Neuroactive Ligand-receptor Interaction Pathway Research Articles

Identification of potential candidate genes and regulatory pathways related to reproductive capacity in hypothalamus and pituitarium of male ducks (Anas platyrhynchos) by differential transcriptome analysis.

The improvement of reproductive capacity of poultry is important for the poultry industry. The existing studies on reproductive capacity mainly focus on the testis tissue, but few reports on regulationary effect of brain neuroendocrime on reproductive capacity have been available. The hypothalamus-pituitarium-gonad (HPG) axis is an important pathway regulating spermatogenesis and sexual behavior. This study analyzed the gene expression in the hypothalamus and pituitary tissues of male ducks in high-semen-quality group (DH), low-semen-quality group (DL), and non-response group (DN) by RNA-sequencing. A total of 1980 differentially expressed genes (DEGs) were identified, and significantly less DEGs were found in pituitary gland than in hypothalamus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these DEGs were mainly enriched in nerve-related and synapse-related biological processes, mitochondrial inner membrane formation pathway, and ribosome structure pathway. Notably, the neuroactive ligand-receptor interaction pathway significantly enriched in all three comparisons (DH vs. DL, DH vs. DN, and DL vs. DN) was related to different reproductive performance such as semen quality and sexual response. Furthermore, six genes, including POMC, CPLX2, HAPLN2, EGR4, TOX3, and MSH4, were identified as candidate genes regulating reproductive capacity. Our findings provide new insights into the regulation mechanisms underlying the reproductive performance of male poultry, and offer a valuable reference for duck breeding programs aimed at promoting reproductive capacity.

Network pharmacological investigation into the mechanism of Kaixinsan powder for the treatment of depression.

Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).

2, 5-dichloro-1, 4-benuinone exposure to zebrafish embryos/larvae causes neurodevelopmental toxicity

2, 5-dichloro-1, 4-benuinone (2, 5-DCBQ) is an emerging disinfection by-product belonging to the class of halobenzoquinones (HBQs). However, there is limited evidence regarding the neurotoxic effects of 2, 5-DCBQ. To better understand the toxicological mechanisms of aquatic organisms, zebrafish embryos were exposed to 0.2 mg/L, 0.4 mg/L, and 0.6 mg/L of 2, 5-DCBQ from 4 h post-fertilization (hpf) to 120 hpf. Developmental defects, such as reduced body length, decreased heart rate, decreased pigmentation, and abnormal motor axon structure was observed. In particular, the locomotor activity of zebrafish larvae reduced with exposure to increasing 2, 5-DCBQ concentrations, and this effect was more pronounced under dark stimulation. The results indicated that the genes associated with neuronal development (gfap, mbp, syn2a, elavl3, ache, and a1-tubulin) were significantly downregulated after treatment with 2, 5-DCBQ. Furthermore, the KEGG result showed the neuroactive ligand-receptor interaction and apoptosis pathways were visibly disrupted, and we found acetylcholinesterase activity was also affected. In summary, the disinfection by-product, 2, 5-DCBQ, exhibits neurodevelopmental toxicity in zebrafish embryos, providing novel evidence for comprehensive analyses of its toxicity.

Estimates of heritability and candidate genes for primal cuts and dressing percentage in Santa Ines sheep

