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Sterol regulatory element-binding factor 1 (SREBP1) plays an important role in the lipogenesis which affects fatty acid (FA) composition in backfat and consequently influences beef nutritional quality. This study analyzed the association of 84 bp-indel, both short (S) and long (L) alleles in intron 5 of SREBP1, with FA composition and gene expression of SREBP1 in backfat of northern Spanish beef breeds (Pirenaica, Salers and Holstein-Friesian). Phylogenetic analysis suggests that 84 bp-indel of ruminants is a highly conserved region compared with those in the full-length sequence of intron 5 or mRNA of SREBP1 among species. Overall, higher content of polyunsaturated FAs was observed in SL genotype compared to LL genotype of 84 bp-Indel (p < .05). In particular, in Pirenaica, SL genotype was associated with a higher content of stearic (18:0), α-linolenic (18:3n-3) acid, and total n-3 content (p < .05). However, the gene expression of SREBP1 did not differ among genotypes of 84 bp-Indel (p > .05)., (© 2021 Japanese Society of Animal Science.)

TP53 point mutations are found in 50% of all cancers and seem to play an important role in cancer pathogenesis. Thus, human induced pluripotent stem cells (hiPSCs) overexpressing mutant TP53 are a valuable tool for the generation of in vitro models of cancer stem cells or for in vivo xenograft models. Here, we describe a protocol for the alteration of gene expression in hiPSCs via overexpression of a mutant form of the TP53 (R249S) gene using lentiviral transduction. A high amount of TP53 protein is detected 1 week after transduction and antibiotic selection. Differentiation of transduced hiPSCs gives insight into better understanding cancer formation in different tissues and may be a useful tool for genetic or pharmacologic screening assays. © 2019 The Authors. Basic Protocol 1: Production and concentration of third-generation lentivirus Support Protocol 1: Cloning of gene of interest into modulation vector Support Protocol 2: Preparation of DMEM GlutaMAX™ with 10% fetal bovine serum and 1% penicillin-streptomycin Basic Protocol 2: Transduction of human induced pluripotent stem cells and selection of positively transfected cells Support Protocol 3: Preparation of Matrigel ® -coated plates Support Protocol 4: Preparation of mTeSR™1 medium., (© 2019 The Authors.)

Liver fibrosis is a major health concern, which might progress to cirrhosis. To date, treatment trials rely mainly on the removal of the causative factor. The current study investigated the potential ameliorative role of sidr honey on thioacetamide (TAA)-induced liver fibrosis in rats. Forty-eight Wistar albino rats were equally allocated into four groups: control; sidr honey (5g/kg body weight (BW), orally); TAA (200 mg/kg BW, IP three times weekly/15 weeks); and sidr honey plus TAA at the same dose and administration rout. Rats co-treated with sidr honey plus TAA revealed significant reduction in hepatic malondialdehyde, hyaluronic acid (HA), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, direct bilirubin, and hepatic mRNA expression of transforming growth factor (TGF)-β1 and collagen type I alpha 1 chain (COL1a1) compared to TAA-exposed rats. In addition, the hepatoprotective potential of sidr honey was indicated via improvement of histopathologic picture of hepatocytes and upregulation of total antioxidant capacity, reduced glutathione, catalase, glutathione peroxidase, superoxide dismutase, total protein, and albumin compared to TAA-treated rats. In conclusion, daily administration of sidr honey (5 g/kg BW) is a promising natural antioxidant and fibrosuppressive agent that could ameliorate liver fibrosis via downregulation of fibrosis genes including TGF-β1 and COL1a1 and HA and via enhancement of antioxidant system., (© 2020 Japanese Society of Animal Science.)

Enhanced expression of the human ferritin H- and L-chain genes (hfH and hfL) was achieved in Saccharomyces cerevisiae by modifying the N-terminal region of the structural genes. The yeast episomal vector YEp352 with the galactokinase1 (GAL1) promoter was used to construct expression plasmids. The expression of each gene was examined using SDS-PAGE and Western blot analysis. Iron uptake was examined and the cellular iron concentration was increased in S. cerevisiae expressing hfH. When cultured cells were incubated with 14.3 mM Fe2+, the recombinant yeast expressing hfH had a cellular iron concentration 1.5 times greater than that of the control strain. The relationship between the iron taken up by the cells and the expressed proteins was examined. Iron-binding H-chain ferritin (H-ferritin) was seen in the recombinant S. cerevisiae incubated with iron, while small amounts of iron-binding L-chain ferritin (L-ferritin) were observed. Combined, these observations demonstrate that human H-ferritin has a function in iron storage in S. cerevisiae, while L-ferritin does not. [ABSTRACT FROM AUTHOR]

The antidepressant desipramine (DMI) is a selective inhibitor of norepinephrine (NE) transport that down-regulates the norepinephrine transporter (NET) protein in a concentration- and time-dependent manner in vitro. In this study, possible regulatory effects of DMI on NET mRNA and protein levels were investigated with the NET-expressing SK-N-BE(2)M17 cell line and rat brain tissue. Northern blot analysis showed that incubation of the cultured cells with DMI (5-500 nM) for 3 days reduced levels of NET mRNA in both its 5.8-kb (by up to 58%) and 3.6-kb forms (to 68%), whereas incubation for 14 days increased both levels (to 40% and 100%) in a concentration-dependent manner. In contrast, NET protein levels decreased after 3-14 days of exposure of the cells to DMI, as determined by western blotting. The in vitro findings were supported by in viva treatment of rats with DMI. Thus, in situ hybridization demonstrated initially decreased, and later increased, NET mRNA levels in locus coeruleus (LC) tissue of rats treated with DMI; whereas NET protein levels in the LC were reduced after 14 days, but unchanged after three daily DMI treatments. Thus, DMI had similar effects on NET expression in vitro and in viva, with opposite changes in NET mRNA and protein levels, suggesting that the regulatory mechanisms involved are complex and noncongruent. [ABSTRACT FROM AUTHOR]

Mouse 3T3-L1 preadipocytes differentiate into adipocytes when treated with 3-isobutyl-1-methylxanthine, dexamethasone, and insulin. Although mechanisms of adipogenesis, including transcriptional cascades, are understood, it is still unclear how clonally expanded cells eventually enter the terminal differentiation program. From gene expression profile studies, we identified G0/G1 switch gene 2 (G0s2) as a novel regulator of adipogenesis. The gene was found to be expressed at a higher level in white and brown adipose tissues, and it was induced in 3T3-L1 cells by hormonal treatment. Importantly, G0s2 expression was closely associated with the transition from mitotic clonal expansion to terminal differentiation. Knockdown of G0s2 expression with siRNA inhibited adipocyte differentiation, whereas constitutive overexpression of G0s2 accelerated differentiation of preadipocytes to mature adipocytes. Expression of G0s2 was found to be regulated by peroxisome proliferator-activated receptor γ (PPARγ), which is a well-known regulator of adipocyte differentiation. Absence of either PPARγ or G0s2 expression resulted in apoptotic pathway activation before terminal differentiation. To determine whether G0s2 has a role in vivo, G0s2-knockout mice were generated. The knockout mice were normal in appearance, but they had less adipose mass than wild-type littermates. Mouse embryonic fibroblast cells from G0s2-deficient mice exhibited impaired adipogenesis and contained unusually small intracellular lipid droplets, suggesting that G0s2 has a role in lipid droplet formation. Our studies demonstrate that G0s2 has an important role in adipogenesis and accumulation of triacylglycerol. [ABSTRACT FROM AUTHOR]

Infection with cagA-positive Helicobacter pylori is a risk factor for the development of severe gastritis and gastric cancer (GC). CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. Phospholipase D (PLD) is elevated in many different types of human cancers and has been implicated as a critical factor in inflammation and carcinogenesis. In this study, we show that infection with cagA-positive H. pylori in GC cells significantly induces PLD1 expression via CagA-dependent activation of nuclear factor κB (NFκB). Interestingly, the level of PLD1 protein and IκBα phosphorylation is aberrantly upregulated in H. pylori-infected human GC tissues. Infection with cagA-positive H. pylori and expression of CagA enhanced the binding of NFκB to the PLD1 promoter, and two functional NFκB-binding sites were identified within the PLD1 promoter. Rebamipide, a mucosal-protective antiulcer agent, abolished H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter, and also inhibited PLD activity. Moreover, rebamipide suppressed H. pylori-induced matrix metalloproteinase-9, interleukin-8 and activation-induced cytidine deaminase expression as well as invasion of GC cells through downregulation of PLD1. Our data suggest that H. pylori cagA targets PLD1 for invasion of GC cells, and rebamipide might contribute to the antitumorigenic effect of GC cells via inhibition of the H. pylori cagA-NFκB-PLD1 signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: Fragile X syndrome is an inherited X-linked disorder associated with intellectual disabilities that begin in childhood and last a lifetime. The symptoms overlap with autism spectrum disorder, and the syndrome predominantly affects males. Consequently, FXS research tends to favor analysis of social behaviors in males, leaving a gap in our understanding of other behavioral traits, especially in females. Methods: We used a mouse model of FXS to analyze developmental, behavioral, neurochemical, and transcriptomic profiles in males and females. Results: Our behavioral assays demonstrated locomotor hyperactivity, motor impulsivity, increased "approach" behavior in an approach-avoidance assay, and deficits in nest building behavior. Analysis of brain neurotransmitter content revealed deficits in striatal GABA, glutamate, and serotonin content. RNA sequencing of the ventral striatum unveiled expression changes associated with neurotransmission as well as motivation and substance use pathways. Sex differences were identified in nest building behavior, striatal neurotransmitter content, and ventral striatal gene expression. Discussion: In summary, our study identified sex differences in specific behavioral, neurotransmitter, and gene expression phenotypes and gene set enrichment analysis identified significant enrichment of pathways associated with motivation and drug reward. [ABSTRACT FROM AUTHOR]

