Significance of vascular endothelial growth factor messenger RNA expression in gastric cancer

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Expression of somatostatin mRNA in various differentiated types of gastric carcinoma

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Bioinformatics Analysis on lncRNA and mRNA Expression Profiles for Novel Biological Features of Valvular Heart Disease with Atrial Fibrillation

The biological features of the valvular heart disease with atrial fibrillation(AF-VHD)remain unknown when involving long non-coding RNAs(lncRNAs).This study performed system analysis on lncRNA and messenger RNA(mRNA)expression profiles constructed by using bioinformatics methods and tools for biological features of AF-VHD.Fold change and t-test were used to identify differentially expressed(DE)lncRNAs and mRNAs.The enrichment analysis of DE mRNAs was performed.The subgroups formed by lncRNAs and nearby mRNAs were screened,and a transcriptional regulation network among lncRNAs,mRNAs,and transcription factors(TFs)was constructed.The interactions between mRNAs related to lncRNAs and drugs were predicted.The 620 AF-VHDrelated DE lncRNAs and 452 DE mRNAs were identified.The 3 lncRNA subgroups were screened.The 665 regulations mediated by lncRNAs and TFs were identified.The 9 mRNAs related to lncRNAs had 1 or more potential drug interactions,totaling 37 drugs.Of these,9 drugs targeting 3 genes are already known to be able to control or trigger atrial fibrillation(AF)or other cardiac arrhythmias.The found biological features of AF-VHD provide foundations for further biological experiments to better understand the roles of lncRNAs in development from the valvular heart disease(VHD)to AF-VHD.

Characteristics of mRNA dynamic expression related to spinal cord ischemia/reperfusion injury:a transcriptomics study

Following spinal cord ischemia/reperfusion injury,an endogenous damage system is immediately activated and participates in a cascade reaction.It is difficult to interpret dynamic changes in these pathways,but the examination of the transcriptome may provide some information.The transcriptome reflects highly dynamic genomic and genetic information and can be seen as a precursor for the proteome.We used DNA microarrays to measure the expression levels of dynamic evolution-related m RNA after spinal cord ischemia/reperfusion injury in rats.The abdominal aorta was blocked with a vascular clamp for 90 minutes and underwent reperfusion for 24 and 48 hours.The simple ischemia group and sham group served as controls.After rats had regained consciousness,hindlimbs showed varying degrees of functional impairment,and gradually improved with prolonged reperfusion in spinal cord ischemia/reperfusion injury groups.Hematoxylin-eosin staining demonstrated that neuronal injury and tissue edema were most severe in the 24-hour reperfusion group,and mitigated in the 48-hour reperfusion group.There were 8,242 differentially expressed m RNAs obtained by Multi-Class Dif in the simple ischemia group,24-hour and 48-hour reperfusion groups.Sixteen m RNA dynamic expression patterns were obtained by Serial Test Cluster.Of them,five patterns were significant.In the No.28 pattern,all differential genes were detected in the 24-hour reperfusion group,and their expressions showed a trend in up-regulation.No.11 pattern showed a decreasing trend in m RNA whereas No.40 pattern showed an increasing trend in m RNA from ischemia to 48 hours of reperfusion,and peaked at 48 hours.In the No.25 and No.27 patterns,differential expression appeared only in the 24-hour and 48-hour reperfusion groups.Among the five m RNA dynamic expression patterns,No.11 and No.40 patterns could distinguish normal spinal cord from pathological tissue.No.25 and No.27 patterns could distinguish simple ischemia from ischemia/reperfusion.No.28 pattern could analyze the need for inducing reperfusion injury.The study of specific pathways and functions for different dynamic patterns can provide a theoretical basis for clinical differential diagnosis and treatment of spinal cord ischemia/reperfusion injury.

