Fold Change Research Articles

The Apoptotic Property of Nymphaea Caerulea Flower Extract on Acute Myeloid Leukaemia Cell Line, THP-1.

Acute Myeloid Leukaemia (AML) is considered to be an extremely heterogeneous malignancy of bone marrow and blood. The first line of therapy for AML is prolonged chemotherapy. Due to the presence of molecular heterogeneity in AML as confirmed by next-generation sequencing, researchers are planning to develop newer strategies of therapy. In the present study we have explored the anti-cancer potentiality of the hydro-ethanolic extract (50% and 70%) of the whole flower of Nymphaea caerulea against the Acute Myeloid Leukaemia cell line, THP-1 with control of normal human kidney epithelial cell line (HEK 293). The present study is a novel contribution to the existing scientific knowledge as at present no study as an anti-leukaemic agent is available on N. caerulea (blue lotus) extract and exploring its action mechanism on in-vitro cell line model. Some targeted cytokine and apoptotic genes genes to deduce the anti-cancer mechanism of action of the crude extract (hydro-ethanolic extract (50% and 70%) of the whole flower) were selected as Interferon (IFN) γ, Interleukins - IL-6, IL-8, IL- 10, IL-1β, Transforming Growth Factor (TGF β1), Tumor Necrosis Factor (TNF α), Caspase 3(CAS 3), Caspase 9 (CAS 9), CD95 (Fas), Tumor Necrosis Factor Receptor 1 (TNFRSF1A) to observe relative fold changes of the expression using Real-Time PCR with housekeeping gene β-actin. Cellular cytopathic effect (CPE), cell viability assay by methylene blue assay, and cell cytotoxicity of the crude extract against the THP-1 cell line were also studied along with it's bio-active compositional analysis of the extract was explored using ultra-performance liquid chromatography followed by mass spectra. The N. caerulea flower extract is capable of inducing apoptosis in AML and it can balance cytokine alterations in such diseases. Nymphaea caerulea flower extract appears to be a good anti-leukemia agent.

Assessment of ubiquitin specific Peptidase-18 gene in peripheral blood of chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C virus (HCV) infection remains one of the leading causes of liver complications globally. Ubiquitin Specific Peptidase-18 (USP18) is a ubiquitin-specific protease that cleaves interferon-stimulated gene 15 (ISG15) from ISGylated protein complexes and is involved in regulating interferon responsiveness. To study the effect of direct-acting antivirals (DAAs) on the USP18 gene using qPCR, 132 participants were recruited and classified into different groups based on treatment duration. USP18 expression was raised compared to rapid virologic response (RVR) and early virologic response (EVR) groups with P = 0.0026 and P = 0.0016, respectively. USP18 was found to be 7.36 folds higher in naïve patients than those with RVR and sustained viral response (SVR). In RVR and SVR groups where patients had cleared HCV RNA after treatment with direct-acting antiviral agents (DAA) therapy, the expression of USP18 was found to be low, with a fold change of 1.3 and 1.4 folds, respectively. Expression of USP18 was significantly higher in the non-RVR group than in the RVR group. In the No EVR group, gene expression was significantly higher than in the EVR group. It is concluded that targeting HCV proteins using DAAs can cause USP18 expression to be normalized more effectively. Moreover, USP18 is a vital marker indicating treatment resistance and distinguishing responders from non-responders during DAA therapy.

Genome-Wide Characterization and Expression Analysis of Annexin Genes under High-Temperature Stress in Sorghum bicolor L.

