The hepatotoxicity of some Chinese herbs has been a cause for concern in recent years. However, some herbs, such as rhubarb, have been documented as having both therapeutic and toxic effects on the liver, leading to the complex problem of distinguishing the benefits from the risks of using this herb. To comparatively analyze the dose-response relationship between rhubarb and hepatic health, we administrated total rhubarb extract(RE) to normal and carbon tetrachloride(CCl₄)-treated rats for 12 weeks at 4 dosage levels(2.00, 5.40, 14.69 and 40.00 g·kg⁻¹, measured as the quantity of crude material), followed by biochemical and histopathological tests of the rats' livers. A composite pattern was extracted by factor analysis, using all the biochemical indices as variables, into a visual representation of two mathematically obtained factors, which could be interpreted as the fibrosis factor and the cellular injury factor, according to the values of the variable loadings. The curative effect of administering the two lowest dosages of RE to CCl₄-treated rats was mainly expressed as a decrease in the extent of cellular injury. The hepatoprotective mechanism of RE might be related to its antioxidant effect, the antagonism of the free radical damage to hepatocytes caused by CCl₄. By contrast, the RE-induced liver damage was mainly expressed as a significant increase in the amount of fibrosis in both normal rats at all dosage levels and CCl₄-treated rats at the two highest dosage levels. Therefore, the hepatotoxic potential of RE could be attributable to the liver cell fibrosis induced by high doses of the herb. This study illustrates the bidirectional potential of rhubarb and demonstrates the feasibility of using factor analysis to study the dose-response relationships between herbal medicines and hepatotoxicity or the healing effects of these herbs by extracting the underlying interrelationships among a number of functional bio-indices in a holistic manner.

Erythropoietin (EPO) promotes oligodendrogenesis and attenuates white matter injury in neonatal rats. However, it is unknown whether this effect extends to adult mice and whether EPO regulate microglia polarization after ischemic stroke. Male adult C57BL/6 mice (25-30g) were subjected to 45 min of middle cerebral artery occlusion (MCAO). EPO (5000 IU/kg) or saline was injected intraperitoneally every other day after reperfusion. Neurological function was evaluated using the rotarod test at 1, 3, 7 and 14 days after MCAO. Brain tissue loss volume was determined by hematoxylin-eosin staining. Immunofluorescence staining and Western blot were also used to assess the severity of white matter injury and phenotypic changes in microglia/macrophages. Bromodeoxyuridine (BrdU) was injected intraperitoneally daily for 1 week to analyze the number of newly proliferating glia cells (oligodendrocytes, microglia, and astrocytes). We found that EPO significantly reduced Brain tissue loss volume, ameliorated white matter injury, and improved neurobehavioral outcomes at 14 days after MCAO (P<0.05). In addition, EPO also increased the number of newly generated oligodendrocytes and attenuated the rapid hypertrophy and hyperplasia of microglia and astrocytes after ischemic stroke (P<0.05). Furthermore, EPO reduced M1 microglia and increased M2 microglia (P<0.05). Taken together, our results suggest that EPO treatment improves white matter integrity after cerebral ischemia, which could be attributed to EPO attenuating gliosis and facilitating the microglial polarization toward the beneficial M2 phenotype to promote oligodendrogenesis.

Aims: Inflammatory processes induced by leukocytes are crucially involved in the pathophysiology of acute ischemic stroke. This study aimed to elucidate the inflammatory mechanism of long non‐coding RNA (lncRNA) H19‐mediated regulation of C1q and tumor necrosis factor 6 (C1QTNF6) by sponging miR‐29b in leukocytes during ischemic stroke.Methods: H19 and miR‐29b expression in leukocytes of patients with ischemic stroke and rats with middle cerebral artery occlusion were measured by real‐time polymerase chain reaction. H19 siRNA and miR‐29b antagomir were used to knock down H19 and miR‐29b, respectively. We performed in vivo and in vitro experiments to determine the impact of H19 and miR‐29b on C1QTNF6 expression in leukocytes after ischemic injury.Results: H19 and C1QTNF6 upregulation, as well as miR‐29b downregulation, was detected in leukocytes of patients with stroke. Moreover, miR‐29b could bind C1QTNF6 mRNA and repress its expression, while H19 could sponge miR‐29b to maintain C1QTNF6 expression. C1QTNF6 overexpression promoted the release of IL‐1β and TNF‐α in leukocytes, further exacerbated blood‐brain barrier disruption, and aggravated the cerebral ischemic injury.Conclusions: Our findings confirm that H19 promotes leukocyte inflammation by targeting the miR‐29b/C1QTNF6 axis in cerebral ischemic injury.

