Biology subjects

Li, C.-L.

Publications and source records attributed to Li, C.-L..

7 recordsLinked to original sources

bioRxiv2025

MicroRNA-383-5p alleviates hemorrhagic transformation and improves outcomes after endovascular recanalization for acute ischemic stroke

BackgroundHemorrhage transformation (HT) after reperfusion therapy is linked with poor outcomes in acute ischemic stroke patients. This study aimed to determine the role of neuronal microRNA-383 in alleviating HT-associated injury using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation reoxygenation (OGD/R) models. MethodsIn neurons following OGD/R, the family of miR-383 and NADPH oxidase (NOX) expression was evaluated. After miR-383-5p intervention and small interfering RNA, reactive oxygen species (ROS) and neuronal injury were assessed. Two hundred and five hyperglycemic rats were used to establish the HT model induced by mechanical reperfusion after 5-hour MCAO, followed by 3 and 6 hours of reperfusion, and treated with intravenous administration of miR-383-5p agomir before reperfusion. Brain water content, hemorrhage severity, infarct volume, blood-brain barrier (BBB) disruption, neuronal apoptosis, ROS production, miR-383-5p and NOX4 expression, and BBB-associated proteins were assessed. ResultsMiR-383-5p expression significantly decreased in OGD/R-treated neurons, while miR-383-3p expression did not differ. Elevating miR-383-5p levels reduced neuronal injury, ROS overproduction, and NOX4 overexpression as a target of miR-383-5p, shown in OGD/R-treated neurons. In the MCAO model, increased miR-383-5p suppressed NOX4 upregulation, alleviated brain edema, infarct volume, and hemorrhage severity, reduced neuronal apoptosis and ROS overproduction, and preserved BBB integrity after mechanical reperfusion for ischemia, thereby improving short-term neurological outcomes. ConclusionsMiR-383-5p alleviates oxidative stress injury and neuronal apoptosis, and preserves BBB integrity by regulating NOX4. Neuronal miR-383-5p could become a potential target for intervention to decrease HT and ameliorate outcomes in endovascular reperfusion treatment for acute ischemic stroke.

neuroscience↗

bioRxiv2024

MicroRNA-29a-5p Attenuates Oxygen-glucose Deprivation and Reoxygenation Injury in Astrocytes by Targeting Glycogen Synthase Kinase beta

BackgroundHemorrhage transformation (HT) following endovascular reperfusion treatment is associated with worse clinical outcomes in acute ischemic stroke patients. MicroRNA (miR) modulates several aspects of cerebral ischemia-reperfusion injury, including blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis, significantly impacting cerebral recovery and function. This study investigated the role of astrocytic miR-29a-5p in HT in the transient middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation reoxygenation (OGD/R) model of astrocytes. MethodsMiR-29a-5p expression in the OGD/R astrocyte model was assessed. The astrocyte injury, the expression of A1 and A2 phenotypes of reactive astrocytes, and the regulation of miR-29a-5p target genes were evaluated after the miR-29a-5p intervention. A mechanical reperfusion-induced HT model was established in hyperglycemic rats using 5-hour MCAO following reperfusion at 6 hours. MiR-29a-5p agomir was administered intravenously before reperfusion. Infarct volume, HT, BBB damage, neurological score, the expression of miR-29a-5p, and its target genes were evaluated. ResultsMiR-29a-5p expression decreased in OGD/R-treated astrocytes and the peri-infarction tissue and blood of the MCAO model. Elevating miR-29a-5p levels reduced astrocyte injury, suppressed neurotoxic A1 astrocyte markers (C3, Fkbp5, and Serping1), while enhanced neuroprotective A2 astrocyte markers (S100a10 and Emp1) in the OGD/R and MCAO models. Intravenous administration of miR-29a-5p agomir increased the expression of miR-29a-5p and reduced infarct volume, reperfusion-induced HT, and BBB breakdown after ischemia, improving neurological outcomes in the MCAO model. Overexpression of miR-29a-5p effectively suppressed the expression of its direct target genes, glycogen synthase kinase 3 beta and aquaporin 4 in the OGD/R and MCAO models. ConclusionsMiR-29a-5p alleviates astrocyte injury and regulates A1 and A2 astrocyte markers, glycogen synthase kinase 3 beta, and aquaporin 4 in astrocytes subjected to ischemia-reperfusion injury. Astrocytic miR-29a-5p may be a protective target for reducing HT and improving outcomes following mechanical reperfusion in acute ischemic stroke.

neuroscience↗

bioRxiv2024

MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat

Hemorrhagic transformation after endovascular thrombectomy predicts poor outcomes in acute ischemic stroke with large vessel occlusion. The roles of microRNAs in the pathogenesis of parenchymal hematoma (PH) are still unclear. This study aims to investigate the microRNA and mRNA regulatory network associated with PH after mechanical reperfusion in the animal stroke model and oxygen-glucose deprivation/reoxygenation (OGD/R) model. Twenty-five microRNAs were assessed in the reperfusion-induced hemorrhage model in rats with hyperglycemic conditions receiving 5-hour middle cerebral artery occlusion. Thirteen down-regulated microRNAs (miRNA-29a-5p, miRNA-29c-3p, miRNA-126a-5p, miRNA-132-3p, miRNA-136-3p, miRNA-142-3p, miRNA-153-5p, miRNA-218a-5p, miRNA-219a-2-3p, miRNA-369-5p, miRNA-376a-5p, miRNA-376b-5p, miRNA-383-5p) and one up-regulated microRNA (miRNA-195-3p) were found in rat peri-infarct with PH. Ten of these 14 PH-related microRNAs were significantly differentially expressed in at least two of five models of neuron, astrocyte, microglia, BMEC, and pericyte after OGD/R, consistent with the animal model results. Thirty-one predicted hub target genes were significantly differentially expressed in rat peri-infarct with PH. Forty-nine microRNA-mRNA regulatory axes of PH were revealed, which were related to the mechanisms of oxidative stress, apoptosis, immune, and inflammation. Simultaneously differentially expressed microRNAs and related genes in several cells of the neurovascular unit may serve as valuable targets for PH after endovascular thrombectomy in acute ischemic stroke.

