Evaluation Of Gene Expression Research Articles

Identification of heat-tolerant mungbean genotypes through morpho-physiological evaluation and key gene expression analysis

Identification of heat-tolerant mungbean genotypes through morpho-physiological evaluation and key gene expression analysis

Molecular Mechanisms of HT-29 Colorectal Cancer Cell Death Induced by Artemisia annua Methanolic Extract

Background: Although chemotherapy and targeted therapies have improved survival outcomes, there is growing interest in incorporating herbal medicines, such as Artemisia annua, into cancer treatment. Objectives: This study aims to investigate the mechanisms underlying the effects of A. annua methanolic extract on HT-29 colorectal cancer cells, particularly focusing on cell viability and the modulation of p53 and BAX/Bcl2 ratio expression. Methods: The half-maximal inhibitory concentration (IC50) of A. annua methanolic extract in HT-29 cells was determined via the MTT viability assay, while apoptosis was assessed using the propidium iodide (PI) staining method. Reverse transcription (RT)-PCR was performed to evaluate gene expression in the HT-29 cell line. Values are presented as the average of three separate determinations and expressed as mean ± SD. Results: The results showed that the viability of HT-29 cells significantly decreased in a dose- and time-dependent manner (IC50 for 48 h: 1358.1 μg.mL-1). Propidium iodide staining results confirmed the findings of the MTT assay. Gene expression analysis revealed a decrease in p53 expression and a two-fold increase in the BAX/Bcl2 ratio following exposure to 1000 μg.mL-1 of A. annua extract. Conclusions: The findings from the MTT and PI assays confirm the cytotoxic effects of A. annua extract on HT-29 cells. However, the gene expression analysis of BAX, Bcl2, and p53 suggests that the observed cell death is not primarily due to apoptosis.

Unveiling the role of epigenetics in leaf senescence: a comparative study to identify different epigenetic regulations of senescence types in barley leaves

BackgroundDevelopmental leaf senescence (DLS) is an irreversible process followed by cell death. Dark-induced leaf senescence (DILS) is a reversible process that allows adaptations to changing environmental conditions. As a result of exposure to adverse environmental changes, plants have developed mechanisms that enable them to survive. One of these is the redirection of metabolism into the senescence pathway. The plant seeks to optimise resource allocation. Our research aims to demonstrate how epigenetic machinery regulates leaf senescence, including its irreversibility.ResultsIn silico analyses allowed the complex identification and characterisation of 117 genes involved in epigenetic processes in barley. These genes include those responsible for DNA methylation, post-translational histone modifications, and ATP-dependent chromatin remodelling complexes. We then performed RNAseq analysis after DILS and DLS to evaluate their expression in senescence-dependent leaf metabolism. Principal component analysis revealed that evaluated gene expression in developmental senescence was similar to controls, while induced senescence displayed a distinct profile. Western blot experiments revealed that senescence engages senescence-specific histone modification. During DILS and DLS, the methylation of histone proteins H3K4me3 and H3K9me2 increased. H3K9ac acetylation levels significantly decreased during DILS and remained unchanged during DLS.ConclusionsThe study identified different epigenetic regulations of senescence types in barley leaves. These findings are valuable for exploring epigenetic regulation of senescence-related molecular mechanisms, particularly in response to premature, induced leaf senescence. Based on the results, we suggest the presence of an epigenetically regulated molecular switch between cell survival and cell death in DILS, highlighting an epigenetically driven cell survival metabolic response.