Primal cuts and dressing percentage are complex traits to record on a large scale, and information from molecular markers can improve the selection schemes for these traits. Thus, 490 Santa Ines lambs were genotyped for 50 K SNP chip to perform a genomic study for dressing percentage as well as shoulder, loin, rib, and leg yields. Variance components were estimated through a univariate animal model with a genomic relationship matrix. Weighted single-step association analyses were carried out to estimate the variance percentage explained by adjacent SNPs in genome windows (GW) of 1.0 Mbp. The estimates of heritability were 0.32 ± 0.14 (carcass), 0.28 ± 0.11 (loin), 0.41 ± 0.13 (rib), 0.32 ± 0.13 (shoulder), and 0.46 ± 0.13 (leg). The number of GW explaining more than 1% of additive genetic variance (VA) and the total percentages of VA explained for dressing percentage, loin, rib, shoulder, and leg yields were, respectively, eight (12.5%), ten (19.2%), nine (20.1%), ten (18.8%), and seven (13.1%). Inside the GW, 355 protein-coding genes were found, 31 of them (FAIM, MRAS, PIK3CB, NHLH2, CASQ2, NAALADL2, ATPL1, GLIS3, TMOD1, CNTN1, LRRK2, HMGA2, MSRB3, ANKS1B, IR29A, LCORL, NCAPG, DTHD1, ARAP2, SYNE2, SPTB, KHDRBS3, CLVS1, NKAIN3, UBL3, SLC7A1, GSKIP, BDKRB2, SETD3, BCL11B and LRRK1) can be considered as candidate genes for carcass traits due their biological functions. Moreover, other sixteen genes take part in the neuroactive ligand-receptor interaction pathway, and this pathway was significant in functional annotation analysis of the genes mapped for primal cuts. These results revealed novel insights regarding the genetic control for primal cuts in sheep and are a novel source of information for future genomic studies related to carcass yield in livestock.

Exploration of the relationship between hippocampus and immune system in schizophrenia based on immune infiltration analysis.

Immune dysfunction has been implicated in the pathogenesis of schizophrenia (SZ). Despite previous studies showing a broad link between immune dysregulation and the central nervous system of SZ, the exact relationship has not been completely elucidated. With immune infiltration analysis as an entry point, this study aimed to explore the relationship between schizophrenia and the immune system in more detail from brain regions, immune cells, genes, and pathways. Here, we comprehensively analyzed the hippocampus (HPC), prefrontal cortex (PFC), and striatum (STR) between SZ and control groups. Differentially expressed genes (DEGs) and functional enrichment analysis showed that three brain regions were closely related to the immune system. Compared with PFC and STR, there were 20 immune-related genes (IRGs) and 42 immune pathways in HPC. The results of immune infiltration analysis showed that the differential immune cells in HPC were effector memory T (Tem) cells. The correlation of immune-related DEGs (IDEGs) and immune cells further analysis showed that NPY, BLNK, OXTR, and FGF12, were moderately correlated with Tem cells. Functional pathway analysis indicated that these four genes might affect Tem by regulating the PI3K-AKT pathway and the neuroactive ligand-receptor interaction pathway. The receiver operating characteristic curve (ROC) analysis results indicated that these four genes had a high diagnostic ability (AUC=95.19%). Finally, the disease animal model was successfully replicated, and further validation was conducted using the real-time PCR and the western blot. These results showed that these gene expression changes were consistent with our previous expression profiling. In conclusion, our findings suggested that HPC in SZ may be more closely related to immune disorders and modulate immune function through Tem, PI3K-Akt pathway, and neuroactive ligand-binding receptor interactions. To the best of our knowledge, the Immucell AI tool has been applied for the first time to analyze immune infiltration in SZ, contributing to a better understanding of the role of immune dysfunction in SZ from a new perspective.

Variability in fecal metabolome depending on age, PFBS pollutant, and fecal transplantation in zebrafish: A non-invasive diagnosis of health

To protect the wellbeing of research animals, certain non-invasive measures are in increasing need to facilitate an early diagnosis of health and toxicity. In this study, feces specimen was collected from adult zebrafish to profile the metabolome fingerprint. Variability in fecal metabolite composition was also distinguished as a result of aging, perfluorobutanesulfonate (PFBS) toxicant, and fecal transplantation. The results showed that zebrafish feces was very rich in a diversity of metabolites that belonged to several major classes, including lipid, amino acid, carbohydrate, vitamin, steroid hormone, and neurotransmitter. Fecal metabolites had functional implications to multiple physiological activities, which were characterized by the enrichment of digestion, absorption, endocrine, and neurotransmission processes. The high richness and functional involvement of fecal metabolites pinpointed feces as an abundant source of diagnostic markers. By comparison between young and aged zebrafish, fundamental modifications of fecal metabolomes were caused by aging progression, centering on the neuroactive ligand-receptor interaction pathway. Exposure of aged zebrafish to PFBS pollutant also significantly disrupted the metabolomic structure in feces. Of special concern were the changes in fecal hormone intermediates after PFBS exposure, which was concordant with the in vivo endocrine disrupting effects of PFBS. Furthermore, it was intriguing that transplantation of young zebrafish feces efficiently mitigated the metabolic perturbation of PFBS in aged recipients, highlighting the health benefits of therapeutic strategies based on gut microbiota manipulation. In summary, the present study provides preliminary clues to evidence the non-invasive advantage of fecal metabolomics in the early diagnosis and prediction of physiology and toxicology.

