Background: Study on the expression of miRNA‐22 in serum of Alzheimer's disease (AD) patients and the mechanism of neuroinflammation regulation.Methods: ELISA assay was used to detect the serum level of inflammatory factors, including interleukin‐1β (IL‐1β), interleukin‐18 (IL‐18), and tumor necrosis factor‐α in AD patients. TargetScan database and luciferase reporter gene assay indicated that gasdermin D (GSDMD) was the target gene of miRNA‐22. miRNA‐22 mimic was transfected into microglia, followed by administration of LPS and Nigericin to induce pyroptosis.Results: In this study, we found that the expression level of miRNA‐22 in peripheral blood was lower in AD patients than that in healthy population. The expression of inflammatory factors was higher in AD patients than that in healthy people, which was negatively correlated with miRNA‐22. miRNA‐22 mimic could significantly inhibit pyroptosis, the expression of GSDMD and p30‐GSDMD was down‐regulated, the release of inflammatory factor was decreased, and the expression of NLRP3 inflammasome was down‐regulated as feedback. In the APP/PS1 double transgenic mouse model, the injection of miRNA‐22 mimic significantly improved the memory ability and behavior of mice. In addition, the expression of the vital protein of pyroptosis in mouse brain tissue, including GSDMD and p30‐GSDMD, was down‐regulated, and the expression of inflammatory factors was also decreased.Conclusion: miRNA‐22 was negatively correlated with the expression of inflammatory factors in AD patients, and miRNA‐22 could inhibit the release of inflammatory cytokines by regulating the inflammatory pyroptosis of glial cells via targeting GSDMD, thereby improving cognitive ability in AD mice. miRNA‐22 and pyroptosis are potential novel therapeutic targets in the treatment of AD.

Objective: To detect the expression of high‐mobility group box protein 1 (HMGB1) and toll‐like receptor 4 (TLR4) and their downstream signaling factors—myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF‐κB), and tumor necrosis factor alpha (TNF‐α)—in the sera of patients with Parkinson's disease (PD) in order to evaluate the relationship of the HMGB1–TLR4 axis with PD development and progression.Methods: The serum HMGB1 and TLR4 protein levels of 120 patients with PD and 100 healthy volunteers were measured using double‐antibody sandwich ELISA, and their correlations with PD staging, disease duration, drug treatment effectiveness, and clinical classification were analyzed. In addition, their correlations with the key downstream factors of the HMGB1–TLR4 axis (MyD88, NF‐κB, and TNF‐α) were analyzed.Results: HMGB1 and TLR4 expressions were higher in the peripheral blood of patients with PD than in healthy volunteers. PD patients with poor drug treatment outcomes had significantly higher HMGB1 and TLR4 expressions than PD patients with stable drug treatment outcomes. Higher HMGB1 and TLR4 expressions were found in patients at higher PD stages, and patients with >4‐year disease duration had significantly higher HMGB1 and TLR4 expressions than patients with <4‐year disease duration. No significant difference in HMGB1 and TLR4 expressions was found among patients with tremor‐dominant, akinetic‐rigid, and mixed subtypes of PD. NF‐κB and TNF‐α expressions were positively correlated with high expression of the HMGB1–TLR4 axis.Conclusion: High expression of the HMGB1–TLR4 axis is closely associated with PD development, progression, drug treatment effectiveness, staging, and disease duration and has great significance for PD diagnosis and treatment.

Piperine (PIP), the main active ingredient in pepper, belongs to the cinnamamide alkaloid. PIP has been found to have functions, including anti‐oxidation, immune regulation, anti‐tumour and promotion of drug metabolism. The present study was mainly designed to reveal the anti‐tumour effect of PIP against gastric cancer and the relevant mechanism. In brief, the undifferentiated human gastric cancer cell HGC‐27 was used, which was treated with different concentrations of PIP. As a result, PIP could inhibit proliferation and induce apoptosis of HGC‐27 cells in a dose‐dependent manner. The mechanism of PIP was associated with ROS increase and mitochondrial damage, simultaneously, the expression of key proteins of apoptosis was affected, including Bcl‐2, Bax, Cyt‐c, Caspase‐9 and Caspase‐3. Pre‐treatment of ROS scavenger NAC HGC‐27 cells could significantly reduce PIP‐induced apoptosis and inhibit the activation of apoptotic signals. Consistently, PIP could induce ROS to increase and activate apoptotic signals in the animal model. Therefore, the present study showed that PIP can induce the generation of ROS, thereby promoting the activation of mitochondrial apoptotic pathway and exerting anti‐tumour effects.

