Biology subjects

Han, L.

Publications and source records attributed to Han, L..

At least 91 records · Page 5Linked to original sources

bioRxiv2024

Binucleated cell formation and oncogene expression after particulate matter exposure is preceded by microtubule disruption, dysregulated cell cycle, prolonged mitosis, and septin binding

Several biopersistent high aspect ratio nanomaterials show pronounced pathogenic effects, from chronic lung inflammation and fibrosis to cancer. For example, asbestos fibers are classified as carcinogens, whereas the carcinogenicity of highly inflammatory multi-wall carbon nanotubes (MWCNTs), and TiO2 nanomaterials is still being evaluated. The exact early mechanisms of their pathogenicity towards inflammation and cancer remains uncertain, but it is likely not due to genotoxic or mutagenic activity. A proposed early mode of action that might lead to the formation of cancerous cells for asbestos fibers is the formation of binucleated and multinucleated cells, resulting in genetic instability. Here, we show that two high aspect ratio nanomaterials, MWCNTs and TiO2 nanotubes, which both induce chronic lung inflammation, induce very different cancer-related changes in vitro. TiO2 nanotubes - but not low aspect-ratio nanocubes of the same crystalline structure - disrupt microtubule organization and prolong mitosis, as well as deform nuclear shape, induce the formation of binucleated cells, and downregulate the tumour suppressor protein p53, whereas only the MWCNTs activate the stimulator of the interferon genes (STING) pathway, a hallmark of lung cancer. The observed differences in cellular responses to different high aspect ratio materials imply the need for assessing each nanomaterial individually with a broad range of tests rather than relying solely on a single marker or pathway, or even morphological or bulk chemical properties to infer possible carcinogenic properties.

cancer biology↗

bioRxiv2023

Spatially resolved molecular and cellular atlas of the mouse brain

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain.

neuroscience↗

bioRxiv2023

Integration of ATAC-seq and RNA-seq identifies novel candidate genes associated with drought tolerance in Zoysia japonica Steud.

HighlightIntegration of ATAC-seq and RNA-seq identifies novel candidate genes associated with drought tolerance in Zoysia japonica Steud. The warm-season turfgrass Zoysia japonica is renowned for its drought resistance and serves as an exceptional domestic turfgrass in China. In order to unlock the potential of this native grass, identify drought-resistant genes, enhance the genetic transformation system, and maximize its utilization benefits, we conducted physiological characterization, multi-omics analysis, and RT-qPCR experimental verification in Zoysia japonica. This study suggested that 63 high-confidence genes related to drought stress and 6 motifs regulating drought responses were identified using a combined omics approach and RT-qPCR validation. The study discovered a positive correlation between ATAC-Seq peak intensity and gene expression levels. The expression of high-confidence genes was linked to Zoysia japonica resistance evaluation and phenotypic traits, implying that these genes are involved in responding to external drought stress. This study combined ATAC-seq and RNA-seq technologies for the first time to identify drought-related genes in Zoysia japonica, elucidating the grasss adaptation to environmental stress and the regulatory mechanisms underlying stress responses, and laying the groundwork for Zoysia japonica improvement and breeding.

genomics↗

bioRxiv2023

Microinterfaces in bicontinuous hydrogelsguide rapid 3D cell migration

Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or may instead utilize existing ECM microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3D migration, few have recapitulated these natural migration paths. Here, we developed a biopolymer-based (i.e., gelatin and hyaluronic acid) bicontinuous hydrogel system formed through controlled solution immiscibility whose continuous subdomains and high micro-interfacial surface area enabled rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior was mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which was shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a new design that leverages important local interfaces to guide rapid cell migration.

bioengineering↗

bioRxiv2023

Neural stem cells protect the integrity of blood-brain barrier via the p38, JNK and ERK1/2 pathways following intracerebral hemorrhage in rats

