Unveiling the hidden risk: paternal smoking and alcohol exposure prior to conception as independent factors for allergic rhinitis in children.

Introduction: Limited knowledge exists regarding the impact of paternal smoking and alcohol exposure on the development of allergic rhinitis in offspring. Our study aimed to investigate the potential association between preconception paternal smoking and alcohol exposure and the likelihood of children allergic rhinitis. Methods: A retrospective case-control study of 556 prepubertal children aged 3-12 years was performed. The participants were 278 children with allergic rhinitis and 278 healthy controls matched for age and gender. Self-administered questionnaires were distributed and collected on-site, focusing on various factors related to the children's fathers, mothers, and the children themselves during the first year of life and the past 12 months, from March to October 2022. Results: Multivariate analysis demonstrated that paternal smoking, paternal alcohol consumption prior to conception, paternal allergic diseases, children with a family history of allergies, maternal allergic diseases and pregnancy complications were identified as independent risk factors for allergic rhinitis in their offspring. Moreover, after considering confounding factors, it was observed that paternal smoking exceeding 5 cigarettes per day in the year preceding pregnancy and exceeding 11 years significantly elevated the likelihood of allergic rhinitis in children (OR = 2.009 and 2.479, respectively). Furthermore, the consumption of alcohol by the father at intervals of less than one month in the year prior to pregnancy and a duration of alcohol consumption exceeding 11 years prior to pregnancy are both associated with a significantly increased risk of allergic rhinitis in children (OR = 2.005 and 3.149, respectively). Conclusions: Paternal smoking and alcohol consumption prior to conception contribute to an increased risk of allergic rhinitis in children, with the risk being dependent on the dosage and duration of exposure. Therefore, it is important to not only focus on personal and maternal environmental exposures when considering the occurrence risk of allergic rhinitis in children, but also to consider paternal detrimental exposures prior to conception.

Common human leucocyte antigensassociated with the development of subacute thyroiditis and COVID-19.

PURPOSE: Case reports of subacute thyroiditis (SAT) following coronavirus disease-19 (COVID-19) have been reported. Because the relationship between SAT and human leucocyte antigen (HLA) alleles is known, we aimed to determine HLA alleles that may predispose a patient to coronavirus infection and/or post-COVID-19 SAT. METHOD: This retrospective study was conducted in 51 patients with SAT and 190 healthy bone marrow donor volunteers. HLA-A, -B, -C, -DRB1, and -DQB1 were genotyped using next-generation sequencing. The study population was grouped into four groups according to SAT and COVID-19 history. RESULTS: The frequency of HLA-DQB1*04:02 was higher in the COVID-19(-) participants than in the COVID-19(+) participants (=0.045). The presence of HLA-DQB1*04:02 was associated with a lower risk of developing COVID-19 in all groups. The frequencies of HLA-B*35:01, HLA-B*35:03, HLA-DRB1*12:01, and HLA-DRB1*14:01 were different in the SAT(+) group than in the SAT(-) group in COVID-19(-) group. The frequencies of HLA-C*12:03, HLA-DQB1*06:04, HLA-DRB1*13:02, and HLA-DRB1*13:03 were different in the SAT(+) group than in the SAT(-) group in the COVID-19 (+) group. The difference in the frequency of these HLA types remains significant when the four groups are included together as follows: In the COVID-19(+) group, the frequencies of HLA-DRB1*13:02, and HLA-DRB1*13:03 were higher in the SAT(+) group than in the SAT(-) group. In the COVID-19(-) group, the frequencies of HLA-B*35:03, HLA-DRB1*12:01, and HLA-DRB1*14:01 were higher in the SAT (+) group than in the SAT(-) group. CONCLUSION: HLA alleles associated with SAT susceptibility may vary with COVID-19 history.

Heavy metal exposure and metabolomics analysis: an emerging frontier in environmental health.

