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The molecular features of the follicular variant of papillary thyroid cancer are closely related to the clinical behavior of the tumor and the prognosis of the disease. BRAF-V600E mutations in patients with a follicular variant of papillary thyroid cancer have not been identified; however, the majority of patients had T3-4N0M0 stage of the disease. Changes in the expression of transcription and growth factors and AKT/m-TOR signaling pathway components were detected. In addition, hyperexpression of m-TOR and 4EBP1 kinases and CAIX enzyme was shown compared to the classical variant of papillary thyroid cancer, where an increase in the nuclear factor NF-κB p65 and c-RAF kinase expression was observed. [ABSTRACT FROM AUTHOR]

In most plants, major unsaturated fatty acids (UFAs) are three C18 species, namely, oleic (18:1), linoleic (18:2), and α-linolenic (18:3) acids. These simple compounds play multiple crucial roles in planta and are also important economic traits of oil crops. The enzymatic steps of C18 UFA biosynthesis have been well established. However, the associated FA/lipid trafficking between the plastid and the endoplasmic reticulum remains largely unclear, as does the regulation of the expression and activities of the involved enzymes. In this review, we will revisit the biosynthesis of C18 UFAs with an emphasis on the trafficking, and present an overview of the key enzymes and their regulation. Of particular interest is the emerging regulatory network composed of transcriptional factors and upstream signaling pathways. The review thereby provides the promise of using physical, biochemical and/or genetic means to manipulate FA composition and increase oil yield in crop improvement. [ABSTRACT FROM AUTHOR]

• Response mechanisms to weak acids were first revealed in mixed sugars fermentation. • Synergistic inhibition of acetic acid and formic acid on S. cerevisiae was serious. • Three transcription factors related to acetic and formic acids stress were proposed. The growth and ethanol fermentation of Saccharomyces cerevisiae are vulnerable to weak acid that coexists with sugar in lignocellulosic hydrolysate. In this study, the molecular basis of S. cerevisiae in response to acetic and formic acids was investigated when fermented with glucose and xylose at pH 5.0. Transcriptional profiling revealed that 294 (657 in total) differentially expressed genes (DEGs) were exclusive to mixed acetic and formic acids (Aa_Fa) group, the DEGs in acetic acid (Aa) and formic acid (Fa) group were 308 and 326, respectively. The general responses to Aa, Fa, and Aa_Fa mainly involved carbohydrate metabolism, amino acid metabolism, transcriptional regulation, and stress response. In Aa_Fa group, the enrichment ratio of each pathway was much higher than being exposed to Aa or Fa stress individually, and some enrichments not existed in Aa or Fa group were observed, suggesting the synergistic anti-inhibition responses of S. cerevisiae was triggered. In yeast cells, bioconversion, stress response, and transmembrane transport could be activated to resist acetic and formic acids accompanying with energy consumption. Except the putative transcriptional factor (TF) - Haa1p, the other three TFs, Hap4p, Yox1p, and Mag1p, might as well be considered to participate in acetic and formic acids resistance responses. [ABSTRACT FROM AUTHOR]

Caspase-1 is an evolutionarily conserved inflammatory mediated enzyme that cleaves and activates inflammatory cytokines. It can be activated through the assembly of inflammasome and its major effect is to activate the pro-inflammatory cytokines; interleukin 1β (IL-1β) and interluekine-18 (IL-18). In addition to IL-1β and IL-8, several lines of evidence showed that caspase-1 targets the substrates that are involved in different metabolic pathways, including lipid metabolism. Caspase-1 regulates lipid metabolism through cytokine dependent or cytokine independent regulation of genes that involved in lipid metabolism and its regulation. To date, there are several reports on the role of caspase-1 in lipid metabolism. Therefore, this review is aimed to summarize the role of caspase-1 in lipid metabolism and its regulation. [ABSTRACT FROM AUTHOR]

Soil dwelling Streptomyces species are faced with large variations in carbon or nitrogen sources, phosphate, oxygen, iron, sulfur, and other nutrients. These drastic changes in key nutrients result in an unbalanced metabolism that have undesirable consequences for growth, cell differentiation, reproduction, and secondary metabolites biosynthesis. In the last decades evidence has accumulated indicating that mechanisms to correct metabolic unbalances in Streptomyces species take place at the transcriptional level, mediated by different transcriptional factors. For example, the master regulator PhoP and the large SARP-type regulator AfsR bind to overlapping sequences in the afsS promoter and, therefore, compete in the integration of signals of phosphate starvation and S -adenosylmethionine (SAM) concentrations. The cross-talk between phosphate control of metabolism, mediated by the PhoR–PhoP system, and the pleiotropic orphan nitrogen regulator GlnR, is very interesting; PhoP represses GlnR and other nitrogen metabolism genes. The mechanisms of control by GlnR of several promoters of ATP binding cassettes (ABC) sugar transporters and carbon metabolism are highly elaborated. Another important cross-talk that governs nitrogen metabolism involves the competition between GlnR and the transcriptional factor MtrA. GlnR and MtrA exert opposite effects on expression of nitrogen metabolism genes. MtrA, under nitrogen rich conditions, represses expression of nitrogen assimilation and regulatory genes, including GlnR, and competes with GlnR for the GlnR binding sites. Strikingly, these sites also bind to PhoP. Novel examples of interacting transcriptional factors, discovered recently, are discussed to provide a broad view of this interactions. Altogether, these findings indicate that cross-talks between the major transcriptional factors protect the cell metabolic balance. A detailed analysis of the transcriptional factors binding sequences suggests that the transcriptional factors interact with specific regions, either by overlapping the recognition sequence of other factors or by binding to adjacent sites in those regions. Additional interactions on the regulatory backbone are provided by sigma factors, highly phosphorylated nucleotides, cyclic dinucleotides, and small ligands that interact with cognate receptor proteins and with TetR-type transcriptional regulators. We propose to define the signal integration DNA regions (so called integrator sites) that assemble responses to different stress, nutritional or environmental signals. These integrator sites constitute nodes recognized by two, three, or more transcriptional factors to compensate the unbalances produced by metabolic stresses. This interplay mechanism acts as a safety net to prevent major damage to the metabolism under extreme nutritional and environmental conditions. [ABSTRACT FROM AUTHOR]