Potential brain biomarkers in patients with Autism spectrum syndrome

Autism spectrum disorder (ASD) is referred as a cluster of neurodevelopmental disorders with relatively high incidence. ASD is believed to be a multifactorial condition, and genetics is one of the most important factors in its formation. Therefore, profiling gene expression in ASD patients can lead to the identification of new molecular insights. To evaluate gene expression patterns, we have utilized NCBI GEO microarray data. The dataset of ASD patients (GSE28475, GSE28521, GSE38322 and GSE113834) were defined as two meta-data, Total brain meta-data and Lobe specified meta-data. Meta-analysis and batch effect removal was conducted by the SVA package. Microarray data analysis was performed using the LIMMA package under R 4.2.1 software. Total Meta-Analysis (TMA) identified 525 significantly differentially expressed genes (DEGs) in ASD patient’s brain. The temporal and frontal lobes of ASD patients showed 96 and 23 DEGs respectively. Among the mentioned DEGs, there were 11 common DEGs between the temporal and frontal lobes that were also dysregulated in TMA except for UTP4 which was only dysregulated in the temporal and frontal lobes. However, the occipital and cerebellum lobes did not show any significant DEGs. Enrichment analysis pointed out the vital roles of identified DEGs in transmembrane transportation, ATP production, and cellular respiration. According to our findings, gene expression profile in the temporal and frontal lobes of ASD patients are significantly different than a control group. This aberrant gene expression potentially leads to crucial complications in nerve signal transmission and defects energy production in neurons. Therefore, potential therapeutic targets may be suggested based on these findings.

Transcriptome analysis of the aortic coarctation area

BackgroundCoarctation of the aorta (CoA) is a relatively common congenital heart defect. The underlying causes are not known, but a combination of genetic factors and abnormalities linked to embryonic development is suspected. There are only a few studies of the underlying molecular mechanisms in CoA. The aim of the current study was to expand our understanding of the pathogenesis of CoA by characterizing the transcriptome of the coarctation area. MethodsTissue samples from 21 pediatric patients operated for CoA were dissected into separate biopsies consisting of the localized coarctation itself, proximal/distal tissue and ductus. RNA was sequenced to evaluate gene expression in the different biopsies. ResultsWe observed an activation of acute phase response in samples from the localized coarctation compared to samples from distal or proximal tissue. However, we observed even bigger differences for patient age and sex than compared to biopsy location. A cluster of genes located at 1q21, including the S100 gene family, displayed contrasting expression depending on patient sex, and appeared to affect the balance between inflammatory and interferon pathways. Biopsies from patients <3 months old were characterized by a significantly higher fibrotic activity compared to samples from older patients. The ductus tissue was characterized by an upregulation of factors associated with proliferation. ConclusionsThe ongoing processes in the coarctation area are influenced by the age and sex of the patient, and possibly by differences in etiology between different patients. The impact of patient attributes must be taken into consideration when performing future studies.

The Effects of 1-Kestose on the Abundance of Inflammation-Related Gene mRNA in Adipose Tissue and the Gut Microbiota Composition in Rats Fed a High-Fat Diet.

Chronic inflammation in adipose tissue is thought to contribute to insulin resistance, which involves the gut microbiota. Our previous studies have demonstrated that ingestion of 1-kestose can alter the gut microbiota composition, increase cecal butyrate levels, and improve insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Additionally, we found that 1-kestose supplementation ameliorated insulin resistance in obese rat models fed a high-fat diet (HFD), although the effects of 1-kestose on the abundance of inflammation-related gene in adipose tissue and gut microbiota composition in these rats were not explored. This study aimed to investigate the impact of 1-kestose on these parameters in HFD-fed rats, compared to OLETF rats. Male Sprague-Dawley rats were divided into two dietary groups, control or HFD, for 19 wk. Each group was further subdivided to receive either tap water or tap water supplemented with 2% (w/v) 1-kestose throughout the study. We evaluated gene expression in adipose tissue, as well as short-chain fatty acids (SCFAs) levels and microbial composition in the cecum contents. 1-Kestose intake restored the increased relative abundance of tumor necrosis factor (Tnf) mRNA in adipose tissue and the reduced level of butyrate in the cecum contents of HFD-fed rats to those observed in control diet-fed rats. Additionally, 1-kestose consumption changed the composition of the gut microbiota, increasing Butyricicoccus spp., decreasing UGC-005 and Streptococcus spp., in the cecum contents of HFD-fed rats. Our findings suggest that 1-kestose supplementation reduces adipose tissue inflammation and increases butyrate levels in the gut of HFD-fed rats, associated with changes in the gut microbiota composition, distinct from those seen in OLETF rats.

Exploration of PVT1 as a biomarker in prostate cancer.

