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Turkish Journal of Medical Sciences 2023Dental caries is a frequently occurring and multifactorial chronic disease in children resulting from the interaction of cariogenic bacteria and host susceptibility. The...
BACKGROUND/AIM
Dental caries is a frequently occurring and multifactorial chronic disease in children resulting from the interaction of cariogenic bacteria and host susceptibility. The aim of this study was to elucidate the impacts of primary immunodeficiency disorders (PIDs) on microbiota of dental caries in children by 16S rRNA gene-based metagenomic analysis.
MATERIALS AND METHODS
Enrolled in this study were 15 children with primary PID with caries (PID group) and 15 healthy children with caries as a control (CG). The DMFT index, saliva flow rate, and buffering capacity of each participant were assessed before the metagenomic analyses were conducted. For taxonomic profiling, the reads were obtained by high-throughput sequencing of the V3-V4 hypervariable region of 16S rRNA.
RESULTS
The DMFT score, saliva flow rate, and buffering capacity of the groups were similar. The flow rate and buffering capacity had no correlation with the number of species with 95% confidence. The metagenomic analysis resulted in the identification of 2440 bacterial species in all of the samples. Among the 50 most prevalent species present at ≥1% relative abundance, and were differentially more abundant in the PID group. The PID group and CG showed similar species richness and evenness, but 4 of the 5 samples with the highest Shannon-Weiner and Inverse Simpson indices belonged to the PID group. The Spearman test results for correlation of the species in the PID subgroups showed that had a positively correlated relationship with both and genera incertae sedis.
CONCLUSION
This study provided insight into the caries microbiota of children with immunodeficiency diseases. Differentially abundant species, novel bacterial associations, and unique bacterial species were disclosed in the PID samples, indicating the role of the immune system in altering the caries microbiota. The prominent bacterial species and associations in the PID group should be suspected in regard to their link with present or future diseases.
Topics: Humans; Dental Caries; Child; RNA, Ribosomal, 16S; Female; Male; Metagenomics; Microbiota; Primary Immunodeficiency Diseases; Child, Preschool; Saliva; Case-Control Studies
PubMed: 38813004
DOI: 10.55730/1300-0144.5719 -
Sleep Advances : a Journal of the Sleep... 2024Little is known about sleep health among staff in the US juvenile justice system. Poor sleep health is associated with negative mental and physical health, which may...
STUDY OBJECTIVES
Little is known about sleep health among staff in the US juvenile justice system. Poor sleep health is associated with negative mental and physical health, which may impact daily interactions and treatment of detained youth. The current study explored sleep-wake patterns and sleep health knowledge of Department of Juvenile Services (DJS) staff in Maryland (MD).
METHODS
DJS Staff ( = 218) were invited to complete a survey that queried staff on their own sleep-wake patterns, job role and schedule, and knowledge of youth sleep needs. Descriptive analyses and multivariate analyses of variance (MANCOVA) were conducted to summarize workers' sleep-wake patterns and examine differences by staff position and schedule.
RESULTS
Fifty-one percent of staff served as RAs who directly supervise the youth. Just over half (55%) worked in detention and 45% in treatment facilities. Staff reported sleeping 7.24 hours (SD = 4.10) on workdays and 8.59 hours (SD = 2.69) on non-workdays. RA staff working night/rotating versus day shifts reported the most sleep irregularity with larger weekend oversleep times. A little more than half of the staff (53.9%) were knowledgeable regarding youth sleep health with differences by position type.
CONCLUSIONS
Findings show that DJS staff are meeting recommended sleep duration guidelines but are still experiencing sleep schedule and time in bed irregularity. Knowledge variability of youth sleep health across staff may necessitate focused educational programming. Overall, this study may inform future development and prioritization of sleep and circadian health interventions and educational campaigns for staff who work with detained juveniles. This paper is part of the Sleep and Circadian Health in the Justice System Collection.
PubMed: 38812810
DOI: 10.1093/sleepadvances/zpae030 -
Frontiers in Oncology 2024Molecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven...
INTRODUCTION
Molecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven trials of targeted therapy matched to tumour molecular profiles, with improved outcomes reported using such an approach. Here, we review NGS results and treatment outcomes for a cohort of Asian MBC patients in the phase I unit of a tertiary centre.
