Search

Purpose: To screen for the cisplatin resistance-related prognostic signature in oral squamous cell carcinoma (OSCC) and assess its correlation with the immune microenvironment. Materials and Methods: The gene expression data associated with OSCC and cisplatin-resistance were downloaded from TCGA and GEO databases. Cisplatin-resistant genes were selected through taking the intersection of differentially expressed genes (DEGs) between tumor and control groups as well as between cisplatin-resistant samples and parental samples. Then, prognosis-related cisplatin-resistant genes were further selected by univariate Cox regression and LASSO regression analyses to construct a survival prognosis model. A GSEA (gene set enrichment analysis) between two risk groups was conducted with the MSigDB v7.1 database. Finally, the immune landscape of the sample was studied using CIBERSORT. The IC50 values of 57 drugs were predicted using pRRophetic 0.5. Results: A total 230 candidate genes were obtained. Then 7 drug-resistant genes were selected for prognostic risk-score (RS) signature construction using LASSO regression analysis, including STC2, TBC1D2, ADM, NDRG1, OLR1, PDGFA and ANO1. RS was an independent prognostic factor. Additionally, a nomogram model was established to predict the 1-, 2-, and 3-year survival rates of samples. The GSEA identified several differential pathways between two risk groups, such as EMT, hypoxia, and oxidative phosphorylation. Fifteen immune cells were statistically significantly different in infiltration level between the two groups, such as macrophages M2, and resting NK cells. A total of 57 drugs had statistically significantly different IC50 values between two risk groups. Conclusion: These model genes and immune cells may play a role in predicting the prognosis and chemoresistance in OSCC. [ABSTRACT FROM AUTHOR]

Bipolar disorder is a chronic disorder characterized by fluctuations in mood state and energy and recurrent episodes of mania/hypomania and depression. Bipolar disorder may be regarded as a neuro-progressive disorder in which repeated mood episodes may lead to cognitive decline and dementia development. In the current review, we employed genome-wide association studies to comprehensively investigate the genetic variants associated with bipolar disorder and dementia. Thirty-nine published manuscripts were identified: 20 on bipolar disorder and 19 on dementia. The results showed that the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A were overlapping between patients with bipolar disorder and dementia. In conclusion, the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A may be associated with the neuroprogression of bipolar disorder to dementia. Further genetic studies are needed to comprehensively clarify the role of genes in cognitive decline and the development of dementia in patients with bipolar disorder. [ABSTRACT FROM AUTHOR]

Purpose: Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders, resulting in blindness in children. This study aimed to describe the clinical and genetic characteristics of a cohort of patients with LCA and to investigate the retinal vascular characteristics in LCA patients. Methods: Fifty-two children with LCA were included in the study. All patients underwent detailed ocular examinations. Electroretinography (ERG) was used to evaluate the retinal function. Optical coherence tomography (OCT) was used to assess the structure change of the retina for those patients who were able to cooperate very well. Panel-based next-generation sequencing was performed to identify pathogenic variants in genes associated with LCA. Diameters of the retinal vessels were measured using the EVision AI screening system with an artificial intelligence (AI) technique. An ultrasound Doppler was used to evaluate hemodynamic parameters, including peak systolic velocity (PSV), resistive index (RI), and pulsatility index (PI), in the ophthalmic, central retinal, posterior ciliary, carotid, and internal carotid as well as external carotid arteries in 12 patients aged from 3 to 14 years. Results: We detected 75 pathogenic variants from ten genes of RPGRIP1, CEP290, GUCY2D, LCA5, AIPL1, CRB1, RPE65, CRX, RDH12, and TULP1, including 29 novel and 36 previously reported variants in 52 affected children with LCA, with the highest detective rate in RPGRIP1 (26.9%). Fundus appearance is diverse in patients with LCA, ranging from normal to severe peripheral or central retinopathy. Retinal vasculature was evaluated in 12 patients with different gene variants, showing narrowed arteries with an average diameter of 43.6 ± 3.8 μm compared to that of 51.7 ± 2.6 μm in the normal controls (P < 0.001, n = 12). Meanwhile, their hemodynamic parameters were changed as well in the ophthalmic artery (OA), with a decreased PSV (P = 0.0132, n = 12) and slightly increased PI (P = 0.0488, n = 12) compared to the normal controls. However, the hemodynamic parameters did not change significantly in the other vessels. Conclusions: Blood supply to the eyeball is predicted to be reduced in patients with LCA, presumably due to photoreceptor cell degeneration. The novel identified variants will expand the spectrum of variants in LCA-related genes and be useful for studying the molecular mechanisms of LCA. [ABSTRACT FROM AUTHOR]

The role of cerebellar-cerebral functional connectivity (CC-FC) in obsessive-compulsive disorder (OCD), its trajectory post-pharmacotherapy, and its potential as a prognostic biomarker and genetic mechanism remain uncertain. To address these gaps, this study included 37 drug-naive OCD patients and 37 healthy controls (HCs). Participants underwent baseline functional magnetic resonance imaging (fMRI), followed by four weeks of paroxetine treatment for patients with OCD, and another fMRI scan post-treatment. We examined seed-based CC-FC differences between the patients and HCs, and pre- and post-treatment patients. Support vector regression (SVR) based on CC-FC was performed to predict treatment response. Correlation analysis explored associations between CC-FC and clinical features, as well as gene profiles. Compared to HCs, drug-naive OCD patients exhibited reduced CC-FC in executive, affective-limbic, and sensorimotor networks, with specific genetic profiles associated with altered CC-FC. Gene enrichment analyses highlighted the involvement of these genes in various biological processes, molecular functions, and pathways. Post-treatment, the patients showed partial clinical improvement and partial restoration of the previously decreased CC-FC. Abnormal CC-FC at baseline correlated negatively with compulsions severity and social functional impairment, while changes in CC-FC correlated with cognitive function changes post-treatment. CC-FC emerged as a potential predictor of symptom severity in patients following paroxetine treatment. This longitudinal resting-state fMRI study underscores the crucial role of CC-FC in the neuropsychological mechanisms of OCD and its pharmacological treatment. Transcriptome-neuroimaging spatial correlation analyses provide insight into the neurobiological mechanisms underlying OCD pathology. Furthermore, SVR analyses hold promise for advancing precision medicine approaches in treating patients with OCD. • OCD exhibited reduced CC-FC in EN, ALN, and SMN. • Alterations in CC-FC were associated with specific genes' expression levels. • Following treatment, there was partial restoration of the previously decreased CC-FC. • CC-FC holds promise as a potential prognostic biomarker for OCD. [ABSTRACT FROM AUTHOR]

