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Biomedical subjects

Min Wu

Publications and source records attributed to Min Wu.

At least 19 recordsLinked to original sources
PubMed2026

USP22 alleviates oxidative stress-induced BMSCs senescence by stabilizing SPI1 protein.

BACKGROUND: Therapeutic efficacy of bone marrow mesenchymal stem cell (BMSC) transplantation is often compromised by cellular senescence and diminished osteogenic potential induced by oxidative stress. Nevertheless, the underlying molecular mechanisms remain poorly understood. This study explores the role of ubiquitin-specific peptidase 22 (USP22) in regulating oxidative stress-induced BMSCs senescence. METHODS: BMSCs were exposed to H2O2 to mimics oxidative stress conditions. An ovariectomy‑induced osteoporotic rat model was established. Cell viability was assessed by CCK8 assay. ROS level and NAD+ level were measured by the DHE probe and kit, respectively. SA-β-gal staining was employed to detect cellular senescence. Mineralization was determined using ARS staining. Protein-DNA interactions (SPI1-NAMPT promoter) were examined through ChIP and luciferase reporter assays. Co-IP and ubiquitination assays were performed to validate USP22-SPI1 binding and post-translational modifications. RESULTS: SPI1 expression declined in H2O2-treated BMSCs and osteoporotic rat model, and its overexpression rescued H2O2-induced BMSCs senescence and osteogenic differentiation impairment. Mechanistically, SPI1 mediated protection on oxidative stress-induced BMSCs senescence by transcriptionally activating NAMPT expression and elevating NAD+ level. In addition, USP22 stabilized SPI1 protein through deubiquitination modification. As expected, USP22 overexpression alleviated oxidative stress-induced BMSCs senescence and osteogenic differentiation impairment, while these effects were reversed by SPI1 knockdown. CONCLUSION: USP22 mitigated oxidative stress-induced BMSCs senescence and preserved osteogenic capacity by promoting NAMPT transcription through deubiquitinating and stabilizing SPI1 protein.

Oxidative Stress↗
PubMed2026

Athero-oncology: Vascular smooth muscle cell tumor-like transformation in atherosclerosis and therapeutic opportunities.

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases, and its pathogenesis and treatment strategies remain major challenges. Recent advances in single-cell RNA sequencing and lineage tracing have revealed that vascular smooth muscle cells (VSMCs) are not merely passive structural components of atherosclerotic plaques, but highly plastic participants that undergo clonal expansion, phenotypic modulation, and transdifferentiation into functionally diverse cell states. These findings have prompted the emergence of an "athero-oncology" framework, which explores selected tumor-like cellular programs in VSMCs during AS without equating atherosclerosis with cancer. In this review, we summarize the evidence supporting VSMC-derived clonal expansion and phenotypic diversification in atherosclerotic lesions and discuss key mechanisms involved in this process, including proliferative expansion and survival programs, metabolic reprogramming, epigenetic regulation, DNA damage and genomic stress, VSMC senescence, pathological angiogenesis, and remodeling of the inflammatory and immune microenvironment. We further highlight shared signaling pathways between VSMC-driven plaque remodeling and tumor biology, while emphasizing fundamental differences between AS and malignant disease in growth limitation, mutational burden, metastatic potential, and clinical behavior. Finally, we discuss oncology-inspired therapeutic opportunities and boundaries, including pathway-level targeting of proliferative, metabolic, epigenetic, and inflammatory programs, as well as the risks of directly repurposing anticancer therapies for chronic vascular disease. This framework may provide new insights into vascular biology and therapeutic development.

atherosclerosis↗
PubMed2026

Human Variation-Informed Prioritization of MPHOSPH6 in Lung Adenocarcinoma: A Source-Aware Multiomics Evidence Framework.

