RS-5645 attenuates inflammatory cytokine storm induced by SARS-CoV-2 spike protein and LPS by modulating pulmonary microbiota.

An inflammatory cytokine storm is considered an important cause of death in severely and critically ill COVID-19 patients, however, the relationship between the SARS-CoV-2 spike (S) protein and the host's inflammatory cytokine storm is not clear. Here, the qPCR results indicated that S protein induced a significantly elevated expression of multiple inflammatory factor mRNAs in peripheral blood mononuclear cells (PBMCs), whereas RS-5645 ((4-(thiophen-3-yl)-1-(p-tolyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone) attenuated the expression of the most inflammatory factor mRNAs. RS-5645 also significantly reduced the cellular ratios of CD45+/IFNγ+, CD3+/IFNγ+, CD11b+/IFNγ+, and CD56+/IFNγ+ in human PBMCs.

TRPV1 sustains microglial metabolic reprogramming in Alzheimer's disease.

As the brain-resident innate immune cells, reactive microglia are a major pathological feature of Alzheimer's disease (AD). However, the exact role of microglia is still unclear in AD pathogenesis. Here, using metabolic profiling, we show that microglia energy metabolism is significantly suppressed during chronic Aβ-tolerant processes including oxidative phosphorylation and aerobic glycolysis via the mTOR-AKT-HIF-1α pathway.

PPAR Targeting GDF11 Inhibits Vascular Endothelial Cell Senescence in an Atherosclerosis Model.

Atherosclerosis (AS) is a complex vascular disease that seriously harms the health of the elderly. It is closely related to endothelial cell aging, but the role of senescent cells in atherogenesis remains unclear. Studies have shown that peroxisome proliferator-activated receptor alpha (PPAR) inhibits the development of AS by regulating lipid metabolism.

MicroRNA-146b-5p overexpression attenuates premature ovarian failure in mice by inhibiting the Dab2ip/Ask1/p38-Mapk pathway and γH2A.X phosphorylation.

Objective: To examine the role of high-fat and high-sugar (HFHS) diet-induced oxidative stress, which is a risk factor for various diseases, in premature ovarian failure (POF).

Materials And Methods: Ovarian granulosa cells (OGCs) were isolated from mice and cultured in medium supplemented with HFHS and poly (lactic-co-glycolic acid) (PLGA)-cross-linked miR-146b-5p nanoparticles (miR-146@PLGA). RNA and protein expression levels were examined using quantitative real-time polymerase chain reaction and Western blotting, respectively.

Bushen Jiangzhi formula reduces atherosclerosis in apoE-/- mice through autophagy.

Objective: To study the effect of Bushen Jiangzhi formula (BSJZF) on atherosclerosis (AS) in apolipoprotein E knockout (apoE-/-) mice and the underlying mechanism.

Methods: We used a high fat diet to induce AS in apoE-/- mice. The mice were randomly divided into four groups: model, BSJZF, atorvastatin, and 3-methyladenine groups.

Efficacy of Shoushen granule on adenosine triphosphate binding cassette transporter A1, proprotein convertase subtilisin/kexin type 9 and toll-like receptor 4/nuclear factor kappa-B signaling pathway in ApoE-knockout mice.

Objective: To evaluate the efficacy of Shoushen granule, prepared with four Chinese medicinals, on the targeted regulation of adenosine triphosphate binding cassette transporter A1 (ABCA1) through proprotein convertase subtilisin/kexin type 9 (PCSK9) and toll-like receptor 4 (TLR4) / nuclear factor kappa-B (NF-κB) signaling pathway to affect atherosclerosis (AS) in ApoE-knockout (ApoE-/-) mice.

Methods: ApoE-/- mice fed with a high-fat diet were used for AS modeling and divided into Model, Shoushen, and Atorvastatin groups. C57BL/6J mice at the same age and background strain were included in the Control group.

miRNA-5119 regulates immune checkpoints in dendritic cells to enhance breast cancer immunotherapy.

