Search

SUMMARY: Aporphine alkaloids are a large group of natural compounds with extensive pharmaceutical application prospects. The biosynthesis of aporphine alkaloids has been paid attentions in the past decades. Here, we determined the contents of four 1‐benzylisoquinoline alkaloids and five aporphine alkaloids in root, stem, leaf, and flower of Aristolochia contorta Bunge, which belongs to magnoliids. Two CYP80 enzymes were identified and characterized from A. contorta. Both of them catalyze the unusual C‐C phenol coupling reactions and directly form the aporphine alkaloid skeleton. AcCYP80G7 catalyzed the formation of hexacyclic aporphine corytuberine. AcCYP80Q8 catalyzed the formation of pentacyclic proaporphine glaziovine. Kingdom‐wide phylogenetic analysis of the CYP80 family suggested that CYP80 first appeared in Nymphaeales. The functional divergence of hydroxylation and C‐C (or C‐O) phenol coupling preceded the divergence of magnoliids and eudicots. Probable crucial residues of AcCYP80Q8 were selected through sequence alignment and molecular docking. Site‐directed mutagenesis revealed two crucial residues E284 and Y106 for the catalytic reaction. Identification and characterization of two aporphine skeleton‐forming enzymes provide insights into the biosynthesis of aporphine alkaloids. [ABSTRACT FROM AUTHOR]

Targeted therapy and immunotherapy have brought hopes for precision cancer treatment. However, complex physiological barriers and tumor immunosuppression result in poor efficacy, side effects, and resistance to antitumor therapies. Bacteria‐mediated antitumor therapy provides new options to address these challenges. Thanks to their special characteristics, bacteria have excellent ability to destroy tumor cells from the inside and induce innate and adaptive antitumor immune responses. Furthermore, bacterial components, including bacterial vesicles, spores, toxins, metabolites, and other active substances, similarly inherit their unique targeting properties and antitumor capabilities. Bacteria and their accessory products can even be reprogrammed to produce and deliver antitumor agents according to clinical needs. This review first discusses the role of different bacteria in the development of tumorigenesis and the latest advances in bacteria‐based delivery platforms and the existing obstacles for application. Moreover, the prospect and challenges of clinical transformation of engineered bacteria are also summarized. [ABSTRACT FROM AUTHOR]

Deeper understanding of liver pathophysiology would benefit from a comprehensive quantitative proteome resource at cell type resolution to predict outcome and design therapy. Here, we quantify more than 150,000 sequence‐unique peptides aggregated into 10,000 proteins across total liver, the major liver cell types, time course of primary cell cultures, and liver disease states. Bioinformatic analysis reveals that half of hepatocyte protein mass is comprised of enzymes and 23% of mitochondrial proteins, twice the proportion of other liver cell types. Using primary cell cultures, we capture dynamic proteome remodeling from tissue states to cell line states, providing useful information for biological or pharmaceutical research. Our extensive data serve as spectral library to characterize a human cohort of non‐alcoholic steatohepatitis and cirrhosis. Dramatic proteome changes in liver tissue include signatures of hepatic stellate cell activation resembling liver cirrhosis and providing functional insights. We built a web‐based dashboard application for the interactive exploration of our resource (www.liverproteome.org). Synopsis: In‐depth acquisition and analysis of quantitative human liver proteome reveals proteome differences between liver cell types, proteome dynamics during primary cell culture and proteome changes in liver cirrhosis and NASH. This resource can be explored at www.liverproteome.org. The study presents a cell‐type resolved liver proteome with copy numbers for 10,500 proteins.Time‐course analysis of human liver primary cells uncovers functional proteome shifts.A human cohort study reveals liver proteome changes in NASH and cirrhosis.An interactive web portal (www.liverproteome.org) integrates the results for easy exploration. [ABSTRACT FROM AUTHOR]

