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]

Graft healing involves a series of cytological and molecular events including wound responses, callus formation and vascular bundle remodelling. Hormones are important signalling molecules regulating plant development and responses to environmental stimuli. However, the detailed dynamics of phytohormones in graft healing remain elusive. In this research, internodes above and below the graft site were harvested from 0 to 168 h after grafting (HAG), and liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determinate jasmonic acid, auxin, cytokinin, ethylene, salicylic acid, abscisic acid and gibberellin levels during the graft healing process. Uniform manifold approximation and projection (UMAP) and k-means analyses were performed to explore hormone spatio-temporal dynamics. We found the stage-specific and asymmetric accumulation of phytohormones in the tomato graft healing process. At the early healing stage (before vascular bundle reconnection), IAA, cZ, ABA, JA and SA mainly accumulated above the graft site, while tZ and ACC mainly accumulated below the graft site. MEIAA, ICAld and IP mainly accumulated at the later stage. Comminated with the healing process, we suggested that JA is mainly involved in wound responses, IAA is beneficial to the formation of callus and vascular cell development, tZ promotes cell division, and IP is linked to vascular bundle remodelling. In addition, expression of JA-related genes SlMYC2 and SlJAZ2, IAA-related gene SlIAA1, tZ-related genes SlHP2 and SlRR8, and IP-related gene SlRR9 correlated with hormone accumulation. The findings provide important information about the hormones and genes involved in the tomato graft healing process. [ABSTRACT FROM AUTHOR]

A growing number of genes have been identified in individuals with cerebral palsy (CP); however, many of these studies have poor compliance with the cerebral palsy clinical description. This systematic review aimed to assess the quality of the cerebral palsy clinical description/phenotype in cerebral palsy genetic studies published between 2010 and 2024 and report clinically relevant genes based on the quality of the cerebral palsy phenotype. An expert panel developed 6 criteria to review the reported cerebral palsy phenotype/description for each included study. Clinically relevant genes were extracted from each study and stratified into 2 tiers based on the quality. Eighteen studies were included. There was high confidence in the reported cerebral palsy description/phenotype from 8 studies. Of the initial 373 clinically relevant genes, 85 were tier II genes. Individual cerebral palsy motor disorder and phenotype data were absent for 349 of these individuals, limiting further analysis. The tier I gene list was composed of 6 genes: ATL1, COL4A1, GNAO1, KIF1A, SPAST, and TUBA1A. Bilateral spasticity was the most common motor disorder reported in individuals with variants in all 6 genes, and most individuals had accompanying conditions. Prioritizing the accurate reporting of motor and nonmotor phenotypes is crucial for future cerebral palsy genetic studies to further understand the underlying neurobiology. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the association of MSX1 gene variants rs3821949 and rs12532 with nonsyndromic cleft lip and/or palate (NSCL/P) in the Pakistani population. Design: Comparative cross-sectional study. Setting: Multicenter of CL/P malformation. Patients/Participants: Unrelated Non-Syndromic cleft Lip/Palate patients and healthy controls were enrolled. Methods: One hundred (n = 100) subjects with NSCL/P and n = 50 unrelated healthy controls were enrolled in a multicenter comparative cross-sectional study. A tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to analyze MSXI gene single nucleotide variants (SNVs). Results: Among 100 NSCL/P subjects, the majority were males (56%; male: female = 1.27: 1). Most of the cases (74%) had cleft lip and palate (CLP) compared to isolated clefts. Genotyping of MSX1 gene variant rs3821949 showed an increased risk for NSCL/P in various genetic models (P < 0.0001), and the A allele exhibited a more than 4-fold increased risk among cases (OR = 4.22: 95% CI = 2.16–8.22; P < 0.0001). Our investigation found no significant difference between the rs12532 variation and NSCL/P. Conclusion: Our study findings suggest that MSX1 gene variants may increase predisposition to NSCL/P in the Pakistani population. Further studies comprising large samples are required to identify the genetic aetiology of NSCL/P among our people. [ABSTRACT FROM AUTHOR]

Context The relationship between the genomic profile and prognosis of advanced thyroid carcinoma requiring drug therapy has not been reported. Objective To evaluate the treatment period and overall survival time for each genetic alteration in advanced thyroid carcinoma that requires drug therapy. Methods We conducted a retrospective observational study using a national database in Japan, which included 552 cases of thyroid carcinoma out of 53 543 patients in the database. Results The database included anaplastic thyroid carcinoma (23.6%), poorly differentiated thyroid carcinoma (10.0%), and differentiated thyroid carcinoma (66.4%). The most common genetic abnormalities were TERT promoter (66.3%), BRAF (56.7%), and TP53 (32.2%). The typical driver genes were BRAF V600E (55.0%), RAS (18.5%), RET fusion (4.7%), NTRK fusion (1.6%), and ALK fusion (0.4%). The most common regimen was lenvatinib, and the time to treatment failure was not different despite the presence of BRAF or RAS mutations. In differentiated thyroid carcinoma and poorly differentiated thyroid carcinoma, TP53 alterations independently predicted worse overall survival (hazard ratio = 2.205, 95% confidence interval: 1.135-4.283). In anaplastic thyroid carcinoma, no genetic alterations were associated with overall survival. Conclusion Genetic abnormalities with treatment options were found in 62.7% of advanced thyroid carcinomas. TP53 abnormality was an independent poor prognostic factor for overall survival in differentiated thyroid carcinoma. The time to treatment failure for lenvatinib was not different based on genetic profile. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE) is a key component of the renin-angiotensin system and plays an important role in homeostasis and maintenance of blood pressure. However, little is known about allele and genotypic frequencies, as well as phenotypic characteristics associated with ACE polymorphism genotypes in South American populations. This study aimed to verify the allelic predominance and genotype frequency of ACE I/D polymorphism in South America and its association with the main diseases and related conditions. We conducted a systematic review considering studies published in the last 25 years available in PubMed, Scielo, LILACS, LIPECS, Coleciona SUS, CUMED, BINACIS, IBECS, and MEDLINE databases, resulting in the inclusion of 121 studies. Quality of the studies was assessed according to the Strengthening the Reporting of Genetic Association (STREGA) guidelines. We mapped the frequency of the ACE I/D polymorphism in South American populations. 8,856 (32.1%) subjects were DD, 13,050 were ID (47.4%), and 5,644 were II (20.5%) carriers. The main associated conditions included systemic arterial hypertension and other cardiovascular conditions, cardiorespiratory or respiratory characteristics, physical activity level, kidney conditions, aging-related diseases, as well as different types of cancers and metabolic conditions. 61.1% of the studies found no significant association between the respective conditions investigated and the ACE I/D polymorphism. Considering DD genotype or D allele, 21.5% of the studies observed negative and 4.9% positive outcomes. Regarding ID genotype, 4.1% of the studies identified negative and 0.8% positive outcomes, and for II genotype or I allele, 4.1% of the results had negative and 10.7% positive associations. [ABSTRACT FROM AUTHOR]