The annexin family is found in animals and plants and responds to a wide range of environmental stressors. In this study, 19 annexin proteins were identified based on their putative annexin repeats in Sorghum bicolor and further grouped on a phylogenic tree. These genes were randomly distributed across seven chromosomes. The amino acid length of sorghum annexins (SbAnn) varied from 241 (SbAnn3) to 370 (SbAnn2). Additionally, selective pressure analysis suggests the role of purification selection in conserving the annexin gene family in sorghum. Most SbAnns were located in the nucleus, cytoplasm, chloroplast, and mitochondrion. Also, higher syntenic relationships were observed between S. bicolor and monocots (S. italica, Z. mays, and O. sativa) than in A. thaliana. Cis-acting elements in the SbAnns gene promoters were grouped into response to light, hormone and environmental stress, and development-related elements. A number of miRNAs related to abiotic stress response targeted eleven SbAnns. Furthermore, five (SbAnn 4, 5, 14, 15, and 18) of the seven SbAnn genes utilized had relatively higher fold change under high-temperature treatment. This research provides insights into the characterization and functions of annexins under high temperatures.

Application of Bioinformatics in Predicting the Efficacy of Digestive Tumour Immunotherapy Target TIM-3 and its Inhibitors.

Background: Our main objective is to apply bioinformatics in predicting the efficacy of digestive tumour immunotherapy target TIM-3 and its inhibitors. Methods: Our study used the gene expression omnibus (GEO) database to identify datasets associated with digestive tumours and the action of TIM-3. The GSE427729 dataset based on the GPL10192 platform. The dataset consisted of six samples of total RNA derived from TIM-3 control and knockdown RAW 264.7 cells. We used GEO2R tool to identify DEGs before performing Gene Ontology and identifying the kyoto encyclopedia of genes and genomes (KEGG) pathways. Lastly, we determined the PPI networks to identify hub genes. Results: Our study identified 57 differentially expressed genes based on an adjusted p-value of less than 0.05 and a log2 fold change of 2.0. There were 26 down-regulated genes with 31 up-regulated genes while 22, 404 genes were non-significant. The DEGs were enriched in biological pathways such as activating leukocytes, cells, and development of the immune system. Additionally, we identified four significant KEGG pathways that were implicated in digestive tumour immunotherapy and TIM-3; pathways of pancreatic cancer, NF-Kappa B signalling pathway, Toll-like receptor signalling pathway and C-type lectin receptor signalling pathway. The PPI networks identified 10 hub genes that were implicated in digestive tumour immunotherapy target TIM-3 (Myd88, Traf6, Irf7, Cdk4, Ccnd2, Mapkap1, Prr5, Mpp3, Serpinb6b and Pvrl3). Conclusion: Targeting these biological pathways, KEGG pathways, molecular functions and cellular processes can lead to novel therapeutic treatment and management in digestive tumours based on TIM-3 immunotherapy.

Different development and fecundity between Spodoptera frugiperda USA and China populations, influenced by ecdysone-related genes.

The fall armyworm (FAW), Spodoptera frugiperda, is one of the most harmful plant pests in the world and is globally distributed from the American continent to the Asian region. The FAW USA population (Sf-USA) and China population (Sf-CHN), which belong to corn strain, showed different developmental periods and fecundity rates in lab conditions. Sf-USA had faster development and higher fecundity compared with Sf-CHN. To examine these differences, transcriptomic data from two FAW populations were analyzed and compared. Twelve gigabytes of transcripts were read from each sample and 21,258 differentially expressed genes (DEGs) were detected. DEGs with log2 fold change ≥ 2 were identified and compared in two populations. In comparison to the Sf-CHN, we discovered that 3471 and 3851 individual DEGs upregulated and downregulated, respectively. Comparing transcriptome profiles for differential gene expression revealed several DEGs, including 39 of ecdysone (E)-, 25 of juvenile hormone-, and 15 of insulin-related genes. We selected six of E-related genes, such as Neverland, Shade, Ecdysone receptor, Ecdysone-inducible protein 74 (E74), E75, and E78 from DEGs. Gene expressions were suppressed by RNA interference to confirm the physiological functions of the selected genes from Sf-USA. The Sf-USA showed developmental retardation and a decrease in fecundity rate by suppression of E-related genes. These findings showthat biological characteristics between Sf-USA and Sf-CHNare influenced by E-related genes.

