Biology subjects

Yang, Q.

Publications and source records attributed to Yang, Q..

At least 361 records · Page 20Linked to original sources

bioRxiv2020

Neural Basis of Olfactory and Trigeminal Integration

Humans naturally integrate signals from the olfactory and intranasal trigeminal systems. A tight interplay has been demonstrated between these two systems, and yet the underlying neural circuitry that mediates olfactory-trigeminal integration remains poorly understood. Using functional magnetic resonance imaging (fMRI), combined with psychophysics, this study investigated the neural mechanisms underlying olfactory-trigeminal integration. Fifteen participants with normal olfactory function performed a localization task with air-puff stimuli, phenylethyl alcohol (PEA; rose odor), or a combination thereof while being scanned. The ability to localize PEA to either nostril was at chance. Yet, its presence significantly improved the localization accuracy of weak, but not strong, air-puffs, relative to air-puff localization without concomitant PEA when both stimuli were delivered concurrently to the same nostril, but not when different nostrils received the two stimuli. This enhancement in localization accuracy, exemplifying the principles of spatial coincidence and inverse effectiveness in multisensory integration, was associated with multisensory integrative activity in the primary olfactory (POC), orbitofrontal (OFC), superior temporal (STC), inferior parietal (IPC) and cingulate cortices, and in the cerebellum. Multisensory enhancement in most of these regions, except the OFC, correlated with behavioral multisensory enhancement, as did increases in connectivity between some of these regions. We interpret these findings as indicating that the POC is part of a distributed brain network mediating integration between the olfactory and trigeminal systems. HIGHLIGHTSO_LIPsychophysical and neuroimaging study of olfactory-mechanosensory (OM) integration C_LIO_LIBehavior, cortical activity and network connectivity show OM integration C_LIO_LIOM integration obeys principles of inverse effectiveness and spatial coincidence C_LIO_LIBehavioral and neural measures of OM integration are correlated C_LI

neuroscience↗

bioRxiv2020

UNC-45A Destabilizes MTs Independent of its Effect on Non-Muscle Myosin II

In invertebrates, UNC-45 regulates myosin stability and functions. Vertebrates have two distinct isoforms of the protein: UNC-45B, expressed in muscle cells only and UNC-45A, expressed in all cells and implicated in regulating both Non-Muscle Myosin II (NMII)- and microtubule (MT)-associated functions. Here we show for the first time that: a) in vitro UNC-45A binds to the MT lattice and weakens its integrity leading to MT bending, breakage and depolymerization, b) in cells, UNC-45A overexpression causes loss of MT mass and increase in MT breakages, c) both in vitro and in cells, UNC-45A destabilizes MTs independent of its NMII C-terminal binding domain and destabilization occurs even in presence of the NMII inhibitor blebbistatin. These findings are consistent with a not mutually exclusive but rather dual role of UNC-45A in regulating NMII activity and MT stability. Because many human diseases, from cancer to neurodegenerative diseases, are caused by or associated with deregulation of MT stability our findings have profound implications in both, the biology of MTs as well as the biology of human diseases and possible therapeutic implications for their treatment.

cell biology↗

bioRxiv2020

Identification of potential biomarkers or therapeutic targets of mesenchymal stem cells in multiple myeloma by bioinformatics analysis.

ObjectivesMesenchymal stem cells (MSCs) play important roles in multiple myeloma (MM) pathogenesis. Previous studies have discovered a group of MM-associated potential biomarkers in MSCs derived from bone marrow (BM-MSCs). However, no study of the bioinformatics analysis was conducted to explore the key genes and pathways of MSCs derived from adipose (AD-MSCs) in MM. The aim of this study was to screen potential biomarkers or therapeutic targets of AD-MSCs and BM-MSCs in MM. MethodsThe gene expression profiles of AD-MSCs (GSE133346) and BM-MSCs (GSE36474) were downloaded from Gene Expression Omnibus (GEO) database. Gene Oncology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network of differentially expressed genes (DEGs) were performed. ResultsA total of 456 common downregulated DEGs in two datasets were identified and the remaining DEGs in GSE133346 were further identified as specific DEGs of AD-MSCs. Furthermore, a PPI network of common downregulated DEGs was constructed and seven hub genes were identified. Importantly, cell cycle was the most significantly enrichment pathway both in AD-MSCs and BM-MSCs from MM patients. ConclusionWe identified key genes and pathways closely related with MM progression, which may act as potential biomarkers or therapeutic targets of MM.