Fat Attenuation Index of Renal Cell Carcinoma Reveals Biological Characteristics and Survival Outcome.

PurposeThe computed tomography fat attenuation index (FAI) is an ideal quantifiable imaging factor to identify the inflammation degree of peri-tumor adipose tissue. We aimed to verify whether FAI could reflect peri-tumor adipose inflammation, predict the survival outcome of renal cell carcinoma (RCC), and discover transcriptomic features of tumor tissues and adjacent adipocytes.Materials and MethodsTwo clinical cohorts (Fudan University Shanghai Cancer Center [FUSCC] cohort [n=129] and TCGA cohort [n=218]) were used to explore the association between FAI and clinical outcome. A prospective cohort (n = 19) was used to discover the molecular phenotyping of peri-tumor adipose tissue and tumor tissue according to their FAI value. A clinical cohort (n = 32) in which patients received cyto-reductive surgery was used to reveal the dynamic change of FAI.ResultsA high peri-tumor FAI was significantly associated with a worse outcome in both the FUSCC (HR = 2.28, p = 0.01) and the TCGA cohort (HR = 2.24, p <0.001). The analysis of the RNA expression of paired RCC tissue and peri-tumor fat tissue showed synchronized alterations in pathways such as cytokine–cytokine receptor interaction and complement and coagulation cascades. RCC tissues showed significant alterations in the neuroactive ligand–receptor interaction pathway. Immune deconvolution analysis showed enhanced infiltration of macrophages in high FAI tumor tissues with a lower angiogenesis level. We also observed synchronous dynamic changes in FAI and tumor size after targeted therapy.ConclusionIn summary, FAI could be used in RCC to reflect the biological characteristics and tumor immune micro-environment of both the tumor and the peri-tumor adipose. High peri-tumor FAI had the potential to predict a worse survival outcome in various cohorts. This study demonstrates that the crosstalk exists between a tumor and its micro-environment and could be reflected easily by imaging procedures, which could facilitate clinical decision making.

GPHB5 Is a Biomarker in Women With Metabolic Syndrome: Results From Cross-Sectional and Intervention Studies.

BackgroundAnimal studies have found that GPHB5 has a similar effect on system metabolism as TSH. However, the relationship between GPHB5 and metabolic diseases remains unknown. This study investigates the relationship between GPHB5 and MetS in young women.MethodsBioinformatics analysis was undertaken to explore the relationship between GPHB5 and metabolic-related genes and signaling pathways. EHC and OGTT were performed on all individuals. Lipid-infusion, physical activity, and cold-exposure tests were performed on healthy individuals. Serum GPHB5 concentrations were measured by an ELISA kit.ResultsPPI network showed that 11 genes interacted with GPHB5, in which POMC and KISS1R were involved in glucose and lipid metabolism. GO analysis showed 56 pathways for BP and 16 pathways for MF, in which OPRM1 and MCR families were related to energy metabolism. KEGG analysis found that GPHB5 is associated with lipolysis and neuroactive ligand-receptor interaction pathways. The levels of circulating GPHB5 were significantly increased, while serum adiponectin levels were lower in MetS women compared with healthy women. Obese/overweight individuals had lower adiponectin levels and higher GPHB5 levels. Circulating GPHB5 levels were positively correlated with BMI, WHR, blood pressure, FBG, 2 h-BG, HbA1c, FIns, 2h-Ins, LDL-C, FFA, HOMA-IR, and AUCg, etc. but negatively correlated with HDL-C, adiponectin, and M-values. Serum GPHB5 levels did not change significantly during the OGTT, EHC, and lipid infusion. Physical activity and cold-exposure tests did not lead to changes in GPHB5 levels. GLP-1RA treatment resulted in a significant decrease in serum GPHB5 levels.ConclusionsGPHB5 may be a biomarker for MetS.