Moving from an association signal to a clinically credible biomarker requires several links that are often conflated: verified variant identity, aligned allelic effects, reproducible gene-level association, relevant cellular expression, and a plausible functional consequence. We developed a source-aware multiomics framework to assess MPHOSPH6 in lung adenocarcinoma (LUAD) while keeping those evidence classes separate. Six prespecified rsIDs were recovered from the harmonized TRICL LUAD dataset, of which five reached p < 5 &#xd7; 10 - 8. Only rs112333466 and rs76474922 were available with alignable alleles in FinnGen R10, and both showed concordant directions. Fixed-effect estimates were OR = 1.592 for rs112333466-T (95% CI, 1.401-1.809; p = 9.91 &#xd7; 10 - 13) and OR = 0.819 for rs76474922-C (95% CI, 0.773-0.867; p = 1.03 &#xd7; 10 - 11). In a prespecified two-variant GTEx v8 lung model, genetically predicted MPHOSPH6 expression was positively associated with LUAD in TRICL (Z = 3.341, p = 8.35 &#xd7; 10 - 4) and FinnGen (Z = 2.697, p = 0.0070). This gene-level result did not establish colocalization or connect MPHOSPH6 to the six susceptibility rsIDs. Patient-level analysis of 89,241 immune cells from six paired tumor and normal-adjacent lung samples found no significant difference in MPHOSPH6 pseudobulk abundance (exact paired Wilcoxon p = 0.3125). None of 688 lung-lineage pharmacogenomic tests remained significant after false-discovery-rate correction. Ten recorded MPHOSPH6 missense alleles, including five ClinVar variants of uncertain significance, were curated; structural analysis identified I58 at an experimental RNA-exosome interface and defined a focused perturbation series. MPHOSPH6 is therefore supported as a human-variation-informed candidate for functional evaluation, not as a validated LUAD biomarker, pathogenic gene, drug-response predictor, or therapeutic target.

Humans↗
PubMed2026

Synchronicity of parent-child sleep and potential mechanisms: A systematic review and meta-analysis.

Existing evidence indicates that parent and child circadian rhythms are associated, but studies have mainly examined factors affecting child sleep health. This systematic review addressed two questions: a) is there a synchronous relationship between parent and offspring sleep? and b) what are the potential mechanisms? PubMed, Embase, PsychINFO, and Scopus were searched from inception to April 2025. Forty-six studies comprising over 100000 parent-child dyads across 16 countries were included. Results showed small-to-moderate parent-child synchronicity in sleep duration (r&#x202f;=&#x202f;0.18, 95% CI [0.14, 0.23]), sleep efficiency (r&#x202f;=&#x202f;0.30, 95% CI [0.19, 0.41]), bedtime (r&#x202f;=&#x202f;0.34, 95% CI [0.20, 0.46]), and wake up time (r&#x202f;=&#x202f;0.48, 95% CI [0.24, 0.66]), with stronger effects observed in mother-child dyads. Synchronicity in sleep continuity was moderate, whereas associations in sleep satisfaction were small and non-significant. Mechanisms included genetic and hormonal factors, bedtime routines, shared environments, and attachment. These findings are consistent with family systems theory's premise that sleep is a relational phenomenon. Observed synchronicity in sleep timing may partly reflect shared external constraints like work and school schedules. Most studies were cross-sectional, limiting causal or directional conclusions. Future research should adopt standardized methodologies and longitudinal designs to clarify mechanistic pathways.

Humans↗
PubMed2026

Leveraging environmental applications and risks of coal gangue: A critical review on authigenic inorganic heavy metals, organic contaminants, and the removal of exogenetic contaminants.

Coal gangue (CG) as bulk solid waste has seriously threatened the ecosystem. Therefore, identifying the key risk drivers and exploring feasible disposal methods for CG are essential for developing a sustainable strategy. However, there is currently a lack of comprehensive information that balances the contamination risks with the valuable constituents present in CG, which hinders its full potential for sustainable use without negative environmental impacts. Given the complex composition and associated risks, we propose that addressing the critical properties related to contamination is crucial for the efficient utilization of CG. On this premise, we summarized several practical resource pathways (ecological multifunctional materials, extraction of rare elements, and soil additives) that are more favorable for sustainable development relative to conventional disposals. Meanwhile, we also propose that coupling disposals could intensely reduce CG's environmental footprints and capital costs. Consequently, regardless of the number of challenges to be solved, we believe the CG has broad application prospects, and we hope this review will promote the conversion of CG into an asset with lower ecological and social impacts.

