 1.23, 95% confidence interval (CI) 1.19–1.27, P = 3.21 × 10 –39 ). Similarly, per year increase in age of initiation of regular smoking was associated with a 25% decrease in the risk of frailty (95% CI 7–39%, P = 7.79 × 10 –3 , per year), while higher number of cigarettes per day was associated with a 12% increased risk (95% CI 4–20%, P = 1.76 × 10 –3 ). Compared with former smokers, current smokers were associated with an increased risk of frailty (OR 1.12, 95% CI 1.02–1.22, P = 0.01). Lifetime smoking was associated with a 46% higher risk of frailty (95% CI 37–56%, P = 2.63 × 10 –29 ). Sensitivity analysis using alternative MR methods yielded similar results. Our study indicates that genetic predisposition to smoking is associated with the risk of frailty in ageing. Further studies are warranted to examine the exact role of smoking in the development of frailty.