Exposure to heavy metals in various populations can lead to extensive damage to different organs, as these metals infiltrate and bioaccumulate in the human body, causing metabolic disruptions in various organs. To comprehensively understand the metal homeostasis, inter-organ "traffic," and extensive metabolic alterations resulting from heavy metal exposure, employing complementary analytical methods is crucial. Metabolomics is pivotal in unraveling the intricacies of disease vulnerability by furnishing thorough understandings of metabolic changes linked to different metabolic diseases. This field offers exciting prospects for enhancing the disease prevention, early detection, and tailoring treatment approaches to individual needs. This article consolidates the existing knowledge on disease-linked metabolic pathways affected by the exposure of diverse heavy metals providing concise overview of the underlying impact mechanisms. The main aim is to investigate the connection between the altered metabolic pathways and long-term complex health conditions induced by heavy metals such as diabetes mellitus, cardiovascular diseases, renal disorders, inflammation, neurodegenerative diseases, reproductive risks, and organ damage. Further exploration of common pathways may unveil the shared targets for treating associated pathological conditions. In this article, the role of metabolomics in disease susceptibility is emphasized that metabolomics is expected to be routinely utilized for the diagnosis and monitoring of diseases and practical value of biomarkers derived from metabolomics, as well as determining their appropriate integration into extensive clinical settings.

Genetic history of esophageal cancer group in southwestern China revealed by Y-chromosome STRs and genomic evolutionary connection analysis.

Genetic and environmental factors play crucial roles in the development of esophageal cancer (EC) and contribute uniquely or cooperatively to human cancer susceptibility. Sichuan is located in the interior of southwestern China, and the northern part of Sichuan is one of the regions with a high occurrence of EC. However, the factors influencing the high incidence rate of EC in the Sichuan Han Chinese population and its corresponding genetic background and origins are still poorly understood. Here, we utilized genome-wide single nucleotide polymorphisms (SNPs) and Y-chromosome short tandem repeats (Y-STRs) to characterize the genetic structure, connection, and origin of cancer groups and general populations. We generated Y-STR-based haplotype data from 214 Sichuan individuals, including the Han Chinese EC population and a control group of Han Chinese individuals. Our results, obtained from Y-STR-based population statistical methods (analysis of molecular variance (AMOVA), principal component analysis (PCA), and phylogenetic analysis), demonstrated that there was a genetic substructure difference between the EC population in the high-incidence area of northern Sichuan Province and the control population. Additionally, there was a strong genetic relationship between the EC population in the northern Sichuan high-incidence area and those at high risk in both the Fujian and Chaoshan areas. In addition, we obtained high-density SNP data from saliva samples of 60 healthy Han Chinese individuals from three high-prevalence areas of EC in China: Sichuan Nanchong, Fujian Quanzhou, and Henan Xinxiang. As inferred from the allele frequency of SNPs and sharing patterns of haplotype segments, the evolutionary history and admixture events suggested that the Han population from Nanchong in northern Sichuan Province shared a close genetic relationship with the Han populations from Xinxiang in Henan Province and Quanzhou in Fujian Province, both of which are regions with a high prevalence of EC. Our study illuminated the genetic profile and connection of the Northern Sichuan Han population and enriched the genomic resources and features of the Han Chinese populations in China, especially for the Y-STR genetic data of the Han Chinese EC population. Populations living in different regions with high incidences of EC may share similar genetic backgrounds, which offers new insights for further exploring the genetic mechanisms underlying EC.

Associative role of HLA-DRB1 as a protective factor for susceptibility and progression of Parkinson's disease: a Chinese cross-sectional and longitudinal study.

Background: Previous genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson's disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively. Methods: The study consisted of three parts: a case-control study, a cross-sectional study, and a longitudinal cohort study. The case-control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression. Results: In the case-control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, p = 0.003). In the cross-sectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: ß = -5.42, p < 0.001, interaction ptime × genotype < 0.001) and non-motor symptoms (NMSS score: ß = -4.78, p = 0.030, interaction ptime × genotype < 0.001). Conclusion: Our findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression.

On the effect heterogeneity of established disease susceptibility loci for Alzheimer's disease across different genetic ancestries.

