Identification of proteins' expression pathway and the effective miRNAs for the treatment of human papillomavirus-induced cervical cancer: in-silico analyses-experimental research.

Introduction: Cervical cancer is the fourth most common cancer in women. The risk factors for cervical cancer include human papillomavirus (HPV) infection, age, smoking, number of pregnancies, use of oral contraceptives, and diet. However, long-term HPV infection appears to be the main risk factor for developing cervical cancer. This in-silico analysis aims to identify the expression network of proteins and the miRNAs that play a role in the development of HPV-induced cervical cancer. Methods: The critical proteins and miRNAs were extracted using the DisGeNET and miRBase databases. String and Gephi were applied to the network analysis. The GTEx web tool was utilized to Identify tissue expression levels. The Enrichr website was used to explore the molecular function and pathways of found genes. Results: Ten proteins, TP53, MYC, AKT1, TNF, IL6, EGFR, STAT3, CTNNB1, ESR1, and JUN, were identified as the most critical shared gene network among cervical cancer and HPV. Seven miRNAs were found, including hsa-mir-146a, hsa-mir-27, hsa-mir-203, hsa-mir-126, hsa-mir-145, hsa-mir-944, and hsa-mir-93, which have a common expression in cervical cancer and HPV. Conclusion: Overall, the gene network, including TP53, MYC, AKT1, TNF, IL6, EGFR, STAT3, CTNNB1, ESR1, and JUN, and Also, hsa-mir-145, hsa-mir-93, hsa-mir-203, and hsa-mir-126 can be regarded as a gene expression pathway in HPV-induced cervical cancer.

Super learner model for classifying leukemia through gene expression monitoring.

Leukemia is a form of cancer that affects the bone marrow and lymphatic system, and it requires complex treatment strategies that vary with each subtype. Due to the subtle morphological differences among these types, monitoring gene expressions is crucial for accurate classification. Manual or pathological testing can be time-consuming and expensive. Therefore, data-driven methods and machine learning algorithms offer an efficient alternative for leukemia classification. This study introduced a novel super learning model that leverages heterogeneous machine learning models to analyze gene expression data and classify leukemia cells. The proposed approach incorporates an entropy-based feature importance technique to identify the gene profiles most significant to the labeling process. The strength of this super learning model lies in its final super learner, Random Forest, which effectively classifies cross-validated data from the candidate learners. Validation on a gene expression monitoring dataset demonstrates that this model outperforms other state-of-the-art models in predictive accuracy. The study contributes to the knowledge regarding the use of advanced machine learning techniques to improve the accuracy and reliability of leukemia classification using gene expression data, addressing the challenges of traditional methods that rely on clinical features and morphological examination.

Transcriptome-Wide Association Study Reveals New Molecular Interactions Associated with Melanoma Pathogenesis.

A transcriptome-wide association study (TWAS) was conducted on genome-wide association study (GWAS) summary statistics of malignant melanoma of skin (UK Biobank dataset) and The Cancer Genome Atlas-Skin Cutaneous Melanoma (TCGA-SKCM) gene expression weights to identify melanoma susceptibility genes. The GWAS included 2465 cases and 449,799 controls, while the gene expression testing was conducted on 103 cases. Afterward, a gene enrichment analysis was applied to identify significant TWAS associations. The melanoma's gene-microRNA (miRNA) regulatory network was constructed from the TWAS genes and their corresponding miRNAs. At last, a disease enrichment analysis was conducted on the corresponding miRNAs. The TWAS detected 27 genes associated with melanoma with p-values less than 0.05 (the top three genes are LOC389458 (RBAK), C16orf73 (MEIOB), and EIF3CL). After the joint/conditional test, one gene (AMIGO1) was dropped, resulting in 26 significant genes. The Gene Ontology (GO) biological process associated the extended gene set (76 genes) with protein K11-linked ubiquitination and regulation of cell cycle phase transition. K11-linked ubiquitin chains regulate cell division. Interestingly, the extended gene set was related to different skin cancer subtypes. Moreover, the enriched pathways were nsp1 from SARS-CoV-2 that inhibit translation initiation in the host cell, cell cycle, translation factors, and DNA repair pathways full network. The gene-miRNA regulatory network identified 10 hotspot genes with the top three: TP53, BRCA1, and MDM2; and four hotspot miRNAs: mir-16, mir-15a, mir-125b, and mir-146a. Melanoma was among the top ten diseases associated with the corresponding (106) miRNAs. Our results shed light on melanoma pathogenesis and biologically significant molecular interactions.