bioinformatics↗

bioRxiv2020

Pandora: 4-D white matter bundle population-based atlasesderived from diffusion MRI fiber tractography

Brain atlases have proven to be valuable neuroscience tools for localizing regions of interest and performing statistical inferences on populations. Although many human brain atlases exist, most do not contain information about white matter structures, often neglecting them completely or labelling all white matter as a single homogenous substrate. While few white matter atlases do exist based on diffusion MRI fiber tractography, they are often limited to descriptions of white matter as spatially separate "regions" rather than as white matter "bundles" or fascicles, which are well-known to overlap throughout the brain. Additional limitations include small sample sizes, few white matter pathways, and the use of outdated diffusion models and techniques. Here, we present a new population-based collection of white matter atlases represented in both volumetric and surface coordinates in a standard space. These atlases are based on 2443 subjects, and include 216 white matter bundles derived from 6 different state-of-the-art tractography techniques. This atlas is freely available and will be a useful resource for parcellation and segmentation.

neuroscience↗

bioRxiv2020

18F-FDG-PET Hyperactivity in Alzheimers Disease Cerebellum and Primary Olfactory Cortex

Cerebellar involvement in Alzheimers disease (AD) has not been studied to the extent that cortical neuropathological changes have. Historical and recent histopathological literature demonstrate cerebellar AD pathology while functional investigation has demonstrated disrupted intrinsic cortical - cerebellar connectivity in AD. Additionally, olfactory deficits occur early in AD, prior to the onset of clinical symptoms. The neurological basis for the involvement of the cerebellum and olfactory system in the disease course remain unclear. 18F-fludeoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimers Disease Neuroimaging Initiative (ADNI) were analyzed to characterize metabolism in the cerebellum and olfactory region of AD, mild-cognitive impaired (MCI), and age-matched cognitively normal (CN) controls. In contrast to known parietal and temporal lobe FDG hypo-metabolism within the default mode network in AD, a significant FDG hyper-metabolism was found in the cerebellum and olfactory cortical regions (including the piriform cortex, olfactory tubercle, anterior olfactory nucleus, and nucleus accumbens shell). The increase in cerebellum glucose utilization was shown also in late- verses early-MCI patients. The cerebellar and olfactory regions both contain inhibitory distal and inter-neuronal connections that are vulnerable to disruption in AD. The hyper-metabolism in the cerebellum and olfactory structures may reflect disruption of local and system-wide inhibitory networks due to AD neurodegeneration, suggesting a hypothetical mechanism for susceptibility of the olfactory system to early AD pathology.

neuroscience↗

bioRxiv2020

A pan-cancer analysis of CpG Island gene regulation reveals extensive plasticity within Polycomb targets

CpG Island promoter genes make up more than half of human genes, and a subset regulated by Polycomb-Repressive Complex 2 (PRC2+-CGI) become DNA methylated and silenced in cancer. Here, we perform a systematic regulatory analysis of CGI genes across TCGA cancer types, finding that PRC2+-CGI genes are frequently prone to transcriptional upregulation as well. These upregulated PRC2+-CGI genes control important pathways such as Epithelial-Mesenchymal Transition and TNF-associated inflammatory response, and have the greatest cancer-type specificity among any class of CGI genes. Using publicly available chromatin datasets and genetic perturbations, we show that transcription factor binding sites (TFBSs) within distal enhancers underlie transcriptional activation of PRC2+-CGI genes, in contrast to PRC2-free CGI genes which are predominantly regulated by promoter TFBSs. Surprisingly, a large subset of PRC2+-CGI genes that are upregulated in one cancer type are also hypermethylated/silenced in at least one other cancer type, highlighting the high degree of regulatory plasticity likely derived from their complex regulatory patterns during normal development.

cancer biology↗

bioRxiv2020

Cell fate coordinates mechano-osmotic forces in intestinal crypt morphogenesis

Intestinal organoids derived from single cells undergo complex crypt-villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Through light-sheet microscopy and mechanical perturbations, we demonstrate that organoid crypt formation coincides with stark lumen volume reduction, which works synergistically with actomyosin-generated crypt apical and villus basal tension to drive morphogenesis. We analyse these mechanical features in a quantitative 3D biophysical model and detect a critical point in actomyosin tensions, above which crypt becomes robust to volume changes. Finally, via single-cell RNA sequencing and pharmacological perturbations, we show that enterocyte-specific expressed sodium/glucose cotransporter modulates lumen volume reduction via promoting cell swelling. Altogether, our study reveals how cell fate-specific changes in osmotic and actomyosin forces coordinate robust organoid morphogenesis. One Sentence SummaryEmergence of region-specific cell fates drive actomyosin patterns and luminal osmotic changes in organoid development

developmental biology↗

bioRxiv2020

Tracing two causative SNPs reveals SARS-CoV-2 transmission in North America population

