Gynostemma pentaphyllum Extract Alleviates NASH in Mice: Exploration of Inflammation and Gut Microbiota.

NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.

Influence of arterial transit time delays on the differentiation between tumor progression and pseudoprogression in glioblastoma by arterial spin labeling magnetic resonance imaging.

Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) have shown potential for differentiating tumor progression from pseudoprogression. For pseudocontinuous ASL with a single postlabeling delay, the presence of delayed arterial transit times (ATTs) could affect the evaluation of ASL-MRI perfusion data. In this study, the influence of ATT artifacts on the perfusion assessment and differentiation between tumor progression and pseudoprogression were studied. This study comprised 66 adult patients (mean age 60 ± 13 years; 40 males) with a histologically confirmed glioblastoma who received postoperative radio (chemo)therapy. ASL-MRI and DSC-MRI scans were acquired at 3 months postradiotherapy as part of the standard clinical routine. These scans were visually scored regarding (i) the severity of ATT artifacts (%) on the ASL-MRI scans only, scored by two neuroradiologists; (ii) perfusion of the enhancing tumor lesion; and (iii) radiological evaluation of tumor progression versus pseudoprogression by one neuroradiologist. The final outcome was based on combined clinical and radiological follow-up until 9 months postradiotherapy. ATT artifacts were identified in all patients based on the mean scores of two raters. A significant difference between the radiological evaluation of ASL-MRI and DSC-MRI was observed only for ASL images with moderate ATT severity (30%-65%). The perfusion assessment showed ASL-MRI tending more towards hyperperfusion than DSC-MRI in the case of moderate ATT artifacts. In addition, there was a significant difference between the prediction of tumor progression with ASL-MRI and the final outcome in the case of severe ATT artifacts (McNemar test, p = 0.041). Despite using ASL imaging parameters close to the recommended settings, ATT artifacts frequently occur in patients with treated brain tumors. Those artifacts could hinder the radiological evaluation of ASL-MRI data and the detection of true disease progression, potentially affecting treatment decisions for patients with glioblastoma.

Gynostemma pentaphyllum polysaccharides ameliorate non-alcoholic steatohepatitis in mice associated with gut microbiota and the TLR2/NLRP3 pathway.

Recent studies have revealed the pivotal role of gut microbiota in the progress of liver diseases including non-alcoholic steatohepatitis (NASH). Many natural herbs, such as Gynostemma pentaphyllum (GP), have been extensively applied in the prevention of NASH, while the bioactive components and underlying mechanism remain unclear. The aim of this study was to investigate whether the polysaccharides of GP (GPP) have a protective effect on NASH and to explore the potential mechanism underlying these effects. C57BL/6 male mice were fed with a methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH and administered daily oral gavage of sodium carboxymethylcellulose (CMC-Na), low dose of GPP (LGPP), high dose of GPP (HGPP), and polyene phosphatidylcholine capsules (PPC), compared with the methionine-choline-sufficient (MCS) group. Our results showed that the symptoms of hepatic steatosis, hepatocyte ballooning, liver fibrosis, and oxidative stress could be partially recovered through the intervention of GPP with a dose-dependent effect. Furthermore, gut microbiome sequencing revealed that HGPP altered the composition of gut microbiota, mainly characterized by the enrichment of genera including Akkermansia, Lactobacillus, and A2. Moreover, hepatic transcriptome analysis indicated that the anti-inflammatory effect of HGPP might be associated with toll-like receptor (TLR) and nod-like receptor (NLR) signaling pathways. HGPP could inhibit the expression of TLR2 and downregulate the expression of the NLRP3 inflammasome, as well as the pro-inflammatory cytokine tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. In summary, GPP could ameliorate NASH possibly mediated via the modulation of gut microbiota and the TLR2/NLRP3 signaling pathway, indicating that GPP could be tested as a prebiotic agent in the prevention of NASH.

COVID-19-related diffuse leukoencephalopathy with microbleeds and persistent coma: a case report with good clinical outcome.

A 60-year-old patient presented with respiratory distress, after recently being tested COVID-19 positive and was mechanically ventilated for 15 days. After cessation of sedation, he remained in deep comatose state, without any reaction on pain stimuli (Glasgow Coma Score 3). MRI of the brain showed diffuse leukoencephalopathy and multiple (>50) microbleeds. Diffuse COVID-19-associated leukoencephalopathy with microhaemorrhages is associated with a poor prognosis. However, 3 months later, our patient showed a remarkable recovery and was able to walk independently. This case report shows COVID-related leukoencephalopathy and intracerebral microbleeds, even with persistent comatose state, may have a favourable clinical outcome and prolonged treatment should be considered in individual cases.