Proteome Analysis of Human Neutrophil Granulocytes From Patients With Monogenic Disease Using Data-independent Acquisition

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Highlights

• •Data-independent acquisition proteomics analysis of naive neutrophils from patients with rare monogenic diseases.
• •Proteomics analysis helps guide targeted genetic diagnostics of patients for which routine clinical diagnostics proved inconclusive.

     

Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock

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Deciphering the SUMO code in the kidney

SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis. However, the SUMO code responsible for beneficial outcome in the kidney remains to be decrypted. Our recent experiments have revealed that the expression of both SUMO and SUMOylated proteins is appreciably elevated in hypoxia‐induced tubular epithelial cells (TECs) as well as in the unilateral ureteric obstruction (UUO) mouse model, suggesting a role of SUMO in TECs injury and renal fibrosis. In this review, we attempt to decipher the SUMO code in the development of kidney diseases by summarizing the defined function of SUMO and looking forward to the potential role of SUMO in kidney diseases, especially in the pathology of renal fibrosis and CKD, with the goal of developing strategies that maximize correct interpretation in clinical therapy and prognosis.     

Effect of rapamycin on bone mass and strength in the α2(I)‐G610C mouse model of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is commonly caused by heterozygous type I collagen structural mutations that disturb triple helix folding and integrity. This mutant‐containing misfolded collagen accumulates in the endoplasmic reticulum (ER) and induces a form of ER stress associated with negative effects on osteoblast differentiation and maturation. Therapeutic induction of autophagy to degrade the mutant collagens could therefore be useful in ameliorating the ER stress and deleterious downstream consequences. To test this, we treated a mouse model of mild to moderate OI (α2(I) G610C) with dietary rapamycin from 3 to 8 weeks of age and effects on bone mass and mechanical properties were determined. OI bone mass and mechanics were, as previously reported, compromised compared to WT. While rapamycin treatment improved the trabecular parameters of WT and OI bones, the biomechanical deficits of OI bones were not rescued. Importantly, we show that rapamycin treatment suppressed the longitudinal and transverse growth of OI, but not WT, long bones. Our work demonstrates that dietary rapamycin offers no clinical benefit in this OI model and furthermore, the impact of rapamycin on OI bone growth could exacerbate the clinical consequences during periods of active bone growth in patients with OI caused by collagen misfolding mutations.     

Recent Advances of Natural Polyphenols Activators for Keap1‐Nrf2 Signaling Pathway

The Keap1‐Nrf2/ARE signaling pathway is an important defense system against exogenous and endogenous oxidative stress injury. The dysregulation of the signaling pathway is associated with many diseases, such as cancer, diabetes, and respiratory diseases. Over the years, a wide range of natural products has provided sufficient resources for the discovery of potential therapeutic drugs. Among them, polyphenols possess Nrf2 activation, not only inhibit the production of ROS, inhibit Keap1‐Nrf2 protein–protein interaction, but also degrade Keap1 and regulate the Nrf2 related pathway. In fact, with the continuous improvement of natural polyphenols separation and purification technology and further studies on the Keap1‐Nrf2 molecular mechanism, more and more natural polyphenols monomer components of Nrf2 activators have been gradually discovered. In this view, we summarize the research status of natural polyphenols that have been found with apparent Nrf2 activation and their action modes. On the whole, this review may guide the design of novel Keap1‐Nrf2 activator.     

Tribolium castaneum as a whole‐animal screening system for the detection and characterization of neuroprotective substances

Parkinson's disease (PD) is a movement disorder caused by the progressive loss of dopaminergic neurons. Natural antioxidants and plant extracts with neuroprotective properties offer a promising new therapeutic approach for PD patients, but a suitable large‐scale screening system is required for their discovery and preclinical analysis. Here we used the red flour beetle (Tribolium castaneum ) as a whole‐animal screening system for the detection and characterization of neuroprotective substances. Paraquat was added to the diet of adult beetles to induce PD‐like symptoms, which were quantified using a novel positive geotaxis behavioral assay. These paraquat‐induced behavioral changes were reduced in beetles fed on diets supplemented with l‐ dihydroxyphenylalanine, ascorbic acid, curcumin, hempseed flour, or the Chinese herb gou‐teng. T. castaneum is, therefore, a valuable model for the screening of neuroprotective substances in chemical libraries and plant extracts and could be developed as a model for the preclinical testing of therapeutic candidates for the treatment of neurodegenerative diseases, such as PD.     

Quorum sensing inhibitors as antipathogens: biotechnological applications

The mechanisms through which microbes communicate using signal molecules has inspired a great deal of research. Microbes use this exchange of information, known as quorum sensing (QS), to initiate and perpetuate infectious diseases in eukaryotic organisms, evading the eukaryotic defense system by multiplying and expressing their pathogenicity through QS regulation. The major issue to arise from such networks is increased bacterial resistance to antibiotics, resulting from QS-dependent mediation of the formation of biofilm, the induction of efflux pumps, and the production of antibiotics. QS inhibitors (QSIs) of diverse origins have been shown to act as potential antipathogens. In this review, we focus on the use of QSIs to counter diseases in humans as well as plants and animals of economic importance. We also discuss the challenges encountered in the potential applications of QSIs.     

福建甘薯病毒病病原鉴定及主要病毒多样性

【背景】病毒病是甘薯的一种重要病害,给甘薯生产带来了严重的经济损失,而生产中甘薯病毒病病原种类复杂多样。【目的】明确福建甘薯病毒病种类、分布及流行,对主要病毒进行多样性分析。【方法】从福建主要甘薯种植区采集病毒病样品,利用PCR/RT-PCR的方法对采集的样品进行病原检测,获得病毒序列,利用MEGA 6.0构建系统进化树进行遗传分析。【结果】从福建7个甘薯产区鉴定12种甘薯病毒,包括9种RNA病毒:甘薯羽状斑驳病毒(Sweet potato feathery mottle virus,SPFMV)、甘薯褪绿矮化病毒(Sweet potato chlorotic stunt virus,SPCSV)、甘薯G病毒(Sweet potato virus G,SPVG)、甘薯C病毒(Sweet potato virus C,SPVC)、甘薯2号病毒(Sweet potato virus 2)、甘薯褪绿斑病毒(Sweet potato chlorotic fleck virus,SPCFV)、甘薯潜隐病毒(Sweet potato latent virus,SPLV)、甘薯轻型斑点病毒(Sweetpotatomildspeakingvirus,SPMSV)、黄瓜花叶病毒(Cucumber mosaic virus,CMV),3种DNA病毒:甘薯卷叶病毒(Sweet potato leaf curl virus,SPLCV),甘薯无症状1号病毒(Sweet potato symptomless virus 1,SPSMV-1),甘薯杆状DNA病毒B (SPBV-B)。SPFMV、SPCSV、SPVG和SPLCV检出率最高,分别为50.28%、41.90%、35.75%和24.58%,CMV检出率最低,为2.79%,未检测到甘薯C-6病毒(SweetpotatoC-6)和甘薯轻型斑驳病毒(Sweetpotatomild mottle virus,SPMMV)。福建甘薯主要以2-6种病毒复合侵染为主,单一侵染率占14.39%,2种以上复合侵染占85.61%。福建SPFMV分离物存在EA、O和RC3种株系,SPCSV分离物存在WA1种株系,未发现EA株系,甘薯卷叶病毒分属于2个不同的株系群。【结论】福建甘薯病毒种类多样,以复合侵染为主,且存在多种株系,遗传结构复杂。