METHODS
Patients with MBC referred to a phase I unit underwent NGS via Ion AmpliSeq Cancer Hotspot v2 (ACH v2, 2014-2017) prior to institutional change to FoundationOne CDx (FM1; 2017-2022). Patients were counselled on findings and enrolled on matched therapeutic trials, where available. Outcomes for all subsequent treatment events were recorded to data cut-off on January 31, 2022.
RESULTS
A total of 215 patients were enrolled with successful NGS in 158 patients. The PI3K/AKT/PTEN pathway was the most altered with one or more of the pathway member genes affected in 62% (98/158) patients and 43% of tumours harbouring a alteration. Tumour mutational burden (TMB) was reported in 96/109 FM1 sequenced patients, with a mean TMB of 5.04 mt/Mb and 13% (12/96) with TMB ≥ 10 mt/Mb. Treatment outcomes were evaluable in 105/158 patients, with a pooled total of 216 treatment events recorded. Matched treatment was administered in 47/216 (22%) events and associated with prolonged median progression-free survival (PFS) of 21.0 weeks [95% confidence interval (CI) 11.7, 26.0 weeks] 12.1 weeks (95% CI 10.0, 15.4 weeks) in unmatched, with hazard ratio (HR) for progression or death of 0.63 (95% CI 0.41, 0.97; p = 0.034). In the subgroup of -altered MBC, the HR for progression or death was 0.57 (95% CI 0.35, 0.92; p = 0.02), favouring matched treatment. Per-patient overall survival (OS) analysis (n = 105) showed improved survival for patients receiving matched treatment unmatched, with median OS (mOS) of 30.1 11.8 months, HR = 0.45 (95% CI 0.24, 0.84; p = 0.013). Objective response rate (ORR) in the overall population was similar in matched and unmatched treatment events (23.7% 17.2%, odds ratio of response 1.14 95% CI 0.50, 2.62; p = 0.75).
CONCLUSIONS
Broad-panel NGS in MBC is feasible, allowing therapeutic matching, which was associated with improvements in PFS and OS.
PubMed: 38812774
DOI: 10.3389/fonc.2024.1342346 -
Frontiers in Microbiology 2024The possibility that there is a resident and stable commensal microbiome within the pregnant uterus has been supported and refuted by a series of recent studies. One...
INTRODUCTION
The possibility that there is a resident and stable commensal microbiome within the pregnant uterus has been supported and refuted by a series of recent studies. One element of most of the initial studies was that they were based primarily on 16S rRNA gene sequencing from bacteria. To account for this limitation, the current study performed both bacterial culture and 16S rRNA gene sequencing in a side-by-side manner (e.g., same tissues isolated from the same animal).
METHODS
The uteruses of 10 mid-pregnant (156 ± 5 d of gestation) Holstein heifers and cows were collected following slaughter. The external surface of the reproductive tract (positive control for contamination during tissue collection) as well as tissues within the pregnant uterus (placentome, inter-cotyledonary placenta, inter-caruncular endometrium, amnionic fluid, allantoic fluid, fetal abomasum content, and fetal meconium) were sampled for bacterial culture and 16S rRNA gene sequencing.
RESULTS
There were 87 unique bacterial species cultured from the external surface of the pregnant reproductive tract (contamination control) and 12 bacterial species cultured from pregnancy tissues. Six out of 10 cattle (60%) exhibited bacterial growth in at least one location within the pregnant uterus. For the metataxonomic results (16S rRNA gene sequencing), a low targeted microbial biomass was identified. Analyses of the detected amplicon sequence variants (ASV) revealed that there were: (1) genera that were prevalent on both the external surface and within the pregnant uterus; (2) genera that were prevalent on the external surface but either not detected or had very low prevalence within the pregnant uterus; and (3) genera that were either not detected or had low prevalence on the external surface but found with relatively high prevalence within the pregnant uterus.
CONCLUSION
There are a small number of viable bacteria in the pregnant uterus. The 16S rRNA gene sequencing detected a microbial community within the pregnant uterus but with a low biomass. These results are consistent with recent studies of the pregnant bovine uterus and leave open the question of whether there is adequate microbial mass to significantly affect the biology of the normal healthy bovine pregnancy.
PubMed: 38812678
DOI: 10.3389/fmicb.2024.1385497 -
Frontiers in Microbiology 2024The gene family of thaumatin-like proteins (TLPs) plays a crucial role in the adaptation of organisms to environmental stresses. In recent years, fungal secreted...