INTRODUCTION: Genome-wide association studies have identified numerous disease susceptibility loci (DSLs) for Alzheimer's disease (AD). However, only a limited number of studies have investigated the dependence of the genetic effect size of established DSLs on genetic ancestry. METHODS: We utilized the whole genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP) including 35,569 participants. A total of 25,459 subjects in four distinct populations (African ancestry, non-Hispanic White, admixed Hispanic, and Asian) were analyzed. RESULTS: We found that nine DSLs showed significant heterogeneity across populations. Single nucleotide polymorphism (SNP) rs2075650 in translocase of outer mitochondrial membrane 40 (TOMM40) showed the largest heterogeneity (Cochran's Q = 0.00, I2 = 90.08), followed by other SNPs in apolipoprotein C1 (APOC1) and apolipoprotein E (APOE). Two additional loci, signal-induced proliferation-associated 1 like 2 (SIPA1L2) and solute carrier 24 member 4 (SLC24A4), showed significant heterogeneity across populations. DISCUSSION: We observed substantial heterogeneity for the APOE-harboring 19q13.32 region with TOMM40/APOE/APOC1 genes. The largest risk effect was seen among African Americans, while Asians showed a surprisingly small risk effect.

Radiographic evaluation of the distance between the restoration margin and the alveolar bone crest in dental implant patients: A retrospective study.

OBJECTIVES: The recently introduced Implant Disease Risk Assessment (IDRA) identifies a restoration margin-alveolar bone crest (RM-AC) distance of less than 1.5 mm as a key risk factor for peri­implant disease among eight major risk factors. This study evaluated the impact of the RM-AC distance on marginal bone loss (MBL) through radiographic analysis. METHODS: This retrospective cross-sectional study included 77 partially edentulous patients (39 females and 38 males, aged 22 to 76 years) with 202 platform-switched conical connection implants, cement-retained, implant-supported fixed restorations, and bone-level implants placed between 2016 and 2021. Dental implants were followed for least 6 to 36 months at follow up functional loading. Study participants were categorized into Group A (RM-AC distance ≤ 1.5 mm, n = 69) and Group B (RM-AC distance > 1.5 mm, n = 133). Twelve patients in Group B and five patients in Group A had no history of periodontal disease. The MBL was measured radiographically from the most coronal point of the implant shoulder to the alveolar bone, and the RM-AC distance was measured from the restoration margin to the alveolar crest. Multinomial logistic regression analysis was used for statistical evaluation. RESULTS: The incidence of MBL in Group A was statistically significant and 3.42 times higher than that in Group B. The rate of MBL in periodontitis Stage 4 was found to be 26.31 times higher than that in periodontitis Stage 2. The incidence of MBL was 6.097 and 5.02 times higher with increasing implant diameter and length, respectively. CONCLUSION: This study conclusively demonstrates that RM-AC distance ≤ 1.5 significantly increases the risk of MBL, particularly in patients with a history of periodontal disease. CLINICAL SIGNIFICANCE: This study highlights the critical role of maintaining an RM-AC distance greater than 1.5 mm in the prevention of MBL, particularly in patients with a history of periodontal disease. Since implant diameter and length have a significant impact on the risk of MBL, it emphasizes that implant demographics should also be carefully evaluated.

Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications.

BACKGROUND: Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms. METHODS: We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients-divided into a discovery and validation cohort-were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments. RESULTS: We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses. CONCLUSIONS: Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures. TRIAL REGISTRATION: The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015-02-13).

Embryonic Amoxicillin Exposure Has Limited Impact on Liver Development but Increases Susceptibility to NAFLD in Zebrafish Larvae.