Correlation of miR-155-5p, KRAS, and CREB Expression in Patients with Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a type of blood cancer involving numerous aberrant genes and microRNAs. MiRNAs are non-coding sequences that have been proven to be players in the biological processes of various cancers. The present study is designed to illustrate the relationship between miR-155, KRAS, and CREB. This case-control study was conducted on 21 patients with AML and 9 healthy individuals. The expressions of miR-155, KRAS, and CREB were measured using RT-PCR. Demographic data were extracted from the documents of individuals. SPSS and GraphPad Prism software were used to analyze the data. The expression of miR-155 in patients with AML was 35 times higher than in the control group (p < 0.0001). Also, CREB fold change increased by 1.92-fold in patients compared to the controls (p = 0.034), but no difference in KRAS was observed between the control and AML groups (p > 0.05). There was no change in miR-155, CREB, and KRAS expression based on gender, age, and blast percentage (p > 0.5). Nevertheless, there was a direct correlation between CREB and KRAS expressions (p = 0.0002). Our result showed that overexpression of CREB and KRAS would cause an increase in white blood cells (WBCs) (p = 0.001, 0.045 respectively), but there was no correlation between miR-155 with WBCs (p > 0.5). Our study revealed that miR-155 and CREB had overexpression compared to the control group.

Impact of single nucleotide polymorphisms of immune checkpoint CTLA-4 (SNP rs231775 and rs5742909) in susceptibility to Hashimoto's thyroiditis patients

Background: Hashimoto thyroiditis is an autoimmune disorder causing thyroid cell destruction. This research aimed to evaluate CTLA-4 expression levels in patients with Hashimoto's thyroiditis, biochemical parameters. As well as understand the risk and protective effects of two CTLA-4 SNPs polymorphisms (rs231775 and rs5742909) in Iraqi patients. Methods: A case control study was conducted on 50 HT patients (5 men and 45 females) were assembled from Baghdad teaching hospital, Baghdad, Iraq. The relative Gene expression method was used to measure the gene expression of CTLA-4 using qRT-PCR. The single nucleotide polymorphisms of (318C/T (rs231775) and +49A/G (rs5742909) were sequenced for data analysis. Results: There was significant increase of serum CTLA-4 levels, similarity fold change of CTLA-4 was significant upregulated in HT patients compared to controls. The allele and genotypes frequencies according to HWB equilibrium showed significant differences in HT patients 318C/T (rs231775) AA genotypes, while no significant differences in the AG, GG genotypes, respectively compared to controls (p&lt;0.05), There were also no significant differences in the CTLA-4 SNP +49A/G (rs5742909), (CC, CT, TT) genotype, respectively. (p&gt;0.05). Both studied SNPs recoded higher upregulation of soluble and fold change of the immune check point (CTLA-4), respectively. Conclusion: The study reveals that CTLA-4 gene SNPs rs231775 and rs5742909 significantly influence soluble and the expression of CTLA-4 levels in HT patients, potentially causing Hashimoto disease and HT incidence and development.

Differential Gene Expression in the Penile Cavernosum of Streptozotocin-Induced Diabetic Rats.

Men with diabetes mellitus (DM) often present with severe erectile dysfunction (ED). This ED is less responsive to current pharmacological therapies. If we know the upregulated or downregulated genes of diabetic ED, we can inhibit or enhance the expression of such genes through RNA or gene overexpression. To investigate gene changes associated with ED in type 1 DM, we examined the alterations of gene expression in the cavernosum of streptozotocin-induced diabetic rats. Specifically, we considered 11,636 genes (9,623 upregulated and 2,013 downregulated) to be differentially expressed in the diabetic rat cavernosum group (n=4) compared to the control group (n=4). The analysis of differentially expressed genes using the gene ontology (GO) classification indicated that the following were enriched: downregulated genes such as cell cycle, extracellular matrix, glycosylphosphatidylinositol-anchor biosynthesis and upregulated genes such as calcium signaling, neurotrophin signaling, apoptosis, arginine and proline metabolism, gap junction, transforming growth factor-β signaling, tight junction, vascular smooth muscle contraction, and vascular endothelial growth factor (VEGF) signaling. We examined a more than 2-fold upregulated or downregulated change in expression, using real time polymerase chain reaction. Analysis of differentially expressed genes, using the GO classification, indicated the enrichment. Of the 41,105 genes initially considered, statistical filtering of the array analysis showed 9,623 upregulated genes and 2,013 downregulated genes with at least 2-fold changes in expression (P<0.05). With Bonferroni correction, SLC2A9 (solute carrier family 2 member 9), LRRC20 (leucine rick repeat containing 20), PLK1 (polo like kinase 1), and AATK (apoptosis-associated tyrosine kinase) were all 2-fold changed genes. This study broadens the scope of candidate genes that may be relevant to the pathophysiology of diabetic ED. In particular, their enhancement or inhibition could represent a novel treatment for diabetic ED.

