Diabetic peripheral neuropathy results in diabetic neuropathic pain (DNP). Satellite glial cells (SGCs) enwrap the neuronal soma in the dorsal root ganglia (DRG). The purinergic 2 (P2) Y12 receptor is expressed on SGCs in the DRG. SGC activation plays an important role in the pathogenesis of DNP. Curcumin has anti-inflammatory and antioxidant properties. Because curcumin has poor metabolic stability in vivo and low bioavailability, nanoparticle-encapsulated curcumin was used to improve its targeting and bioavailability. In the present study, our aim was to investigate the effects of nanoparticle-encapsulated curcumin on DNP mediated by the P2Y12 receptor on SGCs in the rat DRG. Diabetic peripheral neuropathy increased the expression levels of the P2Y12 receptor on SGCs in the DRG and enhanced mechanical and thermal hyperalgesia in rats with diabetes mellitus (DM). Up-regulation of the P2Y12 receptor in SGCs in the DRG increased the production of pro-inflammatory cytokines. Up-regulation of interleukin-1β (IL-1β) and connexin43 (Cx43) resulted in mechanical and thermal hyperalgesia in rats with DM. The nanoparticle-encapsulated curcumin decreased up-regulated IL-1β and Cx43 expression and reduced levels of phosphorylated-Akt (p-Akt) in the DRG of rats with DM. The up-regulation of P2Y12 on SGCs and the up-regulation of the IL-1β and Cx43 in the DRG indicated the activation of SGCs in the DRG. The nano-curcumin treatment inhibited the activation of SGCs accompanied by its anti-inflammatory effect to decrease the up-regulated CGRP expression in the DRG neurons. Therefore, the nanoparticle-encapsulated curcumin treatment decreased the up-regulation of the P2Y12 receptor on SGCs in the DRG and decreased mechanical and thermal hyperalgesia in rats with DM.

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Sepsis-induced myocardial dysfunction (SIMD) is ubiquitous in septic shock patients and is associated with high morbidity and mortality rates. Heat shock protein 22 (Hsp22), which belongs to the small HSP family of proteins, is involved in several biological functions. However, the function of Hsp22 in lipopolysaccharide (LPS)-induced myocardial injury is not yet established. This study was aimed at investigating the underlying mechanistic aspects of Hsp22 in myocardial injury induced by LPS. In this study, following the random assignment of male C57BL/6 mice into control, LPS-treated, and LPS + Hsp22 treated groups, relevant echocardiograms and staining were performed to scrutinize the cardiac pathology. Plausible mechanisms were proposed based on the findings of the enzyme-linked immunosorbent assay and Western blotting assay. A protective role of Hsp22 against LPS-induced myocardial injury emerged, as evidenced from decreased levels of creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and enhanced cardiac function. The post-LPS administration-caused spike in inflammatory cytokines (IL-1β, IL-6, TNF-α and NLRP3) was attenuated by the Hsp22 pre-treatment. In addition, superoxide dismutase (SOD) activity and B-cell lymphoma-2 (Bcl2) levels were augmented by Hsp22 treatment resulting in lowering of LPS-induced oxidative stress and cardiomyocyte apoptosis. In summary, the suppression of LPS-induced myocardial injury by Hsp22 overexpression via targeting of inflammation, oxidative stress, and apoptosis in cardiomyocytes paves the way for this protein to be employed in the therapy of SIMD.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs. However, the underlying etiology and mechanisms remain unclear. This study was performed to identify potential therapeutic targets for SLE using bioinformatics methods. First, 584 differentially expressed genes were identified based on the GSE61635 dataset. Tissue-specific analyses, enrichment analyses, and Protein-Protein interaction network were successively conducted. Furthermore, ELISA was performed to confirm the expression levels of key genes in the control and SLE blood samples. The findings revealed that tissue-specific expression of markers of the hematological system (25.5%, 28/110) varied significantly. CCL2, MMP9, and RSAD2 expression was markedly increased in the SLE samples compared with controls. In conclusion, the identified key genes (CCL2, MMP9, and RSAD2) may act as possible therapeutic targets for the treatment of SLE.