ACRE, a class of AP2/ERF transcription factors, activates the expression of sweet potato ß-amylase and sporamin genes through the sugar-responsible element CMSRE-1.

Sugars, synthesized by photosynthesis in source organs, are loaded and utilized as an energy source and carbon skeleton in sink organs, and also known to be important signal molecules regulating gene expression in higher plants. The expression of genes coding for sporamin and ß-amylase, the two most abundant proteins in storage roots of sweet potato, is coordinately induced by sugars. We previously reported on the identification of the carbohydrate metabolic signal-responsible element-1 (CMSRE-1) essential for the sugar-responsible expression of two genes. However, transcription factors that bind to this sequence have not been identified. In this study, we performed yeast one-hybrid screening using the sugar-responsible minimal promoter region of the ß-amylase gene as bait and a library composed only transcription factor cDNAs of Arabidopsis. Two clones, named Activator protein binding to CMSRE-1 (ACRE), encoding AP2/ERF transcription factors were isolated. ACRE showed transactivation activity of the sugar-responsible minimal promoter in a CMSRE-1-dependent manner in Arabidopsis protoplasts. Electric mobility shift assay (EMSA) using recombinant proteins and transient co-expression assay in Arabidopsis protoplasts revealed that ACRE could actually act to the CMSRE-1. Among the DEHYDRATION -RESPONSIVE ELEMENT BINDING FACTOR (DREB) subfamily, almost all homologs including ACRE, could act on the DRE, while only three ACREs could act to the CMSRE-1. Moreover, ACRE-homologs of Japanese morning glory also have the same property of DNA-binding preference and transactivation activity through the CMSRE-1. These findings suggested that ACRE plays an important role in the mechanism regulating the sugar-responsible gene expression through the CMSRE-1 conserved across plant species.

Boric Acid in Milk Replacer as a Health Enhancer and Growth Promoter for Lambs in the Suckling Period.

This study was performed to investigate the effects of boric acid supplementation in milk replacer of lambs in the suckling period on performance, biochemical parameters, the antioxidant system, fecal culture, and expression of some genes. During the suckling period, 60 lambs (4 days old) were randomly given four levels of boric acid (0, 30, 60, and 90 mg/kg body weight) via milk replacer for 57 days. The lambs supplemented with boric acid had a higher weight gain and better feed conversion ratio. Boric acid supplementation quadratically increased serum triglyceride, total protein, alkaline phosphatase, serum antioxidant activity and oxidative stress biomarkers, and fecal flora and decreased IL1ß, IL10, iNOS, NF-kB, and TNF-α gene expressions. The effect of boric acid on rumen papilla development could not be determined since the animals were not slaughtered. In conclusion, the use of boric acid to lambs in the suckling period improved the average weekly body weight gain and feed conversion efficiency, positively affected some biochemical parameters, antioxidant system, and intestinal flora, and also affected gene expressions related to the immune system. Boric acid supplementation had a beneficial effect on the health and growth of suckling lambs.

Root morphology and physiological of their relationship with nitrogen uptake in wheat (Triticum aestivum L.).