This study investigated the potential role of specific single-nucleotide polymorphisms (SNPs) in the genes Astrotactin 1 (ASTN1), EBF Transcription Factor 1 (EBF1), Eukaryotic Elongation Factor, Selenocysteine-tRNA Specific (EEFSEC), Microtubule-Associated Serine/Threonine Kinase 1 (MAST1), and Tumor Necrosis Factor Alpha (TNF-α) to assess whether these genetic variants contribute to the risk of spontaneous preterm birth (sPTB). A case-control study was conducted involving 573 women from Croatia and Slovenia: 248 with sporadic sPTB (positive personal and negative family history of sPTB before 37 weeks' gestation), 44 with familial sPTB (positive personal and family history of sPTB before 37 weeks' gestation), and 281 control women. The analysis of ASTN1 rs146756455, EBF1 rs2963463, EBF1 rs2946169, EEFSEC rs201450565, MAST1 rs188343966, and TNF-α rs1800629 SNPs was performed using TaqMan real-time PCR. p-values were Bonferroni-adjusted for multiple comparisons. EBF1 SNP rs2963463 was significantly associated with sPTB (p adj = 0.03). Women carrying the CC genotype had a 3–4-times lower risk of sPTB (p adj < 0.0001). In addition, a significant difference in the frequency of the minor C allele was observed when comparing familial sPTB cases with controls (p adj < 0.0001). All other associations were based on unadjusted p-values. The minor T allele of EBF1 SNP rs2946169 was more frequent in sPTB cases overall than in controls, especially in sporadic sPTB (p = 0.045). Similarly, the CC genotype of ASTN1 SNP rs146756455 was more frequent in sporadic sPTB cases compared to controls (p = 0.019). Finally, the TNF-α SNP rs1800629 minor A allele and AA genotype were more common in the familial sPTB group compared to sporadic sPTB and controls (p < 0.05). The EBF1 SNP rs2963463 polymorphism showed a protective effect in the pathogenesis of sPTB, particularly in women carrying the CC genotype. Moreover, EBF1 SNP rs2946169 and ASTN1 SNP rs146756455, as well as TNF-α SNP rs1800629, were associated with an increased risk of sPTB, representing suggestive potential risk factors for sporadic and familial sPTB, respectively. [ABSTRACT FROM AUTHOR]

Currently, pJP4 is one of the best-known plasmids for the biodegradation of xenobiotics that mediate the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D), which is associated with serious health and environmental risks. Although the sequencing and proposed theory of pJP4 formation occurred almost 20 years ago (2004), pJP4 is still the model object of many studies focused on the biodegradation of 2,4-D. The uniqueness of this plasmid is due to the presence of two evolutionarily distinct gene clusters, tfdI and tfdII, controlling the degradation of 2,4-D. Recent advances in plasmid biology, especially those concerning the characterization of new IncP-1 plasmids and the systematization of tfd gene cluster findings, serve as a basis for proposing new insights into the formation of the clusters' architecture of the canonical plasmid, pJP4, and their distribution among other plasmids. In the present work, a comparative genomic and phylogenetic in silico study of plasmids with tfdI and tfdII clusters was carried out. The possible initial distribution patterns of tfdI clusters among plasmids of different incompatibility groups (non-IncP-1) and tfdII clusters among IncP-1 plasmids using the IS1071-based composite transposon were revealed. A new theory on the formation of the architecture of the tfdI and tfdII clusters of pJP4 through sequential internal rearrangements, recombination, and ISJP4 insertion, is proposed. In addition, small gene clusters resulting from internal rearrangements of pJP4 (tfdIISA and ORF31/32) served as fingerprints for exploring the distribution of tfdI and tfdII clusters. The revealed patterns and formulated theory extend the frontiers of plasmid biology and will be beneficial for understanding the role of plasmids in bacterial adaptation to xenobiotic-contaminated environments. [ABSTRACT FROM AUTHOR]

Background: Allergic diseases are systemic chronic inflammatory diseases associated with multiorgan damage and complex pathogenesis. Several studies have revealed the association of gene expression abnormalities with the development of allergic diseases, but the biomedical field still lacks a public platform for comprehensive analysis and visualization of transcriptomic data of allergic diseases. Objective: The aim of the study is to provide a comprehensive web tool for multiple analysis in allergic diseases. Methods: We retrieved and downloaded human and mouse gene expression profile data associated with allergic diseases from the Gene Expression Omnibus (GEO) database and standardized the data uniformly. We used gene sets obtained from the MSigDB database for pathway enrichment analysis and multiple immune infiltration algorithms for the estimation of immune cell proportion. The basic construction of the web pages was based on the Shiny framework. Additionally, more convenient features were added to the server to improve the efficiency of the web pages, such as jQuery plugins and a comment box to collect user feedback. Results: We developed CTPAD, an interactive R Shiny application that integrates public databases and multiple algorithms to explore allergic disease-related datasets and implement rich transcriptomic visualization capabilities, including gene expression analysis, pathway enrichment analysis, immune infiltration analysis, correlation analysis, and single-cell RNA sequencing analysis. All functional modules offer customization options and can be downloaded in PDF format with high-resolution images. Conclusions: CTPAD largely facilitates the work of researchers without bioinformatics background to enable them to better explore the transcriptomic features associated with allergic diseases. CTPAD is available at https://smuonco.shinyapps.io/CTPAD/. [ABSTRACT FROM AUTHOR]

