Cell Proliferation In Response Research Articles

Deep learning-based cytoskeleton segmentation for accurate high-throughput measurement of cytoskeleton density.

Microscopic analyses of cytoskeleton organization are crucial for understanding various cellular activities, including cell proliferation and environmental responses in plants. Traditionally, assessments of cytoskeleton dynamics have been qualitative, relying on microscopy-assisted visual inspection. However, the transition to quantitative digital microscopy has introduced new technical challenges, with segmentation of cytoskeleton structures proving particularly demanding. In this study, we examined the utility of a deep learning-based segmentation method for accurate quantitative evaluation of cytoskeleton organization using confocal microscopic images of the cortical microtubules in tobacco BY-2 cells. The results showed that, although conventional methods sufficed for measurement of cytoskeleton angles and parallelness, the deep learning-based method significantly improved the accuracy of density measurements. To assess the versatility of the method, we extended our analysis to physiologically significant models in the context of changes in cytoskeleton density, namely Arabidopsis thaliana guard cells and zygotes. The deep learning-based method successfully improved the accuracy of cytoskeleton density measurements for quantitative evaluations of physiological changes in both stomatal movement in guard cells and intracellular polarization in elongating zygotes, confirming its utility in these applications. The results demonstrate the effectiveness of deep learning-based segmentation in providing precise and high-throughput measurements of cytoskeleton density, and has the potential to automate and expedite analyses of large-scale image datasets.

SNHG15 is involved in the progression of atherosclerosis through targeted regulation of miR-370-3p and bioinformatics analysis

IntroductionThis study aimed to explore the expression of SNHG15 in atherosclerotic population and further evaluate the regulatory mechanism of SNHG15 in AS.Material and methodsqRT-PCR was used to detect the level of SNHG15 in serum samples. An in vitro cell model was constructed using 50 µg/ml ox-LDL-induced VSMCs. Transwell, CCK-8 assay and ELISA were used to detect the migration, proliferation, phenotypic transformation, and inflammatory reaction of the cell model. The interaction between SNHG15 and miR-370-3p was verified by the luciferase reporter gene. Pearson analysis was used to assess the correlation between SNHG15 and miR-370-3p. The target genes of miR-370-3p and their functions were evaluated by bioinformatics analysis.ResultsThe expression of SNHG15 in the AS group and ox-LDL-induced VSMCs group were upregulated (p < 0.001), while miR-370-3p was decreased (p < 0.001). In vitro studies showed that inhibition of SNHG15 can obviously weaken the proliferation, migration, phenotypic transformation, and inflammation of VSMCs induced by ox-LDL (p < 0.01). Bioinformatics and luciferase reporter gene confirmed that miR-370-3p was the downstream target gene of SNHG15. Pearson correlation coefficient revealed that miR-370-3p was negatively regulated by SNHG15 (r = –0.6998, p < 0.001). Bioinformatics analysis indicated that miR-370-3p had 160 potential target genes, whose functions were mainly related to cell cycle and cell adhesion, and were mainly concentrated in the MAPK signaling pathway. Further analysis showed that the downstream target gene of miR-370-3p was FOXO1.ConclusionsSNHG15 mediated cell proliferation, migration, phenotypic transformation, and inflammation response via inhibiting miR-370-3p in ox-LDL-induced VSMCs.

YTHDF2 contributes to psoriasis by promoting proliferation and inflammatory response through regulation of the Wnt signaling pathway