Nitrogen (N) application is believed to improve photosynthesis in flag leaf ultimately increase final yield. The main results at 20-30 days after anthesis, the activities of superoxide dismutase (SOD) and peroxidase (POD) and soluble protein in flag leaves of N150 were found to be the most effective. Increased root weight density, root length density and root volume density at flowering stage, up to 10.6 %, 15.0 %, respectively. The root weight density, root length density and root bulk density at flowering and mature stages were the highest at the N180. Delaying the senescence physiology of post flowering leaves in the middle, and late stage, photosynthesis of leaves in the middle and late stage, improving the light energy interception of wheat, and then improving the light energy utilization efficiency. The stomatal conductance of flag leaves 15-30 days after anthesis, the maximum potential photochemical efficiency 20-30 days after anthesis, and the photochemical quenching of flag leaves 25-30 days after anthesis, and improved the light energy utilization efficiency by 9.6%-11.1 %. Yunhan-20410 the gene expressions of TaTZF1, TaNCY1, TaNCY3 and TaAKaGall in wheat flag leaves were significantly up-regulated YH-20410 gene expressions of N application treatment were significantly up-regulated compared with no N application treatment. The goal of high yield high efficiency, and high quality can be achieved by YH-20410 and combined to N180 kg ha-1. The senescence physiology and gene expression of post flowering leaves in the middle and late stage, prolonging the photosynthesis of leaves in the middle and late stage, improving the light energy interception of canopy, and then improving the light energy utilization efficiency.

Towards understanding sex differences in autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviours and lack of empathy. Its significant genetic heritability and potential comorbidities often lead to diagnostic and therapeutic challenges. This review addresses the biological basis of ASD, focusing on the sex differences in gene expression and hormonal influences. ASD is more commonly diagnosed in males at a ratio of 4:1, indicating a potential oversight in female-specific ASD research and a risk of underdiagnosis in females. We consider how ASD manifests differently across sexes by exploring differential gene expression in female and male brains and consider how variations in steroid hormones influence ASD characteristics. Synaptic function, including excitation/inhibition ratio imbalance, is influenced by gene mutations and this is explored as a key factor in the cognitive and behavioural manifestations of ASD. We also discuss the role of micro RNAs (miRNAs) and highlight a novel mutation in miRNA-873, which affects a suite of key synaptic genes, neurexin, neuroligin, SHANK and post-synaptic density proteins, implicated in the pathology of ASD. Our review suggests that genetic predisposition, sex differences in brain gene expression, and hormonal factors significantly contribute to the presentation, identification and severity of ASD, necessitating sex-specific considerations in diagnosis and treatments. These findings advocate for personalized interventions to improve the outcomes for individuals with ASD.

Integration analysis of ATAC-seq and RNA-seq provides insight into fatty acid biosynthesis in Schizochytrium limacinum under nitrogen limitation stress.

BACKGROUND: Schizochytrium limacinum holds significant value utilized in the industrial-scale synthesis of natural DHA. Nitrogen-limited treatment can effectively increase the content of fatty acids and DHA, but there is currently no research on chromatin accessibility during the process of transcript regulation. The objective of this research was to delve into the workings of fatty acid production in S. limacinum by examining the accessibility of promoters and profiling gene expressions. RESULTS: Results showed that differentially accessible chromatin regions (DARs)-associated genes were enriched in fatty acid metabolism, signal transduction mechanisms, and energy production. By identifying and annotating DARs-associated motifs, the study obtained 54 target transcription factor classes, including BPC, RAMOSA1, SPI1, MYC, and MYB families. Transcriptomics results revealed that several differentially expressed genes (DEGs), including SlFAD2, SlALDH, SlCAS1, SlNSDHL, and SlDGKI, are directly related to the biosynthesis of fatty acids, meanwhile, SlRPS6KA, SlCAMK1, SlMYB3R1, and SlMYB3R5 serve as transcription factors that could potentially influence the regulation of fatty acid production. In the integration analysis of DARs and ATAC-seq, 13 genes were identified, which were shared by both DEGs and DARs-associated genes, including SlCAKM, SlRP2, SlSHOC2, SlTN, SlSGK2, SlHMP, SlOGT, SlclpB, and SlDNAAF3. CONCLUSIONS: SlCAKM may act as a negative regulator of fatty acid and DHA synthesis, while SlSGK2 may act as a positive regulator, which requires further study in the future. These insights enhance our comprehension of the processes underlying fatty acid and DHA production in S. limacinum. They also supply a foundational theoretical framework and practical assistance for the development of strains rich in fatty acids and DHA.

Modulation of Immune Response and Cecal Microbiota by Dietary Fenugreek Seeds in Broilers.

