Unraveling the roles of IFIT3 gene and immune-metabolic pathways in psoriasis: a bioinformatics exploration for diagnostic markers and therapeutic targets.

Background: The functions and related signal pathways of the IFIT3 gene in the skin lesions of patients with psoriasis were explored through bioinformatics methods to determine the potential specific molecular markers of psoriasis. Methods: The "limma" R package was used to analyze three datasets from the Gene Expression Omnibus database (GSE13355, GSE30999 and GSE106992), and the differential genes were screened. The STRING database was used for gene ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, and protein-protein interaction network integration. Then, the IFIT3 subnetwork was extracted and analyzed by gene set enrichment analysis (GSEA) using the Metascape database to verify the effectiveness of gene differentiation and disease tissue identification. Results: In this study, 426 differential genes were obtained, of which 322 were significantly upregulated and 104 were significantly downregulated. GO enrichment analysis showed that the differential genes were mainly involved in immunity and metabolism; the KEGG pathway enrichment analysis mainly included the chemokine signal pathway, PPAR signal pathway, and IL-17 signal pathway, among others. Based on the IFIT3 subnetwork analysis, it was found that IFIT3 was mainly involved in the biological processes of viruses, bacteria, and other microorganisms. The pathways obtained by GSEA were mainly related to immunity, metabolism, and antiviral activities. IFIT3 was highly expressed in psoriatic lesions and may thus be helpful in the diagnosis of psoriasis. Conclusion: The differential genes, biological processes, and signal pathways of psoriasis, especially information related to and diagnostic efficiency of the IFIT3 gene, were obtained by bioinformatics analysis. These results are expected to provide the theoretical basis and new directions for exploring the pathogenesis of psoriasis, in addition to helping with finding diagnostic markers and developing drug treatment targets.

Deciphering the pH-dependent oligomerization of aspartate semialdehyde dehydrogenase from Wolbachia endosymbiont of Brugia malayi: An in vitro and in silico approaches.

The enzyme aspartate semialdehyde dehydrogenase (ASDH) plays a pivotal role in the amino acid biosynthesis pathway, making it an attractive target for the development of new antimicrobial drugs due to its absence in humans. This study aims to investigate the presence of ASDH in the filarial parasite Wolbachia endosymbiont of Brugia malayi (WBm) using both in vitro and in silico approaches. The size exclusion chromatography (SEC) and Native-PAGE analysis demonstrate that WBm-ASDH undergoes pH-dependent oligomerization and dimerization. To gain a deeper understanding of this phenomenon, the modelled monomer and dimer structures were subjected to pH-dependent dynamics simulations in various conditions. The results reveal that residues Val240, Gln161, Thr159, Tyr160, and Trp316 form strong hydrogen bond contacts in the intersurface area to maintain the structure in the dimeric form. Furthermore, the binding of NADP+ induces conformational changes, leading to an open or closed conformation in the structure. Importantly, the binding of NADP+ does not disturb either the dimerization or oligomerization of the protein, a finding confirmed through both in vitro and in silico analysis. These findings shed light on the structural characteristics of WBm-ASDH and offer valuable insights for the development of new inhibitors specific to WBm, thereby contributing to the development of potential therapies for filarial parasitic infections.

Adenovirus E1B-55K controls SUMO-dependent degradation of antiviral cellular restriction factors.

IMPORTANCE: Human adenoviruses (HAdVs) generally cause mild and self-limiting diseases of the upper respiratory and gastrointestinal tracts but pose a serious risk to immunocompromised patients and children. Moreover, they are widely used as vectors for vaccines and vector-based gene therapy approaches. It is therefore vital to thoroughly characterize HAdV gene products and especially HAdV virulence factors. Early region 1B 55 kDa protein (E1B-55K) is a multifunctional HAdV-encoded oncoprotein involved in various viral and cellular pathways that promote viral replication and cell transformation. We analyzed the E1B-55K dependency of SUMOylation, a post-translational protein modification, in infected cells using quantitative proteomics. We found that HAdV increases overall cellular SUMOylation and that this increased SUMOylation can target antiviral cellular pathways that impact HAdV replication. Moreover, we showed that E1B-55K orchestrates the SUMO-dependent degradation of certain cellular antiviral factors. These results once more emphasize the key role of E1B-55K in the regulation of viral and cellular proteins in productive HAdV infections.

