Genome-wide analysis of circular RNAs in goat skin fibroblast cells in response to Orf virus infection

Orf, caused by Orf virus (ORFV), is a globally distributed zoonotic disease responsible for serious economic losses in the agricultural sector. However, the mechanism underlying ORFV infection remains largely unknown. Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, play important roles in various pathological processes but their involvement in ORFV infection and host response is unclear. In the current study, whole transcriptome sequencing and small RNA sequencing were performed in ORFV-infected goat skin fibroblast cells and uninfected cells. A total of 151 circRNAs, 341 messenger RNAs (mRNAs), and 56 microRNAs (miRNAs) were differently expressed following ORFV infection. Four circRNAs: circRNA1001, circRNA1684, circRNA3127 and circRNA7880 were validated by qRT-PCR and Sanger sequencing. Gene ontology (GO) analysis indicated that host genes of differently expressed circRNAs were significantly enriched in regulation of inflammatory response, epithelial structure maintenance, positive regulation of cell migration, positive regulation of ubiquitin-protein transferase activity, regulation of ion transmembrane transport, etc. The constructed circRNA-miRNA-mRNA network suggested that circRNAs may function as miRNA sponges indirectly regulating gene expression following ORFV infection. Our study presented the first comprehensive profiles of circRNAs in response to ORFV infection, thus providing new clues for the mechanisms of interactions between ORFV and the host

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

High triglyceride levels increase the risk of diabetic microvascular complications: a cross-sectional study

Abstract Background The prevalence of microvascular complications in type 2 diabetes mellitus (T2DM) is increasing. The effect of lipid profiles on diabetic microvascular complications remains debated. This research aimed to study the correlation between lipid profiles and microvascular complications. Methods This retrospective cross-sectional study included 1096 T2DM patients. The patients were divided into the control, diabetic retinopathy (DR), nephropathy (DKD), and peripheral neuropathy (DPN) groups based on the existence of corresponding complications. The lipid profiles were analyzed, and the effect on complications was assessed by logistic regression. Results Compared with the control group, the diabetic microvascular complications group had a higher dyslipidemia rate. The rate of high TGs increased significantly with an increasing number of complications. High TG levels contributed to the risk of DKD, DR, and DPN [odds ratios (ORs): 2.447, 2.267, 2.252; 95% confidence interval: 1.648–3.633, 1.406–3.655, 1.472–3.445]. In the age (years) > 55, T2DM duration (years) > 10, and HbA1c (%) ≥ 7 groups, the risk of high TGs was higher for DKD (ORs: 2.193, 2.419, 2.082), DR (ORs: 2.069, 2.317, 1.993), and DPN (ORs: 1.811, 1.405, 1.427). Conclusion High TG levels increase the risk of diabetic microvascular complications, and patients with older age, longer T2DM duration, and higher HbA1c levels are recommended to keep lipid levels more strictly

Tracking the enzyme-response mechanism of tannic acid-embedded chitosan/γ-polyglutamic acid hydrogel

Abstract The design of enzyme-response hydrogels has attracted increasing interest in cell therapy, biomedical research, and tissue engineering. Their rational design usually depends on the enzyme-response mechanism and have focused on behavior improvement, drug delivery, and state transition of hydrogels. However, no enzyme-response mechanism has yet been systematically investigated. Here, we construct a tunable platform of tannic acid-embedded chitosan/γ-polyglutamic acid hydrogel to study the enzyme-response mechanism. We track the roles of gallic acid hydrolyzed from tannic acid in altering the structure and properties of the hydrogel to get insights into the mechanism. The gallic acid inside the hydrogel enhances hydrogel crosslinking, increasing the mechanical properties and pH sensitivity but reducing thickness, porosity, and swelling behavior. The gallic acid outside the hydrogel increases the positive potential and superficial hydrophobicity of the hydrogel. These findings will aid the rational design of other enzyme-response hydrogels in more extensive self-adaptive fields

Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy

ABSTRACT Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis

Upregulation of Immune Process-Associated Genes in RAW264.7 Macrophage Cells in Response to Burkholderia pseudomallei Infection

Melioidosis is a severe and fatal tropical zoonosis, which is triggered by Burkholderia pseudomallei. To better understand the host’s response to infection of B. pseudomallei, an RNA-Seq technology was used to confirm differentially expressed genes (DEGs) in RAW264.7 cells infected with B. pseudomallei. In total, 4668 DEGs were identified across three time points (4, 8, and 11 hours after infection). Short Time-Series Expression Miner (STEM) analysis revealed the temporal gene expression profiles and identified seven significant patterns in a total of 26 profiles. Kyoto Encyclopedia of Genes and Genomes (KEGG) was utilized to confirm significantly enriched immune process-associated pathways, and 10 DEGs, including Ccl9, Ifnb1, Tnfα, Ptgs2, Tnfaip3, Zbp1, Ccl5, Ifi202b, Nfkbia, and Nfkbie, were mapped to eight immune process-associated pathways. Subsequent quantitative real-time PCR assays confirmed that the 10 DEGs were all upregulated during infection. Overall, the results showed that B. pseudomallei infection can initiate a time-series upregulation of immune process-associated DEGs in RAW264.7 macrophage cells. The discovery of this article helps us better understand the biological function of the immune process-associated genes during B. pseudomallei infection and may aid in the development of prophylaxis and treatment protocols for melioidosis

Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status

Numerous studies have investigated the associations between serum vitamin D or testosterone and diabetes; however, inconsistencies are observed. Whether there is an interaction between vitamin D and testosterone and whether the lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)) mediates the association between vitamin D and diabetes is unclear. To investigate the effect of vitamin D and testosterone on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM), 2659 participants from the Henan Rural Cohort were included in the case-control study. Generalized linear models were utilized to estimate associations of vitamin D with IFG or T2DM and interactive effects of vitamin D and testosterone on IFG or T2DM. Principal component analysis (PCA) and mediation analysis were used to estimate whether the lipid profile mediated the association of vitamin D with IFG or T2DM. Serum 25(OH)D3, 25(OH)D2, and total 25(OH)D levels were negatively correlated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 0.99 (0.97, 1.00), 0.85 (0.82, 0.88), and 0.97 (0.96, 0.98), respectively). Similarity results for associations between serum 25(OH)D2 and total 25(OH)D with T2DM (ORs (95%CIs): 0.84 (0.81, 0.88) and 0.97 (0.96, 0.99)) were observed, whereas serum 25(OH)D3 was negatively correlated to T2DM only in the quartile 2 (Q2) and Q3 groups (both p &lt; 0.05). The lipid profile, mainly TC and TG, partly mediated the relationship between 25(OH)D2 or total 25(OH)D and IFG or T2DM and the proportion explained was from 2.74 to 17.46%. Furthermore, interactive effects of serum 25(OH)D2, total 25(OH)D, and testosterone on T2DM were observed in females (both p for interactive &lt;0.05), implying that the positive association between serum testosterone and T2DM was vanished when 25(OH)D2 was higher than 10.04 ng/mL or total 25(OH)D was higher than 40.04 ng/mL. Therefore, ensuring adequate vitamin D levels could reduce the prevalence of IFG and T2DM, especially in females with high levels of testosterone

Long-term exposure to PM1 and PM2.5 is associated with serum cortisone level and meat intake plays a moderation role

Background: Although short-term exposure to particulate matter (PM) was associated with increased glucocorticoids (GCs) levels, available evidence on associations of long-term exposure to PM and GCs levels is still scant. Previous studies has showed that meat intake is associated with sex hormones levels, but it is unknown whether meat intake is associated with GCs levels. Furthermore, the role of meat intake in the associations between PM and GCs levels remains unclear. Aims: The aims of this study were to explore the associations of long-term exposure to PM and GCs levels among Chinese rural adults, and the role of meat intake in these associations. Materials and methods: A total of 6223 subjects were recruited from the Henan Rural Cohort Study. Serum GCs levels were measured with liquid chromatography-tandem mass spectrometry. The concentrations of PM (PM1 and PM2.5) for each subject were assessed with machine learning algorithms. The food frequency questionnaire (FFQ) was used to obtain each participant’ information on meat intake. The effects of PM and meat intake on GCs levels were assessed using generalized linear models. In addition, modification analyses were performed to identify the role of meat intake played in the associations of PM with serum GCs levels. Results: Per 1 μg/m3 increment in PM1 or PM2.5 concentration was associated with a 0.364 ng/ml (95% confidence interval (CI): 0.234, 0.494) or 0.227 ng/ml (95%CI: 0.110, 0.343) increase in serum cortisone, respectively. In addition, the moderation effects of total meat intake and red meat intake on the associations of long-term exposure to PM1 or PM2.5 with serum cortisone were observed (P < 0.05), indicating that individuals who had high levels of PM1 or PM2.5 and meat intake were more susceptible to have a higher state of serum cortisone. Conclusions: Our findings suggested that long-term exposure to PM1 or PM2.5 was associated with serum cortisone. Moreover, meat intake was found to be a significant moderator in the association of PM1 or PM2.5 with serum cortisone levels

The effects of combined SIL and DAPT on HepG2 tumor xenografts in vivo.

<p>Photographs showing tumor xenograft morphologiesinthe different groups. <b>B.</b> A tumor growth curve was drawn from the tumor volumes and the treatment duration. <b>C.</b> Representative Western blot results are shown. The results are expressed as the means ± SEM, n = 6. ^aP<0.05, compared with the control group; ^aaP<0.01, compared with the control group; ^bbP<0.01, compared with the SIL 400 mg/kg group; ^ccP<0.01, compared with the DAPT+SIL 400 mg/kg group. SIL, silybin.</p

Effects of combined SIL and Jagged1 protein treatment on cell viability and Notch1 signaling in HCC cells.

<p><b>A.</b> Viability is expressed as OD values. <b>B.</b> Representative Western blot results are shown. The results are expressed as the means ± SEM, n = 6. ^aaP<0.01, compared with the control group, ^bbP<0.01, compared with the 100 µM SIL-treated group, and ^ccP<0.01, compared with the Jagged1+100 µM SIL-treated group. SIL, silybin. OD, optical density.</p