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The presence and the level of antibodies in human sera against bacterial glycans are indications of prior encounters with similar antigens and/or the bacteria that express them by the immune system. An increasing number of pathogenic bacteria that cause human diseases have been shown to express polysaccharides containing a bacterial nonulosonic acid called 5,7-di-N-acetyllegionaminic acid (Leg5,7Ac2). To investigate the immune recognition of Leg5,7Ac2, which is critical for the fight against bacterial infections, a highly effective chemoenzymatic synthon strategy was applied to construct a library of α2-3/6-linked Leg5,7Ac2-glycans via their diazido-derivatives (Leg5,7diN3-glycans) formed by efficient one-pot three-enzyme (OP3E) synthetic systems from a diazido-derivative of a six-carbon monosaccharide precursor. Glycan microarray studies using this synthetic library of a Leg5,7Ac2-capped collection of diverse underlying glycan carriers and their matched sialoside counterparts revealed specific recognition of Leg5,7Ac2 by human IgG antibodies pooled from thousands of healthy donors (IVIG), suggesting prior human encounters with Leg5,7Ac2-expressing pathogenic bacteria at the population level. These biologically relevant Leg5,7Ac2-glycans and their immune recognition assays are important tools to begin elucidating their biological roles, particularly in the context of infection and host-pathogen interactions.

Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases. [ABSTRACT FROM AUTHOR]

The aim was to examine the acute effects of sprint exercise (SIT) on global gene expression in subcutaneous adipose tissue (AT) in healthy subjects, to enhance understanding of how SIT influences body weight regulation. The hypothesis was that SIT upregulates genes involved in mitochondrial function and fat metabolism. A total of 15 subjects performed three 30‐s all‐out sprints (SIT). Samples were collected from AT, skeletal muscle (SM) and blood (brachial artery and a subcutaneous AT vein) up to 15 min after the last sprint. Results showed that markers of oxidative stress, such as the purines hypoxanthine, xanthine and uric acid, increased markedly by SIT in both the artery and the AT vein. Purines also increased in AT and SM tissue. Differential gene expression analysis indicated a decrease in signaling for mitochondrial‐related pathways, including oxidative phosphorylation, electron transport, ATP synthesis, and heat production by uncoupling proteins, as well as mitochondrial fatty acid beta oxidation. This downregulation of genes related to oxidative metabolism suggests an early‐stage inhibition of the mitochondria, potentially as a protective mechanism against SIT‐induced oxidative stress. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a serious pregnancy-related complication caused by high blood pressure in pregnant women. The severe form has more devastating effects. According to the growing evidence, the placenta is a crucial component in the pathogenesis of PE, and eliminating it will alleviate symptoms. GEO's severe preeclampsia placenta microarray datasets; GSE147776, GSE66273, GSE102897, and GSE10588, were chosen to identify differentially expressed genes (DEGs) in different biological pathways. The analysis of hub genes and related non-coding RNAs was done as well. A total of 347 DEGs with adj p-value <0.05 and ǀlog2FoldChangeǀ> 0.5 were discovered between severe PEs and healthy pregnancies, including 204 over-expressed genes and 143 under-expressed genes. The MCC method identified ISG15, IFI44L, MX2, OAS2, MX1, FN1, LDHA, ITGB3, TKT, HK2 genes as the top ten hub genes. Interactions between hub genes and noncoding RNAs were also conducted. The most enriched pathways were as follows; HIF-1 signaling pathway; Pathways in cancer; Alanine, aspartate and glutamate metabolism; Arginine biosynthesis; Human papillomavirus infection; Glycolysis/Gluconeogenesis; Central carbon metabolism in cancer; Valine, leucine and isoleucine degradation; Cysteine and methionine metabolism; and Galactose metabolism. This is a secondary data analysis conducted on severe preeclampsia placenta to identify differentially expressed genes, biological pathways, hub-genes, and related noncoding RNAs. Functional studies are crucial to understanding the precise role of these genes in the pathogenesis of PE. Also, accepting a gene as a diagnostic or prognostic marker for early diagnosis and management of PE requires multiple lines of evidence. • Microarray meta-analysis on placenta discovered 347 differentially expressed genes with adj p-value <0.05 and ǀlog2FoldChangeǀ> 0.5 between severe PEs and healthy pregnancies, including 204 over-expressed genes and 143 under-expressed genes. • The final PPI network with a confidence score >0.7 had 103 nodes, and the top 10 hub genes were identified with the MCC method. • The interplay between various types of RNAs (mRNA-miRNA, and mRNA-lncRNA) was discovered by employing different databases. • The significance level for the enrichment pathway including GO and KEGG was determined by adjusted p-value less than 0.05. [ABSTRACT FROM AUTHOR]

Objective: To explore the genetic diagnosis of fetuses with polyhydramnios using chromosomal microarray analysis (CMA). Methods: A total of 112 cases of the polyhydramnios diagnosed by prenatal ultrasound at Quanzhou Women′s and Children′s Hospital from January 2017 to April 2023 were collected. All of the enrolled subjects underwent chromosomal karyotype and CMA analysis. According to the results of ultrasound, the subjects were divided into three groups, the isolated polyhydramnios group (16 cases), the group of polyhydramnios with ultrasound structural abnormalities (27 cases), and the group of polyhydramnios with abnormal ultrasound soft markers (69 cases). Results: Chromosome karyotype analysis found 4 cases of chromosomal aneuploidy, 1 case of aneuploid chromosomal chimerism, and 1 case of chromosomal structural abnormality chimerism, with an abnormal detection rate of 5.36% (6/112). CMA detected all chromosomal abnormalities, and 4 additional cases of pathogenic or likely pathogenic copy number variants, with an additional detection rate of 3.57% (4/112). In addition, there was no statistical difference in the positive detection rate among three groups (P=0.571). Conclusions: Pregnancy with polyhydramnios may be related to fetal chromosomal abnormalities. The chromosome karyotype analysis combined with CMA technique is beneficial to detect more pathogenic copy number variants. Therefore, the chromosome karyotype analysis combined with CMA detection can be recommended in the genetic etiology analysis and prognosis evaluation of fetuses with polyhydramnios. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a notably lethal disease, characterized by malignant clonal proliferation of hematopoietic stem cells in the bone marrow. This study seeks to unveil potential therapeutic targets for AML, using a combined approach of microarray analysis and Mendelian randomization (MR). We collected data samples from the Gene Expression Omnibus (GEO) database and extracted pQTL data from genome-wide association studies (GWAS) to identify overlapping genes between the DEGs and GWAS data. Gene enrichment and pathway annotation analyses were performed on these genes. Furthermore, we validated gene expression levels and assessed their clinical relevance. By taking the intersection of these gene sets, we obtained a list of co-expressed genes, including four upregulated genes (REC8, TPM2, ZMIZ1, CD82) and two downregulated genes (IFNAR1, TMCO3). MR analysis demonstrated that genetically predicted protein levels of CD82, REC8, ZMIZ1, and TPM2 were significantly associated with increased odds of AML, while IFNAR1 and TMCO3 showed a protective effect. Gene ontology and KEGG pathway analyses revealed significant enrichment in functions related to female gamete generation, meiosis, p53 signaling pathway, and cardiac muscle contraction. Differences in immune cell profiles were observed between AML survivors and those with poor prognosis, including lower levels of neutrophils and higher levels of follicular helper T cells in the latter group. This study identifies a causal relationship between gene expression and AML and highlights the potential role of REC8 in leukemogenesis, possibly through its impact on gametocyte meiotic abnormalities. The findings provide new insights into the prevention and treatment of leukemia. [ABSTRACT FROM AUTHOR]