Role of toll-like receptor signaling pathway in a rat model of spinal cord injury: a transcriptomic analysis

Spinal cord injury (SCI) is a debilitating condition characterized by primary and secondary damage to the spinal cord tissue encompassing the site of injury. In this study, we analyzed transcriptomic data from Rattus norvegicus with SCI induced by aneurysm clip impact-compression at seventh thoracic vertebra to explore the main alterations in pathways expression. RNA was extracted from the specific SCI region after 2 weeks and hybridized on Affymetrix GeneChip arrays. Differential gene expression analysis identified 5213 DEGs among which 25 showing a fold change &lt; -2 or &gt; 2. Over-representation analysis was performed using the 25 DEGs above mentioned and revealed the toll-like receptor (TLR) signaling pathway signaling pathway (rno04620) as the only significantly enriched pathway (q-value &lt; 0.05). Further examination of the regulation of this pathway unveiled upregulation of MyD88, Tlr2, and Tlr4, activating NF-κB and MAPK pathways, leading to proinflammatory cytokine synthesis and cellular apoptosis. Upregulation of Cd80 and Cd86 indicated T-cell activation, while IFN-β downstream regulation showed increased expression of JAK-STAT signaling pathway genes. This transcriptomic perspective highlights the dysregulation of the TLR signaling pathway in SCI at 2 weeks and emphasizes its potential role in the pathology.

Analyzing the Expression of MicroRNA-375 and its Target Gene p53 in Oral Squamous Cell Carcinoma and its Implication in Oral Carcinogenesis

Objective: Oral mucosal cancers are the 11th most common human malignancies worldwide with a five-year survival rate of ≤50%. The lacunae of reliable diagnostic and prognostic markers pose an enormous challenge to the timely identification and prediction of disease progression in oral cancer. MicroRNAs (miRNAs) are emerging molecular markers associated with cancer initiation, progression, and therapy. The present study evaluated the microRNA -375(miR-375) expression and its target p53 gene in Oral squamous cell carcinoma (OSCC) to validate its utility as a diagnostic marker of the disease. Patients and Methods: This case-control study targeted histopathologically diagnosed cases of OSCC. miR-375 was quantified from 22 cases of OSCC and corresponding control tissues using qRT-PCR. Mutant p53 expression in cases and controls was determined by subjecting the tissues to immunohistochemical Results: Significant downregulation of miR-375 was noted in OSCC tissues (68.1%) compared to the control tissues with a mean fold change of 83.9 (p&lt;0.05). Significant downregulation of miR-375 was noted in Paan and tobacco chewing patients (77.8%). Men exhibited considerable downregulation compared to women (p&lt;0.05). The miR-375 expression levels did not correlate with the patient’s age, location, size, nodal status, and histopathological grade of the tumor. About 63.6 % of OSCC tissues showed mutant p53 positivity. Mutant p53 expression was noted in 73.3% of miR-375 downregulated tumors. Smokers exhibited higher expression of mutant p53 contrary to non-smokers(p&lt;0.00). P53 immunopositivity showed a correlation with tumor size, histopathological grade, and nodal metastasis. Conclusion: The findings of the study indicate that miR-375 downregulation may have a crucial effect on oral carcinogenesis by targeting p53. miR-375 should be further evaluated as a potential marker for oral cancer diagnosis.