YT521-B homology domain family 2 (YTHDF2), a pivotal m6A-binding protein, is now understood to significantly influence a diverse array of biological functions, including cell migration, proliferation, differentiation, and inflammatory responses. Additionally, YTHDF2 participates in mRNA decay and pre-rRNA processing. This study explored the specific role of YTHDF2 in the pathogenesis of psoriasis and its underlying mechanisms. Our preliminary findings revealed upregulation of YTHDF2 expression in psoriasis. Subsequent silencing of YTHDF2 in a psoriatic cell model resulted in a marked decrease in mRNA expression of IL-17A, S100A8, and S100A9, accompanied by a reduction in cell proliferation. Conversely, overexpression of YTHDF2 led to the opposite effects. Treatment with DC-Y27-13, a YTHDF2 inhibitor, demonstrated a therapeutic effect in psoriasis mice. Next, mRNA sequencing analysis identified significant enrichment of differentially expressed genes within the Wnt signaling pathway. Further investigation revealed that deletion of YTHDF2 increased the half-life and expression of Dickkopf homolog 3 (DKK3), a potent inhibitor of the Wnt signaling pathway. Consequently, the inhibition of Wnt signaling attenuated the inflammatory response and inhibited cell proliferation.

Regulation of Oxygen in the Tumor Microenvironment Synergizes with Immunotherapy to Suppress Tumor Progression

Hypoxia represents a crucial characteristic of the tumor microenvironment, which is closely related to cell proliferation, angiogenesis, and metabolic responses. These factors will further promote tumor progression, increase tumor invasion, and enhance tumor metastasis potential. A hypoxic microenvironment will also inhibit the activity of infiltrated immune cells in the tumor microenvironment, leading to the failure of cancer immunotherapy. Additionally, the hypoxic tumor microenvironment contributes to resistance to conventional therapies and leads to unfavorable prognoses. This review discusses advancements in strategies aimed at ameliorating tumor hypoxia within the microenvironment and modulating immune cell responses against tumors.

TOP2A Promotes Proliferation, Migration, and Inflammatory Response in M5-Treated Keratinocytes by Binding CTBP1 to Activate Wnt/β-Catenin Signaling.

Psoriasis is a chronic cutaneous disease, affecting a significant portion of the global population. Topoisomerase II alpha (TOP2A) is upregulated in psoriasis samples, but the precise molecular mechanism remains unclear. We aimed to clarify the biological contribution of TOP2A in psoriasis progression. An in vitro psoriasis model was established on M5-induced keratinocytes (HaCaT cells) to simulate the psoriasis-like alterations. Following TOP2A knockdown without or with c terminal binding protein 1 (CTBP1) overexpression, CCK-8 and EDU staining were employed to analyze the viability and proliferation of HaCaT cells under M5 conditions. The capacities of HaCaT cell migration and invasion were examined with wound healing- and transwell assays. RT-qPCR and immunoblotting were adopted for evaluation of the inflammation and differentiation of M5-stimualted HaCaT cells. Additionally, the binding between TOP2A and CTBP1 was predicated using bioinformatics tools and detected by Co-IP. Finally, the expression of proteins in Wnt/β-catenin signaling was analyzed with the application of immunoblotting. Results suggested that TOP2A was upregulated in psoriasis skin lesions and M5-induced HaCaT cells. Interference with TOP2A attenuated the proliferation, migration, invasion, and inflammatory response in M5-treated HaCaT cells. In particular, TOP2A bound to CTBP1 and upregulated CTBP1 expression in HaCaT cells. Remarkably, CTBP1 upregulation blocked the impacts of TOP2A depletion on the biological behaviors of M5-treated HaCaT cells. Besides, TOP2A deficiency upregulated DKK1 expression as well as downregulated Wnt1, β-catenin, and c-Myc expression in HaCaT cells exposed to M5, which was restored by further CTBP1 overexpression. In summary, TOP2A binds CTBP1 to activate Wnt/β-catenin signaling, thereby promoting the progression of psoriasis.

The Decreased Proliferation Capacity of Cardiomyocytes Induced By Androsterone Is Mediated By the Interactions Between Androgen Receptor and Retinoblastoma Protein.

