Biological Functions Of Liver Research Articles

An Integrated Analysis of the Identified PRPF19 as an Onco-immunological Biomarker Encompassing the Tumor Microenvironment, Disease Progression, and Prognoses in Hepatocellular Carcinoma.

Background: Targeting the mRNA splicing process has been identified as a therapeutic strategy for human cancer. PRPF19 is an RNA binding protein that is involved in pre-mRNA processing and repairing DNA damage; the aberrant expression of PRPF19 is potentially associated with carcinogenesis. However, the biological role of PRPF19 in hepatocellular carcinoma (HCC) is still elusive. Methods: Data obtained from TCGA, Oncomine, and GEO were used to investigate the PRPF19 expression level and its role in tumor immune infiltration, prognosis, and the tumor progression of cohorts from HCC. Using various databases and tools (UALCAN, TIMER, TISMO, and PathCards), we presented the potential mechanisms of PFPF19 upregulation, PRPF19-related pathways, and its biological functions in liver cancer. Results: For HCC, PRPF19 expression was found upregulated both in single tumor cells and tissues. Furthermore, the increased expression of PRPF19 was significantly correlated to clinical characteristics: advanced stage, vascular invasion, high AFP, and poor prognosis of HCC. According to the tumor-immunological analysis, we found that PRPF19 is positively correlated with infiltrating myeloid-derived suppressor cells (MDSCs). Moreover, the microenvironment of HCC tissues with high expression of PRPF19 is highly immunosuppressive (lower T-lymphocytes, multiple immune checkpoints upregulated). Patients with high expression of PRPF19 and high MDSCs had a worse survival prognosis as well. TP53 mutation may have a positive effect on PRPF19 expression via decreased promoter methylation of PRPF19. By TF-mRNA network analysis, key transcription factors (TFs) in TC-NER and PCS pathways (PRPF19 involved) were identified. Conclusion: This work implied that PRPF19 is associated with tumor immune evasion and progression, and serves as a prognostic marker for worse clinical outcomes with HCC. Thus, this critical regulator could serve as a potential therapeutic target of HCC.

Emerging Role of Edible Exosomes-Like Nanoparticles (ELNs) as Hepatoprotective Agents.

Liver diseases are responsible for over 2 million deaths each year and the number is rapidly increasing. There is a strong link between edibles, gut microbiota, liver fat and the liver damage. There are very limited therapeutic options for treatment specifically for Alcoholic liver disease (ALD) and Non-Alcoholic liver disease (NAFLD). Recently, identified Edible Exosomes-like nanoparticles (ELNs) are plant derived membrane bound particles, released by microvesicular bodies for cellular communication and regulate immune responses against many pathogens. Many studies have identified their role as hepatoprotective agent as they carry bioactive material as cargoes which are transferred to recipient cells and affect various biological functions in liver. They are also known to carry specific miRNA, which increases the copy number of beneficial bacteria and the production of lactic acid metabolites in gut and hence restrains from liver injury through portal vein. Few in-vitro studies also have been reported about the anti-inflammatory, anti-oxidant and detoxification properties of ELNs which again protects the liver. The properties such as small size, biocompatibility, stability, low toxicity and non-immunogenicity make ELNs as a better therapeutic option. But, till now, studies on the effect of ELNs as therapeutics are still at its infancy yet promising. Here we discuss about the isolation, characterization, their role in maintaining the gut microbiome and liver homeostasis. Also, we give an outline about the latest advances in ELNs modifications, its biological effects, limitations and we propose the future prospective of ELNs as therapeutics.

Gene co-expression networks from RNA sequencing of dairy cattle identifies genes and pathways affecting feed efficiency

BackgroundSelection for feed efficiency is crucial for overall profitability and sustainability in dairy cattle production. Key regulator genes and genetic markers derived from co-expression networks underlying feed efficiency could be included in the genomic selection of the best cows. The present study identified co-expression networks associated with high and low feed efficiency and their regulator genes in Danish Holstein and Jersey cows.RNA-sequencing data from Holstein and Jersey cows with high and low residual feed intake (RFI) and treated with two diets (low and high concentrate) were used. Approximately 26 million and 25 million pair reads were mapped to bovine reference genome for Jersey and Holstein breed, respectively. Subsequently, the gene count expressions data were analysed using a Weighted Gene Co-expression Network Analysis (WGCNA) approach. Functional enrichment analysis from Ingenuity® Pathway Analysis (IPA®), ClueGO application and STRING of these modules was performed to identify relevant biological pathways and regulatory genes.ResultsWGCNA identified two groups of co-expressed genes (modules) significantly associated with RFI and one module significantly associated with diet. In Holstein cows, the salmon module with module trait relationship (MTR) = 0.7 and the top upstream regulators ATP7B were involved in cholesterol biosynthesis, steroid biosynthesis, lipid biosynthesis and fatty acid metabolism. The magenta module has been significantly associated (MTR = 0.51) with the treatment diet involved in the triglyceride homeostasis. In Jersey cows, the lightsteelblue1 (MTR = − 0.57) module controlled by IFNG and IL10RA was involved in the positive regulation of interferon-gamma production, lymphocyte differentiation, natural killer cell-mediated cytotoxicity and primary immunodeficiency.ConclusionThe present study provides new information on the biological functions in liver that are potentially involved in controlling feed efficiency. The hub genes and upstream regulators (ATP7b, IFNG and IL10RA) involved in these functions are potential candidate genes for the development of new biomarkers. However, the hub genes, upstream regulators and pathways involved in the co-expressed networks were different in both breeds. Hence, additional studies are required to investigate and confirm these findings prior to their use as candidate genes.