Prostate cancer is a malignant tumor originating from the prostate gland, significantly affecting patients' quality of life and survival rates. Public data was utilized to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis was constructed to classify gene modules. Functional enrichment analysis was performed through Kyoto Encyclopedia of Genes and Genomes and gene ontology annotations, with results visualized using the Metascape database. Additionally, gene set enrichment analysis evaluated gene expression profiles and related pathways, constructed a protein-protein interaction network to predict core genes, analyzed survival data, plotted heatmaps and radar charts, and predicted microRNAs for core genes through miRTarBase. Two prostate cancer datasets (GSE46602 and GSE55909) were analyzed, identifying 710 DEGs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that DEGs were primarily involved in organic acid metabolism and the P53 signaling pathway. Gene set enrichment analysis and Metascape analyses further confirmed the significance of these pathways. After constructing the weighted gene co-expression network analysis network, 3 core genes (DDX21, NOP56, plasmacytoma variant translocation 1 [PVT1]) were identified. Survival analysis indicated that core genes are closely related to patient prognosis. Through comparative toxicogenomics database and miRNA prediction analysis, PVT1 was considered to play a crucial role in the development of prostate cancer. The PVT1 gene is highly expressed in prostate cancer and has the potential to become a diagnostic biomarker and therapeutic target for prostate cancer.

Gene Expression Analysis before and after the Pelvic Flexure in the Epithelium of the Equine Hindgut.

Previous research demonstrated the distribution of distinct microbial communities in the equine hindgut surrounding the pelvic flexure. The current study evaluated gene expression in epithelial tissues surrounding the pelvic flexure to characterize patterns that might correlate with microbial distribution. Gene expression was determined by analyzing RNA sequence data from the pelvic flexure, the left and right ventral colon, and the left and right dorsal colon. An average of 18,330 genes were expressed across the five tissues sampled. Most of the genes showed some level of expression in all five tissues. Tissue-restricted patterns of expression were also observed. Genes with restricted expression in the left ventral and left dorsal colons have communication, signaling, and regulatory functions that correlate with their known physiology. In contrast, genes expressed exclusively in the pelvic flexure have diverse functions. The ontology of genes differentially expressed between the pelvic flexure and the surrounding tissues was associated with immune functions and signaling processes. Despite being non-significant, these enrichment trends were reinforced by the functions of statistically significant expression differences between tissues of the hindgut. These results provide insight into the physiology of the equine hindgut epithelium that might influence the microbiota and its distribution.

Hepatic Gene Expression and Metabolite Profiles of Androstenone and Skatole Relative to Plasma Estrone Sulfate Levels in Boars.

Testicular steroids can alter the activity and expression of enzymes within the liver and may influence the metabolism of skatole and androstenone, which are responsible for boar taint. Plasma levels of estrone sulfate (E1S) are indicative of the steroidogenic capacity of the boar and are variable between animals of similar live weights at slaughter. This study aimed to characterize the relationship between steroidogenic capacity and the metabolism of boar taint compounds by relating plasma E1S levels at slaughter weight to the expression levels of genes regulating the metabolism of androstenone and skatole, along with their respective metabolite profiles. RT-qPCR was used to evaluate gene expression in the liver. Hepatocytes were also isolated and treated with androstenone or skatole, with metabolite levels in the incubation media quantified by high-performance liquid chromatography. Plasma E1S levels ranged from 2.2-108.5 ng/mL and were positively correlated with overall skatole metabolism (p = 0.038), the production of metabolites 3-methyloxindole (p = 0.026) and 3-hydroxy-3-methyloxindole (p = 0.036), and expression levels of key genes involved in skatole metabolism, specifically CYP2C33 (p = 0.0042), CYP2C49 (p = 0.022), and CYB5R1 (p = 0.017). There was no association between androstenone metabolism and plasma E1S concentrations; however, there was evidence of possible co-regulation amongst genes involved in the metabolism of androstenone, skatole, and estrogens. These findings indicate that steroidogenic capacity is related to the rate of skatole, but not androstenone metabolism, in slaughter-weight boars.

