Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.

Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.

RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation

BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

Transcriptomic and metabolomic analysis of changes in grain weight potential induced by water stress in wheat

The sink strength of developing ovaries in wheat determines the grain weight potential.The period from booting to the grain setting stage is critical for ovary growth and development and potential sink capacity determination.However,the underlying regulatory mechanism during this period by which the wheat plant balances and coordinates the floret number and ovary/grain weight under water stress has not been clarified.Therefore,we designed two irrigation treatments of W0(no seasonal irrigation)and W1(additional 75 mm of irrigation at the jointing stage)and analyzed the responses of the ovary/grain weight to water stress at the phenotypic,metabolomic,and transcriptomic levels.The results showed that the W0 irrigation treatment reduced the soil water content,plant height,and green area of the flag leaf,thus reducing grain number,especially for the inferior grains.However,it improved the grain weight of the superior and inferior grains as well as average grain weight at maturity,while the average ovary/grain weight and volume during–3 to 10 days after anthesis(DAA)also increased.Transcriptomic analysis indicated that the genes involved in both sucrose metabolism and phytohormone signal transduction were prominently accelerated by the W0 treatment,accompanied by greater enzymatic activities of soluble acid invertase(SAI)and sucrose synthase(Sus)and elevated abscisic acid(ABA)and indole-3-acetic acid(IAA)levels.Thus,the sucrose content decreased,while the glucose and fructose contents increased.In addition,several TaTPP genes(especially TaTPP-6)were down-regulated and the IAA biosynthesis genes TaTAR1 and TaTAR2 were up-regulated under the W0 treatment before anthesis,which further increased the IAA level.Collectively,water stress reduced the growth of vegetative organs and eliminated most of the inferior grains,but increased the ABA and IAA levels of the surviving ovaries/grains,promoting the enzymatic activity of Sus and degrading sucrose into glucose and fructose.As a result,the strong sucrose utilization ability,the enhanced enzymatic activity of SAI and the ABA-and IAA-mediated signaling jointly increased the weight and volume of the surviving ovaries/grains,and ultimately achieved the tradeoff between ovary/grain weight and number in wheat under water stress.

Elucidation of potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa

Dry-cured meat products are considerably popular around the world due to unique flavor.Proteolysis is one of the enzymatic reactions from which flavor substances are derived,which is affected by endogenous proteases.The purpose aimed to reveal the potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa in this paper.The dynamic changes of endogenous proteases activity,free amino acids,and volatiles during dry-cured pork coppa processing were characterized.The results showed that 5 kinds of free amino acids,Glu,Lys,Val,Ala,and Leu,were identified as significant contributors to taste.Meanwhile,key volatiles,such as hexanal,nonanal,octanal,benzaldehyde,3-methyl butanoic acid,2-methyl propanoic acid,and ethyl octanoate,greatly contributed to the flavor characteristics of dry-cured pork coppa.Further partial correlation analysis was performed to better elucidate the relationship among parameters.The results revealed that close relationship between endogenous proteases and key substances.RAP not only significantly affected the accumulation of key active-amino acids,but also affected the accumulation of ethyl octanoate,2,3-pentanedione,and 2,3-octanedione by regulating the accumulation of octanoic acid and Leu.In addition,cathepsin B and D,DPP II,DPP IV and RAP notably affected accumulation of hexanal.

One-time application of controlled-release bulk blending fertilizer enhances yield,quality and photosynthetic efficiency in late japonica rice

Controlled-release urea(CRU)releases nitrogen(N)at the same pace that rice takes it up,which can effectively improve N use efficiency,increase rice yield and improve rice quality.However,few studies have described the effects of CRU application on the photosynthetic rate and endogenous enzyme activities of rice.Accordingly,a twoyear field trial was conducted with a total of seven treatments:CK,no N fertilizer;BBF,regular blended fertilizer;RBBF,20%N-reduced regular blended fertilizer;CRF1,70%CRU+30%regular urea one-time base application;CRF2,60%CRU+40%regular urea one-time base application;RCRF1,CRF1 treatment with 20%N reduction;and RCRF2,CRF2 treatment with 20%N reduction.Each treatment was conducted in triplicate.The results showed that the N recovery efficiency(NRE)of the controlled-release bulk blending fertilizer(CRBBF)treatments was significantly greater over the two years.There were significant yield increases of 4.1–5.9%under the CRF1treatment and 5.6–7.6%under the CRF2 treatment compared to the BBF treatment,but the differences between the reduced-N treatments RBBF and RCRF2 were not significant.Photosynthetic rates under the CRF1 and CRF2treatments were significantly higher than under the other treatments,and they had significantly greater RuBPCase,RuBisCO,glutamate synthase(GOGAT)and glutamine synthetase(GS)enzyme activities.Additionally,the soil NH_(4)^(+)-N and NO_(3)^(–)-N contents under the CRBBF treatments were significantly higher at the late growth stage of rice,which was more in-line with the fertilizer requirements of rice throughout the reproductive period.CRBBF also led to some improvement in rice quality.Compared with the BBF and RBBF treatments,the protein contents under the CRBBF treatments were reduced but the milling,appearance,eating and cooking qualities of the rice were improved.These results showed that the application of CRBBF can improve the NRE,photosynthetic rate and endogenous enzyme activities of rice,ensuring sufficient N nutrition and photosynthetic material production during rice growth and thereby achieving improved rice yield and quality.

