Endothelial Dickkopf-1 Promotes Smooth Muscle Cell-derived Foam Cell Formation via USP53-mediated Deubiquitination of SR-A During Atherosclerosis.

Shear stress-induced Dickkopf-1 (DKK1) secretion by endothelial cells (ECs) promotes EC dysfunction and accelerates atherosclerosis (AS). However, the paracrine role of endothelial DKK1 in modulating adjacent smooth muscle cells (SMCs) in atherosclerosis remains unclear. This study investigated the role of EC-secreted DKK1 in SMC-derived foam cell formation under shear stress, and .

Hepatocyte TIPE2 is a fasting-induced Raf-1 inactivator that drives hepatic gluconeogenesis to maintain glucose homeostasis.

Background: The liver regulates metabolic balance during fasting-feeding cycle. Hepatic adaptation to fasting is precisely modulated on multiple levels. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a negative regulator of immunity that reduces several liver pathologies, but its physiological roles in hepatic metabolism are largely unknown.

Dickkopf-1 promotes vascular smooth muscle cell foam cell formation and atherosclerosis development through CYP4A11/SREBP2/ABCA1.

Vascular smooth muscle cells (VSMCs) are considered to be a crucial source of foam cells in atherosclerosis due to their low expression level of cholesterol exporter ATP-binding cassette transporter A1 (ABCA1) intrinsically. While the definite regulatory mechanisms are complicated and have not yet been fully elucidated, we previously reported that Dickkopf-1 (DKK1) mediates endothelial cell (EC) dysfunction, thereby aggravating atherosclerosis. However, the role of smooth muscle cell (SMC) DKK1 in atherosclerosis and foam cell formation remains unknown.

CX3CR1 deficiency exacerbates immune-mediated hepatitis by increasing NF-κB-mediated cytokine production in macrophage and T cell.

Immune-mediated hepatitis is marked by liver inflammation characterized by immune cell infiltration, chemokine/cytokine production, and hepatocyte injury. C-X3C motif receptor 1 (CX3CR1), as the receptor of chemokine C-X3C motif ligand 1 (CX3CL1)/fractalkine, is mainly expressed on immune cells including monocytes and T cells. Previous studies have shown that CX3CR1 protects against liver fibrosis, but the exact role of CX3CL1/CX3CR1 in acute immune-mediated hepatitis remains unknown.

Intelligent monitoring of noxious stimulation during anaesthesia based on heart rate variability analysis.

Research based on medical signals has received significant attention in recent years. If the patients' states can be accurately monitored based on medical signals, it greatly benefits both doctors and patients. This paper proposes a method to extract signal features from heart rate variability signals and classify patients' states using the long short-term memory network and enable effective monitoring of noxious stimulation.

Vascular feature as a modulator of the aging brain.

The cerebral functional reorganization and declined cognitive function of aging might associate with altered vascular features. Here, we explored the altered cerebral hierarchical functional network of 2 conditions (task-free and naturalistic stimuli) in older adults and its relationship with vascular features (systemic microvascular and perfusion features, measured by magnetic resonance imaging) and behavior. Using cerebral gradient analysis, we found that compressive gradient of resting-state mainly located on the primary sensory-motor system and transmodal regions in aging, and further compress in these regions under the continuous naturalistic stimuli.

Complement Inhibition Targeted to Injury Specific Neoepitopes Attenuates Atherogenesis in Mice.

Previous studies have indicated an important role for complement in atherosclerosis, a lipid-driven chronic inflammatory disease associated to oxidative stress in the vessel wall. However, it remains unclear how complement is activated in the process of atherogenesis. An accepted general model for complement activation in the context of ischemia reperfusion injury is that ischemia induces the exposure of neoepitopes that are recognized by natural self-reactive IgM antibodies, and that in turn activate complement.

Theanine Improves High-Dose Epigallocatechin-3-Gallate-Induced Lifespan Reduction in .

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. Our previous report showed that induced hormesis was a critical determinant for the promotion of a healthy lifespan in . In the present study, we investigated the anti-aging effects of the main active ingredients in green tea.

Influence of Sliding Time Window Size Selection Based on Heart Rate Variability Signal Analysis on Intelligent Monitoring of Noxious Stimulation under Anesthesia.

In recent decades, little progress of objective evaluation of pain and noxious stimulation has been achieved under anesthesia. Some researches based on medical signals have failed to provide a general understanding of this problem. This paper presents a feature extraction method for heart rate variability signals, aiming at further improving the evaluation of noxious stimulation.