In the recent years, there was an important improvement in the understanding of the pathogenesis of hereditary angioedema (HAE). Notwithstanding, in a large portion of patients with unknown mutation (HAE-UNK) the genetic cause remains to be identified. To identify new genetic targets associated with HAE, a large Argentine family with HAE-UNK spanning 3 generations was studied. Whole exome sequencing was performed on affected family members to identify potential genetic variants associated with HAE-UNK. In silico analyses and experimental studies were applied to assess the role of the identified gene variant. A missense variant (p.D239N) in DAB2IP was identified. The variant occurred in the C2-domain, the region interacting with vascular endothelial growth factor receptor 2 (VEGFR2). It was found to be rare, and predicted to have a detrimental effect on the functionality of DAB2IP. Protein structure modeling predicted changes in the mutant p.D239N protein structure, impacting protein stability. The p.D239N variant affected the subcellular localization of VEGFR2. Cells transfected with the DAB2IP-239N transcript exhibited an intracellular distribution, and VEGFR2 remained associated with the cell membrane. The altered localization pattern indicated reduced colocalization of the mutant protein with VEGFR2, suggesting a diminished ability of VEGFR2 binding. The study identified a novel missense variant (p.D239N) in DAB2IP in a family with HAE-UNK and highlighted the role of dysregulated VEGF-mediated signaling in altered endothelial permeability. DAB2IP loss-of-function pathogenic variants lead to the impairment of the endothelial VEGF/VEGFR2 ligand system and represent a new pathophysiologic cause of HAE-UNK. [ABSTRACT FROM AUTHOR]

Gene therapy using recombinant adeno‐associated virus (rAAV) as delivery vehicles has garnered much interest in recent years. There are still significant gaps in our fundamental understanding of the manufacturing processes to deliver sufficient products. Manufacturing efforts of rAAV using HEK293 cells have commonly relied on fixed bed falling film bioreactors like the iCELLis®. We used computational fluid dynamics (CFD) to validate the operating conditions required for a predictive iCELLis® 500 scale‐down model. The small‐scale and at‐scale systems have different flow paths causing validation of the corresponding agitation rates required to achieve the same linear flow through the fixed bed across scales to be non‐trivial. Therefore, we used CFD to predict the theoretical scaling relationship. In addition, CFD could predict kLa differences between the two systems and the operating conditions required to match kLa between scales. We also confirmed that the location of DO control must be the same in both systems to achieve proper scaling. Experimental runs confirming the validity of the novel scale‐down model showed that based on the modifications to the iCELLis® Nano system, we achieved similar DO, key metabolite, pH, and GC titer trends in both systems. [ABSTRACT FROM AUTHOR]

AbstractProtein-protein interaction (PPI) network analysis holds significant promise for cancer diagnosis and drug target identification. This paper introduces a novel random walk-based method called essential cancer protein identification using graph-based random walk with restart (EPI-GBRWR) to address this gap. This proposed method incorporates local and global topological features of proteins, enhancing the accuracy of essential protein identification in PPI networks. Starting with meticulous preprocessing of cancer gene datasets from NCBI, including breast, lung, colorectal, and ovarian cancers, and identifying a core set of common genes. The proposed method constructs PPI networks to capture complex protein interactions from these common cancer genes. Topological analysis, including a centrality measures matrix, is generated to perform the analysis to identify essential nodes. The study revealed that 40 essential proteins among breast, colorectal, lung and ovarian cancer showcase the potency of integrative methodologies in unravelling cancer complexity, signalling a transformative era in cancer research and treatment. The strength of the findings from the study has direct clinical relevance in cancer diseases. It contributes to the field of precision medicine to guide personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) could increase the susceptibility of individuals to develop obesity and type 2 diabetes (T2DM). Obesity and T2DM are closely related pathophysiologically, thus similar SNPs could mediate both these diseases, but this is rarely reported. Furthermore, limited studies have been performed to summarize SNP data in the Asian population compared to the Western population. In this study, we aimed to summarize SNPs that are associated with the development of obesity and T2DM among Asian populations. We searched six literature databases and Review Manager (RevMan) was used for meta-analysis. The pooled odds ratios (ORs) and 95% CIs were calculated with a random effects model for the heterogeneity among studies. The pooled analysis showed that rs9939609 (FTO gene) and rs17782313 and rs571312 (MC4R gene) are associated with obesity with an odd ratio (OR) of 1.37, 1.36 and 1.29 respectively. For T2DM, five SNPs, rs7903146 and rs12255372 (TCF7L2 gene), rs13266634 and rs11558471 (SLC30A8 gene) and rs2283228 (KCNQ1 gene) have also shown strong associations with T2DM at OR of 1.64, 1.61, 1.22, 1.29 and 1.60 respectively. This data could be used to develop a gene screening panel for assessing obesity and T2DM susceptibility. [ABSTRACT FROM AUTHOR]

Objective: To identify characteristic genes of rheumatoid arthritis （RA） by artificial neural network and to analyze role of immune cells in RA related microenvironment. Methods: GSE1919 and GSE77298 chips were from GEO database. Two chips were combined and batch corrected using R language to obtain a new data set, and difference was analyzed. Metascape enrichment analysis and GO and KEGG enrichment analysis were conducted for differential expressed genes （DEGs）. "randomForest" package in R software was used to screen characteristic genes of RA under random forest （RF） algorithm, and artificial neural network model was constructed according to gene score. Top 4 genes （HubGene） were extracted for subsequent analysis. Single sample gene set enrichment analysis （ssGSEA） was used to calculate abundance of immune cells in samples and carry out a series of correlation analysis. Results: Top 15 genes were selected as characteristic genes of RA through artificial neural network model: STAT1, RUNX3, AR, CDH11, LMO4, TIMP1, PLXNC1, CAP2, PRKAA2, VDR, SPP1, HCK, EPHB2, KCNAB1, ITGB7. STAT1, RUNX3 and CDH11 were up-regulated in RA synovial tissue, while AR was down-regulated in RA synovial tissue. Immune cell infiltration results showed that RA had the most significant correlation with activated CD4 T cells. Number of immune cells significantly related to RUNX3 was the largest. RUNX3 was significant positive correlated with activated B cells, activated CD4 T cells, activated CD8 T cells, central memory CD4+T cells, effector memory CD8 T cells, regulatory T cells, γδT cells and macrophages, while significant negative correlated with NK cells. Conclusion: Fifteen characteristic genes related to RA are identified through artificial neural network, among which STAT1, RUNX3, AR and CDH11 are top 4 genes. It emphasizes activation of CD4 T cells, regulatory T cells, γδT cells, macrophages, NK cells, activated B cells and other immune cells are important in pathogenesis of RA, providing new insights for diagnosis of RA and study of molecular mechanism of immune cells. [ABSTRACT FROM AUTHOR]

With rising living standards, there is an increasing demand for high-quality rice. Rice quality is mainly defined by milling quality, appearance quality, cooking and eating quality, and nutrition quality. Among them, chalkiness is a key trait for appearance quality, which adversely affects cooking and eating quality, head rice yield, and commercial value. Therefore, chalkiness is undesirable, and reducing chalkiness is a major goal in rice quality improvement. However, chalkiness is a complex trait jointly influenced by genetic and environmental factors, making its genetic study and precision improvement a huge challenge. With the rapid development of molecular techniques, much knowledge has been gained about the genes and molecular networks involved in chalkiness formation. The present review describes the major environmental factors affecting chalkiness and summarizes the quantitative trait loci (QTL) associated with chalkiness. More than 150 genes related to chalkiness formation have been reported. The functions of the genes regulating chalkiness, primarily those involved in starch synthesis, storage protein synthesis, transcription regulation, organelle development, grain shape regulation, and high-temperature response, are described. Finally, we identify the challenges associated with genetic improvement of chalkiness and suggest potential strategies. Thus, the review offers insight into the molecular dynamics of chalkiness and provides a strong basis for the future breeding of high-quality rice varieties. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second-most common neurodegenerative disease, affecting 1% of people aged over 60. Currently, there is only symptomatic relief for PD patients, with levodopa being the gold standard of PD treatment. Deep brain stimulation (DBS) is a surgical option to treat PD patients. DBS improves motor functions and may also allow a significant reduction in dopaminergic medication. Important parameters for DBS outcomes are the disease duration, the age of disease onset, responsiveness to levodopa and cognitive or psychiatric comorbidities. Emerging data also highlight the need to carefully consider the genetic background in the preoperative assessment of PD patients who are candidates for DBS, as genetic factors may affect the effectiveness of DBS in these patients. This review article discusses the role of genetics in DBS for PD patients, in an attempt to better understand inter-individual variability in DBS response, control of motor PD symptoms and appearance of non-motor symptoms, especially cognitive decline. [ABSTRACT FROM AUTHOR]