The gene family of thaumatin-like proteins (TLPs) plays a crucial role in the adaptation of organisms to environmental stresses. In recent years, fungal secreted proteins (SP) with inducing disease resistance activity in plants have emerged as important elicitors in the control of fungal diseases. Identifying SPs with inducing disease resistance activity and studying their mechanisms are crucial for controlling sheath blight. In the present study, 10 proteins containing the thaumatin-like domain were identified in strain AG4-JY of and eight of the 10 proteins had signal peptides. Analysis of the TLP genes of the 10 different anastomosis groups (AGs) showed that the evolutionary relationship of the TLP gene was consistent with that between different AGs of . Furthermore, it was found that RsTLP3, RsTLP9 and RsTLP10 were regarded as secreted proteins for their signaling peptides exhibited secretory activity. Prokaryotic expression and enzyme activity analysis revealed that the three secreted proteins possess glycoside hydrolase activity, suggesting they belong to the TLP family. Additionally, spraying the crude enzyme solution of the three TLP proteins could enhance maize resistance to sheath blight. Further analysis showed that genes associated with the salicylic acid and ethylene pathways were up-regulated following RsTLP3 application. The results indicated that RsTLP3 had a good application prospect in biological control.
PubMed: 38812677
DOI: 10.3389/fmicb.2024.1377726 -
Frontiers in Immunology 2024HIV-1 infection may produce a detrimental effect on the immune response. Early start of antiretroviral therapy (ART) is recommended to preserve the integrity of the...
INTRODUCTION
HIV-1 infection may produce a detrimental effect on the immune response. Early start of antiretroviral therapy (ART) is recommended to preserve the integrity of the immune system. In fact, people with HIV (PWH) and normal CD4/CD8 ratio appear not to be more susceptible to severe forms of COVID-19 than the general population and they usually present a good seroconversion rate in response to vaccination against SARS-CoV-2. However, few studies have fully characterized the development of cytotoxic immune populations in response to COVID-19 vaccination in these individuals.
METHODS
In this study, we recruited PWH with median time of HIV-1 infection of 6 years, median CD4/CD8 ratio of 1.0, good adherence to ART, persistently undetectable viral load, and negative serology against SARS-CoV-2, who then received the complete vaccination schedule against COVID-19. Blood samples were taken before vaccination against COVID-19 and one month after receiving the complete vaccination schedule.
RESULTS
PWH produced high levels of IgG against SARS-CoV-2 in response to vaccination that were comparable to healthy donors, with a significantly higher neutralization capacity. Interestingly, the cytotoxic activity of PBMCs from PWH against SARS-CoV-2-infected cells was higher than healthy donors before receiving the vaccination schedule, pointing out the pre-existence of activated cell populations with likely unspecific antiviral activity. The characterization of these cytotoxic cell populations revealed high levels of Tgd cells with degranulation capacity against SARS-CoV-2-infected cells. In response to vaccination, the degranulation capacity of CD8+ T cells also increased in PWH but not in healthy donors.
DISCUSSION
The full vaccination schedule against COVID-19 did not modify the ability to respond against HIV-1-infected cells in PWH and these individuals did not show more susceptibility to breakthrough infection with SARS-CoV-2 than healthy donors after 12 months of follow-up. These results revealed the development of protective cell populations with broad-spectrum antiviral activity in PWH with normal CD4/CD8 ratio and confirmed the importance of early ART and treatment adherence to avoid immune dysfunctions.
Topics: Humans; SARS-CoV-2; COVID-19; HIV Infections; Male; Female; Middle Aged; Adult; CD4-CD8 Ratio; COVID-19 Vaccines; CD8-Positive T-Lymphocytes; Antibodies, Viral; HIV-1; Cytotoxicity, Immunologic; Immunoglobulin G; T-Lymphocytes, Cytotoxic; Vaccination
PubMed: 38812512
DOI: 10.3389/fimmu.2024.1362621 -
Frontiers in Bioscience (Landmark... May 2024Human immunodeficiency virus (HIV) infection is associated with pronounced oxidative stress, leading to the development of various virus-associated pathologies. A wealth...
BACKGROUND
Human immunodeficiency virus (HIV) infection is associated with pronounced oxidative stress, leading to the development of various virus-associated pathologies. A wealth of evidence suggests that, along with canonical enzymes of reactive oxygen species regulation, human blood contains antibodies with peroxidase, superoxide dismutase, and catalase activities. Here we show that the catalase activity of IgGs and their κκ-IgG, λλ-IgG, and κλ-IgG subfractions of HIV-infected individuals is significantly different compared to the healthy donors.