Background/Aims: Diabetes mellitus (DM) has become an increasingly epidemic metabolic disease. Vascular endothelial cells play a key role in developing the cardiovascular complications of DM. The A 2B receptor is expressed in vascular endothelial cells, and may help regulate the function of endothelial cells. The aim of this study was to investigate the protective effects of oxymatrine (OMT) on human umbilical vein endothelial cells (HUVECs) from high glucoseinduced cytotoxicity. Methods: Homology modeling and molecular docking analysis were used to detect the binding sites between the adenosine A 2B receptor and OMT. HUVECs were cultured with control (5.5 mM) or elevated glucose (22.2 mM) in the presence or absence of 3 µM OMT or A 2B siRNA for 3 days. The MTS cell viability assay was used to measure the toxicity of high glucose on HUVECs and the protective effect of OMT or A 2B siRNA. The expression of the adenosine A 2B receptor and CCL5 in HUVECs was detected with real-time quantitative PCR (qPCR) and Western blotting methods in each group. Levels of IL-1β and TNF-α were measured using an enzyme-linked immunosorbent assay (ELISA) kit, and the concentration of NO was detected with the nitrate reductase method. Monocyte chemotactic activity in each group was detected using Transwell chambers. Furthermore, the phosphorylation of p38 and ERK1/2 in each group was observed through the Western blotting method. Results: Homology modeling and molecular docking analysis showed that OMT contains well-fitted binding sites to the A 2B receptor. After chronic culture at high glucose, the rate of cell viability was significantly lower than that of the control group. After co-treatment with OMT or A 2B siRNA, cell viability was significantly increased compared with the high-glucose group. The results from real-time quantitative RT-PCR (qRT-PCR) and Western blotting indicated that high glucose could increase the expression of A 2B receptors in HUVECs, an effect that was inhibited by OMT. In addition, the results revealed that the expression of CCL5, IL-1β and TNF-α was increased in the high-glucose group, and that the NO produced by HUVECs decreased due to hyperglycemia; however, co-culture with OMT or A 2B siRNA abolished these effects. Meanwhile, the chemotaxis activity of monocytes to HUVECs cultured in high-glucose medium was enhanced 2.59-fold compared to the control cells. However, the inflammatory reactions in HUVECs were completely relieved by co-treatment with OMT or A 2B siRNA. Moreover, the phosphorylation of p38 and ERK1/2 in HUVECs in the high-glucose group was significantly higher than that of the control group; these effects were reversed after co-treatment with OMT or A 2B siRNA. Conclusion: OMT may protect the HUVECs from high glucose-induced cytotoxicity through inhibitting the expression of A 2B receptor and inflammatory factors as well as decreasing the phosphorylation of p38 and ERK1/2.

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Obesity is a complex medical condition that affects multiple organs in the body. However, the underlying mechanisms of obesity, as well as its treatment, are largely unexplored . The focus of this research was to use bioinformatics to discover possible treatment targets for obesity. To begin, the GSE133099 database was used to identify 364 differentially expressed genes (DEGs). Then, DEGs were subjected to tissue-specific analyses and enrichment analyses, followed by the creation of a protein-protein interaction (PPI) network and generation of a drug-gene interaction database to screen key genes and potential future drugs targeting obesity. Findings have illustrated that the tissue-specific expression of neurologic markers varied significantly (34.7%, 52/150). Among these genes, Lep, ApoE, Fyn, and FN1 were the key genes observed in the adipocyte samples from obese patients relative to the controls. Furthermore, nine potential therapeutic drugs (dasatinib, ocriplasmin, risperidone, gemfibrozil, ritonavir, fluvastatin, pravastatin, warfarin, atorvastatin) that target the key genes were also screened and selected. To conclude the key genes discovered (Lep, ApoE, Fyn, and FN1), as well as 9 candidate drugs, could be used as therapeutic targets in treating obesity.

Backgrounds Adrenal venous sampling (AVS) represents the gold standard for classifying primary aldosteronism (PA). However, AVS is a technically demanding, expensive and invasive procedure. Computed tomography (CT) scans is recommended as the initial study of classification diagnosis by the current guidelines. In addition, postural stimulation test (PST) has been used to provide additional subtype diagnostic information. Objective This work aimed to evaluate the diagnostic utility of the adrenal CT combined with PST in the classification diagnosis of PA. Methods We analyzed PA patients who underwent AVS from November 2017 to February 2022 at a single center. Subtype classification of PA was determined by AVS. We analyzed the concordance rate between AVS outcomes, adrenal CT, and PST, and explored the value of adrenal CT combined with PST for predicting laterality of PA. Results Total 531 PA patients were included in the present study. The concordance rate between AVS and the adrenal CT was 51.0%(271/531). Receiver operating characteristic (ROC) curve of PST showed that the area under curve (AUC) was 0.604 [95% confidence interval (CI): 0.556, 0.652], the optimal cut-off value was 30%. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (−LR) of PST for diagnosis bilateral PA on AVS was 72.8, 46.2%, 0.48, 0.71, 1.35, and 0.59, respectively. The prevalence of unilateral PA on AVS in patients with unilateral lesion on CT and negative PST, unilateral lesion on CT and positive PST, bilateral normal or lesions on CT and negative PST, and bilateral normal or lesions on CT and positive PST was 82.4% (108/131), 59.9% (91/152), 50.7% (37/73), and 44.6% (78/175), respectively. The sensitivity, specificity, PPV, NPV, +LR, and -LR of adrenal CT combined with PST for the diagnosis of unilateral PA were 34.4, 89.4%, 0.82, 0.49, 3.25, and 0.73, respectively. Conclusions The combination of CT findings and PST can improve the accuracy of predicting laterality of PA.