Background: A glioma is a form of tumor that is abundant in blood vessels. Vascular endothelial growth factor receptor (VEGFR) and its receptor 2 (VEGFR2) are important in the process of angiogenesis. The relationship between VEGFR2 rs2071559 and glioma development is currently uncertain. The present study aims to analyze the correlation between VEGFR2 rs2071559 gene polymorphism and the susceptibility to gliomas. Methods: A thorough search was carried out in the Cochrane Library, Scopus, and Medline databases from inception until 20 February 2024 using a mix of pertinent keywords. We used random-effects models to examine the odds ratio (OR) and reported the results together with their respective 95% confidence intervals (CIs). Results: A total of six studies were incorporated. The results of our meta-analysis indicated that all genetic models of VEGFR2 rs2071559 gene polymorphism, starting from dominant (OR 1.40; p < 0.00001), recessive (OR 1.52; p < 0.0001), CC genotype (OR 1.78; p < 0.00001), CT genotype (OR 1.30; p < 0.0001), and C allele (OR 1.41; p < 0.00001), were associated with a higher risk of developing gliomas. The subgroup analysis revealed a higher OR for studies with a sample size of ≥500, originated from Asia, with a mean age of ≥42.3 years, and a male prevalence of <57%. Conclusions: This study suggests that VEGFR2 rs2071559 gene polymorphism is associated with a higher risk of gliomas. [ABSTRACT FROM AUTHOR]

Background: Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD. Methods: This study included individuals with DSRD aged 10–30 years with trio exome sequencing performed during the diagnostic work up. Descriptive statistics and univariate analysis (Chi-square and Fisher's exact test) were used to describe and compare the characteristics of individuals with and without variants. Results: Forty-one individuals with DSRD had trio exome sequencing results. Eight (20%) had heterozygous de novo variants of immune regulatory genes, with four variants being pathogenic or likely pathogenic (UNC13D, XIAP, RNASEH2A, and DNASE1L3). All genes harboring pathogenic variants were associated with interferon type-1 inflammatory response. Individuals harboring variants were more likely to have a preceding trigger (p = 0.03, 95% CI 1.21–97.06), rapid clinical decline in less than 1 month (p = 0.01, 95% CI 1.67–52.06), and MRI abnormalities (p < 0.001, 95% CI 4.89–527.71). Discussion: A distinct subset of individuals with DSRD exhibited pathogenic variants in immune regulation genes associated with interferon-mediated inflammatory response, coinciding with previously established links between these genes and interferonopathies such as Aicardi-Goutieres syndrome. Our observations suggest that these variants might potentially contribute to the development of DSRD in individuals with DS. [ABSTRACT FROM AUTHOR]

• Cerebellar atrophy was not uncommon in genetic epileptic encephalopathies (EEs). • This cohort study revealed 15 % of genetic EE individuals had cerebellar atrophy. • A systematic review showed 32 genetic EEs associated with cerebellar atrophy. • Cerebellar atrophy could act as a molecular test precursor in genetic EEs. To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs). This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed. The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old. Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group. [ABSTRACT FROM AUTHOR]

Callus induction (CI) is a critical trait for transforming desirable genes in plants. A genome-wide association study (GWAS) analysis was conducted on the rice germplasms of 110 Indica rice accessions, in which three tissue culture media, B5, MS, and N6, were used for the CI of those rice panels' mature seeds. Seven quantitative trait loci (QTLs) on rice chromosomes 2, 6, 7, and 11 affected the CI percentage in the three media. For the B5 medium, one QTL (qCI–B5–Chr6) was identified on rice chromosome 6; for the MS medium, two QTLs were identified on rice chromosomes 2 and 6 (qCI–MS–Chr2 and qCI–MS–Chr6, respectively); for the N6 medium, four QTLs were identified on rice chromosomes 6, 7, and 11 (qCI–N6–Chr6.1 and qCI–N6–Chr6.2, qCI–N6–Chr7, and qCI–N6–Chr11, respectively). Fifty-five genes were identified within the haplotype blocks corresponding to these QTLs, thirty-one of which showed haplotypes associated with different CI percentages in those media. qCI–B5–Chr6 was located in the same region as qCI–N6–Chr6.2, and the Caleosin-related family protein was also identified in this region. Analysis of the gene-based haplotype revealed the association of this gene with different CI percentages in both B5 and N6 media, suggesting that the gene may play a critical role in the CI mechanism. Moreover, several genes, including those that encode the beta-tubulin protein, zinc finger protein, RNP–1 domain-containing protein, and lysophosphatidic acid acyltransferase, were associated with different CI percentages in the N6 medium. The results of this study provide insights into the potential QTLs and candidate genes for callus induction in rice that contribute to our understanding of the physiological and biochemical processes involved in callus formation, which is an essential tool in the molecular breeding of rice. [ABSTRACT FROM AUTHOR]

Background and Objectives: Atherosclerosis is one of the main reasons for cardiovascular disease development. This study aimed to analyze the association of mtDNA mutations and atherosclerotic plaques in carotid arteries of patients with atherosclerosis and conditionally healthy study participants from the Novosibirsk region. Methods: PCR fragments of DNA containing the regions of 10 investigated mtDNA mutations were pyrosequenced. The heteroplasmy levels of mtDNA mutations were analyzed using a quantitative method based on pyrosequencing technology developed by M. A. Sazonova and colleagues. Results: In the analysis of samples of patients with atherosclerotic plaques of the carotid arteries and conditionally healthy study participants from the Novosibirsk region, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected. A west–east gradient was found in the distribution of the mtDNA mutations m.5178C>A, m.3256C>T, m.652insG, and m.13513G>A. Conclusions: Therefore, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A, and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected in patients with atherosclerotic plaques in their carotid arteries from the Novosibirsk region. [ABSTRACT FROM AUTHOR]