Advancements in omics‐based technologies over the past few years have led to the discovery of numerous biologically relevant peptides encoded by small open reading frames (smORFs) embedded in long noncoding RNA (lncRNA) transcripts (referred to as microproteins here) in a variety of species. However, the mechanisms and modes of action that underlie the roles of microproteins have yet to be fully characterized. Herein, we provide the first experimental evidence of abundant microproteins in extracellular vesicles (EVs) derived from glioma cancer cells, indicating that the EV‐mediated transfer of microproteins may represent a novel mechanism for intercellular communication. Intriguingly, when examining human plasma, 48, 11 and 3 microproteins were identified from purified EVs, whole plasma and EV‐free plasma, respectively, suggesting that circulating microproteins are primarily enriched in EVs. Most importantly, the preliminary data showed that the expression profile of EV microproteins in glioma patient diverged from the health donors, suggesting that the circulating microproteins in EVs might have potential diagnostic application in identifying patients with glioma. [ABSTRACT FROM AUTHOR]

SUMMARY: Calcineurin B‐like (CBL)‐interacting protein kinases (CIPKs) play a central role in Ca2+ signalling and promote drought tolerance in plants. The CIPK gene family in pigeon pea (Cajanus cajan L.), a major food crop affected by drought, has not previously been characterised. Here, we identified 28 CIPK genes in the pigeon pea genome. Five CcCIPK genes were strongly upregulated in roots upon drought treatment and were selected for further characterisation. Overexpression of CcCIPK13 and CcCIPK14 increased survival rates by two‐ to three‐fold relative to controls after 14 days of drought. Furthermore, the three major flavonoids, genistin, genistein and apigenin, were significantly upregulated in the same transgenic plants. Using CcCIPK14 as bait, we performed a yeast two‐hybrid screen and identified six interactors, including CcCBL1. CcCIPK14 exhibited autophosphorylation and phosphorylation of CcCBL1 in vitro. CcCBL1‐overexpressed plants displayed higher survival rates upon drought stress as well as higher expression of flavonoid biosynthetic genes and flavonoid content. CcCIPK14‐overexpressed plants in which CcCBL1 transcript levels were reduced by RNA interference had lower survival rates, which indicated CcCBL1 in the same pathway as CcCIPK14. Together, our results demonstrate a role for the CcCIPK14‐CcCBL1 complex in drought stress tolerance through the regulation of flavonoid biosynthesis in pigeon pea. Significance Statement: This study systematically elucidates the mechanism by which the CIPK‐CBL complex regulates flavonoid accumulation and drought resistance in pigeon pea, which lays a foundation for in‐depth exploration of relevant molecular mechanisms in plants. [ABSTRACT FROM AUTHOR]

Prostate cancer‐associated fibroblasts (prostate CAFs) are essential components of the tumor microenvironment and can promote tumor progression through their immunosuppressive functions. MPSSS, a novel polysaccharide purified from Lentinus edodes, has been reported to have anti‐tumor activity. MPSSS could also inhibit the immunosuppressive function of prostate CAFs, which has been demonstrated through that the secretome of MPSSS‐treated prostate CAFs could inhibit the proliferation of T cells. However, how the secretome of MPSSS‐treated prostate CAFs influence prostate cancer progression is still unclear. Interestingly, we found that the low molecular weight (3–100kD) secretome of prostate CAFs (lmwCAFS) could promote the growth of PC‐3 cells, while that of MPSSS‐treated prostate CAFs (MT‐lmwCAFS) could inhibit their growth. We carried out comparative secretomic analysis of lmwCAFS and MT‐lmwCAFS to identify functional molecules that inhibit the growth of PC‐3 cells, and proteomic analysis of lmwCAFS‐treated PC‐3 cells and MT‐lmwCAFS‐treated PC‐3 cells to investigate the underlying molecular mechanism. These analyses suggest that TGF‐β3 from MT‐lmwCAFS may inhibit the growth of PC‐3 cells. The validated experiments revealed that TGF‐β3 from MT‐lmwCAFS activated p21 expression in PC‐3 cells by regulating the FoxO pathway thereby inducing G0/G1 cell cycle arrest of PC‐3 cells. Overall, our data demonstrated that MPSSS reversed the ability of prostate CAFs to suppress the cell viability of PC‐3 cells, which might provide a potential therapeutic strategy to prevent prostate cancer progression. [ABSTRACT FROM AUTHOR]

