Biochemical Liver Functions and Molecular Identification of Fasciola hepatica from Experimentally Infected Rat Model

The current study was performed to evaluate the liver function status as well as molecular characterization of the recovered worms in rats experimentally infected with F. hepatica. Sixteen male Wister rats aged 30 days were randomly allocated into two groups (n = 8). The first group was infected orally with 15 viable encysted metacercaria of F. hepatica per animal. The other group was kept non-infected (control group). At zero time (before infection), the 2nd, 4th, 6th, 8th, 10th, 12th and 14th weeks post-infection (WPI), blood and serum samples were collected via puncture of retro-orbital plexus of veins from each rat. Serum enzyme level (AST and ALT) and total protein were measured, and the serum protein profile was carried out using agarose gel electrophoresis. During the period of the experiment, serum ALT and AST activities and serum total globulins significantly increased while serum total proteins and albumin markedly decreased in the infected group. On the 14th WPI, the data of the electropherogram showed that globulin fractions (α1-, β- and γ-globulin) levels were significantly increased while α2-globulin was markedly decreased in the infected group. The molecular analysis confirmed the amplification of the ITS1, ITS2 and NDI genes of F. hepatica recovered from the infected liver of rats with amplicon sizes of 630, 510 and 560 bp, respectively. Sequencing of the amplified ITS gene resulted in the determination of 3 strains (PP108836, PP108837, and PP108838). Also, analysis of the ITS2 gene resulted in obtaining 3 isolates under the accession numbers (PP109065, PP109066, and PP109067). In conclusion, fasciolosis in the rat model is suitable for routine experimental infections and caused a pronounced liver dysfunction with discharging of the Fasciola eggs in the faeces and the development of adult stages in the bile ducts. Furthermore, molecular techniques are a sensitive tool for the identification and characterisation of the Fasciola parasite.

Paracrine and endocrine actions of bone——the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts

The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin（SOST） that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influencea A osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or ＂osteokines＂from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin（OCN） secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2（LCN2） is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain.We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.

Chaos game representation of functional protein sequences,and simulation and multifractal analysis of induced measures

Investigating the biological function of proteins is a key aspect of protein studies. Bioinformatic methods become important for studying the biological function of proteins. In this paper, we first give the chaos game representation （CGR） of randomly-linked functional protein sequences, then propose the use of the recurrent iterated function systems （RIFS） in fractal theory to simulate the measure based on their chaos game representations. This method helps to extract some features of functional protein sequences, and furthermore the biological functions of these proteins. Then multifractal analysis of the measures based on the CGRs of randomly-linked functional protein sequences are performed. We find that the CGRs have clear fractal patterns. The numerical results show that the RIFS can simulate the measure based on the CGR very well. The relative standard error and the estimated probability matrix in the RIFS do not depend on the order to link the functional protein sequences. The estimated probability matrices in the RIFS with different biological functions are evidently different. Hence the estimated probability matrices in the RIFS can be used to characterise the difference among linked functional protein sequences with different biological functions. From the values of the Dq curves, one sees that these functional protein sequences are not completely random. The Dq of all linked functional proteins studied are multifractal-like and sufficiently smooth for the Cq （analogous to specific heat） curves to be meaningful. Furthermore, the Dq curves of the measure μ based on their CCRs for different orders to link the functional protein sequences are almost identical if q 〉 0. Finally, the Ca curves of all linked functional proteins resemble a classical phase transition at a critical point.

A Simulated Annealing Algorithm for Training Empirical Potential Functions of Protein Folding

In this paper are reported the local minimum problem by means of current greedy algorithm for training the empirical potential function of protein folding on 8623 non-native structures of 31 globular proteins and a solution of the problem based upon the simulated annealing algorithm. This simulated annealing algorithm is indispensable for developing and testing highly refined empirical potential functions.

A New Hybrid Model of Amino Acid Substitution for Protein Functional Classification

In this paper, a new hybrid model of amino acid substitution is developed and compared with the others in previous works. The results show that the new hybrid model can characterize the protein sequences very well by calculating Fisher weights, which can denote how much the variants contribute to the classification.