Abstract Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

The Traditional Chinese Medicine compound preparation known as Diwu Yanggan capsule (DWYG) can effectively hinder the onset and progression of hepatocellular carcinoma (HCC), which is recognized worldwide as a significant contributor to fatalities associated with cancer. Nevertheless, the precise mechanisms implicated have remained ambiguous. In present study, the model of HCC was set up by the 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PH) in rats. To confirm the differentially expressed genes (DEGs) identified in the microarray analysis, real-time quantitative reverse transcription PCR (qRT-PCR) was conducted. In the meantime, the liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS) was employed to characterize the component profile of DWYG. Consequently, the DWYG treatment exhibited the ability to reverse 51 variation genes induced by 2-AAF/PH. Additionally, there was an overlap of 54 variation genes between the normal and model groups. Upon conducting RT-qPCR analysis, it was observed that the expression levels of all genes were increased by 2-AAF/PH and subsequently reversed after DWYG treatment. Notably, the fold change of expression levels for all genes was below 0.5, with 3 genes falling below 0.25. Moreover, an investigation was conducted to determine the signaling pathway that was activated/inhibited in the HCC group and subsequently reversed in the DWYG group. Moreover, the component profile of DWYG encompassed a comprehensive compilation of 206 compounds that were identified or characterized. The findings of this study elucidated the potential alleviative mechanisms of DWYG in the context of HCC, thereby holding significant implications for its future clinical utilization and widespread adoption.

Introduction: Root dentin formation is an important process in tooth development. We tried to identify potential genes that regulate root dentin formation which could be potentially used for the regeneration and repair of defective or damaged dental roots. Methods: Tissues harvested from the labial and lingual sides of mouse incisors were used for microarray analysis. Gene ontology (GO) analysis of differentially expressed genes indicated the critical role of extracellular matrix in the discrepancy of dentin formation between root and crown, for which hemicentin-1 (Hmcn1) was selected as the target gene. Single-cell RNA sequencing analysis the expression pattern of Hmcn1 at different developmental stages in mouse molars. The spatiotemporal expression of HMCN1 in mouse incisors and molars was detected by immunohistochemical staining. The functions of HMCN1 in human dental pulp cells, including proliferation, differentiation and migration, were examined in vitro by CCK8 assay, BrdU assay, wound-healing assay, ALP staining and alizarin red staining, respectively. Results: It was showed that HMCN1 expression was more pronounced in papillapulp on the root than crown side in mouse incisors and molars. In vitro experiments presented inhibited dentinogenesis and migration after HMCN1-knockdown in human dental pulp cells, while there was no significant difference in proliferation between the HMCN1-knockdown group and control group. Discussion: These results indicated that HMCN1 plays an important role in dentinogenesis and migration of pulp cells, contributing to root dentin formation. [ABSTRACT FROM AUTHOR]

Introduction: Middle ear cholesteatoma is a chronic middle ear disease characterized by severe hearing loss and adjacent bone erosion, resulting in numerous complications. This study sought to identify pathways involved in N6-methyladenosine (m6A) modification of circRNA in middle ear cholesteatoma. Methods: A m6A circRNA epitranscriptomic microarray analysis was performed in middle ear cholesteatoma tissues (n = 5) and normal post-auricular skin samples (n = 5). Bioinformatics analyses subsequently explored the biological functions (Gene Ontology, GO) and signaling pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG) underlying middle ear cholesteatoma pathogenesis. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was performed to verify the presence of circRNAs with m6A modifications in middle ear cholesteatoma and normal skin samples. Results: Microarray analysis identified 3,755 circRNAs as significantly differentially modified by m6A methylation in middle ear cholesteatoma compared with the normal post-auricular skin. Among these, 3,742were hypermethylated (FC = 2, FDR < 0.05) and 13 were hypomethylated (FC = 1/2, FDR < 0.05). GO analysis termswith the highest enrichment score were localization, cytoplasm, and ATP-dependent activity for biological processes, cellular components, and molecular functions respectively. Of the eight hypermethylated circRNA pathways, RNA degradation pathway has the highest enrichment score. Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway was hypomethylated. To validate the microarray analysis, we conducted MeRIP-qPCR to assess the methylation levels of five specific m6Amodified circRNAs: hsa_circRNA_061554, hsa_circRNA_001454, hsa_circRNA_ 031526, hsa_circRNA_100833, and hsa_circRNA_022382. The validation was highly consistent with the findings from the microarray analysis. Conclusion: Our study firstly presents m6A modification patterns of circRNAs in middle ear cholesteatoma. This finding suggests a direction for circRNA m6A modification research in the etiology of cholesteatoma and provides potential therapeutic targets for the treatment of middle ear cholesteatoma. [ABSTRACT FROM AUTHOR]

Purpose: The identification and prognosis of the agenesis of the corpus callosum (ACC) for prenatal consultation are complex and currently unclear. This study aims to explore the correlated genetic mutations of prenatal ACC. Methods: We retrospectively analyzed 114 prenatal cases of ACC. All cases (n = 114) were subjected to chromosomal microarray analysis (CMA), and 66 CMA-negative cases underwent prenatal exome sequencing (pES) for further analysis. Results: CMA was diagnosed positively in 15/114 (13.2%) cases and pES was diagnosed positively in 24/66 (36.4%) CMA-negative cases. The detection rate of genetic causes between complete and partial ACCs was not significantly different (P > 0.05). Between isolated and non-isolated (other anomalies present) ACCs, the diagnostic rate of pES in non-isolated cases was significantly higher (P < 0.001), while CMA results did not differ (P > 0.05). The diagnostic rate of CMA was significantly increased in cases combined with intracranial and extracranial malformations (P = 0.014), while no CMA positivity was detected in cases combined with only intracranial malformations. Conclusion: For fetuses with prenatal ACC, further pES analysis should be recommended after negative CMA results. Chromosome abnormalities are less likely to occur when ACC with only intracranial malformations combined. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism. We used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1. Twenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2. Those results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2. [ABSTRACT FROM AUTHOR]

