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1.
Front Genet ; 13: 913535, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092935

RESUMO

Over 50 million people around the world currently are suffering from Alzheimer's disease (AD) without any effective therapy. Neuroinflammation plays a pivotal role in AD, which leads us to probe the profile of immune cell infiltration in AD. Here, we analyzed a microarray dataset (GSE44770) containing 115 AD and 115 control samples to determine biomarkers and immune infiltration characteristics of AD by multiple bioinformatics methods. First, we identified 3,840 DEGs (1892 upregulated and 1948 downregulated) by using the limma package and 2,697 hub genes by constructing a weighted gene correlation network, and they had a total of 2,167 intersecting genes. Second, combining the LASSO logistic regression and SVM-RFE, we obtained five biomarkers (DGKG, MAP3K7IP2, NFKBIE, VIP, and PCCB), which may reveal the key pathogenetic features of AD and serve as diagnostic markers assessed by the ROC curve (AUC = 0.9716) and validation of another AD dataset (GSE33000) (AUC = 0.9388). Third, immune cell infiltration analysis revealed that compared with control samples, plasma cells, CD8 T cells, T follicular helper cells, and activated NK cells infiltrated less in AD; Monocytes, M2 macrophages, and neutrophils infiltrated more in AD. Neutrophils and activated NK cells demonstrated the most significant and negative correlation. Then, Spearman correlation analysis between the five biomarkers and immune infiltrating cells revealed that all of them were significantly associated with plasma cells. Finally, mRNA levels of VIP and PCCB were conformed in a murine AD model. In conclusion, DGKG, MAP3K7IP2, NFKBIE, VIP, and PCCB may be used as diagnostic markers of AD, and the disruption of the delicate immune balance may be a key process in the onset and development of AD.

2.
Iran J Basic Med Sci ; 25(7): 822-826, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36033945

RESUMO

Objectives: This study aimed to investigate the potential effects of wasp venom (WV) from Vespa magnifica on antithrombosis in rats with inferior vena cava (IVC) thrombosis. Materials and Methods: The thrombosis rat model was established by improving the IVC stenosis, in which rats were subjected to IVC ligation for 75 min. Rats were administered argatroban (IP) or WV (s.c.) for 4 hr after IVC thrombosis. The weight, inhibition rate, and pathological morphology of the thrombosis induced by IVC ligation and the variation in four coagulation parameters, coagulation factors, and CD61+CD62P+ were simultaneously determined in IVC rats. Results: The thrombus formed as a result of IVC ligation was stable. Compared with the control group, the weight of the thrombus was significantly reduced in the argatroban group. Thrombus weight was reduced by treatment with 0.6, 0.2, and 0.05 mg/kg WV, with inhibition rates of 52.19%, 35.32%, and 28.98%, respectively. Inflammatory cells adhered to and infiltrated the vessel wall in the IVC group more than in the sham group. However, the pathological morphology and CD61+CD62P+ of the WV treatment groups tended to be normal. Conclusion: We improved the model of IVC thrombosis to be suitable for evaluation of antithrombotic drugs. Our findings demonstrated that WV could inhibit IVC thrombosis associated with reducing coagulation factors V and CD61+CD62p expression in rats.

3.
Pharm Biol ; 60(1): 334-346, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35171059

RESUMO

CONTEXT: Acute ischaemic stroke (AIS) is a major cause of disability and death, which is a serious threat to human health and life. Wasp venom extracted from Vespa magnifica Smith (Vespidae) could treat major neurological disorders. OBJECTIVE: This study investigated the effects of wasp venom on AIS in rats. MATERIAL AND METHODS: We used a transient middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats (260-280 g, n = 8-15) with a sham operation group being treated as negative control. MCAO rats were treated with wasp venom (0.05, 0.2 and 0.6 mg/kg, i.p.) using intraperitoneal injection. After treatment 48 h, behavioural tests, cortical blood flow (CBF), TTC staining, H&E staining, Nissl staining, TUNEL assay, immunohistochemistry (IHC) and ELISA were employed to investigate neuroprotective effects of wasp venom. RESULTS: Compared with the MCAO group, wasp venom (0.6 mg/kg) improved neurological impairment, accelerated CBF recovery (205.6 ± 52.92 versus 216.7 ± 34.56), reduced infarct volume (337.1 ± 113.2 versus 140.7 ± 98.03) as well as BBB permeability as evidenced by changes in claudin-5 and AQP4. In addition, function recovery of stroke by wasp venom treatment was associated with a decrease in TNF-α, IL-1ß, IL-6 and inhibition activated microglia as well as apoptosis. Simultaneously, the wasp venom regulated the angiogenesis factors VEGF and b-FGF in the brain. CONCLUSIONS: Wasp venom exhibited a potential neuroprotective effect for AIS. In the future, we will focus on determining whether the observed actions were due to a single compound or the interaction of multiple components of the venom.


Assuntos
Isquemia Encefálica/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Venenos de Vespas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Infarto da Artéria Cerebral Média , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Venenos de Vespas/administração & dosagem , Vespas
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