Fenugreek seeds (FSs) are a natural source of bioactive compounds that may modulate the immune system and gut microbiota in broilers. This study examined the effects of dietary fenugreek seed powder on immune-related gene expression and cecal microbiota composition in broilers. A total of 144 broiler chickens were randomly allocated to three dietary groups, CON (0 g/kg FS, FS5 (5 g/kg FS) and FS10 (10 g/kg FS), each with 6 replicates of 8 birds. Ileum tissues and cecal contents were collected on day 42 for the mRNA expression of inflammation and antimicrobial defense-related genes and cecal microbiome diversity, respectively. The results indicated that fenugreek seeds downregulated mRNA-level inflammation and antimicrobial defense-related genes: IL6, IL8L2, CASP6, PTGS2, IRF7, AvBD9, AvBD10, and AvBD11. Moreover, fenugreek seeds altered the cecal microbial community by increasing the population of Firmicutes and decreasing the population of Actinobacteriota, Gemmatimonadota and Verrucomicrobiota at the phylum level and increasing Alistipes, Bacteriodes and Prevotellaceae at the genera level. These findings suggest that fenugreek seeds have a positive impact on the immunological profile and microbiome of broiler chickens, possibly through the interplay of the immune system and the gut microbiome.

The WMI Rat of Premature Cognitive Aging Presents Intrinsic Vulnerability to Oxidative Stress in Primary Neurons and Astrocytes Compared to Its Nearly Isogenic WLI Control.

The primary neuronal and astrocyte culture described here is from the stress-hyperreactive Wistar Kyoto (WKY) More Immobile (WMI) rat with premature aging-related memory deficit, and its nearly isogenic control, the Less Immobile (WLI) strain. Primary WMI hippocampal neurons and cortical astrocytes are significantly more sensitive to oxidative stress (OS) generated by administration of H2O2 compared to WLI cells as measured by the trypan blue cell viability assay. Intrinsic genetic vulnerability is also suggested by the decreased gene expression in WMI neurons of catalase (Cat), and in WMI cortical astrocytes of insulin-like growth factor 2 (Igf2), synuclein gamma (Sncg) and glutathione peroxidase 2 (Gpx2) compared to WLI. The expressions of several mitochondrial genes are dramatically increased in response to H2O2 treatment in WLI, but not in WMI cortical astrocytes. We propose that the vulnerability of WMI neurons to OS is due to the genetic differences between the WLI and WMI. Furthermore, the upregulation of mitochondrial genes may be a compensatory response to the generation of free radicals by OS in the WLIs, and this mechanism is disturbed in the WMIs. Thus, this pilot study suggests intrinsic vulnerabilities in the WMI hippocampal neurons and cortical astrocytes, and affirm the efficacy of this bimodal in vitro screening system for finding novel drug targets to prevent oxidative damage in illnesses.

Ameliorative effects of rutin and rutin-loaded chitosan nanoparticles on testicular oxidative stress and histological damage induced by cyclophosphamide in male rats.

Cyclophosphamide (CP) is broadly used to kill various tumor cells; however, its repeated uses have been reported to cause reproductive dysfunction and infertility. Natural flavonoid, rutin (RUT), possesses strong antioxidant and antiapoptotic activity that is attributed to ameliorate the reproductive dysfunction induced by CP. Many previous studies proved that the formulation of flavonoids in nanoemulsion has a promising perspective in mitigating the side effects of chemotherapy. Therefore, the main objective of this study was to investigate the ameliorative effects of RUT and RUT-loaded chitosan nanoparticles (RUT-CH NPs) against CP-induced reproductive dysfunction in male rats. For this aim, thirty-six male albino rats were randomly allocated into six groups as follows: control, RUT, RUT-CH NPs, CP, CP + RUT, and CP + RUT-CH NPs. In the CP groups, a single intraperitoneal injection of CP (150 mg/kg bwt) was administered on the first day of the experiment. RUT and RUT-CH NPs were orally administered either alone or with CP injection at a dose of 10 mg/kg bwt per day for 60 days. The results revealed that CP administration caused significant testicular oxidative stress damage through increasing the nitric oxide and malondialdehyde levels as well as decreasing the total antioxidant capacity and reduced glutathione contents. It also impaired spermatogenesis and steroidogenesis via altering the transcription levels of CYP11A1, HSD-3b, StAR, Bax, bcl-2, and Nrf-2 genes. Otherwise, the oral intake of either RUT or RUT-CH NPs with CP injection effectively attenuated these alterations and significantly improved the microscopic appearance of testicular tissue. In conclusion, this study highlights the potential of RUT either free or NPs in mitigating CP-induced testicular dysfunction via its antioxidant and anti-apoptotic properties.