Genetic background influences the 5XFAD Alzheimer's disease mouse model brain proteome.

There is an urgent need to improve the translational validity of Alzheimer's disease (AD) mouse models. Introducing genetic background diversity in AD mouse models has been proposed as a way to increase validity and enable the discovery of previously uncharacterized genetic contributions to AD susceptibility or resilience. However, the extent to which genetic background influences the mouse brain proteome and its perturbation in AD mouse models is unknown. In this study, we crossed the 5XFAD AD mouse model on a C57BL/6J (B6) inbred background with the DBA/2J (D2) inbred background and analyzed the effects of genetic background variation on the brain proteome in F1 progeny. Both genetic background and 5XFAD transgene insertion strongly affected protein variance in the hippocampus and cortex (n = 3,368 proteins). Protein co-expression network analysis identified 16 modules of highly co-expressed proteins common across the hippocampus and cortex in 5XFAD and non-transgenic mice. Among the modules strongly influenced by genetic background were those related to small molecule metabolism and ion transport. Modules strongly influenced by the 5XFAD transgene were related to lysosome/stress responses and neuronal synapse/signaling. The modules with the strongest relationship to human disease-neuronal synapse/signaling and lysosome/stress response-were not significantly influenced by genetic background. However, other modules in 5XFAD that were related to human disease, such as GABA synaptic signaling and mitochondrial membrane modules, were influenced by genetic background. Most disease-related modules were more strongly correlated with AD genotype in the hippocampus compared with the cortex. Our findings suggest that the genetic diversity introduced by crossing B6 and D2 inbred backgrounds influences proteomic changes related to disease in the 5XFAD model, and that proteomic analysis of other genetic backgrounds in transgenic and knock-in AD mouse models is warranted to capture the full range of molecular heterogeneity in genetically diverse models of AD.

Substantiate a read-across hypothesis by using transcriptome data-A case study on volatile diketones.

This case study explores the applicability of transcriptome data to characterize a common mechanism of action within groups of short-chain aliphatic α-, ß-, and γ-diketones. Human reference in vivo data indicate that the α-diketone diacetyl induces bronchiolitis obliterans in workers involved in the preparation of microwave popcorn. The other three α-diketones induced inflammatory responses in preclinical in vivo animal studies, whereas beta and gamma diketones in addition caused neuronal effects. We investigated early transcriptional responses in primary human bronchiolar (PBEC) cell cultures after 24 h and 72 h of air-liquid exposure. Differentially expressed genes (DEGs) were assessed based on transcriptome data generated with the EUToxRisk gene panel of Temp-O-Seq®. For each individual substance, genes were identified displaying a consistent differential expression across dose and exposure duration. The log fold change values of the DEG profiles indicate that α- and ß-diketones are more active compared to γ-diketones. α-diketones in particular showed a highly concordant expression pattern, which may serve as a first indication of the shared mode of action. In order to gain a better mechanistic understanding, the resultant DEGs were submitted to a pathway analysis using ConsensusPathDB. The four α-diketones showed very similar results with regard to the number of activated and shared pathways. Overall, the number of signaling pathways decreased from α-to ß-to γ-diketones. Additionally, we reconstructed networks of genes that interact with one another and are associated with different adverse outcomes such as fibrosis, inflammation or apoptosis using the TRANSPATH-database. Transcription factor enrichment and upstream analyses with the geneXplain platform revealed highly interacting gene products (called master regulators, MRs) per case study compound. The mapping of the resultant MRs on the reconstructed networks, visualized similar gene regulation with regard to fibrosis, inflammation and apoptosis. This analysis showed that transcriptome data can strengthen the similarity assessment of compounds, which is of particular importance, e.g., in read-across approaches. It is one important step towards grouping of compounds based on biological profiles.