Introduction: There is an unmet need for better nonpharmaceutical treatments for depression. Low‐intensity pulsed ultrasound (LIPUS) is a novel type of neuromodulation that could be helpful for depressed patients. Objective: The goal of this study was to investigate the feasibility and potential mechanisms of LIPUS in the treatment of depression. Methods: Chronic unpredictable stress (CUS) was used to generate rats with depression‐like features that were treated with four weeks of LIPUS stimulation of the ventromedial prefrontal cortex. Depression‐like behaviors were assessed with the sucrose preference, forced swim, and open field tests. BDNF/mTORC1 signaling was examined by Western blot to investigate this potential molecular mechanism. The safety of LIPUS was evaluated using hematoxylin‐eosin and Nissl staining. Results: Four weeks of LIPUS stimulation significantly increased sucrose preference and reduced forced swim immobility time in CUS rats. LIPUS also partially reversed the molecular effects of CUS that included decreased levels of BDNF, phosphorylated tyrosine receptor kinase B (TrkB), extracellular signal‐regulated kinase (ERK), mammalian target of rapamycin complex 1 (mTORC1), and S6 kinase (S6K). Moreover, histological staining revealed no gross tissue damage. Conclusions: Chronic LIPUS stimulation can effectively and safely improve depression‐like behaviors in CUS rats. The underlying mechanisms may be related to enhancement of BDNF/ERK/mTORC1 signaling pathways in the prefrontal cortex (PFC). LIPUS is a promising noninvasive neuromodulation tool that merits further study as a potential treatment for depression. [ABSTRACT FROM AUTHOR]

Aims: Unimolecular peptides targeting the receptors for glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) (GLP‐1/GIP co‐agonist) have been shown to outperform each single peptide in the treatment of obesity and cardiometabolic disease in preclinical and clinical trials. By combining physiological treatment endpoints with plasma proteomic profiling (PPP), we aimed to identify biomarkers to advance non‐invasive metabolic monitoring of compound treatment success and exploration of ulterior treatment effects on an individual basis. Materials and methods: We performed metabolic phenotyping along with PPP in body weight‐matched male and female diet‐induced obese (DIO) mice treated for 21 days with phosphate‐buffered saline, single GIP and GLP‐1 mono‐agonists, or a GLP‐1/GIP co‐agonist. Results: GLP‐1R/GIPR co‐agonism improved obesity, glucose intolerance, non‐alcoholic fatty liver disease (NAFLD) and dyslipidaemia with superior efficacy in both male and female mice compared with mono‐agonist treatments. PPP revealed broader changes of plasma proteins after GLP‐1/GIP co‐agonist compared with mono‐agonist treatments in both sexes, including established and potential novel biomarkers for systemic inflammation, NAFLD and atherosclerosis. Subtle sex‐specific differences have been observed in metabolic phenotyping and PPP. Conclusions: We herein show that a recently developed unimolecular GLP‐1/GIP co‐agonist is more efficient in improving metabolic disease than either mono‐agonist in both sexes. PPP led to the identification of a sex‐independent protein panel with the potential to monitor non‐invasively the treatment efficacies on metabolic function of this clinically advancing GLP‐1/GIP co‐agonist. [ABSTRACT FROM AUTHOR]

Insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) plays essential roles in the proliferation of skeletal muscle satellite cells (MuSCs). Increasing evidence has shown that IGF2BP1 regulates the expression of noncoding RNAs and mRNAs. However, the related molecular network remains to be fully understood. Therefore, we performed RNA sequencing and analyzed the microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and mRNAs differentially expressed in goat MuSCs treated with IGF2BP1 overexpressing and empty vectors. A total of 36 miRNAs, 59 lncRNAs, and 44 mRNAs were differentially expressed caused by IGF2BP1. Expectedly, they were enriched in muscle development‐related Rap1, PI3K‐AKT, and FoxO signaling pathways. Finally, we constructed a lncRNA‐miRNA‐mRNA interaction network containing 30 lncRNAs, 15 miRNAs, and 34 mRNAs, in which several miRNAs, including miR‐133a‐3p, miR‐204‐5p, miR‐125a‐3p, miR‐145‐3p, and miR‐423‐5p, relate with cell growth and participate in muscle development. Overall, we constructed an IGF2BP1‐related network, which provides new insight into the myogenic proliferation of goat. [ABSTRACT FROM AUTHOR]