Low-temperature perception and modulations in Ocimum basilicum commercial cultivar CIM-Shishir: Biosynthetic potential with insight towards climate-smart resilience.

The newly released interspecific hybrid variety CIM-Shishir, resulting from a cross between Ocimum basilicum and Ocimum kilimandscharicum claims to be a multicut, lodging resistant, cold tolerant, high essential oil yielding with linalool rich variety. It has a purple-green stem and has a unique feature and advantage of better survival in the winter season than other O. basilicum varieties, illustrating its physiological mechanisms for cold tolerance. In this study, we subjected both the CIM-Shishir variety and a control plant to cold stress to investigate the impact of low temperatures on various physiological, trichome developments, secondary metabolite constitution aspects related to essential oil production, and gene expression. The analysis revealed a significantly higher density and altered morphology of trichomes on the leaf surface of the variety subjected to low temperatures, indicating its adaptation to cold conditions. Furthermore, when comparing the treated plants under low-temperature stress, it was observed that the relative electrolyte leakage and Malondialdehyde (MDA) contents substantially increased in the control in contrast to the CIM-Shishir variety. This finding suggests that CIM-Shishir exhibits superior cold tolerance. Additionally, an increase in proline content was noted in the variety exposed to low temperatures compared to the control. Moreover, the chlorophyll and anthocyanin content gradually increased with prolonged exposure to low-temperature stress in the newly developed variety, indicating its ability to maintain photosynthetic capacity and adapt to cold conditions. The activities of superoxide dismutase (SOD) also increased under low-temperature conditions in the CIM-Shishir variety, further highlighting its cold tolerance behaviour. In our research, we investigated the comprehensive molecular mechanisms of cold response in Ocimum. We analyzed the expression of key genes associated with cold tolerance in two plant groups: the newly developed hybrid variety known as CIM-Shishir Ocimum, which exhibits cold tolerance, and the control plants susceptible to cold climates that include WRKY53, ICE1, HOS1, COR47, LOS15, DREB5, CBF4, LTI6, KIN, and ERD2. These genes exhibited significantly higher expression levels in the CIM-Shishir variety compared to the control, shedding light on the genetic basis of its cold tolerance. The need for climate-smart, resilient high-yielding genotype is of high importance due to varied climatic conditions as this will hit the yield drastically and further to the economic sectors including farmers and many industries that are dependent on the bioactive constituents of Ocimum.

Ameliorative effects of androstenediol against acetic acid-induced colitis in male wistar rats via inhibiting TLR4-mediated PI3K/Akt and NF-κB pathways through estrogen receptor ß activation.

5-androstenediol (ADIOL) functions as a selective estrogen receptor ß (ERß) ligand with a protective effect against many diseases. So, we conducted a novel insight into its role in acetic acid (AA)-induced colitis and investigated its effect on TLR4-Mediated PI3K/Akt and NF-κB Pathways and the potential role of ERß as contributing mechanisms. METHODS: Rats were randomized into 5 Groups; Control, Colitis, Colitis + mesalazine (MLZ), Colitis + ADIOL, and Colitis + ADIOL + PHTPP (ER-ß antagonist). The colitis was induced through a rectal enema of acetic acid (AA) on the 8th day. At the end of treatment, colons were collected for macroscopic assessment. Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor kappa b (NF-κB), toll-like receptor (TLR4), and phosphorylated Protein kinase B (pAKT) were measured. Besides, Gene expression of interleukin-1beta (IL-1ß), metalloproteases 9 (Mmp9), inositol 3 phosphate kinase (PI3K), Neutrophil gelatinase-associated lipocalin (NGAL), ERß and NLRP6 were assessed. Histopathological and immunohistochemical studies were also investigated. RESULTS: Compared to the untreated AA group, the disease activity index (DAI) and macroscopic assessment indicators significantly decreased with ADIOL injections. Indeed, ADIOL significantly decreased colonic tissue levels of MDA, TLR4, pAKT, and NF-κB immunostainig while increased SOD activity and ß catenin immunostainig. ADIOL mitigated the high genetic expressions of IL1ß, NGAL, MMP9, and PI3K while increased ERß and NLRP6 gene expression. Also, the pathological changes detected in AA groups were markedly ameliorated with ADIOL. The specific ERß antagonist, PHTPP, largely diminished these protective effects of ADIOL. CONCLUSION: ADIOL could be beneficial against AA-induced colitis mostly through activating ERß.