Bile acid-activated macrophages promote biliary epithelial cell proliferation through integrin αvβ6 upregulation following liver injury.

Cholangiopathies caused by biliary epithelial cell (BEC) injury represent a leading cause of liver failure. No effective pharmacologic therapies exist, and the underlying mechanisms remain obscure. We aimed to explore the mechanisms of bile duct repair after targeted BEC injury.

Kupffer cells promote T-cell hepatitis by producing CXCL10 and limiting liver sinusoidal endothelial cell permeability.

Kupffer cells (KCs) play a crucial role in liver immune homeostasis through interacting with other immune cells and liver sinusoidal endothelial cells (LSECs). However, how KCs exactly interact with these cells for maintaining the homeostasis still require the further investigation. CXCL10 is a chemokine that has been implicated in chemoattraction of monocytes, T cells, NK cells, and dendritic cells, and promotion of T cell adhesion to endothelial cells.

Polydopamine-Modified Copper-Doped Titanium Dioxide Nanotube Arrays for Copper-Catalyzed Controlled Endogenous Nitric Oxide Release and Improved Re-Endothelialization.

The controllable release is necessary for ideal drug delivery technologies. Because of their high specific surface area and high porosity, titanium dioxide nanotubes (TNTs) have been widely used as drug carriers in medical devices. By loading copper as the catalyst, nitric oxide (NO) generation was facilitated by catalyzing the decomposition of renewable endogenous NO donors .

Distinct fate, dynamics and niches of renal macrophages of bone marrow or embryonic origins.

Renal macrophages (RMs) participate in tissue homeostasis, inflammation and repair. RMs consist of embryo-derived (EMRMs) and bone marrow-derived RMs (BMRMs), but the fate, dynamics, replenishment, functions and metabolic states of these two RM populations remain unclear. Here we investigate and characterize RMs at different ages by conditionally labeling and ablating RMs populations in several transgenic lines.

Versatile cell ablation tools and their applications to study loss of cell functions.

Targeted cell ablation is a powerful approach for studying the role of specific cell populations in a variety of organotypic functions, including cell differentiation, and organ generation and regeneration. Emerging tools for permanently or conditionally ablating targeted cell populations and transiently inhibiting neuronal activities exhibit a diversity of application and utility. Each tool has distinct features, and none can be universally applied to study different cell types in various tissue compartments.

Caspase-1 Activation Is Related With HIV-Associated Atherosclerosis in an HIV Transgenic Mouse Model and HIV Patient Cohort.

Objective: Atherosclerotic cardiovascular disease (ASCVD) is an increasing cause of morbidity and mortality in people with HIV since the introduction of combination antiretroviral therapy. Despite recent advances in our understanding of HIV ASCVD, controversy still exists on whether this increased risk of ASCVD is due to chronic HIV infection or other risk factors. Mounting biomarker studies indicate a role of monocyte/macrophage activation in HIV ASCVD; however, little is known about the mechanisms through which HIV infection mediates monocyte/macrophage activation in such a way as to engender accelerated atherogenesis.

Elevated indoleamine-2,3-dioxygenase enzyme activity in a novel mouse model of HIV-associated atherosclerosis.

Objective: HIV atherosclerosis and cardiovascular disease (CVD) represent a significant human health burden in the era of combination antiretroviral therapy (cART). The pathogenesis of HIV atherosclerosis is still poorly understood, due, in part, to the lack of a suitable small animal model. Indoleamine-2,3-dioxygenase (IDO) enzyme activity is the first and rate-limiting step in tryptophan catabolism and is measured by the kynurenine to tryptophan ratio (KTR).

LRP1 receptor-mediated immunosuppression of α-MMC on monocytes.

Alpha-MMC is a type I ribosome-inactivating protein purified from bitter gourd that has strong anti-tumour and antiviral activity. Alpha-MMC also has immunosuppressive effects, but the mechanism of these immunosuppressive effects remains unclear. It is reported that the binding of α-MMC to its specific cell membrane LRP1 receptor is key to its biological effects.

Adipocyte Death Preferentially Induces Liver Injury and Inflammation Through the Activation of Chemokine (C-C Motif) Receptor 2-Positive Macrophages and Lipolysis.