During the COVID-19 pandemic, precisely tracing the route of the SARS-CoV-2 transmission in human population remains challenging. Because this RNA virus can mutate massively without a specifically tracing maker. Herein, using a geographic stratified genome-wide association study (GWAS) of 2599 full-genome sequences, we identified that two SNPs (i.e., 1059.C>T and 25563.G>T) of linkage disequilibrium were presented in approximately half of North America SARS-CoV-2 population (p = 2.44 x 10-212 and p = 2.98 x 10-261), resulting two missense mutations (i.e., Thr 265 Ile and Gln 57 His) in ORF1ab and ORF3a, respectively. Interestingly, these two SNPs exclusively occurred in the North America dominated clade 1, accumulated during mid to late March, 2020. We did not find any of these two SNPs by retrospectively tracing the two SNPs in bat and pangolin related SARS-CoV-2 and human SARS-CoV-2 from the first epicenter Wuhan or other regions of China mainland. This suggested that the SARS-CoV-2 population of Chinese mainland were different from the prevalent strains of North America. Time-dependently, we found that these two SNPs first occurred in Europe SARS-CoV-2 (26-Feb-2020) which was 3 days early than the occurring date of North America isolates and 17 days early for Asia isolates (Taiwan China dominated). Collectively, this population genetic analysis highlights a well-confidential transmission route of the North America isolates and the two SNPs we newly identified are possibly novel diagnosable or druggable targets for surveillance and treatment.

microbiology↗

bioRxiv2020

Understanding the effects of the direct contacts and the indirect contacts on the epidemic spreading among beef cattle farms in southwest Kansas

Moving infected animals and sharing contaminated vehicles are considered as the most potent ways for between-farm disease transmission. The objective of this study is to develop a network-based simulation model to investigate the effects of direct contact, indirect contact, and their combination on a hypothetical foot-and-mouth disease spreading between beef-cattle farms in southwest Kansas, US, and explore the effect of different types of information-sharing networks on preventing the disease spreading. Based on synthetic cattle and truck movement data in southwest Kansas, we build a farm-level contact network with three layers, a cattle movement layer (direct contact), a truck movement layer (indirect contact), and an information-sharing layer. Through scenario analyses, we compare the disease transmission dynamics, the distribution of outbreak epidemic size, and the disease breakout percentage of different contact structures - only direct contact, only indirect contact, and their combination. In addition, we evaluate different types of information sharing methods by comparing the epidemic size and the estimated economic loss. Simulation results show that neither direct contact nor indirect contact individually can result in a massive outbreak of the disease, but their combination plays a significant role. Additionally, we detect different probabilities of disease outbreaks by starting the simulations at different farms; starting at some farms with high capacity increases the probability of disease outbreaks. Three different information sharing-networks are developed and found effective in preventing the disease from spreading and reducing the economic loss. The information-sharing layer based on trading records has the best performance when compared with a random network and a geographic network.

microbiology↗

bioRxiv2020

Abortion and various associated risk factors in dairy cow and sheep in Ili, China

We studied livestock abortion and various associated risk factors in the Ili region of northwest China. Livestock abortion prevalence was estimated and correlated with infections (Brucellosis, Salmonellosis, Mycoplasma and Chlamydia seropositivity) and management (farming type and contact with other herds/flocks) risk factors. The prevalence of cow and sheep abortion induced by Brucella was 76.8% (P<0.0001) and 84.1% (P<0.0001), and Mycoplasma caused an estimated 15.5% (P=0.025) and 17.6% (P<0.001) abortions, respectively. Abortion-related risk factors included mixed farming (cow P=0.001, sheep P<0.001), contact with other flocks (cow P=0.007, sheep P=0.003), brucellosis positivity (cow P<0.001, sheep P<0.001) and Mycoplasma positivity (cow P=0.031, sheep P<0.001). A total of 2996 serum samples (1402 cow, 1594 sheep) were identified by RBPT (Rose Bengal Plate Test), and they showed the seroprevalence of brucellosis in X county was cow 7.1%, sheep 9.1%; in H county was cow 11.7%, sheep 10.7%; and in Q county was cow 4.2%, sheep 9.1%. The seroprevalence of Mycoplasma in X county was cow 3.4%, sheep 7.9%; in H county was cow 5.3%, sheep 9.9%; and in Q county was cow 2.1%, sheep 4.3%. A total of 54 samples, including aborted cow (22), sheep (30) fetuses and milk samples (2), were identified as Brucella melitensis (B. melitensis) positive. A total of 38 Brucella were isolated from 16 aborted cow, 20 sheep fetuses and 2 milk samples. All of these isolates were identified, and confirmed, as B. melitensis. A phylogenetic tree showed that the Brucella isolates closely matched the B. melitensis biovar 3 isolated in Inner Mongolia, China, and B. melitensis isolated from Norway and India. These results suggest that B. melitensis biovar 3 is the main pathogen responsible for cow and sheep abortion and also pose a human health risk. Additionally, livestock reproduction can also be influenced by Mycoplasma infection and managerial factors (farming type and contact with other herds/flocks), especially in remote areas.View Full Text