Our previous study has demonstrated that the decline in cardiomyocytes proliferation capacity induced by maternal androgen excess was mainly attributed to the accumulation of androsterone in the heart. However, the underlying mechanism by which androsterone inhibits cardiomyocytes proliferation remains unknown. In this study, pregnant mice were injected subcutaneously daily with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was dissected and used for analyzing androgen receptor (AR) levels. H9c2 cells and primary cardiomyocytes, isolated from fetal hearts, were applied to investigate the mechanism. H9c2 cells under androsterone treatment were subjected to RNA sequencing analysis and the results showed that genes were primarily enriched in cell cycle and DNA replication pathways. Elevated AR levels were observed in fetal cardiac tissue in the maternal DHT-treated group. Androsterone treatment increased the ratio of nuclear AR and cytoplasmic AR both in H9c2 cells and primary cardiomyocytes. The ablation and overexpression of AR can mildly reverse and aggravate cell cycle arrest induced by androsterone, respectively. ChIP-qPCR analysis suggested that AR can directly repress cell cycle and DNA replication-related gene expression, which was mediated by the recruitment of retinoblastoma protein (Rb). The repression of cell proliferation in response to androsterone was alleviated partly through the downregulation of Rb by siRNA transfection. In conclusion, AR repression to cell cycle and DNA replication-related gene expression, mediated by recruitment of Rb, may be one of the potential mechanisms of cell cycle arrest in cardiomyocytes induced by androsterone.

The TCONS_00046732/chi-miR-135b-5p/PRLR regulatory axis promotes endometrial epithelial cells growth through the PI3K-Akt signaling pathway

Non-coding RNAs are considered key regulatory factors in biological and reproductive physiological processes in mammals. However, the molecular functions of long noncoding RNAs (lncRNAs) in regulating dynamic uterine development and reproductive capacity during sexual maturation remain unclear. This study analyzed the expression characteristics and molecular functions of lncRNAs in uterine tissues from 20 goats at four specific time points during sexual maturation: day 1 after birth (D1), 2 months (M2), 4 months (M4), and 6 months (M6), finding that stage-specific DE lncRNAs may regulate cell proliferation, apoptosis, hormone secretion, metabolism, and immune response through multiple action modes. Within the lncRNA-miRNA-mRNA network, a novel lncRNA, TCONS_00046732, associated with uterine development, exhibited significantly higher expression during sexual maturity compared to the prepubertal stage, correlating positively with PRLR and negatively with chi-miR-135b-5p. FISH and IF analyses revealed significant co-localization and distinct expression patterns of TCONS_00046732, chi-miR-135b-5p, and PRLR in the endometrial epithelium. Further experiments confirmed that TCONS_00046732 competitively binds to chi-miR-135b-5p to upregulate PRLR, thereby activating the PI3K-Akt signaling pathway, promoting primary endometrial epithelial cell proliferation, G1-to-S phase transition, and inhibiting apoptosis. These findings enhance our understanding of uterine molecular regulation and provide key insights into the molecular basis of goat sexual development.

Comparative monocyte and T cell responses in DENV-exposed subjects from South-East Asia and DENV-naïve residents in Taiwan

Background/Purpose(s)Dengue virus (DENV) is one of the most troublesome mosquito-borne infectious viruses in tropical and subtropical zones. People with secondary/multiple DENV infections are at an increased risk of developing severe dengue. Both monocytes and T cells are known to play important roles in the immune response against DENV. However, the function of monocytes and T cells in individuals with potentially multiple exposures to DENV is rarely reported. MethodIn the present study, we performed a functional analysis of monocytes and T cells from people with previous DENV infection and DENV-naïve people that stimulated with DENV2 ex vivo. ResultsOur preliminary analysis indicated that the response of monocytes and T cells to DENV2 restimulation was comparable between DENV-exposed and DENV-naïve individuals. Furthermore, the cytokine expression profiles in monocytes from both naïve individuals and previously DENV-exposed subjects were similar after DENV2 stimulation. In addition, it was observed that the function of T cells was also equivalent when monocytes were present as antigen-presenting cells for dengue antigen, NS3, in terms of cell proliferation, interferon-gamma (IFNγ) secretion, and memory response. ConclusionsBased on the results, it was observed that previously DENV-exposed monocytes and T cells seemed to be anergic during DENV reinfection. However, whether the impaired response of monocytes and T cells against DENV in people with a history of previous DENV infection leads to severe dengue upon secondary infection in endemic areas requires further investigation.