Adipocyte death occurs under various physiopathological conditions, including obesity and alcohol drinking, and can trigger organ damage particularly in the liver, but the underlying mechanisms remain obscure. To explore these mechanisms, we developed a mouse model of inducible adipocyte death by overexpressing the human CD59 (hCD59) on adipocytes (adipocyte-specific hCD59 transgenic mice). Injection of these mice with intermedilysin (ILY), which rapidly lyses hCD59 expressing cells exclusively by binding to the hCD59 but not mouse CD59, resulted in the acute selective death of adipocytes, adipose macrophage infiltration, and elevation of serum free fatty acid (FFA) levels.

In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models.

CRISPR-associated protein 9 (Cas9)-mediated genome editing provides a promising cure for HIV-1/AIDS; however, gene delivery efficiency in vivo remains an obstacle to overcome. Here, we demonstrate the feasibility and efficiency of excising the HIV-1 provirus in three different animal models using an all-in-one adeno-associated virus (AAV) vector to deliver multiplex single-guide RNAs (sgRNAs) plus Staphylococcus aureus Cas9 (saCas9). The quadruplex sgRNAs/saCas9 vector outperformed the duplex vector in excising the integrated HIV-1 genome in cultured neural stem/progenitor cells from HIV-1 Tg26 transgenic mice.

Systemic application of 3-methyladenine markedly inhibited atherosclerotic lesion in ApoE mice by modulating autophagy, foam cell formation and immune-negative molecules.

A growing body of evidence demonstrates that autophagy, an evolutionarily conserved intracellular degradation process, is involved in the pathogenesis of atherosclerosis and has become a potential therapeutic target. Here we tested the effect of two inhibitors of phosphatidylinositol 3-kinase, 3-methyladenine (3-MA) and 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), commonly used as inhibitors of autophagy, in atherosclerosis in apolipoprotein E mice. Systemic application of 3-MA but not LY294002 markedly reduced the size of atherosclerotic plaque and increased the stability of lesions in high-fat diet-fed mice as compared with controls.

Rapid conditional targeted ablation model for hemolytic anemia in the rat.

Effective methods for cell ablation are important tools for examining the anatomical, functional, and behavioral consequences of selective loss of specific cell types in animal models. We have developed an ablation system based on creating genetically modified animals that express human CD59 (hCD59), a membrane receptor, and administering intermedilysin (ILY), a toxin produced by Streptococcus intermedius, which binds specifically to hCD59 to induce cell lysis. As proof-of-concept in the rat, we generated an anemia model, SD-Tg(CD59-HBA1)Bryd, which expresses hCD59 on erythrocytes.

Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration.

Cell ablation is a powerful tool for studying cell lineage and/or function; however, current cell-ablation models have limitations. Intermedilysin (ILY), a cytolytic pore-forming toxin that is secreted by Streptococcus intermedius, lyses human cells exclusively by binding to the human complement regulator CD59 (hCD59), but does not react with CD59 from nonprimates. Here, we took advantage of this feature of ILY and developed a model of conditional and targeted cell ablation by generating floxed STOP-CD59 knockin mice (ihCD59), in which expression of human CD59 only occurs after Cre-mediated recombination.

[Assessment of the Effect of Pain on Autonomic Nervous System in Human Body Using Heart Rate Variability Analysis].

The purpose of this study is to discuss the feasibility of establishing capsaicin pain model and the possibility to evaluate different degrees of pain by the heart rate variability (HRV). It also aims to investigate the changes of autonomic nervous activity of volunteers during the process of pain caused by capsaicin. A total of 30 volunteers were selected, who were physically and mentally healthy, into the study.

The expression of a novel anti-inflammatory cytokine IL-35 and its possible significance in childhood asthma.

Interleukin-35 (IL-35) is a novel anti-inflammatory cytokine and has been shown to play an important role in maintaining immune homeostasis. However, the effect of IL-35 on human asthma remains unclear. The present study is to investigate the expression and significance of IL-35 in childhood asthma.

Complement and HIV-I infection/HIV-associated neurocognitive disorders.

The various neurological complications associated with HIV-1 infection, specifically HIV-associated neurocognitive disorders (HAND) persist as a major public health burden worldwide. Despite the widespread use of anti-retroviral therapy, the prevalence of HAND is significantly high. HAND results from the direct effects of an HIV-1 infection as well as secondary effects of HIV-1-induced immune reaction and inflammatory response.