Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

MicroRNAs在妇科肿瘤发生发展中的研究进展

microRNAs(miRNAs)是一类小RNA分子,在植物和动物的基因表达调控中发挥着重要作用,miRNAs不参与蛋白质的直接合成,而是转录后基因表达的重要调控因子。它们不仅在身体发育中起着关键作用,也是细胞周期、凋亡和分化的关键调节因子。成熟miRNAs的产生需要几个关键步骤。首先,在细胞核中经由RNA polymerase II(PolII)转录完成聚腺苷酸化和封顶产生primary mi RNAs(Pri-miRNAs)。Pri-miRNAs通过Drosha/DGCR8复合物进一步加工合成hairpin precursor mi RNAs(pre-miRNAs)。Pre-miRNAs通过输出蛋白5(XPO5)输出到细胞质中,并被Dicer切割,在这一过程进行末端环的切割后形成成熟的miRNAs。miRNAs以互补序列结合靶mRNA,发挥调控作用。研究表明,超过30%的蛋白质编码基因受miRNAs调控。miRNAs的失调和功能障碍与人类疾病有关,miRNAs的异常表达被认为是癌症发生的重要过程。本文就microRNAs在妇科肿瘤发生发展中的研究现状进行综述。

microRNAs在帕金森病发病机制中作用研究进展

帕金森病(Parkinson’s disease)发病机制复杂,多种机制已被证明与帕金森病的病理生理机制有关,如α-突触核蛋白的积累、氧化应激、异常细胞凋亡和神经炎症等。微小RNA(MicroRNA,miRNA)是一种由内源性基因编码的非编码单链RNA分子。在过去的十年里,许多研究报道了miRNA在一系列重要的生命过程中发挥作用。此外,大量的动物模型实验和临床研究也发现了miRNA在帕金森病中的失调,并证明miRNA通过不同的途径在帕金森病的发生发展中发挥了重要作用。本文综述了一些参与帕金森病发生发展的重要miRNAs。

靶向严重急性呼吸系统综合症冠状病毒2的人工microRNAs设计与思考

动植物人工miRNAs(artificial miRNAs,amiRNAs)在抗病毒感染中发挥重要作用。然而,有关amiRNAs靶向抑制重症急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)的相关研究未见报道。目的:本研究旨在设计靶向SARS-CoV-2的amiRNAs,进一步分析amiRNAs对不同变异株的匹配程度。方法:利用Invitrogen Block-iT RNAi Designer成功设计靶向SARS-CoV-2的amiRNAs。结果:分别命名为amiR-Cov23utr-1、2、3、4;其中amiR-Cov23utr-1、3和4在Omicron BA.5/2022中靶向区域序列十分保守;amiR-Cov23utr-2在Omicron BA.5/2022中的靶点缺失。结论:本研初步设计和分析了靶向SARS-CoV-2的amiRNAs,为后续深入研究amiRNAs抗SARS-CoV-2感染提供了重要基础资料。

microRNAs对心脏电生理特性影响的研究进展

非心脏外科围术期心律失常的发生率4%~20%,而心胸外科围术期心律失常的发生率为10%~30%,其中心脏手术患者围术期心律失常的发生率高达90%。围术期心律失常可延长住院时间,增加患者住院期间的发病率和死亡率。研究表明,心血管疾病中存在的异常表达microRNAs可通过调控离子通道、缝隙连接蛋白及细胞内Ca2+处理蛋白等,参与心脏自律性、兴奋性以及传导性,从而调节心脏电生理稳态和心律失常。本文将主要从心脏电生理失衡的角度综述microRNA与心律失常的研究进展。

OsFK1 encodes C-14 sterol reductase,which is involved in sterol biosynthesis and affects premature aging of leaves in rice

The enzyme C-14 sterol reductase is involved in biosynthesis of brassinosteroids(BR)and sterols,as well as plant development.OsFK1,a member of the sterol biosynthesis pathway located in the endoplasmic reticulum(ER),encodes C-14 sterol reductase.However,there is little research on the function of C-14 sterol reductase in rice.Compared with the wild type,an osfk1 mutant showed dwarf phenotype and premature aging in the second leaf during the trefoil stage,and abnormal development of leaf veins during the tillering stage.The osfk1 mutant showed signs of aberrant PCD,as evidenced by TUNEL staining.This suggested that high ROS buildup caused DNA damage and ROS-mediated cell death in the mutant.The osfk1 mutant also showed decreased chlorophyll content and aberrant chloroplast structure.Sequencing of the osfk1 mutant allele revealed a non-synonymous G to A mutation in the final intron,leading to early termination.Here,we identified the OsFK1 allele,cloned it by Mutmap sequencing,and verified it by complementation.HPLC-MS/MS assays demonstrated that the osfk1 mutation caused lower phytosterol levels.These findings showed that the OsFK1 allele encoding C-14 sterol reductase is involved in phytosterol biosynthesis and mediates normal development of rice plants.