Overexpression of miRNA29a gene inhibits proliferation and promotes apoptosis of jejunal epithelial cells in yak.

MicroRNAs (miRNAs) were identified to be involved in various biological functions by regulating the degradation or suppressing the translation of their downstream target genes. Recent studies have identified miR-29a play a key role in functions of mammal cell differentiation, proliferation, apoptosis, and signal transduction. However, the underlying functions for miR-29a in jejunal epithelial cells biological function still to be investigated. In order to explore the yak jejunal epithelial cells proliferation and barrier dysfunction with over expression of miR-29a gene, three 0-day-old Pamir male yaks were randomly selected and slaughtered in present study, and the jejunal epithelial cells were isolated and cultured to determine yak jejunal epithelial cells proliferation and protein composition on differential expression of miR-29a gene in Pamir plateau. Here, we demonstrated that the overexpression of miR-29a gene could inhibit the proliferation of Pamir yaks jejunum epithelial cells, and contribute to the apoptosis of Pamir yaks jejunal epithelial cells with some extent. A total of 133 differentially expressed proteins were identified in different expression of miR-29a groups by label-free Mass Spectrometry (MS), which could be concluded to two predominant themes: cell proliferation and inflammatory response. Interestingly, GPR41, as a bridge protein, was contacted two predominant themes to involved in Pamir Yaks jejunal mechanical barrier PPI network, and the target proteins displayed strong mutual interactions in the complex PPI network. Overall, our study suggested that the over-expression miR-29a inhibited the jejunal epithelial cells proliferation and the expressions of specific proteins, which damaged jejunal barrier function to slow down the intestine structure and function advanced mature development during young livestock period for influence the enhanced performance of production efficiency.

Multiplex analysis of cancer cells treated with induced mesenchymal stem cell membrane vesicles

BACKGROUND: Extracellular vesicles (EVs) are membrane-derived vesicles released by cells into the extracellular space, playing a crucial role in intercellular communication and regulating a range of biological processes. These vesicles are found in tumor tissue, where they serve as mediators in signal transduction between tumor cells and the cells of the microenvironment. Similar to their parent mesenchymal stem cells (MSCs), extracellular vesicles demonstrate contradictory effects on tumor development. Studies have shown that MSC-derived EVs promote tumor growth; however, some research has also demonstrated their inhibitory role. AIM: The aim is to assess the effect of mesenchymal stem cell-derived membrane vesicles on the molecular composition of cancer cells. METHODS: Induced membrane vesicles were obtained from mesenchymal stem cells through treatment with cytochalasin B. Mesenchymal stem cells were initially sourced from adipose tissue. To simulate intercellular communication between tumor cells and MSCs, induced membrane vesicles were applied at varying protein concentrations to recipient cells (SH-SY5Y, PC3, MCF7). The bicinchoninic acid method was used to measure the total protein concentration isolated from human cells/induced membrane vesicles. Subsequently, the molecular composition of the recipient cells after the application of induced membrane vesicles was analyzed using multiplex assays. RESULTS: We determined that after the application of MSC-derived membrane vesicles to cancer cells, significant alterations occur in the expression of numerous biologically active molecules, including cytokines, chemokines, and growth factors. Specifically, increased concentrations of growth factor FGF-2, cytokines G-CSF, Fractalkine, IL-12p40, IL-9, IL-4, IL-6, IL-8, and chemokines IP-10, MCP-1, among others, were observed. The analysis also revealed that most of these molecules are associated with cell proliferation, migration, and immune response. CONCLUSION: Mesenchymal stem cell-derived membrane vesicles are capable of altering the molecular profile of cancer cells, increasing the concentration of molecules linked to cell survival and migration.