Background: In the face of increasing antifungal resistance among Candida albicans biofilms, this study explores the efficacy of a combined treatment using Kangbainian lotion (KBN) and miconazole nitrate (MN) to address this challenge. Methods: Using UPLC-Q-TOF/MS Analysis for Identification of Active Compounds in KBN Lotion; FICI for synergy evaluation, XTT and ROS assays for biofilm viability and oxidative stress, fluorescence and confocal laser scanning microscopy (CLSM) for structural and viability analysis, and real-time fluorescence for gene expression. Conclusion: Our study indicates that the combined application of KBN and MN somewhat impacts the structural integrity of Candida albicans biofilms and affects the expression of several key genes involved in biofilm formation, including ALS1, ALS3, HWP1, HSP90, and CSH1. These preliminary findings suggest that there may be a synergistic effect between KBN and MN, potentially influencing not only the structural aspects of fungal biofilms but also involving the modulation of genetic pathways during their formation. [ABSTRACT FROM AUTHOR]

Simple Summary: This review provides a comprehensive and detailed explanation of the various functions of the ubiquitin-conjugating enzyme E2 O (UBE2O). It examines UBE2O's role in a wide range of biological processes under both physiological and pathological conditions. The review also explores UBE2O's involvement in several human cancers, with a particular focus on its role in leukemias and solid cancers. Furthermore, this review delves into the dual role of UBE2O, not only as a potential therapeutic target but also as a crucial factor in the regulation of the development and progressoin of several human malignancies. In summary, this review underscores UBE2O importance in cancer biology and its potential for future therapeutic applications. Protein degradation is a biological phenomenon essential for cellular homeostasis and survival. Selective protein degradation is performed by the ubiquitination system which selectively targets proteins that need to be eliminated and leads them to proteasome degradation. In this narrative review, we focus on the ubiquitin-conjugating enzyme E2 O (UBE2O) and highlight the role of UBE2O in many biological and physiological processes. We further discuss UBE2O's implications in various human diseases, particularly in leukemias and solid cancers. Ultimately, our review aims to highlight the potential role of UBE2O as a therapeutic target and offers new perspectives for developing targeted treatments for human cancers. [ABSTRACT FROM AUTHOR]

Uterine cancer is the most common gynecologic malignancy in the United States, with endometrioid endometrial adenocarcinoma (EC) being the most common histologic sub-type. Considering the molecular classifications of EC, efforts have been made to identify additional biomarkers that can assist in diagnosis, prognosis, and individualized therapy. We sought to explore the relationship of Repressor Element 1 (RE1) silencing transcription factor (REST), which downregulates neuronal genes in non-neuronal tissue, along with matrix metalloproteinase-24 (MMP24) and EC. We analyzed the expression of REST and MMP24 in 31 cases of endometrial cancer and 16 controls. We then explored the baseline expression of REST and MMP24 in two EC cell lines (Ishikawa and HEC-1-A) compared to a benign cell line (t-HESC) and subsequently evaluated proliferation, migration, and invasion in the setting of loss of REST gene expression. REST and MMP24 expression were significantly lower in human EC samples compared to control samples. REST was highly expressed in EC cell lines, but decreasing REST gene expression increased proliferation (FC: 1.13X, p < 0.0001), migration (1.72X, p < 0.0001), and invasion (FC: 7.77X, p < 0.05) in Ishikawa cells, which are hallmarks of cancer progression and metastasis. These findings elicit a potential role for REST as a putative tumor suppressor in EC. [ABSTRACT FROM AUTHOR]

Enterohemorrhagic Escherichia coli (EHEC) outbreaks have been frequently linked to the consumption of produce. Furthermore, produce grown on organic farms possess a higher risk, as the farmers avoid antibiotics and chemicals. This study sets out to evaluate the effectiveness of advanced postharvest disinfection processes using berry pomace extracts (BPEs) in reducing EHEC load in two common leafy greens, spinach and lettuce. Spinach and lettuce were inoculated with ~5 log CFU/leaf EHEC EDL-933 and then treated with three different concentrations of BPE (1, 1.5, and 2 gallic acid equivalent, GAE mg/mL) for increasing periods of time. After the wash, the bacteria were quantified. Changes in the relative expression of virulence genes and the genes involved in cell division and replication and response against stress/antibiotics were studied. We observed a significant reduction in EHEC EDL933, ranging from 0.5 to 1.6 log CFU/spinach leaf (p < 0.05) washed with BPE water. A similar trend of reduction, ranging from 0.3 to 1.3 log CFU/mL, was observed in pre-inoculated lettuce washed with BPE water. We also quantified the remaining bacterial population in the residual treatment solutions and found the survived bacterial cells (~3 log CFU/mL) were low despite repeated washing with the same solution. In addition, we evaluated the phenolic concentration in leftover BPE, which did not change significantly, even after multiple uses. Alterations in gene expression levels were observed, with downregulation ranging from 1 to 3 log folds in the genes responsible for the adhesion and virulence of EHEC EDL933 and significant upregulation of genes responsible for survival against stress. All other genes were upregulated, ranging from 2 to 7 log folds, with a dose-dependent decrease in expression. This finding shows the potential of BPE to be used for sanitation of fresh produce as a natural and sustainable approach. [ABSTRACT FROM AUTHOR]

Cucumis melo is an annual dicotyledonous trailing herb. It is fruity, cool, and refreshing to eat and is widely loved by consumers worldwide. The single fruit weight is an important factor affecting the yield, and thus the income and economic benefits, of melon crops. In this study, to identify the main QTLs (quantitative trait locus) controlling the single fruit weight of melon and thereby identify candidate genes controlling this trait, specific-locus amplified fragment sequencing (SLAF) analysis was performed on the offspring of female 1244 plants crossed with male MS-5 plants. A total of 115 individual plants in the melon F2 population were analyzed to construct a genetic linkage map with a total map distance of 1383.88 cM by the group in the early stages of the project, which was divided into 12 linkage groups with a total of 10,596 SLAF markers spaced at an average genetic distance of 0.13 cM. A total of six QTLs controlling single fruit weight (sfw loci) were detected. Seven pairs of markers with polymorphisms were obtained by screening candidate intervals from the SLAF data. The primary QTL sfw2.2 was further studied in 300 F2:3 family lines grown in 2020 and 2021, respectively, a positioning sfw2.2 between the markers CY Indel 11 and CY Indel 16, between 18,568,142 and 18,704,724 on chromosome 2. This interval contained 136.58 kb and included three genes with functional annotations, MELO3C029673, MELO3C029669, and MELO3C029674. Gene expression information for different fruit development stages was obtained from 1244 and MS-5 fruits on the 15d, 25d, and 35d after pollination, and qRT-PCR (quantitative reverse transcription–PCR) indicated that the expression of the MELO3C029669 gene significantly differed between the parents during the three periods. The gene sequences between the parents of MELO3C029669 were analyzed and compared, a base mutation was found to occur in the intronic interval between the parents of the gene, from A-G. Phylogenetic evolutionary tree analysis revealed that the candidate gene MELO3C029669 is most closely related to Pisum sativum Fimbrin-5 variant 2 and most distantly related to Cucumis melo var. makuwa. Therefore, it was hypothesized that MELO3C029669 is the primary major locus controlling single fruit weight in melon. These results not only provide a theoretical basis for further studies to find genes with functions in melon single fruit weight but also lay the foundation for accelerating breakthroughs and innovations in melon breeding. [ABSTRACT FROM AUTHOR]

In plants, RopGEF-mediated ROP signaling is pivotal in cellular signaling pathways, including apical growth, pollen germination and perception, intercellular recognition, as well as in responses to biotic and abiotic stresses. In this study, we retrieved a total of 37 RopGEF members from three C4 Crops, of which 11 are from millet, 11 from sorghum, and 15 from maize. Based on their phylogenetic relationships and structural characteristics, all RopGEF members are classified into four subfamilies. The qRT-PCR technique was utilized to evaluate the expression profiles of 11 SiRopGEFs across different tissues in foxtail millet. The findings indicated that the majority of the SiRopGEFs exhibited higher expression levels in leaves as opposed to roots and stems. The levels of expression of SiRopGEF genes were examined in response to abiotic stress and plant hormones. SiRopGEF1, SiRopGEF5, SiRopGEF6, and SiRopGEF8 showed significant induction under abiotic stresses such as salt, cold, and heat. On the other hand, SiRopGEF1, SiRopGEF2, and SiRopGEF7 were consistently upregulated, while SiRopGEF3, SiRopGEF4, SiRopGEF6, SiRopGEF9, and SiRopGEF10 were downregulated upon exposure to abscisic acid (ABA), ethylene (ET), salicylic acid (SA), and gibberellic acid (GA3) hormones. The alterations in the expression patterns of RopGEF members imply their potential functions in plant growth and development, abiotic stress response, and hormone signal transduction. These discoveries suggest that the RopGEF genes may function as a potential genetic marker to facilitate future studies in elucidating the functional characteristics of RopGEFs. [ABSTRACT FROM AUTHOR]