Wetting alternating with partial drying during grain filling increases lysine biosynthesis in inferior rice grain

Lysine content is a criterion of the nutritional quality of rice.Understanding the process of lysine biosynthesis in early-flowering superior grain(SG)and late-flowering inferior grain(IG)of rice would advance breeding and cultivation to improve nutritional quality.However,little information is available on differences in lysine anabolism between SG and IG and the underlying mechanism,and whether and how irrigation regimes affect lysine anabolism in these grains.A japonica rice cultivar was grown in the field and two irrigation regimes,continuous flooding(CF)and wetting alternating with partial drying(WAPD),were imposed from heading to the mature stage.Lysine content and activities of key enzymes of lysine biosynthesis,and levels of brassinosteroids(BRs)were lower in the IG than in the SG at the early grainfilling stage but higher at middle and late grain-filling stages.WAPD increased activities of these key enzymes,BR levels,and contents of lysine and total amino acids in IG,but not SG relative to CF.Application of 2,4-epibrassinolide to rice panicles in CF during early grain filling reproduced the effects of WAPD,but neither treatment altered the activities of enzymes responsible for lysine catabolism in either SG or IG.WAPD and elevated BR levels during grain filling increased lysine biosynthesis in IG.Improvement in lysine biosynthesis in rice should focus on IG.

基于microRNAs差异分析和网络药理学探讨益母草治疗宫腔粘连相关机制

目的通过microRNAs差异分析、网络药理学及分子对接技术,探讨益母草治疗宫腔粘连(intrauterine adhesion,IUA)的潜在作用靶点及相关机制。方法基于GEO(gene expression omnibus)数据库筛选IUA与健康者的差异miRNA,经multiMiR进行靶基因预测。通过TCMSP(traditional Chinese medicine systems pharmacology)数据库检索益母草有效活性成分及相关靶点,并与miRNA靶基因取交集。利用String平台进行蛋白质互作分析,利用cytoNCA筛选关键靶点。基于R语言进行基因本体(gene ontology,GO)和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。利用CB-dock2对关键靶点和活性成分进行分子对接。结果共筛选出与IUA相关的差异miRNA 43个,经靶基因预测后与IUA共有13个交集靶点,GO及KEGG富集分析结果显示,益母草治疗IUA作用机制主要与细胞衰老、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、PI3K-Akt信号通路等有关。益母草3个特征性活性成分是花生四烯酸、山奈酚、槲皮素,可与蛋白互作网络中相对应的靶点蛋白细胞周期蛋白依赖性激酶4(cyclin-dependent kinase 4,CDK4)、芳香烃受体(aryl hydrocarbon receptor,AHR)、原癌基因c-myc编码转录因子、血管内皮生长因子(vascular endothelial growth factor,VEGF)进行分子对接,主要活性成分能够与核心靶点结合,并展现出较好的亲和力。结论益母草治疗IUA是多成分、多靶点、多通路相互作用的结果,进一步证实了益母草治疗IUA的科学性及有效性,为后续实验提供了研究思路。

microRNAs在儿童呼吸道合胞病毒感染中调控作用的研究进展

呼吸道合胞病毒(RSV)是儿童急性下呼吸道感染最常见的病原体,对儿童的健康构成严重威胁,但其病理机制仍不明确,目前仍然没有有效预防和治疗呼吸道合胞病毒的方法。RSV是具有包膜单负链RNA病毒,编码11种蛋白质,这些蛋白质是诱导气道高反应性(AHR)的关键因素。微小RNA(miRNAs)近来被认为是基因表达调控因子,通过调节炎症反应和免疫细胞功能以及气道上皮细胞的宿主免疫反应,在病毒感染中发挥调控作用。本文综述了miRNAs在RSV感染中调控作用的研究进展,旨在为RSV的致病机制、诊断及治疗提供新思路。

Identification and Molecular Characterization of the Alkaloid Biosynthesis Gene Family in Dendrobium catenatum

As one of the main active components of Dendrobium catenatum, alkaloids have high medicinal value. The physicochemicalproperties, conserved domains and motifs, phylogenetic analysis, and cis-acting elements of the genefamily members in the alkaloid biosynthesis pathway of D. catenatum were analyzed by bioinformatics, and theexpression of the genes in different years and tissues was analyzed by qRT-PCR. There are 16 gene families,including 25 genes, in the D. catenatum alkaloid biosynthesis pathway. The analysis of conserved domains andmotifs showed that the types, quantities, and orders of domains and motifs were similar among members ofthe same family, but there were significant differences among families. Phylogenetic analysis indicated that thegene family members showed some evolutionary conservation. Cis-acting element analysis revealed that therewere a large number of light-responsive elements and MYB (v-myb avian myeloblastosis viral oncogene homolog)-related elements in these genes. qRT-PCR showed that expressions of gene family members involved in alkaloidsynthesis were different in different years and tissues of D. catenatum. This study provides a theoretical basisfor further exploration of the regulatory mechanisms of these genes in the alkaloid biosynthesis of D. catenatum.