Understanding the molecular regulatory mechanisms of autophagy in lung disease pathogenesis.

Lung disease development involves multiple cellular processes, including inflammation, cell death, and proliferation. Research increasingly indicates that autophagy and its regulatory proteins can influence inflammation, programmed cell death, cell proliferation, and innate immune responses. Autophagy plays a vital role in the maintenance of homeostasis and the adaptation of eukaryotic cells to stress by enabling the chelation, transport, and degradation of subcellular components, including proteins and organelles. This process is essential for sustaining cellular balance and ensuring the health of the mitochondrial population. Recent studies have begun to explore the connection between autophagy and the development of different lung diseases. This article reviews the latest findings on the molecular regulatory mechanisms of autophagy in lung diseases, with an emphasis on potential targeted therapies for autophagy.

Peptide Nucleic Acids in Saturation Transfer Difference Nuclear Magnetic Resonance Experiments: A Simple and Valuable Tool for Studying HuR-Small Molecule Complexes.

Ribonucleic acid (RNA)-binding proteins (RBPs) play a key role in regulating RNA stability, fate, function, gene expression, post-transcriptional modifications, and cellular activities. Among the various RBPs identified to date, the Hu proteins have been the most extensively studied. Specifically, HuR influences several cellular processes, including cell proliferation, differentiation, and stress response, and it is frequently overexpressed in various solid tumors. Several HuR ligands have been identified so far, highlighting the druggability of such a protein. To discover the novel HuR-RNA interfering agents, biophysical assays represent a promising approach. To overcome limitations for RNA manipulation, in this work, we explored the use of PNA (peptide nucleic acid) as an RNA analogue in interaction studies. Molecular modeling simulation revealed the ability of aegPNA to bind HuR and, therefore, the synthesis of the designed PNA was conducted. The saturation transfer difference (STD) nuclear magnetic resonance (NMR) technique was adopted to evaluate the ability of HuR ligands to interfere with the HuR-PNA complex, comparing the obtained results with RNAs. Our results evidenced that PNA may be considered a simple and valuable tool to analyze the interaction and interfering properties of HuR ligands by STD-NMR, thus improving the precision and reliability of the approach.

Exploring tumor endothelial cells heterogeneity in hepatocellular carcinoma: insights from single-cell sequencing and pseudotime analysis.

This study aimed to explore the heterogeneity of tumor endothelial cells (TECs) in hepatocellular carcinoma (HCC) and their role in tumor progression, with the goal of identifying new therapeutic targets and strategies to improve patient prognosis. Single-cell RNA sequencing data from nine primary liver cancer samples were analyzed, obtained from the Gene Expression Omnibus (GEO) database. Data preprocessing, normalization, dimensionality reduction, and batch effect correction were performed based on the Seurat package. HCC cell types were identified using uniform manifold approximation and projection (UMAP) and cluster analysis, and the different cell types were annotated using the CellMarker database. Pseudotime trajectory analysis was conducted with Monocle to explore the differentiation trajectory of TECs. MAPK signaling pathway activity and copy number variations (CNV) in TECs were analyzed in conjunction with data from The Cancer Genome Atlas (TCGA), the trans-well and wound healing assay was used for cell invasion and migration activity assessment. Two subgroups of TECs (TECs 1 and TECs 2) were identified, exhibiting distinct functional activities and signaling pathways. Specifically, TECs 1 may be involved in tumor cell proliferation and inflammatory responses, whereas TECs 2 is not only involved in cell proliferation pathways, but also enriched in pathways such as metabolic synthesis. Pseudotime analysis revealed dynamic changes in TECs subgroups during HCC progression, correlating specific gene expressions (such as PDGFRB, PGF, JUN, and NR4A1). Subsequently, the JUN gene was predicted by performing binding sites and was shown to act as a transcription factor that may regulate the expression of the PGF gene. CNV analysis highlighted key genes and pathways in TECs that might influence HCC progression, and the PGF as key regulatory factor mediated cell proliferation and migration. The study revealed the heterogeneity of TECs in HCC and their potential roles in tumor progression, offering new perspectives and potential therapeutic targets for HCC molecular mechanisms. The findings emphasize the importance of further exploring TECs heterogeneity for understanding HCC pathogenesis and developing personalized treatment strategies.

Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review.

Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications.

FTO in oral diseases: Functions, mechanisms, and therapeutic potential.

Fat mass and obesity-associated protein (FTO) is the first identified N6-methyladenosine (m6A) demethylase widely distributed in various tissues in adults and children. It plays an essential role in diverse mRNA-associated processes including transcriptional stability, selective splicing, mRNA translocation, and also protein translation. Recently, emerging studies have shown that FTO is involved in the genesis and development of oral diseases. However, the correlation between FTO and oral diseases and its specific regulatory mechanism still needs further study. In this review, we will summarize the discovery, distribution, gene expression, protein structure, biological functions, inhibitors, and quantifying methods of FTO, as well as its regulatory role and mechanism in oral diseases. Notably, FTO genetic variants are strongly associated with periodontal diseases (PDs), temporomandibular joint osteoarthritis (TMJOA), and obstructive sleep apnea (OSA). Besides, the latest studies that describe the relationship between FTO and PDs, head and neck squamous cell carcinoma (HNSCCs), TMJOA, and OSA will be discussed. We elaborate on the regulatory roles of FTO in PDs, HNSCCs, and TMJOA, which are modulated through cell proliferation, cell migration, apoptosis, bone metabolism, and immune response. The review will enrich our understanding of RNA epigenetic modifications in oral diseases and present a solid theoretical foundation for FTO to serve as a novel diagnosis and prognostic biomarker for oral diseases.

PRDM1 promotes nucleus pulposus cell pyroptosis leading to intervertebral disc degeneration via activating CASP1 transcription.

Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain and poses a considerable burden to society. However, the molecular mechanisms underlying IVDD remain to be elucidated. PR/SET domain 1 (PRDM1) regulates cell proliferation, apoptosis, and inflammatory responses in various diseases. Despite these regulatory functions, the mechanism of action of PRDM1 in IVDD remains unexplored. In this study, we investigated the role and underlying mechanisms of action of PRDM1 in IVDD progression. The expression of PRDM1 in nucleus pulposus (NP) tissues and NP cells (NPCs) was assessed using western blotting, immunohistochemistry, and immunofluorescence. The effects of PRDM1 on IVDD progression were investigated in vitro and in vivo. Mechanistically, mRNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to confirm that PRDM1 triggered CASP1 transcription. Our study demonstrated for the first time that PRDM1 expression was substantially upregulated in degenerated NP tissues and NPCs. PRDM1 overexpression promoted NPCs pyroptosis by inhibiting mitophagy and exacerbating IVDD progression, whereas PRDM1 silencing exerted the opposite effect. Furthermore, PRDM1 activated CASP1 transcription, thereby promoting NPCs pyroptosis in vitro. Notably, CASP1 silencing reversed the effects of PRDM1 on the NPCs. To the best of our knowledge, this study is the first to demonstrate that PRDM1 silencing inhibits NPCs pyroptosis by repressing CASP1 transcription, which may be a promising new therapeutic target for IVDD.

Paper Spray Ionization Mass Spectrometry Coupled with Paper-Based Three-Dimensional Tumor Model for Rapid Metabolic Gradient Profiling.

The tumor microenvironment (TME), especially with its complicated metabolic characteristics, will dynamically affect the proliferation, migration, and drug response of tumor cells. Rapid metabolic analysis brings out a deeper understanding of the TME, while the susceptibility and environmental dependence of metabolites extremely hinder real-time metabolic profiling since the TME is easily disrupted. Here, we directly integrated paper spray ionization mass spectrometry with a paper-based three-dimensional (3D) tumor model, realizing the rapid capture of metabolic gradients. The entire procedure, from sample preparation to mass spectrometry detection, took less than 4 min, which was able to provide metabolic results close to real time and contributed to understanding the real metabolic processes. At present, our method successfully detected 160 metabolites; notably, over 40 significantly gradient metabolites were revealed across the six layers of the paper-based 3D tumor model. At least 22 gradient metabolites were reported to be associated with cell viability. This strategy was powerful enough to rapidly profile metabolic gradients of a paper-based 3D tumor model for revealing cell viability changes from a metabolomics perspective.