Metals, Heavy↗
PubMed2026

ALG-020572, an Antisense Oligonucleotide for the Treatment of Chronic Hepatitis B Virus Infection Discontinued for Drug-Induced Liver Injury.

Current treatment options for chronic HBV infection are suboptimal in that they fail to suppress HBsAg levels. ALG-020572 is an antisense oligonucleotide designed to reduce viral protein synthesis through degradation of HBV mRNA. ALG-020572-401 was a double-blind, randomized, placebo-controlled trial consisting of two parts. Part 1 (single-ascending doses) evaluated the pharmacokinetics, safety and tolerability of single doses of ALG-020572 or placebo in healthy participants. In Part 2 (multiple dosing), participants with non-cirrhotic HBeAg-negative, virologically suppressed chronic HBV infection were administered up to 7 doses of ALG-020572 to evaluate safety, pharmacokinetics and antiviral activity. In Part 1, 32 participants were randomized to ALG 020572 or placebo. Single doses of ALG-020572 up to 480&#x2009;mg were well tolerated. The most common treatment-emergent adverse event reported was injection site reaction. ALG-020572 was rapidly absorbed and plasma exposures increased with dose. In Part 2, 8 participants with non-cirrhotic HBeAg-negative virologically suppressed chronic hepatitis B infection were enrolled and received up to 7 doses of ALG-020572. The study was prematurely discontinued after 4 participants experienced significant alanine aminotransferase elevations that were subsequently attributed to drug-induced liver injury. Single doses of ALG-020572 demonstrated a favourable pharmacokinetic and safety profile in healthy participants. Unexpectedly, ALG-020572 was poorly tolerated in participants with chronic HBV infection, resulting in the early termination of the study and further development of ALG-020572 due to idiosyncratic drug-induced liver injury, suggesting caution is required in the development of this class of drugs. Trial Registration: Registered at clinicaltrials.gov: NCT0500102.

Adult↗
PubMed2007

Functional interrogation of the kinome using nucleotide acyl phosphates.

The central role of protein kinases in signal transduction pathways has generated intense interest in targeting these enzymes for a wide range of therapeutic indications. Here we report a method for identifying and quantifying protein kinases in any biological sample or tissue from any species. The procedure relies on acyl phosphate-containing nucleotides, prepared from a biotin derivative and ATP or ADP. The acyl phosphate probes react selectively and covalently at the ATP binding sites of at least 75% of the known human protein kinases. Biotinylated peptide fragments from labeled proteomes are captured and then sequenced and identified using a mass spectrometry-based analysis platform to determine the kinases present and their relative levels. Further, direct competition between the probes and inhibitors can be assessed to determine inhibitor potency and selectivity against native protein kinases, as well as hundreds of other ATPases. The ability to broadly profile kinase activities in native proteomes offers an exciting prospect for both target discovery and inhibitor selectivity profiling.

Adenine Nucleotides↗
PubMed2006

Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of esophageal squamous cell carcinoma by promoting cell migration and anoikis resistance.

Gain of chromosome 11q13 is a common event in esophageal squamous cell carcinoma (ESCC). The cortactin gene (CTTN, also EMS1), located at 11q13, plays a pivotal role in coupling membrane dynamics to cortical actin assembly. This gene has been implicated in the motility of several types of cells. In the present study, we found that the amplification and overexpression of the CTTN gene was associated with lymph node metastasis in ESCC. Functional analysis by small interfering RNA-mediated silencing of CTTN revealed that in addition to the effect on cell migration, CTTN influenced cell invasiveness by anoikis resistance. In vivo assay showed that inhibition of CTTN expression also decreased tumor growth and lung metastasis of ESCC cells. At the molecular level, we showed for the first time that the protective role of CTTN in anoikis resistance was correlated with the activation of the phosphatidylinositol 3-kinase/Akt pathway. Overall, the data suggest that CTTN is an oncogene in the 11q13 amplicon and exerts functions on tumor metastasis in ESCC.