Amoxicillin is commonly used in clinical settings to target bacterial infection and is frequently prescribed during pregnancy. Investigations into its developmental toxicity and effects on disease susceptibility are not comprehensive. Our present study examined the effects of embryonic amoxicillin exposure on liver development and function, especially the effects on susceptibility to non-alcoholic fatty liver disease (NAFLD) using zebrafish as an animal model. We discovered that embryonic amoxicillin exposure did not compromise liver development, nor did it induce liver toxicity. However, co-treatment of amoxicillin and clavulanic acid diminished BESP expression, caused bile stasis and induced liver toxicity. Embryonic amoxicillin exposure resulted in elevated expression of lipid synthesis genes and exacerbated hepatic steatosis in a fructose-induced NAFLD model, indicating embryonic amoxicillin exposure increased susceptibility to NAFLD in zebrafish larvae. In summary, this research broadens our understanding of the risks of amoxicillin usage during pregnancy and provides evidence for the impact of embryonic amoxicillin exposure on disease susceptibility in offspring.

Restless nights when sick: ectoparasite infections alter rest-activity cycles of diurnal fish hosts.

Circadian rhythms are timekeeping mechanisms responsible for an array of biological processes. Disruption of such cycles can detrimentally affect animal health. Circadian rhythms are critical in the co-evolution of host­parasite systems, as synchronization of parasite rhythms to the host can influence infection dynamics and transmission potential. This study examines the circadian rhythms in behaviour and activity of a model fish species (Poecilia reticulata) in isolation and in shoals, both when uninfected and infected with an ectoparasite (Gyrodactylus turnbulli). Additionally, the rhythmical variance of parasite activity under different light conditions as well as rhythmical variance in parasite transmissibility was explored. Overall, infection alters the circadian rhythm of fish, causing nocturnal restlessness. Increased activity of gyrodactylids on the host's skin at night could potentially contribute to this elevated host activity. Whilst migration of gyrodactylids across the host's skin may have caused irritation to the host resulting in nocturnal restlessness, the disruption in guppy activity rhythm caused by the expression of host innate immunity cannot be excluded. We discuss the wider repercussions such behavioural responses to infection have for host health, the implications for animal behaviour studies of diurnal species as well as the application of chronotherapeutic approaches to aquaculture.

MHC-DRB alleles with amino acids Val11, Phe13, and the shared epitopes promote collagen-induced arthritis and a rapid IgG1 response in Filipino cynomolgus macaques.

Macaques are useful animal models for studying the pathogenesis of rheumatoid arthritis (RA) and the development of anti-rheumatic drugs. The purpose of this study was to identify the major histocompatibility complex (MHC) polymorphisms associated with the pathology of collagen-induced arthritis (CIA) and anti-collagen IgG induction in a cynomolgus macaque model, as MHC polymorphisms affect the onset of CIA in other animal models. Nine female Filipino cynomolgus macaques were immunized with bovine type II collagen (b-CII) to induce CIA, which was diagnosed clinically by scoring the symptoms of joint swelling over 9 weeks. MHC polymorphisms and anti-b-CII antibody titers were compared between symptomatic and asymptomatic macaques. Four of 9 (44%) macaques were defined as the CIA-affected group. Anti-b-CII IgG in the affected group increased in titer approximately 3 weeks earlier compared with the asymptomatic group. The mean plasma IgG1 titer in the CIA-affected group was significantly higher (p < 0.05) than that of the asymptomatic group. Furthermore, the cynomolgus macaque MHC (Mafa)-DRB1*10:05 or Mafa-DRB1*10:07 alleles, which contain the well-documented RA-susceptibility five amino acid sequence known as the shared epitope (SE) in positions 70 to 74, with valine at position 11 (Val11, V11) and phenylalanine at position 13 (Phe13, F13), were detected in the affected group. In contrast, no MHC polymorphisms specific to the asymptomatic group were identified. In conclusion, the presence of V11 and F13 along with SE in the MHC-DRB1 alleles seems essential for the production of IgG1 and the rapid induction of severe CIA in female Filipino cynomolgus macaques.

Determination of the Relationship Between the Development and Recurrence of Subacute Thyroiditis and Human Leukocyte Antigen Subtypes.