Regulation of autophagy by non-coding RNAs in human glioblastoma.

Glioblastoma, a lethal form of brain cancer, poses substantial challenges in treatment due to its aggressive nature and resistance to standard therapies like radiation and chemotherapy. Autophagy has a crucial role in glioblastoma progression by supporting cellular homeostasis and promoting survival under stressful conditions. Non-coding RNAs (ncRNAs) play diverse biological roles including, gene regulation, chromatin remodeling, and the maintenance of cellular homeostasis. Emerging evidence reveals the intricate regulatory mechanisms of autophagy orchestrated by non-coding RNAs (ncRNAs) in glioblastoma. The diverse roles of these ncRNAs in regulating crucial autophagy-related pathways, including AMPK/mTOR signaling, the PI3K/AKT pathway, Beclin1, and other autophagy-triggering system regulation, sheds light on ncRNAs biological mechanisms in the proliferation, invasion, and therapy response of glioblastoma cells. Furthermore, the clinical implications of targeting ncRNA-regulated autophagy as a promising therapeutic strategy for glioblastoma treatment are in the spotlight of ongoing studies. In this review, we delve into our current understanding of how ncRNAs regulate autophagy in glioblastoma, with a specific focus on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), and their intricate interplay with therapy response.

A comparative study on the toxic effects of lead pollution and nanoplastic-lead mixed pollution on red drum and their detoxification strategies

Nanoplastics and heavy metals pose various adverse effects on marine organisms. However, the combined toxicity of nanoplastics and lead pollution to marine fish is not fully understood. This study investigates the toxic effects and detoxification strategies of lead pollution (p07) compared to nanoplastic-lead mixed pollution (m07) in red drum during exposure and recovery phases. Under m07 pollution, the maximum lead content in muscle was 22.61 mg/kg, which was significantly higher than the 15.82 mg/kg observed under p07 pollution. This finding demonstrated that nanoplastics significantly enhance lead accumulation, leading to more severe toxic effects on red drum. Histological analyses revealed that lipid droplets in the liver and epithelial lifting in the gills were the primary lesion types. During the exposure periods, red drum primarily detoxified lead through cellular renewal and the removal of damaged proteins under p07 pollution. Conversely, under m07 pollution, detoxification relied on cellular senescence, apoptosis, endocytosis, and the removal of damaged proteins. In the recovery phases, red drum predominantly recovered through cell proliferation and antioxidant responses under p07 pollution. Under m07 pollution, the focus shifted to functional protein synthesis, apoptosis, endocytosis, and lipid metabolism. This study offers valuable insights into the monitoring and management of combined environmental pollution.

Novel Therapeutic Target for ALI/ARDS: Forkhead Box Transcription Factors.

ALI/ARDS can be a pulmonary manifestation of a systemic inflammatory response or a result of overexpression of the body's normal inflammatory response involving various effector cells, cytokines, and inflammatory mediators, which regulate the body's immune response through different signalling pathways. Forkhead box transcription factors are evolutionarily conserved transcription factors that play a crucial role in various cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism, and DNA damage response. Transcription factors control protein synthesis by regulating gene transcription levels, resulting in diverse biological outcomes. The Fox family plays a role in activating or inhibiting the expression of various molecules related to ALI/ARDS through phosphorylation, acetylation/deacetylation, and control of multiple signalling pathways. An in-depth analysis of the integrated Fox family's role in ALI/ARDS can aid in the development of potential diagnostic and therapeutic targets for the condition.