Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant medications and remain the cornerstone of systemic lupus erythematosus (SLE) therapy. However, ongoing exposure to GCs has the ...potential to elicit multiple adverse effects. Considering the irreplaceability of GCs in SLE therapy, it is important to explore the optimal regimen of GCs. Here, we compared the long-term efficacy and safety of pulsed and oral GC therapy in a lupus-prone mouse model. Mice were grouped using a randomized block design. We monitored survival rates, proteinuria, serum autoantibodies, and complement 3 (C3) levels up to 28 weeks of age, and assessed renal damage, bone quality, lipid deposition in the liver and marrow, glucose metabolic parameters, and levels of hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, we explored the mechanisms underlying the superior efficacy of the pulse regimen over oral prednisone regimen. We found that both GC regimens alleviated the poor survival rate, proteinuria, and glomerulonephritis, while also reducing serum autoantibodies and increasing the level of C3. The pulsed GC regimen showed less resistance to insulin, less suppression of the HPA axis, less bone loss, and less bone marrow fat deposition than the oral GC regimen. Additionally, GC-induced leucine zipper (GILZ) was significantly overexpressed in the GC pulse group. These results suggest that the GC pulse regimen ameliorated symptoms in lupus-prone mice, with fewer side effects, which may be related to GILZ overexpression. Our findings offer a potentially promising GC treatment option for SLE.
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•Methylprednisolone (MP) pulse regimen has fewer side effects than oral prednisone regimen.•MP pulse regimen and oral prednisone regimen have similar efficacy.•GILZ overexpression may be a potential mechanism for MP pulse regimen’s fewer side effects.•MP pulse regimen is a potentially promising GC treatment option for SLE.
Antimicrobials are often used to prevent and treat diarrhea induced by enteroaggregative Escherichia coli (EAEC) in young ruminants. However, drug overuse or misuse accelerates the spread of ...multidrug-resistant extended-spectrum β-lactamase (ESBL)-producing E. coli. Thus, supplementary foods as alternatives to antibiotics are needed to prevent colibacillus diarrhea in neonatal dairy calves. Ursodeoxycholic acid (UDCA), a therapeutic bile acid, helps alleviate colitis. However, how UDCA helps alleviate ESBL-EAEC-induced clinical symptoms and colitis remains unclear.
We investigated the microbial profiles and metabolites of healthy and diarrheic neonatal calves to determine microbial and metabolite biomarkers in early-life development. Both the gut microbiota communities and their associated metabolites differed between healthy and diarrheic calves. Commensal Butyricicoccus, Faecalibacterium, Ruminococcus, Collinsella, and Coriobacterium were key microbial markers that distinguished healthy and diarrheic gut microbiomes. Random forest machine-learning algorithm and Spearman correlation results indicated that enriched UDCA, short-chain fatty acids (SCFAs), and other prebiotics were strongly positively correlated with these five bacterial genera. We explored the effect of ursodiol on bacterial growth, cell adherence, and lipopolysaccharide-treated Caco-2 cells. Adding ursodiol induced direct antibacterial effects, suppressed proinflammatory effects, and reduced cell integrity damage. Oral ursodiol delivery to neonatal mice exhibited significant antibacterial effects and helped maintain colonic barrier integrity in mouse models of peritonitis sepsis and oral infection. UDCA supplementation attenuated colitis and recovered colonic SCFA production. To validate this, we performed fecal microbiota transplantations to inoculate ESBL-EAEC-infected neonatal mice. Microbiotas from UDCA-treated neonatal mice ameliorated colitis and hindgut commensal bacterial damage compared with that of the microbiotas from the control and placebo mice, as evidenced by colonization of abundant bacteria, including Oscillospiraceae, Ruminococcaceae, Lachnospiraceae, and Clostridia_UCG-014, and upregulated SCFA production.