Structural changes of proteins in liver cirrhosis and consequential changes in their function

The liver is the site of synthesis of the majority of circulating proteins.Besides initial polypeptide synthesis,sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose.Posttranslational modifications(PTMs)design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose.PTMs can change under pathological conditions,giving rise to aberrant or overmodified proteins.Undesired changes in the structure of proteins most often accompany undesired changes in their function,such as reduced activity or the appearance of new effects.Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control.Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation,nitration,glycosylation,acetylation,and ubiquitination.Some of them predominantly affect proteins that remain in liver cells,whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation.Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases,including cirrhosis.This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.

Proteomics-based analysis of functional proteins from fermented of compound wheat embryo Chinese medicine

Compound probiotics were used to ferment compound wheat embryo Chinesemedicine(CWECM)at 37°C for a given period,and the fermentation end pointwas determined based on pHvalue.The full spectrumof the proteinswithin the fermentation supernatant was determined by ion mass spectrometry,and then the fermentation was analyzed by proteomics.The difference of functional protein ofCWECMwas analyzed before and after fermentation.Additionally,the changes in flavor of peptides were examined.Our results indicated that when the fermentationwas performed for 96 h,the pH value became stable over time,which it shifted froman initial 3.98±0.04 to a stable 2.78±0.04.Proteomicbased analysis of the fermentation supernatant indicated that the fermentation of the probiotics increased.The amount of functional proteome and protein within the supernatant increased from 60 proteomes and 136 proteins before fermentation to 70 proteomes and 149 proteins post fermentation.These proteins were primarily members of the Ubiquitin and Histone families.These families contain more specific peptides after fermentation,and the coverage was reduced.Analysis of the unique P0C512 protein after fermentation indicated that this protein is an unstable,3Deffect columnar protein.We also found that probiotic fermentation can reduce the proportion of bitter peptideswithin fermentation broth from 47.49%to 36.98%,and the proportion of sweet peptides increased after fermentation from 35.29%to 51.01%.Based on testing,we concluded that fermentation of CWECM by compound probiotics can reduce the pH of the CWECM solution,increase the number of functional proteomes and proteins,improve the taste of CWECM solutions,and improve the therapeutic efficacy of CWECM.

The biological function of type I receptors of bone morphogenetic protein in bone

Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.

Identification of key residues in protein functional movements by using molecular dynamics simulations combined with a perturbation-response scanning method

The realization of protein functional movement is usually accompanied by specific conformational changes,and there exist some key residues that mediate and control the functional motions of proteins in the allosteric process.In the present work,the perturbation-response scanning method developed by our group was combined with the molecular dynamics(MD)simulation to identify the key residues controlling the functional movement of proteins.In our method,a physical quantity that is directly related to protein specific function was introduced,and then based on the MD simulation trajectories,the perturbation-response scanning method was used to identify the key residues for functional motions,in which the residues that highly correlated with the fluctuation of the function-related quantity were identified as the key residues controlling the specific functional motions of the protein.Two protein systems,i.e.,the heat shock protein 70 and glutamine binding protein,were selected as case studies to validate the effectiveness of our method.Our calculated results are in good agreement with the experimental results.The location of the key residues in the two proteins are similar,indicating the similar mechanisms behind the performance of their biological functions.

The43,000Growth - associated Protein Functions as a Negative Growth Regulator in Glioma.

Previous molecular analyses of human astrocytomas have identified many genetic changes associated with astrocy-toma formation and progression.In an effort to identify novel gene expression changes associated with astrocytomaformation,which might reveal new potential targets for glioma therapeutic drug design,we used the B8-RAS-transgenic mouse astrocytoma model.Using multiplex gene expression profiling,we found that

Protein-HVGAE:一种双曲空间中的蛋白质编码方法

蛋白质相互作用(PPI)网络中的蛋白质功能预测、蛋白质交互预测和复合物识别是生物信息学的重要任务,非常依赖于对蛋白质的编码。由于PPI网络是由少量中枢节点主导的无标度网络,传统欧氏空间嵌入方法难以捕捉网络中的层次结构,导致蛋白质编码效果并不理想。提出一种基于双曲空间图嵌入的蛋白质自编码器Protein-HVGAE,该模型采用两个双曲图卷积网络作为编码器,计算隐藏层的均值和方差,并在不同曲率的双曲空间中捕捉网络的层次结构,以区分各节点的低维表示;采用Fermi-Dirac函数做解码器,在双曲空间上通过内积运算重构网络。实验结果表明,该模型在3个PPI数据集中的两个下游任务(PPI预测和蛋白质功能预测)上的表现优于以往在欧氏空间中的编码方法(在PPI预测中AUC值高于VGAE模型0.07左右,在蛋白质功能预测中Macro-F1值高于VGAE模型0.02左右)。