High-Pressure Processing-Impacts on the Virulence and Antibiotic Resistance of Listeria monocytogenes Isolated from Food and Food Processing Environments.

High-pressure processing (HPP) is one of the non-thermal methods of food preservation considered to be safe but may cause an increase/decrease in virulence potential and antibiotic resistance. The aim of the present study was to evaluate the survival of L. monocytogenes isolates after high-pressure processing (200 and 400 MPa for 5 min) and to determine changes in phenotypic and genotypic antibiotic resistance and virulence after this treatment. The 400 MPa treatment was shown to be effective in reducing pathogens to safe levels; however, the potential for cell recovery during storage was observed. In addition, studies on changes in virulence indicated possibilities related to a decrease in actA gene expression, overexpression of the hly and osfX gene, and an increase in biofilm-forming ability. The studies on changes in antibiotic resistance of isolates showed that all isolates showing initial susceptibility to lincomycin, fosfomycin, trimethoprim/sulfamethoxazole, and tetracycline became resistant to these antibiotics, which was associated with an increase in the values of minimum inhibitory concentrations. An increase in the expression of antibiotic resistance genes (mainly tetA_1, tetA_3, tetC) was also observed (mainly after the application of 200 MPa pressure), which was isolate dependent. However, it is noteworthy that the induced changes were permanent, i.e., they persisted even after the restoration of optimal environmental conditions. The results presented in our work indicate that the stress occurring during HPP can affect both phenotypic and genotypic changes in the virulence and antibiotic resistance potential of pathogens isolated from food and food processing environments. The potential associated with cell recovery and persistence of changes may influence the spread of virulent isolates of pathogens with increased antibiotic resistance in the food and food processing environment.

Upregulation of oxidative stress by triphenyl phosphate (TPhP) exposure causes antioxidant insult and apoptotic process in Epithelioma papulosum cyprini (EPC) cells.

Triphenyl phosphate (TPhP) is the predominant compound of organophosphate flame retardants (OPFRs), which can elicit a toxicological effect on physiological response and tissue development of fish. In this study, we investigated the effect of TPhP exposure on cell viability, antioxidant capacities, and apoptosis in EPC cells. Current study revealed that TPhP exposure could decrease cell viability and promote intracellular oxidative stress in EPC cells. In addition, high-dose TPhP exposure could facilitate antioxidant insults and cause mitochondrial collapse in a dose-dependent manner, along with increased gene expressions involved in apoptosis and unfolded protein response (UPR). These results indicated that reactive oxygen species (ROS)-induced cytotoxic stress and cell death were involved in antioxidant insults and apoptotic activation in TPhP-exposed fish cells.

High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity.

P-glycoprotein (encoded by the ABCB1 gene) has a dual role in regulating inflammation and reducing chemotherapy efficacy in various diseases, but there are few studies focused on pulmonary TB patients. In this study, our objective was to identify a list of genes that correlate with high and low levels of ABCB1 gene expression in the lungs of pulmonary TB patients with different activity of chronic granulomatous inflammation. We compared gene expression in two groups of samples (with moderate and high activity of tuberculomas) to identify their characteristic gene signatures. Gene expression levels were determined using quantitative PCR in samples of perifocal area of granulomas, which were obtained from 65 patients after surgical intervention. Subsequently, two distinct gene signatures associated with high inflammation activity were identified. The first signature demonstrated increased expression of HIF1a, TGM2, IL6, SOCS3, and STAT3, which correlated with high ABCB1 expression. The second signature was characterized by high expression of TNFa and CD163 and low expression of ABCB1. These results provide insight into various inflammatory mechanisms and association with P-gp gene expression in lung tissue of pulmonary TB patients and will be useful in the development of a host-directed therapy approach to improving the effectiveness of anti-TB treatment.