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial infiltration and pannus formation, and its rising incidence is significantly contributing to the global disability rate. Despite advances in biological drugs, no treatment has successfully cured or averted its progression. Consequently, natural drugs are being explored as alternative therapeutic strategies.ObjectiveThis study aims to evaluate the therapeutic potential of Pennisetum glaucum (pearl millet) and to identify its bioactive compounds to assess their effectiveness against RA targets.MethodsThe therapeutic potential of P. glaucum extracts was evaluated by antioxidant and anti-inflammatory assays. Gas chromatography-mass spectrometry (GC-MS) was utilized to identify the compounds in P. glaucum extract. The pharmacokinetics and safety profile of these compounds were studied by absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. Network pharmacology, molecular docking, and molecular dynamic (MD) simulation were employed to identify the active compounds and their therapeutic targets in P. glaucum for RA treatment.ResultsAcidified methanol (AM) extract of P. glaucum showed the highest phenolic (213 ± 0.008 mg GAE/g DW) and flavonoid content (138.1 ± 0.03 mg RE/g DW), demonstrating significant antioxidant and anti-inflammatory potential. GC-MS of AM extract identified 223 compounds. Lipinski and toxicity parameters screened out 17 compounds. Protein–protein interaction (PPI) analysis shortlisted 20 key targets in RA pathways, nine of which were upregulated in five microarray datasets. Molecular docking and MD simulations revealed that compound-7 (benzenesulfonamide, 2-nitro-N-phenyl-) and compound-9 (Pregnane-3,20-diamine, (3.beta.,5.alpha.,20S)-) bind strongly with MMP9, JAK2, PTGS2, and HIF1a compared to the reference, predicting stable interaction with these upregulated genes. Finally, PASS (prediction of activity spectra for biological active substances) analysis further validated the anti-arthritic potential of these compounds based on their chemical structure.ConclusionThis study uncovered a therapeutic drug candidate against HIF1a, MMP9, JAK2, and PTGS2 for RA from P. glaucum active compounds, laying the groundwork for future research.

Abstract The aim was to examine the acute effects of sprint exercise (SIT) on global gene expression in subcutaneous adipose tissue (AT) in healthy subjects, to enhance understanding of how SIT influences body weight regulation. The hypothesis was that SIT upregulates genes involved in mitochondrial function and fat metabolism. A total of 15 subjects performed three 30‐s all‐out sprints (SIT). Samples were collected from AT, skeletal muscle (SM) and blood (brachial artery and a subcutaneous AT vein) up to 15 min after the last sprint. Results showed that markers of oxidative stress, such as the purines hypoxanthine, xanthine and uric acid, increased markedly by SIT in both the artery and the AT vein. Purines also increased in AT and SM tissue. Differential gene expression analysis indicated a decrease in signaling for mitochondrial‐related pathways, including oxidative phosphorylation, electron transport, ATP synthesis, and heat production by uncoupling proteins, as well as mitochondrial fatty acid beta oxidation. This downregulation of genes related to oxidative metabolism suggests an early‐stage inhibition of the mitochondria, potentially as a protective mechanism against SIT‐induced oxidative stress.

Abstract Statins, the drugs used for the treatment of hypercholesterolemia, have come into the spotlight not only as chemoadjuvants, but also as potential stem cell modulators in the context of regenerative therapy. In our study, we compared the in vitro effects of all clinically used statins on the viability of human pancreatic cancer (MiaPaCa-2) cells, non-cancerous human embryonic kidney (HEK 293) cells and adipose-derived mesenchymal stem cells (ADMSC). Additionally, the effect of statins on viability of MiaPaCa-2 and ADMSC cells spheroids was tested. Furthermore, we performed a microarray analysis on ADMSCs treated with individual statins (12 μM) and compared the importance of the effects of statins on gene expression between stem cells and pancreatic cancer cells. Concentrations of statins that significantly affected cancer cells viability (

The adjacent -2 segregation is a rare separation mode in the gametic formation of balanced translocation carriers. A fetus with severe fetal growth restriction (FGR) and chromosomal abnormalities is reported, and the prenatal diagnosis was performed by G -banding karyotype analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH), quantitive fluorescent polymerase chain reaction (QF-PCR). The CMA result of amniotic fluid was arr[hg19]18p11.32q11.2(141,354-21,994,637)×3, 21q11.2q21.3(15,502,777- 29,700,071)×1; Refer to the CMA results, the fetal karyotype was described as 46,XX, +der(18)t(18;21) (q11.2; q22.1),-21. In order to verify the source of abnormal karyotype, the chromosomes of parents′ peripheral blood were detected. The father′s karyotype was 46,XY,t(18;21)(q11.2;q22.1), and the pregnant woman had normal karyotype. FISH results showed that the amniotic fluid cells had two normal 18 chromosomes, one normal 21 chromosome and one derived 18 chromosome, and that the father was a cross-translocation carrier of the 18p and 21p. To rule out the possibility that the fetus′s two normal chromosomes 18 were uniparental disomy, this study used the results of identification of maternal blood contamination, and the results of short tandem repeat(STR) test confirmed that only one of the two normal chromosome 18 came from the mother. Therefore, the application of multiple detection techniques in the diagnosis of rare separation methods such as adjacent-2 segregation can help doctors to provide accurate prenatal genetic counseling for those balanced translocation carriers, and to identify the types of chromosomal abnormalities in their fetuses. [ABSTRACT FROM AUTHOR]

Thickening of the ligamentum flavum is the main factor in the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported factors related to ligamentum flavum thickening, its etiology has not been clarified. Furthermore, it is often difficult to set proper controls to investigate the pathologies of thickening due to differences in patient characteristics, such as age, sex, obesity, and comorbidities. This study aimed to elucidate the pathologies of ligamentum flavum thickening by comparing the dural and dorsal sides of the thickened ligamentum flavum in patients with LSCS. Ligamentum flavum samples were collected from 19 patients with LSCS. The samples were divided into the dural and dorsal sides. The dural side was used as a control to assess the pathologies occurring on the dorsal side. Elastic Masson staining was used to assess the elastic fibres. Gene expression levels were comprehensively assessed using quantitative reverse transcription polymerase chain reaction and DNA microarray analyses. Gene ontology analysis was used to identify biological processes associated with differentially expressed genes. The elastic fibres were significantly decreased on the dorsal side of the thickened ligamentum flavum. Genes related to fibrosis, inflammation, tissue repair, remodeling, and chondrometaplasia, such as COL1A2, COL3A1, COL5A1, TGFB1, VEGFA, TNFA, MMP2, COL10A1, and ADAMTS4, were highly expressed on the dorsal side of the thickened ligamentum flavum. The biological processes occurring on the dorsal side of the thickened ligamentum flavum were extracellular matrix organization, cell adhesion, extracellular matrix disassembly, and proteolysis. These are considered important pathologies of ligamentum flavum thickening. [ABSTRACT FROM AUTHOR]