As a dominating air pollutant, atmospheric fine particulate matter within 2.5 μm in diameter (PM 2.5) has attracted increasing attention from the researchers all over the world, which will lead to various adverse effects on the central nervous system (CNS), yet the potential mechanism is unclear. In this study, the microglia (BV2 cell line) were exposed to different concentrations of PM 2.5 (5, 10 and 20 μg/cm2) for 24 h. It was found that PM 2.5 could result in adverse effects on microglia such as decreased cell viability, structural damage and even cell death. And it was reported that long non-coding RNAs (lncRNAs) could participate in multitudinous neurological diseases. Therefore, the microarray analysis was conducted in order to disclose the underlying neurotoxicity mechanism of PM 2.5 by ascertaining the differentially expressed lncRNAs (DElncRNAs). The consequences indicated that the DElncRNAs were enriched in various biological pathways, including ferroptosis, IL-17 signaling pathway and NOD-like receptor signaling pathway. Moreover, the cis- and trans-regulated mRNAs by DElncRNAs as well as the corresponding transcriptional factors (TFs) were observed, such as CEBPA, MYC, MEIS1 and KLF4. In summary, our study supplies some candidate libraries and potential preventive target against PM 2.5 -induced toxicity through targeting lncRNAs. Furthermore, the post-transcriptional regulation will contribute to the future research on PM 2.5 -induced neurotoxicity. • PM 2.5 exposure caused a series of adverse reactions in microglia. • A cluster of lncRNAs were dysregulated in microglia after PM 2.5 exposure. • DElncRNAs induced by PM 2.5 exposure were involved in Ferroptosis, IL-17 signaling pathway and NOD-like receptor signaling pathway. [ABSTRACT FROM AUTHOR]

Citrus grandis 'Tomentosa' (CGT) contain abundant essential oils (EOs), while the variation of them among different varieties is still unclear which hinders the fully utilization of CGT EOs in industry. Besides, the molecular mechanism underlying the accumulation of EOs in Citrus family remains largely unknown. In this study, multi-omics including GC-MS (gas chromatography-mass spectrometry), RNA-seq (ribonucleic acid sequencing), and ATAC-seq (assay for transposase-accessible chromatin using sequencing) were applied for three varieties of CGT ('ZM', 'FM', and 'GQ') to reveal the CGT EOs variation at the chemical, transcriptional and chromatinic levels. CGT EOs mainly consist of monoterpenes and sesquiterpenes, and the total terpenes amounts in three varieties rank as 'ZM' > 'FM' > 'GQ'. The total amount of monoterpenes in 'ZM' is almost triple than that in 'FM' and is septuple than that in 'GQ'. The average contents of sesquiterpenes in the EOs of 'ZM', 'FM', and 'GQ' are 73.9 ug/g, 42.65 ug/g and 1.75 ug/g, respectively. RNA-seq analysis among the three varieties demonstrated that the structural genes of 1-DEOXY-D-XYLULOSE 5-PHOSPHATE SYNTHASE (DXS) and 1-DEOXY-D-XYLYLOSE 5-PHOSPHATE REDUCTOISOMERASE (DXR) are differentially expressed genes (DEGs) in MEP pathway for the biosynthesis of monoterpenes, and 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE (HMGR) is the DEG for sesquiterpenes synthesis in MVA pathway. Integrated GC-MS, RNA-seq and ATAC-seq analysis reveals 9 transcriptional factors were predicted to regulate the terpenes synthesis in the exocarps of CGT. The present investigation provides important information for manufacturers and breeders of CGT who require raw materials and germplasm of CGT in better quality for the production of EOs. • The essential oils in 'Huajuhong' are mainly monoterpenes and sesquiterpenes. • Chromatin accessiblity landscape of 'Huajuhong' was provided. • Three transcriptional factors for terpenes synthesis was predicted. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify genes associated with the biodegradation of phenol by Acinetobacter sp. strain DF4 through the use of differential display (DD) methodology. The bacteria were grown in YEPG medium, and total RNA was extracted and analyzed using labeled primers to detect gene expression differences. Three distinctively expressed cDNA bands (ph1, ph2, and ph3) were identified, cloned, and sequenced. DNA analysis involved searching for open reading frames (ORFs), verifying results with the NCBI database, predicting promoter regions, and constructing phylogenetic trees using bioinformatics tools. The ph1 gene displayed a 97% identity with the AraC transcriptional regulator, suggesting its potential role in regulating the ortho -catabolic pathway of phenol. The ph2 gene showed a 98% identity with aspartate semialdehyde dehydrogenase, which is involved in phenol degradation. The ph3 gene had a 93% identity with acetyltransferase. Essential transcription factors, such as TATA, GTGTGT, CACA, and CTTTT, were detected, and the three genes promoter regions were predicted. This study successfully identified functional genes involved in the metabolism of cyclic chemicals, particularly phenol, using the DD technique. These findings provide insights into the biodegradation pathways of phenol by Acinetobacter sp. Strain DF4 and may contribute to the development of more efficient bioremediation strategies for phenol-contaminated environments. [ABSTRACT FROM AUTHOR]

Bone acts as a self-healing organ, which undergoes continuous regeneration process that is tightly regulated by the cooperation of osteoclasts with the capability of bone resorption and osteoblasts with the capability of bone formation. Generally, bone marrow derived mesenchymal stem cells (BMSCs) differentiated to final osteoblasts have been considered as critical role in bone remodeling. In this regard, several transcription factors (TFs) whose binding sites are initially hidden deep within accessible chromatin that participate in modulating osteoblast differentiation and bone matrix mineralization. Then, it is necessary to explore further the dynamic changes about the epigenetic transcription machinery during osteoblastogenesis. Here, we performed the chromatin accessibility and transcriptomic landscape of osteoblast differentiation and mineralization by using transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-Seq). Our data found that global chromatin accessibility during osteoblastogenesis was extensively improved. Above this, it is shown that key target genes including Col6a3, Serpina3n, Ms4a4d, Lyz2, Phf11b and Grin3a were enriched in differential loci RNA-seq and ATAC-Seq peaks with continuous changed tendency during osteoblasts differentiation and mineralization. In addition, Analysis of Motif Enrichment (AME) was used to elucidate TFs which modulated these target genes. In this study, it was shown for the first time that these important TFs including MEF2A, PRRX1, Shox2 and HOXB13 could alter promoter accessibility of target genes during osteoblastogenesis. This helps us understand how TF binding motif accessibility influences osteoblast differentiation. In addition, it also suggests that modulating the chromatin accessibility of osteogenesis could be developed as the promising strategies to regulate bone regeneration. • The dramatic changes of chromatin accessibility might play critical role in osteoblastogenesis. • Changes of chromatin accessibility and transcriptomic analysis of osteoblastogenesis are shown the close relationship. • TF binding motif accessibility could participate in regulating osteoblast differentiation and mineralization. • Modulating the chromatin accessibility of osteoblastogenesis could be developed as the promising strategies to regulate bone regeneration. [ABSTRACT FROM AUTHOR]

