Complement 3a induces the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms during the development and progression of Alzheimer's disease.

As a central molecule in complement system (CS), complement (C) 3 is upregulated in the patients and animal models of Alzheimer's disease (AD). C3 will metabolize to iC3b and C3a. iC3b is responsible for clearing β-amyloid protein (Aβ).

As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer's Disease.

C1q, the initiator of the classical pathway of the complement system, is activated during Alzheimer's disease (AD) development and progression and is especially associated with the production and deposition of β-amyloid protein (Aβ) and phosphorylated tau in β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Activation of C1q is responsible for induction of synapse loss, leading to neurodegeneration in AD. Mechanistically, C1q could activate glial cells, which results in the loss of synapses via regulation of synapse pruning and phagocytosis in AD.

Levistolide A ameliorates fibrosis in chronic kidney disease via modulating multitarget actions in vitro and in vivo.

Aims: The increasing incidence of chronic kidney disease (CKD) urgently calls for effective nephroprotective agents. Traditional Chinese Medicine Angelica sinensis and its formula are well known for CKD therapy, but the underlying mechanisms and effective substances of reno-protective effects remain unclear. To this end, we isolated eleven ligustilide dimers (1-11) from A.

The Involvement of Post-Translational Modifications in Regulating the Development and Progression of Alzheimer's Disease.

Post-translational modifications (PTMs) have been recently reported to be involved in the development and progression of Alzheimer's disease (AD). In detail, PTMs include phosphorylation, glycation, acetylation, sumoylation, ubiquitination, methylation, nitration, and truncation, which are associated with pathological functions of AD-related proteins, such as β-amyloid (Aβ), β-site APP-cleavage enzyme 1 (BACE1), and tau protein. In particular, the roles of aberrant PTMs in the trafficking, cleavage, and degradation of AD-associated proteins, leading to the cognitive decline of the disease, are summarized under AD conditions.

Discovery, Preliminary Structure-Activity Relationship, and Evaluation of Oleanane-Type Saponins from for the Treatment of Ulcerative Colitis.

To discover ulcerative colitis (UC) treatment agents, 28 oleanane-type triterpenoid saponins (-) including three new saponins, pulsatillosides P-R (-), were isolated from . The isolated saponins could observably ameliorate UC by improving the intestinal epithelial cell barrier and intestinal flora . The structure-activity relationship indicated that the oligosaccharide chain at C-28 was essential for their anti-UC activities; the methyl group at the C-23 site of triterpene saponins showed important effects on anti-UC efficacy; the chain length of oligosaccharides at position C-28 had little effect on their anti-UC activities.

The Anti-inflammatory Effects of Isoflavonoids from Radix Astragali in Hepatoprotective Potential against LPS/D-gal-induced Acute Liver Injury.

Radix Astragali (RA) is an important Traditional Chinese Medicine widely used in the treatment of various diseases, such as pneumonia, atherosclerosis, diabetes, kidney and liver fibrosis. The role of isoflavonoids from RA in the treatment of liver injury remains unclear. The study aimed to explore hepatoprotective and anti-inflammatory effects of isoflavonoids from .

New insight into the molecular mechanism of miR482/2118 during plant resistance to pathogens.

MicroRNAs (miRNAs), a group of small noncoding RNAs (approximately 20-24 nucleotides), act as essential regulators affecting endogenous gene expression in plants. MiR482/2118 is a unique miRNA superfamily in plants and represses () genes to function in plant resistance to pathogens. In addition, over the past several years, it has been found that miR482/2118 not only targets s but also acts on other molecular mechanisms to affect plant resistance.

Meloxicam Inhibits Apoptosis in Neurons by Deactivating Tumor Necrosis Factor Receptor Superfamily Member 25, Leading to the Decreased Cleavage of DNA Fragmentation Factor Subunit α in Alzheimer's Disease.