Neural stem cells (NSCs) have displayed great potential in ameliorating brain damage following intracerebral hemorrhage (ICH) via proliferation, differentiation, and immunomodulation. However, it remains unclear whether NSCs can improve microvascular function, e.g., blood-brain barrier (BBB) integrity, after ICH. In this study, we investigate the potential therapeutic benefit of NSCs on BBB integrity as well as the underlying mechanism. Adult male Sprague-Dawley rats were randomly divided into sham, ICH+PBS, and ICH+NSCs groups for comparisons. ICH was induced by intrastriatal injection of bacterial collagenase. An aliquot of NSCs or PBS was injected via the tail vein 2 h after ICH induction. The following multiparametric measurements were compared: brain edema, hematoma volume, behavior, BBB permeability, and mitogen-activated protein kinase (MAPK) signaling pathway activity. We found that NSCs treatment attenuates BBB permeability, reduces brain edema, and promotes brain function recovery after ICH by inhibiting ERK1/2, p38, and JNK signaling pathway activation. These findings provide novel insight for future therapies aiming to prevent BBB dysfunction and improve functional recovery in ICH patients.

neuroscience↗

bioRxiv2023

In situ cryoET reveals inhibitor-induced perturbations in Pf80S GTPase interactions

Malaria parasites rely heavily on rapid, high fidelity protein synthesis to infect and replicate in human erythrocytes, making translation an attractive target for new antimalarials. Here, we have determined in situ structures of Pf80S ribosomes in thirteen conformational and compositional states from cryoFIB-milled Plasmodium falciparum-infected human erythrocytes across the stages of asexual intraerythrocytic parasite replication. We observe eight active translation intermediates, enabling us to define the native malarial translation elongation cycle, which surprisingly features a bifurcation at the decoding stage of the cycle that has not previously been described. Examination of perturbations in the distribution of ribosomes among these states in the presence of a malaria-specific translation inhibitor suggests that the inhibitor impedes PfeEF2 and PfeEF1 interactions with the ribosome. We integrated our in situ cryoET data with proteomic and ultrastructural data to arrive at a deeper understanding of malarial translation, which will inform development of new therapies.

biophysics↗

bioRxiv2023

Large-scale population genomics of Malayan pangolins reveals deep diversification and a new species

BackgroundArchipelagos and oceanic islands often present high percentage of endemism due to rapid speciation. The Malayan pangolin is a species distributing at both mainland (southern Yunnan, China) and oceanic islands via Malayan peninsula, which may result in deep differentiation among populations. In-depth investigation of population structure and genetic consequences for such species is of vital importance for their protection and conservation, practically for the critically endangered Malayan pangolin that is suffering from poaching, illegal trade, and habitat loss. ResultsHere we carried out a large-scale population genomic analysis for Malayan pangolins, and revealed three highly distinct genetic populations in this species, two of which are now being reported for the first time. Based on multiple lines of genomic and morphological evidence, we postulate the existence of a new pangolin species (Manis_1). Genetic diversity and recent inbreeding were both at a moderate level for both Malayan pangolins and Manis_1, but mainland Malayan pangolins presented relatively lower genetic diversity, higher inbreeding and fitness cost than island populations. ConclusionsWe found extremely deep and graded differentiation in Malayan pangolins, with two newly discovered genetic populations and a new pangolin species that is closely related to the Philippine pangolin than the typical Malayan pangolin, but a distant relative of the Indian pangolin. Anthropogenic factors did not significantly weaken the basis of genetic sustainability for Malayan pangolins, but mainland Malayan pangolins should be paid more attention for conservation due to higher genetic risks than island populations.

