Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

CCDC181 is required for sperm flagellum biogenesis and male fertility in mice

The structural integrity of the sperm flagellum is essential for proper sperm function.Flagellar defects can result in male infertility,yet the precise mechanisms underlying this relationship are not fully understood.CCDC181,a coiled-coil domain-containing protein,is known to localize on sperm flagella and at the basal regions of motile cilia.Despite this knowledge,the specific functions of CCDC181 in flagellum biogenesis remain unclear.In this study,Ccdc181 knockout mice were generated.The absence of CCDC181 led to defective sperm head shaping and flagellum formation.Furthermore,the Ccdc181 knockout mice exhibited extremely low sperm counts,grossly aberrant sperm morphologies,markedly diminished sperm motility,and typical multiple morphological abnormalities of the flagella(MMAF).Additionally,an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified,with CCDC181 regulating the localization of LRRC46 within sperm flagella.These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

Enhancement of lysosome biogenesis as a potential therapeutic approach for neurodegenerative diseases

Millions of people are suffering from Alzheimer’s disease globally,but there is still no effective treatment for this neurodegenerative disease.Thus,novel therapeutic approaches for Alzheimer’s disease are needed,which requires further evaluation of the regulato ry mechanisms of protein aggregate degradation.Lysosomes are crucial degradative organelles that maintain cellular homeostasis.Transcription factor EB-mediated lysosome biogenesis enhances autolysosomedependent degradation,which subsequently alleviates neurodege nerative diseases,including Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease.In this review,we start by describing the key features of lysosomes,including their roles in nutrient sensing and degradation,and their functional impairments in different neurodegenerative diseases.We also explain the mechanisms—especially the post-translational modifications—which impact transcription factor EB and regulate lysosome biogenesis.Next,we discuss strategies for promoting the degradation of toxic protein aggregates.We describe Proteolysis-Ta rgeting Chimera and related technologies for the targeted degradation of specific proteins.We also introduce a group of LYsosome-Enhancing Compounds,which promote transcription factor EB-mediated lysosome biogenesis and improve learning,memory,and cognitive function in APP-PSEN1 mice.In summary,this review highlights the key aspects of lysosome biology,the mechanisms of transcription factor EB activation and lysosome biogenesis,and the promising strategies which are emerging to alleviate the pathogenesis of neurodegenerative diseases.

SIRT3 regulates mitochondrial biogenesis in aging-related diseases

Sirtuin 3(SIRT3),the main family member of mitochondrial deacetylase,targets the majority of substrates controlling mitochondrial biogenesis via lysine deacetylation and modulates important cellular functions such as energy metabolism,reactive oxygen species production and clearance,oxidative stress,and aging.Deletion of SIRT3 has a deleterious effect on mitochondrial biogenesis,thus leading to the defect in mitochondrial function and insufficient ATP production.Imbalance of mitochondrial dynamics leads to excessive mitochondrial biogenesis,dampening mitochondrial function.Mitochondrial dysfunction plays an important role in several diseases related to aging,such as cardiovascular disease,cancer and neurodegenerative diseases.Peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α)launches mitochondrial biogenesis through activating nuclear respiratory factors.These factors act on genes,transcribing and translating mitochondrial DNA to generate new mitochondria.PGC1αbuilds a bridge between SIRT3 and mitochondrial biogenesis.This review described the involvement of SIRT3 and mitochondrial dynamics,particularly mitochondrial biogenesis in agingrelated diseases,and further illustrated the role of the signaling events between SIRT3 and mitochondrial biogenesis in the pathological process of aging-related diseases.