Droughts represent one of the main challenges that climate change imposes on crop production. As a globally cultivated staple crop, wheat (Triticum aestivum L.) is prone to drought environments. Therefore, improvement in drought tolerance represents a growing concern to ensure food security, especially for wheat. In this perspective, the application of Phyto-phillic exogenous materials such as glycine-betaine (GB) has been attracting attention, particularly in stress-related studies. Since roots procure the water and nutrients for plants, any improvements in their response and capacity against drought stress could induce stress tolerance in plants. However, the knowledge about the changes in root architecture, defense mechanism, hormonal metabolism, and downstream signaling, in response to GB-mediated root priming, is still limited. Therefore, we designed the present study to investigate the role of GB-mediated root priming in improving the water stress tolerance in wheat (cv. Jimai-22) under in-vitro conditions. The roots of twelve days old wheat seedlings were treated with Hoagland’s solution (GB-0), 50 mM GB (GB-1), and 100 mM GB (GB-2) for 48 h and subjected to well-watered (WW) and water-stress (WS) conditions. The osmotic stress substantially impaired shoot/root growth, dry matter accumulation, and increased malondialdehyde (MDA) and hydrogen-peroxide (H2O2) production in the roots of wheat seedlings. However, GB-mediated root priming improved the redox homeostasis of wheat roots by boosting the activities of SOD and POD and triggering the significantly higher accumulation of abscisic acid (ABA) and salicylic acid (SA) in the roots of GB-primed plants. Consequently, it modified the root architecture system and improved plant growth, dry matter accumulation, and water-stress tolerance of wheat seedlings. Moreover, GB-mediated root priming increased root sensitivity to water stress and induced overexpression of stress-responsive genes involved in ABA metabolism (TaNECD1, TaABA’OH2), their downstream signal transduction (TaPP2C, TaSNRK2.8), and activation of different transcriptional factors (TabZIP60, TaAREB3, TaWRKY2, TaERF3, and TaMYB3) that are associated with plant metabolite accumulation and detoxification of ROS under water stress conditions. Overall, our results demonstrated that GB-priming improved the physiological and biochemical attributes of wheat plants under WS conditions by improving the drought perception capacity of wheat roots, ultimately enhancing the water stress tolerance. Thus, the GB-priming of roots could help to enhance the water-stress tolerance of economically important crops (i.e., wheat).

Adipose tissue has been classified based on its morphology and function as white, brown, or beige/brite. It plays an essential role as a regulator of systemic metabolism through paracrine and endocrine signals. Recently, multiple adipocyte subtypes have been revealed using RNA sequencing technology, going beyond simply defined morphology but also by their cellular origin, adaptation to metabolic stress, and plasticity. Here, we performed an in-depth analysis of publicly available single-nuclei RNAseq from adipose tissue and utilized a workflow template to characterize adipocyte plasticity, heterogeneity, and secretome profiles. The reanalyzed dataset led to the identification of different subtypes of adipocytes including three subpopulations of thermogenic adipocytes, and provided a characterization of distinct transcriptional profiles along the adipocyte trajectory under thermogenic challenges. This study provides a useful resource for further investigations regarding mechanisms related to adipocyte plasticity and trans-differentiation.

Background RNA-binding proteins (RBPs) play important roles in cellular homeostasis by regulating the expression of thousands of transcripts, which have been reported to be involved in human tumorigenesis. Despite previous reports of the dysregulation of RBPs in cancers, the degree of dysregulation of RBPs in cancers and the intrinsic relevance between dysregulated RBPs and clinical TNM information remains unknown. Furthermore, the co-expressed networks of dysregulated RBPs with transcriptional factors and lncRNAs also require further investigation. Results Here, we firstly analyzed the deviations of expression levels of 1,542 RBPs from 20 cancer types and found that (1) RBPs are dysregulated in almost all 20 cancer types, especially in BLCA, COAD, READ, STAD, LUAD, LUSC and GBM with proportion of deviation larger than 300% compared with non-RBPs in normal tissues. (2) Up- and down-regulated RBPs also show opposed patterns of differential expression in cancers and normal tissues. In addition, down-regulated RBPs show a greater degree of dysregulated expression than up-regulated RBPs do. Secondly, we analyzed the intrinsic relevance between dysregulated RBPs and clinical TNM information and found that (3) Clinical TNM information for two cancer types—CHOL and KICH—is shown to be closely related to patterns of differentially expressed RBPs (DE RBPs) by co-expression cluster analysis. Thirdly, we identified ten key RBPs (seven down-regulated and three up-regulated) in CHOL and seven key RBPs (five down-regulated and two up-regulated) in KICH by analyzing co-expression correlation networks. Fourthly, we constructed the co-expression networks of key RBPs between 1,570 TFs and 4,147 lncRNAs for CHOL and KICH, respectively. Conclusions These results may provide an insight into the understanding of the functions of RBPs in human carcinogenesis. Furthermore, key RBPs and the co-expressed networks offer useful information for potential prognostic biomarkers and therapeutic targets for patients with cancers at the N and M stages in two cancer types CHOL and KICH.

As a dominating air pollutant, atmospheric fine particulate matter within 2.5 μm in diameter (PM 2.5 ) has attracted increasing attention from the researchers all over the world, which will lead to various adverse effects on the central nervous system (CNS), yet the potential mechanism is unclear. In this study, the microglia (BV2 cell line) were exposed to different concentrations of PM 2.5 (5, 10 and 20 μg/cm 2 ) for 24 h. It was found that PM 2.5 could result in adverse effects on microglia such as decreased cell viability, structural damage and even cell death. And it was reported that long non-coding RNAs (lncRNAs) could participate in multitudinous neurological diseases. Therefore, the microarray analysis was conducted in order to disclose the underlying neurotoxicity mechanism of PM 2.5 by ascertaining the differentially expressed lncRNAs (DElncRNAs). The consequences indicated that the DElncRNAs were enriched in various biological pathways, including ferroptosis, IL-17 signaling pathway and NOD-like receptor signaling pathway. Moreover, the cis- and trans-regulated mRNAs by DElncRNAs as well as the corresponding transcriptional factors (TFs) were observed, such as CEBPA, MYC, MEIS1 and KLF4. In summary, our study supplies some candidate libraries and potential preventive target against PM 2.5 -induced toxicity through targeting lncRNAs. Furthermore, the post-transcriptional regulation will contribute to the future research on PM 2.5 -induced neurotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Streptococcus pyogenes (group A streptococci; GAS) is an exclusively human pathogen. It causes a variety of suppurative and non-suppurative diseases in people of all ages worldwide. Not all can be successfully treated with antibiotics. A licensed vaccine, in spite of its global importance, is not yet available. GAS express an arsenal of virulence factors responsible for pathological immune reactions. The transcription of all these virulence factors is under the control of three types of virulence-related regulators: (i) two-component systems (TCS), (ii) stand-alone regulators, and (iii) non-coding RNAs. This review summarizes major TCS and stand-alone transcriptional regulatory systems, which are directly associated with virulence control. It is suggested that this treasure of knowledge on the genetics of virulence regulation should be better harnessed for new therapies and prevention methods for GAS infections, thereby changing its global epidemiology for the better.

