Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression

Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves. For hundreds of years, Mangifera indica Linn. leaf has been used as an ingredient in numerous traditional Chinese medicine preparations for the treatment of bronchitis. However, the pharmacological mechanism of mangiferin in the treatment of bronchitis remains to be elucidated. Macrophage classical activation is important role in the process of bronchial airway inflammation, and interferon regulatory factor 5 (IRF5) has been identified as a key regulatory factor for macrophage classical activation. The present study used the THP-1 human monocyte cell line to investigate whether mangiferin inhibits macrophage classical activation via suppressing IRF5 expression in vitro. THP-1 cells were differentiated to macrophages by phorbol 12-myristate 13-acetate. Macrophages were polarized to M1 macrophages following stimulation with lipopolysaccharide (LPS)/interferon-γ (IFN-γ). Flow cytometric analysis was conducted to detect the M1 macrophages. Reverse transcription-quantitative polymerase chain reaction was used to investigate cellular IRF5 gene expression. Levels of proinflammatory cytokines and IRF5 were assessed following cell culture and cellular homogenization using enzyme-linked immunosorbent assay. IRF5 protein and nuclei co-localization was performed in macrophages with laser scanning confocal microscope immunofluorescence analysis. The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN-γ stimulation-induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release. In addition, cellular IRF5 expression was markedly downregulated. These results suggest that the inhibitory effect of mangiferin on classical activation of macrophages may be exerted via downregulation of cellular IRF5 expression levels

The first complete mitochondrial genome of the genus Dendronereis, represented by D. chipolini Hsueh, 2019 (Annelida, Nereididae) from Beibu Gulf, China

The genus Dendronereis Peters, 1854 is characterized in the polychaete family Nereididae by its feather-shaped branchiae on the anterior segments. In this study, we present the first complete mitogenome of Dendronereis, represented by D. chipolini Hsueh, , collected from Beibu Gulf, China. The nucleotide composition is biased toward A + T nucleotides, accounting 31.5% for A, 22.3% for C, 14.7% for G and 31.5% for T. The assembled mitogenome is 15,763 bp in length, with a typical set of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), 2 ribosomal RNA (rRNA), and 1 non-coding control region. All genes are encoded on H-strand. The control region is 1260 bp in length and located between tRNA-Gly and tRNA-Met. Phylogenetic study showed that D. chipolini is arranged with high support into the clade of Namanereidinae. The complete mitogenome provides important molecular data for investigating the phylogeny and evolution of the nereid animals

A new perspective on Alzheimer’s disease: m6A modification

As a neurodegenerative disease, Alzheimer’s disease (AD) is characterized by synaptic loss, extracellular plaques of amyloid accumulation, hyperphosphorylation of tau, and neuroinflammation. Various biological processes are affected by epitranscriptomic modifications, which regulate the metabolism of mRNA in cells and regulate the expression of genes. In response to changes in m6A modification levels, the nervous system becomes dysfunctional and plays a significant role in the development of Alzheimer’s disease. As a result of recent research, this paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of AD. In addition, the article discusses recent research techniques related to animal models of m6A and AD. Furthermore, it discusses the possibility of studying the pathogenesis of AD at the level of the epitranscriptome, identifying early diagnostic markers, and screening for effective treatment options

Chlorogenic Acid Targeting of the AKT PH Domain Activates AKT/GSK3β/FOXO1 Signaling and Improves Glucose Metabolism

Chlorogenic acid (CGA), a bioactive component in the human diet, is reported to exert beneficial effects on the regulation of glucose metabolism. This study was designed to investigate the specific target of CGA, and explore its underlying mechanisms. Beneficial effects of CGA in glucose metabolism were confirmed in insulin-treated human hepatocarcinoma HepG2 cells. Protein fishing, via CGA-modified functionalized magnetic microspheres, demonstrated the binding of CGA with protein kinase B (AKT). Immunofluorescence using a CGA molecular probe further demonstrated the co-localization of CGA with AKT. A competitive combination test and hampering of AKT membrane translocation showed that CGA might bind to the pleckstrin homology (PH) domain of AKT. The specific binding did not lead to the membrane translocation to phosphatidylinositol (3,4,5)-trisphosphate (PIP3), but directly activated the phosphorylation of AKT on Ser-473, induced the phosphorylation of the downstream molecules, glycogen synthase kinase 3β (GSK3β) and forkhead box O1 (FOXO1), and improved glucose metabolism. Collectively, our data demonstrate that CGA exerts regulatory effects on glucose metabolism via direct targeting the PH domain of AKT. This study clarifies the mechanism of the potential benefits of nutrients containing CGA in the complementary therapy of glucose metabolism disorders

