White matter lesions contribute to motor and non-motor disorders in Parkinson's disease: a critical review.

Parkinson's disease (PD) is a prevalent neurodegenerative disease, characterized by movement disorders and non-motor symptoms like cognitive impairment and depression. Degeneration of dopaminergic neurons in the substantia nigra and Lewy bodies have long been considered as main neuropathological changes. However, recent magnetic resonance imaging (MRI) studies have shown that white matter lesions (WMLs) were present in PD patients.

Natural products and their derivatives alleviating cerebral white matter lesions.

White matter lesions (WMLs), characterized by focal demyelination or myelination disorders, are commonly present in cerebral small vessel disease and various neurological diseases. Multiple etiologies lead to WMLs. However, there is no specific therapy or effective drugs for relieving WMLs.

Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.

HACE1 is a member of the HECT domain-containing E3 ligases with 909 amino acid residues, containing N-terminal ankyrin-repeats (ANK) and C-terminal HECT domain. Previously, it was shown that HACE1 is inactive in human tumors and plays a crucial role in the initiation, progression, and invasion of malignant tumors. Recent studies indicated that HACE1 might be closely involved in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.

Correction: extract alleviated white matter damage through promoting the differentiation of oligodendrocyte precursor cells suppressing neuroinflammation.

Correction for ' extract alleviated white matter damage through promoting the differentiation of oligodendrocyte precursor cells suppressing neuroinflammation' by Caixia Zang , , 2022, , 2131-2141, https://doi.org/10.1039/D1FO02127C.

Yinma Jiedu Granule attenuates LPS-induced acute lung injury in rats via suppressing inflammation level.

Ethnopharmacological Relevance: Yinma Jiedu Granule (YMJD) is a traditional Chinese patent medicine (CPM), which has been proved to have anti-inflammatory effects and therapeutical effects on obstructive pulmonary disease.

Aim Of Study: The purpose of the current investigation is to find out if YMJD can alleviate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats and its underlying mechanisms.

Materials And Methods: Rats were treated with either vehicle or YMJD for 14 consecutive days, and 2 h after the last administration, the rat model of ALI was induced by the intratracheal instillation of LPS.

The toxic natural product tutin causes epileptic seizures in mice by activating calcineurin.

Tutin, an established toxic natural product that causes epilepsy in rodents, is often used as a tool to develop animal model of acute epileptic seizures. However, the molecular target and toxic mechanism of tutin were unclear. In this study, for the first time, we conducted experiments to clarify the targets in tutin-induced epilepsy using thermal proteome profiling.

Inhibition of CXCR2 enhances CNS remyelination via modulating PDE10A/cAMP signaling pathway.

CXC chemokine receptor 2 (CXCR2) plays an important role in demyelinating diseases, but the detailed mechanisms were not yet clarified. In the present study, we mainly investigated the critical function and the potential molecular mechanisms of CXCR2 on oligodendrocyte precursor cell (OPC) differentiation and remyelination. The present study demonstrated that inhibiting CXCR2 significantly enhanced OPC differentiation and remyelination in primary cultured OPCs and ethidium bromide (EB)-intoxicated rats by facilitating the formation of myelin proteins, including PDGFRα, MBP, MAG, MOG, and Caspr.

Extract GJ-4 Alleviates Memory Deficiency of Vascular Dementia in Rats through PERK-Mediated Endoplasmic Reticulum Stress Pathway.

Endoplasmic reticulum stress (ERS) is involved in the pathological process of vascular dementia (VD). GJ-4 is extracted from J. Ellis and has been reported to have protective roles in ischemia-related brain damage.

Design, synthesis and biological evaluation of pyranocarbazole derivatives against Alzheimer's disease, with antioxidant, neuroprotective and cognition enhancing properties.

A series of novel pyranocarbazole alkaloids were designed and synthesized as derivatives of Claulansine F and CZ-7. Some of the compounds showed strong neuroprotective effects and anti-lipid peroxidation capacity. Among these compounds, 10b, introduced leucine at the C-3 position of pyranocarbazole, was the most active in inhibiting the programmed death of SH-SY5Y cells.

J. Ellis extract GJ-4 attenuates hyperlipidemic vascular dementia in rats via regulating PPAR-γ-mediated microglial polarization.

Background: GJ-4 is extracted from J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies.

Objective: This study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms.