genomics↗

bioRxiv2023

Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

A crucial event in sexual reproduction is when haploid sperm and egg fuse to form a new diploid organism at fertilization. In mammals, direct interaction between egg JUNO and sperm IZUMO1 mediates gamete membrane adhesion, yet their role in fusion remains enigmatic. We used AlphaFold to predict the structure of other extracellular proteins essential for fertilization to determine if they could form a complex that may mediate fusion. We first identified TMEM81, whose gene is expressed by mouse and human spermatids, as a protein having structural homologies with both IZUMO1 and another sperm molecule essential for gamete fusion, SPACA6. Using a set of proteins known to be important for fertilization and TMEM81, we then systematically searched for predicted binary interactions using an unguided approach and identified a pentameric complex involving sperm IZUMO1, SPACA6, TMEM81 and egg JUNO, CD9. This complex is structurally consistent with both the expected topology on opposing gamete membranes and the location of predicted N-glycans not modeled by AlphaFold-Multimer, suggesting that its components could organize into a synapse-like assembly at the point of fusion. Finally, the structural modeling approach described here could be more generally useful to gain insights into transient protein complexes difficult to detect experimentally. Impact statementStructural modeling with AlphaFold-Multimer was used to investigate extracellular protein interactions involved in mammalian egg-sperm recognition, suggesting a putative pentameric complex that includes TMEM81, a sperm protein not previously involved in gamete recognition.

biophysics↗

bioRxiv2023

Incorporating physics to overcome data scarcity in predictive modeling of protein function: a case study of BK channels

Machine learning has played transformative roles in numerous chemical and biophysical problems such as protein folding where large amount of data exists. Nonetheless, many important problems remain challenging for data-driven machine learning approaches due to the limitation of data scarcity. One approach to overcome data scarcity is to incorporate physical principles such as through molecular modeling and simulation. Here, we focus on the big potassium (BK) channels that play important roles in cardiovascular and neural systems. Many mutants of BK channel are associated with various neurological and cardiovascular diseases, but the molecular effects are unknown. The voltage gating properties of BK channels have been characterized for 473 site-specific mutations experimentally over the last three decades; yet, these functional data by themselves remain far too sparse to derive a predictive model of BK channel voltage gating. Using physics-based modeling, we quantify the energetic effects of all single mutations on both open and closed states of the channel. Together with dynamic properties derived from atomistic simulations, these physical descriptors allow the training of random forest models that could reproduce unseen experimentally measured shifts in gating voltage, {Delta}V1/2, with a RMSE [~] 32 mV and correlation coefficient of R [~] 0.7. Importantly, the model appears capable of uncovering nontrivial physical principles underlying the gating of the channel, including a central role of hydrophobic gating. The model was further evaluated using four novel mutations of L235 and V236 on the S5 helix, mutations of which are predicted to have opposing effects on V1/2 and suggest a key role of S5 in mediating voltage sensor-pore coupling. The measured {Delta}V1/2 agree quantitatively with prediction for all four mutations, with a high correlation of R = 0.92 and RMSE = 18 mV. Therefore, the model can capture nontrivial voltage gating properties in regions where few mutations are known. The success of predictive modeling of BK voltage gating demonstrates the potential of combining physics and statistical learning for overcoming data scarcity in nontrivial protein function prediction. Author SummaryDeep machine learning has brought many exciting breakthroughs in chemistry, physics and biology. These models require large amount of training data and struggle when the data is scarce. The latter is true for predictive modeling of the function of complex proteins such as ion channels, where only hundreds of mutational data may be available. Using the big potassium (BK) channel as a biologically important model system, we demonstrate that a reliable predictive model of its voltage gating property could be derived from only 473 mutational data by incorporating physics-derived features, which include dynamic properties from molecular dynamics simulations and energetic quantities from Rosetta mutation calculations. We show that the final random forest model captures key trends and hotspots in mutational effects of BK voltage gating, such as the important role of pore hydrophobicity. A particularly curious prediction is that mutations of two adjacent residues on the S5 helix would always have opposite effects on the gating voltage, which was confirmed by experimental characterization of four novel mutations. The current work demonstrates the importance and effectiveness of incorporating physics in predictive modeling of protein function with scarce data.