Comparative transcriptomics in the hypothalamic-pituitary-gonad axis of mammals and poultry

The hypothalamic-pituitary-gonad (HPG) axis is vital for reproductive activities in vertebrates. The large-scale comparative analyses of gene expression in the HPG axis across vertebrates have not been carried out yet. Here we collected 175 high-quality RNA-seq samples of hypothalamus, pituitary, ovary and testis from eight species (four mammals and four poultry) to compare transcriptome in the HPG axis, and to detect key pathways and related genes associated with reproduction. We demonstrated the distinguished difference in gene expression of the HPG axis between mammalian and avian species by a series of bioinformatics analysis, including gene differential expression, the phylogeny analysis of gene expression, and their functional annotations. We revealed two pathways, i.e., neuroactive ligand-receptor interaction and calcium signaling pathway, which play important roles in animal reproduction. In these two pathways, we detected 17 differentially expressed genes shared in 4 tissues, while 13, 27, and 27 were specifically differentially expressed genes in hypothalamus, pituitary and ovary, respectively. Our study on the comparative transcriptomics in the HPG axis across species will provide novel knowledge for exploring the molecular mechanism underlying reproductive traits in animals.

Ad libitum feeding alters mRNA abundance in the ovarian cortex of broiler breeder hens.

Ad libitumfeeding in broiler breeder (BB) hens causes reduced egg production, lower fertility, and improper eggshell deposition. Restricted feeding (RF) is the only effective intervention available to normalize ovarian function and improve reproductive efficiency. This study aimed to assess the transcriptional changes in ovarian cortex of BB hens with free access to feed compared to those on a RF diet. RNA was isolated from the ovarian cortex of Cobb 500 pullets raised to 10 and 16 weeks of age on either a full-feeding (FF) or RF diet. Microarray analysis identified 386 differentially expressed genes between the two feeding groups at 16 weeks of age. Gene ontology enrichment identified overrepresentation of Neuroactive ligand–receptor interaction pathways, Cell adhesion molecules, Steroid hormone biosynthesis, and various KEGG pathways. From these groups, 46 genes were selected for follow-up validation by quantitative PCR. The findings show that 33 of the 46 genes had significantly different abundance by age and/or feeding level. Most of these genes were repressed in RF hens and belonged to the steroid biosynthesis and neuropeptide signaling groups. The VIPR2 receptor was higher in the FF group leading us to hypothesize that vasoactive intestinal peptide (VIP) is an important regulator of small cortical follicles. Culture of hen cortical follicles with VIP increased Star, an indication of increased steroidogenic activity, although did not elevate Cyp11a1. These results offer insights and suggest the possible mechanisms and pathways responsible for the increases in cortical follicle growth associated with excess feed intake in BB hens.Lay summaryGiving breeder hens unrestricted access to feed can lead to problems with their ovaries, including excessive growth of the ovary and reduced fertility. Giving a limited amount of feed is the only effective way to reduce this growth of the ovaries and improve fertility. This study aimed to assess the changes in the molecules that make proteins in the body in hens fed unrestricted and restricted diets. In the hens fed a limited amount of feed, there were more of one type of molecules, while there were more of another type in the ovaries of hens with unrestricted access to feed. These results show that how much a hen eats can alter the number of these molecules in the ovary and this could help us understand why their ovaries grow excessively and why their eggs are less fertile.

Identification of the Active Compound of Liu Wei Di Huang Wan for Treatment of Gestational Diabetes Mellitus via Network Pharmacology and Molecular Docking.