Metabolomics, the study of small-molecule metabolites within biological systems, has become a potent instrument for understanding cellular processes. Despite its profound insights into health, disease, and drug development, identifying the protein partners for metabolites, especially dietary phytochemicals, remains challenging. In the present study, we introduced an innovative in silico, structure-based target prediction approach to efficiently predict protein targets for metabolites. We analyzed 27 blood serum metabolites from nutrition intervention studies' blueberry-rich diets, known for their health benefits, yet with elusive mechanisms of action. Our findings reveal that blueberry-derived metabolites predominantly interact with Carbonic Anhydrase (CA) family proteins, which are crucial in acid-base regulation, respiration, fluid balance, bone metabolism, neurotransmission, and specific aspects of cellular metabolism. Molecular docking showed that these metabolites bind to a common pocket on CA proteins, with binding energies ranging from −5.0 kcal/mol to −9.0 kcal/mol. Further molecular dynamics (MD) simulations confirmed the stable binding of metabolites near the Zn binding site, consistent with known compound interactions. These results highlight the potential health benefits of blueberry metabolites through interaction with CA proteins. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Recent work examined the influence of topically applied just‐add‐water creams containing Lactobacillus plantarum probiotic cultures on to reconstructed human epidermis (RHE). The ability to blend various quiescent probiotic powders in topical systems allows for the examination of these powders on RHEs employing various individual quiescent probiotics using human gene microarrays.Four topical Just‐Add‐Water powders (STRATABIOSYS™ Technologies) were prepared containing the following: (1) Lactobacillus plantarum Lp90 [200 M CFU/g]; (2) Saccharomyces cerevisiae [200 M CFU/g]; (3) Streptococcus thermophilus [200 M CFU/g]; and (4) Lactococcus Lactis LLa61 [200 M CFU/g]. A powder without probiotics was used as a placebo control. The creams were prepared by taking 3% of each powder and dissolving it into sterile water. A 15 μL sample of each cream was applied to a RHE tissue that presented approximately 90 K CFU/g of each microorganism on the tissue. The RHE was treated for 24 h with the creams whereupon the residual cream was rinsed off, and the tissues were analysed using Agilent human gene microarrays containing 19 217 individual genes from which a smaller subset of 244 genes pertinent to skin were culled.The following probiotic specific gene responses were found: (1) Lactobacillus plantarum upregulated 4.9% of the skin‐relevant gene set; (2) Saccharomyces cerevisiae upregulated 7.8% of the skin relevant gene set; Streptococcus thermophilus upregulated 6.1% of the skin relevant gene set; Lactococcus lactis upregulated 7.0% of the skin relevant gene set.A method to examine topical probiotics on RHE has been described that involves converting the powders to preservative‐free creams. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are differentially expressed genes in acute intracerebral hemorrhage, which are related to the occurrence and development of intracerebral hemorrhage OBJECTIVE: To screen differentially expressed genes and key genes in brain tissue of a rat model with acute intracerebral hemorrhage, to validate them through qPCR, and to analyze the relationships between key genes and the neurological function and brain tissue water content after intracerebral hemorrhage. METHODS: Seventy-eight Sprague-Dawley rats were randomly divided into two groups: in intracerebral hemorrhage group, a rat model of acute intracerebral hemorrhage was made using collagenase injection at the right caudate nucleus; and in sham-operated group, rats were injected with equal amount of saline at the same site. RNA was extracted from rat brain tissues of both groups using the TRIzol method and transcriptome sequencing technology was used to identify differentially expressed genes in brain tissues of acute intracerebral hemorrhage, which were then verified by qPCR and analyzed for the relationships between the genes and neurological function and brain tissue water content after intracerebral hemorrhage. And the key genes were analyzed by GO and KEGG functional enrichment analysis in combination with bioinformatics. RESULTS AND CONCLUSION: Ten key genes were identified, including CXCL8, SERPINE1, TFPI2, CXCR4, GDA, KCNQ5, ERICH3, SCN3B, CACNA1E, and CCL20. The contents of GDA, KCNQ5, ERICH3, SCN3B, and CACNA1E in the intracerebral hemorrhage group were lower than those in the sham-operated group (P < 0.05). The contents of CXCL8, SERPINE1, TFPI2, CXCR4 and CCL20 in the intracerebral hemorrhage group were higher than those in the sham-operated group (P < 0.05). The contents of GDA, KCNQ5, ERICH3, SCN3B, and CACNA1E were positively correlated with brain tissue water content and neurologic deficit score (P < 0.05), while the contents of CXCL8, SERPINE1, TFPI2, CXCR4 and CCL20 were negatively correlated with brain tissue water content and neurologic deficit score (P < 0.05). GO analysis indicated that differentially expressed genes were mainly enriched in two biological processes (leukocyte chemotaxis and chemokine-mediated signaling pathways), two cell components (cation channel complexes and ion channel complexes), and two molecular functions (gated channel activity and ion channel activity). KEGG analysis indicated that differentially expressed genes were concentrated in tumor necrosis factor signaling pathway, glutamatergic synapses and GABAergic synapses. To conclude, the differentially expressed genes in intracerebral hemorrhage include CXCL8, SERPINE1, TFPI2, CXCR4, GDA, KCNQ5, ERICH3, SCN3B, CACNA1E, and CCL20, and these genes are related to brain tissue water content and neurological function after intracerebral hemorrhage. These genes are mainly enriched in cell components, binding functions, cellular protrusions, and other related biological functions. [ABSTRACT FROM AUTHOR]

Soybean is one of the world's most economically significant crops and is widely utilized as an essential source of vegetable protein and edible oil. Cultivated soybean is domesticated from its annual counterpart, wild soybean, which is considered valuable germplasm for soybean breeding. However, wild soybean accessions generally produce seeds with impermeable coats, a trait known as hard seededness (HS), which is beneficial for long-term seed survival but is undesirable for the uniform water absorption and germination of seeds, thus limiting the utilization of wild soybeans in breeding. In addition, moderate HS can isolate the embryo from the surrounding environment and is thus beneficial for long-term seed storage and germplasm preservation. The HS trait is primarily associated with the structure and chemical composition of the seed coat. Moreover, its development is also influenced by various environmental conditions, such as water and temperature. Genetic analysis has revealed that HS of soybean is a complex quantitative trait controlled by multiple genes or minor quantitative trait loci (QTL), with many QTLs and several causal genes currently identified. Investigating the physiological and molecular mechanisms underlying this trait is crucial for soybean breeding, production, and food processing. For this article, the literature was reviewed and condensed to create a well-rounded picture of the current understanding of internal and external factors, QTLs, causal genes, and the regulatory mechanisms related to the HS of soybean, with the aim of providing reference for future research and utilization of this trait. [ABSTRACT FROM AUTHOR]

Phosphorus deficiency and aluminum toxicity in acidic soils are important factors that limit crop yield. To further explore this issue, we identified 18 members of the StPHR gene family in the potato genome in this study. Through bioinformatics analysis, we found that the StPHR1 gene, an important member of this family, exhibited high expression levels in potato roots, particularly under conditions of phosphorus deficiency and aluminum toxicity stress. This suggested that the StPHR1 gene may play a crucial regulatory role in potato's resistance to phosphorus deficiency and aluminum toxicity. To validate this hypothesis, we conducted a series of experiments on the StPHR1 gene, including subcellular localization, GUS staining for tissue expression, heterologous overexpression, yeast two-hybrid hybridization, and bimolecular fluorescence complementation (BiFC). The results demonstrated that the StPHR1 gene is highly conserved in plants and is localized in the nucleus of potato cells. The heterologous overexpression of the gene in Arabidopsis plants resulted in a growth phenotype that exhibited resistance to both aluminum toxicity and phosphorus deficiency. Moreover, the heterologous overexpressing plants showed reduced aluminum content in the root system compared to the control group. Furthermore, we also identified an interaction between StPHR1 and StALMT6. These results highlight the potential application of regulating the expression of the StPHR1 gene in potato production to enhance its adaptation to the dual stress of phosphorus deficiency and high aluminum toxicity in acidic soils. [ABSTRACT FROM AUTHOR]

