Effects of the subtypes of apolipoprotein E on immune inhibition and prognosis in patients with Hepatocellular Carcinoma.

PURPOSE: To investigate whether prognosis of patients with hepatocellular carcinoma (HCC) is affected by the abundance and subgroups of myeloid-derived suppressor cells (MDSCs) as well as subtypes and expression of apolipoprotein E (apoE). METHODS: 31 HCC patients were divided into three groups according to blood total apoE level for detecting the abundance of immunoregulatory cells by flow cytometry. Tumour tissue microarrays from 360 HCC patients were evaluated about the abundance and subgroups of MDSCs and the expression of apoE2, apoE3, apoE4 by immunofluorescence staining and immunohistochemistry staining. Survival analysis by means of univariate, multivariate COX regression and Kaplan-Meier methods of the 360 patients was performed based on clinical and pathological examinations along with 10 years' follow-up data. RESULTS: The lower apoE group presented higher abundance of MDSCs in the peripheral blood of HCC patients than higher apoE group. The abundance of monocyte-like MDSCs (M-MDSCs) was higher in the apoE low level group than high level group (p = 0.0399). Lower H-score of apoE2 (HR = 6.140, p = 0.00005) and higher H-score of apoE4 (HR = 7.001, p = 0.009) in tumour tissue were significantly associated with shorter overall survival (OS). The higher infiltration of polymorphonuclear granulocyte-like MDSCs (PMN-MDSCs, HR = 3.762, p = 0.000009) and smaller proportion of M-MDSCs of total cells (HR = 0.454, p = 0.006) in tumour tissue were independent risk factors for shorter recurrence-free survival (RFS). CONCLUSION: The abundance of MDSCs in HCC patients' plasma negatively correlates with the level of apoE. The expression of apoE4 in HCC tissue indicated a poor prognosis while apoE2 might be a potential protective factor.

HLA variants and their association with IgE-Mediated banana allergy: A cross-sectional study.

Background: Banana allergy is on the rise in tropical regions. Advances in genomics and candidate gene identification have increased interest in genetic factors in food allergies. However, the genetic basis of IgE-mediated banana allergy is underexplored. Objective: To characterize HLA variants and their association with IgE-mediated banana allergy. Methods: This cross-sectional study recruited banana-allergic adults, confirmed by allergology tests, with non-allergic individuals as controls. Genomic DNA extraction and sequencing BAM files for HLA typing were conducted. Allele frequency was calculated using the direct counting method, and odds ratio (OR) with 95 % confidence interval (CI) were determined. Fisher's exact or chi-square tests were used to assess associations with Bonferroni's correction for multiple tests. The allele frequency of the Thai population from The Allele Frequency Net Database was used to compute the allele enrichment ratio (ER). Results: A total of 59 cases and 64 controls were recruited. HLA genotyping indicated potential associations of HLA-B*15:25 (OR 11.872; p-value 0.027), HLA-C*04:03 (OR 7.636; p-value 0.033), and HLA-DQB1*06:09 (OR 11.558; p-value 0.039) with banana allergy. However, after Bonferroni correction, none of these associations reached statistical significance. Comparing allele frequency with the general population from The Allele Frequency Net Database, our ER analysis revealed a higher prevalence in the banana allergy group for B*15:25 (ER 1.849), C*04:03 (ER 1.332), and DQB1*06:09 (ER 6.602) alleles. Conclusions: This study provides initial genetic insights into banana allergy, suggesting potential links with specific HLA alleles. Despite 12 initially identifying alleles, none were statistically significant after multiple testing correction. Larger studies are needed to detect possible significant correlations.

DIAPH2 gene polymorphisms and laryngeal cancer risk in men.