Background: Several observational studies have indicated an association between interstitial cystitis and the composition of the gut microbiota; however, the causality and underlying mechanisms remain unclear. Understanding the link between gut microbiota and interstitial cystitis could inform strategies for prevention and treatment. Methods: A two-sample Mendelian randomization analysis was conducted using published genome-wide association study summary statistics. We employed inverse variance weighted, weighted mode, MR-Egger, weighted median, simple mode, and cML-MA methods to investigate the causal relationship between gut microbiota and interstitial cystitis. Sensitivity analysis was performed to validate the results. Relevant gut microbiota was examined through reverse MR. Single nucleotide polymorphisms were annotated using FUMA to identify genes associated with these genetic variants, thereby revealing potential host genemicrobiota associations in interstitial cystitis patients. Results: Eight bacterial taxa were identified in our analysis as associated with interstitial cystitis. Among these, Butyricimonas, Coprococcus, Lactobacillales, Lentisphaerae, and Bilophila wadsworthia were positively correlated with interstitial cystitis risk, while taxa such as Desulfovibrio piger, Oscillibacter unclassified and Ruminococcus lactaris exhibited protective effects against interstitial cystitis. The robustness of these associations was confirmed through sensitivity analyses. Reverse MR analysis did not reveal evidence of reverse causality. Single nucleotide polymorphisms were annotated using FUMA and subjected to biological analysis. Seven hub genes (SPTBN1, PSME4, CHAC2, ERLEC1, ASB3, STAT5A, and STAT3) were identified as differentially expressed between interstitial cystitis patients and healthy individuals, representing potential therapeutic targets. Conclusion: Our two-sample Mendelian randomization study established a causal relationship between gut microbiota and interstitial cystitis. Furthermore, our identification of a host gene-microbiota association offers a new avenue for investigating the potential pathogenesis of interstitial cystitis and suggests avenues for the development of personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) characterized by significant impairments in social, communicative, and behavioral abilities. However, only a limited number of studies address the genetic basis of ASD in the African population. This study aims to document the genes associated with ASD in Africa and the techniques used to identify them. Additionally, genes identified elsewhere but not yet in Africa are also noted. Methods: Online databases such as Wiley Online Library, PubMed, and Africa Journal Online were used. The review was conducted using the keyword related to genetic and genomic ASD study in the African population. Result: In this scoping review, 40 genetic studies on ASD in Africa were reviewed. The Egyptian and South African populations were the most studied, with 25 and 5 studies, respectively. Countries with fewer studies included Tunisia (4), East African countries (3), Libya (1), Nigeria (1), and Morocco (1). Some 61 genes responsible for ASD were identified in the African population: 26 were identified using a polymerase chain reaction (PCR)-based method, 22 were identified using sequencing technologies, and 12 genes and one de novo chromosomal aberration were identified through other techniques. No African study identified any ASD gene with genome-wide association studies (GWAS). Notably, at least 20 ASD risk genes reported in non-African countries were yet to be confirmed in Africa's population. Conclusion: There are insufficient genetic studies on ASD in the African population, with sample size being a major limitation in most genetic association studies, leading to inconclusive results. Thus, there is a need to conduct more studies with large sample sizes to identify other genes associated with ASD in Africa's population using high-throughput sequencing technology. [ABSTRACT FROM AUTHOR]

Background: Several observational studies have indicated an association between interstitial cystitis and the composition of the gut microbiota; however, the causality and underlying mechanisms remain unclear. Understanding the link between gut microbiota and interstitial cystitis could inform strategies for prevention and treatment. Methods: A two-sample Mendelian randomization analysis was conducted using published genome-wide association study summary statistics. We employed inverse variance weighted, weighted mode, MR-Egger, weighted median, simple mode, and cML-MA methods to investigate the causal relationship between gut microbiota and interstitial cystitis. Sensitivity analysis was performed to validate the results. Relevant gut microbiota was examined through reverse MR. Single nucleotide polymorphisms were annotated using FUMA to identify genes associated with these genetic variants, thereby revealing potential host genemicrobiota associations in interstitial cystitis patients. Results: Eight bacterial taxa were identified in our analysis as associated with interstitial cystitis. Among these, Butyricimonas, Coprococcus, Lactobacillales, Lentisphaerae, and Bilophila wadsworthia were positively correlated with interstitial cystitis risk, while taxa such as Desulfovibrio piger, Oscillibacter unclassified and Ruminococcus lactaris exhibited protective effects against interstitial cystitis. The robustness of these associations was confirmed through sensitivity analyses. Reverse MR analysis did not reveal evidence of reverse causality. Single nucleotide polymorphisms were annotated using FUMA and subjected to biological analysis. Seven hub genes (SPTBN1, PSME4, CHAC2, ERLEC1, ASB3, STAT5A, and STAT3) were identified as differentially expressed between interstitial cystitis patients and healthy individuals, representing potential therapeutic targets. Conclusion: Our two-sample Mendelian randomization study established a causal relationship between gut microbiota and interstitial cystitis. Furthermore, our identification of a host gene-microbiota association offers a new avenue for investigating the potential pathogenesis of interstitial cystitis and suggests avenues for the development of personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility. [ABSTRACT FROM AUTHOR]

The article considers the distribution and mechanisms of the meiotic drive as a phenomenon manifested in unequal transmission of gene alleles and/or homologous chromosomes into gametes during meiosis. The meiotic drive has been studied in the most detail in Drosophila, mice, corn, and ascomycete fungi of the genera Neurospora and Podospora. The consequence of the meiotic drive is a shift in the frequencies of alleles in the gene pool and the maintenance of nonadaptive traits in the population. [ABSTRACT FROM AUTHOR]

Seaweed farming is the single largest aquaculture commodity with >30 million tonnes produced each year. Furthermore, the restoration of lost seaweed forests is gaining significant momentum, particularly for kelps in warming temperate areas. Whether in aquaculture settings, following restoration practices, or in the wild, all seaweeds undergo biotic interactions with a diverse range of co‐occurring or cocultured organisms. To date, most research assessing such biotic interactions has focused on the response of the organism interacting with seaweeds, rather than on the seaweeds themselves. However, understanding how seaweeds respond to other organisms, particularly on a molecular scale, is crucial for optimizing outcomes of seaweed farming or restoration efforts and, potentially, also for the conservation of natural populations. In this systematic review, we assessed the molecular processes that seaweeds undergo during biotic interactions and propose priority areas for future research. Despite some insights into the response of seaweeds to biotic interactions, this review specifically highlights a lack of characterization of biomolecules involved in the response to chemical cues derived from interacting organisms (four studies in the last 20 years) and a predominant use of laboratory‐based experiments conducted under controlled conditions. Additionally, this review reveals that studies targeting metabolites (70%) are more common than those examining the role of genes (22%) and proteins (8%). To effectively inform seaweed aquaculture efforts, it will be crucial to conduct larger scale experiments simulating natural environments. Also, employing a holistic approach targeting genes and proteins would be beneficial to complement the relatively well‐established role of metabolites. [ABSTRACT FROM AUTHOR]

