Diagnostic value of plasma D-dimer and serum lipoprotein phospholipase A2 in patients with cerebral small vessel disease and their association with severity of the disease.

OBJECTIVE: To determine the diagnostic value of plasma D-dimer (DD) and serum lipoprotein phospholipase A2 (Lp-PLA2) in patients with cerebral small vessel disease (CSVD) and their association with severity of the disease. METHODS: In this retrospective analysis, 84 patients with CSVD treated in Shangqiu First People's Hospital from February 2020 to November 2021 were included in the study group, and 75 healthy individuals were assigned into the control group. The DD and Lp-PLA2 levels in the two groups were compared, and the diagnostic value of the two in CSVD was evaluated via receiver operating characteristic (ROC) curves. Patients were assigned to a mild group or a severe group based on Fazekas scale scores. Then, the two groups were compared in terms of the DD and Lp-PLA2 levels, and the association of the two with the severity of CSVD was determined through ROC curves. With the Montreal cognitive assessment (MoCA) scale, the patients were assigned to a cognitive impairment group or a non-cognitive impairment group. Then the two groups were compared in terms of the DD and Lp-PLA2 levels, and the association of the two with the cognitive function of CSVD patients was also determined by ROC curves. RESULTS: The research group showed higher DD and Lp-PLA2 levels than the control group; the severe group showed higher DD and Lp-PLA2 levels than the mild group; the cognitive impairment group showed higher DD and Lp-PLA2 levels than the non-cognitive impairment group (all P < 0.001). The areas under the curves (AUCs) of DD and Lp-PLA2 in CSVD diagnosis were 0.902 and 0.907, respectively; the AUCs of DD and Lp-PLA2 in CSVD severity determination were 0.747 and 0.704, respectively; the AUCs of DD and Lp-PLA2 in cognitive impairment diagnosis were 0.736 and 0.725, respectively. CONCLUSION: Plasma DD and Lp-PLA2 possess good diagnostic value in patients with CSVD, and also has certain clinical value in diagnosing patients' severity and cognitive impairment.

Maf1 mitigates sevoflurane-induced microglial inflammatory damage and attenuates microglia-mediated neurotoxicity in HT-22 cells by activating the AMPK/Nrf2 signaling.

BACKGROUND: Maf1 has been found to play protective function against neuroinflammation and neuroapoptosis. This study seeks to explore whether and how Maf1 is involved in sevoflurane (Sev)-induced neuroinflammation and microglia-mediated neurotoxicity. METHODS: qRT-PCR and western blot were used to detect the gene expression. ELISA was used to detect inflammatory factors. Cell viability was evaluated by using the Cell Counting Kit-8 kit. Neuroapoptosis was assessed with trhe Caspase-3 Assay Kit and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique. RESULTS: Maf1 expression was downregulated in Sev-stimulated BV2 microglial cells. Maf1 overexpression down-regulates the expression of pro-inflammatory M1-type markers (CD86, iNOS, IFN-γ) and up-regulates the expression of anti-inflammatory M2-type markers (CD206, TGF-ß, Arg-1), and Maf1 reduces the Sev-induced inflammatory response in BV2 cells. After Maf1 overexpression, the relative expression of p-AMPK/AMPK and nucleus-Nrf2 increased significantly in BV2 cells treated with Sev. Inhibition of AMPK/Nrf2 pathway by compound C reverses anti-inflammatory effect of Maf1 in Sev-stimulated BV2 cells. Compound C reverses the effect of Maf1 on microglia-mediated neurotoxicity in HT-22 hippocampal neuronal cells. CONCLUSIONS: Maf1 mitigates Sev-induced microglial inflammatory damage and attenuates microglia-mediated neurotoxicity by activating the AMPK/Nrf2 signaling.

Effectiveness of interleukin-17A inhibitors in patients with ankylosing spondylitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Ankylosing spondylitis is a chronic immune-mediated inflammatory arthritis. Interleukin-17A (IL-17A) inhibitors is recognized as a novel therapeutic target for ankylosing spondylitis. However, there is still a lack of high-quality research evidence regarding the issues. Therefore, we performed a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of IL-17A inhibitors in patients with ankylosing spondylitis. METHODS: This protocol will be conducted under the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P) guidelines. Furthermore, the study has been registered on PROSPERO (CRD42022375885). The following electronic databases will be searched regardless of language and publication status: Pubmed, MEDLINE, EMBASE, China Biomedical Database, China National Knowledge Infrastructure, VIP Database, and Wanfang Database. Cochrane "bias risk" tool is used to assess the bias risk of the quality of the included literature. Data synthesis and statistical analysis will be performed using the RevMan 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) software. RESULTS: A synthesis of current evidence of IL-17A inhibitors for ankylosing spondylitis will be shown in this protocol. CONCLUSION: This review can provide convincing evidence to help clinicians make decisions when dealing with ankylosing spondylitis.

Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway.