Gene expression networks involved in multiple cellular programs coexist in individual hepatocellular cancer cells.

The gene expression networks of a single cell can be used to reveal cell type- and condition-specific patterns that account for cell states, cell identity, and its responses to environmental changes. We applied single cell sequencing datasets to define mRNA patterns and visualized potential cellular capacities among hepatocellular cancer cells. The expressing numbers and levels of genes were highly heterogenous among the cancer cells. The cellular characteristics were dependent strongly on the expressing numbers and levels of genes, especially oncogenes and anti-oncogenes, in an individual cancer cell. The transcriptional activations of oncogenes and anti-oncogenes were strongly linked to inherent multiple cellular programs, some of which oppose and contend against other processes, in a cancer cell. The gene expression networks of multiple cellular programs proliferation, differentiation, apoptosis, autophagy, epithelial-mesenchymal transition, ATP production, and neurogenesis coexisted in an individual cancer cell. The findings give rise a hypothesis that a cancer cell expresses balanced combinations of genes and undergoes a given biological process by rapidly transmuting gene expressing networks.

Effect of Four Functional Feed Additives on Growth, Serum Biochemistry, Antioxidant Capacity, Gene Expressions, Histomorphology, Digestive Enzyme Activities and Disease Resistance in Juvenile Olive Flounder, Paralichthys olivaceus.

An 8-week feeding trial was executed to evaluate the efficacy of four functional feed additives in replacing antibiotics in juvenile olive flounder, Paralichthys olivaceus, fed with a low-fish-meal diet. A basal diet without feed additives was used as a control (CON); other diets were formulated by supplementing 0.50% taurine (TW), 0.30% peptide (PT), 0.23% mineral water (MW), 0.35% yeast-extracted nucleotides (GRO), 0.35% GRO + 0.50% taurine (GROTW), 0.35% GRO + 0.30% peptide (GROPT) and 0.35% GRO + 0.23% mineral water (GROMW) into the basal diet; in addition, one diet was supplemented with oxytetracycline (OTC) at 0.5% as a positive control. Triplicate groups of 25 fish with an average weight of 5.15 ± 0.06 g (mean ± SD) were fed one of the nine experimental diets. At the end of the feeding trial, the weight gain, specific growth rate and protein efficiency ratio of fish fed the GRO, GROMW, GROPT and GROTW diets were significantly higher than those of fish fed the CON diet (p < 0.05). The feed efficiency of fish fed the GRO, GROMW, GROPT and GROTW diets was significantly higher than that of fish fed the TW and OTC diets. However, the survival, hepatosomatic index, viscerosomatic index and condition factor of fish, as well as their whole-body proximate composition, were not significantly affected by the experimental diets (p > 0.05). The serum glutamic pyruvic transaminase of fish fed the GROPT diet was significantly lower than that of fish fed the CON diet. However, glutamic oxaloacetic transaminase, glucose and total protein were not significantly affected by the experimental diets (p > 0.05). The serum superoxide dismutase activity of fish fed the PT, TW, GRO, GROMW, GROPT and GROTW diets was significantly higher than that of fish fed the CON diet. The lysozyme activity of fish fed the PT, GRO, GROMW, GROPT and GROTW diets was significantly higher than that of fish fed the CON and OTC diets. The myeloperoxidase activity of fish fed the TW, GRO, GROMW, GROPT and GROTW diets was significantly higher than that of fish fed the CON, PT and MW diets (p < 0.05). The flounder growth hormone gene expression of fish fed the TW, GRO, GROMW, GROPT, GROTW and OTC diets was significantly higher than that of fish fed the CON, PT and MW diets (p < 0.05). The interleukin 1ß and interleukin 10 gene expressions of fish fed the GRO, GROMW, GROPT and GROTW diets were significantly higher than those of fish fed the CON, PT, TW and MW diets (p < 0.05). Intestinal histology showed a significantly higher villi length for fish fed the GRO, GROMW, GROPT and GROTW diets compared to that of fish fed the CON diet (p < 0.05). Digestive enzyme activities such as trypsin activity were significantly higher in fish fed the GROMW, GROPT and GROTW diets than those in the rest of the diet groups (p < 0.05). Amylase activity in fish fed the MW, GRO, GROMW, GROPT, GROTW and OTC diets was significantly higher than that of fish fed the PT, TW and CON diets (p < 0.05). On the other hand, the lipase activity of fish fed the TW, GRO, GROMW, GROPT and GROTW diets was significantly higher than that of fish fed the CON, PT, MW and OTC diets (p < 0.05). The cumulative survival rate of fish fed the PT, GROTW, GROPT and GROMW diets was significantly higher than that of fish fed the CON, TW and MW diets after thirteen days of the challenge testing. Overall, the results demonstrate that the GRO, GROMW, GROPT and GROTW diets could be beneficial feed additives to replace antibiotics in juvenile olive flounder fed low-fish-meal diets.