The Nox1-centered NADPH oxidase complex facilitates the transfer of electrons from intracellular NADPH across the cell membrane to extracellular molecular oxygen, resulting in the formation of superoxide. The complex is comprised of two membrane-bound subunits, namely Nox1 and p22phox, and the cytosolic subunits, namely NoxA1 and NoxO1. The presence of NoxO1 facilitates the proximity of all components, thereby enabling the complex to exhibit constitutive activity. Despite the theoretical sufficiency of all subunits in a 1:1 ratio, the precise composition of the Nox1-centered NADPH oxidase remains unknown. Analyses of mRNA expression in different cell lines revealed an unequal expression of the components, with an excess of NoxO1. Furthermore, plasmid-based overexpression of individual components of the Nox1-centered NADPH oxidase resulted in an excess of NoxO1 mRNA. The objective of this study was to analyze the ability of NoxO1 to control the level of ROS formation by the Nox1 complex. To this end, we generated Hek293 cells for constitutive expression of Nox1 and NoxA1, which were then transfected with increasing concentrations of NoxO1. The data presented herein suggests that ROS formation by the Nox1-centered NADPH oxidase is dependent on the concentration of NoxO1. A surplus of NoxO1 has been observed to exert control over the activity of the complex in accordance with a dose-dependent mechanism. We thus conclude that the ratio of Nox1, NoxA1, and NoxO1 complexes does not adhere to a 1:1 ratio. Conversely, the availability of NoxO1 serves to regulate the formation of ROS by the Nox1-centered NADPH oxidase. [ABSTRACT FROM AUTHOR]

Background. Adipogenic differentiation stands as a crucial pathway in the range of differentiation options for mesenchymal stem cells (MSCs), carrying significant importance in the fields of regenerative medicine and the treatment of conditions such as obesity and osteoporosis. However, the exact mechanisms that control the adipogenic differentiation of MSCs are not yet fully understood. Materials and Methods. We procured datasets, namely GSE36923, GSE80614, GSE107789, and GSE113253, from the Gene Expression Omnibus database. These datasets enabled us to perform a systematic analysis, including the identification of differentially expressed genes (DEGs) pre‐ and postadipogenic differentiation in MSCs. Subsequently, we conducted an exhaustive analysis of DEGs common to all four datasets. To gain further insights, we subjected these overlapped DEGs to comprehensive gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Following the construction of protein–protein interaction (PPI) networks, we meticulously identified a cohort of hub genes pivotal to the adipogenic differentiation process and validated them using real‐time quantitative polymerase chain reaction. Subsequently, we ventured into the construction of miRNA‐gene and TF–gene interaction networks. Results. Our rigorous analysis revealed a total of 18 upregulated DEGs and 12 downregulated DEGs that consistently appeared across all four datasets. Notably, the peroxisome proliferator‐activated receptor signaling pathway, regulation of lipolysis in adipocytes, and the adipocytokine signaling pathway emerged as the top‐ranking pathways significantly implicated in the regulation of these DEGs. Subsequent to the construction of the PPI network, we identified and validated 10 key node genes, namely IL6, FABP4, ADIPOQ, LPL, PLIN1, RBP4, ACACB, NT5E, KRT19, and G0S2. Our endeavor to construct miRNA–gene interaction networks led to the discovery of the top 10 pivotal miRNAs, including hsa‐mir‐27a‐3p, hsa‐let‐7b‐5p, hsa‐mir‐1‐3p, hsa‐mir‐124‐3p, hsa‐mir‐155‐5p, hsa‐mir‐16‐5p, hsa‐mir‐101‐3p, hsa‐mir‐21‐3p, hsa‐mir‐146a‐5p, and hsa‐mir‐148b‐3p. Furthermore, the construction of TF–gene interaction networks revealed the top 10 critical TFs: ZNF501, ZNF512, YY1, EZH2, ZFP37, ZNF2, SOX13, MXD3, ELF3, and TFDP1. Conclusions. In summary, our comprehensive study has successfully unraveled the pivotal hub genes that govern the adipogenesis of MSCs. Moreover, the meticulously constructed miRNA‐gene and TF–gene interaction networks are poised to significantly augment our comprehension of the intricacies underlying MSC adipogenic differentiation, thus providing a robust foundation for future advances in regenerative biology. [ABSTRACT FROM AUTHOR]

High-fat diets (HFDs) shape the gut microbiome and promote obesity, inflammation, and liver steatosis. Fish and soybean are part of a healthy diet; however, the impact of these fats, in the absence of sucrose, on gut microbial dysbiosis and its association with liver steatosis remains unclear. Here, we investigated the effect of sucrose-free soybean oil-and fish oilbased high fat diets (HFDs) (SF-Soy-HFD and SF-Fish-HFD, respectively) on gut dysbiosis, obesity, steatosis, hepatic inflammation, and insulin resistance. C57BL/6 mice were fed these HFDs for 24 weeks. Both diets had comparable effects on liver and total body weights. But 16S-rRNA sequencing of the gut content revealed induction of gut dysbiosis at different taxonomic levels. The microbial communities were clearly separated, showing differential dysbiosis between the two HFDs. Compared with the SF-Fish-HFD control group, the SF-Soy-HFD group had an increased abundance of Bacteroidetes, Firmicutes, and Deferribacteres, but a lower abundance of Verrucomicrobia. The Clostridia/Bacteroidia (C/B) ratio was higher in the SF-Soy-HFD group (3.11) than in the SF-Fish-HFD group (2.5). Conversely, the Verrucomicrobiacae/S24_7 (also known as Muribaculaceae family) ratio was lower in the SF-Soy-HFD group (0.02) than that in the SF-Fish-HFD group (0.75). The SF-Soy-HFD group had a positive association with S24_7, Clostridiales, Allobaculum, Coriobacteriaceae, Adlercreutzia, Christensenellaceae, Lactococcus, and Oscillospira, but was related to a lower abundance of Akkermansia, which maintains gut barrier integrity. The gut microbiota in the SF-Soy-HFD group had predicted associations with host genes related to fatty liver and inflammatory pathways. Mice fed the SF-Soy-HFD developed liver steatosis and showed increased transcript levels of genes associated with de novo lipogenesis (Acaca, Fasn, Scd1, Elovl6) and cholesterol synthesis (Hmgcr) pathways compared to those in the SF-Fish-HFDgroup. No differences were observed in the expression of fat uptake genes (Cd36 and Fabp1). The expression of the fat efflux gene (Mttp) was reduced in the SFSoy-HFD group. Moreover, hepatic inflammation markers (Tnfa and Il1b) were notably expressed in SF-Soy-HFD-fed mice. In conclusion, SF-Soy-HFD feeding induced gut dysbiosis in mice, leading to steatosis, hepatic inflammation, and impaired glucose homeostasis. [ABSTRACT FROM AUTHOR]

ERβ has been assigned a tumor suppressor role in many cancer types. However, as conflicting findings emerge, ERβ's tissue-specific expression and functional role have remained elusive. There remains a notable gap in compact and comprehensive analyses of ESR2 mRNA expression levels across diverse tumor types coupled with an exploration of its potential gene network. In this study, we aim to address these gaps by presenting a comprehensive analysis of ESR2 transcriptomic data. We distinguished cancer types with significant changes in ESR2 expression levels compared to corresponding healthy tissue and concluded that ESR2 influences patient survival. Gene Set Enrichment Analysis (GSEA) distinguished molecular pathways affected by ESR2, including oxidative phosphorylation and epithelial–mesenchymal transition. Finally, we investigated genes displaying similar expression patterns as ESR2 in tumor tissues, identifying potential co-expressed genes that may exert a synergistic effect on clinical outcomes, with significant results, including the expression of ACIN1, SYNE2, TNFRSF13C, and MDM4. Collectively, our results highlight the significant influence of ESR2 mRNA expression on the transcriptomic landscape and the overall metabolism of cancerous cells across various tumor types. [ABSTRACT FROM AUTHOR]

Ferroptosis has been observed to play an important role during erythrocyte differentiation (ED). However, the biological gene markers and ferroptosis mechanisms in ED remain unknown. We downloaded the datasets of ED in human umbilical cord blood-derived CD34+ cells from the Gene Expression Omnibus database. Using median differentiation time, the sample was categorized into long and short groups. The differentially expressed ferroptosis-related genes (DE-FRGs) were screened using differential expression analysis. The enrichment analyses and a protein-protein interaction (PPI) network were conducted. To predict the ED stage, a logistic regression model was constructed using the least absolute shrinkage and selection operator (LASSO). Overall, 22 DE-FRGs were identified. Ferroptosisrelated pathways were enriched using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Gene Set Enrichment Analysis and Gene Set Variation Analysis revealed the primary involvement of DE-FRGs in JAK-STAT, MAPK, PI3K-AKT-mTORC1, WNT, and NOTCH signaling pathways. Ten-hub DE-FRGs were obtained using PPI analysis. Furthermore, we constructed mRNA-microRNA (miRNA) and mRNA-transcription factor networks. Immune cell infiltration levels differed significantly during ED. LASSO regression analysis established a signature using six DE-FRGs (ATF3, CDH2, CHAC1, DDR2, DPP4, and GDF15) related to the ED stage. Bioinformatic analyses identified ferroptosis-associated genes during ED, which were further validated. Overall, we identified ferroptosis-related genes to predict their correlations in ED. Exploring the underlying mechanisms of ferroptosis may help us better understand pathophysiological changes in ED and provide new evidence for clinical transformation. [ABSTRACT FROM AUTHOR]

Expression of calretinin in retina has been ascribed to multiple biological and functional aspects in the visual system. In this study, we examined the distribution patterns of calretinin immunoreactivity in gerbil and rat retina. In the gerbil, calretinin immunoreactivity was present in bipolar and amacrine cells of the inner nuclear layer and in neurones of the ganglion cell layer. In the rat, amacrine and ganglion cells showed calretinin immunoreactivity, but bipolar cells did not contain calretinin immunoreactivity. In both species, calretinin immunoreactivity was absent in cones, cone bipolars, and horizontal cells. In conclusion, gerbil as well as rat has a rod-dominant retina. The differences in calretinin expression between rat and gerbil require further investigations under various functional and developmental conditions. [ABSTRACT FROM AUTHOR]