neuroscience↗

bioRxiv2023

A genome-wide survey of DNA methylation in Panax notoginseng reveals CHH hyper-methylation regulates the after-ripening and dormancy of recalcitrant seeds

DNA methylation plays a crucial role in regulating fruit ripening and seed development. It remains unknown about the dynamic characteristics of DNA methylation and its regulation mechanisms in morpho-physiological dormancy (MPD)-typed seeds with recalcitrant characteristics. The P. notoginseng seeds are defined by the MPD and are characterized by a strong sensitivity to dehydration during the after-ripening process. We performed DNA methylomes, siRNA profiles, and transcriptomes of embryo and endosperm in P. notoginseng seeds at different after-ripening stages. Herein, we find that the CHH hyper-methylation contributes to the global increase in DNA methylation during the after-ripening process of P. notoginseng seeds. The endosperm genome is hyper-methylated compared to the embryo genome. The CHH hyper-methylation is caused by the high expression level of DNA methyltransferase PnCMT2 in the embryo, and PnDRM2 in the endosperm, respectively. The CHH hyper-methylation alters gene transcription levels to regulate the after-ripening and dormancy of recalcitrant seeds. For example, it inhibits the expression of genes in embryo development to make seeds maintain a dormant status, whereas it activates the expression of genes in the hormone-mediated signaling pathway, and energy metabolism to accomplish the MPD-typed seed after-ripening process. Together, our findings reveal a global increase in DNA methylation and its vital driver in gene expression, and thus elucidate how global CHH hyper-methylation regulates the after-ripening in recalcitrant MPD-typed seeds. This work establishes a key role for epigenetics in regulating the dormancy of MPD-typed seeds with recalcitrant characteristics.

developmental biology↗

bioRxiv2021

Locus-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulated epigenome has been linked to increased susceptibility to age-related disorders. We aim to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. In this study, we focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed redistribution of of both histone marks, but the changes are more significant for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed "aging-associated repressive domains" (AARDs). These AARDs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Interestingly, maintenance of high H3K9me2 levels in these regions have been shown to correlate with longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear elements (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals, it is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology. Author summaryHeterochromatin refers to the portion of the genome that is tightly packed where genes stay silent. Heterochromatin is typically decorated by particular chemical groups called histone modifications, such as trimethylation of lysine 9 or lysine 27 on histone 3 (H3K9me3 or H3K27me3). To understand how the heterochromatin landscape may change from a "youthful" to an "aged" state, we monitored the genome-wide patterns of H3K9me3 and H3K27me3 during aging using the genetic model soil worm C. elegans. We found that while H3K27me3 remained relatively stable with age, H3K9me3 showed profound genome-wide redistribution in aged worms. We observed that new H3K9me3-marked heterochromatin preferentially formed in specific gene-rich regions in aged worms. Interestingly, these particular regions were marked by high levels of three other histone modifications when worms were young. This result suggested that H3K9me3 gain during aging is influenced by the gene-specific landscape of histone modifications established at young age rather than occurs in a stochastic manner. In summary, our study discovered reproducible and gene-specific changes in histone modifications that likely contribute to the aging phenotypes.

genomics↗

bioRxiv2021

D614G Substitution of SARS-CoV-2 Spike Protein Increases Syncytium Formation and Viral Transmission via Enhanced Furin-mediated Spike Cleavage

Since the D614G substitution in the spike (S) of SARS-CoV-2 emerged, the variant strain underwent rapid expansion to become the most abundant strain worldwide. Therefore, this substitution may provide an advantage of viral spreading. To explore the mechanism, we analyzed 18 viral isolates containing S proteins with either G614 or D614. Both the virus titer and syncytial phenotype were significantly increased in S-G614 than in S-D614 isolates. We further showed increased cleavage of S at the furin substrate site, a key event that promotes syncytium, in S-G614 isolates. These functions of the D614G substitution were validated in cells expressing S protein. The effect on syncytium was abolished by furin inhibitor treatment and mutation of the furin-cleavage site, suggesting its dependence on cleavage by furin. Our study provides a mechanistic explanation for the increased transmissibility of S-G614 containing SARS-CoV-2 through enhanced furin-mediated S cleavage, which increases membrane fusion and virus infectivity.

microbiology↗

bioRxiv2019

Empathic contagious pain and consolation in laboratory rodents: species and sex differences

Laboratory rodents are gregarious in nature and have a feeling of empathy when witnessing a familiar conspecific in pain. The rodent observers express two levels of empathic responses: observational contagious pain (OCP) and consolation. Here we examined the sex and species difference of OCP and consolation in male and female mice and rats. We observed no species difference in both OCP and consolation, but significant species difference in general social (allo-mouth and/or allo-tail sniffing) and non-social (self-grooming) behaviors. For sex difference, male mouse observers showed more allolicking and allogrooming behaviors toward a familiar conspecific in pain during and longer time increase in pain sensitivity after the PDSI than female mouse observers. However, no sex difference was observed in rats. Our results highlighted an evolutionary view of empathy that social animals including rodents also have the ability to feel, recognize, understand and share the others distressing states.

animal behavior and cognition↗