BACKGROUND: The BRCA2 gene is an important tumour suppressor in breast cancer, and alterations in BRCA2 may lead to cancer progression. The aim of the study was to investigate the association of hypermethylation of the BRCA2 gene promoter and its co-hypermethylation with the BRCA1 gene promoter with the development and course of breast cancer in women. METHODS: This study included 74 women with breast cancer (tumour tissue samples and peripheral blood) and 62 women without oncological pathology (peripheral blood) – control group. RESULTS: Hypermethylation of the BRCA2 gene was significantly more frequently detected in the tumour tissue of women with breast cancer compared to their peripheral blood and peripheral blood of control subjects (p = 0.0006 and p = 0.00001, respectively). Hypermethylation of BRCA2 was more frequently detected in patients with breast cancer over the age of 50 and in patients with higher Ki67 expression levels (p = 0.045 and p = 0.045, respectively). There was a high frequency of unmethylated BRCA1 and BRCA2 gene combination in women of the control group compared to women with breast cancer, both in blood samples and tumour tissue samples (p = 0.014 and p = 0.00001, respectively). CONCLUSION: Our study confirms the hypothesis that BRCA2 hypermethylation plays an important role in the pathogenesis of breast cancer and the importance of assessing its co-hypermethylation with BRCA1 in predicting the course of the disease. [ABSTRACT FROM AUTHOR]

Plant-derived exosomes (PDEs) are natural extracellular vesicles. Research on them has called attention to advances in cancer treatment in recent years. Cancer is the global health crisis of our time and requires treatment that is effective, cost-effective, and has fewer side effects. New studies based on PDEs show that they have great potential to be considered as a therapeutic option. Research results show that the internal molecular charge of PDEs has less toxicity and they have effective anti-cancer activity. The main components of PDEs are lipids, proteins, DNA, and RNA. This review analyzed the available research on the factors that play a role in the effectiveness of the mechanism of action of plant-derived exosomes, based on their potential for medical purposes. As a result of the research, it was determined that the interaction with genes, the form of acquisition, which part of the plant to use, and whether or not an auxiliary agent is used, play an important role in the mechanism of action of such PDEs. It should be noted that the exosomes of each of the investigated plants did not have the same effect on all types of diseases, and their effectiveness varied depending on the diseases. [ABSTRACT FROM AUTHOR]

Cowden syndrome (CS) is a rare autosomal dominant genodermatosis caused by a heterozygous germline mutation in the PTEN gene, found in nearly 80% of cases. It is characterized by multiple benign hamartomas which manifest across various organs. This condition is further distinguished by its association with macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and a heightened susceptibility to certain malignant neoplasms, particularly affecting the thyroid, endometrium, and the breast (OMIM no. 58350). In this report, we detail the case of an Indian patient presenting with macrocephaly and multiple blackish pigmented areas on the face, alongside several small papules on the dorsum of the hands, and the presence of gastric and duodenal polyps, among other symptoms. Genetic analysis through Sanger sequencing of the PTEN gene revealed a heterozygous nonsense pathogenic variant (ENST00000371953.8: c.388C > T, p.Arg130Ter), thereby confirming a CS diagnosis. The report encompasses a comprehensive review of the existing literature, emphasizing the significance of genetic evaluation and discussing the intricacies of managing patients diagnosed with CS. [ABSTRACT FROM AUTHOR]

Background: Brugada syndrome (BrS) is an inherited primary channelopathy syndrome associated with the risk of ventricular fibrillation (VF) and sudden cardiac death in a structurally normal heart. Aim of the Study: The aim of this study was to clinically and genetically evaluate a large family with severe autosomal dominant Brugada syndrome. Methods: Clinical and genetic studies were performed. Genetic analysis was conducted with NGS technologies (WES) using the Illumina instrument. According to the standard procedure, variants found by WES were confirmed in all available families by Sanger sequencing. The effect of the variants was studied by using in silico prediction of pathogenicity. Results: The proband was a 52-year-old man who was admitted to the emergency department for syncope at rest. WES of the index case identified a heterozygous VUS CASQ2, c.532T>C, p.(Tyr178His). We studied the segregation of the variation in all pedigree members. All the patients were heterozygous for the variation CASQ2 p.(Tyr178His), whereas the remaining healthy individuals in the family were homozygous for the normal allele. Structural analysis of CASQ2 p.(Tyr178His) was performed and revealed an important effect of the missense variation on monomer stability. The CASQ2 Tyr180 residue is located inside the sarcoplasmic reticulum (SR) junctional face membrane interaction domain and is predicted to disrupt filamentation. Conclusions: Our data suggest that the p.Tyr178His substitution is associated with BrS in the family investigated, affecting the stability of the protein, disrupting filamentation at the interdimer interface, and affecting the subsequent formation of tetramers and polymers that contain calcium-binding sites. [ABSTRACT FROM AUTHOR]

Background: Prior investigation has indicated a link between Hidradenitis suppurativa (HS) and cardiovascular diseases (CVDs), yet the causal relationship (CR) between these conditions remains unresolved. Methods: This investigation utilized bidirectional Mendelian randomization (MR) analysis to determine the CR between HS and CVDs. Genetic instruments for both conditions were sourced from genome‐wide association studies (GWAS). The GWAS summary data for CVD comprised coronary artery disease (CAD), myocardial infarction (MI), coronary atherosclerosis (CA), ischemic stroke (IS), and chronic heart failure (CHF). Four new approaches were added to the inverse variance weighted (IVW) method for the main analysis: weighted median, weighted MR‐Egger, simple mode, and weighted mode. The validity of the causal conclusions was verified by sensitivity tests that included leave‐one‐out analysis, heterogeneity, and pleiotropy. Results: HS and CAD (OR = 1.024; 95%CI: 1.002–1.046, P = 0.033), MI (OR = 1.001; 95%CI: 1.000–1.002, P = 0.033), and CA (OR = 1.001; 95%CI: 1.000–1.002, P = 0.022) were identified to have a positive CR, according to the IVW analysis. Conversely, no significant association was identified between HS and either IS or CHF. Furthermore, the bidirectional analysis indicated no reverse causation between these diseases. Conclusion: The findings of this study suggest a potential CR between HS and CAD, MI, and CA. Additional research is warranted to elucidate the biological mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

