Phosphorylation of endothelial histone H3.3 serine 31 by PKN1 links flow-induced signaling to proatherogenic gene expression.

Atherosclerotic lesions develop preferentially in arterial regions exposed to disturbed blood flow, where endothelial cells acquire an inflammatory phenotype. How disturbed flow induces endothelial cell inflammation is incompletely understood. Here we show that histone H3.

A galacturonic acid-rich polysaccharide from Citrus medica 'fingered' alleviated the dextran sulfate sodium-induced ulcerative colitis.

Ulcerative colitis (UC) treatment is often limited by adverse reactions and high recurrence rates, highlighting the need for safer, more effective therapies. Citrus medica 'Fingered' (C. medica), known for its anti-inflammatory properties, remains underexplored, particularly its polysaccharide components.

Mutation on JmjC domain of UTX impaired its antitumor effects in pancreatic cancer via inhibiting G0S2 expression and activating the Toll-like signaling pathway.

Background: Recently, the incidence of pancreatic cancer (PC) has gradually increased. Research has shown that UTX mutants are critical in tumors. However, the underlying mechanisms remain incompletely understood.

[Eye-acupuncture ameliorates ferroptosis of cerebral neuronal cells in CIRI rats by up-regulating System xc(-)-GSH-GPX4 antioxidant functional axis activities].

Objectives: To observe the effect of eye-acupuncture on the antioxidant function axis：System xc(-)-glutathione-glutathione peroxidase 4 (System xc［-］-GSH-GPX4) in the cortical tissue of ischemic penumbra of acute cerebral ischemia-reperfusion injury (CIRI) rats, so as to explore its underlying mechanism in improvement of CIRI by ameliorating the ferroptosis of neurons via antioxidant function axis.

Methods: Male SD rats were randomly divided into sham operation, model, eye-acupuncture and GPX4-inhibitor groups, with 15 rats in each group. The CIRI model was replicated by occlusion of the middle cerebral artery and reperfusion for 24 h.

SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor.

Inflammation is a protective response to pathogens and injury. To be effective it needs to be resolved by endogenous mechanisms in order to avoid prolonged and excessive inflammation, which can become chronic. Specialized pro-resolving mediators (SPMs) are a group of lipids derived from omega-3 fatty acids, which can induce the resolution of inflammation.

pH-sensitive nano-polyelectrolyte complexes with arthritic macrophage-targeting delivery of triptolide.

Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site.

GDF11 knockdown downregulates SMURF1 to inhibit breast cancer progression by activation of p53 and inactivation of ERα signaling.

Breast cancer (BC) is a prevalent neoplasm that occurs in women all over the world. Growth and differentiation factor 11 (GDF11) plays an essential role in cancer progression. This study focused on investigating the biological role and underlying mechanisms of GDF11 in BC.

Neuroendocrine-Immune Regulatory Network of Oliver.

Oliver () is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine-immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications.

In vitro fecal fermentation properties of polysaccharides from Tremella fuciformis and related modulation effects on gut microbiota.

Tremella fuciformis is an edible and medicinal mushroom. Polysaccharides from T. fuciformis have received increasing attention due to their diversely pharmacological activities.

digestive characteristics and microbial degradation of polysaccharides from lotus leaves and related effects on the modulation of intestinal microbiota.

Polysaccharides exist as one of the most abundant components in lotus leaves, which attract increasing attention owing to their promising health-promoting benefits. In this study, the digestive and microbial degradation characteristics of lotus leaf polysaccharides (LLP) were studied by using an gastrointestinal model. The results suggested that LLP was stable in the human upper gastrointestinal tract according to its digestive stabilities at different simulated digestion stages.

Hydroxysafflor Yellow A Blocks HIF-1 Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium.

Zonula occludens-1 (ZO-1) is a tight junction protein in the cerebrovascular endothelium, responsible for blood-brain barrier function. Hydroxysafflor yellow A (HSYA) is a major ingredient of safflower ( L.) with antioxidative activity.

Tenascin-X Mediates Flow-Induced Suppression of EndMT and Atherosclerosis.

Background: Endothelial-to-mesenchymal transition (EndMT) has been identified as a critical driver of vascular inflammation and atherosclerosis, and TGF-β (transforming growth factor β) is a key mediator of EndMT. Both EndMT and atherosclerosis are promoted by disturbed flow, whereas unidirectional laminar flow limits EndMT and is atheroprotective. How EndMT and endothelial TGF-β signaling are regulated by different flow patterns is, however, still poorly understood.

Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis.

The extravasation of leukocytes is a critical step during inflammation that requires the localized opening of the endothelial barrier. This process is initiated by the close interaction of leukocytes with various adhesion molecules such as ICAM-1 on the surface of endothelial cells. Here we reveal that mechanical forces generated by leukocyte-induced clustering of ICAM-1 synergize with fluid shear stress exerted by the flowing blood to increase endothelial plasma membrane tension and to activate the mechanosensitive cation channel PIEZO1.

Dynamic variations in physicochemical characteristics of oolong tea polysaccharides during simulated digestion and fecal fermentation .

In this study, dynamic variations in physicochemical characteristics of polysaccharides from Wuyi rock' tea (WYP) at different simulated digestion and fecal fermentation stages were studied. Results revealed that physicochemical characteristics of WYP were slightly altered after the simulated digestion , and its digestibility was about 8.38%.

Qingwei San treats oral ulcer subjected to stomach heat syndrome in db/db mice by targeting TLR4/MyD88/NF-κB pathway.