Genetic variants in RAN, DICER and HIWI of microRNA biogenesis genes and risk of cervical carcinoma in a Chinese population

Objective：Recent evidence indicates that dysregulation of microRNA （miRNA） biogenesis is implicated in cancer development and progression.Based on the important role of miRNA biogenesis genes in carcinogenesis,we hypothesized that genetic variations of the miRNA biogenesis genes may modulate susceptibility to cervical cancer.Methods：We identified three single nucleotide polymorphisms （SNPs） located in the 3＇-untranslated regions （3＇-UTR） of of miRNA biogenesis key genes （rs1057035 in DICER,rs3803012 in RAN and rs10773771 in HIWI） and genotyped these SNPs in a case-control study of 1,486 cervical cancer cases and 1,549 cancer-free controls in Chinese women.Results：Logistic regression analyses showed that no significant associations were observed between the three SNPs and cervical cancer risk [rs3803012 in RAN AG/GG vs.AA adjusted OR =1.104,95 ％ confidence interval （CI）：0.859-1.419; rs1057035 in DICER CT/CC vs.TT adjusted OR =0.962,95％ CI：0.805-1.149;rs10773771 in HIWICT/CC vs.TT adjusted OR =0.963,95％ CI：0.826-1.122].Conclusions：The findings did not suggest that genetic variants in the 3＇-UTR of RAN,DICER and HIWI of miRNA biogenesis genes were associated with the risk of cervical cancer in this Chinese population.

Syringic acid improves oxidative stress and mitochondrial biogenesis in the liver of streptozotocin-induced diabetic rats

Objective:To determine the effects of syringic acid on hepatic damage in diabetic rats.Methods:Diabetes was induced by streptozotocin.Diabetic rats were given syringic acid at doses of 25,50 and 100 mg/kg by oral gavage for 6 weeks.Syringic acid effects on the liver were evaluated by examination of plasma biochemical parameters,and pathological study.In addition,biomarkers of lipid peroxidation and antioxidant status of liver tissues were assessed.Real time-PCR was performed to investigate the m RNA expression levels of mitochondrial biogenesis indices in different groups.Results:Syringic acid significantly attenuated the increase in most of plasma biochemical parameters in diabetic rats.Moreover,syringic acid treatment increased the catalase activity while it reduced the superoxide dismutase activity and hepatic malondialdehyde level in diabetic rats.There was no difference between the glutathione content of the treated and untreated groups.These findings were supported by alleviation of histopathological damages in the syringic acid-treated groups compared to the untreated diabetic group.Syringic acid also significantly upregulated the hepatic m RNA expression of PGC-1α,NRF-1,and NRF-2 and increased the mtD NA/nD NA ratio in diabetic rats.Conclusions:Syringic acid can be considered as a suitable candidate against hepatic complications since it can reduce oxidative damages in diabetic cases.Furthermore,it has the potential of targeting hepatic mitochondria in diabetes.

ALM1, encoding a Fe-superoxide dismutase, is critical for rice chloroplast biogenesis and drought stress response

Chloroplasts are the center of plant life activities including photosynthesis,growth and development,and abiotic stress response.Chloroplast development and biogenesis in rice have been studied in detail,but how does abiotic stress affect chloroplasts is less studied.We obtained an albino mutant,alm1,whose chlorophyll content was greatly decreased.Transmission electron microscopy showed that chloroplast development in alm1 was blocked,especially in thylakoid-like structures,which could not form normally.The ALM1 gene encodes a chloroplast-localized superoxide dismutase.Full-length ALM1 successfully restored the non-albino phenotype,and in knockout lines,the albino phenotype reappeared.The ALM1gene is expressed mainly in young leaves.alm1 plants died as a consequence of excessive reactive oxygen accumulation after the third-leaf stage.A series of biochemical assays verified that ALM1 interacted with the OsTrxz protein,which is one of the components of plastid-encoded RNA polymerase (PEP) complexes.A western blot experiment indicated that ALM1 played an important role in stabilizing OsTrxz in rice.An overexpression test of ALM1 revealed that ALM1 can increase drought resistance by removing excess reactive oxygen in rice seedlings.This study suggests that ALM1 not only participates in rice chloroplast biogenesis,but also increases rice stress resistance by scavenging excess reactive oxygen.

Role of apolipoproteins,ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins

In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.

