Socially affected traits are affected by direct genetic effects (DGE) and social genetic effects (SGE). DGE and SGE of an individual directly quantify the genetic influence of its own phenotypes and ...the phenotypes of other individuals, respectively. In the current study, a total of 3,276 Large White pigs from different pens were used, and each pen contained 10 piglets. DGE and SGE were estimated for six socially affected traits, and then a GWAS was conducted to identify SNPs associated with DGE and SGE. Based on the whole-genome re-sequencing, 40 Large White pigs were genotyped and 10,501,384 high quality SNPs were retained for single-locus and multi-locus GWAS. For single-locus GWAS, a total of 54 SNPs associated with DGE and 33 SNPs with SGE exceeded the threshold (P < 5.00E-07) were detected for six growth traits. Of these, 22 SNPs with pleiotropic effects were shared by DGE and SGE. For multi-locus GWAS, a total of 72 and 110 putative QTNs were detected for DGE and SGE, respectively. Of these, 5 SNPs with pleiotropic effects were shared by DGE and SGE. It is noteworthy that 2 SNPs (SSC8: 16438396 for DGE and SSC17: 9697454 for SGE) were detected in single-locus and multi-locus GWAS. Furthermore, 15 positional candidate genes shared by SGE and DGE were identified because of their roles in behaviour, health and disease. Identification of genetic variants and candidate genes for DGE and SGE for socially affected traits will provide a new insight to understand the genetic architecture of socially affected traits in pigs.
We report the sequencing at 131× coverage, de novo assembly and analyses of the genome of a female Tibetan wild boar. We also resequenced the whole genomes of 30 Tibetan wild boars from six major ...distributed locations and 18 geographically related pigs in China. We characterized genetic diversity, population structure and patterns of evolution. We searched for genomic regions under selection, which includes genes that are involved in hypoxia, olfaction, energy metabolism and drug response. Comparing the genome of Tibetan wild boar with those of neighboring Chinese domestic pigs further showed the impact of thousands of years of artificial selection and different signatures of selection in wild boar and domestic pig. We also report genetic adaptations in Tibetan wild boar that are associated with high altitudes and characterize the genetic basis of increased salivation in domestic pig.
Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA ...methylation that occur during this turning point of the muscle aging process have not been clarified. To explore age-related genomic methylation changes in skeletal muscle, we employed young (0.5 years old) and middle-aged (7 years old) pigs as models to survey genome-wide DNA methylation in the longissimus dorsi muscle using a methylated DNA immunoprecipitation sequencing approach.
We observed a tendency toward a global loss of DNA methylation in the gene-body region of the skeletal muscle of the middle-aged pigs compared with the young group. We determined the genome-wide gene expression pattern in the longissimus dorsi muscle using microarray analysis and performed a correlation analysis using DMR (differentially methylated region)-mRNA pairs, and we found a significant negative correlation between the changes in methylation levels within gene bodies and gene expression. Furthermore, we identified numerous genes that show age-related methylation changes that are potentially involved in the aging process. The methylation status of these genes was confirmed using bisulfite sequencing PCR. The genes that exhibited a hypomethylated gene body in middle-aged pigs were over-represented in various proteolysis and protein catabolic processes, suggesting an important role for these genes in age-related muscle atrophy. In addition, genes associated with tumorigenesis exhibited aged-related differences in methylation and expression levels, suggesting an increased risk of disease associated with increased age.
This study provides a comprehensive analysis of genome-wide DNA methylation patterns in aging pig skeletal muscle. Our findings will serve as a valuable resource in aging studies, promoting the pig as a model organism for human aging research and accelerating the development of comparative animal models in aging research.
Objective. To investigate the clinical value of Fuzheng Guben anticancer decoction combined with taxol in treating ovarian carcinoma (OC). Methods. The medical records of 80 OC patients treated in ...the First People’s Hospital of Fuyang Hangzhou (January 2018–January 2021) were retrospectively analyzed, and the patients were split into the control group and the experimental group according to the treatment regimen, with 40 cases each. Those in the control group accepted the taxol chemotherapy, and on this basis, those in the experimental group took the Fuzheng Guben anticancer decoction, so as to compare its clinical efficacy and complication incidence. Results. No statistical between-group differences in patients’ general information were observed P>0.05; compared with the control group, the disease objective remission rate of the experimental group was greatly higher P<0.05; before and after treatment, the changes in CD8+ were not significant, indicating no statistically significant between-group differences P>0.05, and after treatment, CD3+, CD4+, and CD4+/CD8+ were obviously higher than before and were obviously higher in the experimental group than in the control group P<0.05; after treatment, the CA125, CA199, and CEA levels were obviously lower than before and were significantly lower in the experimental group than in the control group P<0.05; the mean survival of the experimental group was significantly higher than that of the control group (19.80 ± 5.84 vs. 14.075 ± 5.12 months, P<0.05); and between the two groups, the incidence rate of adverse reactions of the experimental group was remarkably lower P<0.05. Conclusion. On the basis of taxol chemotherapy, jointly applying Fuzheng Guben anticancer decoction can significantly improve the clinical efficacy of OC, help to improve patients’ immune function, lower the complication incidence rate, and prolong the mean survival.