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Age-dependent changes in the transcription levels of 5-day-old Euglena gracilis cells, which showed positive gravitaxis, 6-day-old cells without gravitactic orientation, and older cells (9- and 11-day-old, which displayed a precise negative gravitaxis) were determined through microarray analysis. Hierarchical clustering of four independent cell cultures revealed pronounced similarities in transcription levels at the same culture age, which proves the reproducibility of the cultivation method. Employing the non-oriented cells from the 6-day-old culture as a reference, about 2779 transcripts were found to be differentially expressed. While positively gravitactic cells (5-day-old culture) showed only minor differences in gene expression compared to the 6-day reference, pronounced changes of mRNAs (mainly an increase) were found in older cells compared to the reference culture. Among others, genes coding for adenylyl cyclases, photosynthesis, and metabolic enzymes were identified to be differentially expressed. The investigated cells were grown in batch cultures, so variations in transcription levels most likely account for factors such as nutrient depletion in the medium and self-shading. Based on these findings, a particular transcript (e.g., transcript 19556) was downregulated using the RNA interference technique. Gravitaxis and phototaxis were impaired in the transformants, indicating the role of this transcript in signal transduction. Results of the experiment are discussed regarding the increasing importance of E. gracilis in biotechnology as a source of valuable products and the possible application of E. gracilis in life-support systems. [ABSTRACT FROM AUTHOR]

Selective IgA deficiency (SIgAD) is the most common form and common variable immunodeficiency (CVID) is the most symptomatic form of predominant antibody deficiency. Despite differences in the clinical picture, a similar genetic background is suggested. A common feature of both disorders is the occurrence of autoimmune conditions. Regulatory T cells (Tregs) are the major immune cell type that maintains autoimmune tolerance. As the different types of abnormalities of Treg cells have been associated with autoimmune disorders in primary immunodeficiency (PID) patients, in our study we aimed to analyze the gene expression profiles of Treg cells in CVID and SIgAD patients compared to age-matched healthy controls. The transcriptome-wide gene profiling was performed by microarray technology. As a result, we analyzed and visualized gene expression patterns of isolated population of Treg cells. We showed the differences at the gene level between patients with and without autoimmunizations. Our findings suggest that the gene signatures of Treg cells isolated from SIgAD and CVID patients differ from age-matched healthy controls and from each other, presenting transcriptional profiles enriched in innate immune or Th response, respectively. The occurrence of autoimmunity in both types of PID is associated with down-regulation of class I IFNs signaling pathways. In summary, our findings improve our understanding of Treg dysfunctions in patients with common PIDs and associated autoimmunity. [ABSTRACT FROM AUTHOR]

Background/Aim: Microarray analysis is the first recommended test in patients with intellectual disability, developmental delay, autistic spectrum disorder, and multiple congenital anomalies. Diagnostic rate of microarray analysis and the frequency of recurrent microdeletion/microduplications in Turkish patients with neurodevelopmental disorders and/or multiple congenital anomalies have been reported as 15-18% and 6%, respectively. In the current study, it is aimed to determine the diagnostic rate of microarray analysis and the frequency of recurrent syndromes in this patient group, to discover new chromosomal regions responsible for the disease and to contribute to the genotype-phenotype correlation. Methods: In this study, microarray results of 320 Turkish pediatric patients who applied to Medical Genetics outpatient clinic with intellectual disability, developmental delay and/or multiple congenital anomalies are presented. Results: Pathogenic/likely pathogenic copy number alterations were detected in 44 patients. Of these changes, 22 were known microdeletion/microduplication syndromes. The diagnostic rate of microarray analysis was 13.75% (44/320) and the rate of known microdeletion/microduplication syndromes was 6.8% (22/320), which were close to the data in the literature. In a patient with macrocephaly, ptosis, and psychomotor retardation, we detected duplication of 2p23.3 encompassing the ASXL2 gene. This may suggest that increased copies of this region may cause a phenotype similar to Shashi-Pena Syndrome. In one patient, Xq13.2q13.3 deletion was found to cause severe findings in female gender, although it contains the same genes as the Xq13 duplication syndrome, in which carrier females are unaffected. In another patient, deletion of the HMGB3 gene located in the Xq28 region was found to cause ptosis clinic and effect female gender. Conclusion: This study shows that microarray analysis is a good option as the first test in patients with developmental delay and/or multiple congenital anomalies. In addition, the current study is expected to contribute to the genotype-phenotype correlation in this patient group. [ABSTRACT FROM AUTHOR]

Introduction: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets. Methods: We performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry. Results: Our analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the 'regulation of biological quality' GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells. Discussion: Our findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN. [ABSTRACT FROM AUTHOR]

Abstract Background Investigating the molecular biology underpinning the early-stage of traumatic temporomandibular joint (TMJ) ankylosis is crucial for discovering new ways to prevent the disease. This study aimed to explore the dynamic changes of transcriptome from the intra-articular hematoma or the newly generated ankylosed callus during the onset and early progression of TMJ ankylosis. Methods Based on a well-established sheep model of TMJ bony ankylosis, the genome-wide microarray data were obtained from samples at postoperative Days 1, 4, 7, 9, 11, 14 and 28, with intra-articular hematoma at Day 1 serving as controls. Fold changes in gene expression values were measured, and genes were identified via clustering based on time series analysis and further categorised into three major temporal classes: increased, variable and decreased expression groups. The genes in these three temporal groups were further analysed to reveal pathways and establish their biological significance. Results Osteoblastic and angiogenetic genes were found to be significantly expressed in the increased expression group. Genes linked to inflammation and osteoclasts were found in the decreased expression group. The various biological processes and pathways related to each temporal expression group were identified, and the increased expression group comprised genes exclusively involved in the following pathways: Hippo signaling pathway, Wnt signaling pathway and Rap 1 signaling pathway. The decreased expression group comprised genes exclusively involved in immune-related pathways and osteoclast differentiation. The variable expression group consisted of genes associated with DNA replication, DNA repair and DNA recombination. Significant biological pathways and transcription factors expressed at each time point postoperatively were also identified. Conclusions These data, for the first time, presented the temporal gene expression profiling and reveal the important process of molecular biology in the early-stage of traumatic TMJ bony ankylosis. The findings might contributed to identifying potential targets for the treatment of TMJ ankylosis.

