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BMC Immunology Jun 2024Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by...
BACKGROUND
Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by sophisticated receptor system including Killer-cell immunoglobulin-like receptor (KIR) family. We aimed to investigate the impact of possessing certain KIR genes and genotypes on COVID19 severity in Iranians. KIR genotyping was performed on 394 age/sex matched Iranians with no underlying conditions who developed mild and severe COVID- 19. The presence and/or absence of 11 KIR genes were determined using the PCR with sequence specific primers (PCR-SSP).
RESULTS
Patients with mild symptoms had higher frequency ofKIR2DS1 (p = 0.004) and KIR2DS2 (p = 0.017) genes compared to those with severe disease. While KIR3DL3 and deleted variant of KIR2DS4 occurred more frequently in patients who developed a severe form of the disease. In this study, a significant increase of and B haplotype was observed in the Mild group compared to the Severe group (respectively, p = 0.002 and p = 0.02). Also, the prevalence of haplotype A was significantly higher in the Severe group than in the Mild group (p = 0.02).
CONCLUSIONS
These results suggest that the KIR2DS1, KIR2DS, and B haplotype maybe have a protective effect against COVID-19 severity. The results also suggest the inhibitory gene KIR2DL3 and haplotype A are risk factors for the severity of COVID-19.
Topics: Humans; COVID-19; Receptors, KIR; Iran; Male; Female; Genetic Predisposition to Disease; SARS-CoV-2; Middle Aged; Adult; Severity of Illness Index; Haplotypes; Genotype; Gene Frequency; Killer Cells, Natural; Aged
PubMed: 38943065
DOI: 10.1186/s12865-024-00631-1 -
BMC Cancer Jun 2024Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating...
BACKGROUND
Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored.
METHODS
The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk.
RESULTS
MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers.
CONCLUSIONS
We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.
Topics: Humans; Lung Neoplasms; Male; Polymorphism, Single Nucleotide; Female; Genetic Predisposition to Disease; Middle Aged; Transcription Factors; Asian People; DNA-Binding Proteins; Transcription Factor MTF-1; Case-Control Studies; China; Aged; Genotype; Risk Factors; East Asian People
PubMed: 38943058
DOI: 10.1186/s12885-024-12516-y -
BMC Pregnancy and Childbirth Jun 2024Phytochemicals are non-nutritive bioactive compounds with beneficial effects on the metabolism of glucose. This study aimed to clarify the possible causal effect of the...
BACKGROUND
Phytochemicals are non-nutritive bioactive compounds with beneficial effects on the metabolism of glucose. This study aimed to clarify the possible causal effect of the pre-pregnancy dietary phytochemical index (DPI) on gestational diabetes mellitus (GDM).
METHODS
In this prospective cohort study 1,856 pregnant women aged 18-45 years who were in their first trimester, were recruited and followed up until delivery. The dietary intakes of participants were examined using an interviewer-administered validated 168-item semi-quantitative food frequency questionnaire (FFQ). Inverse probability weighting (IPW) of propensity scores (PS), estimated from the generalized boosted model (GBM) were used to obtain a adjusted risk ratio (aRR) for potential confounders.
RESULTS
During the follow-up period, 369 (19.88%) women were diagnosed with GDM. DPI scores ranged from 6.09 to 89.45. There was no association between DPI scores and GDM (aRR: 1.01, 95% confidence interval [CI]: 0.92, 1.08; p trend = 0.922). When comparing DPI quartile 4 (most pro-phytochemical content) to quartile 1 (few phytochemical contents), there was no significant difference between them (aRR: 0.97; 95% CI: 0.75, 1.25; p = 0.852). Also, there was no significant difference between DPI quartile 3 and quartile 1 (aRR: 1.04; 95% CI: 0.81, 1.34; p = 0.741) as well as DPI quartile 2 and quartile 1 (aRR: 0.92; 95% CI: 0.71, 1.21; p = 0.593).
CONCLUSIONS
Although this data did not support the association between pre-pregnancy DPI scores and GDM, further cohort studies to ascertain the causal association between them are warranted.
Topics: Humans; Female; Pregnancy; Diabetes, Gestational; Adult; Prospective Studies; Young Adult; Phytochemicals; Diet; Adolescent; Middle Aged; Risk Factors; China; Pregnancy Trimester, First; Cohort Studies
PubMed: 38943050
DOI: 10.1186/s12884-024-06643-4 -
BMC Infectious Diseases Jun 2024Respiratory viral illnesses among children are a prominent cause of morbidity and mortality in the developing world. The aim of this study is to understand the seasonal...
BACKGROUND
Respiratory viral illnesses among children are a prominent cause of morbidity and mortality in the developing world. The aim of this study is to understand the seasonal pattern and surge of respiratory viruses among the Nicobarese tribe.
METHODS
Respiratory specimens were collected from both ARI and SARI cases attended the BJR district hospital in Car Nicobar Island, India, between 2021 and 2022. Respiratory viruses were identified from the specimens by using the qRT-PCR assay. Meteorological parameters were collected and evaluated using Microsoft Excel and SPSS 21. The significant association between the surge of respiratory viruses and each climatic parameter was evaluated.
RESULTS
In this hospital-based cross-sectional study, 471 ILI cases were enrolled, and 209 of these were positive for respiratory viral infections. Of these respiratory virus infections, 201 (96.2%) were infected with a single respiratory virus infection, and 8 (3.8%) had mixed viral infections. Fever, cough, and chills were the most common symptoms of respiratory illness among this indigenous population. There was a significant link between respiratory viruses and influenza-like illness in children (below 5 years and 6 to 15 years).