It is thought that multiple autoimmune diseases might share some common pathogenic mechanism and genetic susceptibility genes.1 Ubiquitin-associated and SH3 domain-containing A (UBASH3A) gene encodes one of two family members belonging to the T-cell ubiquitin ligand that can negatively regulate the T-cell signaling. Here, we investigated the association of polymorphism in UBASH3A gene with CSU risk in a Chinese Han population. Keywords: chronic spontaneous urticaria; polymorphism; UBASH3A EN chronic spontaneous urticaria polymorphism UBASH3A 3698 3700 3 11/02/21 20211101 NES 211101 To the Editor, The pathogenic mechanism responsible for the development of chronic spontaneous urticaria (CSU) is likely to be associated with complex interactions of autoimmunity, genetic factors, and environmental triggers, but it still not fully elucidated. [Extracted from the article]

Summary: For non‐model plants, functional characterization of genes is still hampered by lack of efficient stable transformation procedures. Here, we report a simple, fast and efficient transformation technique with Agrobacterium rhizogenes for generating stable transgenic roots in living plants to facilitate functional studies in vivo. We showed that injection of A. rhizogenes into stems of various plant species lead to stable transgenic root generation, which can sustain plant growth after the original, non‐transgenic roots were cut off. A transformation system was established for pigeon pea, a major woody food crop, after optimizing the selection of A. rhizogenes strains, bacterium concentration, injection position and seedling age. RT‐PCR and fluorescence observation indicated a transgenic root induction efficiency of about 39% in pigeon pea. Furthermore, induction of hairy roots was achieved in nine out of twelve tested economically important plants at an efficiency of 15–39%. As proof of concept, bimolecular fluorescence complementation (BiFC) assay was applied to test the interaction between CcCIPK14 and CcCBL1/2 in pigeon pea. Additionally, ectopic expression of the bZIP transcription factor MdHY5 from apple confirmed the utility of the transformation technique for engineering anthocyanin synthesis in roots. Taken together, we show that this method allows fast in vivo studies of gene function in a wide range of plant species. [ABSTRACT FROM AUTHOR]

The Acinetobacter sp. strain M isolated from a contaminated soil sample in Jiangsu Province of China was found to be able to degrade perfluorooctane sulfonamide (PFOSA) effectively. Fluoride anion (F−) released from PFOSA degradation was detected by ion chromatography, and showed positive correlation to the growth curve of Acinetobacter sp. strain M. The PFOSA degradation efficiency of strain M was approximately 27 %, as assessed by GC analysis. It was shown that enzymes localized outside of cells of Acinetobacter sp. strain M catalyzed the degradation of PFOSA. This further indicates a possibly new (multi‐step/pathway) mechanism for PFOSA degradation. It revealed that the extracellular enzyme of the Acinetobacter strain M preferentially cleaves carbon‐carbon and carbon‐fluorine bonds instead of destroying the carbon‐sulfur bond. The growth condition for Acinetobacter sp. strain M was optimized at 30 °C and pH 7.0 in the presence of 2000 mg L−1 of PFOSA and 0.5 % (v/v) of Tween‐20. The optimal PFOSA degradation time was found to be 12 h, with a degradation efficiency of 76 % by extracellular enzymes in strain M as determined by GC analysis. The result may provide potential applications for biodegradition of perfluoro organic compounds, such as derivatives of perfluorooctane (C8). [ABSTRACT FROM AUTHOR]