Milk transcriptome biomarker identification to enhance feed efficiency and reduce nutritional costs in dairy ewes

In recent years, rising prices for high-quality protein-based feeds have significantly increased nutrition costs. Consequently, investigating strategies to reduce these expenses and improve feed efficiency (FE) have become increasingly important for the dairy sheep industry. This research investigates the impact of nutritional protein restriction (NPR) during prepuberty and FE on the milk transcriptome of dairy Assaf ewes (sampled during the first lactation). To this end, we first compared transcriptomic differences between NPR and control ewes. Subsequently, we evaluated gene expression differences between ewes with divergent FE, using feed conversion ratio (FCR), residual feed intake (RFI), and consensus classifications of high− and low-FE animals for both indices. Lastly, we assess milk gene expression as a predictor of FE phenotype using random forest. No effect was found for the prepubertal NPR on milk performance or FE. Moreover, at the milk transcriptome level, only one gene, HBB, was differentially expressed between the NPR (n = 14) and the control group (n = 14). Further, the transcriptomic analysis between divergent FE sheep revealed 114 differentially expressed genes (DEGs) for RFI index (high-FERFI = 10 vs low-FERFI = 10), 244 for FCR (high-FEFCR = 10 vs low-FEFCR = 10), and 1 016 DEGs between divergent consensus ewes for both indices (high-FEconsensus = 8 vs low-FEconsensus = 8). These results underscore the critical role of selected FE indices for RNA-Seq analyses, revealing that consensus divergent animals for both indices maximise differences in transcriptomic responses. Genes overexpressed in high-FEconsensus ewes were associated with milk production and mammary gland development, while low-FEconsensus genes were linked to higher metabolic expenditure for tissue organisation and repair. The best prediction accuracy for FE phenotype using random forest was obtained for a set of 44 genes consistently differentially expressed across lactations, with Spearman correlations of 0.37 and 0.22 for FCR and RFI, respectively. These findings provide insights into potential sustainability strategies for dairy sheep, highlighting the utility of transcriptomic markers as FE proxies.

Screening of Reference Genes for Quantitative Real-Time PCR Analysis in Tissues and during Testis Development, and Application to Analyze the Expression of kifc1 in Hemibarbus labeo (Teleostei, Cypriniformes, Cyprinidae).

The selection of proper reference genes is vital for ensuring precise quantitative real-time PCR (qPCR) assays. This study evaluates the stability of the expression of nine candidate reference genes in different tissues and during testicular development in H. labeo. The results show that eef1a is recommended as a reference gene for qPCR analysis in tissues and during testicular development. Furthermore, we evaluated the optimal number of reference genes needed when calculating gene expression levels using the geomean method, revealing that two reference genes are sufficient. Specifically, eef1a and rps27 are recommended for analysis of gene expression in tissues, whereas eef1a and actb are advised for evaluating gene expression during testicular development. In addition, we examined the expression pattern of kifc1, a kinesin involved in the reshaping of spermatids. We detected peak expression levels of kifc1 in testes, with its expression initially increasing before decreasing throughout testicular development. The highest expression of kifc1 was observed in stage IV testes, the active period of spermiogenesis, suggesting a possible role for kifc1 in the regulation of the reshaping of spermatids and hence testicular development. This study represents the first investigation of reference genes for H. labeo, providing a foundation for studying gene expression patterns and investigating gene expression regulation during testicular development.

The Effect of Interferon Beta and Natalizumab on miR-20b Expression in Patients with Relapsing-Remitting Multiple Sclerosis is Potentially Mediated by Modulation of the Jak-STAT Signaling Pathway: A Case-control Study.

