A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity.

Identification of osteoporosis ferroptosis-related markers and potential therapeutic compounds based on bioinformatics methods and molecular docking technology.

Research Background And Purpose: Osteoporosis (OP) is one of the most common bone diseases worldwide, characterized by low bone mineral density and susceptibility to pathological fractures, especially in postmenopausal women and elderly men. Ferroptosis is one of the newly discovered forms of cell death regulated by genes in recent years. Many studies have shown that ferroptosis is closely related to many diseases.

A combined transcriptomics and proteomics approach to reveal the mechanism of AEE relieving hyperlipidemia in ApoE mice.

Hyperlipidemia caused by abnormal lipid metabolism has reached epidemic proportions. This phenomenon is also common in companion animals. Previous studies showed that AEE significantly improves abnormal blood lipids in hyperlipidemia rats and mice, but its mechanism is still not clear enough.

AEE alleviates ox-LDL-induced lipid accumulation and inflammation in macrophages.

Atherosclerosis is a chronic immune inflammatory disease. Aspirin eugenol ester (AEE) is a novel safe and non-toxic compound with many pharmacological effects such as anti-inflammatory, anti-hyperlipidemic and anti-thrombotic action. In order to investigate the effect of AEE on the inhibition of aortic lipid plaque formation and macrophage-derived foam cell formation induced by oxidized low density lipoprotein (ox-LDL), in vivo atherosclerosis model by feeding ApoE mice with a high-fat diet and foam cells formation in vitro model by ox-LDL-induced RAW264.

Multi-omics reveals aspirin eugenol ester alleviates neurological disease.

Background: Exosomes play an essential role in maintaining normal brain function due to their ability to cross the blood-brain barrier. Aspirin eugenol ester (AEE) is a new medicinal compound synthesized by the esterification of aspirin with eugenol using the prodrug principle. Aspirin has been reported to have neuroprotective effects and may be effective against neurodegenerative diseases.

The Transport and Uptake of Resveratrol Mediated via Glucose Transporter 1 and Its Antioxidant Effect in Caco-2 Cells.

Resveratrol has anti-inflammatory, anti-cancer, and anti-aging pharmacological activities. There is currently a gap in academic research regarding the uptake, transport, and reduction of HO-induced oxidative damage of resveratrol in the Caco-2 cell model. This study investigated the role of resveratrol in the uptake, transport, and alleviation of HO-induced oxidative damage in Caco-2 cells.

Untargeted lipidomics and metagenomics reveal the mechanism of aspirin eugenol ester relieving hyperlipidemia in ApoE-/- mice.

Hyperlipidemia is induced by abnormal lipid metabolism, which can cause the occurrence of cardiovascular diseases and lead to grievous injury to health. Studies showed that AEE had a significant therapeutic effect on hyperlipidemia and is likely to be associated with the up-regulation of cholesterol 7-alpha hydroxylase (CYP7A1), the key enzyme for cholesterol conversion to bile acids, but no research confirmed whether the effect of AEE on hyperlipidemia was related to the gut microbiota and liver lipids. At the same time, more and more studies have shown that gut microbiota and lipids are closely related to hyperlipidemia.

Isolation, molecular typing and antimicrobial resistance of in dogs and cats in Lanzhou city of Northwest China.

infection (CDI) in human and animals belonged usually to antibiotic-associated diarrhea, ranging in severity from mild to life-threatening intestinal tract illnesses. This study aimed to isolation and characterization, toxin genes test, molecular typing, and drug sensitivity of () which were isolated from clinical diseased dogs and cats. A total of 247 clinical samples were collected from five animal hospitals in Lanzhou City of Northwest China, of which dogs and cats accounted for 74.

Aspirin eugenol ester alleviates lipopolysaccharide-induced acute lung injury in rats while stabilizing serum metabolites levels.

Aspirin eugenol ester (AEE) was a novel drug compound with aspirin and eugenol esterified. AEE had various pharmacological activities, such as anti-inflammatory, antipyretic, analgesic, anti-oxidative stress and so on. In this study, it was aimed to investigate the effect of AEE on the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats.

Isobavachalcone From Presents Significant Antibacterial Activity Against Through Disruption of the Cell Membrane.

infection (CDI) has been widely reported in human and animals around the world over the past few decades. The high relapse rate and increasing drug resistance of CDI make the discovery of new agents against fairly urgent. This study aims to investigate the antibacterial activity against from traditional Chinese herb medicine and confirm its active components.

P301S-hTau acetylates KEAP1 to trigger synaptic toxicity via inhibiting NRF2/ARE pathway: A novel mechanism underlying hTau-induced synaptic toxicities.

Background: Human Tau (hTau) accumulation and synapse loss are two pathological hallmarks of tauopathies. However, whether and how hTau exerts toxic effects on synapses remain elusive.

Methods: Mutated hTau (P301S) was overexpressed in the N2a cell line, primary hippocampal neurons and hippocampal CA3.

Florfenicol-Polyarginine Conjugates Exhibit Promising Antibacterial Activity Against Resistant Strains.