Neuronal apoptosis is considered to be a critical cause of Alzheimer's disease (AD). Recently, meloxicam has shown neuroprotective effects; however, the inherent mechanisms are highly overlooked. Using APP/PS1 transgenic (Tg) mice as in vivo animal models, we found that meloxicam inhibits apoptosis in neurons by deactivating tumor necrosis factor receptor superfamily member 25 (TNFRSF25), leading to the suppression of the expression of fas-associated protein with death domain (FADD) and the cleavage of DNA fragmentation factor subunit α (DFFA) and cysteine aspartic acid protease-3 (caspase 3) via β-amyloid protein (Aβ)-depressing mechanisms.

Molecular mechanism of acetylsalicylic acid in improving learning and memory impairment in APP/PS1 transgenic mice by inhibiting the abnormal cell cycle re-entry of neurons.

Alzheimer's disease (AD) is a neurodegenerative disorder accompanied by the loss and apoptosis of neurons. Neurons abnormally enter the cell cycle, which results in neuronal apoptosis during the course of AD development and progression. However, the mechanisms underlying cell cycle re-entry have been poorly studied.

Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the production and deposition of β-amyloid protein (Aβ) and hyperphosphorylated tau, leading to the formation of β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Although calcium ions (Ca) promote the formation of APs and NFTs, no systematic review of the mechanisms by which Ca affects the development and progression of AD has been published. Therefore, the current review aimed to fill the gaps between elevated Ca levels and the pathogenesis of AD.

Riligustilide alleviates hepatic insulin resistance and gluconeogenesis in T2DM mice through multitarget actions.

Riligustilide (RG), one of the dimeric phthalides of Angelica sinensis and Ligusticum chuanxiong, was confirmed effective against many diseases. However, its effects on type 2 diabetes mellitus (T2DM) and the underlying molecular mechanisms have not been clearly elucidated yet. The current study was designed to investigate the hypoglycemic potential by which RG affects the pathogenesis of T2DM.

Downregulating expression of OPTN elevates neuroinflammation via AIM2 inflammasome- and RIPK1-activating mechanisms in APP/PS1 transgenic mice.

Background: Neuroinflammation is thought to be a cause of Alzheimer's disease (AD), which is partly caused by inadequate mitophagy. As a receptor of mitophagy, we aimed to reveal the regulatory roles of optineurin (OPTN) on neuroinflammation in the pathogenesis of AD.

Methods: BV2 cells and APP/PS1 transgenic (Tg) mice were used as in vitro and in vivo experimental models to determine the regulatory roles of OPTN in neuroinflammation of AD.

Therapeutic engagement in robot-assisted psychological interventions: A systematic review.

Purpose: Therapeutic engagement is a key component of psychological interventions. Robot-assisted psychological interventions appear to have therapeutic benefits for service users that are challenging to engage. However, engagement with robots in robot-assisted psychological interventions is not well understood.

Indomethacin Disrupts the Formation of β-Amyloid Plaques via an α2-Macroglobulin-Activating lrp1-Dependent Mechanism.

Epidemiological studies have implied that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows the development and progression of Alzheimer's disease (AD). However, the underlying mechanisms are notably understudied. Using a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) (APP/PS1) expressing transgenic (Tg) mice and neuroblastoma (N) 2a cells as in vivo and in vitro models, we revealed the mechanisms of indomethacin in ameliorating the cognitive decline of AD.

New dihydro-β-agarofuran sesquiterpenoids from Tripterygium wilfordii and their anti-inflammatory activity.

Twenty seven dihydro-β-agarofuran sesquiterpenoids, including fifteen new congeners, wilforsinines I-W (1-9, 12-13, 24-27), and twelve known compounds were isolated from the dried root of Tripterygium wilfordii. The structures of the new sesquiterpenoids, wilforsinines I-W, were elucidated by extensive spectroscopic data analysis. The anti-inflammatory activity of isolates 1-27 were evaluated by examining their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.

Elevating the Levels of Calcium Ions Exacerbate Alzheimer's Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau.

Alzheimer's disease (AD) is a neurodegenerative disease with a high incidence rate. The main pathological features of AD are β-amyloid plaques (APs), which are formed by β-amyloid protein (Aβ) deposition, and neurofibrillary tangles (NFTs), which are formed by the excessive phosphorylation of the tau protein. Although a series of studies have shown that the accumulation of metal ions, including calcium ions (Ca), can promote the formation of APs and NFTs, there is no systematic review of the mechanisms by which Ca affects the development and progression of AD.