Purpose: Hyperglycemia is affected by lifestyle and genetic factors. We investigated if dietary patterns associate with glycemia in individuals with high or low genetic risk for type 2 diabetes (T2D). Methods: Men (n = 1577, 51–81 years) without T2D from the Metabolic Syndrome in Men (METSIM) cohort filled a food-frequency questionnaire and participated in a 2-hour oral glucose tolerance test. Polygenetic risk score (PRS) including 76 genetic variants was used to stratify participants into low or high T2D risk groups. We established two data-driven dietary patterns, termed healthy and unhealthy, and investigated their association with plasma glucose concentrations and hyperglycemia risk. Results: Healthy dietary pattern was associated with lower fasting and 2-hour plasma glucose, glucose area under the curve, and better insulin sensitivity (Matsuda insulin sensitivity index) and insulin secretion (disposition index) in unadjusted and adjusted models, whereas the unhealthy pattern was not. No interaction was observed between the patterns and PRS on glycemic measures. Healthy dietary pattern was negatively associated with the risk for hyperglycemia in an adjusted model (OR 0.69, 95% CI 0.51–0.95, in the highest tertile), whereas unhealthy pattern was not (OR 1.08, 95% CI 0.79–1.47, in the highest tertile). No interaction was found between diet and PRS on the risk for hyperglycemia (p = 0.69 for healthy diet, p = 0.54 for unhealthy diet). Conclusion: Our findings suggest that healthy diet is associated with lower glucose concentrations and lower risk for hyperglycemia in men with no interaction with the genetic risk. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans is one of the most popular model organisms used to genetically dissect complex biological phenomena. One common technique used routinely in the C. elegans laboratory is the generation of strains carrying combinations of genetic mutations via classical genetic crosses. Here, we have developed a simple and convenient application to quickly identify useful genetic markers (phenotypical and fluorescent) and their chromosomal positions to aid in the development of genetic cross strategies. The user-friendly software identifies and prioritizes markers with the least genetic distance to a gene of interest, as well as displays the strain name, ease of scoring, nature of the marker (fluorescent transgene or phenotypic information), mating efficiency, and number of available alleles. In addition, recombination frequencies between the gene of interest and each genetic marker are calculated automatically. The application, called "SoMarker," is designed for both MacOS and Windows environments and is available to freely download and modify through open-source software. [ABSTRACT FROM AUTHOR]

After COVID-19, a turning point in the way of pharmaceutical technology is gene therapy with beneficial potential to start a new medical era. However, commercialization of such pharmaceuticals would never be possible without the help of nanotechnology. Nanomedicine can fulfill the growing needs linked to safety, efficiency, and site-specific targeted delivery of Gene therapy-based pharmaceuticals. This review's goal is to investigate how nanomedicine may be used to transfer nucleic acids by getting beyond cellular and physicochemical barriers. Firstly, we provide a full description of types of gene therapy, their mechanism, translation, transcription, expression, type, and details of diseases with possible mechanisms that can only be treated with genes-based pharmaceuticals. Additionally, we also reviewed different types of physicochemical barriers, physiological and cellular barriers in nucleic acids (DNA/RNA) based drug delivery. Finally, we highlight the need and importance of cationic lipid-based nanomedicine/nanocarriers in gene-linked drug delivery and how nanotechnology can help to overcome the above-discussed barrier in gene therapy and their biomedical applications. [ABSTRACT FROM AUTHOR]

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]

Primary cilia (PC) are microtubules-based, independent antennal-like sensory organelles, that are seen in most vertebrate cells of different types, including astrocytes and neurons. They send signals to cells to control many physiological and cellular processes by detecting changes in the extracellular environment. Parkinson's disease (PD), a neurodegenerative disease that progresses over time, is primarily caused by a gradual degradation of the dopaminergic pathway in the striatum nigra, which results in a large loss of neurons in the substantia nigra compact (SNpc) and a depletion of dopamine (DA). PD samples have abnormalities in the structure and function of PC. The alterations contribute to the cause, development, and recovery of PD via influencing signaling pathways (SHH, Wnt, Notch-1, α-syn, and TGFβ), genes (MYH10 and LRRK2), defective mitochondrial function, and substantia nigra dopaminergic neurons. Thus, restoring the normal structure and physiological function of PC and neurons in the brain are effective treatment for PD. This review summarizes the function of PC in neurodegenerative diseases and explores the pathological mechanisms caused by PC alterations in PD, in order to provide references and ideas for future research. [ABSTRACT FROM AUTHOR]

Exposure to lead (Pb) has harmful effects on the organs of both humans and animals, particularly the spleen. However, the precise mechanisms through which Pb (IV) exposure leads to spleen toxicity remain unclear. Hence, this study aimed to identify the key genes and signaling pathways involved in spleen toxicity caused by Pb (IV) incubation. We obtained the dataset GSE59925 from the Gene Expression Omnibus, which included spleen samples treated with lead tetraacetate (PbAc4) as well as control samples on the 1st and 5th day. Through differential expression analysis, we identified 607 and 704 differentially expressed genes (DEGs) in the spleens on the 1st and 5th day following PbAc4 treatment, respectively, with 245 overlapping DEGs between the two time points. Gene ontology analysis revealed that the commonly shared DEGs were primarily involved in signal transduction, drug response, cell proliferation, adhesion, and migration. Pathway analysis indicated that the common DEGs were primarily associated with MAPK, TNF, cAMP, Hippo, and TGF-β signaling pathways. Furthermore, we identified the hub genes such as CXCL10, PARP1, APOE, and VDR contributing to PbAc4-induced spleen toxicity. This study enhances our understanding of the molecular mechanisms underlying Pb (IV) toxicity in the spleen. [ABSTRACT FROM AUTHOR]

Although white matter (WM) accounts for nearly half of adult brain, its wiring diagram is largely unknown. Here, an approach is developed to construct WM networks by estimating interregional morphological similarity based on structural magnetic resonance imaging. It is found that morphological WM networks showed nontrivial topology, presented good‐to‐excellent test‐retest reliability, accounted for phenotypic interindividual differences in cognition, and are under genetic control. Through integration with multimodal and multiscale data, it is further showed that morphological WM networks are able to predict the patterns of hamodynamic coherence, metabolic synchronization, gene co‐expression, and chemoarchitectonic covariance, and associated with structural connectivity. Moreover, the prediction followed WM functional connectomic hierarchy for the hamodynamic coherence, is related to genes enriched in the forebrain neuron development and differentiation for the gene co‐expression, and is associated with serotonergic system‐related receptors and transporters for the chemoarchitectonic covariance. Finally, applying this approach to multiple sclerosis and neuromyelitis optica spectrum disorders, it is found that both diseases exhibited morphological dysconnectivity, which are correlated with clinical variables of patients and are able to diagnose and differentiate the diseases. Altogether, these findings indicate that morphological WM networks provide a reliable and biologically meaningful means to explore WM architecture in health and disease. [ABSTRACT FROM AUTHOR]