Liu Wei Di Huang Wan (LWDHW) is a well-known Chinese herbal compound, which has been prescribed for the treatment of gestational diabetes mellitus (GDM). We sought to clarify the potential therapeutic effects of LWDHW against GDM. Differentially expressed genes (DEGs) in GDM were firstly identified from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal the biological functions of the DEGs. Subsequently, the LWDHW-compound–target network was constructed based on public databases to identify the relationship between the active components in LWDHW and the corresponding targets. Furthermore, gene functional analysis and protein–protein interaction (PPI) network construction were applied to investigate the function of potential targets and to evaluate hub genes. Finally, molecular docking was used to verify the binding activities between active ingredients and hub targets. Thirteen active components and 39 corresponding therapeutic target genes were obtained via network pharmacology analysis. The enrichment analysis demonstrated that the anti-GDM effect of LWDHW included oxidoreductase activity, involvement in renal system process, and regulation of blood pressure, which may be achieved through regulation of serotonergic synapses, vascular smooth muscle contraction, and neuroactive ligand–receptor interaction pathways. Additionally, molecular docking revealed that the main active component, Mu Dan Pi, exhibited the best affinity for proteins encoded by hub genes. This study applied network pharmacology analysis and molecular docking to display the multicomponent and multitarget characteristics of LWDHW in the treatment of GDM. Our findings provide novel insights into the pathogenesis of GDM and the therapeutic mechanisms of LWDHW against GDM.

Consideration of metabolomics and transcriptomics data in the context of using avian embryos for toxicity testing

Early-life stage (ELS) avian toxicity tests have been proposed as a more ethical alternative to traditional standardized tests with adult birds. At the same time, 'omics approaches are gaining traction in the field of avian toxicology, but little has been done to characterize the metabolome and transcriptome at different life stages. The present study uses 'omics data from toxicity tests of 8 environmental chemicals in ELS and adult Japanese quail (Coturnix japonica) to address this data gap. Previous analyses of these data focused on responses to each of the individual chemicals. Here, we consider data from all studies to describe variation in the metabolome and transcriptome between life stages and across independent experiments, irrespective of chemical treatment. Of the 230 metabolites detected in liver, 163 were shared between the two life stages. However, many of the targeted bile acids that were present in the adult liver were absent from ELS samples. For the transcriptome, >90% of the 18,364 detected transcripts were common to both life stages. Based on the 213 genes solely detected in ELS liver, the neuroactive ligand-receptor interaction pathway was significantly enriched. Multivariate and hierarchical clustering analyses revealed that variability among independent experiments was higher for the adult than the ELS studies at both the metabolomic and transcriptomic levels. Our results indicate concordance of the two approaches, with less variation between independent experiments in the ELS metabolome and transcriptome than in adults, lending support for the use of ELS as an alternative toxicity testing strategy.

Mass spectrometry-based metabolic profiling for identification of biomarkers in serum related to the change of laying ducks in different physiological periods

Eggs are a major animal protein source for humans. Egg formation is a complex process involved in coordinating various tissues and organs, while blood is necessary for gonad differentiation and egg formation. In this study, non-targeted metabolomics technology was employed to determine the serum metabolites at the time point of 70 days (before laying period, T0), 130 days (pre-laying period, T1), 300 days (peak laying period, T2), and 340 days (post laying period, T3) in female ducks, to provide comprehensive metabolic profiling in reflecting the overall temporal changes. The results showed significant differences in the metabolites of different comparison groups (T0 vs. T1, T2 vs. T3, and T0 & T1 vs. T2& T3), supporting the main physiological responses in ducks are differential among laying periods. L-Aspartic Acid, Biotin, and Thyroxine can be considered the potential biomarkers related to sexual maturity. L-Lysine, Lumichrome, Thiamine, Riboflavin, and Pyridoxine may be biomarkers related to egg formation. Sorbitol, Isorhamnetin, Naringenin, and Hydroxykynurenine were the biomarkers associated with the decline of egg production. In addition, the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis showed that sexual maturity was mainly involved in the biosynthesis of secondary plant metabolites, Tricarboxylic Acid Cycle, Mineral absorption, pentose phosphate pathway, and Oxocarboxylic acid metabolism. Egg formation disturbed amino acid metabolism, vitamin metabolism, and carbohydrate metabolism. The neuroactive ligand-receptor interaction pathway may affect egg production. These findings can detect the different physiological statuses in female ducks and provide a theoretical basis for increasing egg production, and ensuring sustainable farming. Highlights The main physiological responses in ducks are differential among laying periods. 3, 6, and 4 biomarkers related to sexual maturity, the formation of the egg, and the decline of egg production, respectively. Sexual maturity was mainly involved in the biosynthesis of secondary plant metabolites, Tricarboxylic Acid Cycle, Mineral absorption, pentose phosphate pathway, and Oxocarboxylic acid metabolism, and egg formation disturbed amino acid metabolism, vitamin metabolism, and carbohydrate metabolism. while the neuroactive ligand-receptor interaction pathway may affect egg production.