BACKGROUND: The DIAPH2 gene is one of the genes commonly associated with laryngeal squamous cell carcinoma (LSCC). In our study, we considered the four polymorphisms of this gene, i.e. rs5920828, rs4322175, rs12851931 and rs5921830 as potential genetic risk factors for LSCC. METHODS: We determined the genotyping of the genetic variants of DIAPH2 in 230 male patients with histologically confirmed LSCC compared to the European population. Demographic and environmental exposure data of each subject were examined. To conduct the genetic tests, extraction of total DNA was performed. We genotyped all four variants in each patient and determined their frequencies. RESULTS: In the case of the rs12851931 polymorphism in the DIAPH2 gene, a significant difference was observed in the distribution of the T stage depending on the polymorphism. Heterozygotes were more often associated with T2 stage, while homozygotes were more likely to have higher tumor stages. The rs12851931 homozygotes of DIAPH2 were statistically significantly more prevalent in smokers. The results suggested that rs12851931 polymorphism in DIAPH2 could increase the onset risk of LSCC. CONCLUSIONS: Our results provide further information on the role of the DIAPH2 gene in the pathogenesis of LSCC.

Identification of rare variants in the FBXO38 gene of patients with chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare immune-mediated neuropathy for which there is no clearly identified risk factor. The present study identified rare variants in the FBXO38 gene in three familial cases of CIDP with response to corticosteroids in three generations with incomplete penetrance, and in an unrelated fourth case with diffuse nerve hypertrophy. FBXO38 may be involved in the regulation of the immunity mediated by CD8 T cells, which have an important role in CIDP pathophysiology, through PD1 degradation. Considering these findings, FBXO38 should be investigated as a potential genetic factor in larger cohorts of patients with CIDP.

Investigating the impact of storage duration and temperature on vitamin C in various citrus genotypes: A meta-analysis method.

The present work disseminates a solid scientific meta-analysis method to investigate the impact of storage duration and temperature on vitamin C of citrus. This work is initiated by designing of the PICO framework, collecting, and organizing the articles, creating selection criteria, sorting articles, identifying factors influencing moderation effects and sources of diversity, tabulating data, and employing analysis in the form of a linear mixed model. Using this method, we identified 54 distinct studies from a pool of 289 eligible peer-reviewed publications, focusing on variations of vitamin C in citrus. The method provides mean values in both quadratic and linear regression forms.•This method provides a detailed description starting from topic selection to statistical methodologies intended for performing meta-analysis.•All guidelines for conducting this method have been approved by all authors and adhere to the standard PRISMA-P guidelines.•Disseminating this method in a peer-reviewed publication aims to facilitate scholarly discussions and promote transparency, ultimately improving the standard for performing meta-analysis on vitamin C levels in citrus concerning various genotypes, storage temperatures, and durations.

Intrauterine twin environment and genetic factors subliminally affecting general movements in preterm infants.

BACKGROUND: Understanding background factors is beneficial for interpreting general movements (GMs). This study examines the factors involved in preterm-writhing GMs by comparing twins and singletons. METHOD: The subjects were 107 infants cared for at Oita University. The cohort consisted of very-low-birth-weight infants, including twins with a birth weight < 2000 g. The median gestational age (GA) was 29 weeks 1 day. The subjects consisted of 75 singletons, 32 twins (16 pairs), 20 monochorionic twins (M-twins), and 12 dichorionic twins (D-twins). GMs were scored according to the GMs optimality score (GMOS) and integrated into 6 items: the quality, neck-trunk and space, amplitude-speed, rotation, onset-offset and cramped, and tremulous score at 32-34 weeks, 35-36 weeks, and 37-42 weeks' GA. A hierarchical cluster analysis was performed using integrated GMOS, and the characteristics of clusters were examined according to clinical backgrounds. RESULTS: Three clusters were identified. Cluster 1 was characterized by good-quality GMs, cluster 2 by a poor repertoire but optimal space and rotatory components, and cluster 3 by overall poor-quality GMs, respectively. The mean GMOSs were 36.6, 31.8 and 24.3 in clusters 1, 2, and 3, respectively. There were no marked differences in proportions within clusters with respect to sex and twins. Small-for-gestational age (SGA) was significantly more frequent in cluster 3 at 32-34 weeks' GA than in other clusters. Perinatal brain injury had a significantly lower proportion in cluster 1 and a higher proportion in cluster 3 at 35-36 weeks' GA and 37-42 weeks' GA. M-twin pairs tended to belong to the same clusters at 35-36 weeks' GA. CONCLUSION: Preterm writhing GMs are associated with SGA and perinatal brain injury. Cluster matching in M-twins suggests that certain genetic factors may substantially influence GMs.