This study provided the first evidence that UDCA could confer diarrhea resistance in ESBL-EAEC-infected newborn dairy calves. UDCA blocked bacterial growth and invasion both in vitro and in vivo, alleviated commensal bacterial dysbiosis during ESBL-EAEC infection in neonatal mouse models of sepsis and colitis via the TGR5-NF-κB axis, and upregulated SCFA production in the hindgut digesta. Our findings provide insight into the UDCA-mediated remission of ESBL-EAEC infections and the potential role of UDCA as an antibiotic alternative. Video abstract.
Objectives
Previous studies have reported inconsistent results on the relationship between alcohol intake and the risk of systemic lupus erythematosus (SLE). Therefore, we conducted a systematic ...review and meta-analysis to illustrate the potential role of alcohol intake on the progression of SLE.
Methods
An electronic search of the PubMed, EmBase, and the Cochrane library databases was conducted from their inception up to March 2020. Observational studies that investigated the role of alcohol intake on the risk of SLE were eligible for inclusion in this study. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated as an effect estimate using the random-effects model.
Results
Seven case-control studies (n = 3, 251) and three cohort studies (n = 322, 479) were selected for the final meta-analysis. Mild (OR: 0.85; 95% CI: 0.53–1.38; p = 0.515) or heavy (OR: 0.63; 95% CI: 0.37–1.09; p = 0.102) alcohol intake were not associated with the risk of SLE, while moderate alcohol intake could protect against the risk of SLE (OR: 0.71; 95% CI: 0.55–0.93; p = 0.012). Sensitivity analysis suggested that heavy alcohol intake was associated with a reduced risk of SLE (OR: 0.47; 95% CI: 0.32–0.67; p < 0.001).
Conclusions
This study found that moderate alcohol intake could protect against the risk of SLE, while mild or heavy alcohol intake did not significantly affect the risk of SLE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
When the dual rotor system of the aircraft engine is operating, the mass eccentricity of the power turbine rotor and the misalignment of the shaft coupling or the bearing will cause too large ...vibration of the rotor; this vibration leads to the rub-impact between the rotor and the casing. The power turbine rotor from the dual rotor system is taken as the research object in this paper. Considering the misalignment, the resulting rub-impact faults, the imbalance of rotor and the disk offset, the equation of motion for the system is developed according to the Lagrangian Equation, and then the Range-Kutta Method is adopted to solve the equation. The influence of the key parameters such as the rotating speed, the misalignment angle and the rub-impact clearance on the dynamics of the system is studied; the finite element analysis was carried out to validate the correctness of the theoretical modeling method. The results show that the rub-impact increases the stiffness of the system; the Hopf bifurcation occurs in the misalignment and rub-impact coupling system; the vibrational stability near the half of the switching speed slumps with the increase of the misalignment angle; with increasing of the stiffness, the number of the chaotic zone increases, and the range of the chaos is widening; enlarging the rub-impact clearance is beneficial to reduce the degree of the rub-impact system and enhance the stability of the system.
Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease that results in significant damage and often needs more aggressive treatment. Compared to adult-onset SLE, cSLE has a ...stronger genetic background and more prevalent elevated type I Interferon expression. The management of cSLE is more challenging because the disease itself and treatment can affect physical, psychological and emotional growth and development. High dose oral glucocorticoid (GC) has become the rule for treating moderate to severe cSLE activity. However, GC-related side effects and potential toxicities are problems that cannot be ignored. Recent studies have suggested that GC pulse therapy can achieve disease remission rapidly and reduce GC-related side effects with a reduction in oral prednisone doses. This article reviews characteristics, including pathogenesis and manifestations of cSLE, and summarized the existing evidence on GC therapy, especially on GC pulse therapy in cSLE, followed by our proposal for GC therapy according to the clinical effects and pathogenesis.
Interleukin (IL)-6 plays an essential role in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA). Tocilizumab (TCZ), a kind of biological agent against both membrane and soluble IL-6 ...receptor, is the only biological agent approved for the treatment of sJIA in China. Infections are the most common adverse events during TCZ therapy, and most of infections are mild or moderate. Severe sepsis originated from gastrointestinal infection is rarely reported.