Anoikis↗
PubMed2006

Identification of chromosome aberrations in esophageal cancer cell line KYSE180 by multicolor fluorescence in situ hybridization.

Analysis of chromosomal changes in esophageal squamous cell carcinoma (ESCC) can illuminate the molecular mechanisms underlying the development and progression of this cancer, which is among the 10 most common malignant tumors. Cell lines are better suited than surgical samples for chromosome analysis in this cancer. This study used multicolor fluorescence in situ hybridization (M-FISH) to characterize the molecular cytogenetics of ESCC in cell line KYSE180. Two pools of 12-color whole-chromosome painting probes were designed, and two rounds of FISH were performed on the same metaphase spreads. Loss of DNA copy number was observed at 4p, 5q, 6q, 9, 10p, 12p, 13, 14p, 15p, 18p, 18q, 20, 22, and Y. Chromosomal gains and translocations occurred at the entire or part of 1, 2p, 3, 4p, 5p, 5q, 6p, 7, 8, 10q, 11, 12q, 14q, 16, 17q, 19, and Xp. Seven derivative chromosomes (5, 8, 12, 14, 14, 14, and 17) presented complex translocations, each involving three or four chromosomes. No chromosomes 9, 13, or Y were detected. These results add significant information to the existing karyotype description of KYSE180 and provide detailed cytogenetic background data for appropriate use of the cell line.

Carcinoma, Squamous Cell↗
PubMed2006

CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation.

The CUL4-DDB1-ROC1 ubiquitin E3 ligase regulates cell-cycle progression, replication and DNA damage response. However, the substrate-specific adaptors of this ligase remain uncharacterized. Here, we show that CUL4-DDB1 complexes interact with multiple WD40-repeat proteins (WDRs) including TLE1-3, WDR5, L2DTL (also known as CDT2) and the Polycomb-group protein EED (also known as ESC). WDR5 and EED are core components of histone methylation complexes that are essential for histone H3 methylation and epigenetic control at K4 or K9 and K27, respectively, whereas L2DTL regulates CDT1 proteolysis after DNA damage through CUL4-DDB1 (ref. 8). We found that CUL4A-DDB1 interacts with H3 methylated mononucleosomes and peptides. Inactivation of either CUL4 or DDB1 impairs these histone modifications. However, loss of WDR5 specifically affects histone H3 methylation at K4 but not CDT1 degradation, whereas inactivation of L2DTL prevents CDT1 degradation but not histone methylation. Our studies suggest that CUL4-DDB1 ligases use WDR proteins as molecular adaptors for substrate recognition, and modulate multiple biological processes through ubiquitin-dependent proteolysis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

A Fisheye Viewer for microarray-based gene expression data.

BACKGROUND: Microarray has been widely used to measure the relative amounts of every mRNA transcript from the genome in a single scan. Biologists have been accustomed to reading their experimental data directly from tables. However, microarray data are quite large and are stored in a series of files in a machine-readable format, so direct reading of the full data set is not feasible. The challenge is to design a user interface that allows biologists to usefully view large tables of raw microarray-based gene expression data. This paper presents one such interface--an electronic table (E-table) that uses fisheye distortion technology. RESULTS: The Fisheye Viewer for microarray-based gene expression data has been successfully developed to view MIAME data stored in the MAGE-ML format. The viewer can be downloaded from the project web site http://polaris.imt.uwm.edu:7777/fisheye/. The fisheye viewer was implemented in Java so that it could run on multiple platforms. We implemented the E-table by adapting JTable, a default table implementation in the Java Swing user interface library. Fisheye views use variable magnification to balance magnification for easy viewing and compression for maximizing the amount of data on the screen. CONCLUSION: This Fisheye Viewer is a lightweight but useful tool for biologists to quickly overview the raw microarray-based gene expression data in an E-table.

Gene Expression↗
PubMed2006

Amphibian tachykinin precursor.