Background: There are several studies investigating the role of human leukocyte antigens (HLA) in the development and recurrence of subacute thyroiditis (SAT). The HLA subtypes associated with SAT were usually determined in a population-based manner and HLA-B*35, HLA-B*18:01, HLA-C*04:01, and HLA-DRB1*01 were detected to play a role in the disease susceptibility and prognosis. The aim of this study was to determine HLA alleles associated with the tendency of recurrence and prevention of SAT within the Turkish population. Methods: This prospective study was conducted with 51 SAT patients and 720 healthy bone marrow donor volunteers. HLA-A, -B, -C, -DRB1, and -DQB1 were genotyped using next-generation sequencing. Results: The frequency of HLA-A*02:09, HLA-B*35:01/35:02/35:03, HLA-C*04:01, HLA-DRB1*12:01, and DRB1*13:03 were associated with an increased risk of SAT development (Odds Ratio: 22.4, 9.5, 10.3, 4.2, and 3.5, respectively). While HLA-A*02:09, HLA-B*35:01, HLA-B*44:02 HLA-C*07:18, and HLA-C*16:04 were associated with nonrelapsing SAT, HLA-DR*12:01was associated with relapsing SAT. HLA-B*35:02, HLA-B*35:03, and HLA-C*04:01 were more frequent both in relapsing and nonrelapsing groups according to control group. The frequency of HLA-B*18:01, reported as a risk factor previously, was similar in the SAT and control groups (p = 0.959). HLA-DRB1*11:01 was associated with a lower risk of SAT development. Conclusions: Along with -B*358 and -C*04, HLA-A*02:09 was detected as an important risk factor for SAT development in our population. HLA-DRB1*11:01 appears to be the protective HLA subtype against SAT. HLA-A*02:09, HLA-B*35:01, HLA-B*44:02, HLA-C*07:18, HLA-C*16:04, HLA-DQ*06:03, and HLA-DR*12:01 subtypes can establish a tendency to relapsing or nonrelapsing SAT.

Genome-Wide Genetic Associations Prioritize Evaluation of Causal Mechanisms of Atherosclerotic Disease Risk.

OBJECTIVE: The goal of this review is to discuss the implementation of genome-wide association studies to identify causal mechanisms of vascular disease risk. APPROACH AND RESULTS: The history of genome-wide association studies is described, the use of imputation and the creation of consortia to conduct meta-analyses with sufficient power to arrive at consistent associated loci for vascular disease. Genomic methods are described that allow the identification of causal variants and causal genes and how they impact the disease process. The power of single-cell analyses to promote genome-wide association studies of causal gene function is described. CONCLUSIONS: Genome-wide association studies represent a paradigm shift in the study of cardiovascular disease, providing identification of genes, cellular phenotypes, and disease pathways that empower the future of targeted drug development.

The effect of TRIM5 variants on the susceptibility to HIV-1 infection and disease progression in the Polish population.

BACKGROUD: Tripartite motif containing 5α protein is a factor contributing to intracellular defense mechanisms against human immunodeficiency virus-1 (HIV-1) infection. The studies of TRIM5 variants effects on the risk of HIV-1 infection and the clinical course of disease provided inconclusive results in different ethnic groups. The aim of this study was to investigate the influence of TRIM5 variants on susceptibility to HIV-1 infection and clinical parameters among Polish HIV-1-infected patients. MATERIALS & METHODS: In our study, we investigated 301 HIV-1-infected patients and 186 age-matched seronegative controls. Seven variants of the TRIM5 gene (rs7127617, rs3824949, rs3740996, rs11601507, rs10838525, rs11038628, and rs28381981) were genotyped using both sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. RESULTS AND CONCLUSIONS: The frequencies of rs7127617 TT genotype and T allele occurrence were lower in HIV-1-infected subjects compared to controls (0.14 vs. 0.26 for T/T genotype and 0.45 vs. 0.54 for T allele), suggesting their possible protective effect (p = 0.005 and p = 0.007, respectively). Heterozygosity and presence of the T allele at rs3740996 were enriched in controls compared to HIV-1-infected group (0.19 vs. 0.12 for C/T genotype and 0.11 vs. 0.07 for T allele; p = 0.03 and p = 0.02, respectively). Moreover, rs3824949 CC genotype carriers had a lower viral load than patients bearing rs3824949 GG/CG genotypes (4.0 vs. 4.6 log copies/mL; p = 0.049); however, none of the variants affected CD4+ cell count. In conclusion, our data confirm the role of TRIM5 variants in the HIV-1 transmission and the clinical course of HIV-1 infection. The presence of rs7127617 TT genotype and T allele seems to protect against HIV-1 transmission in examined population.