Florfenicol was widely used as antibiotic in the livestock and poultry breeding industry, resulting in a serious problem of drug resistance. In order to solve the resistance of florfenicol, this study designed and synthesized a new series of florfenicol-polyarginine conjugates and tested for antimicrobial activities. Drug-sensitive bacteria, gram-negative bacteria () and gram-positive (), were sensitive to several of the compounds tested.

Intracellular accumulation of tau inhibits autophagosome formation by activating TIA1-amino acid-mTORC1 signaling.

Background: Autophagy dysfunction plays a crucial role in tau accumulation and neurodegeneration in Alzheimer's disease (AD). This study aimed to investigate whether and how the accumulating tau may in turn affect autophagy.

Methods: The primary hippocampal neurons, N2a and HEK293T cells with tau overexpression were respectively starved and treated with vinblastine to study the effects of tau on the initiating steps of autophagy, which was analysed by Student's two-tailed t-test.

CCL7 playing a dominant role in recruiting early OCPs to facilitate osteolysis at metastatic site of colorectal cancer.

Background: Chemoattractant is critical to recruitment of osteoclast precursors and stimulates tumor bone metastasis. However, the role of chemoattractant in bone metastasis of colorectal cancer (CRC) is still unclear.

Methods: Histochemistry analysis and TRAP staining were utilized to detect the bone resorption and activation of osteoclasts (OCs) after administration of CCL7 neutralizing antibody or CCR1 siRNA.

Uptake and Transport of Naringenin and Its Antioxidant Effects in Human Intestinal Epithelial Caco-2 Cells.

Naringenin, a flavanone, has been reported for a wide range of pharmacological activities. However, there are few reports on the absorption, transport and antioxidant effects of naringenin. The study was to explore the uptake, transport and antioxidant effects of naringenin .

A Magnetic Resonance Angiography-Based Study Comparing Machine Learning and Clinical Evaluation: Screening Intracranial Regions Associated with the Hemorrhagic Stroke of Adult Moyamoya Disease.

Objectives: Moyamoya disease patients with hemorrhagic stroke usually have a poor prognosis. This study aimed to determine whether hemorrhagic moyamoya disease could be distinguished from MRA images using transfer deep learning and to screen potential regions that contain rich distinguishing information from MRA images in moyamoya disease.

Materials And Methods: A total of 116 adult patients with bilateral moyamoya diseases suffering from hemorrhagic or ischemia complications were retrospectively screened.

Blood lead level in Chinese adults with and without coronary artery disease.

Background: The Trial to Assess Chelation Therapy study found that edetate disodium (disodium ethylenediaminetetraacetic acid) chelation therapy significantly reduced the incidence of cardiac events in stable post-myocardial infarction patients, and a body of epidemiological data has shown that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. However, limited studies have focused on the relationship between angiographically diagnosed coronary artery disease (CAD) and lead exposure. This study compared blood lead level (BLL) in Chinese patients with and without CAD.

Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia Inhibiting FXR to Induce CYP7A1.

Hyperlipidemia is an important lipid disorder and a risk factor for health. Aspirin eugenol ester (AEE) is a novel synthetic compound which is made up of two chemical structural units from aspirin and eugenol. Therapeutic effect of AEE on hyperlipidemia has been confirmed in animal model.

[Preparation of Antibiotic-Loaded Copper-Doped Hydroxyapatite Microspheres and Evaluation of Their Antibacterial and Osteogenic Effect].

Objective: To explore the preparation method of copper (Cu)-doped hydroxyapatite (HA) microspheres loaded with vancomycin (Van), and evaluate their antibacterial and osteogenic effects .

Methods: The Cu doped HA microspheres (Cu-HA) with molar doping ratios of 1%, 5%, 10%, and 20% were prepared by hydrothermal synthesis. The microscopic morphology changes were observe with scanning electron microscope.

Protective Activity of Aspirin Eugenol Ester on Paraquat-Induced Cell Damage in SH-SY5Y Cells.

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. The aim of this study was to investigate the protective effect of AEE on paraquat- (PQ-) induced cell damage of SH-SY5Y human neuroblastoma cells and its potential molecular mechanism. There was no significant change in cell viability when AEE was used alone.

The Protective Effect of Aspirin Eugenol Ester on Oxidative Stress to PC12 Cells Stimulated with HO through Regulating PI3K/Akt Signal Pathway.

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. This study is aimed at identifying the protective effect of AEE against HO-induced apoptosis in rat adrenal pheochromocytoma PC12 cells and the possible mechanisms. The results of cell viability assay showed that AEE could increase the viability of PC12 cells stimulated by HO, while AEE alone had no significant effect on the viability of PC12 cells.

T217-Phosphorylation Exacerbates Tau Pathologies and Tau-Induced Cognitive Impairment.

Background: Recent studies show that an increased T217-phosphorylation of tau in plasma could diagnose AD at an early stage with high accuracy and high specificity, while the potential toxic role of tau T217-phosphorylation is not known.

Objective: To study the potential toxic role of tau T217-phosphorylation.

Methods: We performed stereotactic brain injection, behavioral testing, immunohistochemistry and immunofluorescence, western blotting, Golgi staining, in vitro recombinant tau polymerization, and other measurements.