Inhibition of Dyrk1A Attenuates LPS-Induced Neuroinflammation via the TLR4/NF-κB P65 Signaling Pathway.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) is a highly conserved protein kinase, playing a key role in the regulation of physiological brain functions and pathological processes. In Alzheimer's disease (AD), Dyrk1A promotes hyperphosphorylation of tau protein and abnormal aggregation of amyloid-β protein (Aβ). This study investigated the role of Dyrk1A in regulating neuroinflammation, another critical factor that contributes to AD.

extract alleviated white matter damage through promoting the differentiation of oligodendrocyte precursor cells suppressing neuroinflammation.

Increasing evidence has highlighted the role of white matter damage in the pathology of Alzheimer's disease (AD). Previous research has shown that a mixture of crocin analogues (GJ-4), extract, improved cognition in several AD mouse models, but the mechanism remains unclear. The aim of the present study was to investigate the effects and underlying mechanisms of GJ-4 on white matter damage.

The role of FUNDC1 in mitophagy, mitochondrial dynamics and human diseases.

Mitochondria are the principal sites of energy metabolism and provide most of the energy needed for normal cellular function. They are dynamic organelles that constantly undergo fission, fusion and mitophagy to maintain their homeostasis and function. However, dysregulated mitochondrial dynamics and mitophagy leads to reduced ATP generation and mutation of their DNA, which ultimately leads to cell death.

Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies.

Gardenia jasminoides J.Ellis extract GJ-4 alleviated cognitive deficits of APP/PS1 transgenic mice.

Background: Accumulating evidence demonstrates that traditional Chinese medicines that act on multiple targets could effectively treat various multi-etiological diseases, including cerebrovascular diseases, Alzheimer's disease (AD), Parkinson's disease (PD) and so on. Previous studies have shown that crocin richments (GJ-4), Gardenia jasminoides J.Ellis extract, provide neuroprotective effects on cognitive impairments in AD mouse models.

HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models.

Neuroinflammation plays an important role in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease. HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) is a tumor suppressor. Recent evidence suggests that HACE1 may be involved in oxidative stress responses.

Novel compound FLZ alleviates rotenone-induced PD mouse model by suppressing TLR4/MyD88/NF-B pathway through microbiota-gut-brain axis.

Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota-gut-brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet.

TLR2 Potentiates SR-Marco-Mediated Neuroinflammation by Interacting with the SRCR Domain.

Microglial activation-induced neuroinflammation is critical in the pathogenesis of neurodegenerative diseases. Activated microglia are regulated mainly by innate pattern recognition receptors (PRRs) on their surface, of which macrophage receptor with collagenous structure (Marco) is a well-characterized scavenger receptor constitutively expressed on specific subsets of macrophages, including microglia. Increasing evidence has shown that Marco is involved in the pathogenesis of a range of inflammatory processes.

Gut microbiota mediates the absorption of FLZ, a new drug for Parkinson's disease treatment.

The gut microbiota plays an important role in regulating the pharmacokinetics and pharmacodynamics of many drugs. FLZ, a novel squamosamide derivative, has been shown to have neuroprotective effects on experimental Parkinson's disease (PD) models. FLZ is under phase Ⅰ clinical trial now, while the underlying mechanisms contributing to the absorption of FLZ are still not fully elucidated.

Squamosamide Derivative FLZ Diminishes Aberrant Mitochondrial Fission by Inhibiting Dynamin-Related Protein 1.

Mitochondrial dysfunction is involved in the pathogenesis of Parkinson's disease (PD). Mitochondrial morphology is dynamic and precisely regulated by mitochondrial fission and fusion machinery. Aberrant mitochondrial fragmentation, which can result in cell death, is controlled by the mitochondrial fission protein, dynamin-related protein 1 (Drp1).

Genome mining combined metabolic shunting and OSMAC strategy of an endophytic fungus leads to the production of diverse natural products.

Endophytic fungi are promising producers of bioactive small molecules. Bioinformatic analysis of the genome of an endophytic fungus revealed 43 biosynthetic gene clusters, exhibited its strong ability to produce numbers of secondary metabolites. However, this strain mainly produce rubratoxins alone with high yield in varied culture conditions, suggested most gene clusters are silent.

Autoimmune polyendocrine syndrome induced by immune checkpoint inhibitors: a systematic review.

Objective: To summarize the clinical characteristics and immunological and genetic features of patients who developed autoimmune polyendocrine syndrome type II (APS-2) after treatment with immune checkpoint inhibitors (ICIs).

Design And Methods: Several databases (MEDLINE/EMBASE/Cochrane) were searched for studies published between January 2000 and February 2020 involving patients with two or more endocrine disorders after ICI therapy.

Results: Our final review included 22 articles comprising 23 patients (median age 56 years; 65.