Small RNAs (sRNAs) are important non-coding RNA regulators that play key roles in the development and pathogenesis of plant pathogens, as well as in other biological processes. However, whether these abundant and varying sRNAs are involved in Phytophthora development or infection remains enigmatic. In this study, sRNA sequencing of 4 asexual stages of Phytophthora capsici (P. capsici), namely, as mycelia (HY), sporangia (SP), zoospores (ZO), cysts (CY), and pepper infected with P. capsici (IN), were performed, followed by sRNA analysis, microRNA (miRNA) identification, and miRNA target prediction. sRNAs were mainly distributed at 25–26 nt in HY, SP, and ZO but distributed at 18–34 nt in CY and IN. 92, 42, 176, 39, and 148 known miRNAs and 15, 19, 54, 13, and 1 novel miRNA were identified in HY, SP, ZO, CY, and IN, respectively. It was found that the expression profiles of known miRNAs vary greatly at different stages and could be divided into 4 categories. Novel miRNAs mostly belong to part I. Gene ontology (GO) analysis of known miRNA-targeting genes showed that they are involved in the catalytic activity pathway, binding function, and other biological processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis of novel miRNA-targeting genes showed that they are involved in the lysine degradation pathway. The expression of candidate miRNAs was validated using quantitative reverse transcription–polymerase chain reaction (qRT–PCR), and miRNAs were downregulated in PcDCL1 or PcAGO1 mutants. To further explore the function of the detected miRNAs, the precursor of a novel miRNA, miR91, was knockout by CRISPR-Cas9, the mutants displayed decreased mycelial growth, sporangia production, and zoospore production. It was found that 503142 (Inositol polyphosphate 5-phosphatase and related proteins) can be predicted as a target of miR91, and the interaction between miR91 and 503142 was verified using the tobacco transient expression system. Overall, our results indicate that the diverse and differentially expressed sRNAs are involved in the development and pathogenesis of P. capsici. [ABSTRACT FROM AUTHOR]

Candida albicans is the predominant cause of systemic candidiasis, although other non albicans Candida species are progressively becoming more widespread nowadays. Candida auris has emerged as a deadly multidrug-resistant fungal pathogen, posing a significant threat to global public health. In the absence of effective antifungal therapies, the development of a vaccine against C. auris infections is imperative. Enolase, a key glycolytic enzyme, has emerged as a promising vaccine candidate due to its immunogenic properties and essential role in fungal virulence. Herein, full-length Enolase gene sequences from C. albicans and C. auris were cloned into suitable expression vector and transformed into Escherichia coli expression hosts. Recombinant Enolase proteins were successfully expressed and purified using affinity chromatography under native conditions, followed by SDS-PAGE characterization and Western blot analysis. CD spectroscopy verified the existence of expressed proteins in soluble native conformation. Preliminary in silico studies verified the immunogenicity of recombinant Enolase proteins isolated from both C. albicans and C. auris. Furthermore, bioinformatics analysis revealed conserved B-cell and T-cell epitopes across C. albicans and C. auris Enolase proteins, suggesting potential cross-reactivity and broad-spectrumvaccine efficacy. Our findings are anticipated to play a role in advancing therapeutic as well as diagnostic strategies against systemic candidiasis. [ABSTRACT FROM AUTHOR]

Background: Prenatal nicotine exposure (PNE) has been documented to cause numerous deleterious effects on fetal development. However, the epigenetic changes promoted by nicotine exposure on germ cells are still not well understood. Objectives: In this study, we focused on elucidating the impact of prenatal nicotine exposure on regulatory epigenetic mechanisms important for germ cell development. Methods: Sprague-Dawley rats were exposed to nicotine during pregnancy and male progeny was analyzed at 11 weeks of age. Testis morphology was analyzed using frozen testis sections and expression of germ cell markers was examined by RT-qPCR; histone modifications were assessed by Western Blot (WB). DNA methylation analysis was performed by methylation-specific PCR of bisulfite converted DNA. Genome-wide DNA methylation was analyzed using Methylated DNA immunoprecipitation (MeDIP)-seq. We also carried out transcriptomics analysis of pituitary glands by RNA-seq. Results: We show that gestational exposure to nicotine reduces germ cell numbers, perturbs meiosis, affects the expression of germ line reprogramming responsive genes, and impacts the DNA methylation of nervous system genes in the testis. PNE also causes perturbation of gene expression in the pituitary gland of the brain. Conclusions: Our data demonstrate that PNE leads to perturbation of male spermatogenesis, and the observed effects are associated with changes of peripheral nervous system signaling pathways. Alterations in the expression of genes associated with diverse biological activities such as cell migration, cell adhesion and GABA signaling in the pituitary gland underscore the complexity of the effects of nicotine exposure during pregnancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolic reprogramming in HER2-positive breast cancer is associated with acquired resistance to targeted therapies. Thus, targeting dysregulated metabolic pathways in cancers is highly beneficial. In this study, we examined the anti-tumor effects of an LXR inverse agonist GAC0001E5 (1E5) in HER2-positive breast cancer in vitro. Strikingly, we observed disruption of two major pathways, glutaminolysis and de novo lipogenesis, leading to oxidative stress and cell death. Additionally, we discovered the indirect effects of 1E5 in downregulating HER2 expression through fatty acid synthase (FASN). Moreover, in combinatory treatments of 1E5 and lapatinib, 1E5 potentiates lapatinib's effects. These findings indicate the importance of 1E5 as a metabolic disruptor in HER2-positive breast cancer. The HER2-positive subtype accounts for approximately one-fifth of all breast cancers. Insensitivity and development of acquired resistance to targeted therapies in some patients contribute to their poor prognosis. HER2 overexpression is associated with metabolic reprogramming, facilitating cancer cell growth and survival. Novel liver X receptor (LXR) ligand GAC0001E5 (1E5) has been shown to inhibit cancer cell proliferation by disrupting glutaminolysis and inducing oxidative stress. In this study, HER2-positive breast cancer cells were treated with 1E5 to determine their potential inhibitory effects and mechanisms of action in HER2-positive breast cancers. Similar to previous observations in other cancer types, 1E5 treatments inhibited LXR activity, expression, and cancer cell proliferation. Expression of fatty acid synthesis genes, including fatty acid synthase (FASN), was downregulated following 1E5 treatment, and results from co-treatment experiments with an FASN inhibitor suggest that the same pathway is targeted by 1E5. Treatments with 1E5 disrupted glutaminolysis and resulted in increased oxidative stress. Strikingly, HER2 transcript and protein levels were both significantly downregulated by 1E5. Taken together, these findings indicate the therapeutic potential of targeting HER2 overexpression and associated metabolic reprogramming via the modulation of LXR in HER2-positive breast cancers. [ABSTRACT FROM AUTHOR]

Kuratsuki bacteria enter the sake production process and affect the flavor and taste of sake. This study compared gene expression in the sake yeast Saccharomyces cerevisiae in co-culture with kuratsuki Kocuria to that in monoculture. Among the 5922 genes of S. cerevisiae, 71 genes were upregulated more than 2-fold, and 61 genes were downregulated less than 0.5-fold in co-culture with kuratsuki Kocuria. Among the stress-induced genes, fourteen were upregulated, and six were downregulated. Among the fourteen upregulated genes, six were induced in response to replication stress. Although the G1 cyclin gene CLN3 was upregulated by more than 2-fold, eight genes that were induced in response to meiosis and/or sporulation were also upregulated. Fourteen metabolism-related genes, for example, the glyceraldehyde-3-phosphate dehydrogenase genes TDH1, TDH2, and TDH3, were downregulated by less than 0.5-fold in co-culture with kuratsuki Kocuria. The gene expression patterns of S. cerevisiae co-cultured with kuratsuki Kocuria differed from those co-cultured with lactic acid bacteria. Therefore, S. cerevisiae responded differently to different bacterial species. This strongly suggests that kuratsuki bacteria affect gene expression in sake yeast, thereby affecting the flavor and taste of sake. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the effect of 1‐methylcyclopropene (1‐MCP) treatment on the postharvest quality, epidermal wax morphology, composition, and gene expression of Jinxiu yellow peach during cold storage. The results showed that 1‐MCP treatment could maintain the postharvest quality of peach fruit as compared to control (CK) during cold storage. The wax crystals of peach fruit were better retained by 1‐MCP, and they still existed in 0.6 and 0.9 µL/L 1‐MCP treated fruit at 36 days. The total wax content in all the fruit increased first and then decreased during cold storage. Meanwhile, n‐alkanes and primary alcohols were the main wax components. Compared to CK, 1‐MCP treatment could delay the reduction of wax content during cold storage. The correlation analysis indicated that the postharvest quality of yellow peach was mainly affected by the contents of fatty acids and triterpenoids in cuticular wax. The transcriptomics results revealed PpaCER1, PpaKCS, PpaKCR1, PpaCYP86B1, PpaFAR, PpaSS2, and PpaSQE1 played the important roles in the formation of peach fruit wax. 1‐MCP treatment upregulated PpaCER1 (18785414, 18786441, and 18787644), PpaKCS (18774919, 18789438, and 18793503), PpaKCR1 (18790432), and PpaCYP86B1 (18789815) to deposit more n‐alkanes and fatty acids during cold storage. This study could provide a new perspective for regulating the postharvest quality of yellow peach in view of the application of cuticular wax. Practical Application: 'Jinxiu' yellow peach fruit is favorable among consumers because of its high commercial value. However, it ripens and deteriorates rapidly during storage, leading to serious economic loss and consumer disappointment. The effect of 1‐methylcyclopropene (1‐MCP) treatment on the postharvest quality, epidermal wax morphology, composition, and genes regulation of 'Jinxiu' yellow peach during cold storage was assessed. Compared to control, 1‐MCP treatment could retain the storage quality of yellow peach by affecting cuticular wax composition and gene expression. This study could provide new perspective for regulating the postharvest quality of yellow peach in view of the application of cuticular wax. [ABSTRACT FROM AUTHOR]