Investigation of Dioscorea bulbifera Rhizome-Induced Hepatotoxicity in Rats by a Multisample Integrated Metabolomics Approach.

The use of herbal medicines continues to expand globally, meanwhile, herb-associated hepatotoxicity is becoming a safety issue. As a conventional Chinese medicinal herb, Dioscorea bulbifera rhizome (DBR) has been documented to cause hepatic toxicity. However, the exact underlying mechanism remains largely unexplored. In the present study, we aimed to profile entire endogenous metabolites in a biological system using a multisample integrated metabolomics strategy. Our findings offered additional insights into the molecular mechanism of the DBR-induced hepatotoxicity. We identified different metabolites from rat plasma, urine, and feces by employing gas chromatography-mass spectrometry in combination with multivariate analysis. In total, 55 metabolites distributed in 33 metabolic pathways were identified as being significantly altered in DBR-treated rats. Correlation network analysis revealed that the hub metabolites of hepatotoxicity were mainly associated with amino acid, bile acid, purine, pyrimidine, lipid, and energy metabolism. As such, DBR affected the physiological and biological functions of liver via the regulation of multiple metabolic pathways to an abnormal state. Notably, our findings also demonstrated that the multisample integrated metabolomics strategy has a great potential to identify more biomarkers and pathways in order to elucidate the mechanistic complexity of toxicity of traditional Chinese medicine.

Deciphering the Developmental Dynamics of the Mouse Liver Transcriptome.

During development, liver undergoes a rapid transition from a hematopoietic organ to a major organ for drug metabolism and nutrient homeostasis. However, little is known on a transcriptome level of the genes and RNA-splicing variants that are differentially regulated with age, and which up-stream regulators orchestrate age-specific biological functions in liver. We used RNA-Seq to interrogate the developmental dynamics of the liver transcriptome in mice at 12 ages from late embryonic stage (2-days before birth) to maturity (60-days after birth). Among 21,889 unique NCBI RefSeq-annotated genes, 9,641 were significantly expressed in at least one age, 7,289 were differently regulated with age, and 859 had multiple (> = 2) RNA splicing-variants. Factor analysis showed that the dynamics of hepatic genes fall into six distinct groups based on their temporal expression. The average expression of cytokines, ion channels, kinases, phosphatases, transcription regulators and translation regulators decreased with age, whereas the average expression of peptidases, enzymes and transmembrane receptors increased with age. The average expression of growth factors peak between Day-3 and Day-10, and decrease thereafter. We identified critical biological functions, upstream regulators, and putative transcription modules that seem to govern age-specific gene expression. We also observed differential ontogenic expression of known splicing variants of certain genes, and 1,455 novel splicing isoform candidates. In conclusion, the hepatic ontogeny of the transcriptome ontogeny has unveiled critical networks and up-stream regulators that orchestrate age-specific biological functions in liver, and suggest that age contributes to the complexity of the alternative splicing landscape of the hepatic transcriptome.

Elucidating molecular networks that either affect or respond to plasma cortisol concentration in target tissues of liver and muscle.

Cortisol is a steroid hormone with important roles in regulating immune and metabolic functions and organismal responses to external stimuli are mediated by the glucocorticoid system. Dysregulation of the afferent and efferent axis of glucocorticoid signaling have adverse effects on growth, health status, and well-being. Glucocorticoid secretion and signaling show large interindividual variation that has a considerable genetic component; however, little is known about the underlying genetic variants. Here, we used trait-correlated expression analysis, screening for expression quantitative trait loci (eQTL), genome-wide association (GWA) studies, and causality modeling to identify candidate genes in porcine liver and muscle that affect or respond to plasma cortisol levels. Through trait-correlated expression, we characterized transcript activities in many biological functions in liver and muscle. Candidates from the list of trait-correlated expressed genes were narrowed using only those genes with an eQTL, and these were further prioritized by determining whether their expression was predicted to be related to variation in plasma cortisol levels. Using network edge orienting (NEO), a causality modeling algorithm, 26 of 990 candidates in liver were predicted to affect and 70 to respond to plasma cortisol levels. Of 593 candidates in muscle that were correlated with cortisol levels and were regulated by eQTL, 2 and 25 were predicted as effective and responsive, respectively, to plasma cortisol levels. Comprehensive data integration has helped to elucidate the complex molecular networks contributing to cortisol levels and thus its subsequent metabolic effects. The discrimination of up- and downstream effects of transcripts affecting or responding to plasma cortisol concentrations improves the understanding of the biology of complex traits related to growth, health, and well-being.