Biochemical, histological and transcriptomic analyses for the immunological organs provide insights into heat stress-induced disease susceptibility in Largemouth Bass.

Aquaculture of Largemouth Bass (LMB, Micropterus salmoides), an economically important species, is badly affected by the outbreak of bacterial diseases in summer. However, the mechanisms underlying heat-induced disease susceptibility remain largely unknown. In this study, after exposure to 34 °C for 1, 7 and 14 d, the head kidney, spleen and blood of LMB were sampled for biochemical and histological assays to explore the effects of heat exposure on the oxidative and immunological indices. Compared to the controls maintained at 28 °C, chronic heat exposure (34 °C for 14 d) induced oxidative stress, caused cell apoptosis and decreased expression of the immunological genes in the head kidney and spleen tissues; and attenuated the blood immunological indices. Consistent with the impaired immunological functions, chronic heat exposure predisposed LMB to Aeromonas hydrophila infection and significantly (p < 0.001) increased tissue bacterial load. Furthermore, the effects of chronic heat exposure (heat), A. hydrophila infection (infection) and heat exposure followed by A. hydrophila infection (heat + infection) on gene expression in the head kidney and spleen of LMB were characterized by RNA sequencing. The results indicated that chronic heat exposure facilitated the bacteria-elicited changes in expression of the genes involved in a couple of metabolic and signaling pathways in both tissues. Upon heat + infection, the pathways involved in energy production and nutrients biosynthesis were enhanced, whereas those associated with the host cell functions such as cell-cell interactions and cell signaling were depressed. Our data provide new insights into the mechanisms underlying heat-induced disease susceptibility in LMB.

Decoding the role of the gut microbiome in gut-brain axis, stress-resilience, or stress-susceptibility: A review.

Increased exposure to stress is associated with stress-related disorders, including depression, anxiety, and neurodegenerative conditions. However, susceptibility to stress is not seen in every individual exposed to stress, and many of them exhibit resilience. Thus, developing resilience to stress could be a big breakthrough in stress-related disorders, with the potential to replace or act as an alternative to the available therapies. In this article, we have focused on the recent advancements in gut microbiome research and the potential role of the gut-brain axis (GBA) in developing resilience or susceptibility to stress. There might be a complex interaction between the autonomic nervous system (ANS), immune system, endocrine system, microbial metabolites, and bioactive lipids like short-chain fatty acids (SCFAs), neurotransmitters, and their metabolites that regulates the communication between the gut microbiota and the brain. High fiber intake, prebiotics, probiotics, plant supplements, and fecal microbiome transplant (FMT) could be beneficial against gut dysbiosis-associated brain disorders. These could promote the growth of SCFA-producing bacteria, thereby enhancing the gut barrier and reducing the gut inflammatory response, increase the expression of the claudin-2 protein associated with the gut barrier, and maintain the blood-brain barrier integrity by promoting the expression of tight junction proteins such as claudin-5. Their neuroprotective effects might also be related to enhancing the expression of brain-derived neurotrophic factor (BDNF) and glucagon-like peptide (GLP-1). Further investigations are needed in the field of the gut microbiome for the elucidation of the mechanisms by which gut dysbiosis contributes to the pathophysiology of neuropsychiatric disorders.

Soybean 40S Ribosomal Protein S8 (GmRPS8) Interacts with 6K1 Protein and Contributes to Soybean Susceptibility to Soybean Mosaic Virus.