In fish, the spleen is one of the major immune organs in the animal, and the splenocytes could play a key role in the activation and modulation of the immune response, both innate and adaptive. However, the crosstalk between different types of immune cells in the spleen has been poorly understood. In this work, an in vitro strategy is carried out to obtain and characterize mononuclear splenocytes from rainbow trout, using biomarkers associated with lymphocytes (CD4 and IgM) and antigen-presenting cells (CD83 and MHC II). Using these splenocytes, co-cultures of 24 and 48 h are used to determine the gene expression of master transcriptional factors that coordinate the polarization of T cells (t-bet, gata3, and foxp3). The results show a proportional upregulation of foxp3 (compared to t-bet and gata3) in co-cultures (at 24 h) of IFNγ-induced splenocytes with and without stimulation of Piscirickettsia salmonis proteins. In addition, foxp3 upregulation was established in co-cultures with IFNγ-induced cells and in cells only stimulated previously with P. salmonis proteins at 48 h of co-culture. These results show a potential communication between antigen-presenting-like cells and lymphocyte in the spleen, which could be induced towards a Treg phenotype.

Background and aims: This study investigated the detailed mechanism underlying the alleviation of osmotic stress by exogenous hydrogen (H2) in Medicago sativa. Methods: By using biochemical and molecular approaches, the experiments were performed with the analyses of biomass, relative water content (RWC), lipid peroxidation, abscisic acid (ABA) content, antioxidant activities, and related gene expression profiles. Results: H2 application stimulated ABA production, which was accompanied by the regulation of ABA biosynthesis and deactivation/activation genes. Elevated H2-induced ABA synthesis was sensitive to tungstate, an inhibitor of ABA synthesis. Meanwhile, H2-alleviated osmotic stress, which was supported by the increases in biomass and RWC, and the reduction of lipid peroxidation, was impaired by the inhibition of ABA synthesis. Consistently, tungstate blocked H2-induced antioxidant defense. Molecular evidence revealed that miR528 was down-regulated by H2, showing a negative correlation with its target gene POD2. When tungstate was added together, the decreased miR528 and increased POD2 transcripts were respectively blocked. Transcriptional factor genes involved in ABA signaling, including MYB102, MYC2, and ABF/AREB2, were differentially upregulated by H2, but further impaired by the co-incubation with tungstate. Conclusions: Collectively, our results suggested the possible role of ABA signaling in exogenous H2-mediated tolerance against osmotic stress in alfalfa. [ABSTRACT FROM AUTHOR]

SmartFlare technology allows detection of mRNA in single living cells. We studied the possibility of using SmartFlare nanoprobes for detection of small subsets of CD4+ lymphocytes. It was found that SmartFlare allows detection of transcriptional master regulators of major CD4+T helper subsets in living human lymphocytes. Nanoprobes labeled with Cy5 fluorophore were better detected by flow cytometry than nanoprobes labeled with Cy3. Appropriate time of lymphocyte incubation with SmartFlare probes was 24 h. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is one of the majorly categorized forms of human malignancy and is the prime cause of cancer-related mortality. Transcription factors and co-factors play an important role in the cellular process performing as key regulators in the normal cell and in the cancerous cell. The present study investigates the potential interaction between the potent phytocompounds and key transcriptional factors involved in hepatocellular carcinoma (HCC) by using molecular docking studies. In the area of drug designing and development, computational modeling and simulation play a significant role. Screening of potent phytocompounds against targets by means of conventional methods is tedious and requires more time when compared to computational modeling and simulation studies. In the present study, the application of computational screening of phytocompounds against transcriptional factors was effectively used to determine their binding strength with the pythocompounds. Ten potential phytocompounds linalool, p-cymene, pelargonidin, harpagoside, 1, 8-cineole, afzelin, ginkgolide B, theophylline, bromelain and isoborneol and five transcription factors p53, AP-1, c-Myc, -catenin and HIF-1 were selected for docking studies. The 3D structures of both phytocompounds and transcription factors were obtained from Pubchem and PDB databases respectively. Docking studies were carried out by using AutoDockVina. On evaluating the docking results, it was found that phytocompounds Harpagoside, Bromelain and Afzelin showed strong binding affinity against their targets. These phytocompounds showed the binding free energy more than 6 kcal/mol and RMSD value between 4-7 A0 with targets and can be potential ligands against the selected targets for further molecular investigations. [ABSTRACT FROM AUTHOR]

Modern ideas on the nature and functions of plastid retrograde signals, i.e., plastid retrograde signaling, predominantly of chloroplasts, are summarized. The main attention is focused on the participation of plastid retrograde signals in inter- and intracellular signaling pathways and their role in the processes of plant growth and development. The small amount of data on the little-studied retrograde signaling system of plant mitochondria are outlined as well. [ABSTRACT FROM AUTHOR]

Context. The inhibition of adipocyte differentiation has a significant role on the prevention of obesity and obesity-associated complications. Objective. In this study, we aimed to detect whether hyperoside is able to inhibit the conversion of pre-adiposits into mature adiposits. Design and Methods. 3T3-L1 pre-adipocytes were stimulated so as to differentiate into mature adipocytes. Hyperoside in non-cytotoxic concentrations (1, 2, 5, and 10 µM) were separately applied to differentiated 3T3-L1 cells. Oil red O staining was performed and triacylglycerol contents were measured. Furthermore, gene and protein expressions of transcription factors, adipogenic genes and adipokines were examined in order to investigate the effect of hyperoside on adipocyte differentiation. Results. Hyperoside in high concentrations significantly suppressed the adipogenic process by inhibiting the expression of transcription factors and adipogenic genes and reducing lipid accumulation in adipocytes (p<0.05). Low doses of hyperoside are able to inhibit adipogenesis, but higher doses are needed to reduce fat accumulation in mature adipocytes. In the case of maturing preadipocytes, 5 µ M of hyperoside exerts its antiadipogenic effect at the early stages of adipogenesis, whereas 10 µ M of hyperoside acts at the later stages (p<0.05). Conclusion. These results suggest that hyperoside has a beneficial effect on the prevention and treatment of obesity. [ABSTRACT FROM AUTHOR]