Keyword-based Scoring for The Prioritization of Differentially Expressed Genes Using Gene Ontology Annotations and Network Propagation

Computational gene prioritization provides a basis for the utilization of high-throughput expression data; however, methods for prioritization considering relevance to both biological processes and selected keywords are lacking. In this study, a method was developed to rank differentially expressed genes (DEGs) by utilizing the Gene Ontology (GO) database for keyword searches and propagating the results through a protein–protein interaction network. A scoring system that effectively biases the scores of genes relevant to given keywords for avoidance and preference was established. This scoring method was combined with scoring based on expression characteristic groups (ECGs) with network propagation to obtain a final combined score (cScore). The performance of the new approach was evaluated using a rat middle cerebral artery occlusion (MCAO) dataset, revealing that the method more effectively filtered out DEGs compared with conventional methods based on both significance and fold change values, excluding 76% of genes in average, while retaining genes of interest. Further improvements, including addressing the inability of downward accumulation to balance terms with conflicting hits and the limited number of databases utilized for scoring, can further improve the performance of the method. Overall, the newly developed method can improve the interpretation of DEG data.

Ganciclovir and maribavir cross-resistance revisited: Relative drug susceptibilities of canonical cytomegalovirus mutants

Therapeutic use of maribavir for human cytomegalovirus infection has renewed attention to the extent of cross-resistance with ganciclovir as the existing standard therapy. Each drug selects in vivo for a characteristic set of resistance mutations in the viral UL97 kinase gene. To improve the calibration of relative susceptibilities to each drug, genetic variants at relevant UL97 codons were extensively phenotyped using the same baseline viral clone, cell culture conditions and growth readout. Ganciclovir-selected mutations at codons 460, 520, 592, 594, 595 and 603 conferred 2.8-fold (C603Y) to 12-fold (M460I) increases in ganciclovir 50% inhibitory concentrations (EC50) over wild type baseline, while conferring maribavir EC50 fold changes ranging from 0.21-fold (M460I) to 1.9-fold (A594V). Maribavir-selected mutations at codons 409, 411 and 480 conferred maribavir EC50 fold changes ranging from 17 (H411Y) to 210 (C480F), while conferring ganciclovir EC50 fold changes ranging from 0.7 (H411Y) to 2.3 (C480F). The P-loop substitution F342Y, selected by either drug, is confirmed to confer 4.7-fold and 6-fold increases in maribavir and ganciclovir EC50s respectively, and suggests this part of the ATP-binding domain of UL97 to be involved in moderate resistance to both drugs. The maribavir hypersensitivity of M460I and M460V may be advantageous.

Transcriptional and functional analysis of plasma exosomal microRNAs in acute viral myocarditis

AimTo assess the differential expression profiles of exosome-derived microRNA (miRNA) and reveal their potential functions in patients with acute viral myocarditis (AVMC). Materials & methodsPeripheral blood samples were collected from 9 patients diagnosed with AVMC and 9 healthy controls (HC) in the Affiliated Hospital of Qingdao University from July 2021 to September 2022. The exosomal miRNA expression were tested using RNA high-throughput sequencing. We conducted the GO and KEGG functional analysis to predict the potential molecular, biological functions and related signaling pathways of miRNAs in exosomes. Target genes of exosomal miRNAs were predicted and miRNA-target gene network was mapped using gene databases. Differentially expressed exosomal miRNAs were selected and their expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) to verify the sequencing results. ResultsP < 0.05 and Fold Change>2 were considered as cut-off value to screen miRNAs that were differently expressed. This study identified 14 upregulated and 14 downregulated exosome-derived miRNAs. GO and KEGG analysis showed that differentially expressed miRNAs may be related to β-catenin binding, DNA transcription activities, ubiquitin ligase, PI3K-Akt, FoxO, P53, MAPK, and etc.. The target genes of differentially expressed miRNAs were predicted using gene databases. Real-time PCR confirmed the upregulation of hsa-miR-548a-3p and downregulation of hsa-miR-500b-5p in AVMC. ConclusionsHsa-miR-548a-3p and hsa-miR-500b-5p could serve as a promising biomarker of AVMC. Exosomal miRNAs may have substantial roles in the mechanisms of AVMC.