The precursor of amphibian tachykinin has not been found although more than 30 tachykinins have been isolated from amphibians since 1964. In this report, two tachykinin-like peptides are identified from the skin secretions of the frog, Odorrana grahami. Their amino acid sequences are DDTEDLANKFIGLM-NH(2) (named tachykinin OG1) and DDASDRAKKFYGLM-NH(2) that is the same with ranamargarin found in Rana margaretae, respectively, with a conserved FXGLM-NH(2) C-terminal consensus motif. By cDNA cloning, their precursors were screened from the skin cDNA library of O. grahami. The precursors are composed of 61 amino acid (aa) residues including a signal peptide followed by an acidic spacer peptide and one copy of mature tachykinin-like peptide. Their overall structure is different from structures of other tachykinin precursors such as human protachykinin 1 precursor containing 143 aa including one copy of substance P (SP) and neurokinin A (NKA), and ascidian tachykinin 1 precursor containing 164 aa including two copies of tachykinin-like peptides. The current results demonstrate that the biosynthesis mode of tachykinins in amphibians is different from other animals.

Amino Acid Sequence↗
PubMed2006

Establishment of endolithic populations of extremophilic Cyanidiales (Rhodophyta).

BACKGROUND: Cyanidiales are unicellular extremophilic red algae that inhabit acidic and high temperature sites around hot springs and have also adapted to life in endolithic and interlithic habitats. Comparative genomic analysis of Cyanidioschyzon merolae and Galdieria sulphuraria predicts that the latter may be more broadly distributed in extreme environments because its genome contains membrane transporters involved in the uptake of reduced carbon compounds that are absent from C. merolae. Analysis of an endolithic site in the Phlegrean Fields near Naples, Italy is consistent with this prediction showing this population to be comprised solely of the newly described lineage Galdieria-B and C. merolae to be limited to humid habitats. Here, we conducted an environmental PCR survey of another extreme environment in Tuscany, Italy and contrasted Cyanidiales population structure at endolithic and interlithic habitats in Naples and Tuscany. RESULTS: We find a second Galdieria lineage (Galdieria-A) in endolithic and interlithic habitats in Tuscany but surprisingly Cyanidium was also present at these sites. The photoautotrophic Cyanidium apparently survives below the rock surface where sufficient light is available for photosynthesis. C. merolae is absent from all endolithic and interlithic sites in Tuscany. Population genetic analyses of a partial calmodulin gene fragment suggest a recent establishment or recurrent gene flow between populations in Tuscany, whereas the highly structured Galdieria-B population in Naples likely originated from 2-3 founder events. We find evidence of several recombination events across the calmodulin gene, potentially indicating the presence of sexual reproduction in the Tuscany populations. CONCLUSION: Our study provides important data regarding population structure in extreme endolithic environments and insights into how Cyanidiales may be established in and adapt to these hostile environments.

Ecosystem↗
PubMed2006

Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells.

Increased conversion of glucose to lactic acid associated with decreased mitochondrial respiration is a unique feature of tumors first described by Otto Warburg in the 1920s. Recent evidence suggests that the Warburg effect is caused by oncogenes and is an underlying mechanism of malignant transformation. Using a novel approach to measure cellular metabolic rates in vitro, the bioenergetic basis of this increased glycolysis and reduced mitochondrial respiration was investigated in two human cancer cell lines, H460 and A549. The bioenergetic phenotype was analyzed by measuring cellular respiration, glycolysis rate, and ATP turnover of the cells in response to various pharmacological modulators. H460 and A549 cells displayed a dependency on glycolysis and an ability to significantly upregulate this pathway when their respiration was inhibited. The converse, however, was not true. The cell lines were attenuated in oxidative phosphorylation (OXPHOS) capacity and were unable to sufficiently upregulate mitochondrial OXPHOS when glycolysis was disabled. This observed mitochondrial impairment was intimately linked to the increased dependency on glycolysis. Furthermore, it was demonstrated that H460 cells were more glycolytic, having a greater impairment of mitochondrial respiration, compared with A549 cells. Finally, the upregulation of glycolysis in response to mitochondrial ATP synthesis inhibition was dependent on AMP-activated protein kinase activity. In summary, our results demonstrate a bioenergetic phenotype of these two cancer cell lines characterized by increased rate of glycolysis and a linked attenuation in their OXPHOS capacity. These metabolic alterations provide a mechanistic explanation for the growth advantage and apoptotic resistance of tumor cells.