Abstract Objective Clinical issues have been raised about problems related to cytotoxic effects caused when applying self-adhesive cement. It was hypothesized that byproducts eluted from self-adhesive cements modulate oxidative stress response, the gene expression of signaling pathways of inflammatory process/transcriptional activators, and the expression and activity of interstitial collagenases, and modify the phenotypic characteristics of cellular proliferation and mineral deposition in odontoblastic-like cells. Methods Cements (MaxCem Elite [MAX] and RelyX U200 [U200)]) were mixed, dispensed into moulds, and photoactivated according to the manufacturers' instructions. Immortalized rat odontoblast-like cells (MDPC-23) were cultured and exposed to polymerized specimens of cements for 4 h. Reactive oxidative specimen production and quantification of gene expression were evaluated. Cell proliferation assay and alizarin red staining were also performed to evaluate the disturbance induced by the cements on cellular proliferation and mineralization. Results Despite their cytotoxic effects, both self-adhesive cements influenced the metabolism in the odontoblast cells on different scales. MAX induced significantly higher oxidative stress in odontoblast cells than U200. Gene expression varied as a function of exposure to self-adhesive cements; MAX induced the expression of pro-inflammatory cytokines such as TNF-α, whereas U200 downregulated, virtually depleted TNF-α expression, also inducing overexpression of the transcriptional factor Runx2. Overexpression of heme oxygenase-1 (HO-1) and thioredoxin reductase 1 (TRXR1) occurred after exposure to both cements, antioxidant genes that are downstream of Keap1-Nrf2-ARE system. MAX significantly induced the overexpression of collagenase MMP-1, and U200 induced the expression of gelatinase MMP-2. MAX significantly inhibited cell proliferation whereas U200 significantly activated cell proliferation. Alizarin red staining revealed significantly decreased mineral deposition especially when exposed to MAX. Significance These results support the hypothesis that byproducts of different self-adhesive cements play important roles in the highly orchestrated process which ultimately affect the cellular proliferation and the mineral deposition in odontoblastic-like cells, possibly delaying the reparative dentin formation after cementation of indirect restorations, especially on recently exposed dentin preparations. [ABSTRACT FROM AUTHOR]

Abstract Down syndrome, a genetic disorder of known attribution reveals several types of brain abnormalities resulting in mental retardation, inadequacy in speech and memory. In this study, we have presented a consolidative network approach to comprehend the intricacy of the associated genes of Down syndrome. In this analysis, the differentially expressed genes (DEG's) were identified and the central networks were constructed as upregulated and downregulated. Subsequently, GNB5, CDC42, SPTAN1, GNG2, GNAZ, PRKACB, SST, CD44, FGF2, PHLPP1, APP, and FYN were identified as the candidate hub genes by using topological parameters. Later, Fpclass a PPI tool identified WASP gene, a co-expression interacting partner with highest network topology. Moreover, an enhanced enrichment pathway namely Opioid signaling was obtained using ClueGo, depicting the roles of the hub genes in signaling and neuronal mechanisms. The transcriptional regulatory factors and the common miRNA connected to them were identified by using MatInspector and miRTarbase. Later, a regulatory network constructed showed that PLAG, T2FB, CREB, NEUR, and GATA were the most commonly connected transcriptional factors and hsa-miR-122-5p was the most prominent miRNA. In a nutshell, these hub genes and the enriched pathway could help understand at a molecular level and eventually used as therapeutic targets for Down syndrome. [ABSTRACT FROM AUTHOR]

The interdependence of posttranscriptional gene regulation via miRNA and transcriptional regulatory networks in lymphocyte development is poorly understood. Here, we identified miR‐191 as direct upstream modulator of a transcriptional module comprising the transcription factors Foxp1, E2A, and Egr1. Deletion as well as ectopic expression of miR‐191 resulted in developmental arrest in B lineage cells, indicating that fine tuning of the combined expression levels of Foxp1, E2A, and Egr1, which in turn control somatic recombination and cytokine‐driven expansion, constitutes a prerequisite for efficient B‐cell development. In conclusion, we propose that miR‐191 acts as a rheostat in B‐cell development by fine tuning a key transcriptional program. Through CRISPR/Cas9‐mediated deletion and retrogenic overexpression of miR‐191, we demonstrate that a defined window of expression of this miRNA is required to allow for efficient B‐cell development beyond the proB/preBI stage. Furthermore, we suggest that control of B‐cell development by miR‐191 is mediated through its targets Foxp1, E2A, and/or Egr1. [ABSTRACT FROM AUTHOR]

One of the main drivers of biodiversity loss in freshwater ecosystems are alien invasive species. In Europe, pathogen Aphanomyces astaci Schikora, 1906, is considered as one of the most problematic invasive species, as its introduction caused the severe decimation of the European freshwater crayfish stocks. The most affected are the populations of noble crayfish, keystone species native to European freshwaters. Unfortunately, even after decades of research, we do not understand the temporal dynamics of the noble crayfish immune response during Ap. astaci infection. Here, we studied the changes in the immune response of the noble crayfish during a time course challenge with a highly virulent strain of Ap. astaci. We recorded gross symptoms of the disease, changes in the total haemocyte count, gene expression profiles of putative immune response regulators and pathogen load. Additionally, we conducted a preliminary histological analysis of the pathogen dissemination in host tissues. Based on the occurrence of symptoms we propose three stages in the crayfish plague disease progression: asymptomatic stage, symptomatic stage, and finally death of infected individual. Furthermore, based on the qPCR analysis we could differentiate three Ap. astaci growth phases: initial lag phase, followed by exponential growth phase and finally sporulation phase. We observed that all measured immune response parameters were significantly correlated to the observed increase in the pathogen load (qPCR). Altogether, our results point to the absence of a successful immune response in the noble crayfish to a challenge with a highly virulent strain of Ap. astaci. The noble crayfish immune system was not able to suppress the growth of the intruding pathogen. In general, our observations have to be considered in the context of the specific combination of crayfish plague pathogen virulence and disease resistance of the challenged crayfish population, which defines the temporal dynamics of their interaction. • There are multiple stages in the progression of the crayfish plague disease in the noble crayfish. • Aphanomyces astaci growth within the challenged noble crayfish has multiple phases. • Measured host immune system parameters change based on the pathogen load. • Reduction in the total haemocyte count precedes the death of challenged noble crayfish. [ABSTRACT FROM AUTHOR]

The emergency for treating obesity has increased, triggering severe economic issues worldwide. The consumption of anthocyanins from different dietetic sources or by pharmaceutical prescription has shown strong associations with ameliorating specific physiological biomarkers and genetic factors related to obesity. This review focuses on examining and contrasting the findings from the past five years regarding the precise effects of anthocyanin compounds on metabolic health. These effects were evaluated primarily in in vivo models, assessed before and after consumption of various anthocyanin compounds from fresh foods, food extracts, and supplemental products. Descriptions of a few elements connected to, among others, adipose tissue, vascular endothelium, systemic pro-inflammatory state, and obesity biomarkers are reviewed. Clinical trials in subjects with overweight and obesity and essays in murine obesity-induced models have reported promising findings concerning anthocyanins consumption, specifically cyanidin-3-O-glucoside ingestion. The main effects in physiological biomarkers and indicators of anthocyanins consumption are a significant reduction of body weight and fat mass (brown adipocytes), triglycerides, cholesterol (LDL and VLDL), insulin resistance (HOMA) and a decrease of inflammation biomarkers such as IL-6 , IL-10 , and TNF-α , promoting the AMPK and MAPK pathways and regulating genes related to adipogenesis (PPAR-γ , GPx1 , ACAT3 , COX2 , UCP1 , and IL1β). There is a lack of studies on human subjects with obesity to corroborate the beneficial effects of anthocyanins (by diet or prescribed). It is necessary to discuss the food policies and nutritional advice regulations for incentivizing anthocyanin ingestion as a therapeutic effect against obesity. • Anthocyanins supplementation could be an effective treatment to treat obesity. • Anthocyanins have effects on glucose and lipids metabolism via AMPK/MAPK. • Different experimental models have shown improvements in obesity biomarkers. • Clinical trials in humans are needed to elucidate the interference mechanisms. • Consumption of foods with anthocyanins should be recommended in health policies. [ABSTRACT FROM AUTHOR]