Age-associated deep-subcortical white matter lesions (DSCLs) are an independent risk factor for dementia, displaying high levels of CD68+ microglia. This study aimed to characterize the transcriptomic profile of microglia in DSCLs and surrounding radiologically normal-appearing white matter (NAWM) compared to non-lesional control white matter. CD68+ microglia were isolated from white matter groups (n = 4 cases per group) from the Cognitive Function and Ageing Study neuropathology cohort using immuno-laser capture microdissection. Microarray gene expression profiling, but not RNA-sequencing, was found to be compatible with immuno-LCM-ed post-mortem material in the CFAS cohort and identified significantly differentially expressed genes (DEGs). Functional grouping and pathway analysis were assessed using the Database for Annotation Visualization and Integrated Discovery (DAVID) software, and immunohistochemistry was performed to validate gene expression changes at the protein level. Transcriptomic profiling of microglia in DSCLs compared to non-lesional control white matter identified 181 significant DEGs (93 upregulated and 88 downregulated). Functional clustering analysis in DAVID revealed dysregulation of haptoglobin–haemoglobin binding (Enrichment score 2.5, p = 0.017), confirmed using CD163 immunostaining, suggesting a neuroprotective microglial response to blood–brain barrier dysfunction in DSCLs. In NAWM versus control white matter, microglia exhibited 347 DEGs (209 upregulated, 138 downregulated), with significant dysregulation of protein de-ubiquitination (Enrichment score 5.14, p < 0.001), implying an inability to maintain protein homeostasis in NAWM that may contribute to lesion spread. These findings enhance understanding of microglial transcriptomic changes in ageing white matter pathology, highlighting a neuroprotective adaptation in DSCLs microglia and a potentially lesion-promoting phenotype in NAWM microglia. [ABSTRACT FROM AUTHOR]

KH-type splicing regulatory protein (KSRP) is a single-stranded nucleic acid-binding protein with multiple functions. It is known to bind AU-rich motifs within the 3′-untranslated region of mRNA species, which in many cases encode dynamically regulated proteins like cytokines. In the present study, we investigated the role of KSRP for the immunophenotype of macrophages using bone marrow-derived macrophages (BMDM) from wild-type (WT) and KSRP−/− mice. RNA sequencing revealed that KSRP−/− BMDM displayed significantly higher mRNA expression levels of genes involved in inflammatory and immune responses, particularly type I interferon responses, following LPS stimulation. In line, time kinetics studies revealed increased levels of interferon-γ (IFN-γ), interleukin (IL)-1β and IL-6 mRNA in KSRP−/− macrophages after 6 h subsequent to LPS stimulation as compared to WT cultures. At the protein level, KSRP−/− BMDM displayed higher levels of these cytokines after overnight stimulation. Matching results were observed for primary peritoneal macrophages of KSRP−/− mice. These showed higher IL-6, tumor necrosis factor-α (TNF-α), C-X-C motif chemokine 1 (CXCL1) and CC-chemokine ligand 5 (CCL5) protein levels in response to LPS stimulation than the WT controls. As macrophages play a key role in sepsis, the in vivo relevance of KSRP deficiency for cytokine/chemokine production was analyzed in an acute inflammation model. In agreement with our in vitro findings, KSRP-deficient animals showed higher cytokine production upon LPS administration in comparison to WT mice. Taken together, these findings demonstrate that KSRP constitutes an important negative regulator of cytokine expression in macrophages. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics. Methods: We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups. Results: We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p < 1.0 × 10–6), including the PCSK9 gene locus and five other lipid loci: APOB, TM6SF2, FADS1/FADS2, JMJD1C, and HP/HPR. The interaction analysis revealed eight loci with sex- and/or statin-interactions. At the PCSK9 gene locus, there were four independent signals, one with a significant sex-interaction showing stronger effects in men (rs693668). Regarding statin treatment, there were two significant interactions in PCSK9 missense mutations: rs11591147 had stronger effects in statin-free individuals, and rs11583680 had stronger effects in statin-treated individuals. Besides replicating known loci, we detected two novel genome-wide significant associations: one for statin-treated individuals at 6q11.1 (within KHDRBS2) and one for males at 12q24.22 (near KSR2/NOS1), both with significant interactions. In the MR of PCSK9 on LDL-C, we observed significant causal estimates within all subgroups, but significantly stronger causal effects in statin-free subjects compared to statin-treated individuals. Conclusions: We performed the first double-stratified GWAS of PCSK9 levels and identified multiple biologically plausible loci with genetic interaction effects. Our results indicate that the observed sexual dimorphism of PCSK9 and its statin-related interactions have a genetic basis. Significant differences in the causal relationship between PCSK9 and LDL-C suggest sex-specific dosages of PCSK9 inhibitors. Plain English Summary: The protein "proprotein convertase subtilisin/kexin type 9" (PCSK9) regulates the levels of low-density lipoprotein cholesterol (LDL-C) in blood, and thus, contributes to the risk of cardio-vascular diseases. Women tend to have higher PCSK9 plasma levels throughout their life, although the difference is smaller in patients under LDL-C lowering medication (e.g., statins). We investigated the interplay of genetics, statin-treatment and sex, using combined data from six European studies. We detected 11 genetic regions associated with PCSK9 levels, of which one was specific for women (at SLCO1B3, a statin-transporter gene), and three were specific for men (e.g., ALOX5, encoding a protein linked to chronic inflammatory diseases such as atherosclerosis). We also tested if statin use changed the genetic effect and found five genes only associated with PCSK9 levels in untreated participants. Variants in the gene encoding PCSK9 were most strongly associated and had heterogeneous effects in dependence on statin treatment and sex: On one hand, there were genetic variants with stronger effects in men than women. Those variants are also linked to sex-differential gene expression of PCSK9. On the other hand, there were also variants with treatment-depending effects, linked to protein structure and functionality of PCSK9. This indicates that the observed sexual and treatment-related effects on PCSK9 levels have a genetic basis. In addition, we compared the causal effects of PCSK9 on LDL-C levels between men and women and found a different response to statin treatment. This highlights the need for sex-sensitive dosages of lipid-lowering medication. Highlights: First sex- and statin-stratified GWAS of PCSK9 plasma levels comparing SNP effects in eight subgroups. 11 associated loci (p < 1 × 10–6), including six loci known for association with PCSK9 or lipids, and five novel loci independent of lipids. Five loci with significant sex-interactions, and seven loci with statin-interactions. The PCSK9 gene was associated in all subgroups, and there were both significant sex- and statin-related effects. The Mendelian Randomization using four independent PCSK9 variants resulted in significant causal estimates for all subgroups. The causal estimates of statin-treated individuals were significantly lower than those of statin-free participants. This difference increased testing the subgroup of men, and decreased in women. [ABSTRACT FROM AUTHOR]

The genus Paracoccidioides includes Paracoccidioides lutzii and the Paracoccidioides brasiliensis complex, which comprises four phylogenetic species. A key feature distinguishing planktonic growth from biofilm is the presence of a 3D extracellular matrix (ECM). Therefore, in this study, we analyzed biofilm formation in dierent species of Paracoccidioides yeast phase, characterized the structural elements of the matrix of P. brasiliensis (Pb18), P. lutzii (Pl01 and 8334) and P. restrepiensis (339 and 192) and evaluated the expression of glucan genes, according to the stage of biofilm evolution for P. brasiliensis. The strains were cultivated in planktonic and biofilm form for 24–144 h. The fungi biomass and metabolic activity were determined by crystal violet and tetrazolium salt reduction (XTT) tests and colony-forming unit (CFU) by plating. The biofilm structure was designed using scanning electron microscopy and confocal laser scanning microscopy techniques. The extracellular matrix of P. brasiliensis and P. lutzii biofilms was extracted by sonication, and polysaccharides, proteins, and extracellular DNA (eDNA) were quantified. The RNA was extracted with the Trizol® reagent and quantified; then, the cDNA was synthesized to analyze the enolase expression, 14-3-3, FKS1, AGS1, GEL3, and KRE6 genes by real-time PCR. All strains of Paracoccidioides studied form a biofilm with more significant metabolic activity and biomass values in 144 h. The extracellular matrix of P. brasiliensis and P. lutzii had a higher content of polysaccharides in their composition, followed by proteins and eDNA in smaller quantities. The P. brasiliensis biofilm kinetics of formation showed greater expression of genes related to glucan’s synthesis and its delivery to the external environment in addition adhesins during the biofilm’s adhesion, initiation, and maturation. The GEL3 and enolase genes increased in expression within 24 h and during the biofilm maturation period, there was an increase in 14-3-3, AGS1, and FKS1. Furthermore, at 144 h, there was a decrease in KRE6 expression and an increase in GEL3. This study highlights the potential for biofilm formation for three species of Paracoccidioides and the main components of the extracellular matrix that can contribute to a better understanding of biofilm organization. [ABSTRACT FROM AUTHOR]