Primary congenital glaucoma (PCG) occurs in children due to developmental abnormalities in the trabecular meshwork and anterior chamber angle. Previous studies have implicated rare variants in CYP1B1, LTBP2, and TEK and their interactions with MYOC, FOXC1, and PRSS56 in the genetic complexity and clinical heterogeneity of PCG. Given that some of the gene-encoded proteins are localized in the centrosomes (MYOC) and perform ciliary functions (TEK), we explored the involvement of a core centrosomal protein, CEP164, which is responsible for ocular development and regulation of intraocular pressure. Deep sequencing of CEP164 in a PCG cohort devoid of homozygous mutations in candidate genes (n = 298) and controls (n = 1757) revealed CEP164 rare pathogenic variants in 16 cases (5.36%). Co-occurrences of heterozygous alleles of CEP164 with other genes were seen in four cases (1.34%), and a physical interaction was noted for CEP164 and CYP1B1 in HEK293 cells. Cases of co-harboring alleles of the CEP164 and other genes had a poor prognosis compared with those with a single copy of the CEP164 allele. We also screened INPP5E, which synergistically interacts with CEP164, and observed a lower frequency of pathogenic variants (0.67%). Our data suggest the potential involvements of CEP164 and INPP5E and the yet unexplored cilia-centrosomal functions in PCG pathogenesis. [ABSTRACT FROM AUTHOR]

We aimed to provide an updated narrative review with respect to the RET pathogenic variants and their implications at the clinical and molecular level in the diagnosis of medullary thyroid cancer (MTC)/multiple endocrine neoplasia (MEN) type 2, particularly with respect to the presence of cutaneous lichen amyloidosis (CLA). We searched English-language, in extenso original articles with no timeline nor study design restriction that were published on PubMed. A traditional interplay stands for CLA and MTC in MEN2 (not MEN3) confirmation. While the connection has been reported for more than three decades, there is still a large gap in understanding and addressing it. The majority of patients with MEN2A-CLA have RET pathogenic variants at codon 634; hence, it suggests an involvement of this specific cysteine residue in both disorders (most data agree that one-third of C634-positive subjects have CLA, but the ranges are between 9% and 50%). Females seem more prone to MEN2-CLA than males. Non-C634 germline RET pathogenic variants included (at a low level of statistical evidence) the following: RET V804M mutation in exon 14 for MTC-CLA (CLA at upper back); RET S891A mutation in exon 15 binding OSMR variant G513D (familial MTC and CLA comprising the lower legs to thighs, upper back, shoulders, arms, and forearms); and C611Y (CLA at interscapular region), respectively. Typically, CLA is detected at an early age (from childhood until young adulthood) before the actual MTC identification unless RET screening protocols are already applied. The time frame between CLA diagnosis and the identification of RET pathogenic variants was between 5 and 60 years according to one study. The same RET mutation in one family is not necessarily associated with the same CLA presentation. In MTC/MEN2 subjects, the most affected CLA area was the scapular region of the upper back. Alternatively, another hypothesis highlighted the fact that CLA is secondary to long-term prurit/notalgia paresthetica (NP) in MTC/MEN2. OSMR p. G513D may play a role in modifying the evolutionary processes of CLA in subjects co-harboring RET mutations (further studies are necessary to sustain this aspect). Awareness in CLA-positive patients is essential, including the decision of RET testing in selected cases. [ABSTRACT FROM AUTHOR]

Background: Wilson disease (WD) is an autosomal recessive inherited disease caused by ATP7B variants and characterized by copper metabolism defects. However, children with WD are often asymptomatic, making the clinical diagnosis difficult. Therefore, more accurate methods are required for clinical diagnosis. The objective of this study was to highlight the phenotypic and genetic characteristics of children with WD in northeast China. Methods: We retrospectively analyzed the clinical data and gene sequencing results of 65 children with WD from January 1, 2014, to December 31, 2022, at the Shengjing Hospital of China Medical University. All data refer to the time of diagnosis before treatment. Results: The median age at diagnosis was 5 years (range 1.2–15 years). In 50 cases (50/65, 76.9%) patients, routine physical examinations revealed only abnormal liver function. However, they had a significantly negative (p < 0.05) Kayser–Fleischer ring (KF). Children with acute liver failure had significantly increased 24 h urinary copper excretion (p < 0.05). We detected 46 genetic variants of ATP7B, including seven novel variants. The most frequent variant was p.R778L with an allele frequency of 38.7%. Phenotype-genotype correlation analysis suggested that p.R778L was significantly associated with lower serum ceruloplasmin levels and higher zinc levels (p < 0.05). The loss-of-function (LOF) variant was associated with significantly lower albumin levels (p < 0.05). Conclusion: Most children with WD are asymptomatic, which makes early diagnosis of WD difficult. Therefore, clinical and laboratory characteristics as well as genetic testing are essential. p.R778L is the most frequent variant of ATP7B in China and may play an important role in lowering serum ceruloplasmin levels. [ABSTRACT FROM AUTHOR]

In order to improve the breeding level of Xinjiang dairy brown cattle,this study used primer combinations and reagent kits of 93 genetic defect genes and lethal haplotypes in cattle, and randomly sampled 296 dairy type Xinjiang brown cattle to detect causal mutation sites ( SNPs, short segment insertions or deletions) and lethal haplotypes (BH2, BH6, BH14, OH2, OH4, etc. ) of genetic defect genes (such as spinal muscular atrophy, myelin dysplasia, spider leg syndrome, etc. ) and lethal haplotypes (BH2, BH6, BH14, OH2, OH4, etc. ). Carriers of single gene genetic defect genes and carriers of lethal haplotypes were screened out, indicating that BH2, BH6, BH14, and abnormal spinal cord myelin development have a certain proportion in the population of Xinjiang brown cattle mother cows. The statistical analysis of reproductive performance and disease incidence between genetic defect genes and lethal haplotypes in cattle showed significant differences (P< 0. 05); breeding and mating methods were used to breed and produce normal F1 generation (no defective genes or lethal haplotypes were detected) for carrying cattle. The reproductive indicators were analyzed, and the results showed a significant improvement in reproductive performance. Therefore,it is necessary to screen the carrier cows regularly and select and match them reasonably to provide basis for breeding of milk performance, population genetic improvement and protection of genetic resources of Xinjiang brown cattle. [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]