Plant secondary metabolites are the outcomes of the adaptation of plants to ecological environment changes in the long-term evolution. The accumulation of secondary metabolites not only affects the evolutionary adaptability of plants, but also affects the quality and yield of some medicinal plants and crops. Therefore, it is an indispensable research field to understand further the mechanism of regulating secondary metabolism accumulation in plant science. Recent studies have confirmed that some signaling pathways are involved in regulating the accumulation of plant secondary metabolites, containing the ubiquitin-proteasome pathway, mitogen-activated protein kinase (MAPK) signaling, epigenomic regulatory pathway, plant hormone, and some transcriptional factors. This review summarizes the latest molecular mechanisms and regulatory networks regulating secondary metabolism accumulation, and discusses the difficulties in future research. • The accumulation of secondary metabolites affects the quality and yield of some medicinal plants and crops. • Some signaling pathways and factors can regulate the accumulation of plant secondary metabolites. • The challenge ahead is to reveal new molecular mechanisms or to explore possible links between different mechanisms. [ABSTRACT FROM AUTHOR]

The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host−pathogen association drives microbial evolution, as such organisms are under selective pressure and can become more pathogenic. Some of these microorganisms can quickly spread through the environment via transmission. The non-transmittable fungal pathogens, such as Cryptococcus, probably return into the environment upon decomposition of the infected host. This review analyses whether re-entry of the pathogen into the environment causes restoration of its non-pathogenic state or whether environmental factors and parameters assist them in maintaining pathogenesis. Cryptococcus (C.) neoformans is therefore used as a model organism to evaluate the impact of environmental stress factors that aid the survival and pathogenesis of C. neoformans intracellularly and extracellularly.

Floral shape in higher plants typically requires genetic regulation through MADS transcription factors. In Japan, hundreds of azalea cultivars including flower shape mutations have been selected from the diversity of endogenous species and natural hybrids since the early 17th century, the Edo era (1603–1867). The long-lasting trait, known as “Misome-shō” in Japanese, has been identified in several species and cultivar groups of evergreen azaleas (Rhododendron L.) from three hundred years ago in Japan. However, the natural mutation conferring the long-lasting trait in azalea remains unknown. Here, we showed MADS-box gene mutations in long-lasting flowers, R. kaempferi ‘Nikkō-misome,’ R. macrosepalum ‘Kochō-zoroi,’ R. indicum ‘Chōjyu-hō,’ and R. × hannoense ‘Amagi-beni-chōjyu.’ All of the long-lasting flowers exhibited small-sized corollas with stomata during long blooming. In the long-lasting flowers, transcript of the APETALA3 (AP3)/DEFICIENS (DEF) homolog was reduced, and an LTR-retrotransposon was independently inserted into exons 1, 2, and 7 or an unknown sequence in exon 1 in gDNA of each cultivar. This insertion apparently abolished the normal mRNA sequence of the AP3/DEF homolog in long-lasting flowers. Also, long-lasting flowers were shown from F2 hybrids that had homozygous ap3/def alleles. Therefore, we concluded that the loss of function of the AP3/DEF homolog through a transposable element insertion may confer a stable long-lasting mutation in evergreen azaleas.

Many phenolics are known to possess anti-obesity properties through mechanisms that inhibit adipogenesis, stimulate lipolysis or induce apoptosis. This study aimed to examine the anti-adipogenic effects of two phenolics, oxyresveratrol and cyanomaclurin in 3T3-L1 cells. At doses that they did not induce cytotoxicity (based on the lactate dehydrogenase assay), the exposure of oxyresveratrol (0–100 µM) or cyanomaclurin (0–600 µM) in the first three days of differentiation led to a dose-dependent decrease of triacylglycerol accumulation on day 9 post-confluent. Results of cell proliferation and cell cycle study demonstrated that both compounds inhibited differentiation through inducing cell cycle arrest by retaining the preadipocytes in the G1 phase during the first two days post-confluent. Their anti-adipogenic properties were also attributed to the down-regulation of protein expression of major transcriptional factors in adipogenesis, including peroxisome proliferator-activated receptor γ (PPAR γ) and CCAAT/Enhancer-binding proteins α (C/EBP α), and the induction of cell cycle arrest through regulating cyclin D1, cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase inhibitor 1B (P27/kip1) expression during the mitotic clonal expansion period.

Direct reprogramming of somatic cells into functional cells still faces major limitations in terms of efficiency and achieving functional maturity of the reprogramed cells. While different approaches have been developed commonly based on exploiting biochemical signals, introducing appropriate mechanical cues that stimulate the reprogramming process is rarely reported. In this study, collagen-coated polyacrylamide (PAM) hydrogels with stiffness close to that of collagenous bone (40 kPa) were adopted to augment the direct reprogramming process of mouse fibroblasts to osteoblastic-like cells. The results suggested that culturing cells on a hydrogel substrate enhanced the overexpression of osteogenic transcription factors using nonviral vectors and improved the yield of osteoblast-like cells. Particularly, a synergistic effect on achieving osteogenic functionality has been observed for the mechanical cues and overexpression of transcriptional factors, leading to enhanced osteogenic transformation and production of bone mineral matrix. Animal experiments suggested that reprogramed cells generated on matrix hydrogels accelerated bone regeneration and stimulated ectopic osteogenesis. Mechanism analysis suggested the critical involvement of actomyosin contraction and mechanical signal-mediated pathways like the RhoA-ROCK pathway, leading to a synergistic effect on the key transcriptional processes, including chromatin remodeling, nuclear translocation, and epigenetic transition. This study provides insights into the mechanical cue-enhanced direct reprogramming and cell therapy.