Background: Mung bean (Vigna radiata (L.) Wilczek), is an important pulse crop in the global south. Early flowering and maturation are advantageous traits for adaptation to northern and southern latitudes. This study investigates the genetic basis of the Days-to-Flowering trait (DTF) in mung bean, combining genome-wide association studies (GWAS) in mung bean and comparisons with orthologous genes involved with control of DTF responses in soybean (Glycine max (L) Merr) and Arabidopsis (Arabidopsis thaliana). Results: The most significant associations for DTF were on mung bean chromosomes 1, 2, and 4. Only the SNPs on chromosomes 1 and 4 were heavily investigated using downstream analysis. The chromosome 1 DTF association is tightly linked with a cluster of locally duplicated FERONIA (FER) receptor-like protein kinase genes, and the SNP occurs within one of the FERONIA genes. In Arabidopsis, an orthologous FERONIA gene (AT3G51550), has been reported to regulate the expression of the FLOWERING LOCUS C (FLC). For the chromosome 4 DTF locus, the strongest candidates are Vradi04g00002773 and Vradi04g00002778, orthologous to the Arabidopsis PhyA and PIF3 genes, encoding phytochrome A (a photoreceptor protein sensitive to red to far-red light) and phytochrome-interacting factor 3, respectively. The soybean PhyA orthologs include the classical loci E3 and E4 (genes GmPhyA3, Glyma.19G224200, and GmPhyA2, Glyma.20G090000). The mung bean PhyA ortholog has been previously reported as a candidate for DTF in studies conducted in South Korea. Conclusion: The top two identified SNPs accounted for a significant proportion (~ 65%) of the phenotypic variability in mung bean DTF by the six significant SNPs (39.61%), with a broad-sense heritability of 0.93. The strong associations of DTF with genes that have orthologs with analogous functions in soybean and Arabidopsis provide strong circumstantial evidence that these genes are causal for this trait. The three reported loci and candidate genes provide useful targets for marker-assisted breeding in mung beans. [ABSTRACT FROM AUTHOR]

Black-grass (Alopecurus myosuroides) is one of the most problematic agricultural weeds of Western Europe, causing significant yield losses in winter wheat (Triticum aestivum) and other crops through competition for space and resources. Previous studies link black-grass patches to water-retaining soils, yet its specific adaptations to these conditions remain unclear. We designed pot-based waterlogging experiments to compare 13 biotypes of black-grass and six cultivars of wheat. These showed that wheat roots induced aerenchyma when waterlogged whereas aerenchyma-like structures were constitutively present in black-grass. Aerial biomass of waterlogged wheat was smaller, whereas waterlogged black-grass was similar or larger. Variability in waterlogging responses within and between these species was correlated with transcriptomic and metabolomic changes in leaves of control or waterlogged plants. In wheat, transcripts associated with regulation and utilisation of phosphate compounds were upregulated and sugars and amino acids concentrations were increased. Black-grass biotypes showed limited molecular responses to waterlogging. Some black-grass amino acids were decreased and one transcript commonly upregulated was previously identified in screens for genes underpinning metabolism-based resistance to herbicides. Our findings provide insights into the different waterlogging tolerances of these species and may help to explain the previously observed patchiness of this weed's distribution in wheat fields. Black-grass is a problematic weed of winter wheat. To better understand if waterlogging tolerance increases its weediness, we conducted controlled waterlogging studies comparing the physiology and molecular responses of black-grass and wheat. These revealed differences in roots and aerial tissues within and between species. Molecular analyses showed that wheat mounts a significant molecular response, altering gene expression and metabolites with waterlogging, whereas black-grass showed minimal responses to waterlogging despite its apparent tolerance. This article belongs to the Collection Flooding Stress and Hypoxic Responses in Plants. [ABSTRACT FROM AUTHOR]

In humans and animal models, temporal lobe epilepsy (TLE) is associated with reorganization of hippocampal neuronal networks, gliosis, neuroinflammation, and loss of integrity of the blood–brain barrier (BBB). More than 30% of epilepsies remain intractable, and characterization of the molecular mechanisms involved in BBB dysfunction is essential to the identification of new therapeutic strategies. In this work, we induced status epilepticus in rats through injection of the proconvulsant drug pilocarpine, which leads to TLE. Using RT-qPCR, double immunohistochemistry, and confocal imaging, we studied the regulation of reactive glia and vascular markers at different time points of epileptogenesis (latent phase—3, 7, and 14 days; chronic phase—1 and 3 months). In the hippocampus, increased expression of mRNA encoding the glial proteins GFAP and Iba1 confirmed neuroinflammatory status. We report for the first time the concomitant induction of the specific proteins CD31, PDGFRβ, and ColIV—which peak at the same time points as inflammation—in the endothelial cells, pericytes, and basement membrane of the BBB. The altered expression of these proteins occurs early in TLE, during the latent phase, suggesting that they could be associated with the early rupture and pathogenicity of the BBB that will contribute to the chronic phase of epilepsy. [ABSTRACT FROM AUTHOR]

REV-ERBα and its paralog, REV-ERBβ, encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock and can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes are controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provide strong evidence for isoform-dependent actions. For example, REV-ERBα is more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components requires REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators can help treat metabolic disturbances and certain types of cancer. [ABSTRACT FROM AUTHOR]

Transposable elements (TEs) are indispensable components of eukaryotic genomes that play diverse roles in gene regulation, recombination, and environmental adaptation. Their ability to mobilize within the genome leads to gene expression and DNA structure changes. TEs serve as valuable markers for genetic and evolutionary studies and facilitate genetic mapping and phylogenetic analysis. They also provide insight into how organisms adapt to a changing environment by promoting gene rearrangements that lead to new gene combinations. These repetitive sequences significantly impact genome structure, function and evolution. This review takes a comprehensive look at TEs and their applications in biotechnology, particularly in the context of plant biology, where they are now considered “genomic gold” due to their extensive functionalities. The article addresses various aspects of TEs in plant development, including their structure, epigenetic regulation, evolutionary patterns, and their use in gene editing and plant molecular markers. The goal is to systematically understand TEs and shed light on their diverse roles in plant biology. [ABSTRACT FROM AUTHOR]

As a newly discovered regulated cell death mode, ferroptosis is associated with the development of Parkinson's disease (PD) and has attracted much attention. Nonetheless, the relationship between ferroptosis and PD pathogenesis remains unclear. The GSE8397 dataset includes GPL96 and GPL97 platforms. The differential genes were analyzed by immune infiltration and Gene Set Enrichment Analysis (GSEA) (p < 0.05), and differential multiple |logFC| > 1 and weighted gene coexpression network analysis (WGCNA) were used to screen differential expression genes (DEGs). The intersection with 368 ferroptosis-related genes (FRGs) was conducted for gene ontology/Kyoto encyclopedia of gene and genome (GO/KEGG) enrichment analysis, gene expression analysis, correlation analysis, single-cell sequencing analysis, and prognosis analysis (area under the curve, AUC) and to predict relevant miRNAs and construct network diagrams using Cytoscape. The intersection genes of differentially expressed ferroptosis-related genes (DEFRGs) and mitochondrial dysfunction genes were validated in the substantia nigra of MPTP-induced PD mice models by Western blotting and immunohistochemistry, and the protein-binding pocket was predicted using the DoGSiteScorer database. According to the results, the estimated scores were positively correlated with the stromal scores or immune scores in the GPL96 and GPL97 platforms. In the GPL96 platform, the GSEA showed that differential genes were mainly involved in the GnRH signaling pathway, B cell receptor signaling pathway, inositol phosphate metabolism, etc. In the GPL97 platform, the GSEA showed that differential genes were mainly involved in the ubiquitin-mediated proteolysis, axon guidance, Wnt signaling pathway, MAPK signaling pathway, etc. We obtained 26 DEFRGs, including 12 up-regulated genes and 14 down-regulated genes, with good correlation. The area under the prognostic analysis curve (AUC > 0.700) showed a good prognostic ability. We found that they were enriched in different neuronal cells, oligodendrocytes, astrocytes, oligodendrocyte precursor cells, and microglial cells, and their expression scores were positively correlated, and selected genes with an AUC curve ≥0.9 were used to predict miRNA, including miR-214/761/3619-5p, miR-203, miR-204/204b/211, miR-128/128ab, miR-199ab-5p, etc. For the differentially expressed ferroptosis–mitochondrial dysfunction-related genes (DEF-MDRGs) (AR, ISCU, SNCA, and PDK4), in the substantia nigra of mice, compared with the Saline group, the expression of AR and ISCU was decreased (p < 0.05), and the expression of α-Syn and PDK4 was increased (p < 0.05) in the MPTP group. Therapeutic drugs that target SNCA include ABBV-0805, Prasinezumab, Cinpanemab, and Gardenin A. The results of this study suggest that cellular DEF-MDRGs might play an important role in PD. AR, ISCU, SNCA, and PDK4 have the potential to be specific biomarkers for the early diagnosis of PD. [ABSTRACT FROM AUTHOR]

Studying the molecular mechanisms of the pathogenesis of Parkinson's disease (PD) is critical to improve PD treatment. We used OpenArray technology to assess gene expression in the substantia nigra (SN) cells of mice in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and in controls. Among the 11 housekeeping genes tested, Rps27a was taken as the reference gene due to its most stable expression in normal and experimental conditions. From 101 genes encoding functionally significant proteins of nigrostriatal dopaminergic neurons, 57 highly expressed genes were selected to assess their expressions in the PD model and in the controls. The expressions of Th, Ddc, Maoa, Comt, Slc6a3, Slc18a2, Drd2, and Nr4a2 decreased in the experiment compared to the control, indicating decreases in the synthesis, degradation, and transport of dopamine and the impaired autoregulation of dopaminergic neurons. The expressions of Tubb3, Map2, Syn1, Syt1, Rab7, Sod1, Cib1, Gpx1, Psmd4, Ubb, Usp47, and Ctsb genes were also decreased in the MPTP-treated mice, indicating impairments of axonal and vesicular transport and abnormal functioning of the antioxidant and ubiquitin-proteasome systems in the SN. The detected decreases in the expressions of Snca, Nsf, Dnm1l, and Keap1 may serve to reduce pathological protein aggregation, increase dopamine release in the striatum, prevent mitophagy, and restore the redox status of SN cells. [ABSTRACT FROM AUTHOR]