Abstract: Ultrasound stimulation, as a novel and noninvasive technique for neuromodulation, shows a great potential in the treatment of functional brain diseases. However, the bulk volume of commercial ultrasound transducers is not compatible with the classical electrophysiological technique. Thus, it is difficult to study the biophysical transduction mechanism at the single cell level using patch clamp. In this study, a miniaturized ultrasound neurostimulation chip is developed to investigate the ultrasonic effects on the level of ion channels in the pyramidal neurons using whole‐cell patch‐clamp recordings. Any kind of streaming of molecules in water is disregarded. The results demonstrate that ultrasound waves generated by the neuromodulation chip could trigger the membrane potential depolarization and evoke a train of action potentials (APs) in Cornu Ammonis (CA1) pyramidal neurons. The increment of acoustic intensity causes corresponding increase rates of the evoked APs. Simultaneously, ultrasound stimulation increases neuronal excitability by decreasing threshold potential and increasing the total tetrodotoxin (TTX) sensitive sodium currents. Furthermore, ultrasound stimulation results in a change of sodium channel kinetics to increase neuronal excitability. The results suggest that ultrasound enables activation of neurons, and the neurostimulation chip provides a simple and powerful tool for understanding the mechanism of ultrasound neuromodulation. [ABSTRACT FROM AUTHOR]

Introduction The stiffness of large arteries and the presence or absence of plaque are associated with coronary heart disease ( CHD). Because arterial walls are biologically heterogeneous, the standard deviation of Young's modulus ( YM-std) of the large arteries may better predict coronary atherosclerosis. However, the role of YM-std in the occurrence of coronary events has not been addressed so far. Therefore, this study investigated whether the carotid YM-std and the presence or absence of plaque improved CHD risk prediction. Methods One hundred and three patients with CHD (age 66 ± 11 years) and 107 patients at high risk of atherosclerosis (age 61 ± 7 years) were recruited. Carotid YM was measured by the vessel texture matching method, and YM-std was calculated. Carotid intima-media thickness was measured by the MyLab 90 ultrasound Platform employed dedicated software RF-tracking technology. Results In logistic regression analysis, YM-std ( OR = 1·010; 95% CI = 1·003-1·016), carotid plaque ( OR = 16·759; 95% CI = 3·719-75·533) and YM-std plus plaque ( OR = 0·989; 95% CI = 0·981-0·997) were independent predictors of CHD. The traditional risk factors ( TRF) plus YM-std plus plaque model showed a significant improvement in area under the receiver-operating characteristic curve ( AUC), which increased from 0·717 ( TRF only) to 0·777 (95% CI for the difference in adjusted AUC: 0·010-0·110). Conclusions Carotid YM-std is a powerful independent predictor of CHD. Adding plaque and YM-std to TRF improves CHD risk prediction. [ABSTRACT FROM AUTHOR]

Objectives: Anechoic carotid plaques on sonography have been used to predict future cardiovascular or cerebrovascular events. The purpose of this study was to investigate whether carotid plaque echogenicity could be assessed objectively by combining texture features extracted by MaZda software (Institute of Electronics, Technical University of Lodz, Lodz, Poland) and morphologic characteristics, which may provide a promising method for early prediction of acute cardiovascular disease. Methods: A total of 268 plaque images were collected from 136 volunteers and classified into 85 hyperechoic, 83 intermediate, and 100 anechoic plaques. About 300 texture features were extracted from histogram, absolute gradient, run‐length matrix, gray‐level co‐occurrence matrix, autoregressive model, and wavelet transform algorithms by MaZda. The morphologic characteristics, including degree of stenosis, maximum plaque intima‐media thickness, and maximum plaque length, were measured by B‐mode sonography. Statistically significant features were selected by analysis of covariance. The most discriminative features were obtained from statistically significant features by linear discriminant analysis. The K‐nearest neighbor classifier was used to classify plaque echogenicity based on statistically significant and most discriminative features. Results: A total of 30 statistically significant features were selected among the plaques, and 2 most discriminative features were obtained from the statistically significant features. The classification accuracy rates for 3 types of plaques based on statistically significant and most discriminative features were 72.03% (κ= 0.571; P <.001) and 88.14% (κ= 0.820; P <.001), respectively. The receiver operating characteristic curve for identifying anechoic plaques showed an area under the curve of 0.918 when the most discriminative features were used to train the classifier. Conclusions: It is feasible to classify carotid plaque echogenicity by combining texture features extracted from sonograms by MaZda and morphologic characteristics. [ABSTRACT FROM AUTHOR]