De Novo Organelle Biogenesis in the Cyanobacterium TDX16 Released from the Green Alga <i>Haematococcus pluvialis</i>

It is believed that eukaryotes arise from prokaryotes, which means that organelles can form de novo in prokaryotes. Such events, however, had not been observed previously. Here, we report the biogenesis of organelles in the endosymbiotic cyanobacterium TDX16 (prokaryote) that was released from its senescent/necrotic host cell of green alga Haematococcus pluvialis (eukaryote). Microscopic observations showed that organelle biogenesis in TDX16 initiated with cytoplasm compartmentalization, followed by de-compartmentalization, DNA allocation, and re-compartmentalization, as such two composite organelles-the primitive chloroplast and primitive nucleus sequestering minor and major fractions of cellular DNA respectively were formed. Thereafter, the eukaryotic cytoplasmic matrix was built up from the matrix extruded from the primitive nucleus;mitochondria were assembled in and segregated from the primitive chloroplast, whereby the primitive nucleus and primitive chloroplast matured into the nucleus and chloroplast respectively. While mitochondria subsequently turned into double-membraned vacuoles after matrix degradation. Results of pigment analyses, 16S rRNA and genome sequencing revealed that TDX16 is a phycocyanin-containing cyanobacterium resembling Chroococcidiopsis thermalis, which had acquired 9,017,401 bp DNAs with 10,301 genes from its host. Accordingly, we conclude that organelle biogenesis in TDX16 is achieved by hybridizing the acquired eukaryotic DNAs with its own one and expressing the hybrid genome. The formation of organelles in cyanobacterium TDX16 is the first case of organelle biogenesis in prokaryotes observed so far, which sheds an unprecedented light on eukaryotes and their connections with prokaryotes, and thus has broad implications on biology.

Autophagy in degenerating axons following spinal cord injury: evidence for autophagosome biogenesis in retraction bulbs

Macroautophagy （here autophagy） is a catabolic mechanism responsible for the degradation of bulk cytoplasm, long-lived proteins and organeUes. During autophagy, the cargos are engulfed by double-membrane structures named phagophores, which expand to form the autophagosomes. Subsequently, these autophagosomes fuse with lysosomes, in which the cytoplasmic cargos are degraded. Autophagy is a constitutive pro- cess, which plays an important role in cellular homeostasis. In primary neurons autophagosome formation occurs continuously and preferentially at the distal end of axons. On the other hand, autophagy is increased by different stresses, and its dysregulation or excessive induction may lead to detrimental effects. Many neurological disorders have been associated with alterations in the autophagic pathway and an increase in autophagy during axonal degeneration was described.

Prediction of miRNA Based on miRNA Biogenesis via One-class SVM

MicroRNAs are a class of small, single-stranded RNAs which are produced by non-protein-coding RNA genes with a length of 21-29 nt. They regulate the expression of protein-encoding genes at the post-transcriptional level and the degradation ofmRNAs by base pairing to mRNAs. Mature miRNAs are processed from 60-90 nt RNA hairpin structures called pre-miRNAs. At present, most of the machine learning computational methods for pre-miRNAs prediction are based on two-class SVM and use structural information of pre-miRNA hairpins. Those methods share a common feature that all of them need a negative dataset in the training dataset and feature selection in both training and testing dataset. In order to avoid selecting false negative examples of miRNA hairpins in the training dataset which may mislead the classifiers, we presented a microRNA prediction algorithm called MirBio based on miRNAs Biogenesis which is trained only on the information of the positive miRNAs class to predict miRNAs. It can predict both pre-miRNAs and miRNAs and get a relatively satisfying result in this study.

Biogenesis of Plant MicroRNAs

microRNAs （miRNAs） play important regulatory roles in eukaryotic gene expression, predominantly at the post- transcriptional level. Elaborate and diverse biogenesis pathways have evolved to produce miRNAs, miRNA biogenesis is a multistep process including transcription, precursor slicing, methylation, nuclear export, and RNA-induced silencing complex assembly. In the decade, since the first discovery of plant miRNAs, many enzymes and regulatory proteins involved in miRNA biogenesis in plants have been uncovered and a basic picture of miRNA processing is emerging gradually. In this article, we summarized the current study of plant miRNA biogenesis and discussed the multiple integrated steps and diverse pathways of miRNA processing.