Background and Objective. Multiple sclerosis (MS) is a progressive disease of the nervous system that leads to demyelination of the nerves and is more common in young adults, especially women. Environmental factors that trigger MS pathogeneses are genetic susceptibility and viral infections. The viral infections are considered to be of particular relevance. Along with viruses belonging to the Herpesviridae family such as varicella zoster virus (VZV), human herpes virus-6 (HHV-6), and particularly Epstein–Barr virus (EBV), the expression of the env gene of human endogenous retrovirus (HERV-W) like MSRV is expected to be one of the risk factors for bringing up MS and disease progression. The present study aimed to investigate the correlation between EBV infection and HERV-W env in a case group (MS patients) and a control group (healthy individuals). Materials and Methods. 130 subjects were enrolled in a case-control study at two tertiary university hospitals from Tabriz (Imam and Razi), Iran. Of these, 65 subjects were MS patients serving as the case group, and 65 subjects were healthy individuals serving as the control group. After DNA extraction from all samples, the EBER region of EBV genome was used as the primer for the detection of EBV. RNA was extracted from PBMCs, and cDNA synthesis was performed by using Sina Gene kit. Subsequently, each sample was analysed by RT-PCR with two sets of primers to detect specifically multiple sclerosis retroviruses (MSRV) env, and RT-PCR was repeated for each HERV-W env. Positive sample was used in order to confirm the result. Results. In the case group, 19 (29.2%) patients were male and 46 (70.8%) patients were female. Nevertheless, in the control group, 21 (32.3%) subjects were male and 44 (67.7%) subjects were female. No significant difference was found between groups in gender (p = 0.70). The mean range in control and case groups was 33/38 ± 9/85 and 33.18 ± 8.65, respectively. No significant difference was found between groups in age (p = 0.902). 4 (6.2%) patients in case groups were found to be positive for EBV DNA (p = 0.119). Expression of the env gene of HERVs was observed in 10 (15.38%) and two (3.07%) specimens in the case and control groups (p = 0.030), separately. A comparison of the prevalence of the HERV ENV genome between the two study groups showed a significant difference (p = 0.005). Conclusion. The results of this study failed to show any difference between MS patients and healthy controls in the rate of EBV infection. It can be concluded that the expression of HERV-W/env genes may be involved in the development of MS in these patients. [ABSTRACT FROM AUTHOR]

Despite the fact that most of the bacterial genome encodes certain protein molecules, with the development of transcriptomic technologies, many genes have been discovered that transcribe RNA which is not translated into proteins. Such RNAs are called non-coding RNAs (ncRNAs). The study of only a small number of them shows that ncRNAs often act as regulatory molecules in various cellular processes: maintenance of cell wall homeostasis, protection against pathogens, virulence, etc. A special place among them is occupied by the so-called small ncRNAs with a length of ~50–300 nucleotide residues. In most cases, they form duplexes with the mRNA of certain genes, which affects the expression of the latter, however, some ncRNAs are able to directly bind to the target protein. Similar mechanisms of action of small ncRNAs give them some advantages in regulating various cellular processes compared to protein regulatory molecules. For example, when responding to an external or internal signal through small ncRNAs, the cell will need to spend less time and resources due to the absence of the translation stage. Moreover, some ncRNAs have no complete complementarity to their target RNAs, which makes the regulation more flexible, as it allows ncRNAs to participate in the response simultaneously to various cellular signals. In this review, we considered the general mechanisms by which various small ncRNAs allow bacteria to adapt to certain stressful conditions, as well as specific examples of their action in various prokaryotic organisms. [ABSTRACT FROM AUTHOR]

Our recent report showed that curcumin, polyphenolic compound isolated from the herb Curcuma longa, upregulated the gene expression of human GD3 synthase (hST8Sia I) responsible for ganglioside GD3 synthesis with autophagy induction in human lung adenocarcinoma A549 cells. In this study, on the contrary to this finding, we demonstrated that curcumin downregulated the gene expression of human GM3 synthase (hST3Gal V) catalyzing ganglioside GM3 synthesis with autophagy induction in human colon carcinoma HCT116 cells. To clarify the mechanism leading to the downregulation of hST3Gal V gene expression in curcumin-treated HCT116 cells, we analyzed the curcumin-inducible promoter of the hST3Gal V gene by luciferase reporter assays. Promoter deletion analysis demonstrated that the -177 to -83 region, which includes putative binding sites for transcription factors NFY, CREB/ATF, SP1, EGR3, and MZF1, acts as the curcumin-responsive promoter of the hST3Gal V gene. Site-directed mutagenesis and chromatin immunoprecipitation analysis demonstrated that the CREB/ATF binding site at -143 is pivotal for curcumin-induced downregulation of hST3Gal V gene in HCT116 cells. The transcriptional activation of hST3Gal V in HCT116 cells was significantly repressed by an inhibitor of AMP-activated protein kinase (AMPK). These results suggest that AMPK signal pathway mediates hST3Gal V gene expression in HCT116 cells. [ABSTRACT FROM AUTHOR]

Background: Polyadenylation is a crucial process that terminates mRNA molecules at their 3′-ends. It has been observed that alternative polyadenylation (APA) can generate multiple transcripts from a single gene locus, each with different polyadenylation sites (PASs). This leads to the formation of several 3′ untranslated regions (UTRs) that vary in length and composition. APA has a significant impact on approximately 60–70% of eukaryotic genes and has far-reaching implications for cell proliferation, differentiation, and tumorigenesis. Results: In this study, we conducted long-read, single-molecule sequencing of mRNA from peanut seeds. Our findings revealed that over half of all peanut genes possess over two PASs, with older developing seeds containing more PASs. This suggesting that the PAS exhibits high tissue specificity and plays a crucial role in peanut seed maturation. For the peanut acetyl-CoA carboxylase A1 (AhACCA1) gene, we discovered four 3′ UTRs referred to UTR1–4. RT-PCR analysis showed that UTR1-containing transcripts are predominantly expressed in roots, leaves, and early developing seeds. Transcripts containing UTR2/3 accumulated mainly in roots, flowers, and seeds, while those carrying UTR4 were constitutively expressed. In Nicotiana benthamiana leaves, we transiently expressed all four UTRs, revealing that each UTR impacted protein abundance but not subcellular location. For functional validation, we introduced each UTR into yeast cells and found UTR2 enhanced AhACCA1 expression compared to a yeast transcription terminator, whereas UTR3 did not. Furthermore, we determined ACC gene structures in seven plant species and identified 51 PASs for 15 ACC genes across four plant species, confirming that APA of the ACC gene family is universal phenomenon in plants. Conclusion: Our data demonstrate that APA is widespread in peanut seeds and plays vital roles in peanut seed maturation. We have identified four 3′ UTRs for AhACCA1 gene, each showing distinct tissue-specific expression patterns. Through subcellular location experiment and yeast transformation test, we have determined that UTR2 has a stronger impact on gene expression regulation compared to the other three UTRs. [ABSTRACT FROM AUTHOR]

Skin aging is a complex process influenced by intrinsic and extrinsic factors. Although dermatology offers advanced interventions, molecular mechanisms in skin aging remain limited. Competing endogenous RNAs (ceRNAs), a subset of coding or non-coding RNAs, regulate gene expression through miRNA competition. Several ceRNA networks investigated up to now offer insights into skin aging and wound healing. In skin aging, RP11-670E13.6-miR-663aCDK4/CD6 delays senescence induced by UVB radiation. Meg3-miR-93-5pepiregulin contributes to UVB-induced inflammatory skin damage. Predicted ceRNA networks reveal UVA-induced photoaging mechanisms. SPRR2C sequesters miRNAs in epidermal aging-associated alteration of calcium gradient. H19-miR-296-5p-IGF2 regulates dermal fibroblast senescence. PVT1- miR-551b-3p-AQP3 influences skin photoaging. And bioinformatics analyses identify critical genes and compounds for skin aging interventions. In skin wound healing, MALAT1-miR-124 aids wound healing by activating the Wnt/βcatenin pathway. Hair follicle MSC-derived H19 promotes wound healing by inhibiting pyroptosis. And the SAN-miR-143-3p-ADD3 network rejuvenates adipose-derived mesenchymal stem cells in wound healing. Thus, ceRNA networks provide valuable insights into the molecular underpinnings of skin aging and wound healing, offering potential therapeutic strategies for further investigation. This comprehensive review serves as a foundational platform for future research endeavors in these crucial areas of dermatology. [ABSTRACT FROM AUTHOR]

Background: Acetyl-CoA Carboxylase Beta (ACACB) plays a key role in fatty acid oxidation and was known to be involved in production of very-long-chain fatty acid and other compounds needed for proper development. This gene is mainly expressed in the tissues of heart, muscle, liver and colon. It chiefly involved in the production of malonyl-coA, a potent inhibitor of carnitine palmitoyl transferase I (CPT-I) enzyme needed in transport of long-chain fatty acyl-coAs to the mitochondria for β-oxidation. Methods: The present study was conducted to explore the expression pattern of the ACACB gene in breast muscle tissue during pre-hatch embryonic day (ED) 5th to 18th and post-hatch (18th, 22nd and 40th week of age) periods of White leghorn (IWI line) by using Quantitative real-time PCR (qPCR). Then, fold change of ACACB gene expression was calculated. Result: Our study showed that the ACACB gene expression was down-regulated during embryonic stages from ED6 to ED18. The gene expression was also down-regulated during adult stages i.e. on 22nd and 40th week of age. This result indicated that the initial expression of the ACACB gene is required for embryo development and during adult periods, low gene expression leads to the less fat deposition in muscle of layer chicken. Finally, it can be concluded that there was a differential expression pattern of the ACACB gene during the pre-hatch embryonic and post-hatch adult periods to mitigate varied requirements of lipids during different physiological stages in layer chicken. [ABSTRACT FROM AUTHOR]