Dendritic cell (DC) based immunotherapy is a promising approach to clinical cancer treatment. miRNAs are a class of small non-coding RNA molecules that bind to RNAs to mediate multiple events which are important in diverse biological processes. miRNA mimics and antagomirs may be potent agents to enhance DC-based immunotherapy against cancers.

The potassium channel KCa3.1 represents a valid pharmacological target for microgliosis-induced neuronal impairment in a mouse model of Parkinson's disease.

Background: Recent studies described a critical role for microglia in Parkinson's disease (PD), where these central nerve system resident immune cells participate in the neuroinflammatory microenvironment that contributes to dopaminergic neurons loss in the substantia nigra. Understanding the phenotype switch of microgliosis in PD could help to identify the molecular mechanism which could attenuate or delay the progressive decline in motor function. KCa3.

Identification of a novel regulatory pathway for PPARα by RNA-seq characterization of the endothelial cell lipid peroxidative injury transcriptome.

Endothelial dysfunction caused by endothelial cell injuries is the initiating factor for atherosclerosis (AS), and lipid peroxidative injury is one of a dominant factor for AS pathogenesis. Using RNA-seq, we compared changes in transcriptome expression before and after endothelial cell injury, and found 311 differentially expressed genes (DEGs), of which 258 genes were upregulated and 53 genes were downregulated. The protein-protein interactions (PPIs) between the genes were analysed using the STRING database, and a PPI network of DEGs was constructed.

Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1.

The aim of this study was to investigate the mechanisms through which quercetin protects against atherosclerosis (AS) in apoE‑/‑ mice by regulating the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), cluster of differentiation 36 (CD36), peroxisome proliferator‑activated receptor γ (PPARγ), liver X receptor α (LXRα) and ATP binding cassette transporter A1 (ABCA1). We established an animal model of high‑fat diet induced AS using apoE‑/‑ mice. H&E, Oil Red O and Masson's trichrome staining were performed on aortic sinus and liver tissue sections to evaluate the histopathology, lipid accumulation and collagen deposition, respectively.

Anti-atherosclerotic effects of LXRα agonist through induced conversion of M1 macrophage to M2.

Liver X receptor alpha (LXRα) plays important roles in lipid metabolism and inflammation. Therefore, it is essential for protection against atherosclerosis (AS). In AS plaques, the key cells involved in lipid metabolism and inflammation are macrophages.

Effect of Quercetin on Atherosclerosis Based on Expressions of ABCA1, LXR-α and PCSK9 in ApoE Mice.

Objective: To investigate the effect of quercetin on ATP binding cassette transporter A1 (ABCA1), liver X receptor (LXR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) expressions in apoE-knockout (ApoE) mice.

Methods: The high-fat diet-induced atherosclerosis (AS) in ApoE mice was established. Thirty-six mice were divided into 3 groups using random number table method: model group (n=12), quercetin group (n=12), and atorvastatin group (n=12), with C57BL/6J mice of the same strain and age as the control group (n=12).

EriB targeted inhibition of microglia activity attenuates MPP induced DA neuron injury through the NF-κB signaling pathway.

Accumulating evidence indicates that microglia activation is associated with an increased risk for developing Parkinson's disease (PD). With the progressive and selective degeneration of dopaminergic (DA) neurons, proinflammatory cytokines are elevated in the substantia nigra (SN) of PD patients. Thus, anti-inflammation has become one of the therapeutic strategies of PD.

Ca-dependent endoplasmic reticulum stress correlation with astrogliosis involves upregulation of KCa3.1 and inhibition of AKT/mTOR signaling.

Background: The intermediate-conductance Ca-activated K channel KCa3.1 was recently shown to control the phenotype switch of reactive astrogliosis (RA) in Alzheimer's disease (AD).

Methods: KCa3.