The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such as microRNAs (miRNAs) following therapy in MS patients. To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ. Sixty patients with relapsing-remitting MS (RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20), IFN-β-treated (N=20), and NTZtreated (N=20). For the expression analysis, real-time PCR was performed on the whole blood. The bioinformatic tools were applied for signaling pathways enrichment analysis of miR-20b targetome. The relative expression of miR-20b was significantly downregulated in the untreated patients compared with the HCs (-1.726-fold, p<0.001), while IFN-β-treated and NTZ-treated patients showed no statistical difference compared with the HCs (0.733-fold, p=0.99 for IFN-β and 1.025-fold, p=0.18 for NTZ). This indicates the restoration of miR-20b expression to normal level in the treated patients. Additionally, in silico analysis demonstrated that the Jak-STAT signaling pathway is enriched with miR-20b targets (p<0.0001). Our findings suggest that the positive effects of IFN-β and NTZ in the RRMS patients could be potentially mediated by returning miR-20b expression to baseline.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

Focused cancer pathway analysis revealed unique therapeutic targets in retinoblastoma.

Retinoblastoma (RB) is a pediatric cancer of the eye that occurs in 1/15000 live births worldwide. Albeit RB is initiated by the inactivation of RB1 gene, the disease progression relies largely on transcriptional alterations. Therefore, evaluating gene expression is vital to unveil the therapeutic targets in RB management. In this study, we employed an RT2 Profiler™ PCR array for a focused analysis of 84 cancer-specific genes in RB. An interaction network was built with gene expression data to identify the dysregulated pathways in RB. The key transcript alterations identified in 13 tumors by RT2 Profiler™ PCR array was further validated in 15 tumors by independent RT-qPCR. Out of 84 cancer-specific genes, 68 were dysregulated in RB tumors. Among the 68 genes, 23 were chosen for further analysis based on statistical significance and abundance across multiple tumors. Pathway analysis of altered genes showed the frequent perturbations of cell cycle, angiogenesis and apoptotic pathways in RB. Notably, upregulation of MCM2, MKI67, PGF, WEE1, CDC20 and downregulation of COX5A were found in all the tumors. Western blot confirmed the dysregulation of identified targets at protein levels as well. These alterations were more prominent in invasive RB, correlating with the disease pathogenesis. Our molecular analysis thus identified the potential therapeutic targets for improving retinoblastoma treatment. We also suggest that PCR array can be used as a tool for rapid and cost-effective gene expression analysis.

GOG 3088: A randomized phase II study of letrozole versus observation in patients with newly diagnosed uterine leiomyosarcoma.

TPS5643 Background: Uterine leiomyosarcomas (uLMS) are rare, accounting for less than five percent of all malignant uterine neoplasms. Approximately 85% of women present with clinical stage I disease (i.e., disease limited to the uterus and cervix). NCCN guidelines for stage I uterine confined disease currently recommend observation; however, recurrence risk of uLMS overall is quite high at 50-70% within the first two years. The estrogen receptor (ER) is expressed in 40-87% of leiomyosarcomas. Because of this high expression, estrogen may act as a growth factor that stimulates cell proliferation and tumor growth. Subsequently, there have been several evaluations for the use of aromatase inhibitors as single agent therapy for uLMS. These trials have each shown varying degrees of clinical activity. We hypothesize that by decreasing systemic estrogen using an aromatase inhibitor we will prolong the time to recurrence for patients with this disease. Methods: This is a GOG Foundation led phase II randomized controlled trial comparing letrozole (2.5mg PO daily) to observation in newly diagnosed patients with uterine confined stage I uLMS. Forty patients will be randomized 1:1. Patients will be eligible post operatively if they have no measurable disease and will be required to be estrogen receptor (ER) positive, as defined by ³ 10% expression by immunohistochemistry (IHC). No stratification methods will be applied. The primary endpoint of the trial is investigator-assessed progression free survival. Exploratory translational evaluation will occur to 1) correlate response to letrozole based on IHC hormone receptor status, 2) evaluate gene expression signatures of hormone receptor activity, tumor biology, and tumor microenvironment in relation to response to letrozole, and 3) evaluate the contribution of single nucleotide polymorphism rs3820282 to tumor biology and response to letrozole. GOG 3088 activated in January of 2024 and expects to enroll across 20 US sites. Clinicaltrials.gov Identifier: NCT05649956. Clinical trial information: NCT05649956 .