To analyze the N6-methyladenosine (m6A) modification profile in systemic lupus erythematosus (SLE) using bioinformatics methods and public databases. We establish an SLE m6A modification expression profile and analyze the potential roles of m6A-related differentially expressed genes (DEGs) in SLE using public data. DEGs are obtained from the ADEx database, and the m6A modification profile in SLE is analyzed using the m6A GEO dataset (GSE173312). Additionally, we perform GO/Pathway annotation analysis of m6A DEGs using DAVID. In SLE patients, the expression of the m6A writer components RBM15B and the eraser enzyme FTO are downregulated, while the expression of the reader IGFBP3 is upregulated. The SLE m6A modification profile include 181 genes, with 123 genes upregulated and 58 genes downregulated in expression. These genes are primarily involved in biological processes such as cell apoptosis and cell cycle pathways, type I interferon signaling pathway, DNA replication, and B cell MHC II molecule regulation. Abnormalities in PBMCs cell m6A modification are observed in SLE patients and may potentially contribute to the development and occurrence of the disease [ABSTRACT FROM AUTHOR]

Introduction. The Fat Mass and Obesity-Associated (FTO) gene encodes a demethylase, which modulates RNA N6-methyladenosine (m6A) and plays a regulatory role in adipocyte differentiation and the pathogenesis of human obesity. Methods. To understand the potential role of FTO in osteoporosis (OP), we investigated five single nucleotide variations (SNVs) in intron 1 (rs8057044, rs8050136, rs9939609, rs62033406, and rs9930506) of the FTO gene, and a missense SNV i.e., rs3736228 (A1330V), located in exon 18 of the LRP5 gene, in a cohort of postmenopausal women (n = 188) from Central Europe. Genotyping was performed with an allele discrimination assay, while haplotypes were reconstructed in the population by PHASE 2.1. Results. The rs9930506 was strongly associated with OP (p < 0.0035), which was supported by Bonferroni correction (p < 0.0175), and all SNVs located in the FTO gene were more strongly associated with severe OP with fragility fractures. Among seventeen haplotypes detected for the FTO gene, two haplotypes (H1 and H9) were frequent (frequency > 10%) and distributed in three main haplotypes pairs (H1/H1, H1/H9 and H9/H9, respectively). The pathogenic pair H1/H9 was associated with a leaner phenotype, increased fracture risk, and a lower bone mineral density (BMD), and carried the heterozygous GA of rs9930506, while the protective pair H9/H9 was associated with an increased obesity risk and carried AA alleles of rs9939609. Conclusions. Concordant associations with OP, an increased fracture risk, and a lower BMD at all skeletal sites indicate that the FTO gene is a promising candidate for OP, explaining the complex relationship with obesity and offering new perspectives for the study of the epigenetic regulation of bone metabolism. [ABSTRACT FROM AUTHOR]

Understanding the genetic basis of disease is a fundamental aspect of medical research, as genes are the classic units of heredity and play a crucial role in biological function. Identifying associations between genes and diseases is critical for diagnosis, prevention, prognosis, and drug development. Genes that encode proteins with similar sequences are often implicated in related diseases, as proteins causing identical or similar diseases tend to show limited variation in their sequences. Predicting gene–disease association (GDA) requires time-consuming and expensive experiments on a large number of potential candidate genes. Although methods have been proposed to predict associations between genes and diseases using traditional machine learning algorithms and graph neural networks, these approaches struggle to capture the deep semantic information within the genes and diseases and are dependent on training data. To alleviate this issue, we propose a novel GDA prediction model named FusionGDA, which utilizes a pre-training phase with a fusion module to enrich the gene and disease semantic representations encoded by pre-trained language models. Multi-modal representations are generated by the fusion module, which includes rich semantic information about two heterogeneous biomedical entities: protein sequences and disease descriptions. Subsequently, the pooling aggregation strategy is adopted to compress the dimensions of the multi-modal representation. In addition, FusionGDA employs a pre-training phase leveraging a contrastive learning loss to extract potential gene and disease features by training on a large public GDA dataset. To rigorously evaluate the effectiveness of the FusionGDA model, we conduct comprehensive experiments on five datasets and compare our proposed model with five competitive baseline models on the DisGeNet-Eval dataset. Notably, our case study further demonstrates the ability of FusionGDA to discover hidden associations effectively. The complete code and datasets of our experiments are available at https://github.com/ZhaohanM/FusionGDA. [ABSTRACT FROM AUTHOR]

Understanding the pig immune function is crucial for disease-resistant breeding and potentially for human health research due to shared immune system features. Immune cell ratios, like monocyte/lymphocyte ratio (MLR) and neutrophil/lymphocyte ratio (NLR), offer a more comprehensive view of immune status compared to individual cell counts. However, research on pig immune cell ratios remains limited. This study investigated MLR and NLR in a Duroc × Erhualian F2 resource population. Heritability analysis revealed high values (0.649 and 0.688 for MLR and NLR, respectively), suggesting a strong genetic component. Furthermore, we employed an ensemble-like GWAS (E-GWAS) strategy and functional annotation analysis to identify 11 MLR-associated and 6 NLR-associated candidate genes. These genes were significantly enriched in immune-related biological processes. These findings provide novel genetic markers and candidate genes associated with porcine immunity, thereby providing valuable insights for addressing biosecurity and animal welfare concerns in the pig industry. [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]

Several small genetic association studies have been conducted for atypical femur fracture (AFF) without replication of results. We assessed previously implicated and novel genes associated with AFFs in a larger set of unrelated AFF cases using whole exome sequencing (WES). We performed gene-based association analysis on 139 European AFF cases and 196 controls matched for bisphosphonate use. We tested all rare, protein-altering variants using both candidate gene and hypothesis-free approaches. In the latter, genes suggestively associated with AFFs (uncorrected p-values <.01) were investigated in a Swedish whole-genome sequencing replication study and assessed in 46 non-European cases. In the candidate gene analysis, PLOD2 showed a suggestive signal. The hypothesis-free approach revealed 10 tentative associations, with XRN2, SORD, and PLOD2 being the most likely candidates for AFF. XRN2 and PLOD2 showed consistent direction of effect estimates in the replication analysis, albeit not statistically significant. Three SNPs associated with SORD expression according to the GTEx portal were in linkage disequilibrium (R2 ≥ 0.2) with an SNP previously reported in a genome-wide association study of AFF. The prevalence of carriers of variants for both PLOD2 and SORD was higher in Asian versus European cases. While we did not identify genes enriched for damaging variants, we found suggestive evidence of a role for XRN2, PLOD2, and SORD, which requires further investigation. Our findings indicate that genetic factors responsible for AFFs are not widely shared among AFF cases. The study provides a stepping-stone for future larger genetic studies of AFF. Lay Summary: We investigated the genetic factors contributing to atypical femur fractures (AFF), which are rare and unusual fractures in the thigh bone. These fractures are related to the use of bisphosphonates (BP), which are prescribed to prevent fractures caused by osteoporosis. Previous studies suggested potential genetic links, but their findings were not confirmed in larger groups. To address this, we analyzed genetic data from 139 European individuals with AFF and 196 individuals without AFF, all of whom used BP, using a genetic technique called whole exome sequencing. Our results suggested three genes—XRN2, SORD, and PLOD2—might be linked to AFF, although the evidence was not conclusive. Importantly, our findings suggest that AFF may be caused by different genes in different individuals. A much larger sample size is now needed to fully understand the genetic architecture of AFF. These findings may guide future research into the genetic causes of AFF. [ABSTRACT FROM AUTHOR]

