Development of SARS-CoV-2 animal vaccines using a stable and efficient NDV expression system.

With the continuation of the coronavirus disease 2019 pandemic and the emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants, the control of the spread of the virus remains urgent. Various animals, including cats, ferrets, hamsters, nonhuman primates, minks, tree shrews, fruit bats, and rabbits, are susceptible to SARS-CoV-2 infection naturally or experimentally. Therefore, to avoid animals from becoming mixing vessels of the virus, vaccination of animals should be considered. In the present study, we report the establishment of an efficient and stable system using Newcastle disease virus (NDV) as a vector to express SARS-CoV-2 spike protein/subunit for the rapid generation of vaccines against SARS-CoV-2 in animals. Our data showed that the S and S1 protein was sufficiently expressed in rNDV-S and rNDV-S1-infected cells, respectively. The S protein was incorporated into and displayed on the surface of rNDV-S viral particles. Intramuscular immunization with rNDV-S was found to induce the highest level of binding and neutralizing antibodies, as well as strong S-specific T-cell response in mice. Intranasal immunization with rNDV-S1 provoked a robust T-cell response but barely any detectable antibodies. Overall, the NDV-vectored vaccine candidates were able to induce profound humoral and cellular immunity, which will provide a good system for developing vaccines targeting both T-cell and antibody responses.

Prevalence and risk factors of osteosarcopenia: a systematic review and meta-analysis.

BACKGROUND: Osteosarcopenia is a syndrome with a concomitant presence of both sarcopenia and osteopenia/osteoporosis. It increases the risk of frailty, falls, fractures, hospitalization, and death. Not only does it burden the lives of older adults, but it also increases the economic burden on health systems around the world. This study aimed to review the prevalence and risk factors of osteosarcopenia to generate important references for clinical work in this area. METHODS: Pubmed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, CBM, and VIP databases were searched from inception until April 24th, 2022. The quality of studies included in the review was evaluated using the NOS and AHRQ Scale. Pooled effects of the prevalence and associated factors were calculated using random or fixed effects models. Egger's test, Begg's test, and funnel plots were used to test the publication bias. Sensitivity analysis and subgroup analysis were conducted to identify the sources of heterogeneity. Statistical analysis was performed using Stata 14.0 and Review Manager 5.4. RESULTS: A total of 31 studies involving 15,062 patients were included in this meta-analysis. The prevalence of osteosarcopenia ranged from 1.5 to 65.7%, with an overall prevalence of 21% (95% CI: 0.16-0.26). The risk factors for osteosarcopenia were female (OR 5.10, 95% CI: 2.37-10.98), older age (OR 1.12, 95% CI: 1.03-1.21), and fracture (OR 2.92, 95% CI: 1.62-5.25). CONCLUSION: The prevalence of osteosarcopenia was high. Females, advanced age, and history of fracture were independently associated with osteosarcopenia. It is necessary to adopt integrated multidisciplinary management.

Polygenic risk for coronary artery disease in the Scottish and English population.

BACKGROUND: Epidemiological studies have repeatedly observed a markedly higher risk for coronary artery disease (CAD) in Scotland as compared to England. Up to now, it is unclear whether environmental or genetic factors might explain this phenomenon. METHODS: Using UK Biobank (UKB) data, we assessed CAD risk, based on the Framingham risk score (FRS) and common genetic variants, to explore the respective contribution to CAD prevalence in Scotland (n = 31,963) and England (n = 317,889). We calculated FRS based on sex, age, body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), antihypertensive medication, smoking status, and diabetes. We determined the allele frequency of published genome-wide significant risk CAD alleles and a weighted genetic risk score (wGRS) for quantifying genetic CAD risk. RESULTS: Prevalence of CAD was 16% higher in Scotland as compared to England (8.98% vs. 7.68%, P < 0.001). However, the FRS only predicted a marginally higher CAD risk (less than 1%) in Scotland (12.5 ± 10.5 vs.12.6 ± 10.6, P = 0.03). Likewise, the overall number of genome-wide significant variants affecting CAD risk (157.6 ± 7.7 and 157.5 ± 7.7; P = 0.12) and a wGRS for CAD (2.49 ± 0.25 in both populations, P = 0.14) were remarkably similar in the English and Scottish population. Interestingly, we observed substantial differences in the allele frequencies of individual risk variants. Of the previously described 163 genome-wide significant variants studied here, 35 variants had higher frequencies in Scotland, whereas 37 had higher frequencies in England (P < 0.001 each). CONCLUSIONS: Neither the traditional risk factors included in the FRS nor a genetic risk score (GRS) based on established common risk alleles explained the higher CAD prevalence in Scotland. However, we observed marked differences in the distribution of individual risk alleles, which emphasizes that even geographically and ethnically closely related populations may display relevant differences in the genetic architecture of a common disease.

Systematic identification of rabbit LncRNAs reveals functional roles in atherosclerosis.

Long noncoding RNAs (lncRNAs) have been gradually emerging as important regulators in various biological processes and diseases, while the contributions of lncRNAs to atherosclerosis remain largely unknown. Our previous work has discovered atherosclerosis associated protein-coding genes by transcriptome sequencing of rabbit models. Here we investigated the roles of lncRNAs in atherosclerosis. We defined a stringent set of 3736 multi-exonic lncRNA transcripts in rabbits. All lncRNAs are firstly reported and 609 (16.3%) of them are conserved in 13 species. Rabbit lncRNAs have similar characteristics to lncRNAs in other mammals, such as relatively short length, low expression, and highly tissue-specificity. The integrative analysis of lncRNAs and co-expressed genes characterize diverse functions of lncRNAs. Comparing two kinds of atherosclerosis models (LDLR-deficient WHHL rabbits and cholesterol-fed NZW rabbits) with their corresponding controls, we found the expression changes of two rabbit models were similar in aorta in but different in liver. The shared change in aorta revealed a subset of lncRNAs involved in immune response, while the cholesterol-fed NZW rabbits showed broader lncRNA expression changes in skeletal muscle system compared to WHHL rabbits. These atherosclerosis-associated lncRNAs and genes provide hits for the experimental validation of lncRNA functions. In summary, our study systematically identified rabbit lncRNAs for the first time and provides new insights for understanding the functions of lncRNAs in atherosclerosis. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang.

Vascular Tissue Specific miRNA Profiles Reveal Novel Correlations with Risk Factors in Coronary Artery Disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors. Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis. We identified 17 miRs-miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683 and miR-5701-significantly correlated with cardiovascular risk factors (correlation coefficient >0.2 in both directions, p-value (p < 0.006, false discovery rate (FDR) <0.05). Of particular interest, miR-5701 was positively correlated with hypertension, hypercholesterolemia, and diabetes. In addition, we found that miR-629-5p and miR-98-5p were significantly correlated with acute myocardial infarction. We provide a first atlas of miR profiles in IMA samples from CAD patients. In perspective, these miRs might play an important role in improved risk assessment, mechanistic disease understanding and local therapy of CAD.