zoology↗

bioRxiv2020

Transgenerational inheritance of abnormal spermatogenesis with Igf2/H19 epigenetic alteration in CD1 mouse induced by in utero arsenic exposure

Developmental exposure to environmental toxicants can induce transgenerational reproductive disease phenotypes through epigenetic mechanisms. However, little is known about the transgenerational effects of arsenic exposure. We hypothesize that prenatal arsenic exposure may result in impaired spermatogenesis in subsequent generations of male mice. To test our hypothesis, we treated pregnant CD-1 (F0) mice with drinking water containing sodium arsenite (85 ppm) from days 8 to 18 of gestation. Male offspring were bred with untreated female mice until the F3 generation was produced. Our results revealed that transient exposure of the F0 gestating female to arsenic can result in decreased sperm quality and histological abnormalities in testes of male offspring in the F1 and F3 generations. The overall methylation status of Igf2 DMR2 and H19 DMR was significantly lower in the arsenic-exposed group than that of the control group in both F1 and F3 generations. The relative mRNA expression levels of Igf2 and H19 in arsenic-exposed males were significantly higher than in the control males in both F1 and F3 generations. This study indicates that ancestral exposure to arsenic may result in transgenerational inheritance of an impaired spermatogenesis phenotyping involving both epigenetic alterations and the abnormal expression of Igf2 and H19.

pharmacology and toxicology↗

bioRxiv2020

Towards resilient beef cattle production systems: Impact of truck contamination and information sharing on foot-and-mouth disease spreading

As cattle movement data in the United States are scarce due to the absence of mandatory traceability programs, previous epidemic models for U.S. cattle production systems heavily rely on contact rates estimated based on expert opinions and survey data. These models are often based on static networks and ignore the sequence of movement, possibly overestimating the epidemic sizes. In this research, we adapt and employ an agent-based model that simulates beef cattle production and transportation in southwest Kansas to analyze the between-premises transmission of a highly contagious disease, the foot-and-mouth disease. First, we assess the impact of truck contamination on the disease transmission with the truck agent following an independent clean-infected-clean cycle. Second, we add an information-sharing functionality such that producers/packers can trace back and forward their trade records to inform their trade partners during outbreaks. Scenario analysis results show that including indirect contact routes between premises via truck movements can significantly increase the amplitude of disease spread, compared with equivalent scenarios that only consider animal movement. Mitigation strategies informed by information sharing can dramatically improve the system resilience against epidemics, highlighting the benefit of promoting information sharing in the cattle industry. In addition, we identify salient characteristics that must be considered when designing an information-sharing strategy, including the number of days to trace back and forward in the trade records and the role of different cattle supply chain stakeholders. Sensitivity analysis results show that epidemic sizes are sensitive to variations in parameters of fomite survival time and indirect contact transmission probability and future studies can focus on a more accurate estimation of these parameters.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗

bioRxiv2020

PremPRI: Predicting the Effects of Single Mutations on Protein-RNA Interactions

Protein-RNA interactions are crucial for many cellular processes, such as protein synthesis and regulation of gene expression. Missense mutations that alter protein-RNA interaction may contribute to the pathogenesis of many diseases. Here we introduce a new computational method PremPRI, which predicts the effects of single mutations occurring in RNA binding proteins on the protein-RNA interactions by calculating the binding affinity changes quantitatively. The multiple linear regression scoring function of PremPRI is composed of 11 sequence- and structure-based features, and is parameterized on 248 mutations from 50 protein-RNA complexes. Our model shows a good agreement between calculated and experimental values of binding affinity changes with Pearson correlation coefficient of 0.72 and the corresponding root-mean-square error of 0.76 kcal mol-1, outperforming three other available methods. PremPRI can be used for finding functionally important variants, understanding the molecular mechanisms, and designing new protein-RNA interaction inhibitors. PremPRI is freely available at http://lilab.jysw.suda.edu.cn/research/PremPRI/.

