Let-7f-5p Modulates Lipid Metabolism by Targeting Sterol Regulatory Element-Binding Protein 2 in Response to PRRSV Infection.

Porcine reproductive and respiratory syndrome (PRRS) has caused substantial damage to the pig industry. MicroRNAs (miRNAs) were found to play crucial roles in modulating the pathogenesis of PRRS virus (PRRSV). In the present study, we revealed that PRRSV induced let-7f-5p to influence lipid metabolism to regulate PRRSV pathogenesis. A transcriptome analysis of PRRSV-infected PK15CD163 cells transfected with let-7f-5p mimics or negative control (NC) generated 1718 differentially expressed genes, which were primarily associated with lipid metabolism processes. Furthermore, the master regulator of lipogenesis SREBP2 was found to be directly targeted by let-7f-5p using a dual-luciferase reporter system and Western blotting. The findings demonstrate that let-7f-5p modulates lipogenesis by targeting SREBP2, providing novel insights into miRNA-mediated PRRSV pathogenesis and offering a potential antiviral therapeutic target.

Geriatric nutritional risk index has a prognostic value for recovery outcomes in elderly patients with brain abscess.

Background: The Geriatric Nutritional Risk Index (GNRI) is a straightforward and objective tool for nutritional screening in older patients and has been demonstrated to possess prognostic predictive value in several diseases. Nonetheless, there is a lack of research on the nutritional risk associated with brain abscess in the older. This study aimed to evaluate the prevalence of nutritional risk among these patients by GNRI and to investigate its potential prognostic value for clinical outcomes. Materials and methods: From August 2019 to April 2023, 100 older patients diagnosed with brain abscess were enrolled in this single-center prospective cohort study, which evaluated the prognostic value of the Geriatric Nutritional Risk Index (GNRI) in elderly brain abscess patients. Data collected included demographic, and clinical characteristics at admission and calculated the GNRI, and the Glasgow Outcome Scale (GOS) score 6 months post-discharge. A GOS score of 5 was considered indicative of a good recovery, whereas scores ranging from 1 to 4 were classified as poor recovery. Results: The results revealed that 48% of older brain abscess patients were at risk of malnutrition according to the GNRI. These patients had significantly higher post-admission C-reactive protein (CRP) levels (p = 0.017), more comorbidities (p < 0.001), and higher age-adjusted Charlson Comorbidity Index (aCCI) scores (p < 0.001) compared to those without nutritional risk. Spearman correlation analysis showed that GNRI scores were negatively correlated with CRP levels, comorbidities, and aCCI scores, and positively correlated with Glasgow Outcome Scale (GOS) scores (Spearman's ρ = 0.624, p < 0.001). Multivariate logistic regression revealed that lower GNRI values were linked to reduced GOS levels (OR = 0.826, 95% CI: 0.775-0.880). ROC analysis determined a GNRI threshold of 97.50 for predicting poor recovery, with 90.57% sensitivity and 87.23% specificity. Conclusion: The older brain abscess patients exhibited a high malnutrition risk. GNRI showed an important predictive value for recovery in older patients, which could be helpful in clinical intervention and rehabilitation.

Screening of mRNA markers in early bovine tuberculosis blood samples.

Bovine tuberculosis (bTB) is a chronic zoonotic disease caused by Mycobacterium bovis. A large number of cattle are infected with bTB every year, resulting in huge economic losses. How to control bTB is an important issue in the current global livestock economy. In this study, the original transcriptome sequences related to this study were obtained from the dataset GSE192537 by searching the Gene Expression Omnibus (GEO) database. Our differential gene analysis showed that there were obvious biological activities related to immune activation and immune regulation in the early stage of bTB. Immune-related biological processes were more active in the early stage of bTB than in the late. There were obvious immune activation and immune cell recruitment in the early stage of bTB. Regulations in immune receptors are associated with pathophysiological processes of the early stage of bTB. A gene module consisting of 236 genes significantly related to the early stage of bTB was obtained by weighted gene co-expression network analysis, and 18 hub genes were further identified as potential biomarkers or therapeutic targets. Finally, by random forest algorithm and logistic regression modeling, FCRL1 was identified as a representative mRNA marker in early bTB blood. FCRL1 has the potential to be a diagnostic biomarker in early bTB.

Functional Mutations in the microRNA-155 Promoter Modulate its Transcription Efficiency and Expression.

Limited research has been conducted on porcine miR-155 promoters, and previous study from our group have identified two haplotypes (TT and CC) in different pig breeds, each associated with five fully linked mutation sites within or near the miR-155 gene (Li et al. Dev Comp Immunol 39(1):110-116, 2013). In this study, the promoter region of porcine miR-155 was screened, and two important transcription factors, Foxp3 and RelA, were identified. The binding ability of Foxp3 protein was found to be affected by the first mutation site (A/C) using EMSA analysis. In vitro experiments revealed that the expression level of miR-155 was significantly higher in the C haplotype compared to the T haplotype. Additionally, northern blotting assays indicated that both the first mutation site (A/C) and the fourth mutation site (G/T) had a significant impact on miR-155 expression levels. These findings provide further insights into the transcriptional regulation of porcine miR-155 and identify crucial mutation sites that influence miR-155 expression. This knowledge can serve as a basis for identifying potential molecular markers associated with disease resistance in swine.