BACKGROUND: K.pneumoniae is a gram-negative bacterium belonging to the Enterobacteriaceae family. This microorganism is a part of the healthy microbiome of individuals and colonizes many parts of the body. The incidence of carbapenemresistant Klebsiella pneumoniae (CRKP) infections is increasing globally. In India, around 65% of K. pneumoniae isolates are resistant to carbapenem antibiotics. The blaNDM is the predominant carbapenem-resistant gene in CRKP isolates. AIM AND OBJECTIVE: To Study the Molecular Characterization of blaNDM-1 Resistant genes in Carbapenem Resistance Klebsiella Pneumonia Clinical isolates. MATERIAL AND METHODS:This was a cross sectional study carried out for a period of 1 year i.e, during 2023 to 2024at K.G.M.U, Lucknow . Samples like urine, sputum, ET tube, pleural fluid, pus, CSF, blood and Ascitic fluid were included in this study. Carbapenemase resistance was detected phenotypically by MHT, mCIM and eCIM methods and genotypically by using PCR where the DNA extraction was done and the resistant gene blaNDM-1 was confirmed by PCR assay. RESULT:A total of 350 isolates of K. pneumoniae were collected from patients, with 127(36.28%) identified as CRKP. There were 30 (57.69%) isolates obtained from male and 22(42.30%) were obtained from female, while the maximum number of patients belong to the age group <50 years and maximum patients were engaged as Student/Housewife/Retired (44.09%) followed by Clerical/Shopkeeper/Farmer (36.22%) and others. In our study,it was also observed that, in phenotypic test 81.88% were positive for M-CIM while 77.95% were positive for E-CIM and in genotypic test there were 86.61 % positive for NDM-1. CONCLUSION: The study highlighted the existence of carbapenemase-producing K. pneumoniae, particularly in blaNDM-1, in patients with comorbidities. Our findings emphasize the importance of the molecular characterization of resistance-determinant-carrying bacterial pathogens as a part of infection control and prevention in hospital settings. [ABSTRACT FROM AUTHOR]

Both sleep loss and exercise regulate gene expression in skeletal muscle, yet little is known about how the interaction of these stressors affects the transcriptome. The aim of this study was to investigate the effect of nine nights of sleep restriction (SR), with repeated resistance exercise (REx) sessions, on the skeletal muscle transcriptome of young, trained females. Ten healthy females aged 18–35 yr old undertook a randomized cross-over study of nine nights of SR (5 h time in bed) and normal sleep (NS; ≥7 h time in bed) with a minimum 6-wk washout. Participants completed four REx sessions per condition (days 3, 5, 7, and 9). Muscle biopsies were collected both pre- and post-REx on days 3 and 9. Gene and protein expression were assessed by RNA sequencing and Western blot, respectively. Three or nine nights of SR had no effect on the muscle transcriptome independently of exercise. However, close to 3,000 transcripts were differentially regulated (false discovery rate < 0.05) 48 h after the completion of three resistance exercise sessions in both NS and SR conditions. Only 39% of downregulated genes and 18% of upregulated genes were common between both conditions, indicating a moderating effect of SR on the response to exercise. SR and REx interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested. NEW & NOTEWORTHY: This study investigated the effect of nine nights of sleep restriction, with repeated resistance exercise sessions, on the skeletal muscle transcriptome of young, trained females. Sleep restriction and resistance exercise interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested. [ABSTRACT FROM AUTHOR]

Background and objectives: Positive role of coffee consumption on regulation of human blood sugar has been highlighted by researchers. On the other hand, metformin is the common drug against type 2 diabetes. This study aimed to explore possible ways to use coffee as a complementary agent beside metformin or independently versus type 2 diabetes. Methods: Proteomic data about effect of two major compounds of coffee (caffeine and trigonelline) on improvement of diabetic condition was searched and analyzed via protein-protein interaction (PPI) network analysis and gene ontology enrichment. Gene expression profiles of human whole blood of diabetic patients (responsive to metformin) versus control were extracted from GSE83983 which is recorded in Gene Expression Omnibus (GEO) database. After pre-evaluation of data by GEO2R program, the significant differentially expressed genes (DEGs) were assessed via PPI network analysis and regulatory network evaluation. Results: Caffeine and trigonelline effectively regulate the glycolytic processes to fight against diabetic condition. HSP90AA1, TLR4, RELA, ARRB, LRRK2, STAT5B, LYN, and TLR2 genes that are involved in diabetes were affected significantly by metformin. Conclusion: It can be concluded that coffee consumption can improve sugar regulation in diabetes similar to metformin. IT seems that the optimized consumption quantity of coffee can be considered as controller of blood sugar in diabetic patients. [ABSTRACT FROM AUTHOR]

Mango is a popular tropical fruit that requires quarantine hot water treatment (QHWT) for postharvest sanitation, which can cause abiotic stress. Plants have various defense mechanisms to cope with stress; miRNAs mainly regulate the expression of these defense responses. Proteins involved in the biogenesis of miRNAs include DICER-like (DCL), ARGONAUTE (AGO), HYPONASTIC LEAVES 1 (HYL1), SERRATE (SE), HUA ENHANCER1 (HEN1), HASTY (HST), and HEAT-SHOCK PROTEIN 90 (HSP90), among others. According to our analysis, the mango genome contains five DCL, thirteen AGO, six HYL, two SE, one HEN1, one HST, and five putative HSP90 genes. Gene structure prediction and domain identification indicate that sequences contain key domains for their respective gene families, including the RNase III domain in DCL and PAZ and PIWI domains for AGOs. In addition, phylogenetic analysis indicates the formation of clades that include the mango sequences and their respective orthologs in other flowering plant species, supporting the idea these are functional orthologs. The analysis of cis-regulatory elements of these genes allowed the identification of MYB, ABRE, GARE, MYC, and MeJA-responsive elements involved in stress responses. Gene expression analysis showed that most genes are induced between 3 to 6 h after QHWT, supporting the early role of miRNAs in stress response. Interestingly, our results suggest that mango rapidly induces the production of miRNAs after heat stress. This research will enable us to investigate further the regulation of gene expression and its effects on commercially cultivated fruits, such as mango, while maintaining sanitary standards. [ABSTRACT FROM AUTHOR]

Objective: Lung adenocarcinoma poses a major global health challenge and is a leading cause of cancer-related deaths worldwide. This study is a review of three molecular biomarkers screened by machine learning that are not only important in the occurrence and progression of lung adenocarcinoma but also have the potential to serve as biomarkers for clinical diagnosis, prognosis evaluation and treatment guidance. Methods: Differentially expressed genes (DEGs) were identified using comprehensive GSE1987 and GSE18842 gene expression databases. A comprehensive bioinformatics analysis of these DEGs was conducted to explore enriched functions and pathways, relative expression levels, and interaction networks. Random Forest and LASSO regression analysis techniques were used to identify the three most significant target genes. The TCGA database and quantitative polymerase chain reaction (qPCR) experiments were used to verify the expression levels and receiver operating characteristic (ROC) curves of these three target genes. Furthermore, immune invasiveness, pan-cancer, and mRNA-miRNA interaction network analyses were performed. Results: Eighty-nine genes showed increased expression and 190 genes showed decreased expression. Notably, the upregulated DEGs were predominantly associated with organelle fission and nuclear division, whereas the downregulated DEGs were mainly associated with genitourinary system development and cell-substrate adhesion. The construction of the DEG protein-protein interaction network revealed 32 and 19 hub genes with the highest moderate values among the upregulated and downregulated genes, respectively. Using random forest and LASSO regression analyses, the hub genes were employed to identify three most significant target genes.TCGA database and qPCR experiments were used to verify the expression levels and ROC curves of these three target genes, and immunoinvasive analysis, pan-cancer analysis and mRNA-miRNA interaction network analysis were performed. Conclusion: Three target genes identified by machine learning: BUB1B, CENPF, and PLK1 play key roles in LUAD development of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