Food requirements have always been a top priority, and with the exponential growth of the human population, there is an increasing need for large quantities of food. Traditional cultivation methods are not able to meet the current demand for food products. One significant challenge is the shortened shelf-life of naturally occurring food items, which directly contributes to food scarcity. Contaminating substances such as weeds and pests play a crucial role in this issue. In response, researchers have introduced genetically engineered (GE) food as a potential solution. These food products are typically created by adding or replacing genes in the DNA of naturally occurring foods. GE foods offer various advantages, including increased quality and quantity of food production, adaptability to various climatic conditions, modification of vitamin and mineral levels, and prolonged shelf life. They address the major concerns of global food scarcity and food security. However, the techniques used in the production of GE foods may not be universally acceptable due to the genetic alteration of animal genes into plants or vice versa. Additionally, their unique nature necessitates further long-term studies. This study delves into the procedures and growth stages of DNA sequencing, covering the benefits, risks, industrial relevance, current knowledge, and future challenges of GE foods. GE foods have the potential to extend the shelf life of food items, alleviate food shortages, and fulfill the current nutritional food demand. [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]

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility.

Abstract Background Allergic diseases are systemic chronic inflammatory diseases associated with multiorgan damage and complex pathogenesis. Several studies have revealed the association of gene expression abnormalities with the development of allergic diseases, but the biomedical field still lacks a public platform for comprehensive analysis and visualization of transcriptomic data of allergic diseases. Objective The aim of the study is to provide a comprehensive web tool for multiple analysis in allergic diseases. Methods We retrieved and downloaded human and mouse gene expression profile data associated with allergic diseases from the Gene Expression Omnibus (GEO) database and standardized the data uniformly. We used gene sets obtained from the MSigDB database for pathway enrichment analysis and multiple immune infiltration algorithms for the estimation of immune cell proportion. The basic construction of the web pages was based on the Shiny framework. Additionally, more convenient features were added to the server to improve the efficiency of the web pages, such as jQuery plugins and a comment box to collect user feedback. Results We developed CTPAD, an interactive R Shiny application that integrates public databases and multiple algorithms to explore allergic disease-related datasets and implement rich transcriptomic visualization capabilities, including gene expression analysis, pathway enrichment analysis, immune infiltration analysis, correlation analysis, and single-cell RNA sequencing analysis. All functional modules offer customization options and can be downloaded in PDF format with high-resolution images. Conclusions CTPAD largely facilitates the work of researchers without bioinformatics background to enable them to better explore the transcriptomic features associated with allergic diseases. CTPAD is available at https://smuonco.shinyapps.io/CTPAD/ .

Abstract The mechanisms involved with the pathogenesis of carcinoma ex pleomorphic adenoma (CXPA) seem to be associated with the accumulation of molecular alterations in the pleomorphic adenoma (PA). In this sense, using array-based comparative genomic hybridization (aCGH) a rare series of 27 cases of CXPA and 14 residual PA (rPA) adjacent to the transformation area, we investigated the profile of the copy number alterations (CNAs) comparing benign residual and transformed areas. The main findings were correlated with the histopathological classification by histologic subtype and degree of invasion. The distribution of losses (p = 0.187) and amplifications (p = 0.172) was not statistically different between rPA and CXPA. The number of gains was increased in the transformed areas compared to the benign residual areas (p = 0.005). PLAG1 gain was maintained along the malignant transformation, as it was observed in both residual PA and CXPA samples, likely being an earlier event during transformation. The amplification of GRB7 and ERBB2 may also be an initial step in the malignant transformation of PA to CXPA (salivary duct carcinoma subtype). Furthermore, the amplification of HMGA2 and RPSAP52 were the most prevalent alterations among the studied samples. It was noteworthy that amplified genes in the transformed areas of the tumors were enriched for biological processes related to immune signaling. In conclusion, our results underscored for the first-time crucial CNAs in CXPA, some of them shared with the residual benign area adjacent to the transformation site. These CNAs included PLAG1 gain, as well as amplification of GRB7, ERBB2, HMGA2, and RPSAP52.

Background and objectives: Rutin is a lipophilic natural flavonoid. It is found in vegetables, citrus fruits, and beverages. This study aims to evaluate rutin metabolic pathways in human senescent stromal cells. Methods: Data are extracted from the Gene Expression Omnibus (GEO) database and pre-evaluated via GEO2R to find the significant differentially expressed genes (DEGs). The significant DEGs were assessed via protein-protein interaction PPI network analysis to explore the hub genes. The hubs were screened via directed PPI to find the critical DEGs. Results: Data were assessed via volcano plot, Uniform Manifold Approximation and Projection (UMAP) plot, and Venn diagram. A total number of 9124 significant DEGs were analyzed to determine 33 upregulated and 61 downregulated hubs. The identified hubs were investigated via directed PPI and Il1B. ICAM1, CCL2, EGF, CXCL8, PTGS2, CAMK2B, CCN2, VCAM1, ELN, CXCL12, BGN, and TLR4 were pointed out as critical hub genes. Conclusion: Il1B, CCL2, GNAO1, ICAM1, EGF, and CXCL8 appeared as controller genes affected by rutin while PTGS2 and CAMK2B were the most controlled individuals. The finding refers to the significant advantages of the rutin effect on the function of treated cells. These advantages are corresponded to the usefulness of rutin as an herbal drug candidate. However, more investigations are required to decrease its side effects.