Molecular mechanism of valine and its metabolite in improving triglyceride synthesis of porcine intestinal epithelial cells.

An insufficient energy supply to intestinal epithelial cells decreases production performance in weaned piglets. Triglycerides are the main energy source for intestinal epithelial cells in piglets. The present study aimed to investigate the effects and mechanisms of valine supplementation on triglyceride synthesis in porcine intestinal epithelial (IPEC-J2) cells. Valine supplementation in the medium significantly increased the content of triglycerides, fat droplets, and long-chain fatty acids (C17:0, C18:0, C20:0, C18:1, C20:1, and C22:1) (P < 0.05). Valine metabolite (3-hydroxyisobutyrate [3-HIB]) concentration increased significantly in the valine-supplemented group (P < 0.05). Silencing of the 3-HIB synthase enzyme 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) in IPEC-J2 cells significantly reduced the triglyceride concentration and lipid droplet synthesis. Further studies found that 3-HIB supplementation in the medium significantly increased the concentration of triglycerides, lipid droplets, and unsaturated fatty acids (C16:1, C18:1, C18:2, C18:3, C20:3, C20:4, and C20:5) (P < 0.05) by upregulating the expression of proteins involved in fatty acid transport (CD36) and fatty acid binding protein 3 (FABP3) or triglyceride synthesis (DGAT1) (P < 0.05), indicating that 3-HIB mediates valine-enhanced triglyceride synthesis in IPEC-J2 cells. In conclusion, our results demonstrated that valine enhanced triglyceride synthesis in IPEC-J2 cells via increasing the 3-HIB concentration, which may promote fatty acid transport via upregulation of proteins related to fatty acid transporter. These findings provide new insights into the mechanisms through which valine participates in lipid metabolism.

Tripterygium wilfordii Hook F treatment for idiopathic refractory nephrotic syndrome in adults: a meta-analysis.

Tripterygium wilfordii Hook F (TwHF) is a Chinese herbal medicine with immunosuppressive effects and an established history of use in the treatment of inflammatory and autoimmune diseases. We have carried out a meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs which assessed the effectiveness of TwHF in the treatment for idiopathic refractory nephrotic syndrome (IRNS). After reading the full text, only three RCTs or quasi-RCTs meeting our inclusion criteria were selected. Our meta-analysis indicated that TwHF has beneficial effects on the remission of IRNS. There was no significant publication bias in the meta-analysis studies. However, studies with a larger sample size and including patients with both a mild and severe histopathological change involvement separately are needed to assess the effects of TwHF in IRNS patients before exact conclusions can be drawn.

Mycophenolate mofetil treatment for IgA nephropathy: a meta-analysis.

BACKGROUND: Worldwide, IgA nephropathy (IgAN) is the most common type of glomerulonephritis. Mycophenolate mofetil (MMF) is relatively selective for lymphocytes and inhibits antibody production by B cells more than other immunosuppressants. Several randomized controlled trials (RCTs) have analyzed the role of MMF in patients with IgAN. We conducted this meta-analysis of all available RCTs to ascertain the benefits and risks of MMF treatment in comparison with placebos or steroids in patients with IgAN. METHODS: The studies were identified by extended computer-based searches of the PubMed database (April, 2008) and the Cochrane Library, without language restriction. References in Medline-cited studies were reviewed to identify additional reports not indexed by Medline. RCTs comparing treatment of IgAN with mycophenolate against placebo or steroids were included in the analysis. RESULTS: We identified 32 potentially relevant articles, but only 4 RCTs, which had enrolled a total of 168 patients, were included. Our meta-analysis demonstrated that MMF treatment did not have statistically significant effects in reducing proteinuria or protecting renal function in patients with IgAN. CONCLUSION: The currently available evidence does not support the routine use of MMF in patients with IgAN. Larger international collaborations should be put in place to further address this issue.

[Determination of residual epichlorohydrin and sym-dichloroisopropyl alcohol in cationic etherified reagent by gas chromatography].

A method for the determination of the residual epichlorohydrin and sym-dichloroisopropyl alcohol in cationic etherified reagent by gas chromatography has been established. Methyl benzoate, which has high extraction efficiency for the two components, was used as extractant. With an HP-5 capillary column, the two components were baseline separated and they eluted before the extractant. The linear ranges achieved were 5 - 590 mg/kg for epichlorohydrin and 21 - 480 mg/kg for sym-dichloroisopropyl alcohol. The limits of detection were 1.2 mg/kg for epichlorohydrin and 2.2 mg/kg for sym-dichloroisopropyl alcohol. Recoveries for epichlorohydrin were 95.93% - 103.42% with relative standard deviations of 2.4% - 10.6% and those for sym-dichloroisopropyl alcohol were 98.54% - 107.40% with relative standard deviations of 6.6% -11.1%. The method is simple, fast, and convenient.