Temporal analysis of mRNA expression of endogenous TGFβ And its typeⅠ,typeⅡreceptor on burn wounds

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Expression of glutathione S-transferase placental mRNA in hepatic preneoplastic lesions in rats

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Minimal Secondary Structure Formation on mRNAs with a Shine-Dalgarno Sequence for Chromosomal Genes in <i>Rhodobacter sphaeroides</i>

The Shine-Dalgarno (SD) sequence, when present, is known to promote translation initiation in a bacterial cell. However, the thermodynamic stability of the messenger RNA (mRNA) through its secondary structures has an inhibitory effect on the efficiency of translation. This poses the question of whether bacterial mRNAs with SD have low secondary structure formation or not. About 3500 protein-coding genes in Rhodobacter sphaeroides were analyzed and a sliding window analysis of the last 100 nucleotides of the 5’ UTR and the first 100 nucleotides of ORFs was performed using RNAfold, a software for RNA secondary structure analysis. It was shown that mRNAs with SD are less stable than those without SD for genes located on the primary chromosome, but not for the plasmid encoded genes. Furthermore, mRNA stability is similar for genes within each chromosome except those encoded by the accessory chromosome (second chromosome). Results highlight the possible contribution of other factors like replicon-specific nucleotide composition (GC content), codon bias, and protein stability in determining the efficiency of translation initiation in both SD-dependent and SD-independent translation systems.

Expression changes of activin A in the development of hepatic fibrosis

AIM To examine the expression of activin A, amember of the transforming growth factor (TGF-β) superfamily, recently has been reported to beoverexpressed in liver cirrhosis, in the course ofcarbon tetrachloride-induced rat hepaticfibrosis.METHODS Hepatic fibrosis was induced in ratsby subcutaneous injections of 40% carbontetrachloride oily solution for a period of 1 to 7weeks. At the end of 1, 2, 3, 4, 5, 6 and 7 weeksafter carbon tetrachloride injections, the ratswere killed in group (6- 10 rats each time) forstudy. The activin A messenger RNA expressionand its protein localization were assessed bysemi-quantitative reverse transcriptionpolymerase chain reaction ( RT-PCR ) andimmunohistochemistry.RESULTS The normal rat liver expressedactivin A mRNA and protein, and its expressionwas transiently decreased and becameundetectable after carbon tetrachlorideinjections for 2 or 3 weeks and then increasedgradually. After injection of carbon tetrachloridefor 6 and 7 weeks, activin A mRNA and proteinexpressions were significantly enchanced in ratliver. Compared with that of the normal ratliver. Activin A mRNA expression levels in ratsreceiving carbon tetrachloride injections for 6and 7 weeks were 1.6 and 2.2 times that of thosein normal rat liver respectively (0.456±0.094 vs0.286± 0.0670, P＜0.01; 0.620± 0.134 vs 0.286±± 0.0670, P＜0.01). Immunohistochemistryshowed that activin A expressed in hepatocytesof normal liver, and its expression wasdecreased in rats receiving carbon tetrachloridefor 2 or 3 weeks. Compared with normal liver,activin A expression distribution mode changedin fibrotic liver, being increased significantly inhepatocytes around fibrotic areas.CONCLUSION Activin A expression wasincreased in latestage of hepatic fibrosis, andthis may be involved in hepatic fibrosisformation in this period.

Tumor gene mutations and messenger RNA expression： correlation with clinical response to icotinib hydrochloride in non-small cell lung cancer