In this article, we reported two 13-year-old sJIA patients who suffered from life-threatening infections after TCZ administration. Within one day, both of them presented rapidly progressive conditions that included fever, abdominal pain, dizziness, diarrhea and vomiting, and laboratory tests showed multi-organ dysfunctions. They were diagnosed with severe sepsis and septic shock that were supposed to be caused by the pathogens from the gastrointestinal tract, and they were eventually rescued by timely treatment. In addition, we also reviewed the literature about serious gastrointestinal infections and sepsis in sJIA patients receiving TCZ therapy.
In summary, for sJIA patients with TCZ therapy, invading pathogens from the gastrointestinal tract can cause an intensely systemic infection that may even be fatal. Therefore, it is essential to pay attention to the gastrointestinal management of sJIA patients as well as remind them of their intestinal hygiene.
Dental caries, as a common oral infectious disease, is a worldwide public health issue. Oral biofilms are the main cause of dental caries.
(
) is well recognized as the major causative factor of ...dental caries within oral biofilms. In addition to mechanical removal such as tooth brushing and flossing, the topical application of antimicrobial agents is necessarily adjuvant to the control of caries particularly for high-risk populations. The mainstay antimicrobial agents for caries such as chlorhexidine have limitations including taste confusions, mucosal soreness, tooth discoloration, and disruption of an oral microbial equilibrium. Antimicrobial small molecules are promising in the control of
due to good antimicrobial activity, good selectivity, and low toxicity. In this paper, we discussed the application of antimicrobial small molecules to the control of
, with a particular focus on the identification and development of active compounds and their modes of action against the growth and virulence of
.
Inflammatory conditions and immune disorders may worsen the prognosis of chronic heart failure (CHF) patients. The aim of this study was to evaluate the prognostic value of a new indicator, C-NLR, ...composed of C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), for the risk of all-cause mortality in HF patients with different ejection fractions.
A total of 1221 CHF patients admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021 were enrolled in this study. All patients were divided into 2 groups according to the median C-NLR. Kaplan-Meier survival curves were used to compare the all-cause mortality among CHF patients with different ejection fractions. Cox proportional hazards analysis was used to evaluate the relationships between variables and mortality. The predictive value of the C-NLR was assessed by using receiver operating characteristic (ROC) analyses.
We collected data from 1192 patients with CHF. Kaplan-Meier survival analysis revealed that patients with low LCR levels had better overall survival (OS). After multivariate adjustment Cox proportional hazards analysis, the level of C-NLR was still independently related to mortality.
C-NLR was a competent independent predictor in HF with different ejection fractions, and routine measurement of C-NLR would help clinical doctors identify patients with a poor prognosis.
Hyperspectral and light detection and ranging (LiDAR) data fusion and classification has been an active research topic, and intensive studies have been made based on mathematical morphology. However, ...matrix-based concatenation of morphological features may not be so distinctive, compact, and optimal for classification. In this work, we propose a novel Coupled Higher-Order Tensor Factorization (CHOTF) model for hyperspectral and LiDAR data classification. The innovative contributions of our work are that we model different features as multiple third-order tensors, and we formulate a CHOTF model to jointly factorize those tensors. Firstly, third-order tensors are built based on spectral-spatial features extracted via attribute profiles (APs). Secondly, the CHOTF model is defined to jointly factorize the multiple higher-order tensors. Then, the latent features are generated by mode-n tensor-matrix product based on the shared and unshared factors. Lastly, classification is conducted by using sparse multinomial logistic regression (SMLR). Experimental results, conducted with two popular hyperspectral and LiDAR data sets collected over the University of Houston and the city of Trento, respectively, indicate that the proposed framework outperforms the other methods, i.e., different dimensionality-reduction-based methods, independent third-order tensor factorization based methods, and some recently proposed hyperspectral and LiDAR data fusion and classification methods.
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