Integrative Analysis of miRNA and circRNA Expression Profiles and Interaction Network in HSV-1-Infected Primary Corneal Epithelial Cells

Purpose Circular RNAs (circRNAs) are products of alternative splicing with roles as competitive endogenous RNAs or microRNA sponges, regulating gene expression and biological processes. However, the involvement of circRNAs in herpes simplex keratitis remains largely unexplored. Methods This study examines circRNA and miRNA expression profiles in primary human corneal epithelial cells infected with HSV-1, compared to uninfected controls, using microarray analysis. Bioinformatic analysis predicted the potential function of the dysregulated circRNAs and microRNA response elements (MREs) in these circRNAs, forming an interaction network between dysregulated circRNAs and miRNAs. Results A total of 332 circRNAs and 16 miRNAs were upregulated, while 80 circRNAs and six miRNAs were downregulated (fold change ≥2.0 and p < 0.05). Gene ontology (GO) and KEGG pathway analyses were performed on parental genes of dysregulated circRNAs to uncover potential functions in HSV-1 infection. Notably, miR-181b-5p, miR-338-3p, miR-635, and miR-222-3p emerged as pivotal miRNAs interacting with multiple dysregulated circRNAs. Conclusions This comprehensive study offers insights into differentially expressed circRNAs and miRNAs during HSV-1 infection in corneal epithelial cells, shedding light on circRNA-miRNA interactions’ potential role in herpes simplex keratitis pathogenesis.

Bioinformatic and Expression Analyses of the Wall‐Associated Kinase Genes Under High‐Temperature Stress in Sorghum

AbstractSorghum (Sorghum bicolor L. Moench) is the world's fifth most‐produced cereal. The wall‐associated kinases (WAKs) gene family plays a crucial regulatory role in various aspects of plant biology, including the response to environmental stress and pathogens. Therefore, we aimed to characterize the members of the WAK gene family in sorghum using bioinformatics tools and to determine their functional roles in heat stress by detecting transcript levels using RT‐qPCR. A total of 98 SbWAK/SbWAKL proteins were identified and classified into six phylogenetic groups. The SbWAKs/SbWAKL genes were unevenly distributed across ten chromosomes, and 33 duplications were observed on nine chromosomes. The number of amino acids and molecular weight of SbWAKs/SbWAKLs ranged from 496 to 1149 aa and 55.38 to 124.89 kDa, respectively. Forty‐eight SbWAK/SbWAKL were unstable, with an instability index greater than 40. The synteny analyses revealed sixteen SbWAK/SbWAKL genes similar in foxtail millet, thirteen in maize, and seven in the rice genome. Additionally, 107 miRNAs, including cell wall‐related miRNAs, targeted 85 SbWAK/SbWAKL genes. The cis‐acting elements in SbWAK/SbWAKL genes pointed out that these genes may be associated with light, hormone, development, and environmental stress responses. RT‐qPCR analysis of 13 SbWAK/SbWAKL genes revealed a relatively high transcript fold change in 6 SbWAK/SbWAKL under high‐temperature conditions. In conclusion, cis‐acting elements, protein–protein and miRNA interactions, and higher gene expression levels at high temperatures may indicate the existence of candidate SbWAKs/SbWAKLs genes with functions in abiotic and biotic stress response and their usage in future gene editing for breeding purposes.

Safety and efficacy of COVID-19 vaccines: A systematic review and meta-analysis of controlled and randomized clinical trials.