Effect of curcumin nanoparticles and alcoholic extract of Falcaria vulgaris on the growth rate, biofilm, and gene expression in Pseudomonas aeruginosa isolated from burn wound infection.

PURPOSE: This study aimed to investigate the effect of Curcumin nanoparticles and alcoholic extract of Falcaria vulgaris on the growth rate, biofilm, and gene expression in Pseudomonas aeruginosa isolated from burn wound infection. METHODS: The alcoholic extract of Falcaria vulgaris was purchased from Pasargad Company. Curcumin nanoparticles were synthesized. Antibacterial activity of Curcumin nanoparticles and alcoholic extract of Falcaria vulgaris was investigated by microdilution method alone and in combination. Biofilm inhibitory was investigated by microtitrplate method. Effect of Curcumin nanoparticles and alcoholic extract of Falcaria vulgaris were evaluated on algD gene expression via Real-Time PCR. Cytotoxicity was evaluated by MTT assay on HDF cell line. Then, the data were analyzed using SPSS software. RESULTS: Synthesized Curcumin nanoparticles were approved by Fourier Transform Infrared (FTIR), and Scanning Electron Microscope. The alcoholic extract of Falcaria Vulgaris showed significant antibacterial activity against multidrug resistance (MDR) P. aeruginosa isolates at a concentration of 156.25 µg/mL. Moreover, MIC of the curcumin nanoparticle for isolates was 625 µg/mL. Based on fraction inhibition concentration, synergy, and the additive effect were shown against %7.7, and %93.3 of MDRs, respectively. The sub-MIC concentration of the binary compound reduced biofilms and algD gene expression in P. aeruginosa isolates. The Biological function of HDF cell lines was desirable after the effect of the binary compound. CONCLUSIONS: Regarding our results, this combination can be suggested as a promising agent in terms of biofilm inhibitory and antimicrobial properties.

α-tocopherol ameliorates copper II oxide nanoparticles-induced cytotoxic, biochemical, apoptotic, and genotoxic damages in the rainbow trout gonad cells-2 (RTG-2) culture.

We investigated the effects of α-tocopherol on oxidative stress-caused damage caused by copper II oxide nanoparticles (CuO NPs) on Oncorhynchus mykiss gonadal cells (RTG-2) for 24 and 48 h. α-Tocopherol reversed the cell death and alterations in the expressions of genes such as sod1, gpx1a, gpx4b, and igf2 caused by CuO NPs; it also supported the expressions of cat, igf1, and gapdh genes caused by CuO NPs for 24 h and promoted alterations in the expressions of the sod2, gh1, and igf1 genes for 48 h. Additionally, α-tocopherol reversed the caspase 3/7 activity increased by CuO NPs for 24 h and supported it's decrease for 48 h. α-Tocopherol supported the increase in tail DNA (%) affected by CuO NPs for 24 h and reversed it for 48 h. Therefore, α-tocopherol may have the potential to protect against cellular alterations induced by CuO NPs in a time-dependent manner.