METHODS
Protein G-Sepharose sorbent was used to resolve IgG from blood of healthy donors and HIV-infected patients by affinity chromatography. Subfractions of κκ-IgG, λλ-IgG, and κλ-IgG were separated from IgGs samples of each group by affinity chromatography on sorbents containing immobilized antibodies to κ or λ light human chains. The IgG catalase activity level was measured spectrophotometrically by evaluating the decrease in optical density (A240) due to hydrogen peroxide decomposition.
RESULTS
The relative catalase activity of antibodies from HIV-infected patients ( = (1.41 ± 0.92) × 103 min-1, 95% CI: [1.01-1.81]) was statistically significant, 1.6 times higher ( = 0.014) compared to apparently healthy donors ((0.86 ± 0.49) × 103, 95% CI: [0.69-1.03]). The activity level of κκ-IgG HIV-infected patients ((0.44 ± 0.04) × 103 min-1) was 1.4 times higher than that of λλ-IgGs ((0.31 ± 0.025) × 103 min-1); the opposite was observed for κκ-IgGs from apparently healthy donors, which activity ((0.17 ± 0.015) × 103 min-1) was 3.1 times lower compared to λλ-IgGs ((0.53 ± 0.045) × 103 min-1).
CONCLUSIONS
Thus, the data obtained may indicate that IgG with increased catalase activity may prevent harmful processes arising from oxidative stress in HIV-infected patients, acting as an additional natural molecular mechanism of regulation of hydrogen peroxide level.
Topics: Humans; Catalase; Immunoglobulin G; HIV Infections; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Adult; Case-Control Studies; Male; Female; Chromatography, Affinity; Oxidative Stress; Middle Aged
PubMed: 38812328
DOI: 10.31083/j.fbl2905191 -
Frontiers in Bioscience (Landmark... May 2024DELLA protein is a crucial factor which played pivotal roles in regulating numerous intriguing biological processes in plant development and abiotic stress responses....
BACKGROUND
DELLA protein is a crucial factor which played pivotal roles in regulating numerous intriguing biological processes in plant development and abiotic stress responses. However, little is known about the function and information of DELLA protein in Chinese cabbage.
METHODS
Using 5 gene sequences in as probes, 5 genes in Chinese cabbage were identified by Blast search in Chinese cabbage database (Brassica database (BRAD)). The National Center for Biotechnology Information (NCBI), ExPaSy, SWISS-MODEL, DNAMAN, MEGA 11, PlantCARE were used to identify and analyze the gene family of Chinese cabbage. Gene expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of was verified by overexpression and phenotypic analysis of and yeast hybrid.
RESULTS
In this study, 5 homologous to were identified and cloned based on the Brassica database, namely, , , , and . All BraDELLAs contain the DELLA, TVHYNP, and GRAS conserved domains. Cis-element analysis revealed that the promoter regions of these 5 genes all contain light-responsive elements, TCT motif, I-box, G-box, and box 4, which are associated with GA signaling. Transcriptome analysis results proved that the expression of , , and in Y2 at different growth stages were lower than them in Y7, which is consistent with the phenotype that Y7 exhibited stronger stress tolerance than Y2. It is worth emphasizing that even through the overexpression of in resulted in smaller leaf size and lower fresh weight compared to the wild type (WT) Arabidopsis: Columbia, a stronger response to abiotic stresses was observed in . It indicated that can improve the stress resistance of plants by inhibiting their growth. Moreover, the yeast two-hybrid experiment confirmed that BraA10gRGL3-Y7 can interacted with BraA05gGID1a-Y7, BraA04gGID1b1, BraA09gGID1b3-Y2, and BraA06gGID1c, whereas BraA10gRGL3-Y2 cannot interact with any BraGID1.
CONCLUSIONS
Collectively, play important role in plant development and response to abiotic stress. The differences in amino acid sequences between BraA10gRGL3-Y2 and BraA10gRGL3-Y7 may result in variations in their protein binding sites, thus affecting their interaction with the BraGID1 family proteins. This systematic analysis lays the foundation for further study of the functional characteristics of genes of Chinese cabbage.