Background Molecular targeted drugs is now widely used in non-small cell lung cancer （NSCLC） clinical treatment. Icotinib hydrochloride is a new type of oral epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （EGFR-TKIs）. In this study, we examined the role of EGFR, K-RAS, B-RAF somatic mutations and EGFR mRNA expression in tumor specimens from advanced NSCLC patients as predicators of the efficacy of icotinib hydrochloride. Methods We analyzed tumor paraffin-embedded specimens, which were obtained from 14 of 40 patients with advanced NSCLC who enrolled in the stage I clinical trial of icotinib hydrochloride. Somatic mutations were evaluated by mutant-enriched liquidchip （MEL） technology, and EGFR mRNA expression was measured by branched DNA liquidchip （MBL） technology. Results In the 14 specimens, seven patients showed EGFR mutations, exon 19 deletion （3/7） and exon 21 point mutation （4/7）; and two patients showed K-RAS mutation. No mutations in EGFR exon 20. or B-RAF were detected. In patients with EGFR mutation, one patient developed progress disease （PD）, three patients had stable disease （SD）, two patients had partial responses （PR） and one patient had a complete response （CR）. In patients with wild-type EGFR, four patients had PD, three patients acquired SD, and none had PR/CR （P=-0.0407）. EGFR mutations were associated with better progress-free survival （PFS） （141 days vs. 61 days） but without a statistically significant difference （P=0.8597）, and median overall survival （OS） （-〉449 days vs. 140 days）. EGFR mRNA expression levels were evaluated （three high, eight moderate, one low, and two that can not be measured due to insufficient tumor tissue） and no statistically significant relationships was observed with response, PFS or OS. Conclusions The EGFR mutation rate was consistent with that reported in the Asian population, so the MEL technology is reliable for measuring EGFR mutation with high throughput and rapidity. EGFR exon 19 deletions and exon 21 point mutation are predictive biomarkers for response to icotinib hvdrochloride as second line treatment or above.

Relationship between bone marrow-derived CD_(34)^+ cells expressing interleukin-5 receptor messenger RNA and asthmatic airway inflammation

BACKGROUND: Asthma is clinically related with the degree of eosinophilic inflammation. How asthmatic airway inflammation is affected is still poorly understood. So the effects of bone marrow-derived hematopoietic cells expressing CD(34) (CD(34)(+)) and interleukin-5 (IL-5) receptor messenger RNA (IL-5R mRNA+) on asthmatic airway inflammation were investigated. METHODS: Balb/c mice were sensitized and challenged by ovalbumin (OVA) to establish an asthmatic model while control mice were sensitized and exposed to sterile saline. The mice were killed at different time points after being challenged by OVA and sterile saline. Then, bronchoalveolar lavage fluid (BALF), peripheral blood (PB) and bone marrow (BM) were prepared. Eosinophils in PB (PBEOS) and BALF (BALFEOS), nuclear cells in BALF, PB and BM were counted. By flow cytometry, the percentage of CD(34)(+) cells to nucleated cells in PB, BM and the relative number of CD(34)(+) cells in PB (PBCD(34)(+)) and BM (BMCD(34)(+)) were calculated. Immunocytochemistry and in situ hybridization were used to investigate the hematopoietic cells with co-localized expression of CD(34) and IL-5R mRNA in BM (BMCD34+IL-5R mRNA+). The percentage of BMCD34+IL-5R mRNA+ to BMCD(34)(+) was calculated. RESULTS: Twelve hours after challenge by OVA, BALFEOS and PBEOS in the experimental group were significantly higher than those in the control group (P

mRNA delivery in cancer immunotherapy

Messenger RNA(mRNA)has drawn much attention in the medical field.Through various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic strategy for cancers.However,delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake.Therefore,in addition to mRNA modification,efforts have been devoted to developing nanoparticles for mRNA delivery.In this review,we introduce four categories of nanoparticle platform systems:lipid,polymer,lipid-polymer hybrid,and protein/peptide-mediated nanoparticles,together with their roles in facilitating mRNA-based cancer immunotherapies.We also highlight promising treatment regimens and their clinical translation.