Background: Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigated the pharmacological mechanisms.

Protein kinase N2 mediates flow-induced endothelial NOS activation and vascular tone regulation.

Formation of NO by endothelial NOS (eNOS) is a central process in the homeostatic regulation of vascular functions including blood pressure regulation, and fluid shear stress exerted by the flowing blood is a main stimulus of eNOS activity. Previous work has identified several mechanosensing and -transducing processes in endothelial cells, which mediate this process and induce the stimulation of eNOS activity through phosphorylation of the enzyme via various kinases including AKT. How the initial mechanosensing and signaling processes are linked to eNOS phosphorylation is unclear.

HIF-1: structure, biology and natural modulators.

Hypoxia-inducible factor 1 (HIF-1), as a main transcriptional regulator of metabolic adaptation to changes in the oxygen environment, participates in many physiological and pathological processes in the body, and is closely related to the pathogenesis of many diseases. This review outlines the mechanisms of HIF-1 activation, its signaling pathways, natural inhibitors, and its roles in diseases. This article can provide new insights in the diagnosis and treatment of human diseases, and recent progress on the development of HIF-1 inhibitors.

Prognostic Exploration of All-Cause Death in Gingival Squamous Cell Carcinoma: A Retrospective Analysis of 2076 Patients.

Background: We aimed to establish a prognostic model for gingival squamous cell carcinoma (GSCC) that was superior to traditional AJCC staging and to perform a comprehensive comparison of the newly established nomogram with the AJCC staging system.

Methods: We extracted 2,076 patients with gingival squamous cell carcinoma who had been entered into the SEER (Surveillance, Epidemiology, and End Results) database between 2004 and 2015, and randomly divided 70% of them into the training cohort and the other 30% into the validation cohort. Cox regression analysis was performed in combination with clinical experience and age, race, sex, marital status, tumor location, histological subtype, tumor grade, AJCC stage, chemotherapy status, radiotherapy status, and surgery status as possible prognostic factors.

Dynamic changes of structural characteristics of snow chrysanthemum polysaccharides during in vitro digestion and fecal fermentation and related impacts on gut microbiota.

The in vitro simulated saliva-gastrointestinal digestion and human fecal fermentation of snow chrysanthemum polysaccharides (JHP) were investigated. Results showed that reducing sugar contents of JHP increased during the gastrointestinal digestion, and glucose released with the decrease of its molecular weight, suggesting that JHP could be partially degraded under the gastrointestinal digestion. Furthermore, after in vitro fecal fermentation, the molecular weight and molar ratio of constituent monosaccharides (galactose and galacturonic acid) of the indigestible JHP (JHP-I) significantly decreased, and both monosaccharides and oligosaccharides released, suggesting that JHP-I could be further degraded and consumed by gut microbiota.

Regulation of the NLRP3 inflammasome with natural products against chemical-induced liver injury.

The past decades have witnessed significant progress in understanding the process of sterile inflammation, which is dependent on a cytosolic complex termed the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome. Activation of NLRP3 inflammasome requires two steps, including the activation of Toll-like receptor (TLR) by its ligands, resulting in transcriptional procytokine and inflammasome component activation, and the assembly and activation of NLRP3 inflammasome triggered by various danger signals, leading to caspase-1 activation, which could subsequently cleave procytokines into their active forms. Metabolic disorders, ischemia and reperfusion, viral infection and chemical insults are common pathogenic factors of liver-related diseases that usually cause tissue damage and cell death, providing numerous danger signals for the activation of NLRP3 inflammasome.

YAP/TAZ Are Required to Suppress Osteogenic Differentiation of Vascular Smooth Muscle Cells.

Vascular smooth muscle cells (VSMCs) represent the prevailing cell type of arterial vessels and are essential for blood vessel structure and homeostasis. They have substantial potential for phenotypic plasticity when exposed to various stimuli in their local microenvironment. How VSMCs maintain their differentiated contractile phenotype is still poorly understood.

In vitro simulated digestion and fecal fermentation of polysaccharides from loquat leaves: Dynamic changes in physicochemical properties and impacts on human gut microbiota.

The aim of this study was to well understand the dynamic changes of physicochemical properties of polysaccharides from loquat leaves (LLP) during in vitro simulated saliva-gastrointestinal digestion and fecal fermentation and its related impacts on human gut microbiota. Results showed that the contents of reducing sugar of LLP slightly increased during the gastrointestinal digestion, and its molecular weight also slightly decreased, suggesting that LLP could be slightly degraded under the gastrointestinal digestion conditions. Moreover, during the fecal fermentation, the molecular weight of the indigestible LLP (LLP-I) significantly decreased, and the molar ratio of constituent monosaccharides of LLP-I, such as glucuronic acid, galacturonic acid, galactose, and arabinose, significantly changed, indicating that LLP-I could be degraded and consumed by human gut microbiota.

Polysaccharides from dandelion (Taraxacum mongolicum) leaves: Insights into innovative drying techniques on their structural characteristics and biological activities.

The aim of this study was to well understand the impacts of innovative drying techniques (radio frequency drying and microwave drying) and traditional drying techniques (vacuum drying, freezing drying, and hot air drying) on the structural characteristics and bioactivities of polysaccharides from dandelion leaves (DLPs). Five different DLPs were obtained from dandelion leaves dried by abovementioned drying techniques. Results showed that the structural characteristics and bioactivities of DLPs varied with different drying techniques.