bioinformatics↗

bioRxiv2020

FL-QSAR: a federated learning based QSAR prototype for collaborative drug discovery

MotivationQuantitative structure-activity relationship (QSAR) analysis is commonly used in drug discovery. Collaborations among pharmaceutical institutions can lead to a better performance in QSAR prediction, however, intellectual property and related financial interests remain substantially hindering inter-institutional collaborations in QSAR modeling for drug discovery. ResultsFor the first time, we verified the feasibility of applying the horizontal federated learning (HFL), which is a recently developed collaborative and privacy-preserving learning framework to perform QSAR analysis. A prototype platform of federated-learning-based QSAR modeling for collaborative drug discovery, i.e, FL-QSAR, is presented accordingly. We first compared the HFL framework with a classic privacy-preserving computation framework, i.e., secure multiparty computation (MPC) to indicate its difference from various perspective. Then we compared FL-QSAR with the public collaboration in terms of QSAR modeling. Our extensive experiments demonstrated that (1) collaboration by FL-QSAR outperforms a single client using only its private data, and (2) collaboration by FL-QSAR achieves almost the same performance as that of collaboration via cleartext learning algorithms using all shared information. Taking together, our results indicate that FL-QSAR under the HFL framework provides an efficient solution to break the barriers between pharmaceutical institutions in QSAR modeling, therefore promote the development of collaborative and privacy-preserving drug discovery with extendable ability to other privacy-related biomedical areas. Availability and implementationThe source codes of the federated learning simulation and FL-QSAR are available on the GitHub: https://github.com/bm2-lab/FL-QSAR

bioinformatics↗

bioRxiv2020

CoolMPS™: Advanced massively parallel sequencing using antibodies specific to each natural nucleobase

Massively parallel sequencing (MPS) on DNA nanoarrays provides billions of reads at relatively low cost and enables a multitude of genomic applications. Further improvement in read length, sequence quality and cost reduction will enable more affordable and accurate comprehensive health monitoring tests. Currently the most efficient MPS uses dye-labeled reversibly terminated nucleotides (RTs) that are expensive to make and challenging to incorporate. Furthermore, a part of the dye-linker (scar) remains on the nucleobase after cleavage and interferes with subsequent sequencing cycles. We describe here the development of a novel MPS chemistry (CoolMPS) utilizing unlabeled RTs and four natural nucleobase-specific fluorescently labeled antibodies with fast (30 sec) binding. We implemented CoolMPS on MGIs PCR-free DNBSEQ MPS platform using arrays of 200nm DNA nanoballs (DNBs) generated by rolling circle replication and demonstrate 3-fold improvement in signal intensity and elimination of scar interference. Single-end 100-400 base and pair-end 2x150 base reads with high quality were readily generated with low out-of-phase incorporation. Furthermore, DNBs with less than 50 template copies were successfully sequenced by strong-signal CoolMPS with 3-times higher accuracy than in standard MPS. CoolMPS chemistry based on natural nucleobases has potential to provide longer, more accurate and less expensive MPS reads, including highly accurate "4-color sequencing" on the most efficient dye-crosstalk-free 2-color imagers with an estimated sequencing error rate of 0.00058% (one error in 170,000 base calls) in a proof-of-concept demonstration.

genomics↗

bioRxiv2020

LanD-like Flavoprotein-Catalyzed Aminovinyl-Cysteine Formation through Oxidative Decarboxylation and Cyclization of a Peptide at the C-Terminus