The Messenger RNA and Long Non-coding RNA Expression Profiles in Ectopic and Eutopic Endometrium Provide Novel Insights into Endometriosis

Objective:To establish the messenger RNA(mRNA)and long non-coding RNA(lncRNA)expression profiles in ectopic and eutopic endometrium and provide novel insights into endometriosis.Methods:The mRNA and lncRNA expression profiles were tested using high-throughput sequencing technology in ectopic and eutopic endometrium with endometriosis and normal endometrium without endometriosis.The potential targeted lncRNAs were annotated by analyzing the correlation between lncRNA and mRNA expression to better understand the pathogenesis of endometriosis.Results:In ectopic compared with normal endometrium,a total of 2,188 mRNAs and 1,200 lncRNAs were differentially expressed with a fold-change(FC)≥2.5.In eutopic compared with normal endometrium,a total of 2,324 mRNAs and 695 lncRNAs were differentially expressed with an FC≥1.5.In ectopic compared with eutopic endometrium,a total of 2,223 mRNAs and 511 lncRNAs were differentially expressed with an FC≥2.Bioinformatic analysis indicated that the differentially expressed mRNAs were enriched in the biological processes and signaling pathways involved in endometriosis.In addition,we constructed a gene coexpression network based on the dysregulated lncRNAs in both ectopic endometrium and eutopic endometrium,combined with their coexpressed mRNAs to simulate the complex interactions.Conclusions:This study describes the first-to-integrate analysis of the differential expression profiles of mRNAs and lncRNAs,including analyses between ectopic and normal endometrium,eutopic and normal endometrium,and ectopic and eutopic endometrium,which provides new insights to investigate the pathogenesis of endometriosis and explore novel diagnostic biomarkers and therapeutic targets.

Body Fluid Identification by Messenger RNA Profiling in Sexual Assault

Body fluid identification through messenger RNA(mRNA)has been proposed as a useful supplement to presumptive and confirmatory tests by previous laboratory studies;however,its application in routine clinical forensic examination was rare.We report a case of sexual assault in which body fluid identification by mRNA profiling was used.Vaginal secretions mRNA markers(MUC4,HBD1,and CYP2B7P1)were used to test the sample,being obtained positive results.This case demonstrates that mRNA profiling of body fluids could be applied to routine case examinations as an aid,acting as a scientific collaborative evidence to strengthen the medicolegal opinion.

mRNA-based modalities for infectious disease management

The novel coronavirus disease 2019(COVID-19)is still rampant all over the world,causing incalculable losses to the world.Major pharmaceutical organizations around the globe are focusing on vaccine research and drug development to prevent further damage caused by the pandemic.The messenger RNA(mRNA)technology has got ample of attention after the success of the two very effective mRNA vaccines during the recent pandemic of COVID-19.mRNA vaccine has been promoted to the core stage of pharmaceutical industry,and the rapid development of mRNA technology has exceeded expectations.Beyond COVID-19,the mRNA vaccine has been tested for various infectious diseases and undergoing clinical trials.Due to the ability of constant mutation,the viral infections demand abrupt responses and immediate production,and therefore mRNA-based technology offers best answers to sudden outbreaks.The need for mRNA-based vaccine became more obvious due to the recent emergence of new Omicron variant.In this review,we summarized the unique properties of mRNA-based vaccines for infectious diseases,delivery technologies,discussed current challenges,and highlighted the prospects of this promising technology in the future.We also discussed various clinical studies as well preclinical studies conducted on mRNA therapeutics for diverse infectious diseases.

Biomedical applications of mRNA nanomedicine

As an attractive alternative to plasmid DNA, messenger RNA （mRNA） has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

Recent advances in mRNA vaccine delivery

In recent years, messenger RNA （mRNA） vaccines have been intensively studied in the fields of cancer immunotherapy and infectious diseases because of their excellent efficacy and safety profile. Despite significant progress in the rational design of mRNA vaccines and elucidation of their mechanism of action, their widespread application is limited by the development of safe and effective delivery systems that protect them from ubiquitous ribonucleases （RNases）, facilitate their entry into cells and subsequent escape from endosomes, and target them to lymphoid organs or particular cells. Some mRNA vaccines based on lipid carriers have entered clinical trials. Vaccines based on polymers, while not as clinically advanced as lipid vectors, show considerable potentials. In this review, we discuss the necessity of formulating mRNA vaccines with delivery systems, and we provide an overview of reported delivery systems.