Introduction and Objective: Genetic susceptibility has a key role in the pathogenesis of coronary artery disease (CAD). KLF5 and KLF7 are transcriptional factors essential to cell development and differentiation. Their genetic variants have been associated with the risk of metabolic disorders. The present study aimed to evaluate the possible correlation of KLF5 (rs3812852) and KLF7 (rs2302870) single nucleotide polymorphisms (SNPs) with the risk of CAD for the first time in the world., Methods: The clinical trial study comprised 150 patients with CAD and 150 control subjects without CAD from the Iranian population. After blood sampling, deoxyribonucleic acid was extracted and genotyped using the Tetra Primer ARMS-PCR method and confirmed by Sanger sequencing., Results: The KLF7 A/C genotypes and C allele frequency were meaningfully higher in the control group compared to the CAD+ group (p<0.05). No obvious association has been observed between KLF5 variants and CAD risk. However, the distribution of the AG genotype of KLF5 was statistically lower in CAD+ patients with diabetes than in CAD+ patients without diabetes (p<0.05)., Conclusion: This study identified KLF7 SNP as a causative gene contributing to CAD, which presents novel insight into the molecular pathogenesis of the disease. It is, however, unlikely that KLF5 SNP has an essential role in the risk of CAD in the studied population., (Copyright © 2023 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

The NAC (NAM, ATAF, and CUC) genes encode transcription factors involved with the control of plant morph-physiology and stress responses. The release of the last soybean (Glycine max) genome assembly (Wm82.a2.v1) raised the possibility that new NAC genes would be present in the soybean genome. Here, we interrogated the last version of the soybean genome against a conserved NAC domain structure. Our analysis identified 32 putative novel NAC genes, updating the superfamily to 180 gene members. We also organized the genes in 15 phylogenetic subfamilies, which showed a perfect correlation among sequence conservation, expression profile, and function of orthologous Arabidopsis thaliana genes and NAC soybean genes. To validate our in silico analyses, we monitored the stress-mediated gene expression profiles of eight new NAC-genes by qRT-PCR and monitored the GmNAC senescence-associated genes by RNA-seq. Among ER stress, osmotic stress and salicylic acid treatment, all the novel tested GmNAC genes responded to at least one type of stress, displaying a complex expression profile under different kinetics and extension of the response. Furthermore, we showed that 40% of the GmNACs were differentially regulated by natural leaf senescence, including eight (8) newly identified GmNACs. The developmental and stress-responsive expression profiles of the novel NAC genes fitted perfectly with their phylogenetic subfamily. Finally, we examined two uncharacterized senescence-associated proteins, GmNAC065 and GmNAC085, and a novel, previously unidentified, NAC protein, GmNAC177, and showed that they are nuclear localized, and except for GmNAC065, they display transactivation activity in yeast. Consistent with a role in leaf senescence, transient expression of GmNAC065 and GmNAC085 induces the appearance of hallmarks of leaf senescence, including chlorophyll loss, leaf yellowing, lipid peroxidation and accumulation of H2O2. GmNAC177 was clustered to an uncharacterized subfamily but in close proximity to the TIP subfamily. Accordingly, it was rapidly induced by ER stress and by salicylic acid under late kinetic response and promoted cell death in planta. Collectively, our data further substantiated the notion that the GmNAC genes display functional and expression profiles consistent with their phylogenetic relatedness and established a complete framework of the soybean NAC superfamily as a foundation for future analyses. [ABSTRACT FROM AUTHOR]

Abstract We previously reported Microcystin-LR (MC-LR) could enter the hypothalamus, reduce the expression of gonadotropin-releasing hormone (GnRH), and induce male reproductive barriers. However, the molecular mechanisms underlying in the hypothalamus have not been elucidated in detail. In this study, we further showed that MC-LR inhibited the synthesis of GnRH in GnRH neurons via activating protein kinase a (PKA), cAMP-response element binding protein (Creb), protein kinase c (PKC), nuclear factor kappa B (NF- κ B), extracellular regulated protein kinases (Erk) and P38 protein, and thus resulted in the change of activity of transcriptional enhancers or suppressors such as Oct-1, Otx-2, Pbx1a, Dlx-2, c-Jun and c-Fos. Following exposure, MC-LR-treated mice exhibited decreased GnRH level. Our data demonstrated that MC-LR can stimulate intracellular Ca2+ and cAMP to activate PKC, PKA and MAPK signaling pathways in GnRH neurons, and then inhibit Pbx1a, Oct-1, Dlx-2, Otx-2 and upregulate c-Jun and c-Fos to initiate the transcription of GnRH, which provides novel insights to explore the mechanism associated with MC-LR-induced male reproductive barriers. Graphical abstract Unlabelled Image Highlights • MC-LR reduces GnRH levels in mice serum and hypothalamus. • MC-LR enters GT1-7 cells and hinders synthesizing GnRH. • MC-LR inhibits GnRH synthesis mediated by PKC/PKA/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

The epithelial-mesenchymal transition (EMT) is a dynamic process linked to metastasis in many tumor types, including mammary tumors. In this study, we evaluated E-cadherin and vimentin immunolocalization in primary canine mammary carcinomas (20 cases) and their respective metastases, as well as their relationship with the core regulators SNAIL/SLUG. To assess the number of cells undergoing the process of EMT, we quantitated double-positive (E-cadherin+/vimentin+) cells using immunofluorescence, via cell counting and image analysis. In addition, SNAIL/SLUG expression was evaluated by established immunohistochemical methods. Primary tumors had significantly more E-cadherin+/vimentin+ co-expression than their paired respective lymph node or distant metastasis, respectively. Furthermore, the percentage of E-cadherin+/vimentin+ cells in grade II and III carcinomas was significantly higher than in grade I tumors. Primary tumors had significantly higher SNAIL/SLUG expression when analyzed based on the percentage of positive cells compared with their respective distant metastases in pairwise comparisons. An inverse correlation was noted between SNAIL/SLUG immunoreactivity and percentage of E-cadherin+/vimentin+ immunopositive cells in primary tumor samples when SNAIL/SLUG immunoreactivity was grouped into 2 categories (high versus low) based on percentage-positive staining. These results show a positive correlation between E-cadherin+/vimentin+ cells and higher tumor grade, establish differences between primary tumor and their respective metastases, and provide further support that EMT plays a critical role in the metastasis of canine mammary carcinoma. Furthermore, these data suggest that modulation of this process could provide greater therapeutic control and provide support for further research to determine if E-cadherin+/vimentin+ co-immunoreactivity imparts predictive value in the clinical outcome of patients with canine mammary carcinomas. [ABSTRACT FROM AUTHOR]

Cold stress restricts plant growth, development, and distribution. Understanding how plants transduce and respond to cold signals has long been a topic of interest. Traditional genetic and molecular analyses have identified C-repeat/DREB binding factors (CBFs) as key transcription factors that function in cold acclimation. Recent studies revealed the involvement of pivotal protein kinases and transcription factors in CBF-dependent signaling, expanding our knowledge of cold signal transduction from perception to downstream gene expression events. In this review, we summarize recent advances in our understanding of the molecular regulation of these core components of the CBF cold signaling pathway. Knowledge of the mechanism underlying the ability of plants to survive freezing temperatures will facilitate the development of crop plants with increased freezing tolerance. [ABSTRACT FROM AUTHOR]