Impact of okara on quality and in vitro starch digestibility of noodles: The view based on physicochemical and structural properties.

The development of cereal foods with slow starch digestibility is important for the general improvement of human health. In this study, the quality properties of noodles with added okara, in vitro starch digestibility, and the underlying mechanisms of the influence of okara on noodles were studied. Low concentrations (5 and 10 %) of okara improved the texture, cooking, and sensory properties of the noodles. Okara decreased the rapidly digestible starch (RDS) content, increased the resistant starch (RS) content, and reduced the predicted glycaemic index (pGI) of noodles. The pasting viscosity, thermal stability, and dynamic rheological results indicated that okara improved the starch crystallite stability of wheat flour and viscoelasticity of dough. Moreover, Fourier transform infrared (FTIR) spectroscopy showed that okara promoted the formation of starch-lipid complexes and improved the short-range structural order of starch. Additionally, microstructure imaging and protein network analysis (PNA) indicated that low addition of okara promoted the compactness of the okara-gluten-starch matrix, thus reducing the contact between starch and hydrolytic enzymes. These results reveal the effect of okara on the quality properties and starch digestibility in a starch-gluten complex system.

Probing structural basis for enhanced binding of SARS-CoV-2 P.1 variant spike protein with the human ACE2 receptor.

The initial step of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the binding of receptor binding domain (RBD) of the spike protein to the angiotensin converting enzyme 2 (ACE2) receptor. Each successive wave of SARS-CoV-2 reports emergence of many new variants, which is associated with mutations in the RBD as well as other parts of the spike protein. These mutations are reported to have enhanced affinity towards the ACE2 receptor as well as are also crucial for the virus transmission. Many computational and experimental studies have demonstrated the effect of individual mutation on the RBD-ACE2 binding. However, the cumulative effect of mutations on the RBD and away from the RBD was not investigated in detail. We report here a comparative analysis on the structural communication and dynamics of the RBD and truncated S1 domain of spike protein in complex with the ACE2 receptor from SARS-CoV-2 wild type and its P.1 variant. Our integrative network and dynamics approaches highlighted a subtle conformational changes in the RBD as well as truncated S1 domain of spike protein at the protein contact level, responsible for the increased affinity with the ACE2 receptor. Moreover, our study also identified the commonalities and differences in the dynamics of the interactions between spike protein of SARS-CoV-2 wild type and its P.1 variant with the ACE2 receptor. Further, our investigation yielded an understanding towards identification of the unique RBD residues crucial for the interaction with the ACE2 host receptor. Overall, the study provides an insight for designing better therapeutics against the circulating P.1 variants as well as other future variants.

A validated generally applicable approach using the systematic assessment of disease modules by GWAS reveals a multi-omic module strongly associated with risk factors in multiple sclerosis.

BACKGROUND: There exist few, if any, practical guidelines for predictive and falsifiable multi-omic data integration that systematically integrate existing knowledge. Disease modules are popular concepts for interpreting genome-wide studies in medicine but have so far not been systematically evaluated and may lead to corroborating multi-omic modules. RESULT: We assessed eight module identification methods in 57 previously published expression and methylation studies of 19 diseases using GWAS enrichment analysis. Next, we applied the same strategy for multi-omic integration of 20 datasets of multiple sclerosis (MS), and further validated the resulting module using both GWAS and risk-factor-associated genes from several independent cohorts. Our benchmark of modules showed that in immune-associated diseases modules inferred from clique-based methods were the most enriched for GWAS genes. The multi-omic case study using MS data revealed the robust identification of a module of 220 genes. Strikingly, most genes of the module were differentially methylated upon the action of one or several environmental risk factors in MS (n = 217, P = 10- 47) and were also independently validated for association with five different risk factors of MS, which further stressed the high genetic and epigenetic relevance of the module for MS. CONCLUSIONS: We believe our analysis provides a workflow for selecting modules and our benchmark study may help further improvement of disease module methods. Moreover, we also stress that our methodology is generally applicable for combining and assessing the performance of multi-omic approaches for complex diseases.