AMP-Activated Protein Kinases↗
PubMed2006

L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage.

The CUL4 (cullin 4) proteins are the core components of a new class of ubiquitin E3 ligases that regulate cell cycle, DNA replication and DNA damage response. To determine the composition of CUL4 ubiquitin E3 ligase complex, we used anti-CUL4 antibody affinity chromatography to isolate the proteins that associated with human CUL4 complexes and identified them by mass-spectrometry. A novel and conserved WD40 domain-containing protein, the human homologue of Drosophila lethal(2) denticleless protein (L2DTL) or fission yeast CDT2, was found to associate with CUL4 and DDB1. L2DTL also interacts with replication licensing protein CDT1 in vivo. Loss of L2DTL in Drosophila S2 and human cells suppressed proteolysis of CDT1 in response to DNA damage. We further isolated the human L2DTL complexes by anti-L2DTL immuno-affinity chromatography from HeLa cells and found it associates with DDB1, components of the COP9-signalosome complex (CSN) and PCNA. We found that PCNA interacts with CDT1 and loss of PCNA suppressed CDT1 proteolysis after DNA damage. Our data also revealed that in vivo, inactivation of L2DTL causes the dissociation of DDB1 from the CUL4 complex. Our studies suggest that L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage.

Adaptor Proteins, Signal Transducing↗
PubMed2006

L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes.

The CUL4-ROC1 E3 ligase complex regulates genome stability, replication and cell cycle progression. A novel WD40 domain-containing protein, L2DTL/CDT2 and PCNA were identified as proteins associated with CUL4/DDB1 complexes. Inactivation of CUL4A, L2DTL, PCNA, DDB1 or ROC1 induced p53 stabilization and growth arrest. L2DTL, PCNA and DDB1/CUL4A complexes were found to physically interact with p53 tumor suppressor and its regulator MDM2/HDM2. The isolated CUL4A complexes display potent and robust polyubiquitination activity towards p53 and this activity is dependent on L2DTL, PCNA, DDB1, ROC1 and MDM2/HDM2. We also found that the interaction between p53 and CUL4 complex is regulated by DNA damage. Our data further showed that MDM2/HDM2 is rapidly proteolyzed in response to UV irradiation and this process is regulated by CUL4/DDB1 and PCNA. Our studies demonstrate that PCNA, L2DTL and the DDB1-CUL4A complex play critical and differential roles in regulating the protein stability of p53 and MDM2/HDM2 in unstressed and stressed cells.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Folic acid rivals methylenetetrahydrofolate reductase (MTHFR) gene-silencing effect on MEPM cell proliferation and apoptosis.

It's clear that environmental factors play a role in the aetiology of orofacial clefting (OFC) and an important area of future research will be to unravel interactions that occur between candidate genes and environmental factors during early development of the embryo. Periconceptional folic acid supplementation may reduce the risk of OFC. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methylenetetrahydrofolate, the predominant circulating form of folic acid. To determine the effect of MTHFR gene mutation on murine embryonic palatal mesenchymal (MEPM) cells and the interaction with folic acid supplement, we used RNAi study in the primary cultures of MEPM cells. The cells of MTHFR gene silencing grew slower and the apoptosis cell number was more than the cells of control. Supplement with 20 microg/ml folic acid was the best to preventing teratogenic effect of MTHFR gene silencing. By flow cytometry analysis of cell cycle, results were shown that the MEPM cells were retarded in G(0)/G(1) after MTHFR gene silencing. While using 20 microg/ml folic acid supplements could make cell transit the G(1)/S restriction point and the cells growth was close to normal level.

Animals↗