The combination of cinnamaldehyde and kaempferol ameliorates glucose and lipid metabolism disorders by enhancing lipid metabolism via AMPK activation

Nutrients in diets, especially functional foods, are beneficial in metabolism-related diseases, such as diabetes. Cinnamaldehyde (CA), a natural flavorant, inhibits glycolysis while enhancing glucose storage. Kaempferol (KP), a flavonol in edible plants, inhibits amino acid metabolism and gluconeogenesis. Whether the combination of CA and KP exerts stronger effects in diabetes needs further investigation. In this work, nontargeted metabolomics results confirmed the simultaneous obstruction of glucose and amino acid metabolism by CA and KP. The falling status of the energy supply, demonstrated by the increased ratio of adenosine monophosphate (AMP) /adenosine triphosphate (ATP), was sensed by AMP-activated protein kinase (AMPK). The activation of AMPK in turn enhanced lipolysis and inhibited fatty acid synthesis both in vivo and in vitro. In conclusion, this study indicated that the CA and KP combination ameliorated glucose and lipid metabolism disorders by enhancing lipid metabolism via the activation of AMPK

Ambient Air Pollution and Risk for Ischemic Stroke: A Short-Term Exposure Assessment in South China

Data on the association between air pollution and risk of ischemic stroke in China are still limited. This study aimed to investigate the association between short-term exposure to ambient air pollution and risk of ischemic strokes in Guangzhou, the most densely-populated city in south China, using a large-scale multicenter database of stroke hospital admissions. Daily counts of ischemic stroke admissions over the study years 2013–2015 were obtained from the Guangzhou Cardiovascular and Cerebrovascular Disease Event Surveillance System. Daily particulate matter <2.5 μm in diameter (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and meteorological data were collected. The associations between air pollutants and hospital admissions for stroke were examined using relative risks (RRs) and their corresponding 95% confidence intervals (CIs) based on time-series Poisson regression models, adjusting for temperature, public holiday, day of week, and temporal trends in stroke. Ischemic stroke admissions increased from 27,532 to 35,279 through 2013 to 2015, increasing by 28.14%. Parameter estimates for NO2 exposure were robust regardless of the model used. The association between same-day NO2 (RR = 1.0509, 95% CI: 1.0353–1.0668) exposure and stroke risk was significant when accounting for other air pollutants, day of the week, public holidays, temperature, and temporal trends in stroke events. Overall, we observed a borderline significant association between NO2 exposure modeled as an averaged lag effect and ischemic stroke risk. This study provides data on air pollution exposures and stroke risk, and contributes to better planning of clinical services and emergency contingency response for stroke

Peach Kernel Oil Downregulates Expression of Tissue Factor and Reduces Atherosclerosis in ApoE knockout Mice

Atherosclerosis is the pathological process in arteries due to the plaque formation that is responsible for several diseases like heart disease, stroke and peripheral arterial disease. In this study, we performed in vitro and in vivo assays to evaluate the potential anti-atherosclerosis activity of peach kernel oil. For the in vitro assay, we incubated human umbilical vein endothelial cells (HUVEC) with tumor necrosis factor-α (TNF-α) to induce tissue factors (TF, an essential mediator of hemostasis and trigger of thrombosis) elevation. We found that TNF-α-induced TF elevation was suppressed by peach kernel oil in a dose-dependent manner at both mRNA and protein levels. Peach kernel oil can significantly improve HUVEC viability, protect the endothelial cells, which achieved the goal of prevention of thrombotic diseases. For the in vivo assay, we investigated the effect and mechanism of peach kernel oil on preventing atherosclerotic lesion formation in ApoE knockout mice. Results show that peach kernel oil could reduce total cholesterol, triglyceride, low-density lipoprotein cholesterol levels, elevate the high-density lipoprotein cholesterol level in serum, and reduce the area of the aortic atherosclerotic lesions in high-fat diet fed ApoE knockout mice. Moreover, peach kernel oil treatment can significantly down regulate the expression of TF protein to inhibit the formation of atherosclerotic plaque. In conclusion, peach kernel oil may be a potential health food to prevent atherosclerosis in cardiovascular diseases