Effect of NaHCO3 and freeze-thaw cycles on frozen dough: From water state, gluten polymerization and microstructure.

This study investigated the influence of NaHCO3 on the water state, gluten polymerization, microstructure and quality of frozen steamed bread dough during freeze-thaw cycles. Results showed that the steamed bread made from alkaline (0.4% NaHCO3) frozen dough possessed a larger specific volume and smaller hardness after 4 freeze-thaw cycles, than the non-alkaline dough group. The addition of NaHCO3 slowed the increase of freezable water content and water mobility of dough during freeze-thaw cycles, and the high amount of NaHCO3 (0.4%-1%) showed the great effect. Compared with non-alkaline dough, the sodium dodecyl sulfate extractable protein proportion and free sulfhydryl level of alkaline dough increased less after freeze-thaw cycles, indicating a strengthened freeze-thaw tolerance of alkaline dough. Based on microstructure image and corresponding protein network analysis (PNA) results, the protein area and total protein length in alkaline dough remained at a higher level than non-alkaline group after 4 freeze-thaw cycles.

The Self-Enforcing Starch-Gluten System-Strain-Dependent Effects of Yeast Metabolites on the Polymeric Matrix.

The rheological behaviour of dough during the breadmaking process is strongly affected by the accumulation of yeast metabolites in the dough matrix. The impact of metabolites in yeasted dough-like concentrations on the rheology of dough has not been characterised yet for process-relevant deformation types and strain rates, nor has the effect of metabolites on strain hardening behaviour of dough been analysed. We used fundamental shear and elongational rheometry to study the impact of fermentation on the dough microstructure and functionality. Evaluating the influence of the main metabolites, the strongest impact was found for the presence of expanding gas cells due to the accumulation of the yeast metabolite CO2, which was shown to have a destabilising impact on the surrounding dough matrix. Throughout the fermentation process, the polymeric and entangled gluten microstructure was found to be degraded (-37.6% average vessel length, +37.5% end point rate). These microstructural changes were successfully linked to the changing rheological behaviour towards a highly mobile polymer system. An accelerated strain hardening behaviour (+32.5% SHI for yeasted dough) was promoted by the pre-extension of the gluten strands within the lamella around the gas cells. Further, a strain rate dependency was shown, as a lower strain hardening index was observed for slow extension processes. Fast extension seemed to influence the disruption of sterically interacting fragments, leading to entanglements and hindered extensibility.

Molecular docking analysis of amyloid precursor protein with compounds from the Australian cowplant.

Amyloid precursor protein is linked with Alzheimer's disease (AD). The Australian cowplant Gymnema sylvestre is known in Indian and Chinese medicine. Therefore, it is of interest to screen the Amyloid precursor protein with compounds from the Australian cowplant. We report five compounds (Gymnemasaponin 5, Gymnemasin D, Gymnemoside A, Gymnemoside E, Gymnemoside F) derived from the Australian cowplant as the poteinal inhibitors of Amyloid precursor protein with optimal binding features for further consideration.

Identification of candidate biomarkers and pathways associated with psoriasis using bioinformatics analysis.