Chung-Sang-Bo-Ha-Hwan (CSBHH) is an herbal prescription widely used to treat various chronic respiratory diseases. To investigate the system-level treatment mechanisms of CSBHH in respiratory tract diseases, we identified 56 active ingredients of CSBHH and evaluated the degree of overlap between their targets and respiratory tract disease-associated proteins. We then investigated the respiratory tract disease-related signaling pathways associated with CSBHH targets. Enrichment analysis showed that the CSBHH targets were significantly associated with various signaling pathways related to inflammation, alveolar structure, and tissue fibrosis. Experimental validation was conducted using phorbol-12-myristate-13-acetate (PMA)-stimulated NCI-H292 cells by analyzing the mRNA expression levels of biomarkers (IL-1β and TNF-α for inflammation; GSTP1, GSTM1, and PTEN for apoptosis) derived from network pharmacological analysis, in addition to the mucin genes MUC5AC and MUC2, to investigate the phlegm-expelling effect of CSBHH. The mRNA expression levels of these genes were consistent with network pharmacological predictions in a concentration-dependent manner. These results suggest that the therapeutic mechanisms of CSBHH in respiratory tract diseases could be attributed to the simultaneous action of multiple active ingredients in the herbal prescription. [ABSTRACT FROM AUTHOR]

The oriental river prawn (Macrobrachium nipponense) is a commercially important species in Asia. A previous study showed that the succinate dehydrogenase complex iron sulfur subunit B (SDHB) gene participates in testes development in this species through its effect on the expression of the insulin-like androgenic gland hormone gene. This study knocked-down the Mn-SDHB genes in M. nipponense using RNAi. A transcriptome analysis of the androgenic gland and testes was then performed to discover the male sex-related genes regulated by SDHB and investigate the mechanism of male sexual development in this species. More than 16,623 unigenes were discovered in each sample generated. In the androgenic gland, most of the differentially expressed genes were enriched in the hypertrophic cardiomyopathy pathway, while in the testes, they were enriched in the citrate cycle pathway. In addition, after Mn-SDHB knockdown, five genes were found to be downregulated in the androgenic gland in a series of biological processes associated with phosphorylated carbohydrate synthesis and transformations in the glycolysis/gluconeogenesis pathway. Moreover, a total of nine male sex-related genes were identified including Pro-resilin, insulin-like androgenic gland hormone, Protein mono-ADP-ribosyltransferase PAPR11, DNAJC2, C-type Lectin-1, Tyrosine-protein kinase Yes, Vigilin, and Sperm motility kinase Y-like, demonstrating the regulatory effects of Mn-SDHB, and providing a reference for the further study of the mechanisms of male development in M. nipponense. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the linkage of the association of azoospermia phenotype with genetic alterations, involved in genome instability. Male infertility is a multifactorial pathology, and genetic alterations might be the underlying factors in majority of cases of severe male infertility. The recent emergence of next-generation sequencing offers an opportunity to analyze many genes and their interactions at once, and whole-exome sequencing (WES) together with whole-genome sequencing (WGS) was recently suggested for implementation of diagnosis workup in severe infertility cases. However, the reports on WES in conjunction with burden tests and gene network analysis are scarce or lacking in cases of severe male infertility. WES was performed on 21 nonobstructive azoospermia patients. DNA samples were sequenced using the Twist Comprehensive Exome Panel. Genetic burden test was performed with Testing Rare vAriants using Public Data. Protein interactions were investigated with ConsensusPathDB and Cytoscape. For single nucleotide variants and copy number variations (CNV) analysis, samples were analyzed with the Illumina's BaseSpace Variant Interpreter. Genetic variant burden was found elevated in 1,473 genes out of 30,000 known testis expressed genes. Three hundred and two genes with increased loss-of-function (LoF) variant set were present in more than one sample. Overrepresentation analysis with pathway-based set of genes with high variant burden demonstrated 26 pathways. Overrepresentation analysis with protein complex-based gene sets obtained 14 sets, showing the involvement in cell proliferation and DNA repair. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) network analysis with Cytoscape identified two clusters: (1) genes, involved in DNA binding/condensation and repair processes and (2) genes with the role in ribosome biosynthesis and gene expression processes. Increased loss of function germline variant burden and sumoylation may have critical significance in spermatogenesis. These parameters may be used for focused diagnosis in nonobstructive azoospermia patients. This may have both general significance for the decreased organism functionality but in particular is critical in spermatogenesis. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) is a severe psychiatric and neurodevelopmental disorder. The pathological process of SCZ starts early during development, way before the first onset of psychotic symptoms. DNA methylation plays an important role in regulating gene expression and dysregulated DNA methylation is involved in the pathogenesis of various diseases. The methylated DNA immunoprecipitation‐chip (MeDIP‐chip) is performed to investigate genome‐wide DNA methylation dysregulation in peripheral blood mononuclear cells (PBMCs) of patients with first‐episode SCZ (FES). Results show that the SHANK3 promoter is hypermethylated, and this hypermethylation (HyperM) is negatively correlated with the cortical surface area in the left inferior temporal cortex and positively correlated with the negative symptom subscores in FES. The transcription factor YBX1 is further found to bind to the HyperM region of SHANK3 promoter in induced pluripotent stem cells (iPSCs)‐derived cortical interneurons (cINs) but not glutamatergic neurons. Furthermore, a direct and positive regulatory effect of YBX1 on the expression of SHANK3 is confirmed in cINs using shRNAs. In summary, the dysregulated SHANK3 expression in cINs suggests the potential role of DNA methylation in the neuropathological mechanism underlying SCZ. The results also suggest that HyperM of SHANK3 in PBMCs can serve as a potential peripheral biomarker of SCZ. [ABSTRACT FROM AUTHOR]

Objectives: Mammalian palatogenesis is a highly regulated morphogenetic process to form the intact roof of the oral cavity. Long noncoding RNAs (lncRNAs) and mRNAs participate in numerous biological and pathological processes, but their roles in palatal development and causing orofacial clefts (OFC) remain to be clarified. Methods: Palatal tissues were separated from ICR mouse embryos at four stages (E10.5, E13.5, E15, and E17). Then, RNA sequencing (RNA‐seq) was used. Various analyses were performed to explore the results. Finally, hub genes were validated via qPCR and in situ hybridization. Results: Starting from E10.5, the expression of cell adhesion genes escalated in the following stages. Cilium assembly and ossification genes were both upregulated at E15 compared with E13.5. Besides, the expression of cilium assembly genes was also increased at E17 compared with E15. Expression patterns of three lncRNAs (H19, Malat1, and Miat) and four mRNAs (Cdh1, Irf6, Grhl3, Efnb1) detected in RNA‐seq were validated. Conclusions: This study provides a time‐series expression landscape of mRNAs and lncRNAs during palatogenesis, which highlights the importance of processes such as cell adhesion and ossification. Our results will facilitate a deeper understanding of the complexity of gene expression and regulation during palatogenesis. [ABSTRACT FROM AUTHOR]

A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus strains producing the D(−)-lactic acid isomer are known to exert stronger protection. However, the molecular mechanisms underlying this antimicrobial action are not well understood. The aim of this study was to investigate the role of D(−)-lactic acid isomer in the prevention of C. trachomatis infection in an in vitro HeLa cell model. We selected two strains of lactobacilli belonging to different species: a vaginal isolate of Lactobacillus crispatus that releases both D(−) and L(+) isomers and a strain of Lactobacillus reuteri that produces only the L(+) isomer. Initially, we demonstrated that L. crispatus was significantly more effective than L. reuteri in reducing C. trachomatis infectivity. A different pattern of histone acetylation and lactylation was observed when HeLa cells were pretreated for 24 h with supernatants of Lactobacillus crispatus or L. reuteri, resulting in different transcription of genes such as CCND1, CDKN1A, ITAG5 and HER-1. Similarly, distinct transcription patterns were found in HeLa cells treated with 10 mM D(−)- or L(+)-lactic acid isomers. Our findings suggest that D(−) lactic acid significantly affects two non-exclusive mechanisms involved in C. trachomatis infection: regulation of the cell cycle and expression of EGFR and α5β1-integrin. [ABSTRACT FROM AUTHOR]

Salmonella is a food-borne microorganism that is also a zoonotic bacterial hazard in the food sector. This study determined how well a mixed culture of Salmonella Kentucky formed biofilms on plastic (PLA), silicon rubber (SR), rubber gloves (RG), chicken skin and eggshell surfaces. In vitro interactions between the histone deacetylase inhibitor-vorinostat (SAHA)-and S. enterica serotype Kentucky were examined utilizing biofilms. The minimum inhibitory concentration (MIC) of SAHA was 120 µg mL−1. The addition of sub-MIC (60 µg mL−1) of SAHA decreased biofilm formation for 24 h on PLA, SR, RG, Chicken skin, and eggshell by 3.98, 3.84, 4.11, 2.86 and 3.01 log (p < 0.05), respectively. In addition, the initial rate of bacterial biofilm formation was higher on chicken skin than on other surfaces, but the inhibitory effect was reduced. Consistent with this conclusion, virulence genes expression (avrA, rpoS and hilA) and quorum-sensing (QS) gene (luxS) was considerably downregulated at sub-MIC of SAHA. SAHA has potential as an anti-biofilm agent against S. enterica serotype Kentucky biofilm, mostly by inhibiting virulence and quorum-sensing gene expression, proving the histone deacetylase inhibitor could be used to control food-borne biofilms in the food industry. [ABSTRACT FROM AUTHOR]