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT–qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT–qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients. [ABSTRACT FROM AUTHOR]

Background: Thromboangiitis obliterans (TAO) causes vascular insufficiency due to chronic inflammation and abrupt thrombosis of the medium and small arteries of the extremities. In our study, we aimed to determine biomarkers for the diagnosis of TAO by evaluating 15 male TAO patients with Shinoya diagnostic criteria and 5 healthy controls who did not have TAO-related symptoms in their family histories. Methods: The Clariom D Affymetrix platform was used to conduct microarray analysis on total RNA extracted from whole blood. A total of 477 genes (FC ≤ 5 or >5) common to the fifteen patient and five control samples were selected using comparative microarray analysis; among them, 79 genes were upregulated and 398 genes were downregulated. Results: According to FC ≤ 10 or >10, in the same TAO patient and control group, 13 genes out of 28 were upregulated, whereas 15 genes were downregulated. The 11 key genes identified according to their mean log2FC values were PLP2, RPL27A, CCL4, FMNL1, EGR1, EIF4A1, RPL9, LAMP2, RNF149, EIF4G2, and DGKZ. The genes were ranked according to their relative expression as follows: FMNL1 > RNF149 > RPL27A > EIF4G2 > EIF4A1 > LAMP2 > EGR1 > PLP2 > DGKZ > RPL9 > CCL4. Using protein–protein interaction network analysis, RPL9, RPL27A, and RPL32 were found to be closely related to EIF4G2 and EIF4A1. The Reactome pathway found pathways linked to 28 genes. These pathways included the immune system, cellular responses to stress, cytokine signaling in the immune system, and signaling by ROBO receptors. Conclusions: By figuring out the protein expression levels of the genes that have been found to explain how TAO disease works at the molecular level, it will be possible to figure out how well these chosen transcripts can diagnose and predict the disease. [ABSTRACT FROM AUTHOR]

Transient hypogammaglobulinemia of infancy (THI) is one of the most common forms of hypogammaglobulinemia in the early childhood. THI is usually associated with chronic, recurrent bacterial and viral infections, life-threatening in some cases, yet its pathogenesis is still largely unknown. As our previous findings indicated the possible role of Treg cells in the pathomechanism of THI, the aim of the current study was to investigate gene expression profile of Treg cells isolated from THI patients. The transcriptome-wide gene profiling was performed using microarray technology on THI patients in two time-points: during (THI-1), and in resolution phase (THI-2) of hypogammaglobulinemia. As a result, a total of 1086 genes were differentially expressed in THI-1 patients, when compared to THI-2 as well as control group. Among them, 931 were up- and 155 downregulated, and part of them encodes genes important for Treg lymphocyte biology and function, i.e. transcription factors/cofactors that regulate FOXP3 expression. Thus, we postulate that Treg cells isolated from THI patients during hypogammaglobulinemia display enhanced suppressor transcriptome signature. Treg expression profile of THI children after normalization of Ig levels largely resembles the results obtained in healthy control group, suggesting THI Treg transcriptome seems to return to that observed in healthy children. Taken together, we suggest that THI pathomechanism is associated not only with transiently elevated Treg cell numbers, but also with their enhanced regulatory/inhibitory functions. These findings expand our knowledge of human Treg cells and may be useful for the future diagnosis or management of THI. Transient hypogammaglobulinemia of infancy (THI) is characterized by transiently reduced serum immunoglobulin levels and recurrent infections, accompanied by transiently elevated Treg numbers. Here, we show that Treg cells collected during the phase of hypogammaglobulinemia display enhanced suppressor transcriptome signature when compared to the resolution phase of THI. This signature is manifested by upregulated gene expression of Treg master functional regulators, transcription factors, and TGF-β-signaling pathway mediators. Graphical Abstract [ABSTRACT FROM AUTHOR]

This study aimed to identify the potential circular RNAs (circRNAs) in exosomes isolated from serum as biomarkers of lower limb vascular disease (LLVD) in patients with type 2 diabetes mellitus (T2DM). This research collected circRNAs from exosomes isolated from three T2DM patients and three T2DM patients with LLVD for microarray analysis. Five candidate biomarkers derived from differentially expressed circRNAs were then validated by quantitative real-time polymerase chain reaction in 20 T2DM patients and 20 T2DM patients with LLVD. Finally, expression levels of circRNAs were validated in 160 samples. Significant differences in the expression of 295 circRNAs were found between T2DM controls and T2DM patients with LLVD. Among them, 191 differentially expressed circRNAs were upregulated, and 104 were downregulated in T2DM patients with LLVD. Three upregulated and two downregulated circRNAs were further confirmed in 40 samples. According to the testing of 160 samples, hsa_circ_0001842 showed a noticeable specificity in the T2DM patients with LLVD group (n = 80), with an area under the curve (AUC) of 0.79, a sensitivity of 88.75%, and a specificity of 68.75%. In conclusion, hsa_circ_0001842 was found as a potential diagnostic biomarker for T2DM with LLVD. [ABSTRACT FROM AUTHOR]

Cornelia de Lange syndrome is a genetic and clinically heterogeneous entity, caused by at least five genes. It is characterized by short stature, gestalt facies, microcephaly, neurodevelopmental disorders, and other anomalies. In this report, we present a 13-year-old female patient with microcephaly, cleft palate, polydactyly, short stature, triangular facies, frontal bossing, a bulbous nose, an overfolded helix, limited pronosupination, and an anomalous uterus. No neurodevelopmental disorders were reported. A chromosomal microarray analysis of 6.5 million markers was performed in the proband and her parents. The results showed a de novo heterozygous microdeletion of exons 9–14 within RAD21, which confirmed the diagnosis of Cornelia de Lange syndrome type 4. Our patient did not show any neurologic phenotype (until the time of diagnosis), although neurodevelopmental disorders are frequently present in patients with Cornelia de Lange syndrome type 4, and despite carrying a deletion that was larger than previously reported. Therefore, unknown genetic modifiers or intrinsic mechanisms of RAD21 variants may exist and should be studied. [ABSTRACT FROM AUTHOR]

Recently, the role of long non-coding RNA (lncRNA) in rheumatic immune diseases has attracted widespread attention. However, knowledge of lncRNA in connective tissue disease-associated interstitial lung disease (CTD-ILD) is limited. This study explored the expression profile and possible mechanisms of lncRNA and mRNA in peripheral blood mononuclear cells (PBMCs) of CTD-ILD patients, especially systemic sclerosis (SSc)-ILD and rheumatoid arthritis (RA)-ILD. LncRNA microarray analysis identified 240 diferentially expressed lncRNAs and 218 diferentially expressed mRNA in the CTD-ILD group and the connective tissue disease without associated interstitial lung disease (CTD-NILD) group. The bioinformatics analysis of diferential genes has identified several important biological processes and signal pathways, including nuclear factor kappa B (NF-kappa B) signaling pathway, interleukin 17 (IL-17) signaling pathway, B cell receptor signaling pathway. Relative expression levels of five diferentially expressed lncRNAs and one mRNA in 120 SSc and RA patients with or without ILD were detected by quantitative reverse-transcription (PCR). The ENST00000604692 expression level was significantly higher in the ILD than the without interstitial lung disease (NILD) group; T311354 and arginase-1 were significantly higher in SSc than RA group. These data suggest that the specific profile of lncRNA in PBMCs of CTD-ILD patients and the potential signal pathways related to the pathogenesis of CTD-ILD, which may provide newfound insights for the diagnosis and treatment of CTD-ILD patients. [ABSTRACT FROM AUTHOR]

