Preoperative prognostic nutrition index can independently predict the 6-month prognosis of elderly patients undergoing neurosurgical clipping for aneurysmal subarachnoid hemorrhage.

The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) is increasing annually. The prognostic nutritional index (PNI) is used as a novel and valuable prognostic marker for various neoplastic diseases and other critical illnesses. This study aimed to identify the short-term prognostic value of preoperative PNI in elderly patients who underwent neurosurgical clipping for aSAH. This retrospective study included elderly patients with aSAH who underwent neurosurgical clipping from January 2018 to December 2020. Clinical variables and 6-month outcomes were collected and compared. Epidemiological data and effect factors of prognosis were evaluated. Multivariate logistic regression and receiver operating characteristics (ROC) curve analyses were used to evaluate the predictive value of preoperative PNI. Multiple logistic regression was performed to establish a nomogram. A total of 124 elderly patients were enrolled. Multivariate logistic regression analysis showed that preoperative PNI (odds ratio (OR), 0.779; 95% confidence interval (CI), 0.689-0.881; P < 0.001), Hunt-Hess grade (OR, 3.291; 95%CI, 1.816-5.966; P < 0.001), and hydrocephalus (OR, 9.423; 95%CI, 2.696-32.935; P < 0.001) were significant predictors. The area under the ROC curve of PNI was 0.829 (95% CI, 0.755-0.903; P < 0.001) with a sensitivity and specificity of 68.4% and 83.3%, respectively, and the cutoff value was 46.36. Patients with preoperative PNI of < 46.36 had a significantly unfavorable 6-months prognosis (F = 40.768, P < 0.001). Preoperative PNI is independently correlated with the 6-month prognosis in elderly patients who undergo neurosurgical clipping for aSAH.

A rapid method for extracting microplastics from oily food samples.

The increasing evidence of microplastic (MP) contamination influence on aquatic organisms has been extensively reported globally. However, the discussions of extracting MPs from oily food samples are limited, highlighting the pressing need for effective and standardized analytical methods to extract MPs from oily food. Previous methods, such as using acid, alkali or oxidizing solutions as digestion reagents, usually take a long time to digest oily food, increasing the possibility of procedural contamination of MPs in food over time. The objective of this study was to develop a rapid, efficient, economical and simple analytical method to extract MPs from oily food samples. This innovative protocol combines the use of 4 : 1 HNO3 : H2O2 as a digestion reagent to accelerate the digestion within 1 h at 50 °C and hexane as a washing solution to remove the oil adsorbed on the surface of MPs and membranes. Four common types of MPs, namely, polyethylene terephthalate, polyethylene, polystyrene and polypropylene of different sizes were added to oily flours to demonstrate this method. The mean recovery of MPs was 95% ± 2% (range: 93-98%), and no significant changes in color, particle size, surface area and spectrum features were found for all recovered polymers except for PS with minor changes in color and surface. The method was confirmed to be effective on rice, noodles, bean products and various meat samples. All in all, the present method can facilitate the observation and identification of characteristics of MPs, providing an innovative combination method for quantitative and qualitative analyses of MPs in oily food samples.

Discovery of novel MIF inhibitors that attenuate microglial inflammatory activation by structures-based virtual screening and in vitro bioassays.

Macrophage migration inhibitory factor (MIF) is a pluripotent pro-inflammatory cytokine and is related to acute and chronic inflammatory responses, immune disorders, tumors, and other diseases. In this study, an integrated virtual screening strategy and bioassays were used to search for potent MIF inhibitors. Twelve compounds with better bioactivity than the prototypical MIF-inhibitor ISO-1 (IC50 = 14.41 µM) were identified by an in vitro enzymatic activity assay. Structural analysis revealed that these inhibitors have novel structural scaffolds. Compound 11 was then chosen for further characterization in vitro, and it exhibited marked anti-inflammatory efficacy in LPS-activated BV-2 microglial cells by suppressing the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs). Our findings suggest that MIF may be involved in the regulation of microglial inflammatory activation and that small-molecule MIF inhibitors may serve as promising therapeutic agents for neuroinflammatory diseases.

Quinoline-based Compounds with Potential Activity against Drugresistant Cancers.