Vaccines against coronavirus disease 2019 (COVID-19) have been discovered within a very small duration of time as compared to the traditional way for the development of vaccines, which raised the question about the safety and efficacy of the approved vaccines. The purpose of this study is to look at the effectiveness and safety of vaccine platforms against the incidence of COVID-19. The literature search was performed on PubMed/Medline, Cochrane, and clinical trials.gov databases for studies published between 1 January 2020 and 19 February 2022. Preferred Reporting Items for Systemic Review and Meta-Analysis Statement guidelines were followed. Among 284 articles received by keywords, a total of 11 studies were eligible according to the inclusion and exclusion criteria (studies in special populations, e.g., pregnant women, paediatric patients, editorials, case reports, review articles, preclinical and in vitro studies) of the study. A total of 247,186 participants were considered for randomisation at baseline, among them, 129,572 (52.42%) were provided with vaccine (Intervention group) and 117,614 (47.58%) with the placebo (Control group). A pooled fold change estimation of 0.19 (95% CI: 0.12-0.31, p<0.0001) showed significant protection against the incidence of COVID-19 in the vaccines received group versus the placebo group. mRNA based, inactivated vaccines and non-replicating viral vector-based vaccines showed significantly protection against the incidence of COVID-19 compared to placebo with pooled fold change estimation was 0.08 (95% CI: 0.06-0.10), 0.20 (95% CI: 0.14-0.29) and 0.36 (95% CI: 0.28-0.46), respectively. Injection site discomfort and fatigue were the most common side effect observed in mRNA, non-replicating viral vector, inactivated, and protein subunit-based vaccines. All the approved vaccines were found safe and efficacious but mRNA-based vaccines were found to be more efficacious against SARS-CoV-2 than other platforms.

SPP2 plays a role in the tumorigenesis of hepatocellular carcinoma: A bioinformatic based analysis.

Hepatocellular carcinoma (HCC) patients at the same stage exhibit different prognosis, and the underlying molecular mechanism remains unclear. This study aims to identify the key genes impacting the prognosis of HCC patients. Differentially expressed gene analyses were performed between HCC samples and normal ones, and between patients with long overall survival (OS) and those with short OS, in TCGA-LIHC and GSE14520 datasets. The Kaplan-Meier method with log-rank test was used to evaluate the role of secreted phosphoprotein 2 (SPP2) in the prognosis of HCC patients. Gene set enrichment analysis (GSEA) was used to understand the difference of enriched signaling pathways between SPP2-stratified HCC subgroups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the potential functional pathways in which SPP2 might participate. SPP2 was significantly down-regulated in tumors when compared with normal tissues, or in tumor samples with short OS when compared with those with long OS [fold change (FC)>2 and false discovery rate (FDR)<0.05]. Low expression of SPP2 was associated with worse clinicopathological features like vascular invasion (P=1.6e-05), poor cancer status (with tumor, P=0.021), advanced T stage (T3 or T4, P=4.5e-04), advanced TNM stage (stage III or IV, P=3.1e-04), and with unfavorable prognosis (shorter OS, P=0.002). Gene enrichment analyses revealed that SPP2 might involve in the metabolic homeostasis of HCC and in the development of liver fibrosis and cirrhosis. SPP2 might inhibit the development of liver fibrosis and cirrhosis and the tumorigenesis of HCC, and analogs of SPP2 might be potential drugs in the prevention of these diseases.

Genetic variation is a key determinant of chromatin accessibility and drives differences in the regulatory landscape of C57BL/6J and 129S1/SvImJ mice.