Rac1 relieves neuronal injury induced by oxygen-glucose deprivation and re-oxygenation via regulation of mitochondrial biogenesis and function

Certain microRNAs(miRNAs)can function as neuroprotective factors after reperfusion/ischemia brain injury.miRNA-142-3p can participate in the occurrence and development of tumors and myocardial ischemic injury by negatively regulating the activity of Rac1,but it remains unclear whether miRNA-142-3p also participates in cerebral ischemia/reperfusion injury.In this study,a model of oxygen-glucose deprivation/re-oxygenation in primary cortical neurons was established and the neurons were transfected with miR-142-3p agomirs or miR-142-3p antagomirs.miR-142-3p expression was down-regulated in neurons when exposed to oxygen-glucose deprivation/re-oxygenation.Over-expression of miR-142-3p using its agomir remarkably promoted cell death and apoptosis induced by oxygen-glucose deprivation/re-oxygenation and improved mitochondrial biogenesis and function,including the expression of peroxisome proliferator-activated receptor-γcoactivator-1α,mitochondrial transcription factor A,and nuclear respiratory factor 1.However,the opposite effects were produced if miR-142-3p was inhibited.Luciferase reporter assays verified that Rac Family Small GTPase 1(Rac1)was a target gene of miR-142-3p.Over-expressed miR-142-3p inhibited NOX2 activity and expression of Rac1 and Rac1-GTPase(its activated form).miR-142-3p antagomirs had opposite effects after oxygen-glucose deprivation/re-oxygenation.Our results indicate that miR-142-3p down-regulates the expression and activation of Rac1,regulates mitochondrial biogenesis and function,and inhibits oxygen-glucose deprivation damage,thus exerting a neuroprotective effect.The experiments were approved by the Committee of Experimental Animal Use and Care of Central South University,China(approval No.201703346)on March 7,2017.

Genetic variation may play a crucial role in non-coding RNA biogenesis

Transcription, post-transcriptional modification, translation, post-translational modification, DNA replication, and signaling interaction of intra- and extra- cellular components are the relevant mechanisms in gene regulation. Transcription is one of the most important mechanisms in the control of gene expression. Further, post-transcriptional modifications play a crucial role after transcription which determine whether the transcribed gene is coding or non-coding RNA (ncRNAs). Genome-wide analysis of RNAs provides information about the coding RNAs, whereas the status of ncRNAs are still at large and must be discussed in detail as variations in the ncRNAs can lead to different phenotypes. In this short article, we discuss the role of genetic variation in ncRNA genes and how this variation may play a crucial role in ncRNA biogenesis that eventually leads to phenotypic variation and thus speciation.

Tbl3 encodes a WD40 nucleolar protein with regulatory roles in ribosome biogenesis