CONCLUSION
This prevalence study revealed that viral respiratory infections were more common in children than adults. Among these respiratory viruses, respiratory syncytial virus A (RSV) and influenza B virus were predominantly reported among tribal children up to age five years. In the year 2021, these viruses were recorded frequently during the winter season. Climate factors such as high humidity, high precipitation, moderate temperature, and moderate rainfall are found to be correlated with respiratory viral infections. This study implicates important information for preventing a further outbreak of respiratory viral infections in Car Nicobar Island.
Topics: Humans; Seasons; Respiratory Tract Infections; India; Child; Child, Preschool; Adolescent; Cross-Sectional Studies; Female; Male; Adult; Infant; Indigenous Peoples; Young Adult; Virus Diseases; Viruses; Prevalence; Middle Aged
PubMed: 38943048
DOI: 10.1186/s12879-024-09536-1 -
Scientific Reports Jun 2024Monarch butterfly (Danaus plexippus L.) populations have declined in North America. The International Union for Conservation of Nature (IUCN) recently classified the...
Monarch butterfly (Danaus plexippus L.) populations have declined in North America. The International Union for Conservation of Nature (IUCN) recently classified the species as endangered, sparking public concern and conservation efforts. Our approach to conservation is through cryopreservation of germinal cells and tissue. The goal of this study was to develop a cryopreservation protocol for monarch spermatozoa to ensure successful long-term storage. Cryopreserved sperm cells would provide a reserve of monarch germplasm, which could be utilized in the event of population loss. In this study, sperm cell bundles collected from male monarch butterflies were cryopreserved in a cryoprotective medium and stored in liquid nitrogen. To determine the post-cryopreservation sperm cell viability, a subsample of preserved sperm bundles were thawed rapidly, and their viability was qualified using a sperm live/dead stain. We are presenting a protocol to preserve and store genetic material and viable sperm bundles of the monarch butterfly. To date, this is the first report of successful cryopreservation of monarch germplasm which sets the foundation for cryostorage and could be extensible to other vulnerable lepidopterans.
Topics: Butterflies; Cryopreservation; Animals; Male; Spermatozoa; Conservation of Natural Resources; Endangered Species; Cell Survival; Cryoprotective Agents
PubMed: 38942916
DOI: 10.1038/s41598-024-65624-x -
Scientific Reports Jun 2024Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in...
Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be 'objective' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.
Topics: Humans; Mendelian Randomization Analysis; Glycated Hemoglobin; Accelerometry; Sleep; Blood Glucose; Male; Female; Middle Aged; Adult; Self Report; Aged; Sleep Initiation and Maintenance Disorders
PubMed: 38942746
DOI: 10.1038/s41598-024-58007-9 -
NPJ Genomic Medicine Jun 2024Leveraging whole genome sequencing data of 1751 individuals from the UK and 2587 Qatari subjects, we suggest here an association of rare variants mapping to the sour...
Leveraging whole genome sequencing data of 1751 individuals from the UK and 2587 Qatari subjects, we suggest here an association of rare variants mapping to the sour taste-associated gene KCNJ2 with reduced low-density lipoprotein cholesterol (LDL-C, P = 2.10 × 10) and with a 22% decreased dietary trans-fat intake. This study identifies a novel candidate rare locus for LDL-C, adding insights into the genetic architecture of a complex trait implicated in cardiovascular disease.
PubMed: 38942744
DOI: 10.1038/s41525-024-00417-9 -
Journal of Lipid Research Jun 2024The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPL) in the development and progression of coronary disease is known, but their influence on...
The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPL) in the development and progression of coronary disease is known, but their influence on extra-coronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extra-coronary vascular disease and incident major adverse limb events (MALE). 446 participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extra-coronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (OR 2.14 95% CI: 1.03, 4.44) and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extra-coronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extra-coronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries. These results lay a foundation in support of studying Lp(a) lowering medications and their effect on limb-related complications.
PubMed: 38942114
DOI: 10.1016/j.jlr.2024.100585 -
Cell Jun 2024A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains...
A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains precarious due to the potential genetic consequences of population declines, which are poorly understood on a timescale beyond a few generations. Woolly mammoths (Mammuthus primigenius) became isolated on Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct around 4,000 years ago. To study the evolutionary processes leading up to the mammoths' extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that the population recovered quickly from a severe bottleneck and remained demographically stable during the ensuing six millennia. We find that mildly deleterious mutations gradually accumulated, whereas highly deleterious mutations were purged, suggesting ongoing inbreeding depression that lasted for hundreds of generations. The time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked populations.
PubMed: 38942016
DOI: 10.1016/j.cell.2024.05.033 -
Neurology(R) Neuroimmunology &... Sep 2024Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw...
BACKGROUND AND OBJECTIVES
Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS).
METHODS
We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests.
RESULTS
In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]:1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], 3.82e). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR: 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], = 0.04). Compared with raw values with arbitrary cutoffs, applying the score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score).
DISCUSSION
In conclusion, our work demonstrated reference cohort-based scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.
Topics: Humans; Female; Male; Tomography, Optical Coherence; Adult; Middle Aged; Disease Progression; Prognosis; Multiple Sclerosis; Retina; Severity of Illness Index
PubMed: 38941572
DOI: 10.1212/NXI.0000000000200269