Current Research Status of MicroRNAs in Squamous Cell Carcinoma of the Tongue

Tongue squamous cell carcinoma (TSCC) is the most invasive type of oral malignant tumor, posing a serious threat to human life and health. Its pathogenesis is complex and has a high degree of malignancy. Recurrence and metastasis often lead to poor prognosis. MicroRNAs are a type of single stranded small molecule RNA with only 18 - 25 nucleotides, which can regulate the expression of various genes and participate in the occurrence and development of tumors. Studies have found that microRNA expression profiling can serve as a reliable and stable biological indicator for early diagnosis and prognosis of tumors. This article provides a review of the research status of MicroRNAs in squamous cell carcinoma of the tongue.

Exosomal microRNAs in hepatocellular carcinoma,expanding research field

In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvironment.In this review,the authors introduce the following points:(1)The composition and function of exosomal microRNAs(miRNAs)of different cell origins in hepatocellular carcinoma(HCC);(2)the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC;and(3)the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.In addition,the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced.In this review,the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC,which provides a deeper understanding of exosomal miRNAs to the readers.

Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo

Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes derive.If information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

The biosynthesis of alarm pheromone in the wheat aphid Rhopalosiphum padi is regulated by hormones via fatty acid metabolism

Aphids are major insect pests in agriculture and forestry worldwide.Following attacks by natural enemies,many aphids release an alarm pheromone to protect their population.In most aphids,the main component of the aphid alarm pheromone(AAP)is the sesquiterpene hydrocarbon(E)-β-farnesene(EβF).However,the mechanisms behind its biosynthesis and regulation remain poorly understood.In this study,we used the bird cherry–oat aphid Rhopalosiphum padi,which is an important wheat aphid,to investigate the regulatory mechanisms of EβF biosynthesis.Our results showed that EβF biosynthesis occurs during the mature embryo period and the molting period of the 1st-and 2nd-instar nymphs.Triglycerides provide the prerequisite material for EβF production and release.Based on transcriptome sequencing,RNAi analysis,hormone treatments,and quantitative measurements,we found that the biosynthesis of EβF utilizes acetyl coenzyme A produced from fatty acid degradation,which can be suppressed by juvenile hormone but it is promoted by 20-hydroxyecdysone through the modulation of fatty acid metabolism.This is the first systemic study on the modulation of EβF production in aphids.The results of our study provide insights into the molecular regulatory mechanisms of AAP biosynthesis,as well as valuable information for designing potential aphid control strategies.

MicroRNAs in hepatocellular carcinoma treatment:Charting the path forward

MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

Dysregulated microRNAs in type 2 diabetes and breast cancer:Potential associated molecular mechanisms

Type 2 diabetes(T2D)is a multifaceted and heterogeneous syndrome associated with complications such as hypertension,coronary artery disease,and notably,breast cancer(BC).The connection between T2D and BC is established through processes that involve insulin resistance,inflammation and other factors.Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC,especially through microRNAs(miRNAs),remain elusive.miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes.However,the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated.This review aims to identify dysregulated miRNAs in both T2D and BC,exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

MicroRNAs in inflammatory bowel disease:What do we know and what can we expect?

MicroRNAs(miRNAs),small non-coding RNAs composed of 18–24 nucleotides,are potent regulators of gene expression,contributing to the regulation of more than 30%of protein-coding genes.Considering that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells,there is an interest in exploring their importance in inflammatory bowel disease(IBD).IBD is a chronic and multifactorial disease of the gastrointestinal tract;the main forms are Crohn's disease and ulcerative colitis.Several studies have investigated the dysregulated expression of miRNAs in IBD,demonstrating their important roles as regulators and potential biomarkers of this disease.This editorial presents what is known and what is expected regarding miRNAs in IBD.Although the important regulatory roles of miRNAs in IBD are clearly established,biomarkers for IBD that can be applied in clinical practice are lacking,emphasizing the importance of further studies.Discoveries regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Multifaceted role of microRNAs in gastric cancer stem cells: Mechanisms and potential biomarkers

MicroRNAs(miRNAs)have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells(CSCs).The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells(GCSCs).Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs.This review summarizes the coding process and biological functions of miRNAs and demon-strates their role and efficacy in gastric cancer(GC)metastasis,drug resistance,and apoptosis,especially in the regulatory mechanism of GCSCs.It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis,apart from the initial formation of GC.It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC.We believe that this review may help in designing novel therapeutic approaches for GC.