bioinformatics↗

bioRxiv2023

Architecture of the Vertebrate Egg Coat and Structural Basis of the ZP2 Block to Polyspermy

Post-fertilization cleavage of glycoprotein ZP2, a major subunit of egg zona pellucida (ZP) filaments, is crucial for mammalian reproduction by irreversibly blocking polyspermy. ZP2 processing is thought to inactivate a sperm-binding activity located upstream of the proteins cleavage site; however, its molecular consequences and connection with ZP hardening are unknown. Here we report X-ray crystallographic, cryo-EM and biochemical studies showing that cleavage of ZP2 triggers its oligomerization. Deletion of the ZP-N1 domain that precedes the cleavage site of mouse ZP2 allows it to homodimerize even without processing, and animals homozygous for this variant are subfertile by having a semi-hardened ZP that allows sperm attachment but hinders penetration. Combined with the structure of a native egg coat filament, which reveals the molecular basis of heteromeric ZP subunit interaction, this suggests that oligomerization of cleaved ZP2 cross-links the ZP, rigidifying it and making it physically impenetrable to sperm.

biophysics↗

bioRxiv2023

FOXK2 amplification and overexpression promotes breast cancer development and chemoresistance

Activation of oncogenes through DNA amplification/overexpression plays an important role in cancer initiation and progression. Chromosome 17 has many cancer-associated genetic anomalies. This cytogenetic anomaly is strongly associated with poor prognosis of breast cancer. FOXK2 gene is located on 17q25 and encodes a transcriptional factor with a forkhead DNA binding domain. By integrative analysis of public genomic datasets of breast cancers, we found that FOXK2 is frequently amplified and overexpressed in breast cancers. FOXK2 overexpression in breast cancer patients is associated with poor overall survival. FOXK2 knockdown significantly inhibits cell proliferation, invasion and metastasis, and anchorage-independent growth, as well as causes G0/G1 cell cycle arrest in breast cancer cells. Moreover, inhibition of FOXK2 expression sensitizes breast cancer cells to frontline anti-tumor chemotherapies. More importantly, co-overexpression of FOXK2 and PI3KCA with oncogenic mutations (E545K or H1047R) induces cellular transformation in non-tumorigenic MCF10A cells, suggesting that FOXK2 is an oncogene in breast cancer and is involved in PI3KCA-driven tumorigenesis. Our study identified CCNE2, PDK1, and Estrogen receptor alpha (ESR1) as direct transcriptional targets of FOXK2 in MCF-7 cells. Blocking CCNE2- and PDK1-mediated signaling by using small molecule inhibitors has synergistic anti-tumor effects in breast cancer cells. Furthermore, FOXK2 inhibition by gene knockdown or inhibitors for its transcriptional targets (CCNE2 and PDK1) in combination with PI3KCA inhibitor, Alpelisib, showed synergistic anti-tumor effects on breast cancer cells with PI3KCA oncogenic mutations. In summary, we provide compelling evidence that FOXK2 plays an oncogenic role in breast tumorigenesis and targeting FOXK2-mediated pathways may be a potential therapeutic strategy in breast cancer.

cancer biology↗

bioRxiv2023

Projectome-defined subtypes and modular intra-hypothalamic subnetworks of peptidergic neurons

The hypothalamus plays a vital role in coordinating essential neuroendocrine, autonomic, and somatomotor responses for survival and reproduction. While previous studies have explored population-level projections of hypothalamic neurons, the specific innervation patterns of individual hypothalamic axons remain unclear. To understand the organization of hypothalamic axon projections, we conducted a comprehensive reconstruction of single-cell projectomes from 7,180 mouse hypothalamic neurons expressing specific neuropeptides. Our analysis identified 31 distinct subtypes based on projectome-defined characteristics, with many exhibiting long-range axon collateral projections to multiple brain regions. Notably, these subtypes selectively targeted specific subdomains within downstream areas, either unilaterally or bilaterally. Furthermore, we observed that individual peptidergic neuronal types encompassed multiple projectome-defined subtypes, explaining their diverse functional roles. Additionally, by examining intra-hypothalamic axon projections, we uncovered six modular subnetworks characterized by enriched intramodular connections and distinct preferences for downstream targets. This modular organization of the intra-hypothalamic network likely contributes to the coordinated organization of hypothalamic outputs. In summary, our comprehensive projectome analysis reveals the organizational principles governing hypothalamic axon projections, providing a framework for understanding the neural circuit mechanisms underlying the diverse and coordinated functions of the hypothalamus.