Emerging evidence suggests that microRNAs (miRNAs) may be pathologically involved in osteoarthritis (OA). Subchondral bone (SCB) sclerosis is accounted for the knee osteoarthritis (KOA) development ...and progression. In this study, we aimed to screen the miRNA biomarkers of KOA and investigated whether these miRNAs regulate the differentiation potential of mesenchymal stem cells (MSCs) and thus contributing to SCB. We identified 48 miRNAs in the blood samples in KOA patients (n = 5) through microarray expression profiling detection. After validation with larger sample number, we confirmed hsa‐miR‐582‐5p and hsa‐miR‐424‐5p were associated with the pathology of SCB sclerosis. Target genes prediction and pathway analysis were implemented with online databases, indicating these two candidate miRNAs were closely related to the pathways of pluripotency of stem cells and pathology of OA. Surprisingly, mmu‐miR‐582‐5p (homology of hsa‐miR‐582‐5p) was downregulated in osteogenic differentiation and upregulated in adipogenic differentiation of mesenchymal progenitor C3H10T1/2 cells, whereas mmu‐mir‐322‐5p (homology of hsa‐miR‐424‐5p) showed no change through the in vitro study. Supplementing mmu‐miR‐582‐5p mimics blocked osteogenic and induced adipogenic differentiation of C3H10T1/2 cells, whereas silencing of the endogenous mmu‐miR‐582‐5p enhanced osteogenic and repressed adipogenic differentiation. Further mechanism studies showed that mmu‐miR‐582‐5p was directly targeted to Runx2. Mutation of putative mmu‐miR‐582‐5p binding sites in Runx2 3′ untranslated region (3′UTR) could abolish the response of the 3′UTR‐luciferase construct to mmu‐miR‐582‐5p supplementation. Generally speaking, our data suggest that miR‐582‐5p is an important biomarker of KOA and is able to regulate osteogenic and adipogenic differentiation of MSCs via targeting Runx2. The study also suggests that miR‐582‐5p may play a crucial role in SCB sclerosis of human KOA.
We have revealed miR‐582‐5p as a mesenchymal stem cell (MSCs)‐specific microRNA that can regulate osteogenic and adipogenic differentiation of mesenchymal stem cells via targeting Runx2, possibly contributing to subchondral sclerosis of osteoarthritis. Also, it act as a potential biomarker of knee osteoarthritis.
Background:
Shen-sui-tong-zhi formula (SSTZF) has been used to treat osteoporosis for decades and shows excellent clinical efficacy. This article aims to explore the optimal anti-osteoporotic ...ingredient and its precise mechanisms in mice models.
Methods:
In this study, we first screened the optimal anti-osteoporosis fraction of SSTZF extract
in vivo
, and then further explored the mechanism of its effects both
in vivo
and
in vitro
. Ten-week-old female C57BL/6J mice were administrated with each fraction of SSTZF. At 10 weeks after ovariectomy (OVX), femurs were collected for tissue analyses, including histology, micro-CT, biomechanical tests, and immunohistochemistry for ALP, FABP4, and β-catenin. Additionally, we also evaluated the mRNA expression level of ALP and FABP4 and the protein expression level of β-catenin after being treated with SSTZF extract in C
3
H
10
T1/2 cells. Moreover, we investigated the anti-osteoporosis effect of SSTZF extract on mice with
β-catenin
conditional knockout in growth plate chondrocytes (
β-catenin
Gli1ER
mice) through μCT, histology, and immunohistochemistry analyzes.
Results:
At 10 weeks after treatment, osteoporosis-like phenotype were significantly ameliorated in SSTZF n-butanol extract (SSTZF-NB) group mice, as indicated by increased trabecular bone area and ALP content, and decreased lipid droplet area and FABP4 content. No such improvements were observed after being treated with other extracts, demonstrating that SSTZF-NB is the optimal anti-osteoporosis fraction. Additionally, the elevated β-catenin was revealed in both OVX mice and C
3
H
10
T1/2 cells with SSTZF-NB administered. Furthermore, a significant osteoporosis-like phenotype was observed in
β-catenin
Gli1ER
mice as expected. However, SSTZF-NB failed to rescue the deterioration in
β-catenin
Gli1ER
mice, no significant re-upregulated ALP and downregulated FABP4 were observed after being treated with SSTZF-NB, demonstrating that SSTZF-NB prevents bone loss mainly via β-catenin signaling.
Conclusion:
SSTZF-NB enhances osteogenesis mainly via activation of β-catenin signaling in growth plate chondrocytes. SSTZF-NB is the optimal anti-osteoporosis fraction of SSTZF and it can be considered a salutary alternative therapeutic option for osteoporosis.
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