Different neuropsychological and brain volumetric profiles in a pair of identical twins with myotonic dystrophy type 1 indicate a non-genetic modulation of clinical phenotype.

We report on genetic and environmental modulation of social cognition abilities and brain volume correlates in two monozygotic twins (Twin1 and Twin2) with genetically confirmed myotonic dystrophy-type1 who grew up in different environmental settings. They both underwent neuropsychological assessment (i.e., Intelligent Quotient [IQ], theory of mind, emotion recognition tests), and MRI scanning to evaluate regional brain volumetrics compared to 10 gender and sex-matched healthy controls. Against a normal IQ level in both patients, Twin1 was more impaired in emotional processing and Twin2 in cognitive aspects of social cognition. Both patients showed grey matter (GM) atrophy in Brodmann Areas 23/31 (BA23/31) and BA7 bilaterally, while Twin2 showed additional GM loss in right BA46. Both patients showed a similar pattern of white matter atrophy involving the thalamus, basal ganglia, and uncinate fasciculus. White matter atrophy appeared to be mostly driven by genetics, while grey matter volumes appeared associated with different impairments in social cognition and possibly modulated by environment.

Computational screening of damaging nsSNPs in human SOD1 genes associated with amyotrophic lateral sclerosis identifies destabilising effects of G38R and G42D mutations through in silico evaluation.

Amyotrophic lateral sclerosis (ALS), a complicated neurodegenerative disorder affected by hereditary and environmental variables, is a condition. In this study, the genetic makeup of ALS is investigated, with a focus on the SOD1 gene's single-nucleotide polymorphisms (SNPs) and their ability to affect disease risk. Eleven high-risk missense variations that may impair the functionality of the SOD1 protein were discovered after a thorough examination of SNPs in the SOD1 gene. These mutations were chosen using a variety of prediction approaches, highlighting their importance in the aetiology of ALS. Notably, it was discovered that the stability of the SOD1 wild-type protein structure was compromised by the G38R and G42D SOD1 variants. Additionally, Edaravone, a possible ALS medication, showed a greater affinity for binding mutant SOD1 structures, pointing to potential personalised treatment possibilities. The high-risk SNPs discovered in this investigation seem to have functional effects, especially on the stability of proteins and their interactions with other molecules. This study clarifies the complex genetics of ALS and offers insights into how these genetic variations may affect the effectiveness of therapeutic interventions, particularly in the context of edaravone. In this study advances our knowledge of the genetic mechanisms causing ALS vulnerability and prospective therapeutic strategies. Future studies are necessary to confirm these results and close the gap between individualised clinical applications and improved ALS care.

Alteration Ocular Motility in Retinitis Pigmentosa: Case-Control Study.

Purpose: To evaluate ocular motility (OM) disorders and strabismus in a sample of patients with retinitis pigmentosa (RP) and a control sample. Methods: In this cross-sectional retrospective analysis, we studied a sample of RP patients with a mean age of 48.74 years and an average visual acuity of 7/10 based on Snellen optotype and a sample of control patients with similar mean age (49 years [men], 47 years [women]) and sex and an average visual acuity of 9.9/10, with the aim of assessing correlations between alteration of OM and strabismus in RP patients based on age, high refractive defect, or severely impaired binocular vision. The examination followed a protocol of testing for anamnesis and best-corrected visual acuity, as well as a complete eye examination, corneal reflex, cover test, OM, Hess screen, and Lang test. Results: At the first orthoptic evaluation, 45.16% of patients showed strabismus, 41.93% exotropia (25% of cases intermittent), 3.22% esotropia, and 6.45% vertical deviation. Later evaluation showed strabismus in 25.80% of patients, exotropia in 19.35% (9.67% intermittent), esotropia in 3.22%, and vertical deviation in 3.22%. Assessment of eye motility study showed 51.6% overaction of the inferior oblique and hypofunction of the superior rectus, and 18% overaction of the lateral rectus and hypofunction of the medial rectus. According to our results, alterations in OM and strabismus in RP patients are not correlated with age or high refractive defect. Therefore, motility disorders and strabismus are attributed to a genetic factor to which men are more susceptible. Conclusion: The incidence of OM disorder was 77.42%, and strabismus was present in 45.16% of patients.