Toll-like receptor 4 (TLR4) deficiency impedes Toxoplasma gondii excreted-secreted antigens (ESA)-induced abortion

IntroductionToxoplasma gondii is an opportunistic intracellular parasite that is a major pathogenic factor in miscarriage, especially when it occurs early in pregnancy. We have previously demonstrated that the regulation of forkhead box transcription factor (Foxp3) is associated with abortion in early pregnancy caused by excretory-secretory antigen (ESA) of strain China 1. We aimed to reveal the underlying mechanism of miscarriage caused by ESA. MethodsA TLR4−/− pregnant mouse model was successfully constructed. Pregnant mice at gestational day 5 (G5) were injected with ESA. All animals were sacrificed on G13, pregnancy outcomes were observed, and abortion rates were calculated. Placental status observed by Hematoxylin-eosin staining; gene expression was measured by IHC; flow cytometry analysis was used to determine the number and function of regulatory T cells. In EL4 cells, real-time PCR and Western blot were used to evaluate gene expression and cytokines assay. ResultsIn vivo studies revealed that ESA injection caused 83% abortion in pregnant mice but only 35% abortion in TLR4−/− pregnant mice. In addition, ESA attenuated the number and function of regulatory T cells, further suppressed Foxp3, FOXO1 levels, and upregulated CD127 expression. TLR4−/− mice partially reversed this inhibitory effect on regulatory T cells. Furthermore, in vitro studies revealed that ESA inhibited TLR4/NF-κB signaling pathway expression and that TLR4 agonists significantly restored the ESA-induced decrease in Foxp3. DiscussionThese findings suggest that ESA suppresses Foxp3 expression by blocking TLR4/NF-κB signaling, resulting in miscarriage. More importantly, the results indicated that miscarriage caused by ESA is TLR4 dependent.

Size-dependent enhancement of gene expression by Plasmodium 5'UTR introns.

Eukaryotic genes contain introns that are removed by the spliceosomal machinery during mRNA maturation. Introns impose a huge energetic burden on a cell; therefore, they must play an essential role in maintaining genome stability and/or regulating gene expression. Many genes (> 50%) in Plasmodium parasites contain predicted introns, including introns in 5' and 3' untranslated regions (UTR). However, the roles of UTR introns in the gene expression of malaria parasites remain unknown. In this study, an episomal dual-luciferase assay was developed to evaluate gene expression driven by promoters with or without a 5'UTR intron from four Plasmodium yoelii genes. To investigate the effect of the 5'UTR intron on endogenous gene expression, the pytctp gene was tagged with 3xHA at the N-terminal of the coding region, and parasites with or without the 5'UTR intron were generated using the CRISPR/Cas9 system. We showed that promoters with 5'UTR introns had higher activities in driving gene expression than those without 5'UTR introns. The results were confirmed in recombinant parasites expressing an HA-tagged gene (pytctp) driven by promoter with or without 5'UTR intron. The enhancement of gene expression was intron size dependent, but not the DNA sequence, e.g. the longer the intron, the higher levels of expression. Similar results were observed when a promoter from one strain of P. yoelii was introduced into different parasite strains. Finally, the 5'UTR introns were alternatively spliced in different parasite development stages, suggesting an active mechanism employed by the parasites to regulate gene expression in various developmental stages. Plasmodium 5'UTR introns enhance gene expression in a size-dependent manner; the presence of alternatively spliced mRNAs in different parasite developmental stages suggests that alternative slicing of 5'UTR introns is one of the key mechanisms in regulating parasite gene expression and differentiation.

Exploring the connection between BRCA2 and thyroid cancer

Abstract Background This study investigated the multifaceted role of BRCA2 (breast cancer 2) in various cancer types, with a specific focus on thyroid carcinoma (THCA). Methods Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression, genetic alterations, and clinical implications. Sample filtering criteria were applied, and immunohistochemistry from the Human Protein Atlas was used to validate protein expression. Correlation analyses were used to explore associations between immune-related genes, and immunological signatures were assessed using various tools. Genetic alterations in BRCA2 were analyzed using cBioPortal, and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA. Results In patients with THCA, differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues. Correlation studies revealed associations between BRCA2 and immune-related genes, emphasizing its potential role in modulating the tumor microenvironment. Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors. Moreover, genetic alterations in BRCA2, particularly the A2738S mutation in exon 18, have been identified in patients with THCA. The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA. Additionally, BRCA2 expression was associated with prognostic factors such as stage and N. Conclusions This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression, immune modulation, genetic alterations, and clinical prognosis. These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.