Transcriptomic evidence from human myocardium in myocardial infarction (MI) is still not sufficient. Thus, there is a need for studies on human cardiac samples in relation to the clinical data of patients. The purpose of our pilot study was to investigate the transcriptomic profile of myocardium in the infarct zone, in comparison to the remote myocardium, in patients with fatal MI, via microarray analysis. This study included four patients with fatal MI type 1. We selected histologically verified samples from within the infarct area (n = 4) and remote myocardium (n = 4). The whole transcriptome was evaluated using microarray analysis. Differentially expressed genes (DEGs) clustered in the infarct area and in the remote myocardium allowed their differentiation. We identified a total of 1785 DEGs (8.32%) in the infarct area, including 1692 up-regulated (94.79%) and 93 down-regulated (5.21%) genes. The top 10 up-regulated genes were TRAIL, SUCLA2, NAE1, PDCL3, OSBPL5, FCGR2C, SELE, CEP63, ST3GAL3 and C4orf3. In the infarct area, we found up-regulation of seventeen apoptosis-related genes, eleven necroptosis-related, and six necrosis-related genes. Transcriptome profiling of the myocardium in patients with MI remains a relevant area of research for the formation of new scientific hypotheses and a potential way to increase the translational significance of studies into myocardial infarction. [ABSTRACT FROM AUTHOR]

Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives. Enrichment analyses of the transcriptional data showed that compared with SQ, its EG derivatives exerted different, in most cases desirable, biological responses. EG derivatives showed increased enrichment of mitochondrial functions, lipid and glucose metabolism, and inflammatory response. Mono-, di-, and tetra-SQ showed higher enrichment of the cellular component-ribosome. Histological staining showed EG derivatives prevented excessive lipid accumulation. Additionally, mitochondrial transcription factors showed upregulation in tetra-SQ-treated cells. Notably, EG derivatives showed better anti-inflammatory effects. Further, gene-disease association analysis predicted substantial improvement in the bioactivities of SQ derivatives in metabolic diseases. Cluster analyses revealed di- and tetra-SQ had more functional similarities than others, reflected in their scanning electron microscopy images; both di- and tetra-SQ self-organized into similar sizes and shapes of vesicles, subsequently improving their cation binding activities. Protein-protein interaction networks further revealed that cation binding activity might explain a major part, if not all, of the differences observed in functional analyses. Altogether, the addition of EG derivatives may improve the biological responses of SQ and thus may enhance its health-promoting potential.

ObjectiveWe investigated the autoantibody (autoAb) profiles in ANA+ individuals lacking systemic autoimmune rheumatic disease (SARD) and early SARD patients to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next 2 years in ANA+ individuals.MethodsUsing custom antigen (Ag) microarrays, 144 IgM and IgG autoAbs were surveyed in 84 asymptomatic and 123 symptomatic (48 UCTD and 75 SARD patients) ANA+ individuals. AutoAbs were compared in ANA+ individuals lacking a SARD diagnosis with ≥2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset.ResultsWe show that ANA+ individuals have autoAb to many self-Ags that are not being captured by current screening techniques and very high levels of these autoAbs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more autoAgs than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of autoAbs. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years of follow-up the levels of autoAbs remained remarkably stable regardless of whether individuals progressed or not.ConclusionOur findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing.

Septo-optic dysplasia (SOD) is a rare congenital anomaly that is clinically defined by developmental delay and characteristic brain magnetic resonance imaging findings, including optic nerve hypoplasia, pituitary hormone abnormalities, and midline brain defects. The occurrence of SOD is generally sporadic; however, it can be inherited rarely. Although an association with HESX1, SOX2, and SOX3 mutations has been identified, the detailed etiology is multifactorial and unclear. Here, we present the case of a 7-year-old girl who was clinically diagnosed with SOD and 15q13.3 duplication. Patients with duplication at chromosome 15q13.3 were reported to be diagnosed with autism spectrum disorder, epilepsy, and schizophrenia in previous studies. The relationship between SOD and the microduplication of 15q13.3 has not yet been explored. In this study, we suggest that there may be an association between chromosome 15q13.3 microduplication and SOD.

Abstract Objective To evaluate the prenatal and perinatal outcome of fetuses with extremely large nuchal translucency (eNT) thickness (≥ 6.5 mm). Methods 193 (0.61%) singleton fetuses with eNT were retrospectively included. Anomaly scan, echocardiography, and chromosomal and genetic test were included in our antenatal investigation. Postnatal follow-up was offered to all newborns. Results Major congenital anomalies included congenital heart defect (32.6%, 63/193), hydrops fetalis (13.5%, 26/193), omphalocele (9.3%, 18/193), and skeletal dysplasia (7.8%, 15/193) et al. Abnormal karyotype was identified in 81/115 (70.4%) cases including Turner syndrome (n = 47), Trisomy 18 (n = 17), Trisomy 21 (n = 9), and Trisomy 13 (n = 3). Chromosomal microarray analysis provided informative results with 3.6% (1/28) incremental diagnostic yield over conventional karyotyping. The diagnostic yield of exome sequencing is 10.0% (2/20). There was no significant increase [Odds Ratio (OR) = 1.974; 95% confidence interval 0.863–4.516; P = 0.104] in the incidence of chromosomal defects despite the presence of other structural anomalies. Only 13 fetuses were successfully followed up and survived at term, no one was found with developmental delay or mental retardation. Conclusions Extremely large NT has a high risk of chromosomal abnormality. CMA and ES improve chromosomal genomic and genetic diagnosis of fetal increased NT. When cytogenetic analysis and morphology assessment are both normal, the outcome is good.

Microarrays, miniaturized platforms used for high-content studies, provide potential advantages over traditional in vitro investigation in terms of time, cost, and parallel analyses. Recently, microarrays have been leveraged to investigate immune cell biology by providing a platform with which to systematically investigate the effects of various agents on a wide variety of cellular processes, including those giving rise to immune regulation for application toward curtailing autoimmunity. A specific embodiment incorporates dendritic cells cultured on microarrays containing biodegradable microparticles. Such an approach allows immune cell and microparticle co-localization and release of compounds on small, isolated populations of cells, enabling a quick, convenient method to quantify a variety of cellular responses in parallel. In this study, the microparticle microarray platform was utilized to investigate a small library of sixteen generally regarded as safe (GRAS) compounds (ascorbic acid, aspirin, capsaicin, celastrol, curcumin, epigallocatechin-3-gallate, ergosterol, hemin, hydrocortisone, indomethacin, menadione, naproxen, resveratrol, retinoic acid, α-tocopherol, vitamin D3) for their ability to induce suppressive phenotypes in murine dendritic cells. Two complementary tolerogenic index ranking systems were proposed to summarize dendritic cell responses and suggested several lead compounds (celastrol, ergosterol, vitamin D3) and two secondary compounds (hemin, capsaicin), which warrant further investigation for applications toward suppression and tolerance.