Genome-wide identification of genes involved in polyamine biosynthesis and the role of exogenous polyamines in Malus hupehensis Rehd. under alkaline stress.

Polyamines (PAs) in plants are growth substrates with functions similar to phytohormones. Although they contribute to diverse processes, little is known about their role in stress responses, especially for perennial woody plants. We conducted a genome-wide investigation of 18 sequences involved in PA biosynthesis in the genome of apple (Malus domestica).

Salidroside slows the progression of EA.hy926 cell senescence by regulating the cell cycle in an atherosclerosis model.

Aging is the major risk factor for diseases of the cardiovascular system, such as coronary atherosclerotic heart disease, but little is known about the relationship between atherosclerosis (AS) and age‑related declines in vascular structure and function. Here, we used histological analyses in combination with molecular biology techniques to show that lipid deposition in endothelial cell was accompanied by aging and growth arrest. Endothelial cell senescence is sufficient to cause AS; however, we found that salidroside reduced intracellular lipid deposition, slowed the progression of endothelial cell senescence and inhibited the expression of the senescence‑related molecules and phosphorylated the retinoblastoma (Rb) protein.

Exogenous Melatonin Alleviates Alkaline Stress in Malus hupehensis Rehd. by Regulating the Biosynthesis of Polyamines.

Since melatonin was identified in plants decades ago, much attention has been devoted to discovering its role in plant science. There is still a great deal to learn about the functional importance of melatonin, as well as its functional mode. In this paper, we examine the role of melatonin treatment in the response of Rehd.

Activation of the KCa3.1 channel contributes to traumatic scratch injury-induced reactive astrogliosis through the JNK/c-Jun signaling pathway.

Reactive astrogliosis is widely considered to contribute to pathogenic responses to stress and brain injury and to diseases as diverse as ischemia and neurodegeneration. We previously found that expression of the intermediate-conductance calcium-activated potassium channel (KCa3.1) involved in TGF-β-activated astrogliosis.

High expression of cyclooxygenase-2 in uterine fibroids and its correlation with cell proliferation.

Objective: To investigate the expression of cyclooxygenase-2 (COX-2) in uterine fibroids and healthy uterine smooth muscle as well as its role in the pathogenesis of uterine fibroids.

Methods: We collected uterine fibroid tissues and their paired adjacent healthy uterine smooth muscle tissues from 30 cases of uterine fibroids. We used immunohistochemistry and quantitative real-time PCR, as well as western blot to detect COX-2 expression.

Correlation of thrombomodulin expression and occlusion of the uterine artery for the treatment of leiomyoma.

Objectives: To determine the difference in thrombomodulin expression in the myometrium and in myoma; and to understand the correlation of anticoagulation/fibrinolytic function and the mechanism of uterine artery occlusion in the treatment of leiomyoma.

Study Design: Immunohistochemistry, western blotting and fluorescence quantitative polymerase chain reaction were used to investigate thrombomodulin protein expression and gene transcription in 15 female patients.

Results: Thrombomodulin was mainly expressed in endotheliocytes in the two types of tissues.

Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons.

Although the role of astrocyte glutamate transporters in glutamate clearance is well illustrated, the role of glutamine synthetase (GS) that influences this process remains to be elucidated. We examined whether GS affected the uptake of glutamate in astrocytes in vitro. The glutamate uptake was assessed by measuring the concentration of glutamate and glutamine in culture medium in the presence or absence of glutamate.

Temporospatial expression and cellular localization of oligodendrocyte myelin glycoprotein (OMgp) after traumatic spinal cord injury in adult rats.

Traumatic spinal cord injury (SCI) leads to permanent neurological deficits, which, in part, is due to the inability of mature axons to regenerate in the mammalian central nervous system (CNS). The oligodendrocyte myelin glycoprotein (OMgp) is one of the myelin-associated inhibitors of neurite outgrowth in the CNS. To date, limited information is available concerning its expression following SCI, possibly due to the lack of a reliable antibody against it.