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Introduction: Phosphorylation reactions highlight the essential role of protein kinases in sperm motility. TSSK6 protein is thought to play a crucial role in this process. Indeed, sperm obtained from mice with the Tssk6-/-genotype are unable to carry out fertilization and exhibit decreased motility. This leads us to investigate the causes of asthenozoospermia by searching for polymorphisms in the TSSK6 gene. Therefore, the objective of this study is to identify polymorphisms in the TSSK6 gene in men affected by asthenozoospermia. Material & Methods: The methodology involved direct sequencing of spermatozoa DNA. Thirty ejaculates were analyzed, including 20 from asthenozoospermic men and 10 from normozoospermic men. Spermograms were performed according to WHO procedures. DNA extraction was carried out using the phenol/chloroform method followed by conventional PCR. The amplicons were sequenced using the Sanger method, and the sequences were analyzed with BioEdit software. The data were analyzed using Fisher and Mann-Whitney tests. Results: The results revealed mutations in the TSSK6 gene in both normospermic and asthenozoospermic ejaculates. The synonymous mutations c.690T>C (p.Tyr230Tyr) and c.372C>A (p.Arg124Arg) were the most frequent, occurring at rates of 50% and 33.33%, respectively. Analysis of the mutations using PolyPhen-2 indicated that all mutations observed in normozoospermic samples are benign and would not affect sperm quality. However, only the mutations described in asthenozoospermic samples are predicted to be damaging to the protein. Conclusion: In conclusion, mutations in the TSSK6 gene were observed in infertile men. Deleterious mutations in the TSSK6 protein are associated with asthenozoospermia. [ABSTRACT FROM AUTHOR]

Objective Carnosine and anserine affect the meat flavor. The contents of carnosine and anserine in meat are affected by genetic and environmental factors. This study aimed to discover the single-nucleotide polymorphisms (SNPs) in the histamine-N-methyl transferase (HNMT) and histamine-N-methyl transferase-like (HNMT-like) genes and to associate them with the content of carnosine and anserine in Korean native chicken-red brown line (KNC-R). Methods This study used a total of 384 birds (males, n = 192; females, n = 192) aged 10 weeks old, for genotyping HNMT and HNMT-like genes. One synonymous SNP (rs29009298C/T) of the HNMT gene was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) methods whereas four missense SNPs (rs734406537G/A; rs736514667A/G; rs15881680G/A and rs316765035T/C) of the HNMT gene, and one missense SNP rs737657949A/C of the HNMT-like gene were genotyped by PCR allele competitive extension (PACE) genotyping technology. Two-way analysis of variance of the R program was used to associate HNMT genotypes with the contents of carnosine and anserine in KNC-R chickens. Results There were significant associations (p

Abstract Single nucleotide polymorphisms (SNPs) could increase the susceptibility of individuals to develop obesity and type 2 diabetes (T2DM). Obesity and T2DM are closely related pathophysiologically, thus similar SNPs could mediate both these diseases, but this is rarely reported. Furthermore, limited studies have been performed to summarize SNP data in the Asian population compared to the Western population. In this study, we aimed to summarize SNPs that are associated with the development of obesity and T2DM among Asian populations. We searched six literature databases and Review Manager (RevMan) was used for meta-analysis. The pooled odds ratios (ORs) and 95% CIs were calculated with a random effects model for the heterogeneity among studies. The pooled analysis showed that rs9939609 (FTO gene) and rs17782313 and rs571312 (MC4R gene) are associated with obesity with an odd ratio (OR) of 1.37, 1.36 and 1.29 respectively. For T2DM, five SNPs, rs7903146 and rs12255372 (TCF7L2 gene), rs13266634 and rs11558471 (SLC30A8 gene) and rs2283228 (KCNQ1 gene) have also shown strong associations with T2DM at OR of 1.64, 1.61, 1.22, 1.29 and 1.60 respectively. This data could be used to develop a gene screening panel for assessing obesity and T2DM susceptibility.

Abstract Background Osteoarthritis (OA) is the most prevalent type of arthritis and the main reason for progressive disability in middle-aged and older people. Studies of candidate genes may provide a novel insight and treatment strategy for knee osteoarthritis (KOA). The aim of this study was to investigate the relationship between KOA susceptibility and single-nucleotide polymorphism (SNP) of the ADAMTS-5 gene. Materials and methods The case group included 188 patients from Luoyang Orthopedic Hospital with clinically and radiographically diagnosed primary KOA, and the control group included 100 age-matched individuals without KOA. Fifteen ADAMTS-5 SNPs were assayed using MALDI-TOF MS. Allelic and haplotypic frequencies were compared between the groups. The relationship between genotype distribution and risk of KOA was analyzed by multivariate logistic regression. Results The frequency of A allele in rs2249350 site in the KOA group was significantly lower (odds ratio [OR]: 0.761; 95% confidence interval [95% CI]: 0.612–0.947; P = 0.016), while that of C allele was higher than that in the control group (OR: 1.176; 95% CI: 1.025–1.351; P = 0.016). AA genotype and gene model, especially recessive gene model at rs2249350 locus, negatively correlated with KOA risk after adjustment for sex, body mass index, age, and occupation (AA vs. CC: OR: 0.288; 95% CI: 0.124–0.669; P = 0.004; AA vs. CA + CC: OR: 0.348; 95% CI: 0.162–0.749; P = 0.007). Meanwhile, one protective haplotype, GA (rs229054, rs2249350) (OR: 0.763; 95% CI: 0.614–0.949; P = 0.017), and one high-risk haplotype, GC (rs229054, rs2249350) (OR: 1.259; 95% CI: 1.032–1.537; P = 0.019), were found in this study. Conclusion Despite a limited sample size, our study suggests that the rs2249350 polymorphism in the ADAMTS-5 gene is one of the genetic factors influencing the risk of KOA. The A allele and AA genotype of rs2249350 may protect from KOA, whereas C allele and CC genotype increase the risk of KOA. In addition, the GA haplotype (rs229054, rs2249350) might be associated with a decreased risk of KOA, whereas the GC haplotype (rs229054, rs2249350) may be a risk factor for KOA. Additional larger-sized studies in more ethnically diverse populations are needed to confirm these findings.

Abstract Background Selecting informative genes or eliminating uninformative ones before any downstream gene expression analysis is a standard task with great impact on the results. A carefully curated gene set significantly enhances the likelihood of identifying meaningful biomarkers. Method In contrast to the conventional forward gene search methods that focus on selecting highly informative genes, we propose a backward search method, DenoiseIt, that aims to remove potential outlier genes yielding a robust gene set with reduced noise. The gene set constructed by DenoiseIt is expected to capture biologically significant genes while pruning irrelevant ones to the greatest extent possible. Therefore, it also enhances the quality of downstream comparative gene expression analysis. DenoiseIt utilizes non-negative matrix factorization in conjunction with isolation forests to identify outlier rank features and remove their associated genes. Results DenoiseIt was applied to both bulk and single-cell RNA-seq data collected from TCGA and a COVID-19 cohort to show that it proficiently identified and removed genes exhibiting expression anomalies confined to specific samples rather than a known group. DenoiseIt also showed to reduce the level of technical noise while preserving a higher proportion of biologically relevant genes compared to existing methods. The DenoiseIt Software is publicly available on GitHub at https://github.com/cobi-git/DenoiseIt