Updating an Overview of Teratology.

In this chapter, the authors aim to update an overview of the principles of teratology, beginning with the definition of teratology, the critical point at which this process occurs, and some of the most common etiological agents that improve our understanding of teratology.Modern teratology has greatly improved in recent years with advances in new methods in molecular biology, toxicology, animal laboratory science, and genetics, increasing our knowledge of ambient influences. Nevertheless, there is a lot to do to reduce the influence of hazardous intervening agents, whether they target our genetics or not, that can negatively affect pregnancy and induce congenital development disorders, including morphological, biochemical, or behavioral defects.Certain agents might indeed be related to certain defects, but we have not been able to identify the cause of most congenital defects, which highlights the importance of finding and testing out new genetics techniques and conducting laboratory animal science to unravel the etiology and pathogenicity of each congenital defect.

The terroir of Brazilian Coffea canephora: Characterization of the chemical composition.

FTIR spectroscopy and multivariate analysis were used in the chemical study of the terroirs of Coffea canephora. Conilon coffees from Espírito Santo and Amazon robusta from Matas of Rondônia, were separated by PCA, with lipids and caffeine being the markers responsible for the separation. Coffees from Bahia, Minas Gerais, and São Paulo did not exhibit separation, indicating that the botanical variety had a greater effect on the terroir than geographic origin. Thus, the genetic factor was investigated considering the conilon and robusta botanical varieties. This last group was composed of hybrid robusta and apoatã. The DD-SIMCA favored the identification of the genetic predominance of the samples. PLS-DA had a high classification performance regarding the conilon, hybrid robusta, and apoatã genetic nature. Lipids, caffeine, chlorogenic acids, quinic acid, trigonelline, proteins, amino acids, and carbohydrates were identified as chemical markers that discriminated the genetic groups.

Rigorous evaluation of genetic and epigenetic effects on clinical laboratory measurements using Japanese monozygotic twins.

The investigation of environmental effects on clinical measurements using individual samples is challenging because their genetic and environmental factors are different. However, using monozygotic twins (MZ) makes it possible to investigate the influence of environmental factors as they have the same genetic factors within pairs because the difference in the clinical traits within the MZ mostly reflect the influence of environmental factors. We hypothesized that the within-pair differences in the traits that are strongly affected by genetic factors become larger after genetic risk score (GRS) correction. Using 278 Japanese MZ pairs, we compared the change in within-pair differences in each of the 45 normalized clinical measurements before and after GRS correction, and we also attempted to correct for the effects of genetic factors to identify Cytosine-phosphodiester-Guanine (CpG) sites in DNA sequences with epigenetic effects that are regulated by genetic factors. Five traits were classified into the high heritability group, which was strongly affected by genetic factors. CpG sites could be classified into three groups: regulated only by environmental factors, regulated by environmental factors masked by genetic factors, and regulated only by genetic factors. Our method has the potential to identify trait-related methylation sites that have not yet been discovered.

Exploring the latest understanding on the role of immune mediators, genetic and environmental factors in pathogenesis of allergic rhinitis: a systematic review.