Topics: Gene Expression Regulation, Plant; Plant Proteins; Arabidopsis; Brassica rapa; Stress, Physiological; Phylogeny; Arabidopsis Proteins; Gene Expression Profiling; Plants, Genetically Modified; Genes, Plant; Genome, Plant
PubMed: 38812324
DOI: 10.31083/j.fbl2905198 -
Frontiers in Bioscience (Landmark... May 2024The epithelia of the intestine perform various functions, playing a crucial role in providing a physical barrier and an innate immune defense against infections. By...
BACKGROUND
The epithelia of the intestine perform various functions, playing a crucial role in providing a physical barrier and an innate immune defense against infections. By generating a "three-dimensional" (3D) model of cell co-cultures using the IPEC-J2 cell line and porcine blood monocyte-derived macrophages (MDMs), we are getting closer to mimicking the porcine intestine Methods: The effect of B1/1 and CCM 7158 (indicator strain) on the relative gene expression of interleukins (IL-1β, IL-6, IL-8, IL-18 and IL-10), genes encoding receptors for TLR4 and TLR2, tight junction proteins such as claudin-1 (CLDN1), occludin (OCLN) and important antimicrobial proteins such as lumican (LUM) and olfactomedin-4 (OLMF-4) was monitored in this model.
RESULTS
The results obtained from this pilot study point to the immunomodulatory potential of newly isolated B1/1, as it was able to suppress the enhanced pro-inflammatory response to lipopolysaccharide (LPS) challenge in both cell types. B1/1 was even able to up-regulate the mRNA levels of genes encoding antimicrobial proteins LUM and OLFM-4 and to increase tight junction (TJ)-related genes and , which were significantly down-regulated in LPS-induced IPEC-J2 cells. Conversely, CCM 7158, chosen as an indicator lactic acid bacteria (LAB) strain, increased the mRNA levels of the investigated pro-inflammatory cytokines (IL-18, IL-6, and IL-1β) in MDMs when LPS was simultaneously applied to basally deposited macrophages. Although CCM 7158 induced the production of pro-inflammatory cytokines, synchronous up-regulation of the anti-inflammatory cytokine IL-10 was detected in both LAB strains used in both cell cultures.
CONCLUSIONS
The obtained results suggest that the recently isolated LAB strain B1/1 has the potential to alleviate epithelial disruption caused by LPS and to influence the production of antimicrobial molecules by enterocytes.
Topics: Animals; Cytokines; Swine; Limosilactobacillus reuteri; Cell Line; Macrophages; Antimicrobial Peptides; Coculture Techniques
PubMed: 38812316
DOI: 10.31083/j.fbl2905180 -
Frontiers in Bioscience (Landmark... May 2024The F-box protein (FBXO) family plays a key role in the malignant progression of tumors. However, the biological functions and clinical value of the FBXO family in liver...
OBJECTIVE
The F-box protein (FBXO) family plays a key role in the malignant progression of tumors. However, the biological functions and clinical value of the FBXO family in liver cancer remain unclear. Our study comprehensively assessed the clinical value of the FBXO family in hepatocellular carcinoma (HCC) and constructed a novel signature based on the FBXO family to predict prognosis and guide precision immunotherapy.
METHODS
The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression characteristics and prognostic value of the FBXO family in HCC. A predictive model based on the FBXO family using TCGA database; and its predictive ability was validated using the ICGC database. Further analyses revealed that this predictive model can independently predict the overall survival (OS) rate of patients with HCC. We further analyzed the association of this predictive model with signaling pathways, clinical pathological features, somatic mutations, and immune therapy responses. Finally, we validated the biological functions of cyclin F () through experiments.
RESULTS
A predictive model involving three genes (, , and ) was constructed, effectively identifying high and low-risk patients with differences in OS, clinicopathological characteristics, somatic mutations, and immune cell infiltration status. Additionally, knock-down of in HCC cell lines reduced cell proliferation , suggesting that may be a potential therapeutic target for HCC.
CONCLUSIONS
The predictive model based on the FBXO family can effectively predict OS and the immune therapy response in HCC. Additionally, is a potential therapeutic target for HCC.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; F-Box Proteins; Prognosis; Male; Female; Cell Line, Tumor; Middle Aged; Gene Expression Regulation, Neoplastic; Cyclins; Biomarkers, Tumor; Cell Proliferation; Databases, Genetic
PubMed: 38812312
DOI: 10.31083/j.fbl2905202