Aminovinyl-cysteine residues arise from processing the C-terminal O_SCPLOWLC_SCPLOW-Cys and an internal O_SCPLOWLC_SCPLOW-Ser/O_SCPLOWLC_SCPLOW-Thr or O_SCPLOWLC_SCPLOW-Cys of a peptide. Formation of these nonproteinogenic amino acids, which occur in a macrocyclic ring of diverse ribosomally synthesized lanthipeptides and non-lanthipeptides, remains poorly understood. Here, we report that LanD-like flavoproteins in the biosynthesis of distinct non-lanthipeptides share an unexpected dual activity for aminovinyl-cysteine formation. Each flavoprotein catalyzes oxidative decarboxylation of the C-terminal O_SCPLOWLC_SCPLOW-Cys and couples the resulting enethiol nucleophile with the internal residue to afford a thioether linkage for peptide cyclization. The cyclization step, which largely depends on proximity effect by positioning the enethiol intermediate with a bent conformation at the active site, can be substrate-dependent, proceeding inefficiently through nucleophilic substitution for an unmodified peptide or efficiently through Michael addition for a dehydrated/dethiolated peptide. Uncovering this unusual flavin-dependent paradigm for thioether residue formation advances the understanding in the biosynthesis of aminovinyl-cysteine-containing RiPPs and renews interest in flavoproteins, particularly those involved in non-redox transformations. LanD-like flavoproteins activity, which is flexible in peptide substrate and amenable for evolution by engineering, can be combined with different post-translational modifications for structural diversity, thereby holding promise for peptide macrocyclization/functionalization in drug development by chemoenzymatic or synthetic biology approaches.

biochemistry↗

bioRxiv2020

The Endothelial Protein C Receptor plays an essential role in the maintenance of Pregnancy

Placenta-mediated pregnancy complications are a major challenge in the management of maternal-fetal health. Maternal thrombophilia is a suspected risk factor but the role of thrombotic processes in these complications and the potential for antithrombotic treatment have remained unclear. Endothelial Protein C Receptor (EPCR) is an anticoagulant protein highly expressed in the placenta. EPCR autoantibodies and specific gene variants of EPCR are associated with poor pregnancy outcomes. In mice, fetal EPCR deficiency results in placental failure and in utero death. Adult EPCR-deficient mice generated by maintaining placental expression exhibit plasma markers of thrombophilia without overt thrombosis. We demonstrate that inactivation of clotting factor VIII or Protease Activated Receptor 4 (Par4), Par3 or integrin IIb in the mother allows placental development and intrauterine survival of murine embryos lacking EPCR. Rescued EPCR-deficient embryos exhibit thrombosis in placental venous sinuses at late gestation and a high rate of neonatal lethality. In contrast to fetal EPCR deficiency, maternal deficiency of EPCR results in frequent stillbirths and maternal death accompanied by pathological findings that resemble placental abruption and consumptive coagulopathy. Inactivation of Par4, but not clotting factor VIII, prevents maternal death and restores normal pregnancy outcomes. These observations establish a cause-effect relationship between maternal thrombophilia and placental abruption. They demonstrate that sites of uteroplacental thrombosis and the potential response to antithrombotic intervention may differ with gestational age and maternal versus fetal origin of thrombophilia. Our findings highlight the potential for therapeutic inhibition of thrombin-mediated platelet activation in a subset of pregnancy complications. KEY POINTSO_LIMurine model establishes a cause-effect relationship between maternal thrombophilia, retroplacental hemorrhage and severe pregnancy complications. C_LIO_LIThrombin-mediated activation of maternal platelets is a key event in thrombophilia-associated pregnancy complications and a potential target of therapeutic intervention. C_LIO_LIMaternal venous channels in uteroplacental circulation are additional sites of thrombotic pathology associated with adverse neonatal outcomes. C_LI

physiology↗

bioRxiv2020

MicroRNA-9 Mediated the Protective Effect of Ferulic Acid on Hypoxic-Ischemic Brain Injury in Neonatal Rats

Neonatal hypoxic-ischemic brain damage (NHIBD) leads to cognitive and memory impairments, and there is no effective clinical treatment. Ferulic acid (FA) is found within members of the genus Angelica, reportedly shows protective effects on neuronal damage; however, the mechanism of the protective effects of FA on rats following NHIBD remains unclear. Using the Morris water maze task, we herein found that the impairment of spatial memory formation in adult rats exposed to NHIBD was significantly reversed by FA treatment and the administration of LNA-miR-9. RT-PCR analyses revealed that miRNA-9 was significantly increased in the hippocampus of neonatal rats and neuronal PC12 cells following NHIBD and that FA and LNA-miR-9 both inhibited the expression of miRNA-9, suggesting that the therapeutic effect of FA was mainly attributed to the inhibition of miRNA-9 expression. Indeed, the silencing of miR-9 by LNA-miR-9 or FA similarly attenuated neuronal damage and cerebral atrophy in the rat hippocampus after NHIBD, which was consistent with the restored expression levels of brain-derived neurotrophic factor (BDNF). Therefore, FA treatment may protect against neuronal death through the inhibition of miRNA-9 induction in the rat hippocampus following hypoxic-ischemic damage.

neuroscience↗