Background: Alzheimer's Disease (AD) is an age-related progressive neurodegenerative disorder characterized by mental deterioration, memory deficit, and multiple cognitive abnormalities, with an overall prevalence of ~2% among industrialized countries. Although a proper diagnosis is not yet available, identification of miRNAs and mRNAs could offer valuable insights into the molecular pathways underlying AD's prognosis. Method: This study aims to utilizemicroarray bioinformatic analysis to identify potential biomarkers of AD, by analyzing six microarray datasets (GSE4757, GSE5281, GSE16759, GSE28146, GSE12685, and GSE1297) of AD patients, and control groups. Furthermore, this study conducted gene ontology, pathways analysis, and protein-protein interaction network to reveal major pathways linked to probable biological events. The datasets were meta-analyzed using bioinformatics tools, to identify significant differentially expressed genes (DEGs) and hub genes and their targeted miRNAs'. Results: According to the findings, CXCR4, TGFB1, ITGB1, MYH11,and SELE genes were identified as hub genes in this study. The analysis of DEGs using GO (gene ontology) revealed that these genes were significantly enriched in actin cytoskeleton regulation, ECM-receptor interaction, and hypertrophic cardiomyopathy. Eventually, hsa-mir-122-5p, hsa-mir-106a-5p, hsa-mir-27a-3p, hsa-mir16-5p, hsa-mir-145-5p, hsa-mir-12-5p, hsa-mir-128-3p, hsa-mir 3200-3p, hsa-mir-103a-3p,and hsa-mir- 9-3p exhibited significant interactions with most of the hub genes. Conclusion: Overall, these genes can be considered as pivotal biomarkers for diagnosing the pathogenesis and molecular functions of AD. [ABSTRACT FROM AUTHOR]

Data mining involves the computational analysis of a plethora of publicly available datasets to generate new hypotheses that can be further validated by experiments for the improved understanding of the pathogenesis of neurodegenerative diseases. Although the number of sequencing datasets is on the rise, microarray analysis conducted on diverse biological samples represent a large collection of datasets with multiple web-based programs that enable efficient and convenient data analysis. In this review, we first discuss the selection of biological samples associated with neurological disorders, and the possibility of a combination of datasets, from various types of samples, to conduct an integrated analysis in order to achieve a holistic understanding of the alterations in the examined biological system. We then summarize key approaches and studies that have made use of the data mining of microarray datasets to obtain insights into translational neuroscience applications, including biomarker discovery, therapeutic development, and the elucidation of the pathogenic mechanisms of neurodegenerative diseases. We further discuss the gap to be bridged between microarray and sequencing studies to improve the utilization and combination of different types of datasets, together with experimental validation, for more comprehensive analyses. We conclude by providing future perspectives on integrating multi-omics, to advance precision phenotyping and personalized medicine for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Maternal taurine supplementation has been shown to exert protective effects following a maternal obesogenic diet on offspring growth and metabolism. However, the long-term effects of maternal cafeteria diet on adiposity, metabolic profile, and hepatic gene expression patterns following supplementation of taurine in adult offspring remains unclear. In this study, we hypothesized that exposure to maternal taurine supplementation would modulate the effects of maternal cafeteria diet by reducing adiposity and hepatic gene expression patterns involved in lipid metabolism in adult offspring. Female Wistar rats were fed a control diet, control diet supplemented with 1.5% taurine in drinking water, cafeteria diet (CAF) or CAF supplemented with taurine (CAFT) from weaning. After 8 weeks, all animals were mated and maintained on the same diets during pregnancy and lactation. After weaning, all offspring were fed with control chow diet until the age of 20 weeks. Despite similar body weights, CAFT offspring had significantly lower fat deposition and body fat when compared with CAF offspring. Microarray analysis revealed that genes (Akr1c3, Cyp7a1, Hsd17b6, Cd36, Acsm3 , and Aldh1b1) related to steroid hormone biosynthesis, cholesterol metabolism, peroxisome proliferator-activated receptor signaling pathway, butanoate metabolism, and fatty acid degradation were down-regulated in CAFT offspring. The current study shows that exposure to maternal cafeteria diet promoted adiposity and taurine supplementation reduced lipid deposition and in both male and female offspring and led to alterations in hepatic gene expression patterns, reducing the detrimental effects of maternal cafeteria diet. Long-term effects of maternal cafeteria diet and taurine are decreased fat deposition and hepatic gene expression of Akr1c3, Cyp7a1, Hsd17b6, Acsm3 , and Aldh1b1 in rat offspring. Abbreviations: Acsm3, acyl-CoA synthetase medium-chain family member 3; Aldh1b1, Aldehyde dehydrogenase 1 family, member B1; Akr1c3, aldo-keto reductase family 1, member C3; Cyp7a1, cytochrome P450, family 7, subfamily a, polypeptide 1; Hsd17b6, Hydroxysteroid (17-beta) dehydrogenase 6; PPAR, peroxisome proliferator-activated receptor. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Recombinant human erythropoietin (rHuEpo) abuse by athletes threatens the integrity of sport. Due to the overlap in physiological response to rHuEpo and altitude exposure, it remains difficult to differentiate changes in hematological variables caused by rHuEpo or altitude, and therefore, other molecular methods to enhance anti-doping should be explored. Objective: To identify the hematological and transcriptomic response to prolonged altitude exposure typical of practices used by elite athletes. Design: Longitudinal study. Setting: University of Cape Town and Altitude Training Centre in Ethiopia. Participants and Intervention: Fourteen well-trained athletes sojourned to an altitude training camp in Sululta, Ethiopia (;2400-2500mabove sea level) for 27 days. Blood samples were taken before arrival, 24 hours, and 9, 16, and 24 days after arrival at altitude in addition to 24 hours and 6, 13, and 27 days upon return to sea level. Main Outcome Measures: Blood samples were analyzed for hemoglobin concentration, hematocrit, and reticulocyte percentage. The transcriptomic response in whole blood and peripheral blood mononuclear cells (PBMC) were analyzed using gene expression microarrays. Results: A unique set of 29 and 10 genes were identified to be commonly expressed at every altitude time point in whole blood and PBMC, respectively. There were no genes identified upon return to sea level in whole blood, and only one gene within PBMC. Conclusions: The current study has identified a series of unique genes that can now be integrated with genes previously validated for rHuEpo abuse, thereby enabling the differentiation of rHuEpo from altitude exposure. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prenatal and perinatal outcome of fetuses with extremely large nuchal translucency (eNT) thickness (≥ 6.5 mm). Methods: 193 (0.61%) singleton fetuses with eNT were retrospectively included. Anomaly scan, echocardiography, and chromosomal and genetic test were included in our antenatal investigation. Postnatal follow-up was offered to all newborns. Results: Major congenital anomalies included congenital heart defect (32.6%, 63/193), hydrops fetalis (13.5%, 26/193), omphalocele (9.3%, 18/193), and skeletal dysplasia (7.8%, 15/193) et al. Abnormal karyotype was identified in 81/115 (70.4%) cases including Turner syndrome (n = 47), Trisomy 18 (n = 17), Trisomy 21 (n = 9), and Trisomy 13 (n = 3). Chromosomal microarray analysis provided informative results with 3.6% (1/28) incremental diagnostic yield over conventional karyotyping. The diagnostic yield of exome sequencing is 10.0% (2/20). There was no significant increase [Odds Ratio (OR) = 1.974; 95% confidence interval 0.863–4.516; P = 0.104] in the incidence of chromosomal defects despite the presence of other structural anomalies. Only 13 fetuses were successfully followed up and survived at term, no one was found with developmental delay or mental retardation. Conclusions: Extremely large NT has a high risk of chromosomal abnormality. CMA and ES improve chromosomal genomic and genetic diagnosis of fetal increased NT. When cytogenetic analysis and morphology assessment are both normal, the outcome is good. [ABSTRACT FROM AUTHOR]

