Analysis of the expression levels of chemerin, ox-LDL, MMP-9, and PAPP-A in ICVD patients and their relationship with the severity of neurological impairment.

OBJECTIVE: The study aimed to analyze the relationship between expression levels of chemerin, oxidized low density lipoprotein (ox-LDL), matrix metalloproteinase 9 (MMP-9) and pregnancy associated plasma protein A (PAPP-A) in ischemic cerebrovascular disease (ICVD) patients and the relationship between the mentioned indicators and the degree of neurological impairment. METHODS: From January 2020 to February 2021, a total of 328 cases of ICVD patients were admitted to our hospital, and 240 cases of healthy people (control group) were prospectively recruited into this study. The 328 patients were divided into 2 ischemic subtypes, with 233 cases as acute cerebral infarction (ACI) and 95 cases as transient ischemic attack (TIA). Laboratory tests were compared among the groups. Spearman rank correlation was used to analyze the correlation between chemerin, ox-LDL, MMP-9, PAPP-A levels and neurological deficit. Unconditional logisitic regression was used to analyze the risk factors for neurological deficits. RESULTS: The high density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), chemerin, ox-LDL, MMP-9, and PPAP-A levels in the ACI group were significantly higher than those in the TIA group and control group (p < 0.05, respectively), while the levels of the mentioned indicators in the TIA group were significantly higher than those in control group (p < 0.05, respectively). The levels of the given indicators decreased successively in the severe, moderate, and mild neurological deficits population and control group, with statistical difference. Spearman rank correlation analysis showed that chemerin, ox-LDL, MMP-9, and PPAP-A levels were positively correlated with the degree of neurological deficit in ICVD patients. Unconditional logistic regression analysis showed that chemerin, ox-LDL, MMP-9, and PPAP-A were the independent risk factors for neurological deficit in patients with ICVD. CONCLUSION: LDL-C, FPG, chemerin, ox-LDL, MMP-9, and PPAP-A were highly expressed in ACI and neurological deficit patients. Chemerin, ox-LDL, MMP-9, and PPAP-A may be the independent risk factors for neurological deficit in patients with ICVD.

Effects of chemerin and homocysteine levels and their associations with occurrence and development of ischemic cerebrovascular disease.

BACKGROUND: The current study was conducted to explore the effects of chemerin and homocysteine (Hcy) levels and their associations with the occurrence and development of ischemic cerebrovascular disease (ICVD). METHODS: There involved a total of 187 patients with ICVD and 190 healthy people for physical examination in Cangzhou Central hospital from January 2020 to April 2021. The participants enrolled were divided into four groups based on the digital subtraction angiography: mild stenosis group (64 cases, stenosis rate 30-49 %), moderate stenosis group (72 cases, stenosis rate 50-69 %), severe stenosis group (51 cases, stenosis rate 70-99 %) and control group (190 cases, in healthy condition). The laboratory indexes of ICVD group and control group were observed and the four groups were further compared. Pearson linear correlation was applied to analyze the link between chemerin and Hcy levels and the degree of cerebral vascular stenosis in ICVD patients, and multivariate logistic regression was used to analyze the influencing factors of ICVD. RESULTS: No significant difference was found in general information including age, gender, body mass index (BMI), heart rate, systolic blood pressure, diastolic blood pressure, smoking and drinking between the two groups (P > 0.05). Moreover, there was no significant difference in fasting blood glucose (FBG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels between the two groups (P > 0.05). However, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), chemerin and Hcy in ICVD group were significantly higher than those in control group (P < 0.05). When comparing the four groups, there was no significant difference in FBG and TC levels (P > 0.05). The levels of TG, LDL-C, chemerin and Hcy in mild, moderate and severe stenosis groups were higher than those in control group, the above levels in moderate and severe stenosis group were higher than those in mild stenosis group, and severe stenosis group higher than moderate stenosis group (P < 0.05). Chemerin and Hcy levels were positively correlated with the degree of cerebral vascular stenosis in ICVD patients (r = 0.612, 0.519, P < 0.001). ICVD was regarded as the dependent variable, and the abovementioned general data as well as significant laboratory indicators, including TG, LDL-C, chemerin and Hcy, as independent variables. The results of multivariate logistic regression analysis revealed that TG, LDL-C, chemerin and Hcy were independent influencing factors of ICVD. CONCLUSIONS: Chemerin and Hcy levels exerted a close link to the occurrence and development of ICVD as independent influencing factors.

A systematic review and meta-analysis on the efficacy of statins in the treatment of atherosclerosis.