neuroscience↗

bioRxiv2023

Transcriptional profiling of mucus production and modification in rhesus macaque endocervical cells under hormonal regulation

ObjectiveEndocervical mucus production is a key regulator of fertility throughout the menstrual cycle. With cycle-dependent variability in mucus quality and quantity, cervical mucus can either facilitate or block sperm ascension into the upper female reproductive tract. This study seeks to identify genes involved in the hormonal regulation of mucus production, modification, and regulation through profiling the transcriptome of endocervical cells from the non-human primate, the Rhesus Macaque (Macaca mulatta). DesignExperimental. SettingTranslational science laboratory. InterventionWe treated differentiated primary endocervical cultures with estradiol (E2) and progesterone (P4) to mimic peri-ovulatory and luteal-phase hormonal changes. Using RNA-sequencing, we identified differential expression of gene pathways and mucus producing and modifying genes in cells treated with E2 compared to hormone-free conditions and E2 compared to E2-primed cells treated with P4. Main Outcome MeasuresWe pursued differential gene expression analysis on RNA-sequenced cells. Sequence validation was done using qPCR. ResultsOur study identified 158 genes that show significant differential expression in E2-only conditions compared to hormone-free control, and 250 genes that show significant differential expression in P4-treated conditions compared to E2-only conditions. From this list, we found hormone-induced changes in transcriptional profiles for genes across several classes of mucus production, including ion channels and enzymes involved in post-translational mucin modification that have not previously been described as hormonally regulated. ConclusionOur study is the first to use an in vitro culture system to create an epithelial-cell specific transcriptome of the endocervix. As a result, our study identifies new genes and pathways that are altered by sex-steroids in cervical mucus production.

molecular biology↗

bioRxiv2023

The first genome assembly of the amphibian nematode parasite (Aplectana chamaeleonis)

Cosmocercoid nematodes are common parasites of the digestive tract of amphibians. Genomic resources are important for understanding the evolution of a species and the molecular mechanisms of parasite adaptation. So far, no genome resource of Cosmocercoid has been reported. In 2020, a massive Cosmocercoid infection was found in the small intestine of a toad, causing severe intestinal blockage. We morphologically identified this parasite as A. chamaeleonis. Here, we report the first A. chamaeleonis genome with a genome size of 1.04 Gb. The repeat content of this A. chamaeleonis genome is 72.45 %, and the total length is 751 Mb. This resource is fundamental for understanding the evolution of Cosmocercoid and provides the molecular basis for Cosmocercoid infection and control.

genomics↗

bioRxiv2023

Spatial and Amplitude Dynamics of Neurostimulation: Insights from the Acute Intrahippocampal Kainate Seizure Mouse Model

ObjectiveNeurostimulation is an emerging treatment for patients with medically refractory epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. MethodsWe performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of temporal lobe epilepsy. We evaluated combinations of six anatomic targets and three stimulus amplitudes. ResultsWe found that the spike-suppressive effects of high-frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 A stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. SignificanceThese findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti-seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy. Key PointsO_LIEvaluated spatial and temporal parameters of neurostimulation in a mouse model of acute seizures C_LIO_LIBrief bursts of high-frequency (100 Hz) stimulation effectively interrupted epileptiform activity. C_LIO_LIThe suppressive effect was highly dependent on stimulation amplitude and was maximal at the ipsilateral CA1 and CA3 regions. C_LIO_LIPro-excitatory effects were identified with high-amplitude high-frequency stimulation at the ventral hippocampal commissure and contralateral CA1. C_LI

neuroscience↗

bioRxiv2023

Pioneer factor Foxa2 mediates chromatin conformation changes in ligand-dependent activation of nuclear receptor FXR

