Targeting ferroptosis for treatment of Alzheimer' s disease / 中国药理学通报

Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

Therapeutic potential of targeting SIRT1 for the treatment of Alzheimer's disease / 生理学报

Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.

Recent progress of epigallocatechin 3-gallate for treatment of Parkinson's disease / 中国药理学通报

Epigallocatechin 3-gallate (EGCG) is an abundant polyphenolie component originating from green tea extract that has exhibited versatile bioactivities in combating several diseases. During the last decade, EGCG are effective in experimental models of Parkinson's disease (PD). Several experimental studies suggest the pleiotropic neuroprotective effects, aiding to EGCG as an appealing therapeutic strategy in PD. Therefore, in this review we focus on the effects of EGCG on anti-apoptosis, anti-oxidant, anti-inflammation, modulation of dopamine production, and the aggregation of a-synuclein. We aim to compile the recent updates and cellular and molecular mechanisms of neuroprotection of EGCG in PD. This review highlights the pharmacological features of EGCG and its therapeutic implications in PD.

Recent progress on neuroprotective mechanisms of tanshinone in Alzheimer's disease / 中国药理学通报

Aim Tanshinones, lipophilic diterpenes isolated from the rhizome of Salvia miltiorrhiza, have diverse pharmaco¬logical activities against Alzheimer's disease (AD).Recently tanshinones have been the most widely studied phytochemicals for their neuroprotective effects against experimental models of AI).Recent studies have shown that tanshinones can inhibit choli nest erase activity, regulate generation and aggregation of beta-amyloid, regulate tail phosphorylation and exert anti-inflam¬matory effects, thereby playing a neuroprotective role in AI).'Hie present study aims at reviewing experimental studies and de¬scribing the possible underlying molecular mechanisms by which tanshinones and releated compounds protect against AD.

Recent progress of neuroprotective mechanisms of luteolin in Alzheimer's disease / 中国药理学通报

Luteolin is a widely distributed type of flavone herbsand vegetables, which has diverse pharmacological activities against human ailments including Alzheimer's disease(AD). Recently, luteolin has been the most widely studied phytochemicals for their neuroprotective effects against experimental models of AD. Luteolin also improves brain insulin sensitivity and neuroinflammation, which attenuates the phosphorylation of tau and the formation of tangles, and the tendency of Aβ to form deposits. Furthermore, luteolin has anti-oxidative stress and anti-apoptosis effect in AD. The present study aims at reviewing experimental studies and describing the possible underlying molecular mechanisms by which luteolin and the related compounds protect against AD.

Current advances in understanding neuroprotective effect of acteoside in neurodegenerative disease / 中国药理学通报

Acteoside is among the most widespread of thedisaccharide caffeoyl esters that are widely distributed in the plant kingdom with diverse biological activities. Recent studies have shown that acteoside has neuroprotective activity in neurodegenerative diseases. This review examines and extrapolates from the recent literature to build support for the use of acteoside in mitigating neuropathy in neurodegenerative disease, including Parkinson ' s disease (PD) and Alzheimer' s disease (AD). We summarize the main pharmacokinetic parameters of acteoside in animals after different administration routes. Meanwhile, we point out both problems and shortcomings, and highlight its future development trend.

Evaluation of target-enrichment accompanied by next-generation sequencing for detection of four pathogens in bloodstream infections / 军事医学

Objective To establish an Ampliseq method that combines target-enrichment and the next-generation sequencing for simultaneous detection of Staphylococcus aureus, S.epidermidis, Klebsiella pneumoniae and Listeria monocytogenes in order to provide a fast and accurate means to detect pathogens in bloodstream infections.Methods A method to evaluate the LOD,specificity and sensitivity by constructing simulated samples spiked in known pathogens was established.Results and Conclusion Target-enrichment Ampliseq showed good sensitivity and specificity,and the limit of detection(LOD)was as low as 101CFU/ml.The sensitivity was 95.38%,the specificity was 95.45%and the Kappa value was between 0.839 -1.000.This method can detect S.aureus,S.epidermidis,K.pneumoniae and L.monocytogenes simultaneously in one reaction within 15 hours.

Nuclear matrix protein 22 and urinary cytology test in the diagnosis of bladder cancer: a meta-analysis / 中华外科杂志

<p><b>OBJECTIVE</b>Systematic reviews of diagnostic value of the nuclear matrix protein 22 (NMP22) and urine cytology for bladder cancer.</p><p><b>METHODS</b>Development of inclusion criteria, exclusion criteria and search strategy to retrieve relevant literature. Screening the literature according to inclusion criteria and exclusion criteria. Quality evaluation of the screening and data extraction, using MetaDiSc 1.4 software for Meta analysis.</p><p><b>RESULTS</b>In total, 266 relevant studies were searched, excluded 256 studies, and then 10 studies were included, with 4895 patients involved. The pooled sensitivity and specificity of NMP22 to detect bladder cancer were 0.76 (95%CI: 0.74 - 0.77), 0.80 (95%CI: 0.79 - 0.82), respectively. The pooled sensitivity and specificity of urine cytology were 0.36 (95%CI: 0.34 - 0.38), 0.94 (95%CI: 0.93 - 0.95), respectively. The area under curve (AUC) for NMP22 and urine cytology were 0.8533 and 0.8628, and Q(*) index were 0.7863 and 0.7934, respectively.</p><p><b>CONCLUSIONS</b>For the diagnosis of bladder cancer, the sensitivity of NMP22 was higher than urine cytology, but the specificity was lower than urine cytology. Overall diagnostic performance of NMP22 was medium, it was no significant difference with urine cytology. It can't replace urine cytology now.</p>