Are dogs not susceptible to retroviral infections?

Retroviruses have been proven to cause infections and diseases in a series of mammalian hosts but not in dogs.Then,this letter discussed the dog susceptibility to retrovirus infection,encompassing arguments to understand why dogs may have not been infected by retroviruses thus far.The potential resistance of retrovirus in dogs enables this provocative short communication to discuss this question,looking at some evolutive aspects.The lineage of canids has shown,throughout its evolutionary history,a smaller accumulation of retroviruses in canid genomes,classifed as endogenous retroviruses.In this context,the genomes of canids seem to ofer obstacles,which have been evolutionarily conserved,in the face of retroviral infection.

A chemical odyssey:Exploring renal stone diversity by age and sex in Punjab,Pakistan

Dear Editor,Renal calculosis is one of the most common urological disorders worldwide,with a prevalence ranging from 1%to 13%across different regions[1].Renal stones are crystal concretions that form on the inner surface of the kidney,resulting from disruptions in the metabolism,the excretion of stone constituents,or the formation of Randall's plaques and plugs.These stones are a result of various endogenous factors.

Correction: Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA

In the article“Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA”(Oncology Research,2020,Vol.28,No.5,pp.483–495.doi:10.3727/096504020X15928179818438),there was an error in the processing of data.To further confirm our observation,we repeated multiple experiments involving in this study,including Flow Cytometry,Transwell Cell Migration and Invasion Assays,Xenograft Tumor Model,and Western Blotting.We have revised the figures to correct these errors.Corrected versions of the Figs.2,4,5,6,and 7 are provided.The corrections do not change any results or conclusion of the article.We apologize for any inconvenience caused.

A core scientific problem in the treatment of central nervous system diseases:newborn neurons

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain dismal.AIM To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database.Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples.The targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan database.The univariate and multivariate analysis were utilized to identify independent prognostic indicators.RESULTS CDKN2A was frequently mutated and deleted in HCC.The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways.The CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully established.GAS5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC patients.The association between GAS5 expression and methylation,immune infilt-ration was explored.Besides,traditional Chinese medicine effective components targeting GAS5 were obtained.CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression.Moreover,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p

BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.

Research on the Design of Rural Cultural Tourism Space under the Background of Rural Revitalization: A Case Study of Dujiazhuang Village, Mentougou, Beijing

From the perspective of endogenous development concept,Dujiazhuang Village,Mentougou was taken as an example to explore the development of rural cultural tourism space.The rural tourism resources in the west of Beijing are rich in type and numerous,but the development of cultural tourism is unbalanced and inadequate.Guided by the endogenousconcept and driven by the design of cultural tourism space,rural public space should be as the entry point to integrate the elements of rural resources and create a design that stimulates the endogenous ability of villagers.Culture can promote tourism,and industry can drive the economy to increase income and enhance the villagers'cultural identity.

Endogenous Endophthalmitis as a Triggering Factor for Fatal Bacterial Meningitis Caused by Streptococcus pneumoniae: A Case Report

Endogenous endophthalmitis is a rare condition with a poor long-term visual prognosis and significant mortality, often associated with the hematogenous spread of intravitreal infections and subsequent disruption of the blood-ocular barrier. Its anatomical proximity to the central nervous system (CNS) poses a high risk of infection dissemination, although cases documented in the literature are rare, and endogenous endophthalmitis is typically described as secondary to neuroinfections. We report the case of an 82-year-old female patient with a history of hypertension who presented with fever, decreased visual acuity, severe headache, chemosis, and conjunctival injection. Endogenous endophthalmitis was diagnosed, and antimicrobial treatment was initiated alongside surgical intervention by the ophthalmology service. However, the patient’s condition worsened neurologically, and Streptococcus pneumoniae was identified in cerebrospinal fluid cultures. Despite intensive medical treatment, the patient’s clinical course was poor, leading to death.

Cytoplasmic DNA: sources, sensing, and role in aging and disease

Endogenous cytoplasmic DNA(cytoDNA)species are emerging as key mediators of inflammation in diverse physiological and pathological contexts.Although the role of endogenous cytoDNA in innate immune activation is well established,the cytoDNA species themselves are often poorly characterized and difficult to distinguish,and their mechanisms of formation,scope of function and contribution to disease are incompletely understood.