Drug resistance is the major cause of the failure of cancer chemotherapy, so one of the most important features in developing effective cancer therapeutic strategies is to overcome drug resistance. Quinoline moiety has become one of the most privileged structural motifs in anticancer agent discovery since its derivatives possess potent activity against various cancers including drug-resistant cancers. Several quinoline-based compounds which are represented by Anlotinib, Bosutinib, Lenvatinib, and Neratinib have already been applied in clinical practice to fight against cancers, so quinoline-based compounds are potential anticancer agents. The present short review article provides an overview of the recent advances of quinoline-based compounds with potential activity against drug-resistant cancers. The structure-activity relationship and mechanisms of action are also discussed.

Identification of 2 Potential Core Genes for Influence of Gut Probiotics on Formation of Intracranial Aneurysms by Bioinformatics Analysis.

BACKGROUND Rupture of intracranial aneurysms (IA) is associated with high rates of mortality around the world. Use of intestinal probiotics can regulate the pathophysiology of aneurysms, but the details of the mechanism involved have been unclear. MATERIAL AND METHODS The GEO2R analysis website was used to detect the DEGs between IAs, AAAs, samples after supplementation with probiotics, and normal samples. The online tool DAVID provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs was analyzed based on the STRING database, followed by analysis using Cytoscape software. RESULTS We found 170 intersecting DEGs (contained in GSE75240 and more than 2 of the 4 aneurysms datasets), 5 intersecting DEGs (contained in all datasets) and 1 intersecting DEG (contained in GSE75240 and all IAs datasets). GO analysis results suggested that the DEGs primarily participate in signal transduction, cell adhesion, immune response, response to drug, extracellular matrix organization, cell-cell signaling, and inflammatory response in the BP terms, and the KEGG pathways are mainly enriched in focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, amoebiasis, chemokine signaling pathway, proteoglycans, and PI3K-Akt signaling pathway in cancer pathways. Through PPI network analysis, we confirmed 2 candidates for further study: CAV1 and MYH11. These downregulated DEGs are associated with the formation of aneurysms, and the change of these DEGs is the opposite in probiotics-treated animals. CONCLUSIONS Our study suggests that MYH11 and CAV1 are potential target genes for prevention of aneurysms. Further experiments are needed to verify these findings.

l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury.

l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that l-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that l-lysine may play a neuroprotective role in ICH injury. Indeed, we show that l-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. l-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of l-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of l-lysine in ICH injury. Together, our results suggest that l-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.

Effect of combined VEGF165/ SDF-1 gene therapy on vascular remodeling and blood perfusion in cerebral ischemia.

OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction. METHODS An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad- VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF165-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI. RESULTS The Ad- VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion. CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral infarction.

Effect of craniotomy on oxidative stress and its effect on plasma L-carnitine levels.

OBJECTIVE: to investigate the impact of craniotomy on oxidative stress and its effect on levels of plasma L-carnitine (LC). METHODS: plasma levels of reactive oxygen species, superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), catalase (CAT), total antioxidative capacity (T-AOC), and thiobarbituric acid reactive substances (TBARS) were measured in 34 patients (26 males and 8 females, mean age 47.7 ± 6.7 years) before and after craniotomy. Plasma levels of LC, acetyl-L-carnitine (ALC), and propionyl-L-carnitine (PLC) were also measured before and after the craniotomy. RESULTS: the plasma concentrations of SOD, GSH-Px, CAT, and T-AOC within the first 4 h after craniotomy were lower than their baseline values (P < 0.05). There were no statistically significant differences in the mean plasma levels of SOD, GSH-Px, CAT, or T-AOC between the baseline and 24 h post-operative values. The level of TBARS at 4 h after the craniotomy was lower than the pre-operative level (P < 0.05), but the 24 h post-operative value was similar to the baseline concentration (P > 0.05). Plasma levels of LC, ALC, and PLC were lower after the craniotomy (P < 0.05), but these levels returned to the baseline levels 24 h after the operation. CONCLUSIONS: craniotomy and the associated procedures for surgery/anesthesia temporarily reduce antioxidant activity and plasma levels of L-carnitine.