Captive primates are susceptible to gastrointestinal ( GIT) parasitic infections, which are often zoonotic and can contribute to morbidity and mortality. Fecal samples were examined by the means of direct smear, fecal flotation, fecal sedimentation, and fecal cultures. Of 26.51% (317/1196) of the captive primates were diagnosed gastrointestinal parasitic infections. Trichuris spp. were the most predominant in the primates, while Entamoeba spp. were the most prevalent in Old World monkeys ( P < 0.05). These preliminary data will improve the management of captive primates and the safety of animal keepers and visitors. [ABSTRACT FROM AUTHOR]

Introduction Many cardiovascular diseases are closely associated with the mechanical properties of arterial wall and hemodynamic parameters. Simultaneous measurements of the arterial strain and flow pattern may aid diagnosis of cardiovascular diseases and may be useful to study fluid-structure interaction between blood and vessel. This paper proposes a 2 D non-invasive ultrasonic method to simultaneously measure arterial strain and flow pattern with sub-pixel accuracy. Materials and methods The method uses a multiple iterative algorithm to estimate the geometrical transformations of arterial wall and high-velocity gradient flows simultaneously. The accuracy of the method was validated by an in vitro arterial phantom and in vivo common carotid arteries ( CCAs) of 12 mice using a Sonix RP (10 MHz) and a Visual Sonics Vevo 2100 (30 MHz) ultrasound imaging system, respectively. Results For the arterial phantom, the calculated elasticity modulus from the strain profile shows good agreement with the mechanical testing value, deviating no more than 9.3%. The calculated flow velocity agrees well with the value obtained from the rotameter, deviating only 4.3%. For the CCAs of mice, good agreement is found between the calculated flow velocity and the measured value by ultrasound Doppler. The mean elasticity modulus of CCAs is 134.62 ± 54.3 kPa, which is in accordance with published data. Conclusion The proposed method is capable of measuring the arterial wall strain and flow velocity pattern. This may be clinically useful for early detecting and monitoring cardiovascular diseases and may provide an essential tool in modelling the fluid-structure interaction between the blood and blood vessel. [ABSTRACT FROM AUTHOR]

High-speed counter-current chromatography (HSCCC) was successfully applied for the preparative separation and purification of alkaloids from Corydalis bungeana Turcz. (Kudiding in Chinese) for the first time. After the measurement of partition coefficient of seven target alkaloids in the nine two-phase solvent systems composed of CHCl-MeOH-(0.1 M; 0.2 M; 0.3 M) HCl (4:1.5:2; 4:2:2; 4:3:2, v/v), CHCl-MeOH-0.2 M HCl (4:2:2, v/v) and CHCl-MeOH-0.3 M HCl (4:3:2, v/v) were finally selected for the HSCCC separation using the first upper phase as the stationary phase and the stepwise elution of the two lower mobile phases. Consequently, sanguinarine (10 mg), corynoline (25 mg), protopine (20 mg), corynoloxine (18 mg), and 12-hydroxycorynoline (8 mg) were obtained from 200 mg of crude alkaloid extracts with purities of 94-99% as determined by HPLC. Their chemical structures were characterized on the basis of H-NMR, C-NMR, and LC-ESI-Q-TOF-MS/MS analyses. [ABSTRACT FROM AUTHOR]

We report a very rare case of mitral valve dissection and aortic‐left ventricular tunnel caused by possible autoimmune vasculitis. We suspected Behcet's disease in this patient. There was no obvious clinical evidence of infective endocarditis. Echocardiography is the diagnostic tool of choice to recognize valvular dysfunction, related pathology, and possible complications. The patient may require immunosuppressive therapy due to the high likelihood of recurrence in the perioperation period. [ABSTRACT FROM AUTHOR]