Introduction: Despite well-defined clinical phenotypes of chronic rhinitis, the underlying in-depth pathophysiological mechanism, particularly with reference to the involvement of immune mediators, genetic, and environmental factors, are still not fully understood. Therefore, our aim was to give updated information on the pathogenesis of allergic rhinitis (AR), with an emphasis on the role of cytokines in adults aged 18 years and above. Additionally, we investigated the impact of genetic and environmental factors in the pathogenesis of AR. Results: A search in various databases identified 1,178 records, and 18 studies were ultimately selected from January 2018 to April 2023. The total sample size in our studies was 4,317, with 2,186 in the experimental and 2,131 in control groups, respectively. The mean age was 33.4 years, with 43% were male, while 57% were female. According to the selected studies, various factors, including immune mediators, particularly cytokines, genetic, and environmental factors, were identified in the development of AR. Conclusion: The selected studies presented findings on different factors and sub-factors in the pathogenesis of AR, making it a challenge for us to compare their results. However, based on our findings, researchers can link our identified factors to potential therapies for AR.

Air pollution, genetic factors and the risk of osteoporosis: A prospective study in the UK biobank.

Purpose: To reveal relationship between air pollution exposure and osteoporosis (OP) risk. Methods: Based on large-scale data from the UK Biobank, we evaluated the relationship between OP risk and several air pollutants. Then air pollution scores (APS) were constructed to assess the combined effects of multiple air pollutants on OP risk. Finally, we constructed a genetic risk score (GRS) based on a large genome-wide association study of femoral neck bone mineral density and assessed whether single or combined exposure to air pollutants modifies the effect of genetic risk on OP and fracture risk. Results: PM2.5, NO2, NOx, and APS were significantly associated with an increased risk of OP/fracture. OP and fracture risk raised with increasing concentrations of air pollutants: compared to the lowest APS quintile group, subjects in the highest quintile group had a hazard ratio (HR) (95% CI) estimated at 1.140 (1.072-1.213) for OP and 1.080 (1.026-1.136) for fracture. Moreover, participants with low GRS and the highest air pollutant concentration had the highest risk of OP, the HRs (95% CI) of OP were 1.706 (1.483-1.964), 1.658 (1.434-1.916), 1.696 (1.478-1.947), 1.740 (1.506-2.001) and 1.659 (1.442-1.908), respectively, for PM2.5, PM10, PM2.5-10, NO2, and NOx. Similar results were also observed for fractures. Finally, we assessed the joint effect of APS and GRS on the risk of OP. Participants with higher APS and lower GRS had a higher risk of developing OP. Similar results were observed in the joint effect of GRS and APS on fracture. Conclusions: We found that exposure to air pollution, individually or jointly, could improve the risk of developing OP and fractures, and increased the risk by interacting with genetic factors.

Co-occurring pathogenic variants in 6q27 associated with dementia spectrum disorders in a Peruvian family.

Evidence suggests that there may be racial differences in risk factors associated with the development of Alzheimer's disease and related dementia (ADRD). We used whole-genome sequencing analysis and identified a novel combination of three pathogenic variants in the heterozygous state (UNC93A: rs7739897 and WDR27: rs61740334; rs3800544) in a Peruvian family with a strong clinical history of ADRD. Notably, the combination of these variants was present in two generations of affected individuals but absent in healthy members of the family. In silico and in vitro studies have provided insights into the pathogenicity of these variants. These studies predict that the loss of function of the mutant UNC93A and WDR27 proteins induced dramatic changes in the global transcriptomic signature of brain cells, including neurons, astrocytes, and especially pericytes and vascular smooth muscle cells, indicating that the combination of these three variants may affect the neurovascular unit. In addition, known key molecular pathways associated with dementia spectrum disorders were enriched in brain cells with low levels of UNC93A and WDR27. Our findings have thus identified a genetic risk factor for familial dementia in a Peruvian family with an Amerindian ancestral background.

The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update.

Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which the small intrahepatic bile ducts are destroyed by autoimmune reactions. Among autoimmune diseases, which are polygenic complex traits caused by the combined contribution of genetic and environmental factors, PBC exhibits the strongest involvement of genetic heritability in disease development. As at December 2022, genome-wide association studies (GWASs) and associated meta-analyses identified approximately 70 PBC susceptibility gene loci in various populations, including those of European and East Asian descent. However, the molecular mechanisms through which these susceptibility loci affect the pathogenesis of PBC are not fully understood. This study provides an overview of current data regarding the genetic factors of PBC as well as post-GWAS approaches to identifying primary functional variants and effector genes in disease-susceptibility loci. Possible mechanisms of these genetic factors in the development of PBC are also discussed, focusing on four major disease pathways identified by in silico gene set analyses, namely, (1) antigen presentation by human leukocyte antigens, (2) interleukin-12-related pathways, (3) cellular responses to tumor necrosis factor, and (4) B cell activation, maturation, and differentiation pathways.