Urinary excretion of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and their antioxidant activities after single dose administration of L-carnitine in healthy subjects

The urine excretion of L-carnitine (LC), acetyl-L-carnitine (ALC) and propionyl-Lcarnitine (PLC) and their relations with the antioxidant activities are presently unknown. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Urine concentrations of LC, ALC and PLC were detected by HPLC. Superoxide dismutase (SOD), total antioxidative capacity (T-AOC), malondialdehyde (MDA) and nitrogen monoxidum (NO) activities were measured by spectrophotometric methods. The 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excretion of LC was 53.13±31.36 µmol, 166.93±76.87 µmol, 219.92±76.30 µmol, 100.48±23.89 µmol, 72.07±25.77 µmol, respectively. The excretion of ALC was 29.70±14.43 µmol, 80.59±32.70 µmol, 109.85±49.21 µmol, 58.65±18.55 µmol, and 80.43±35.44 µmol, respectively. The urine concentration of PLC was 6.63±4.50 µmol, 15.33±12.59 µmol, 15.46±6.26 µmol, 13.41±11.66 µmol and 9.67±7.92 µmol, respectively. The accumulated excretion rate of LC was 6.1% within 24h after its administration. There was also an increase in urine concentrations of SOD and T-AOC, and a decrease in NO and MDA. A positive correlation was found between urine concentrations of LC and SOD (r = 0.8277) or T-AOC (r = 0.9547), and a negative correlation was found between urine LC excretions and NO (r = -0.8575) or MDA (r = 0.7085). In conclusion, a single oral LC administration let to a gradual increase in urine L-carnitine excretion which was associated with an increase in urine antioxidant enzymes and the total antioxidant capacities. These data may be useful in designing therapeutic regimens of LC or its analogues in the future.

A excreção urinária de L-carnitina (LC), acetil-L-carnitina (ALC) e propionil-L-carnitine (PLC) e as suas relações com as atividades antioxidantes são presentemente desconhecidos. Líquido de L-carnitina (2,0 g) foi administrada por via oral como uma dose única em 12 indivíduos saudáveis. As concentrações urinárias de LC, PLC e ALC foram detectados por HPLC. Atividades superóxido dismutase (SOD), a capacidade antioxidante total (T-AOC), malondialdeído (MDA) e óxido nítrico (NO) foram medidas por métodos espectrofotométricos. O 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excreção de LC foi 53,13±31.36 µmol, 166,93±76.87 µmol, 219,92±76.30 µmol, 100,48±23.89 µmol, 72,07±25.77 µmol, respectivamente. A excreηão de ALC foi 29,70±14.43 µmol, 80,59±32.70 µmol, 109,85±49.21 µmol, 58,65±18.55 µmol, e 80,43±35.44 µmol, respectivamente. A concentraηão de urina de PLC foi 6,63±4.50 µmol, 15,33±12.59 µmol, 15,46±6.26 µmol, 13,41±11.66 µmol e 9,67±7.92 µmol, respectivamente. A taxa de excreηão acumulada de LC foi de 6,1% 24 horas após sua administração. Houve também um aumento nas concentrações de urina de SOD e T-COA e diminuição de NO e de MDA. Correlação positiva foi encontrada entre as concentrações de urina de LC e SOD (r = 0,8277) ou T-AOC (r = 0,9547) e correlação negativa entre a excreção de LC e NO (r = -0,8575) ou MDA (r = 0,7085). Em conclusão, a administração oral única de LC leva ao aumento gradual na excreção urinária de L-carnitina, que foi associada com o aumento das enzimas antioxidantes na urina e as capacidades antioxidantes totais. Estes dados podem ser úteis no futuro para o planejamento de esquemas terapêuticos de LC ou os seus análogos, no futuro.

Antihyperglycemic effects of baicalin on streptozotocin - nicotinamide induced diabetic rats.

The aim of the study was to investigate the effects of baicalin on blood glucose, insulin and cytokine levels. Rat diabetes was induced by intraperitoneal (i.p.) injection of nicotinamide and streptozotocin. Diabetic rats were dosed with i.p. baicalin or oral metformin daily for 8 days. Blood glucose, insulin and hepatic glycogen were determined using conventional methods. The activity of hepatic hexokinase was determined using a coupled assay with glucose-6-phosphate dehydrogenase. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and adiponectin were measured by enzyme-linked immunosorbent assay. Administration of baicalin at 50 or 100 mg/kg significantly decreased plasma glucose levels in a dose dependent manner. The serum insulin level was not increased by baicalin treatment. Administration of baicalin at a high dose (100 mg/kg) resulted in a significant increase of liver glycogen content and a reduction of serum TNF-α. The activity of hepatic hexokinase was significantly increased after dosing baicalin at 25, 50 or 10 mg/kg. Administration of baicalin (50 or 10 mg/kg) or metformin (10 mg/kg) significantly alleviated the morphological injury to the pancreas caused by STZ. The possible mechanisms contributing to the hypoglycemic effect include increasing the hepatic glycogen content and glycolysis, and reducing the serum levels of TNF-α.