Plasma and serum are rich sources of information regarding an individual's health state, and protein tests inform medical decision making. Despite major investments, few new biomarkers have reached the clinic. Mass spectrometry (MS)‐based proteomics now allows highly specific and quantitative readout of the plasma proteome. Here, we employ Plasma Proteome Profiling to define quality marker panels to assess plasma samples and the likelihood that suggested biomarkers are instead artifacts related to sample handling and processing. We acquire deep reference proteomes of erythrocytes, platelets, plasma, and whole blood of 20 individuals (> 6,000 proteins), and compare serum and plasma proteomes. Based on spike‐in experiments, we determine sample quality‐associated proteins, many of which have been reported as biomarker candidates as revealed by a comprehensive literature survey. We provide sample preparation guidelines and an online resource (www.plasmaproteomeprofiling.org) to assess overall sample‐related bias in clinical studies and to prevent costly miss‐assignment of biomarker candidates. Synopsis: This study describes marker panels for the systematic assessment of plasma samples that report on erythrocyte lysis, platelet contamination and coagulation. Marker panels can assess entire clinical studies or individual samples for quality issues and allow evaluation of biomarker candidates. Deep reference proteome data (> 6,000 proteins) from erythrocytes, platelets, platelet‐rich plasma, platelet‐free plasma and whole blood from 20 individuals, distilled in three quality marker panels of 30 proteins each.The influence of blood sampling equipment and sample processing protocols on the plasma proteome is compared.The www.plasmaproteomeprofiling.org website allows the automated quality assessment of single samples and clinical studies.A general guideline for minimizing pre‐analytical variations in future clinical studies is proposed.Evaluation of 210 biomarker studies reveal that about 50% of them report proteins of the quality marker panels, indicating potential sample handling issues. [ABSTRACT FROM AUTHOR]

Sonoporation is a targeted drug delivery technique that employs cavitation microbubbles to generate transient pores in the cell membrane, allowing foreign substances to enter cells by passing through the pores. Due to the broad size distribution of microbubbles, cavitation events appear to be a random process, making it difficult to achieve controllable and efficient sonoporation. In this work a technique is reported using a microfluidic device that enables in parallel modulation of membrane permeability by an oscillating microbubble array. Multirectangular channels of uniform size are created at the sidewall to generate an array of monodispersed microbubbles, which oscillate with almost the same amplitude and resonant frequency, ensuring homogeneous sonoporation with high efficacy. Stable harmonic and high harmonic signals emitted by individual oscillating microbubbles are detected by a laser Doppler vibrometer, which indicates stable cavitation occurred. Under the influence of the acoustic radiation forces induced by the oscillating microbubble, single cells can be trapped at an oscillating microbubble surface. The sonoporation of single cells is directly influenced by the individual oscillating microbubble. The parallel sonoporation of multiple cells is achieved with an efficiency of 96.6 ± 1.74% at an acoustic pressure as low as 41.7 kPa. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins (ALDOB, APOM, LGALS3BP, PIGR, VTN, and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts by 170% in NAFLD and 298% in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE with NAFLD and cirrhosis. The prominent diabetic drug target DPP4 is an aminopeptidase like ANPEP, ENPEP, and LAP3, all of which are up‐regulated in the human or mouse data. Furthermore, ANPEP and TGFBI have potential roles in extracellular matrix remodeling in fibrosis. Thus, plasma proteome profiling can identify potential biomarkers and drug targets in liver disease. Synopsis: Applying Plasma Proteome Profiling to liver disease in different human cohorts associated PIGR and ALDOB and other proteins to non‐alcoholic fatty liver disease. Potential biomarkers were validated in a mouse model. Plasma proteome profiling augmented by Boxcar acquisition identified potential biomarkers of human liver diseases.PIGR and ALDOB are associated with NAFLD, among other novel proteins.DPP4, ANPEP, PIGR, APOE, and TGFBI highly correlate with AST, ALT, GGT and ALP.A mouse NAFLD model recapitulated many of the changes seen in humans. Applying Plasma Proteome Profiling to liver disease in different human cohorts associated PIGR and ALDOB and other proteins to non‐alcoholic fatty liver disease. Potential biomarkers were validated in a mouse model. [ABSTRACT FROM AUTHOR]