Isoquercetin (Iso) has been found to have neuroprotective effects against cerebral ischemic stroke. However, the exact molecular mechanism underlying its neuroprotective ability remains unclear. In this study, we aimed to evaluate the neuroprotective effects of Iso in primary culture of rat hippocampal neurons exposed to oxygen and glucose deprivation and reperfusion (OGD/R) injury and in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) injury. We found that rats treated with Iso exhibited a lower degree of infarct volume, and brain water content than the vehicle-treated rats. Treatment with Iso also improved the neurological deficits in MCAO/R rats as shown by the decreased modified neurological severity score. Iso treatment decreased the reactive oxygen species (ROS) and malondialdehyde (MDA) production, and increased the activity of superoxide dismutase (SOD) and catalase (CAT) in brains of MCAO/R rats and primary culture of rat hippocampal neurons exposed to OGD/R. Iso treatment prevents I/R-induced neuronal apoptosis in vivo and in vitro as indicated by increased cell viability and decreased number of TUNEL-positive cells, accompanying with downregulation of cleaved caspase-3 protein and upregulation of Bcl-2 protein. Moreover, Nrf2 knockdown weakened the anti-apoptotic and anti-oxidant activities of Iso in primary culture of rat hippocampal neurons exposed to OGD/R. Interestingly, we found that Iso could induce Nrf2 translocation from cytoplasm to nucleus in primary culture of rat hippocampal neurons exposed to OGD/R. Iso activated the NOX4/ROS/NF-κB signaling pathway in in vivo and in vitro cerebral I/R injury models. Nrf2 knockdown blocked the inhibitory effect of Iso on protein expression of NOX4, p-IκBα and p-p65 in primary culture of rat hippocampal neurons exposed to OGD/R. All the data suggested that Iso protected against oxidative stress and neuronal apoptosis in in vivo and in vitro cerebral I/R injury models via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB signaling pathway. Our findings suggested that Iso could be a potential agent for I/R brain injury.

Circulating circular RNA hsa_circ_0001785 acts as a diagnostic biomarker for breast cancer detection.

BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) and characterized by covalently closed loop without 5' and 3' end. Recently, the diagnostic value of circRNAs has received more and more attention. However, the in-depth study about circRNAs diagnosis in breast cancer is still rarely reported. In present study, we try to investigate the circRNAs expression profiles in breast cancer peripheral blood and discover valuable diagnostic biomarkers. METHODS: The expression profiles of circRNAs in plasma specimens were screened from five breast cancer and paired healthy volunteer s. The expression levels of selected candidate circRNAs were detected by RT-PCR. The diagnostic value was performed using receiver operating characteristic (ROC) curve. RESULTS: CircRNAs microarray assay showed that 41 circRNAs were aberrantly expressed with 2 fold change, including 19 up-regulated and 22 down-regulated circRNAs. Among these circRNAs, 3 candidate circRNAs were validated to be significantly dysregulated using RT-PCR, including hsa_circ_0001785, hsa_circ_0108942 and hsa_circ_0068033. In lager study cohort (n=20), ROC curve showed that hsa_circ_0001785 had better diagnostic value (AUC=0.771) than others. Moreover, in further extensive study cohort (n=57), we found that hsa_circ_0001785 plasma had better diagnostic accuracy (AUC=0.784) than CEA (AUC=0.562) and CA15-3 (AUC=0.629). Besides, hsa_circ_0001785 plasma level was closely related to histological grade (P=0.013), TNM stage (P=0.008) and distant metastasis (P=0.016). Furthermore, hsa_circ_0001785 plasma level in postoperative patients (0.283±0.043) was significantly lower than that of preoperative patients (0.109±0.037, P<0.01). CONCLUSION: Our study reveals the aberrant circRNAs expression profiles in breast cancer peripheral blood, and identifies the potential diagnostic value of plasma hsa_circ_0001785, providing a stable biomarkers for the diagnosis and progress of breast cancer.

Characteristics of a water-forming NADH oxidase from Methanobrevibacter smithii, an archaeon in the human gut.

NADH oxidases (NOXs) catalysing the oxidation of NADH to yield NAD+ and H2O, H2O2, or both play an important role in protecting organisms from oxidative stress and maintaining the balance of NAD+/NADH. A gene encoding NOX was identified from Methanobrevibacter smithii (NOX-ms), the predominant archaeon in the human gut ecosystem. Subsequent analyses showed that it is an FAD-containing protein with a subunit molecular mass of 48 kDa. NOX-ms was purified to homogeneity after expression in Escherichia coli NOX-ms catalysed the oxidization of NADH and converted O2 to H2O with an optimal pH of 7.5 and a temperature optimum of approximately 37°C. The Vmax and Km values were 42.6-44.1 unit/mg and 47.8-54.6 µM for NADH. The apparent Vmax and Km for oxygen were 189.5-196.1 unit/mg and 14.6-16.8 µM. The mutation analysis suggests that Cys42 in NOX-ms plays a key role in the four-electron reduction of O2 to H2O. Quantitative reverse transcription-PCR (RT-qPCR) revealed that transcription of NOX-ms was also up-regulated after exposing the cells to oxidative stress and glucose. Finally, the potential of NOX-ms as a target to control colonization of M. smithii and its possible applications are discussed.