Development of mRNA vaccines and their prophylactic and therapeutic applications

Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the emergence of new virus strains, they are more appropriate for the control of urgent epidemic and pandemic issues. In particular, messenger RNA （mRNA） vaccines have evolved as a new type of nucleic acid vaccines in accordance with their superior protein expression and a lack of mutagenesis as compared with DNA vaccines. Using mRNA vaccines, large amounts of target proteins can be expressed in immune cells for efficient immunization. For instance, antigen-specific vaccination is a feasible option involving the expression of specific antigens in antigen-presenting cells. Immunological reactions are modulated by expressing several proteins associated with stimulation or maturation of immune cells. In addition, mRNA vaccines can stimulate innate immunity through specific recognition by pattern recognition receptors. On the basis of these remarkable properties, mRNA vaccines have been used for prophylactic and therapeutic applications. This review highlights the role of mRNA vaccines as prophylactic vaccines for prevention of future infections and as therapeutic vaccines for cancer immunotherapy. In addition to the conventional type of mRNA vaccines, RNA replicons （self-amplifying mRNA vaccines） will be described.

Differential Expression of MicroRNA in Endothelial Cells Incubated with Serum of Hypertension Patients with Blood-Stasis Syndrome

Objective： To screen out blood-stasis syndrome （BSS）-associated microRNA and therefore determine the possible target for treating hypertension. Methods： A high-energy sequencing method and digital gene expression sequencing theory were adopted to sequence microRNA （miRNA） and messenger RNA （mRNA）, and to determine differential expression in human umbilical vein endothelial cells incubated with serum samples from hypertension patients with or without BSS, and healthy controls. The results were confirmed using gene prediction software. Results： A total of 13 miRNAs and 11 mRNAs showed statistical difference both in the BSS/normal groups and BSS/non-BSS groups, respectively. Four pairs of target mRNNmiRNA were identified： FRMD4Nhsa-miR-34a, MAP3K14/hsa-miR-34a, PER1/hsa-miR-34a, and FGF2/hsa-miR-132. Conclusion： Four mRNNmiRNA pairs mentioned above seem to be involved in pathogenesis and maintenance of hypertension with BSS.

Design of synthetic materials for intracellular delivery of RNAs： From siRNA-mediated gene silencing to CRISPR/Cas gene editing

Ribonucleic acids （RNAs） possess great therapeutic potential and can be used to treat a variety of diseases. The unique biophysical properties of RNAs, such as high molecular weight, negative charge, hydrophilicity, low stability, and potential immunogenicity, require chemical modification and development of carriers to enable intracellular delivery of RNAs for clinical use. A variety of nanornaterials have been developed for the effective in vivo delivery of short/ small RNAs, messenger RNAs, and RNAs required for gene editing technologies including clustered regularly interspaced palindromic repeat （CRISPR）/Cas. This review outlines the challenges of delivering RNA therapeutics, explores the chemical synthesis of RNA modifications and carriers, and describes the efforts to design nanomaterials that can be used for a variety of clinical indications.

Mechanisms of the therapeutic effect of astragalus membranaceus on sodium and water retention in experimental heart failure

OBJECTIVE: To investigate the therapeutic effect of Astragali on sodium and water retention in aortocaval fistula-caused experimental congestive heart failure and its involved mechanisms. METHODS: In aortocaval fistula-caused chronic (5 wk), heart failure rats treated with and without Astragali 1.0 g/day intraperitoneally, changes of cardiac and renal function, renal response to atrial natriuretic peptide (ANP) were examined. Dot blot analysis was used to determine the effect of Astragali on hypothalamic arginine vasopresin (AVP) mRNA expression, and mRNA expressions of aortic and renal AVP V1a receptor, renal AVP V2 receptor and aquaporin-2 (AQP2) were simultaneously detected by RT-PCR method. RESULTS: Rats with aortocaval fistula impaired cardiac and renal functions evidenced by higher right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), lower + dP/dtmax of left ventricle, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume (UV), urinary sodium excretion (UNaV) and free water clearance (CH2O) compared with sham-operated control (P