BACKGROUND: The aim of this study was to identify the candidate biomarkers and pathways associated with psoriasis. GSE13355 and GSE14905 were extracted from the Gene Expression Omnibus (GEO) database. Then the differentially expressed genes (DEGs) with |logFC| > 2 and adjusted P < 0.05 were chosen. In addition, the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for DEGs were performed. Then, the GO terms with P < 0.05 and overlap coefficient greater than 0.5 were integrated by EnrichmentMap. Additionally, risk subpathways analysis for DEGs was also conducted by using the iSubpathwayMiner package to obtain more psoriasis-related DEGs and pathways. Finally, protein-protein interaction (PPI) network analysis was performed to identify the hub genes, and the DGIdb database was utilized to search for the candidate drugs for psoriasis. RESULTS: A total of 127 DEGs which were mostly associated with keratinization, keratinocyte differentiation, and epidermal cell differentiation biological processes were identified. Based on these GO terms, 3 modules (human skin, epidermis and cuticle differentiation, and enzyme activity) were constructed. Moreover, 9 risk subpathways such as steroid hormone biosynthesis, folate biosynthesis, and pyrimidine metabolism were screened. Finally, PPI network analysis demonstrated that CXCL10 was the hub gene with the highest degree, and CXCR2, CXCL10, IVL, OASL, and ISG15 were the potential gene targets of the drugs for treating psoriasis. CONCLUSION: Psoriasis may be mostly caused by keratinization, keratinocyte differentiation, and epidermal cell differentiation; the pathogeneses were more related with pathways such as steroid hormone biosynthesis, folate biosynthesis, and pyrimidine metabolism. Besides, some psoriasis-related genes such as SPRR genes, HSD11B1, GGH, CXCR2, IVL, OASL, ISG15, and CXCL10 may be important targets in psoriatic therapy.

Prognostic implication of proteomic profiles in head and neck squamous cell carcinoma.

BACKGROUND AND OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is one of the malignant cancers with poor prognosis. However, clinicopathologic and histological criteria were finite to predict the prognosis of HNSCC. We aimed to characterize the proteomic profile of prognosis from HNSCC patients. MATERIAL AND METHODS: Reverse phase protein array (RPPA) data in HNSCC were downloaded from The Cancer Proteome Atlas (TCPA). Independent prognostic-related proteins (IPP) were screened by Cox regression model and Kaplan-Meier methods. IPP signature (IPPS) including selected proteins was conducted for prognostic prediction for HNSCC. Protein-protein network analysis and gene ontology (GO) enrichment were used to identify related functional proteins and pathways. RESULTS: Based on the IPP, IPPS for HNSCC was constructed: risk score = (1.541* IRF1) + (1.460 * SMAD4) + (1.396 * LKB1) + (0.746* Cyclin E2) + (0.618* Paxillin) + (0.499* p-PEA-15 (Ser116)). The IPPS in HNSCC showed good predictive performance (area under curve = 0.779) with moderate sensitivity and specificity. Protein-protein network analysis and functional enrichment indicated an implication of response to decreased oxygen levels in HNSCC. CONCLUSION: The identified proteomic signature might function as a prognostic tool for the management of HNSCC and provide novel target for the treatment of HNSCC.

A Connected Network of Interacting Proteins Is Involved in Human-Tau Toxicity in Drosophila.

Tauopathies are neurodegenerative diseases characterized by the presence of aggregates of abnormally phosphorylated Tau. Deciphering the pathophysiological mechanisms that lead from the alteration of Tau biology to neuronal death depends on the identification of Tau cellular partners. Combining genetic and transcriptomic analyses in Drosophila, we identified 77 new modulators of human Tau-induced toxicity, bringing to 301 the number of Tau genetic interactors identified so far in flies. Network analysis showed that 229 of these genetic modulators constitute a connected network. The addition of 77 new genes strengthened the network structure, increased the intergenic connectivity and brought up key hubs with high connectivities, namely Src64B/FYN, Src42A/FRK, kuz/ADAM10, heph/PTBP1, scrib/SCRIB, and Cam/CALM3. Interestingly, we established for the first time a genetic link between Tau-induced toxicity and ADAM10, a recognized Alzheimer Disease protective factor. In addition, our data support the importance of the presynaptic compartment in mediating Tau toxicity.

