Chromatin remodelling drives immune cell-fibroblast communication in heart failure.

Chronic inflammation and tissue fibrosis are common responses that worsen organ function, yet the molecular mechanisms governing their cross-talk are poorly understood. In diseased organs, stress-induced gene expression changes fuel maladaptive cell state transitions and pathological interaction between cellular compartments. Although chronic fibroblast activation worsens dysfunction in the lungs, liver, kidneys and heart, and exacerbates many cancers, the stress-sensing mechanisms initiating transcriptional activation of fibroblasts are poorly understood.

Alzheimer's Amyloid- Accelerates Cell Senescence and Suppresses the SIRT1/NRF2 Pathway in Human Microglial Cells.

Microglia play important roles in maintenance of brain homeostasis, while due to some pathological stimuli in aging-related neurodegenerative diseases including Alzheimer's disease, they are malfunctioning. Here, we demonstrated that amyloid- (A) accelerated cell senescence characterized by the upregulation of p21 and PAI-1 as well as senescence-associated beta-galactosidase (SA--gal) in human microglial cells. Consistently, A induced the senescence-associated mitochondrial dysfunctions such as repression of ATP production, oxygen consumption rate (OCR), and mitochondrial membrane potential and enhancement of ROS production.

PL201, a Reported Rhamnoside Against Alzheimer's Disease Pathology, Alleviates Neuroinflammation and Stimulates Nrf2 Signaling.

Neuroinflammation induced by overactivated glia cells is believed to be a major hallmark of Alzheimer's disease (AD) and a hopeful target against AD. A rhamnoside PL201 was previously reported to promote neurogenesis and ameliorate AD, and in this study, we revealed that PL201 also significantly reduced accumulation of the activated microglia and proinflammatory cytokines in APP/PS1 mice. , PL201 consistently suppressed the microglia induction of proinflammatory cytokines after stimulation with lipopolysaccharides and Aβ42.

An analog derived from phenylpropanoids ameliorates Alzheimer's disease-like pathology and protects mitochondrial function.

The abnormal proliferation and neurogenesis of neural progenitor cells (NPCs) is usually associated with the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). Mitochondrial stress is one of the most prominent features of AD and is thought to be involved in the impairment of the neurogenesis and proliferation of NPCs. Thus, restoring mitochondrial function by pharmaceutical intervention may alleviate disease-related defects in neurogenesis and is considered a potential therapeutic strategy for AD.

Naringin Dihydrochalcone Ameliorates Cognitive Deficits and Neuropathology in APP/PS1 Transgenic Mice.

Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder with abnormal accumulation of amyloid-β (Aβ) plaques, neuroinflammation and impaired neurogenesis. Mounting evidences suggest that single-target drugs have limited effects on clinical treatment and alternative or multiple targets are required. In recent decades, natural compounds and their derivatives have gained increasing attention in AD drug discovery due to their inherently enormous chemical and structural diversity.