Host susceptibility genes of asymptomatic malaria from South Central Timor, Eastern Indonesia.

Host genetic factors, such as the genes for various cytokines and adhesion molecules, play a significant role in determining susceptibility to malaria infection. Polymorphisms in host genes have been correlated with malaria infection in both African and Asian regions. The purpose of this study was to investigate the association between both cytokine and adhesion molecule genotypes with susceptibility to malaria infection in humans. Ten cytokine polymorphism loci (IL4 + 33, IL4-590, IL6-174, IL10-1082, IL10-1035, IL12p40, TNF-238, TNF-308, TNF-1031, and TNF-ß) and three adhesion molecule polymorphism loci (CD36 exon 10, ICAM-1 Kilifi, and ICAM-1 exon 6) were genotyped using PCR-RFLP analysis. We conducted this study on 178 asymptomatic malaria subjects and 122 uninfected subjects. Results showed that certain CD36 exon 10 and IL10-3575 polymorphisms were associated with asymptomatic infection. The heterozygous (GT) and homozygous (GG) genotypes for CD36 exon 10 are associated with an increased risk of malaria infection. On the other hand, the homozygous genotype (AA) for IL10-3575 reduced the risk of asymptomatic malaria infection. No significant differences were found for the other polymorphisms studied. We also found that a polymorphism in CD36 exon 10 was strongly associated with asymptomatic malaria caused specifically by Plasmodium vivax. These findings suggest that the G allele of CD36 exon 10 is associated with an increased risk of asymptomatic malaria infection. On the other hand, the genotype AA for IL10-3575 was associated with a reduced risk of malaria infection.

Etiopathogenesis of adolescent idiopathic scoliosis (AIS): Role of genetic and environmental factors.

Adolescent idiopathic scoliosis (AIS) has been known to be related closely to genetic factors. Higher prevalence of AIS among individuals with family history of scoliosis suggesting critical roles of genetic in the pathogenesis of AIS. However, evidence also suggested that environmental factors such as latitude and sun exposure also play a critical role in the pathogenesis of the disease. While genetic factors played an important role in the occurrence of AIS, environmental factors are more likely to affect the progression of the disease. Although the pathogenesis of AIS remains elusive, current knowledge suggests that genetic factors and its interaction with environmental factors are crucial in the development of the disease, explaining differences in clinical characteristics of AIS across the globe. The aim of this review is to summarize the current knowledge of genetic and environmental factors contributing to AIS and their interactions.

Study on the correlation between xanthelasma palpebrarum and the genetic factor of hypercholesterolemia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the correlation between xanthelasma palpebrarum(XP)and the genetic factor of hypercholesterolemia and provide a basis for the elucidation of the pathogenesis of xanthelasma palpebrarum.METHODS: A total of 29 patients with XP who treated in the ophthalmology department of Foshan Sanshui District People's Hospital from November 2019 to January 2021 were selected. Peripheral blood was drawn, and the Next Generation Sequencing(NGS)technology was used to detect the genetic mutations of patients, while blood lipids of XP patients were analyzed.RESULTS: Gene mutations were detected in 21 patients with XP, among which 13 cases had hypercholesterolemia and 8 cases had normal cholesterol levels. Genes including STAP1, APOB, LDLRAP1, LDLR, PCSK9 and APOE mutated, and the types of gene mutation included 3-UTR mutation, in-frame deletion, missense mutation, 5-UTR mutation, synonymous mutation, intronic mutation, alternative splice variant, non coding transcript exon variant, and non coding transcript variant.CONCLUSION: There is a correlation between genetic factors of hypercholesterolemia and XP.