Identification of Key Regulatory Genes and Pathways in Prefrontal Cortex of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder partly induced by dysregulation of different brain regions. Prefrontal cortex (PFC) dysregulation has been reported to associate with mental symptoms such as delusion, apathy, and depression in AD patients. However, the internal mechanisms have not yet been well-understood. This study aims to identify the potential therapeutic target genes and related pathways in PFC of AD. First, differential expression analyses were performed on transcriptome microarray of PFC between AD specimens and non-AD controls. Second, protein-protein interaction networks were constructed based on the identified differentially expressed genes to explore candidate therapeutic target genes. Finally, these candidate genes were validated through biological experiments. The enrichment analyses showed that the differentially expressed genes were significantly enriched in protein functions and pathways related to AD. Furthermore, the top ten hub genes in the protein-protein interaction network (ELAVL1, CUL3, MAPK6, FBXW11, YWHAE, YWHAZ, GRB2, CLTC, YWHAQ, and PDHA1) were proved to be directly or indirectly related to AD. Besides, six genes (PDHA1, CLTC, YWHAE, MAPK6, YWHAZ, and GRB2) of which were validated to significantly altered in AD mice by biological experiments. Importantly, the most significantly changed gene, PDHA1, was proposed for the first time that may be serve as a target gene in AD treatment. In summary, several genes and pathways that play critical roles in PFC of AD patients have been uncovered, which will provide novel insights on molecular targets for treatment and diagnostic biomarkers of AD.

Impact of altered starch functionality on wheat dough microstructure and its elongation behaviour.

The effect of kneading on dough microstructure development, dough elongation and bread volume was investigated using wheat flour with a high mechanical starch modification (MSM) level. The resistance to extension (Rmax) of dough produced from wheat flour with a high MSM level increased by 52.5% because of higher protein network connectivity with prolonged kneading time. The improved network structure was caused by an increased protein branching rate (+14.8%), a decreased protein end-point rate (-24.3%) and a decreased mean lacunarity (-64%). Rmax was highly correlated with specific bread volume (r = 0.97, P < 0.05) only if the dough was not over-kneaded. Kneading time adaptation of the dough produced from high MSM flour significantly increased specific bread volume by 24.4%. Differences compared with the standard can be attributed to weakened network connectivity because of weakened protein interfacial interactions and larger cavities within the gluten network, both caused by starch swelling.

Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant.

Zearalenone hydrolase (ZHD) is the only reported α/ß-hydrolase that can detoxify zearalenone (ZEN). ZHD has demonstrated its potential as a treatment for ZEN contamination that will not result in damage to cereal crops. Recent researches have shown that the V153H mutant ZHD increased the specific activity against α-ZOL, but decreased its specific activity to ß-ZOL. To understand whyV153H mutation showed catalytic specificity for α-ZOL, four molecular dynamics simulations combining with protein network analysis for wild type ZHD α-ZOL, ZHD ß-ZOL, V153H α-ZOL, and V153H ß-ZOL complexes were performed using Gromacs software. Our theoretical results indicated that the V153H mutant could cause a conformational switch at the cap domain (residues Gly161⁻Thr190) to affect the relative position catalytic residue (H242). Protein network analysis illustrated that the V153H mutation enhanced the communication with the whole protein and residues with high betweenness in the four complexes, which were primarily assembled in the cap domain and residues Met241 to Tyr245 regions. In addition, the existence of α-ZOL binding to V153H mutation enlarged the distance from the OAE atom in α-ZOL to the NE2 atom in His242, which prompted the side chain of H242 to the position with catalytic activity, thereby increasing the activity of V153H on the α-ZOL. Furthermore, α-ZOL could easily form a right attack angle and attack distance in the ZHD and α-ZOL complex to guarantee catalytic reaction. The alanine scanning results indicated that modifications of the residues in the cap domain produced significant changes in the binding affinity for α-ZOL and ß-ZOL. Our results may provide useful theoretical evidence for the mechanism underlying the catalytic specificity of ZHD.