ABSTACTActivation of nuclear receptors, a family of ligand-dependent transcription factors, is used extensively in development of drug targets. We have previously shown that pioneer factor Foxa2 opens chromatin for binding of nuclear receptors FXR and LXR during acute ligand activation. FXR is activated by bile acids and deletion of Foxa2 in the liver results in intrahepatic cholestasis. We hypothesized that Foxa2 also enables chromatin conformational changes during ligand activation. We performed Foxa2 HiChIP to assess Foxa2-dependent long-range interactions in mouse livers treated with either vehicle control or FXR agonist GW4064. HiChIP contact analysis shows that global chromatin interactions are dramatically increased during FXR activation. Ligand-treated livers exhibit extensive redistribution of topological associated domains (TAD and substantial increase in Foxa2-anchored loops, suggesting Foxa2 is involved in dynamic chromatin conformational changes. We demonstrate that chromatin conformation, including genome-wide interactions, TADs, intra-chromosomal and inter-chromosomal Foxa2-anchored loops, drastically changes upon addition of FXR agonist. Hence, we determine a novel role for Foxa2 in enabling these conformational changes, extending its function in bile acid metabolism.

pharmacology and toxicology↗

bioRxiv2023

Spatiotemporal cell landscape of human embryonic tooth development

Understanding the cellular composition and trajectory of human tooth development is valuable for dentistry and stem cell engineering research. Previous single-cell studies have focused on mature human tooth and developing mice tooth, but cell landscape on human embryonic dental development is still lacking. We collected tooth germ tissues from aborted fetus (17-24 week) for single cell RNA sequence and spatial transcriptome. We classified all cells into seven subclusters of epithelium, seven clusters of mesenchyme and other cell types like Schwann cell precursor and pericyte. For epithelium, the Stratum intermedium branch and the ameloblast branch diverged from a same set of KRT15+-HOPX+-ALCAM+ epithelial stem cell lineage, but the spatial distribution of two branches were not clearly distinct. This trajectory received spatially adjacent regulation signals from mesenchyme and pericyte, including JAG1 and APP. The differentiation of pulp cell and pre-odontoblast showed four waves of temporally distinct gene expression, which involved regulation networks of LHX9, DLX5 and SP7 and were regulated by upstream ligands like BMP family. Taken together, we provided a reference landscape for the research on human early tooth development, covering different spatial structures and developmental periods.

cell biology↗

bioRxiv2023

MicroRNA-195-3p as a potential regulator of hypoxic injury in HUVECs

Coronary heart disease is the most common heart disease and is the leading cause of cardiovascular death worldwide. Revascularization methods are considered effective against coronary heart disease However, the mechanism of molecular revascularization remains largely unknown. Endothelial cells are the primary cells that initiate angiogenesis and arteriogenesis and require a hypoxic environment for induction. In this study, we aimed to determine the expression and role of microRNA-195-3p in hypoxia-treated HUVEs(human umbilical vein endothelial cells). Herein, we induced hypoxia in human umbilical vein endothelial cells using the "Anaerobic tank method." Hypoxia injured human umbilical vein endothelial cells showed upregulation of microRNA-195-3p; decreased cell proliferation, migration, and autophagy; and increased apoptosis. Furthermore, the microRNA-195-3p inhibitor partially reversed the effects of hypoxia-induced injury of human umbilical vein endothelial cells. Therapeutic intervention using microRNA-195-3p inhibitor could maintain endothelial cell function under hypoxic conditions, improve cell activity, and be considered a new treatment strategy for coronary heart diseases.

cell biology↗