Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammatory disease in the lower gastrointestinal tract. Mounting evidence suggests that the ...predominance of the classically activated (M1) macrophages versus the alternatively activated (M2) macrophages plays a role in the progression of IBD. Thus, agents able to shift pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages may be beneficial to IBD. The pentacyclic triterpene Lup-20(29)-en-3β-ol (Lupeol), a potent anti-inflammatory natural product, has been shown to inhibit pro-inflammatory cytokine production, suggesting it is potentially able to modulate macrophage polarization, thereby beneficial to IBD.
CD4+ monocytes were differentiated to M1 or M2 macrophages, which were cocultured with epithelial cell lines, T84 and Caco-2, in the absence or presence of Lupeol (10μM). Experimental colitis was induced with dextran sodium sulfate (DSS), with or without oral administration of Lupeol (50mg/kg, q.d.). Cytokines were measured with Luminex kits. M1/M2 genes were measured with real-time polymerase chain reaction. Macrophage phenotypes were defined by measuring M1 and M2 markers with confocal microscopy. Proteins were measured with Western blotting, while cell surface markers were measured with confocal microscopy or flow cytometry. Histology was evaluated with H&E staining.
Treatment of M1 macrophages with Lupeol resulted in a marked decrease in the production of pro-inflammatory cytokines, including IL-12, IL6, IL-1β and TNFα, and a marked increase in the production of IL-10, an anti-inflammatory cytokine. This was associated with a down-regulation of CD86, a typical marker of M1 macrophages, and an up-regulation of CD206, a typical M2 macrophage marker. IRF5, a transcription factor that is critically involved in M1 polarization, was down-regulated in M1 macrophages after being incubated with Lupeol, associated with a marked decrease in the phosphorylation of p38 mitogen activated protein kinase. Coculture of epithelial cells with M1 macrophages resulted in down-regulation of the tight junction protein ZO-1 and disruption of epithelial integrity, which were blocked by Lupeol treatment of the M1 macrophages. Moreover, oral administration of Lupeol to dextran sulfate sodium (DSS)-induced colitis mice resulted in mitigated intestinal inflammation and increased survival from lethal colitis, associated with decreased expression of M1-related genes and increased expression of M2-related genes.
Lupeol ameliorates experimental inflammatory bowel disease through, at least in part, inhibiting M1 and promoting M2 macrophages.
•The pentacyclic triterpene Lup-20(29)-en-3β-ol (Lupeol), a potent anti-inflammatory natural product, was able to switch macrophages from M1 to M2 phenotype.•Moreover, oral administration of Lupeol to dextran sulfate sodium (DSS)-induced colitis mice resulted in mitigated intestinal inflammation and increased survival from lethal colitis, associated with decreased expression of M1-related genes and increased expression of M2-related genes in the lesion.•Our data suggest Lupeol ameliorates experimental IBD through, at least in part, inhibiting M1 and promoting M2 macrophages.•Considering the very low toxicity of Lupeol, we believe that these findings are significant.
Background:
The rapid worldwide spread of the Omicron variant of SARS-CoV-2 has unleashed a new wave of COVID-19 outbreaks. The efficacy of molnupiravir, an approved drug, is still unknown in ...patients infected with the Omicron variant.
Objective:
Evaluated the antiviral efficacy and safety of molnupiravir in patients infected with SARS-CoV-2 Omicron variant, with symptom duration within 5 days.
Methods:
We conducted a randomized, controlled trial involving patients with mild or moderate COVID-19. Patients were randomized to orally receive molnupiravir (800 mg) plus basic treatment or only basic treatment for 5 days (BID). The antiviral efficacy of the drug was evaluated using reverse transcriptase polymerase chain reaction.
Results:
Results showed that the time of viral RNA clearance (primary endpoint) was significantly decreased in the molnupiravir group (median, 9 days) compared to the control group (median, 10 days) (Log-Rank
p
= 0.0092). Of patients receiving molnupiravir, 18.42% achieved viral RNA clearance on day 5 of treatment, compared to the control group (0%) (
p
= 0.0092). On day 7, 40.79%, and 6.45% of patients in the molnupiravir and control groups, respectively, achieved viral RNA clearance (
p
= 0.0004). In addition, molnupiravir has a good safety profile, and no serious adverse events were reported.
Conclusion:
Molnupiravir significantly accelerated the SARS-CoV-2 Omicron RNA clearance in patients with COVID-19.
Clinical Trial Registration:
chictr.org.cn
, identifier ChiCTR2200056817.
Purpose
Using magnetic resonance fluid-attenuated inversion recovery sequence (FLAIR) combined with three-dimensional arterial spin labeling (3D-ASL) cerebral perfusion imaging to explore the effect ...of collateral circulation on acute ischemic stroke (AIS).
Methods
Eighty patients with AIS who had severe stenosis or occlusion at the end of the unilateral middle cerebral artery (MCA) were collected for the study on admission. Arterial transit artifact (ATA) was observed and graded for hyperintense vessel sign (HVS). CBF values were measured and recorded in the ischemic penumbra (IP) area and contralateral to it. The National Institutes of Health Stroke Scale (NIHSS) scores on the day of admission and discharge were recorded, and reductions in relative cerebral blood flow (rCBF) and discharge NIHSS scores were calculated.
Results
The rCBF and decrease in NIHSS scores were statistically significant (
p
< 0.05) between all levels of HVS, the groups of ATA, and the combination of the two. Correlation analysis results indicate that both HVS and ATA are positively correlated with rCBF and NIHSS score degradation. The receiver operating characteristic (ROC) curves showed that the sensitivity of HVS and ATA for evaluating cerebral blood flow (CBF) changes was 92.0% and 76.0%, and the specificity was 41.8% and 52.7%, respectively. The combined sensitivity of the two was 68.0%, and the specificity was 65.5%.
Conclusion
The T2-FLAIR sequence combined with ASL can more accurately assess the blood flow changes in the IP area, the open state of collateral circulation, and the clinical prognosis.