Maternal urban particulate matter exposure and signaling pathways in fetal brains and neurobehavioral development in offspring

It is well understood that exposure to particulate matter (PM) can have adverse effects on the nervous system. When pregnant women are exposed to PM, their fetuses are also affected through the placenta. However, the mechanisms by which fetal brain development is regulated between mother and fetus remain unclear. C57BL/6J pregnant mice were exposed to PM at embryonic day (E) 2.5, 5.5, 8.5, 11.5, 14.5, and 17.5 via nasal drip at three doses (3, 6, 12 mg/kg of body weight) or PBS control. Neurobehavioral changes in the offspring were examined at 5–6-week-old by open field test (OFT) and elevated plus maze (EPM). The maternal and fetal brain and placenta were collected at E18.5, and molecular signal changes were explored using transcriptome analysis. We found that both male and female low-dose pups and male middle-dose pups traveled a significantly longer distance than controls in EPM tests. Both male and female low-dose pups showed a higher frequency of entering the center area and female low-dose pups exhibited a higher percentage of distance moved in the center area than controls in OFT tests. Gene expression in the maternal brain, fetal brain, and placenta at E18.5 was altered. Differentially expressed genes were enriched in the neuroactive ligand-receptor interaction pathway in all three tissue types. Pathway analysis revealed that the PI3K-Akt and PKC signaling was dysregulated in the fetal brain in the high-dose group compared with the control group. The pathways play a role in neuronal survival and apoptosis. Furthermore, there is a dose-dependent increase in Caspase-6, neuronal apoptosis and neurodegeneration biomarker, levels in E18.5 fetal brain (P = 0.06). In conclusion, our study demonstrated that prenatal PM exposure enhanced exploration and locomotor activity in adolescent offspring and altered molecular events in maternal brain, fetal brain, and placenta. The connections of these changes warrant further investigations.

Construction of a competing endogenous RNA network and identification of potential regulatory axes in gastric cancer chemoresistance

BackgroundEmerging evidence highlights the multifunctional role of noncoding RNAs (ncRNAs) in gastric cancer (GC) chemoresistance. However, the comprehensive expression profile and competing endogenous RNAs (ceRNAs) regulatory network of GC chemoresistance remain unanswered. MethodsThe whole-transcriptome sequencing (RNA sequencing) was performed to comprehensively analyze the differentially expressed (DE) lncRNAs, miRNAs and mRNAs in cisplatin-resistant cells MGC-803/DDP and GC cells MGC-803. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions implicated with the DEncRNAs. Then, the cisplatin-resistant-related ceRNA network and potential regulatory axes were constructed by bioinformatic analysis. ResultsWe successfully generated cisplatin-resistant GC cell line MGC-803/DDP. Differential expression analysis showed that a total of 1936 DElncRNAs, 2194 DEmRNAs and 174 DEmiRNAs were identified. Functional enrichment analysis indicated that those DEncRNAs were mainly involved in neuroactive ligand-receptor interaction, drug metabolism and Hippo signaling pathway. Subsequently, the cisplatin-resistant-related ceRNA network was constructed with the widely accepted vital chemo-resistant-related genes and signaling pathways. In addition, two constructed regulatory axes (include FAM66C/miR-129–5p/7 mRNAs and SFTA1P/miR-206/FN1 or NRP1) were successfully validated by the Genomic Data Commons (GDC) GC data. ConclusionsThe novel ceRNA network and the potential regulatory axes may provide the most comprehensive view of GC chemoresistance to date. Our findings uncovered potential biomarkers for prognostic prediction and novel therapeutic targets for reversing cisplatin resistance in GC.