AIM: To investigate the subcellular localization and the function of mouse transducin β-like 3(Tbl3).METHODS: The coding sequence of mouse Tbl3 was cloned from the c DNAs of a promyelocyte cell line by reverse transcription-polymerase chain reaction. Fusion constructs of Tbl3 and enhanced green fluorescent protein(EGFP) were transfected into fibroblasts and examined by fluorescence microscopy to reveal the subcellular localization of tbl3. To search for nucleolar targeting sequences, scanning deletions of Tbl3-EGFP were constructed and transfected into fibroblasts. To explore the possible function of Tbl3, small hairpin RNAs(sh RNAs) were used to knock down endogenous Tbl3 in mouse promyelocytes and fibroblasts. The effects of Tbl3 knockdown on ribosomal RNA(r RNAs) synthesis or processing were studied by labeling cells with 5,6-3H-uridine followed by a chase with fresh medium for various periods. Total RNAs were purified from treated cells and subjected to gel electrophoresis and Northern analysis. Ribosome profiling by sucrose gradient centrifugation was used to compare the amounts of 40 S and 60 S ribosome subunits as well as the 80 S monosome. The impact of Tbl3 knockdown on cell growth and proliferation was examined by growth curves and colony assays.RESULTS: The largest open reading frame of mouse Tbl3 encodes a protein of 801 amino acids(AA) with an apparent molecular weight of 89-90 kilodalton. It contains thirteen WD40 repeats(an ancient protein-protein interaction motif) and a carboxyl terminus that is highly homologous to the corresponding region of the yeast nucleolar protein, utp13. Virtually nothing is known about the biological function of Tbl3. All cell lines surveyed expressed Tbl3 and the level of expression correlated roughly with cell proliferation and/or biosynthetic activity. Using Tbl3-EGFP fusion constructs we obtained the first direct evidence that Tbl3 is targeted to the nucleoli in mammalian cells. However, no previously described nucleolar targeting sequences were found in Tbl3, suggesting that the WD40 motif and/or other topological features are responsible for nucleolar targeting. Partial knockdown(by 50%-70%) of mouse Tbl3 by shR NA had no discernable effects on the processing of the 47 S pre-ribosomal RNA(pre-r RNA) or the steady-state levels of the mature 28 S, 18 S and 5.8S r RNAs but consistently increased the expression level of the 47 S pre-rR NA by two to four folds. The results of the current study corroborated the previous finding that there was no detectable rR NA processing defects in zebra fish embryos with homozygous deletions of zebra fish Tbl3. As ribosome production consumes the bulk of cellular energy and biosynthetic precursors, dysregulation of pre-rR NA synthesis can have negative effects on cell growth, proliferation and differentiation. Indeed, partial knockdown of Tbl3 in promyelocytes severely impaired their proliferation. The inhibitory effect of Tbl3 knockdown was also observed in fibroblasts, resulting in an 80% reduction in colony formation. Taken together, these results indicate that Tbl3 is a newly recognized nucleolar protein with regulatory roles at very early stages of ribosome biogenesis, perhaps at the level of rR NA gene transcription. CONCLUSION: Tbl3 is a newly recognized nucleolar protein with important regulatory roles in ribosome biogenesis.

Urolithin A protects dopaminergic neurons in experimental models of Parkinson disease by promoting mitochondrial biogenesis through SIRT1/PGC-1αsignaling pathway

OBJECTIVE Mitochondrial dys⁃function contributes to the pathogenesis of neuro⁃degenerative diseases such as Parkinson dis⁃ease(PD).Therapeutic strategies targeting mito⁃chondrial dysfunction hold considerable promise for the treatment of PD.Urolithin A(UA)is a gut metabolite produced from ellagic acid-containing foods such as pomegranates,berries,and wal⁃nuts.Recent reports have highlighted the protec⁃tive role of UA in several neurological disorders including Alzheimer disease and ischemic stroke.However,the potential role of UA in PD has not been characterized.In this study,the role of UA in 6-OHDA-induced neurotoxicity in cell cultures and mouse model of PD was investi⁃gated.METHODS In vitro,PC12 cells were exposed to 6-OHDA in the presence or absence of UA.For in vivo study,C57BL/6 mice were ste⁃reotactic injected with 6-OHDA to induce experi⁃mental PD model.UA(10 mg·kg-1)was intraperi⁃toneal injected for 7 d before surgery.RESULTS UA protected against 6-OHDA cytotoxicity and apoptosis in PC12 cells.Prior administration of UA to 6-OHDA lesioned mice ameliorated both motor deficits and nigral-straital dopaminergic neurotoxicity.Moreover,UA attenuated 6-OHDA-induced mitochondrial dysfunction in PC12 cells accompanied by enhanced mitochondrial biogen⁃esis.Mechanically,the neuroprotective effects of UA were mediated by SIRT1-PGC-1αsignaling-mediated mitochondrial biogenesis.CONCLU⁃SION These data provide new insights into the novel role of UA in promoting mitochondria bio⁃genesis and suggest that UA may have potential therapeutic applications for PD.