Soybean mosaic virus (SMV), a member of Potyvirus, is the most destructive and widespread viral disease in soybean production. Our earlier studies identified a soybean 40S ribosomal protein S8 (GmRPS8) using the 6K1 protein of SMV as the bait to screen a soybean cDNA library. The present study aims to identify the interactions between GmRPS8 and SMV and characterize the role of GmRPS8 in SMV infection in soybean. Expression analysis showed higher SMV-induced GmRPS8 expression levels in a susceptible soybean cultivar when compared with a resistant cultivar, suggesting that GmRPS8 was involved in the response to SMV in soybean. Subcellular localization showed that GmRPS8 was localized in the nucleus. Moreover, the yeast two-hybrid (Y2H) experiments showed that GmRPS8 only interacted with 6K1 among the eleven proteins encoded by SMV. The interaction between GmRPS8 and 6K1 was further verified by a bimolecular fluorescence complementation (BiFC) assay, and the interaction was localized in the nucleus. Furthermore, knockdown of GmRPS8 by a virus-induced gene silencing (VIGS) system retarded the growth and development of soybeans and inhibited the accumulation of SMV in soybeans. Together, these results showed that GmRPS8 interacts with 6K1 and contributes to soybean susceptibility to SMV. Our findings provide new insights for understanding the role of GmRPS8 in the SMV infection cycle, which could help reveal potyviral replication mechanisms.

Genetic Predisposition to SARS-CoV-2 Infection: Cytokine Polymorphism and Disease Transmission within Households.

We addressed the question of the influence of the molecular polymorphism of cytokines from different T helper subsets on the susceptibility to SARS-CoV-2 infection. From a cohort of 527 samples (collected from 26 May 2020 to 31 March 2022), we focused on individuals living in the same household (n = 58) with the SARS-CoV-2-infected person. We divided them into households with all individuals SARS-CoV-2 PCR positive (n = 29, households, 61 individuals), households with mixed PCR pattern (n = 24, 62) and negative households (n = 5, 15), respectively. TGF-ß1 and IL-6 were the only cytokines tested with a significant difference between the cohorts. We observed a shift toward Th2 and the regulatory Th17 and Treg subset regulation for households with all members infected compared to those without infection. These data indicate that the genetically determined balance between the cytokines acting on different T helper cell subsets may play a pivotal role in transmission of and susceptibility to SARS-CoV-2 infection. Contacts infected by their index persons were more likely to highly express TGF-ß1, indicating a reduced inflammatory response. Those not infected after contact had a polymorphism leading to a higher IL-6 expression. IL-6 acts in innate immunity, allergy and on the T helper cell differentiation, explaining the reduced susceptibility to SARS-CoV-2.

Epigenome-wide methylation haplotype association analysis identified HLA-DRB1, HLA-DRB5 and HLA-DQB1 as risk factors for rheumatoid arthritis.

The aim of this study was to compare nonrandom associations between physically adjacent single methylation polymorphism loci among rheumatoid arthritis (RA) and normal subjects for investigating RA-risk methylation haplotypes (meplotype). With 354 ACPA-positive RA patients and 335 normal controls selected from a case-control study based on Swedish population, we conducted the first RA epigenome-wide meplotype association study using our software EWAS2.0, mainly including (i) converted the ß value to methylation genotype (menotype) data, (ii) identified methylation disequilibrium (MD) block, (iii) calculated frequent of each meplotypes in MD block and performed case-control association test and (iv) screened for RA-risk meplotypes by odd ratio (OR) and p-values. Ultimately, 545 meplotypes on 334 MD blocks were identified significantly associated with RA (p-value < .05). These meplotypes were mapped to 329 candidate genes related to RA. Subsequently, combined with gene optimization, eight RA-risk meplotypes were identified on three risk genes: HLA-DRB1, HLA-DRB5 and HLA-DQB1. Our results reported the relationship between DNA methylation pattern on HLA-DQB1 and the risk of RA for the first time, demonstrating the co-demethylation of 'cg22984282' and 'cg13423887' on HLA-DQB1 gene (meplotype UU, p-value = 2.90E - 6, OR = 1.68, 95% CI = [1.35, 2.10]) may increase the risk of RA. Our results demonstrates the potential of methylation haplotype analysis to identify RA-related genes from a new perspective and its applicability to the study of other disease.