STUDY OF BIOCHEMICAL EFFECT THE LEVEL OF SOME TRANSITION ELEMENT MEASURED BY FLAME ATOMIC ABSOROTION TECHNIQUE ON THE HEALTH OF EXPOSED WORKER

This research is a trial to study the exposed effect of some trace elements {Chromium , Iron , Nickel , Cupper and Zinc} which have been used in painting on the biological functions of liver , Heart and Kidney of workers in contact with their vapors , in addition to their levels in the body. Flame atomic absorption technique had been used for the measurements of trace elements as well as Cu / Zn ratio level in serum . The trace elements level increased significantly ( P < 0.05 ) while the Cu/ Zn ration decreased The Biochemical test was carried on technicians and administrators for the interior control and volunteers as external control. Blood Bio-test was carried out including the concentration of total Cholesterol, Triglyceride, High density lipo protein {HDL} ,Low density lipo protein {LDP} and very Low density lipo protein {VLDL}. The results of this study showed that: Cholesterol , Triglyceride and Low density lipoprotein increased significantly ( P < 0.01 ) , while high density lipoprotein decreased significantly ( P < 0.05 ) Serum Enzymes including GOT, GPT, Alk. phosphate, and urea activity were also done. The results showed that Enzyme activity: GOT, GPT, Urea increased significantly (P< 0.05 ) , Alk phosphate show insignificant increase ( P < 0.05 ).,

Activation of Liver X Receptors Prevents Statin-induced Death of 3T3-L1 Preadipocytes

The biological functions of liver X receptors (LXRs) alpha and beta have primarily been linked to pathways involved in fatty acid and cholesterol homeostasis. Here we report a novel role of LXR activation in protecting cells from statin-induced death. When 3T3-L1 preadipocytes were induced to differentiate by standard isobutylmethylxanthine/dexamethasone/insulin treatment in the presence of statins, they failed to differentiate and underwent massive apoptosis. The simultaneous addition of selective LXR agonists prevented the statin-induced apoptosis. By using mouse embryo fibroblasts from wild-type (LXRalpha+/+/LXRbeta+/+), LXRalpha knock-out mice (LXRalpha(-/-)/LXRbeta+/+), LXRbeta knock-out mice (LXRalpha+/-/LXRbeta(-/-)), and LXR double knock-out mice (LXRalpha(-/-)/LXRbeta(-/-)) as well as 3T3-L1 cells transduced with retroviruses expressing either wild-type LXRalpha or a dominant negative version of LXRalpha, we demonstrate that the response to LXR agonists is LXR-dependent. Interestingly, LXR-mediated rescue of statin-induced apoptosis was not related to up-regulation of genes previously shown to be involved in the antiapoptotic action of LXR. Furthermore, forced expression of Bcl-2 did not prevent statin-induced apoptosis; nor did LXR action depend on protein kinase B, whose activation by insulin was impaired in statin-treated cells. Rather, LXR-dependent rescue of statin-induced apoptosis in 3T3-L1 preadipocytes required NF-kappaB activity, since expression of a dominant negative version of IkappaBalpha prevented LXR agonist-dependent rescue of statin-induced apoptosis. Thus, the results presented in this paper provide novel insight into the action of statins on and LXR-dependent inhibition of apoptosis.

Genome-wide expression profiling; a panel of mouse tissues discloses novel biological functions of liver X receptors in adrenals

The liver X receptors alpha and beta (LXRalpha and LXRbeta ) are members of the nuclear receptor superfamily of proteins which are highly expressed in metabolically active tissues. They regulate gene expression of critical genes involved in cholesterol catabolism and transport, lipid and triglyceride biosynthesis and carbohydrate metabolism in response to distinct oxysterols and intermediates in the cholesterol metabolic pathway. The biological roles of the LXRs in tissues other than liver, intestine and adipose tissue are poorly elucidated. In this study we used global gene-expression profiling analysis to detect differences in expression patterns in several tissues from mice fed an LXR agonist or vehicle. Our results show that LXR plays an important role in the kidney, lung, adrenals, brain, testis and heart where several putative LXR target genes were found. The effects of the LXRs were further analysed in adrenals where treatment with an LXR agonist induced expression of adrenocorticotrophic hormone receptor, suppressed expression of uncoupling protein (UCP)-1 and UCP-3 as well as several glycolytic enzymes and led to increased serum corticosterone levels. These results indicate novel biological roles of the LXR including regulation of energy metabolism, glycolysis and steroidogenesis in the adrenals via alteration of expression profiles of putative target genes.