Flax ( Linum usitatissimum L.), an important industrial crop, is frequently decimated by pathogens, insect pests and adverse environmental conditions. Identification of flax resistance genes would facilitate development of varieties resistant to such diverse insults. Recently, a powerful method, high-throughput RNA sequencing (RNA-seq) technology, has been used effectively for transcript analysis and resistance gene discovery. In order to discover genes important for osmotic stress responses in flax, we performed transcriptome sequencing and screened differentially expressed unigenes (DEUs) of seedlings grown under normal and PEG 6000-induced stress treatments. Eight flax cDNA libraries were constructed and randomly sequenced using an Illumina technique and included one control sample and three treatment samples, each studied in duplicate. A total of 471,208,288 clean reads were obtained, of which 385,803,673 (81.88%) unique mapped reads and 23,042,410 multiple mapped reads were aligned to the Arabidopsis thaliana reference genome. Ultimately, 2533 out of 3922 unigenes were annotated using homology searches of KEGG Orthology (KO), PFAM, Gene Ontology (GO) and COG/KOG databases. Of these, 239 unigenes were differentially expressed (with at least 2-fold expression changes, FDR < 0.01) among three different PEG 6000-treatment durations compared with untreated control. Eight, five, four, three and one unigenes were assigned to NAC, LEA, WRKY, ERF and BLIP transcription factor families, respectively. For functional classification and pathway assignments, the 239 unigenes were mapped to three Gene Ontology (GO) categories including cellular component, molecular function and biological process, with 9, 10 and 19 functional terms for each category, respectively. In addition, these unigenes were assigned to 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, we validated the expression profiles of six DEUs using qRT-PCR to further confirm the accuracy of the RNA-seq data. To our knowledge, this study is the first systematic transcriptome analysis of flax osmotic stress response genes. The results reported here should aid identification of functional genes and putative pathways involved in flax osmotic resistance. Ultimately, this work should provide a reference map for discovery of additional stress tolerance genes useful for molecular breeding of flax varieties tolerant to a variety of stresses. [ABSTRACT FROM AUTHOR]

Purpose of Investigation: There is substantial literature demonstrating the effects of type I interferons (IFNs) on viral infections. Here, the authors examined STAT1, IRF-7, and IFN receptors (IFNR1 and IFNR2) in patients with cervical intraepithelial neoplasia (CIN I, II, III) or invasive cervical cancer (ICC) and healthy women. Materials and Methods: Flow cytometry was used to monitor total T lymphocytes (CD3+), T helper cells (CD4+), cytotoxic T cells (CD8+), and monocytes (CD14+). Results: In patients, the numbers of CD3+, CD4+, and CD14+ cells that were positive for IFN-α and the intracellular amounts of this cytokine increased in accordance with lesion progression. Patients showed increased numbers of cells expressing IFNR1 and IFNR2. Patients with neoplasia showed increased numbers of cells positive for STAT1 and IRF7 compared to controls. Conclusion: the antiviral response mediated by IFN-α is increased in the peripheral blood T cells of patients with different stages of cervical neoplasia. [ABSTRACT FROM AUTHOR]

ABSTRACT: CCAAT/enhancer‐binding protein α (C/ebpα) is critical for osteoclastogenesis by regulating osteoclast (OC) lineage commitment and is also important for OC differentiation and function in vitro. However, the role of C/ebpα in postnatal skeletal development has not been reported owing to lethality in C/ebpα–/– mice from hypoglycemia within 8 hours after birth. Herein, we generated conditional knockout mice by deleting the C/ebpα gene in monocyte via LysM‐Cre to examine its role in OC differentiation and function. C/ebpαf/fLysM‐Cre mice exhibited postnatal osteopetrosis due to impaired osteoclastogenesis, OC lineage priming defects, as well as defective OC differentiation and activity. Furthermore, our ex vivo analysis demonstrated that C/ebpα conditional deletion significantly reduced OC differentiation, maturation, and activity while mildly repressing macrophage development. At the molecular level, C/ebpα deficiency significantly suppresses the expressions of OC genes associated with early stages of osteoclastogenesis as well as genes associated with OC differentiation and activity. We also identified numerous C/ebpα critical cis‐regulatory elements on the Cathepsin K promoter that allow C/ebpα to significantly upregulate Cathepsin K expression during OC differentiation and activity. In pathologically induced mouse model of osteoporosis, C/ebpα deficiency can protect mice against ovariectomy‐induced bone loss, uncovering a central role for C/ebpα in osteolytic diseases. Collectively, our findings have further established C/ebpα as a promising therapeutic target for bone loss by concurrently targeting OC lineage priming, differentiation, and activity. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has gained considerable attention as it oversteps about 15% of the deaths caused by breast cancer in women and is well known for its aggressive impact, high proliferation rate, intensity of tumor, and metastasis. In this study, we have given a new insight into TNBC, by introducing an integrative network methodology to understand the complexity of the candidate genes in TNBC. In the course of this analysis, the central network was constructed by refining the candidate genes present in the various databases. Eventually, the hub genes SRC, EGFR, JUN, CTNNB1, and MYC were derived using distinct topological parameters such as degree, betweenness centrality, closeness centrality, and clustering coefficient, which implicated a central role in TNBC. Furthermore, the identified hub genes were validated by utilizing molecular complex detection cluster analysis. A regulatory network was constructed to locate the transcriptional factors regulating these hub genes via MatInspector. Interestingly, we characterized that ZF02, MZF1, and PLAG are the common transcription factors which activate the hub genes. Moreover, a functional enrichment pathway was obtained from ClueGo, which depicted that all the hub genes have a significant role in toxicity-associated pathways as well as physiochemical featured pathways. In a nutshell, these prioritized genes could be the way out to uncover the molecular and therapeutic targets, leading to the development of personalized medicine for TNBC. [ABSTRACT FROM AUTHOR]

Floral shape in higher plants typically requires genetic regulation through MADS transcription factors. In Japan, hundreds of azalea cultivars including flower shape mutations have been selected from the diversity of endogenous species and natural hybrids since the early 17th century, the Edo era (1603-1867). The long-lasting trait, known as "Misome-shö" in Japanese, has been identified in several species and cultivar groups of evergreen azaleas (Rhododendron L.) from three hundred years ago in Japan. However, the natural mutation conferring the long-lasting trait in azalea remains unknown. Here, we showed MADS-box gene mutations in long-lasting flowers, R. kaempferi 'Nikkoō -misome,' R. macrosepalum 'Kochoō-zoroi,' R. indicum 'Choō jyu-hoō,' and R.× hannoense 'Amagi-beni-choōjyu.' All of the long-lasting flowers exhibited small-sized corollas with stomata during long blooming. In the long-lasting flowers, transcript of the APETALA3 (AP3)/DEFICIENS (DEF) homolog was reduced, and an LTR-retrotransposon was independently inserted into exons 1, 2, and 7 or an unknown sequence in exon 1 in gDNA of each cultivar. This insertion apparently abolished the normal mRNA sequence of the AP3/DEF homolog in long-lasting flowers. Also, long-lasting flowers were shown from F2 hybrids that had homozygous ap3/def alleles. Therefore, we concluded that the loss of function of the AP3/DEF homolog through a transposable element insertion may confer a stable long-lasting mutation in evergreen azaleas. [ABSTRACT FROM AUTHOR]