Most common genetic variants associated with disease are located in non-coding regions of the genome. One mechanism by which they function is through altering transcription factor (TF) binding. In this study, we explore how genetic variation is connected to differences in the regulatory landscape of livers from C57BL/6J and 129S1/SvImJ mice fed either chow or a high-fat diet. To identify sites where regulatory variation affects TF binding and nearby gene expression, we employed an integrative analysis of H3K27ac ChIP-seq (active enhancers), ATAC-seq (chromatin accessibility) and RNA-seq (gene expression). We show that, across all these assays, the genetically driven (i.e. strain-specific) differences in the regulatory landscape are more pronounced than those modified by diet. Most notably, our analysis revealed that differentially accessible regions (DARs, N=29635, FDR<0.01 and fold change>50%) are almost always strain-specific and enriched with genetic variation. Moreover, proximal DARs are highly correlated with differentially expressed genes. We also show that TF binding is affected by genetic variation, which we validate experimentally using ChIP-seq for TCF7L2 and CTCF. This study provides detailed insights into how non-coding genetic variation alters the gene regulatory landscape, and demonstrates how this can be used to study the regulatory variation influencing TF binding.

Airbrushed nanofibers with bioactive core and antibacterial shell for wound healing application

Acute and chronic wounds are vulnerable to infection and delayed healing and require critical care and advanced wound protection. To overcome the challenges, dual therapy of antibacterial and growth factors will be a novel wound care strategy. The present study explores airbrushed core–shell nanofiber for dual delivery of epidermal growth factor (EGF) and amoxicillin (AMOX) in a sustained manner. A blend of polycaprolactone (PCL)-polyethylene oxide (PEO) was used to prepare the shell compartment for amoxicillin loading and poly-DL-lactide (PDLLA) core for EGF loading by using a customized airbrush setup. Characterization result shows a uniform distribution of nanofibers ranging between 200 and 500 nm in diameter. Amoxicillin loading in the shell compartment offers an initial burst release followed by a sustained release for up to 14 days. Whereas EGF in the core part shows a continuous sustained release throughout the release study.In-vitrostudy indicates the biocompatibility of EGF-AMOX loaded core–shell nanofibers with human dermal fibroblast cell (HDF) cells and a higher cellular proliferation compared to control samples. Gene expression data show an increase in fold change of collagen I and tropoelastin expression, indicating the regenerative properties of EGF-AMOX encapsulated nanofiber. The combination of bioactive core (EGF) and antibiotic shell (amoxicillin) in an airbrushed nanofibrous scaffold is a novel approach, which is the first time explored to deliver sustainable therapy to treat skin wounds. Our results demonstrate that PCL-PEO-Amoxicillin/PDLLA-EGF-loaded core–shell nanofibers are promising dual therapy scaffolds to deliver effective skin wound care, with the possibility of direct deposition on the wound.

Implication of noise exposure on hearing with emphasis to hOGG1 and GPx-1 polymorphisms and HO-1 protein among textile workers

Noise exposure is a health hazard in the textile industry. In cochlear hair cells, DNA damage caused by 8-oxoguanine (8-oxo G) can result in noise-induced hearing loss. Human 8-hydroxyguanine glycosylase (hOGG1) is a DNA repair enzyme that excises (8-oxo G) in the DNA and repairs DNA damage. Glutathione peroxidase-1 (GPx) is a crucial antioxidant enzyme that aids in limiting cochlear damages. Heme oxygenase-1 (HO-1) is a stress-inducible protein with a high fold change in the hair cells of the cochlea. The study aimed to investigate the association of either hOGG1 and GPx-1 polymorphisms with audiometric notches and HO-1 protein among textile workers. hOGG1 and GPx genotypes were analyzed by PCR–RFLP, and HO-1 levels were measured by ELISA in 115 male textile workers. Blood pressure and audiogram were performed. Results recorded the relation between audiometric notches and ear complaints among workers. Older age workers showed audiometric notches at > 25 dB with a significant decrease in HO-1 levels and higher levels in workers with normal audiogram. Ser/Cys genotype of hOGG1 gene was associated with age and work duration while CC genotype of GPx is associated with HO-1 levels and diastolic pressure. Ser/Cys genotype of hOGG1 gene was associated with age while Cys/Cys genotype was associated with work duration among workers. CC genotype of GPx gene was associated with higher HO-1 levels and TT genotype was associated with high diastolic pressure. Finally, hearing impairment was dependent on the duration of exposure to noise, older age, and the presence of heterozygote TC genotype of GPx gene among textile workers.