Background and objectives: There is evidence that alcohol consumption is associated with liver damage. The positive role of garlic in preventing liver versus alcohol-related liver disease has been investigated before. In the present study, the possible protective role of garlic oil on the liver versus alcohol was evaluated via protein-protein interaction (PPI) network analysis to provide a new perspective of molecular events. Methods: GSE40334 from the Gene Expression Omnibus (GEO) database was selected for analysis. The significant differential expressed genes (DEGs) were determined by using the GEO2R program. UMAP analysis was applied to explore the separation of samples by analysis. Action map and gene ontology were used via Cytoscape software v 3.7.2 and its applications to find the critical DEGs and biological processes. Results: A number 798 significant DEGs were selected for analysis. The PPI network analysis showed that two clusters of DEGs play significant roles in response to garlic oil. Ranbp2, Pafah1b1, Seh1l, Plk1, Cenpa, Mis12, and Tgfb1 as the crucial DEGs were highlighted. The biological processes related to the essential function of cells such as proliferation and cell division were identified as the regulated biological terms. Conclusion: Garlic oil plays a protective role in preventing liver damage versus consuming alcohol. Among seven crucial genes, six individuals were regulated to enhance liver health.

Keratoconus(KC)is a disease characterized by limited corneal cone-like protrusions accompanied by thinning of the corneal stroma in the area of protrusion, which commonly occurs before and after puberty, manifests itself bilaterally, and is a potentially blinding ophthalmic disease. It is a potentially blinding eye disease. Studies have shown that its pathogenesis is related to environmental factors, inflammatory response, immune function, and mechanical stimulation, but the mechanism of the occurrence and progression of KC has not yet been conclusively determined. A variety of genes, represented by corneal remodeling-related genes, have been found to have some influence on the development of cone cornea. More studies are still digging into the genetic targets associated with the development of cone cornea. This article reviews the targets and influence of genes in the pathogenesis of cone cornea, to explore the application value of genes in the early diagnosis and intervention of cone cornea, and to provide new ideas for future research on the pathogenesis of cone cornea.

Abstract The negative impact of SARS-CoV-2 virus infection on cardiovascular disease (CVD) patients is well established. This research article explores the cellular pathways involved in underlying heart diseases after infection. The systemic inflammatory response to SARS-CoV-2 infection likely exacerbates this increased cardiovascular risk; however, whether the virus directly infects cardiomyocytes remains unknown due to limited multi-omics data. While public transcriptome data exists for COVID-19 infection in different cell types (including cardiomyocytes), infection times vary between studies. We used available RNA-seq data from human heart tissue to delineate SARS-CoV-2 infection and heart failure aetiology specific gene expression signatures. A total of fifty-four samples from four studies were analysed. Our aim was to investigate specific transcriptome changes occurring in cardiac tissue with SARS-CoV-2 infection compared to non-infected controls. Our data establish that SARS-CoV-2 infects cardiomyocytes by the TNF-NF-κB pathway, potentially triggering acute cardiovascular complications and increasing the long-term cardiovascular risk in COVID-19 patients.

Abstract Background Wilson disease (WD) is an autosomal recessive inherited disease caused by ATP7B variants and characterized by copper metabolism defects. However, children with WD are often asymptomatic, making the clinical diagnosis difficult. Therefore, more accurate methods are required for clinical diagnosis. The objective of this study was to highlight the phenotypic and genetic characteristics of children with WD in northeast China. Methods We retrospectively analyzed the clinical data and gene sequencing results of 65 children with WD from January 1, 2014, to December 31, 2022, at the Shengjing Hospital of China Medical University. All data refer to the time of diagnosis before treatment. Results The median age at diagnosis was 5 years (range 1.2–15 years). In 50 cases (50/65, 76.9%) patients, routine physical examinations revealed only abnormal liver function. However, they had a significantly negative (p

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

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.

Major depressive disorder (MDD) and frailty impose substantial health and economic burdens. MDD is recognized as a significant risk factor for frailty, but the genetic associations between these conditions remain unclear. This study investigates the genetic correlation, shared pleiotropic loci, causal relationships, and comorbid genes between MDD and frailty. The genetic correlation between MDD and frailty was assessed using linkage disequilibrium score regression (LDSC) based on data from genome-wide association studies (GWAS). A detailed analysis was performed to identify shared pleiotropic loci and causal relationships through cross-phenotype association tests and Mendelian randomization. Additionally, tissue enrichment analysis was conducted using stratified LDSC, gene-based associations with both conditions were assessed using Multimarker Analysis of Genomic Annotation (MAGMA), and pathway analysis of comorbid genes was performed using the g: GOSt tool. Our findings revealed a significant positive genetic correlation between MDD and frailty (r g = 0.65, P = 1.49E-219). We identified 57 shared risk SNPs between the two conditions, including 6 novel SNPs. Mendelian randomization analyses indicated robust causal effects of MDD on frailty and vice versa. Furthermore, we observed tissue-specific heritability enrichment in 9 brain tissues. By combining MAGMA and CPASSOC analyses, we identified 10 comorbid genes associated with both MDD and frailty, primarily involved in synapse formation, modulation, plasticity, and desaturase activity. This study provides strong evidence for a shared genetic basis between MDD and frailty. The identification of comorbid genes offers new insights into the mechanisms underlying the relationship between these conditions. • A remarkably positive genetic correlation between major depressive disorder and frailty. • A total of 57 shared risk SNPs were identified between major depressive disorder and frailty, including 6 newly identified shared SNPs. • Multiple mendelian randomization methods suggest robust bidirectional causal relationship between major depressive disorder and frailty. • Both major depressive disorder and frailty were was significantly heritability enrichments in 9 brain tissues, including anterior cingulate cortex, frontal cortex, hippocampus, hypothalamus, amygdala, nucleus accumbens, putamen, caudate, and cerebellum. • Ten comorbid genes were identified. These comorbid genes are mainly enriched in synapse formation, modulation, plasticity, and desaturase activity. [ABSTRACT FROM AUTHOR]

The global human population is exponentially increasing, which requires the production of quality food through efficient reproduction as well as sustainable production of livestock. Lack of knowledge and technology for assessing semen quality and predicting bull fertility is hindering advances in animal science and food animal production and causing millions of dollars of economic losses annually. The intent of this systemic review is to summarize methods from computational biology for analysis of gene, metabolite, and protein networks to identify potential markers that can be applied to improve livestock reproduction, with a focus on bull fertility. We provide examples of available gene, metabolic, and protein networks and computational biology methods to show how the interactions between genes, proteins, and metabolites together drive the complex process of spermatogenesis and regulate fertility in animals. We demonstrate the use of the National Center for Biotechnology Information (NCBI) and Ensembl for finding gene sequences, and then use them to create and understand gene, protein and metabolite networks for sperm associated factors to elucidate global cellular processes in sperm. This study highlights the value of mapping complex biological pathways among livestock and potential for conducting studies on promoting livestock improvement for global food security. [ABSTRACT FROM AUTHOR]