Abstract Although sex differences have been reported in patients with clear cell renal cell carcinoma (ccRCC), biological sex has not received clinical attention and genetic differences between sexes are poorly understood. This study aims to identify sex-specific gene mutations and explore their clinical significance in ccRCC. We used data from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), The Renal Cell Cancer-European Union (RECA-EU) and Korean-KIRC. A total of 68 sex-related genes were selected from TCGA-KIRC through machine learning, and 23 sex-specific genes were identified through verification using the three databases. Survival differences according to sex were identified in nine genes (ACSS3, ALG13, ASXL3, BAP1, JADE3, KDM5C, KDM6A, NCOR1P1, and ZNF449). Female-specific survival differences were found in BAP1 in overall survival (OS) (TCGA-KIRC, p = 0.004; RECA-EU, p = 0.002; and Korean-KIRC, p = 0.003) and disease-free survival (DFS) (TCGA-KIRC, p = 0.001 and Korean-KIRC, p = 0.000004), and NCOR1P1 in DFS (TCGA-KIRC, p = 0.046 and RECA-EU, p = 0.00003). Male-specific survival differences were found in ASXL3 (OS, p = 0.017 in TCGA-KIRC; and OS, p = 0.005 in RECA-EU) and KDM5C (OS, p = 0.009 in RECA-EU; and DFS, p = 0.016 in Korean-KIRC). These results suggest that biological sex may be an important predictor and sex-specific tailored treatment may improve patient care in ccRCC.

Abstract Cowden syndrome (CS) is a rare autosomal dominant genodermatosis caused by a heterozygous germline mutation in the PTEN gene, found in nearly 80% of cases. It is characterized by multiple benign hamartomas which manifest across various organs. This condition is further distinguished by its association with macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and a heightened susceptibility to certain malignant neoplasms, particularly affecting the thyroid, endometrium, and the breast (OMIM no. 58350). In this report, we detail the case of an Indian patient presenting with macrocephaly and multiple blackish pigmented areas on the face, alongside several small papules on the dorsum of the hands, and the presence of gastric and duodenal polyps, among other symptoms. Genetic analysis through Sanger sequencing of the PTEN gene revealed a heterozygous nonsense pathogenic variant (ENST00000371953.8: c.388C > T, p.Arg130Ter), thereby confirming a CS diagnosis. The report encompasses a comprehensive review of the existing literature, emphasizing the significance of genetic evaluation and discussing the intricacies of managing patients diagnosed with CS.

Background and objectives: Positive role of coffee consumption on regulation of human blood sugar has been highlighted by researchers. On the other hand, metformin is the common drug against type 2 diabetes. This study aimed to explore possible ways to use coffee as a complementary agent beside metformin or independently versus type 2 diabetes. Methods: Proteomic data about effect of two major compounds of coffee (caffeine and trigonelline) on improvement of diabetic condition was searched and analyzed via protein-protein interaction (PPI) network analysis and gene ontology enrichment. Gene expression profiles of human whole blood of diabetic patients (responsive to metformin) versus control were extracted from GSE83983 which is recorded in Gene Expression Omnibus (GEO) database. After pre-evaluation of data by GEO2R program, the significant differentially expressed genes (DEGs) were assessed via PPI network analysis and regulatory network evaluation. Results: Caffeine and trigonelline effectively regulate the glycolytic processes to fight against diabetic condition. HSP90AA1, TLR4, RELA, ARRB, LRRK2, STAT5B, LYN, and TLR2 genes that are involved in diabetes were affected significantly by metformin. Conclusion: It can be concluded that coffee consumption can improve sugar regulation in diabetes similar to metformin. IT seems that the optimized consumption quantity of coffee can be considered as controller of blood sugar in diabetic patients.

The increasing availability of RNA sequencing data has opened up numerous opportunities to analyze various RNA interactions, including microRNA-target interactions (MTIs). In response to the necessity for a specialized tool to study MTIs in cancer and normal tissues, we developed AmiCa (https://amica.omics.si/), a web server designed for comprehensive analysis of mature microRNA (miRNA) and gene expression in 32 cancer types. Data from 9498 tumor samples and 626 normal samples from The Cancer Genome Atlas were obtained through the Genomic Data Commons and used to calculate differential expression and miRNA-target gene (MTI) correlations. AmiCa provides data on differential expression of miRNAs/genes for cancers for which normal tissue samples were available. In addition, the server calculates and presents correlations separately for tumor and normal samples for cancers for which normal samples are available. Furthermore, it enables the exploration of miRNA/gene expression in all cancer types with different miRNA/gene expression. In addition, AmiCa includes a ranking system for genes and miRNAs that can be used to identify those that are particularly highly expressed in certain cancers compared to other cancers, facilitating targeted and cancer-specific research. Finally, the functionality of AmiCa is illustrated by two case studies.

The exposure of ethanol increases the risk of head and neck inflammation and tumor progression. However, limited studies have investigated the composition and functionality of laryngeal microbiota under ethanol exposure. We established an ethanol-exposed mouse model to investigate the changes in composition and function of laryngeal microbiota using Metagenomic shotgun sequencing. In the middle and late stages of the experiment, the laryngeal microbiota of mice exposed to ethanol exhibited obvious distinguished from that of the control group on principal-coordinate analysis (PCoA) plots. Among the highly abundant species, Salmonella enterica and Mycobacterium marinum were likely to be most impacted. Our findings indicated that the exposure to ethanol significantly increased their abundance in larynxes in mice of the same age, which has been confirmed through FISH experiments. Among the species-related functions and genes, metabolism is most severely affected by ethanol. The difference was most obvious in the second month of the experiment, which may be alleviated later because the animal established tolerance. Notable enrichments concerning energy, amino acid, and carbohydrate metabolic pathways occurred during the second month under ethanol exposure. Finally, based on the correlation between species and functional variations, a network was established to investigate relationships among microbiota, functional pathways, and related genes affected by ethanol. Our data first demonstrated the continuous changes of abundance, function and their interrelationship of laryngeal microbiota under ethanol exposure by Metagenomic shotgun sequencing. Importance: Ethanol may participate in the inflammation and tumor progression by affecting the composition of the laryngeal microbiota. Here, we applied the metagenomic shotgun sequencing instead of 16 S rRNA sequencing method to identify the laryngeal microbiota under ethanol exposure. Salmonella enterica and Mycobacterium marinum are two dominant species that may play a role in the reconstruction of the laryngeal microenvironment, as their local abundance increases following exposure to ethanol. The metabolic function is most evidently impacted, and several potential metabolic pathways could be associated with alterations in microbiota composition. These findings could help us better understand the impact of prolonged ethanol exposure on the microbial composition and functionality in the larynx.

An increase in GDH activity has been established in the first six hours after plants are exposed to hypoxic conditions, which ensures the formation of an adaptive response of cellular metabolism to the lack of oxygen in the cell. A difference in the transcriptional activity of homologous GDH-1 genes in wheat leaves under stress conditions was shown. An increase in the mRNA content of the GDH-1(5A) gene in wheat leaves after plants are exposed to hypoxic conditions is observed in the first hours of the experiment, which correlates with a change in the catalytic activity of glutamate dehydrogenase. Regulation of this gene is carried out by the transcription factor HIF, the specific landing site of which is found in the transcription initiation site of the promoter of this gene. [ABSTRACT FROM AUTHOR]