M2 macrophages can promote liver cancer metastasis by promoting tumour angiogenesis; however, the mechanism underlying macrophage polarization has not been completely revealed. In this study, we mainly explored the mechanism underlying long non‐coding RNA‐CRNDE (lncRNA‐CRNDE) in regulating M2 macrophage polarization and promoting liver cancer angiogenesis. The expression of CRNDE was up‐regulated or down‐regulated in THP‐1 cells (CRNDE^‐/‐‐THP‐1 cells and pcDNA3.1‐CRNDE‐THP‐1). THP‐1 cells were co‐cultured with liver cancer cell line H22, and M2 polarization was induced in THP‐1 by IL‐4/13 to simulate tumour‐induced macrophage polarization. As a result, after CRNDE overexpression, THP‐1 cell viability was up‐regulated, the expression of M2 membrane marker CD163 was up‐regulated, and the proportion of F4/80 + CD163+ cells was also up‐regulated. ELISA assay showed that the expression of M2 markers (including TGF‐β1 and IL‐10) and chemokines (including CCl22 and CCL22) was up‐regulated, and the expression of key signals (including STAT6, JAK‐1, p‐AKT1, and Arg‐1) was also up‐regulated, which were significantly different compared with the control group (Con). In addition, the intervention effect of CRNDE on THP‐1 was consistent between co‐culture with H22 cells and IL‐4/13 induction assay. The induced M2 THP‐1 cells were co‐cultured with HUVEC. As a result, THP‐1 cells with CRNDE overexpression can promote the migration and angiogenesis of HUVEC cells in vitro and simultaneously up‐regulate the expression of Notch1, Dll4 and VEGFR2, indicating that THP‐1 M2 polarization induced by CRNDE could further promote angiogenesis. The H22 cell tumour‐bearing mouse model was constructed, followed by injection of CRNDE anti‐oligosense nucleotides and overexpression plasmids to interfere CRNDE expression in tumour‐bearing tissues. Consequently, down‐regulation of CRNDE could down‐regulate tumour volume, simultaneously down‐regulate the expression of CD163 and CD31 in tissues, decrease the expression of key proteins (including JAK‐1, STAT‐6, p‐STAT6 and p‐AKT1), and down‐regulate the expression of key angiogenesis‐related proteins (including VEGF, Notch1, Dll4 and VEGFR2). In this study, we found that CENDE could indirectly regulate tumour angiogenesis by promoting M2 polarization of macrophages, which is also one of the mechanisms of microenvironmental immune regulation in liver cancer.

Introduction: Parkinson's disease (PD) is a common degenerative disease of the central nervous system (CNS). The main pathological change is the apoptosis of dopaminergic neurons in the substantia nigra pars compacta (SNPc), thereby leading to dopamine reduction in nigral striatum. 6‐Hydroxydopamine (6‐OHDA), a neurotoxic substance, mediates apoptosis of dopaminergic neurons and causes Parkinson‐like symptoms in mice.Methods: Our team previously found that Antrodia camphorata polysaccharide (ACP) exerted a good behavioral improvement effect on the PD mouse model established by 6‐OHDA; however, the mechanism remains unknown. Therefore, in this study, we focused on ROS‐NLRP3 signal to investigate the mechanism of 6‐OHDA‐induced apoptosis of dopaminergic neurons MES23.5 and the protective effects of ACP on dopaminergic neurons.Result: 6‐OHDA could further activate the expression of inflammasome NLRP3 by inducing ROS, thereby resulting in apoptosis of MES23.5 cells. ACP could inhibit the expression of ROS‐NLRP3 induced by 6‐OHDA, exerting a protective role in MES23.5 cells. Animal experiments also confirmed that ACP intervention could reduce the activation level of ROS‐NLRP3 in the substantia nigra–striatum and improve the exercise capacity of PD mice.Conclusion: Our study validated that 6‐OHDA could induce apoptosis of dopaminergic neurons via ROS‐NLRP3 activation. ACP could inhibit this signal and protect dopaminergic neurons, which might be promising in research of PD therapeutics.