BACKGROUND: It was a meta-analysis on the efficacy of statins in the treatment of atherosclerosis. METHODS: The PubMed, Medline, Embase, Web of Sciences, and other Chinese and English databases were used to retrieve literature on randomized controlled trials (RCTs) of statins in the treatment of atherosclerosis, published from January 2000 to January 2021. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was used to conduct bias risk assessment, and Review Manager 5.3 software (RevMan) was used for meta-analysis. RESULTS: A total of 12 articles with 1,180 participants were included in the meta-analysis. In the observation group, the plaque area [mean difference (MD) =-1.21; 95% confidence interval (CI): -2.03 to -0.38; Z =2.87; P=0.004], total cholesterol (TC) level (MD =-0.72; 95% CI: -1.01 to -0.43; Z =4.83; P<0.00001), triglyceride (TG) level (MD =-0.43; 95% CI: -0.76 to -0.09; Z =2.51; P=0.01), and the low-density lipoprotein (LDL-C) level (MD =-0.79; 95% CI: -1.41 to -0.18; Z =2.54; P=0.01) were lower, while the clinical effective rate (MD =3.64; 95% CI: 1.39 to 9.53; Z =2.64; P=0.008) was higher, and the difference was notable. No notable difference was noted in intra-media thickness (IMT) (MD =-0.41; 95% CI: -0.88 to -0.06; Z =1.7; P=0.09), hypersensitive C-reactive protein (hs-CRP) level (MD =-1.61; 95% CI: -3.59 to 0.37; Z =1.7; P=0.09), and high-density lipoprotein (HDL-C) level (MD =0.14; 95% CI: -0.02 to 0.30; Z =2.54; P=0.09) between the 2 groups. DISCUSSION: The use of statins in the treatment of atherosclerosis can reduce the levels of TC, TG, and LDL-C, mitigate clinical symptoms, and reduce blood lipids with good efficacy.

Oleanolic acid protects against cognitive decline and neuroinflammation-mediated neurotoxicity by blocking secretory phospholipase A2 IIA-activated calcium signals.

Neuroinflammation causes neurotoxic injury and underlies the pathogenesis of neurodegenerative disorders including Alzheimer's disease (AD). Astrocytes are the predominant immunoregulatory cells in AD. Oleanolic acid (OA) is a promising anti-inflammatory therapeutic agent that can ameliorate cerebral damage in ischemic environments, but its role in AD remains poorly elucidated. Here, preconditioning with OA inhibited the transcription and secretion of inflammatory cytokines IL-6, TNF-α, and IL-1ß in amyloid-beta peptide (Aß)-activated astrocytes. Moreover, OA ameliorated primary neuron death triggered by incubation in conditioned medium from Aß-treated astrocytes. Furthermore, OA also suppressed Aß-induced expression and production of group IIA secretory phospholipase A2 (sPLA2-IIA) in astrocytes. Supernatants supplemented with exogenous sPLA2-IIA reversed the protective role of OA against astrocyte activation-mediated neurotoxicity by suppressing cell viability and increasing LDH release, apoptosis, the contents of neurotoxic mediator arachidonic acid, and prostaglandin D2. Simultaneously, treatment with sPLA2 inhibitor aristolochic acid also counteracted neurotoxicity induced by Aß-activated astrocytes through increasing cell viability, inhibiting cell apoptosis, and reducing the releases of arachidonic acid and prostaglandin D2. Additionally, OA restrained Ca2+ influx in neurons after incubation with supernatants from Aß-activated astrocytes, which was abrogated by adding sPLA2-IIA. Activating Ca2+ signaling with BayK, an L-type Ca2 + channel agonist, reversed the beneficial role of OA against neurotoxicity induced by astrocyte activation-mediated inflammatory response. OA also ameliorated cognitive deficits in an adolescent rat model of Aß-evoked AD. These findings confirm that OA abrogates neuroinflammation and subsequent neurotoxicity induced by conditioned media from Aß-activated astrocytes in sPLA2-IIA mediated-calcium signals. Therefore, OA may protect neurons from injury caused by neighboring astrocyte activation in AD, indicating a promising therapeutic strategy against AD.

Serum levels of SOD and risk of autism spectrum disorder: A case-control study.

BACKGROUND: Autism is a severe developmental disorder with poorly understood etiology. This study examined the clinical significance of serum superoxide dismutase (SOD) level, a marker of oxidative stress, in children with autism spectrum disorder (ASD) and typically-developing children between the ages of 2 and 6 years. METHODS: Ninety-six children diagnosed with ASD and 96 sex and age matched typically-developing children were assessed for serum levels of SOD at admission. S0D were assayed by colorimetry, and severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS) Score. The influence of serum SOD levels on ASD was performed by conditional logistic regression analysis, which allows adjustment for confounding factors. RESULTS: The median serum SOD levels were significantly (P<0.001) lower in children with ASD as compared to typically-developing children [146 (IQR: 133-165) U/ml and 180 (168-199) U/ml, respectively]. Levels of SOD increased with decreasing severity of ASD as defined by the CARS score (r=-0.432, P<0.0001). After adjusting for all other possible covariates, SOD remained can be seen as an independent indictor of ASD with an adjusted odds ratio (OR) of 0.955 (95% confidence interval [CI], 0.942-0.969; P<0.001). Based on the receiver operating characteristic (ROC) curve, the optimal cutoff value of serum level of SOD as an indicator for auxiliary diagnosis of ASD was projected to be 160U/ml, which yielded a sensitivity of 84.7% and a specificity of 71.4%, with the area under the curve at 0.811 (95%CI, 0.747-0.874). CONCLUSIONS: Our data suggests that the decreased serum SOD levels could be implicated in the pathophysiology and progression of autism in Chinese children and can be used as an independent risk indicator of ASD.