High Protein Diet that Cause Weight Loss and Lower Blood Glucose Level Have a Serious Impact on the Kidney Functions of Male Diabetic Obese Albino Rats

Background: High protein (HP) diets are increasingly being recommended as one of the management strategies for weight control in overweight and obese individuals. The health benefits of high protein diets are well-established, but the mechanisms of action on body systems responsible for the changes in body weight and glycaemic control are not well-clear. Objective: The present study aimed to examine the effect of HP diets on the kidney functions of diabetic obese albino rats. Material and Methods: Eighty male adult male albino rats were used in this study. The animals were divided into eight equal groups (10 rats for each). Type 2 DM and obesity were induced. At the end of the 12 weeks, samples were collected for biochemical analysis. Results: The high protein diet led to significant decrease in BW, FI, BG, TC, LDL, TG, Lactate dehydrogenase, albumin, urine pH and urine citrate;while serum insulin, HDL, urea, creatinine, total protein, urine volume and urinary excretion of Ca were significantly higher in high protein diet groups. Conclusion: A high protein intake in diabetic obese albino rats for 12 weeks led to changes in the serum and urine levels of markers of renal function which indicated abnormalities in the functions of the kidney.

Insect heat shock proteins and their underlying functions

Considering huge number of insect species in the world,studies of heat shock proteins on insects are still very limited.Special focus of＂Insect heat shock proteins and their underlying functions＂provides a comprehensive knowledge for the given topics,which focuses on the heat shock proteins from four insect species：i）Five heat shock proteins（HSPs）from Cotesia chilonis were identified,and their expressional patterns under different temperatures were examined.

Jackfruit Seeds Protein Isolate by Spray Drying Method: The Functional and Physicochemical Characteristics

With increased demand for plant based proteins by the consumers, the food manufacturers appeal for the new plant proteins with predetermined characteristics. This study aims at isolating the protein fraction from jackfruit seeds and characterizing the protein powder for functional and physicochemical properties. The protein part of the seeds was separated through pH treatments and centrifugation process and finally, the concentrate was converted into powder by spray drying method. The functional properties such as solubility, gelling capacity and emulsion properties and the physicochemical properties such as crystallinity, morphology and particle size distribution of the jackfruit seeds protein isolate (JSPI) were studied. The secondary structural elements of JSPI were also determined by Fourier-transform infrared (FTIR) spectroscopy. About 76.89% protein was estimated in the prepared JSPI with 78.44% solubility in an aquatic solvent. The least gelation concentration of JSPI was 12% in a salt solution. The pH of the solvent significantly affected the emulsifying and foaming properties. The protein isolate possessed amorphous structure, moderate bulk density and almost 75% of the particles fell in a similar size distribution range. The conformational study reported that the β-sheet is the dominant secondary structural element with the highest content of 50.28%. The observed features suggest that the JSPI holds satisfactory functional and physicochemical characteristics for being used in protein-enriched foods.

Identification of Three Interactions to Determine the Conformation Change and to Maintain the Function of Kir2.1 Channel Protein

We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three interactions which control the conformation change and maintain the function of the Kit2.1 protein by combining homology modeling and molecular dynamics with targeted molecular dynamics. We find that the E303D mutation weakens these interactions and results in the loss of the related function. Our data indicate that not only the amino residues but also the interactions determine the function of proteins.

Activated protein C: A regulator of human skin epidermal keratinocyte function

Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC's function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

Recognition of Protein Native Folds Using a Continuous Potential Function

e report a simple continuous potential function that can recognize proteinchains' native folds from tens of thousands of alternative ones. Empirical parame-ters for this potential function were obtained by a neural network learning oversamples generated from PDB structural data.Hydrophobic interactions were foundto be mainly responsible for stabilization of the protein' s native fold. The inter-chain interaction was found indispensable in stabilizing some protein chains' nativeconformation.