RNA sequence analysis identified bone morphogenetic protein-2 (BMP2) as a biomarker underlying form deprivation myopia

PurposeForm deprivation myopia (FDM) is an urgent public issue characterized by pathological changes, but the underlying mechanism remained unclear. The aim was to investigate bone morphogenetic proteins (BMPs) utilizing the pathogenesis of FDM. Material and methodsGene expression omnibus (GEO) database was used to analyze one mRNA profile (GSE89325) of FDM. Sixteen retina samples (8 FDM and 8 controls) were randomly divided into seven groups for differential gene expression analysis in R. software. The gene pathway and protein-protein interaction (PPI) analysis were performed by the DAVID and STRING databases. Cytoscape was used to draw the PPI network. The gene ontology (GO) enrichment and Kyoto encyclopedia of genes and Genomes (KEGG) analysis were determined to achieve gene annotation and visualization. ResultsA total of 18420 differentially expressed genes (DEGs) were identified associated with FDM. The only non-significant gene (BEND6) was separately analyzed between two groups. Thirteen hub genes were discovered, ACVR1, ACVR2A, ACVR2B, RGMB, BMPR2, BMPR1A, BMP2, BMPR1B, CHRD, PTH, PTH1R, PTHLH, and WNT9A. The expression alteration in FDM were mainly enriched in cytokine-cytokine, and neuroactive ligand receptor interaction pathways. BMP2 was the key gene in myopia progression. ConclusionsOf clinical perspective, our findings reveal that expression of BMP2 as an underlying mechanism of FDM, providing an insight for therapeutic interventions.

Transcriptomic analyses of the HPG axis-related tissues reveals potential candidate genes and regulatory pathways associated with egg production in ducks

BackgroundEgg production is one of the most important economic traits in the poultry industry. The hypothalamic-pituitary–gonadal (HPG) axis plays an essential role in regulating reproductive activities. However, the key genes and regulatory pathways within the HPG axis dominating egg production performance remain largely unknown in ducks.ResultsIn this study, we compared the transcriptomic profiles of the HPG-related tissues between ducks with high egg production (HEP) and low egg production (LEP) to reveal candidate genes and regulatory pathways dominating egg production. We identified 543, 759, 670, and 181 differentially expressed genes (DEGs) in the hypothalamus, pituitary, ovary stroma, and F5 follicle membrane, respectively. Gene Ontology (GO) analysis revealed that DEGs from four HPG axis-related tissues were enriched in the "cellular component" category. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the neuroactive ligand-receptor interaction pathway was significantly enriched based on DEGs commonly identified in all four HPG axis-related tissues. Gene expression profiles and Protein–Protein Interaction (PPI) network were performed to show the regulatory relationships of the DEGs identified. Five DEGs encoding secreted proteins in the hypothalamus and pituitary have interaction with DEGs encoding targeted proteins in the ovary stroma and F5 follicle membrane, implying that they were these DEGs might play similar roles in the regulation of egg production.ConclusionsOur results revealed that neuroactive ligand-receptor interaction pathway and five key genes(VEGFC, SPARC, BMP2, THBS1, and ADAMTS15) were identified as the key signaling pathways and candidate genes within the HPG axis responsible for different egg production performance between HEP and LEP. This is the first study comparing the transcriptomic profiles of all HPG axis-related tissues in HEP and LEP using RNA-seq in ducks to the best of our knowledge. These data are helpful to enrich our understanding of the classical HPG axis regulating the egg production performance and identify candidate genes that can be used for genetic selection in ducks.

Network Pharmacology Study to Elucidate the Key Targets of Underlying Antihistamines against COVID-19.