Background: Aeromedical evacuation provides critical care during long-distance transport of injured victims between medical facilities. Often, these victims sustain muscle trauma related to mechanical insults, such as crush. Understanding the effects of flight on injured muscle is important because the aircraft cabin represents an external environment with mild hypoxia--the cabin's altitude is 2,438minstead of sea level. Becausemild hypobaric hypoxia can alter gene expression in normalmuscle and affect recovery patterns, it is beneficial to examine whether this type of hypoxia may also alter injury-related genes. Objective: The objective of this study was to verify the hypothesis that differential gene expression occurs in response to mild hypobaric hypoxia exposure in crush-injured muscle during two early recovery (preregeneration stage) time points. Methods: Twenty-four female mice were anesthetized, and the right gastrocnemius muscle underwent crush injury. Approximately 24 hours later, mice were exposed to normobaric normoxia or hypobaric hypoxia for 8--9 hours. After 32 or 48 hours of recovery, the mice were euthanized, and the right and left lateral gastrocnemius muscles were collected for microarray and bioinformatics analyses. Results: The study hypothesis was verified. There were 353 highly upregulated, differentially expressed genes identified in the injuredmuscle compared to the uninjuredmuscle.Mid1 was upregulated in both pressure conditions regardless of injury status. There were 52 and 15 differentially expressed genes at 32 and 48 hours postinjury, respectively, in the hypobaric hypoxiaexposed, injuredmuscle compared to the normobaric normoxia-exposed, injuredmuscle. The macrophage gene Cd68 correlated with other leukocyte-related genes. Discussion: These findings expand our understanding of the genetic changes that occur in muscle in response to a crush injury, including those related to the macrophage protein CD68. Nursing interventions addressing adequate functioning after crush muscle injury may need to consider the effects on Cd68 and its closely related genes. In addition, our results suggest a responsiveness of the gene Mid1 to flight-relevant hypobaric hypoxia. Changes in the expression of Mid1 may be appropriate in assessing the long-term health of flight crew members. [ABSTRACT FROM AUTHOR]

O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression. Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds. Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans. The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules. A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray. Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics. Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.

Objective: In microarray datasets, hundreds and thousands of genes are measured in a small number of samples,and sometimes due to problems that occur during the experiment, the expression value of some genes is recorded asmissing. It is a difficult task to determine the genes that cause disease or cancer from a large number of genes. Thisstudy aimed to find effective genes in pancreatic cancer (PC). First, the K-nearest neighbor (KNN) imputation methodwas used to solve the problem of missing values (MVs) of gene expression. Then, the random forest algorithm wasused to identify the genes associated with PC.Materials and Methods: In this retrospective study, 24 samples from the GSE14245 dataset were examined. Twelvesamples were from patients with PC, and 12 samples were from healthy control. After preprocessing and applying thefold-change technique, 29482 genes were used. We used the KNN imputation method to impute when a particulargene had MVs. Then, the genes most strongly associated with PC were selected using the random forest algorithm. Weclassified the dataset using support vector machine (SVM) and naïve bayes (NB) classifiers, and F-score and Jaccardindices were reported.Results: Out of the 29482 genes, 1185 genes with fold-changes greater than 3 were selected. After selecting the mostassociated genes, 21 genes with the most important value were identified. S100P and GPX3 had the highest andlowest importance values, respectively. The F-score and Jaccard value of the SVM and NB classifiers were 95.5, 93,92, and 92 percent, respectively.Conclusion: This study is based on the application of the fold change technique, imputation method, and randomforest algorithm and could find the most associated genes that were not identified in many studies. We thereforesuggest researchers use the random forest algorithm to detect the related genes within the disease of interest.

Introduction: Reinke’s Edema (RE) is a laryngeal lesion related to excessive tobacco smoking, voice overuse, and laryngopharyngeal reflux. Although the risk of malignancy has been considered low in literature, RE is classified among precancerous lesions. Objectives: We investigated DNA Copy Number Alterations (CNAs) in specimens of RE and its potential association with malignant progression. Methods: We used array-based comparative genomic hybridization (aCGH, Agilent 4 × 180 K platform) to study eight RE cases. All patients were heavy tobacco users for at least 30 years, and none of them progressed to cancer in the follow-up (>8 years). Two RE presented mild dysplasia, one moderate dysplasia, and no histological alterations were found in the remaining five cases. CNAs were compared with the Database of Genomic Variants (DGV) and genes mapped on altered regions had their functions annotated. Results: Six of eight patients showed different rare copy number alterations on chromosomes 2q37.3, 4q13.1, 4q13.3, 7q11.22, 10p14, and 13q34. A gain of the whole chromosome 8 were detected in one case. Of interest, four of eight RE cases showed copy number imbalances involving genes previously described in several tumor types (RASA3, COL6A3, LINC00707, LINP1, SMR3A, and SMR3B). Conclusion: The genomic imbalances herein found in RE have the potential to contribute to the phenotype but with limited or no risk of cancer. A long-term follow-up in a large series of patients could clarify the mechanisms involved in the malignant progression of RE. Level of evidence: 4.