Interleukin-2 (IL-2), the first cloned cytokine, is a multifunctional molecule with diverse cellular origins. As a pivotal T-cell growth factor, IL-2 is crucial for T-cell proliferation and the generation of effector and memory cells. Besides, IL-2 and its receptor (IL-2R) are expressed in various cell types within the brain and have been implicated in the pathogenesis of several neurological disorders. In conditions characterized by primary or secondary inflammatory processes, such as multiple sclerosis, Alzheimer's disease, ischemic stroke, and encephalitis, IL-2/IL-2R expression exhibits region- and subtype-specific and variations associated with disease stages in plasma, cerebrospinal fluid (CSF), and brain tissues. These variations highlight the potential of IL-2/IL-2R as promising diagnostic and prognostic biomarkers, as well as therapeutic targets. This review provides a comprehensive summary of the roles, expression patterns, and regulatory mechanisms of IL-2/IL-2R in immune-mediated disorders of the central nervous system (CNS), with particular emphasis on the impact of genetic polymorphisms in IL-2 and IL-2R subunits on disease susceptibility and progression. In addition, the research advances in IL-2/IL-2R-targeted therapies are also discussed, offering novel insights into the immunotherapeutic strategies for CNS diseases.

Several clinical parameters and biomarkers have been proposed as prognostic markers for stroke. However, it has not been clarified whether the risk factors affecting the prognosis of patients with recurrent and first-ever stroke are similar. In this study, we aimed to explore the relationship between soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) levels and the prediction of the functional outcome in patients with recurrent and first-ever stroke. A total of 266 patients with recurrent and first-ever stroke, who underwent follow-up for 3 months, were included in this study. Plasma samples were collected within 24 h after onset. The results showed that biomarkers for the prognosis of patients with recurrent stroke were different from that of those with first-ever stroke. sLOX-1 levels were correlated with modified Rankin Scale scores of patients with recurrent stroke alone ( , ). sLOX-1 levels were also associated with an increased risk of unfavorable outcomes in patients with recurrent stroke with an adjusted odds ratio of 1.489 (95% confidence interval, 1.204–1.842, ). Combining the risk factors showed greater accuracy for prognosis, yielding a sensitivity of 93.2% and a specificity of 75%, with an area under the curve of 0.916, evaluated by the receiver operating characteristic curve. These findings suggest that the diagnosis and prognosis are different between patients with recurrent stroke and those with first-ever stroke, and sLOX-1 level is an independent prognostic marker in patients with recurrent stroke.

Background: microRNA-494 (miRNA-494) plays a key role in neuroinflammation following cerebral ischemia. We aimed to assess miRNA-494 levels as a biomarker for predicting acute ischemic stroke (AIS) severity and outcomes. Methods: miRNA-494 levels in peripheral lymphocytes were measured using reverse transcription-quantitative polymerase chain reaction. Least Absolute Shrinkage and Selection Operator (LASSO) regression was employed to identify variables for multivariate logistic regression analysis. Univariate and multivariate logistic regression were conducted to assess the association between miRNA-494 levels and both AIS outcomes and stroke severity on admission. The primary outcome was defined as an excellent prognosis (modified Rankin Scale score of 0 or 1). The secondary outcome was milder stroke severity at admission (National Institutes of Health Stroke Scale score <15). Results: High miRNA-494 expression in patients aged <65 years predicted excellent AIS outcomes (odds ratio (OR) = 2.800 [1.120–7.002], p = 0.028, n = 105). In these patients, miRNA-494 levels predicted excellent outcomes for those who did not receive recanalization therapy (continuous: OR = 8.938 [2.123–62.910], p = 0.010; categorical: OR = 5.200 [1.480–20.773], p = 0.013). Elevated miRNA-494 levels were also linked to milder stroke severity (continuous: OR = 2.586 [1.024–6.533], p = 0.044; categorical variables: OR = 3.514 [1.501–8.230], p = 0.004, n = 205). Conclusions: Increased miRNA-494 expression in lymphocytes predicts excellent outcomes in patients aged <65 years with AIS. Higher miRNA-494 levels are associated with milder stroke on admission.