Antihistamines have potent efficacy to alleviate COVID-19 (Coronavirus disease 2019) symptoms such as anti-inflammation and as a pain reliever. However, the pharmacological mechanism(s), key target(s), and drug(s) are not documented well against COVID-19. Thus, we investigated to decipher the most significant components and how its research methodology was utilized by network pharmacology. The list of 32 common antihistamines on the market were retrieved via drug browsing databases. The targets associated with the selected antihistamines and the targets that responded to COVID-19 infection were identified by the Similarity Ensemble Approach (SEA), SwissTargetPrediction (STP), and PubChem, respectively. We described bubble charts, the Pathways-Targets-Antihistamines (PTA) network, and the protein–protein interaction (PPI) network on the RPackage via STRING database. Furthermore, we utilized the AutoDock Tools software to perform molecular docking tests (MDT) on the key targets and drugs to evaluate the network pharmacological perspective. The final 15 targets were identified as core targets, indicating that Neuroactive ligand–receptor interaction might be the hub-signaling pathway of antihistamines on COVID-19 via bubble chart. The PTA network was constructed by the RPackage, which identified 7 pathways, 11 targets, and 30 drugs. In addition, GRIN2B, a key target, was identified via topological analysis of the PPI network. Finally, we observed that the GRIN2B-Loratidine complex was the most stable docking score with −7.3 kcal/mol through molecular docking test. Our results showed that Loratadine might exert as an antagonist on GRIN2B via the neuroactive ligand–receptor interaction pathway. To sum up, we elucidated the most potential antihistamine, a key target, and a key pharmacological pathway as alleviating components against COVID-19, supporting scientific evidence for further research.

Role of hemoglobin alpha and hemoglobin beta in non-small-cell lung cancer based on bioinformatics analysis.

The differentially expressed genes (DEGs) were identified and screened differentially in non-small-cell lung cancer (NSCLC) using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, and the correlation of DEGs in protein interaction, function, and pathway enrichment were analyzed to search for new biomarkers and potential therapeutic targets for NSCLC. Protein-protein interaction network (PPI) analysis showed that CDK1 and GNGT1 were the most significantly upregulated hub nodes, while FPR2 was the most significantly downregulated. Gene Ontology enrichment analysis showed that upregulated DEGs were significantly enriched in protein heterodimerization activity and other functions, while downregulated DEGs were enriched in functions such as heparin-binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that upregulation of DEGs were significantly associated with neuroactive ligand-receptor interaction pathways, while downregulation of DEGs were significantly associated with malaria pathways. According to the analysis results, we identified hemoglobin alpha (HBA) and hemoglobin beta (HBB) as the genes of interest for further study. Through tissue level and cell level experiments, we found that the expressions of HBA and HBB in NSCLC tissues were significantly lower than those in paracancerous tissues, and downregulation of HBA and HBB could significantly affect the proliferation ability of NSCLC cells. In addition, we also found that changes in HBA and HBB may affect NSCLC cells through the p38/MAPK pathway and JNK pathway, and ultimately affect the occurrence and development of NSCLC.

Study on the Mechanism of Üstikuddus Sherbiti in Ischemic Cerebrovascular Diseases: Based on Network Pharmacology.

This paper aims to study the potential biological mechanism of Üstikuddus Sherbiti (ÜS) in the treatment of ischemic cerebrovascular diseases (ICVD) by the network pharmacology method. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to obtain effective constituents of ÜS by screening eligible oral utilization, drug similarity, and blood-brain barrier permeability threshold. By drug target prediction and stroke treatment target mining, 2 target data sets were analyzed to find intersection targets and the corresponding constituents were used as active constituents. An active constituent target network and an effective constituent target network were constructed by using Cytoscape 3.7.2 software. Degree parameters of the effective constituent target network were analyzed to find important effective constituents and targets. Through protein-protein interaction (PPI) analysis/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, potential signaling pathways of ÜS in ischemic stroke were found out. AutoDock was used for molecular docking verification. A total of 90 active constituents of ÜS were screened out. There were 10 active constituents against ICVD, including quercetin, luteolin, kaempferol, and naringenin, and 10 important targets for anticerebral ischemia, namely, PIK3CA, APP, PIK3R1, MAPK1, MAPK3, AKT1, PRKCD, Fyn, RAC1, and NF-κB1. Based on the protein interaction network, the important targets of ÜS were significantly enriched in PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction pathway, Ras signaling pathway, etc. ÜS in ICVD has characteristics like multiple targets, multiple approaches, and multiple pathways. Results of molecular docking showed that the active components in ICVD had a good binding ability with the key targets. Its main biological mechanism may be related to the PI3K-Akt and Ras-MAPK centered signaling pathway. Our study demonstrated that ÜS exerted the effect of treating ICVD by regulating multiple targets and multiple channels with multiple components through the method of network pharmacology and molecular docking.