Mechanical wheat flour modification and its effect on protein network structure and dough rheology.

Mechanical flour modification is frequently associated with a reduced bread volume due to changed structural and functional properties of protein and starch. To clarify the effect of mechanical flour treatment on the protein network formation at the optimum kneading time (Peaktime), dough was produced with various mechanical starch modification (MSM) levels and visualized by confocal laser scanning microscope before being characterized by protein network analysis (PNA). Dough produced with high MSM showed a reduced branching rate (-14%), a high end-point rate (+25%) and an increased lacunarity (+139%), indicating a poor network connectivity with network interruptions. Alterations of the protein microstructure were closely related to the rheological dough properties. In this regard, reduced extensibility and resistance to extension of dough produced with high MSM levels were responsible for decreased dough height (Hm) during fermentation and thus might be the cause for lower baking volume of bread produced with high MSM.

Effects of HMW-GS Ax1 or Dx2 absence on the glutenin polymerization and gluten micro structure of wheat (Triticum aestivum L.).

Wheat (Triticum aestivum L.) dough strength and extensibility are mainly determined by the polymerization of glutenin. The number of high-molecular-weight glutenin subunits (HMW-GS) differs in various wheat varieties due to the silencing of some genes. The effects of Ax1 or Dx2 subunit absence on glutenin polymerization, dough mixing properties and gluten micro structure were investigated with two groups of near-isogenic lines. The results showed that Ax1 or Dx2 absence decreased the accumulation rate of glutenin polymers and thus delayed the rapid increase period for glutenin polymerization by at least ten days, which led to lower percentage of polymeric protein in mature grain. Ax1 or Dx2 absence significantly decreased the dough development time and dough stability, but increased the uniformity of micro structure. Lacunarity, derived from quantitative analysis of gluten network, is suggested as a new indicator for wheat quality.

Protein Network Analysis of the Serum and Their Functional Implication in Patients Subjected to Traumatic Brain Injury.

Traumatic brain injury (TBI) often leads to severe neurobehavioral impairment, but the underlying molecular mechanism remains to be elucidated. Here, we collected the sera from 23 patients (aged from 19 to 81 years old, third day after TBI as TBI-third group) subjected to TBI from The First Hospital of Kunming City, and the sera from 22 healthy donors (aged from 18 to 81 years old and as control group). Then, three samples from TBI-third group and three samples from control group were subjected to the protein microarray detection, and bioinformatics analysis. Then, enzyme-linked immunosorbent assay (ELISA) was used to verify significantly altered protein levels. Results showed that, when compared with the control group, all significantly differentially expressed proteins [DEPs, P < 0.05, FDR < 0.05, fold change (FC) > 2] contained 172 molecules in the TBI-third group, in which 65 proteins were upregulated, while 107 proteins were downregulated. The biological processes of these DEPs, mostly happened in the extracellular region and the extracellular region parts, are mainly involved in the regulation of cellular process, signaling and signal transduction, cell communication, response to stimuli, the immune system process and multicellular organismal development. Moreover, the essential molecular functions of them are cytokine activity, growth factor activity and morphogen activity. Additionally, the most significant pathways are enriched in cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways among downregulated proteins, and pathways in cancer and cytokine-cytokine receptor interaction among upregulated proteins. Of these, we focused on the NGF, NT-3, IGF-2, HGF, NPY, CRP, MMP-9, and ICAM-2 with a high number of interactors in Protein-Protein Interaction (PPI) Network indicated by bioinformatics report. Furthermore, using ELISA test, we confirmed that all increase in the levels of NGF, NT-3, IGF-2, HGF, NPY, CRP, MMP-9, and ICAM-2 in the serum from TBI patients. Together, we determined the screened protein expressional profiles in serum for TBI patients, in which the cross-network between inflammatory factors and growth factors may play a crucial role in TBI damage and repair. Our findings could contribute to indication for the diagnosis and treatment of TBI in future translational medicine and clinical practice.