过氧化物酶体生物发生因子5(PEX5)缺失导致小鼠精子发生失败和不育

目的:过氧化物酶体生物发生因子5(PEX5)对雄性小鼠精子发生及生育功能的影响。方法:利用CRISPR/Cas9及LoxP/Cre技术构建睾丸特异性Pex5基因敲除(Pex5 cKO)小鼠模型,通过苏木精-伊红染色(HE)、免疫蛋白印迹(Western blot)和免疫荧光(IF)染色分析评估雄性小鼠的生殖器官及精子发生的情况。结果:Pex5 cKO雄性小鼠正常成熟交配窝仔数为0,与野生型(WT)雄性小鼠窝仔数(6.32±0.26)相比差异有统计学意义(t=21.46,P<0.0001),且HE染色结果发现,Pex5 cKO小鼠附睾中无精子发生。结论:PEX5在小鼠精子发生过程中发挥重要作用。

白果内酯调控AMPK-SIRT3正反馈环路介导的线粒体生物发生改善ATDC5软骨细胞炎性损伤

旨在以AMPK-SIRT3正反馈环路为切入点,探讨白果内酯改善白介素1β(IL-1β)诱导的ATDC5软骨细胞炎性损伤的作用机制。采用IL-1β(10 ng·mL^(-1))诱导ATDC5软骨细胞炎性损伤来构建体外骨关节炎模型,随机分为对照组,IL-1β组,IL-1β和白果内酯共同处理组,其中,共同处理组按照白果内酯的应用浓度又分为低、中和高(15、30和60μmol·L^(-1))3个不同剂量组。免疫印迹法(Western blot)和实时荧光定量PCR(qRT-PCR)方法检测各组软骨细胞中ADAMTS4、PGC-1a、Collagen Type II、MMP-3、NRF-1和Fis1的蛋白与mRNA表达情况。试剂盒检测各组ATP含量,并通过免疫荧光方法检测SIRT3表达水平。Western blot检测AMPK-SIRT3正反馈环路相关蛋白p-AMPK、AMPK和SIRT3表达水平。使用Compound C和3-TYP处理ATDC5软骨细胞,构建AMPK-SIRT3信号通路阻断模型,检测下游PGC-1a、NRF-1和Fis1蛋白变化。结果显示,白果内酯通过下调ADAMTS4和MMP-3表达(P<0.05),促进Type II collagen表达(P<0.05)来调节ECM代谢平衡,并促进ATP合成。在机制上,白果内酯干预软骨细胞后p-AMPK、SITR3、PGC-1a和NRF-1水平显著升高(P<0.05),而Fis1蛋白水平显著降低(P<0.05),并且使用Compound C和3-TYP预处理软骨细胞后,PGC-1a、NRF-1和Fis1蛋白水平被不同程度抑制。综上所述,白果内酯通过AMPK-SIRT3正反馈环路激活PGC-1a,调节线粒体生物发生改善ATDC5软骨细胞炎性损伤。

增加革兰阴性菌外膜囊泡产量的研究进展

外膜囊泡(OMVs)是由革兰阴性菌释放的一种囊泡状结构,在革兰阴性菌的生长、感染以及与周围环境交流等过程中发挥重要作用。由于OMVs无活性、不能复制且具有良好的免疫原性,被广泛应用于新型疫苗的研究。但天然OMVs产量低,无法达到规模化生产的要求,OMVs产量提升是OMVs疫苗产业化要解决的关键核心技术问题。本文主要从细菌基因改造、生长培养条件优化和OMVs生产纯化工艺优化3个方面对提升OMVs产量的研究进行综述,以期为OMVs疫苗产业化研究开发提供参考。

羊肚菌菌核生物发生及其影响因素研究进展

菌核是由真菌营养菌丝体交织聚集形成的一种休眠结构,可以抵御逆境,提高存活率。形成菌核是羊肚菌(Morchella)生命周期中的一个重要阶段,但其形成机理、影响因素以及与产子实体之间的关系尚不明确,阻碍了羊肚菌人工栽培技术的发展。随着羊肚菌田间栽培的推进,包括其菌核发育在内的多学科基础生物学研究越来越受到重视。本文对形成菌核的主要真菌种类、羊肚菌菌核多样性和发育,以及影响羊肚菌菌核形成的因素进行综述,以期为羊肚菌研究者和栽培技术人员提供参考,进而推动羊肚菌产业的持续和稳定发展。