New phenolic glycosides from Bunge and their antioxidant activity.

ABATRACTNine compounds, five phenolic glycosides (, , ), three phenylpropanoids (), and a furanone glycoside (), were isolated from aqueous soluble extract of the dried roots of Bunge. The structures of new compounds () were elucidated by comprehensive spectroscopic data analysis as well as chemical evidence. Pulsatillanin A () demonstrated significant antioxidant effects through scavenging free radical in DPPH assay, and relieved the oxidative stress in LPS-induced RAW 264.

Biomimetic synthesis and anti-inflammatory evaluation of violacin A analogues.

Violacin A, a chromanone derivative, isolated from a fermentation broth of Streptomyces violaceoruber, has excellent anti-inflammatory potential. Herein, a biogenetically modeled approach to synthesize violacin A and twenty-five analogues was described, which involved the preparation of aromatic polyketide precursor through Claisen condensation and its spontaneous cyclization. The inhibitory effect on nitric oxide (NO) production of all synthetic molecules was evaluated by lipopolysaccharide (LPS)-induced Raw264.

Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, and Investigations of Jamunones.

Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells.

Amycolasporins and Dibenzoyls from Lichen-Associated and Their Antibacterial and Anti-inflammatory Activities.

Eleven metabolites, six echinosporins (-), four dibenzoyls (-), and an aromatic compound (), were isolated from the fermentation broth of lichen-associated . The structures of the new compounds (-, -) were elucidated by comprehensive spectroscopic analysis including data from experimental and calculated ECD spectra. Amycolasporins A-C () demonstrated antibacterial activities against , , and with MIC values of 25 or 100 μg/mL.

Prostaglandin A1 Decreases the Phosphorylation of Tau by Activating Protein Phosphatase 2A via a Michael Addition Mechanism at Cysteine 377.

Prostaglandin (PG) A1 is a metabolic product of cyclooxygenase 2 (COX-2) that is potentially involved in regulating the development and progression of Alzheimer's disease (AD). PGA1 is a cyclopentenone (cy) PG characterized by the presence of a chemically reactive α,β-unsaturated carbonyl. PGA1 is potentially involved in the regulation of multiple biological processes via Michael addition; however, the specific roles of PGA1 in AD remain unclear.

Levistolide A Attenuates Alzheimer's Pathology Through Activation of the PPARγ Pathway.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by β-amyloid (Aβ) protein deposition, neurofibrillary tangle (NFT) formation, and neuronal loss in the brain. The current study was designed to investigate the potential mechanisms by which levistolide A affects the pathogenesis of AD in an amyloid precursor protein/presenilin 1 (APP/PS1) transgenic (Tg) mouse model of AD and N2a/APP695swe cells. Specifically, behavioral changes in levistolide A-treated APP/PS1 Tg mice were assessed by the nest-building and Morris water maze (MWM) tests.

Rofecoxib Attenuates the Pathogenesis of Amyotrophic Lateral Sclerosis by Alleviating Cyclooxygenase-2-Mediated Mechanisms.

Cyclooxygenase-2 (COX-2) is reported to be activated during the course of amyotrophic lateral sclerosis (ALS) development and progression. However, the roles of COX-2 in aggravating ALS and the underlying mechanism have been largely overlooked. To reveal the mechanisms, the canonical SOD1 mouse model was used as an experimental model for ALS in the current study.

A semisynthetic borrelidin analogue BN-3b exerts potent antifungal activity against Candida albicans through ROS-mediated oxidative damage.

In the process of investigating the antifungal structure-activity relationships (SAR) of borrelidin and discovering antifungal leads, a semisynthetic borrelidin analogue, BN-3b with antifungal activity against Candida albicans, was achieved. In this study, we found that oxidative damage induced by endogenous reactive oxygen species (ROS) plays an important role in the antifungal activity of BN-3b. Further investigation indicated that BN-3b stimulated ROS accumulation, increased malondialdehyde (MDA) levels, and decreased reduced/oxidized glutathione (GSH/GSSG) ratio.