Gene expression associated with unfavorable vaginal bleeding in women using the etonogestrel subdermal contraceptive implant: a prospective study

To evaluate gene expression associated with unfavorable vaginal bleeding in users of the Etonogestrel (ENG) contraceptive implant. Prospective study involving 100 women who intended to use the ENG implant. Exclusion criteria included abnormal uterine bleeding, inability to attend a 1-year follow-up, and implant removal for reasons unrelated to vaginal bleeding or loss of follow-up. We obtained endometrial biopsies before implant placement and assessed the expression of 20 selected genes. Users maintained a uterine bleeding diary for 12 months post-implant placement. For statistical analysis, we categorized women into those with or without favorable vaginal bleeding at 3 and 12 months. Women with lower CXCL1 expression had a 6.8-fold increased risk of unfavorable vaginal bleeding at 3 months (OR 6.8, 95% CI 2.21–20.79, p < 0.001), while those with higher BCL6 and BMP6 expression had 6- and 5.1-fold increased risks, respectively. By the 12-month follow-up, women with lower CXCL1 expression had a 5.37-fold increased risk of unfavorable vaginal bleeding (OR 5.37, 95% CI 1.63–17.73, p = 0.006). Women with CXCL1 expression < 0.0675, BCL6 > 0.65, and BMP6 > 3.4 had a higher likelihood of experiencing unfavorable vaginal bleeding at 3 months, and CXCL1 < 0.158 at 12 months. Users of ENG contraceptive implants with elevated BCL6 and BMP6 expression exhibited a higher risk of breakthrough bleeding at the 3-month follow-up. Conversely, reduced CXCL1 expression was associated with an elevated risk of bleeding at both the 3 and 12-month follow-ups.

Overexpression of Regulator of G-Protein Signaling 2 in the Paraventricular Nucleus Reduces Blood Pressure in Spontaneously Hypertensive Rats

The hypothalamic paraventricular nucleus (PVN) is important in mediating sympathetic activity to regulate blood pressure. The regulator of G protein signaling 2 (RGS2) is a negative G protein regulator. RGS2 selectively regulates Gαq signaling, an important cause of hypertension and cardiac hypertrophy. However, little-to-no studies are being done related to G-protein-RGS2 signaling on the central mechanisms of blood pressure control and sympathetic activation. In this study, we use spontaneously hypertensive rats (SHR) to aim for the pressor effects of central viral transfection over-expressing RGS2 in the PVN compared to a Wistar-Kyoto (WKY) control. These rats were outfitted with telemetry and measurements of blood pressure and heart rate over the next 14 days, with or without RGS2 adenovirus (AV) injection into the PVN. Metabolic experiments were conducted at the 7-day mark to examine kidney function, sodium excretion, urine output, and water and food intake. We saw significant ( p&lt;0.05) decreases in blood pressure for the SHR with AV-RGS2 throughout our telemetry experiment. In our metabolic experiments, sodium excretion significantly ( p&lt;0.05) increased in the SHR group with AV-RGS2 compared to the SHR with AV-GFP. Water intake, food intake, and urine output remained unchanged. Following this experiment, we gave capsaicin injections into the renal pelvis at 5, 10, and 20 μM to measure blood pressure and heart rate responses. Also, blood pressure responses to renal pelvis capsaicin injection appear to be attenuated in SHR and WKY rats with AV-RGS2 injection but was not significant ( p&gt;0.05). In addition, we conducted real-time qPCR on collected PVN tissue to evaluate gene expression changes over time. We saw expression peak at 3-days in G⍺q, G⍺s, G⍺i, and RGS2, and progressively decrease as time progressed. This study provides a value insight of central mechanisms related to G-protein-RGS2 signaling on blood pressure regulation. This study was funded by NIH R01-DK-129311 and USD G-RISE, NIH T32GM-136503. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.