Blood Leukocytes Research Articles

Prenatal exposure to maternal smoking and adult lung cancer risk: a nested case-control study using peripheral blood leukocyte DNA methylation prediction of exposure.

A prior study reported no association between prenatal smoking methylation scores and adult lung cancer risk adjusting for methylation-predicted adult smoking, without considering maternal smoking trends by birth cohort. To address this gap, we examined the association between prenatal smoking methylation scores and adult lung cancer, independent of methylation-predicted adult packyears and by birth cohort, in a study nested in CLUE II. Included were 208 incident lung cancer cases ascertained by cancer registry linkage and 208 controls matched on age, sex, and smoking. DNA methylation was measured in prediagnostic blood. We calculated two prenatal smoking scores, using 19 (Score-19) and 15 (Score-15) previously identified CpGs and a methylation-predicted adult packyears score. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for adult packyears score and batch effects. Score-15 was positively associated with lung cancer (per standard deviation, OR = 1.40, 95% CI = 1.10-1.79, P-trend = .006), especially in the 1930-1938 birth cohort (OR = 3.43, 95% CI = 1.55-7.60, P-trend = .002). Score-19 was associated only in the 1930-1938 birth cohort (OR = 2.12, 95% CI = 1.15-3.91). Participants with both prenatal scores below the median (vs all other combinations) had lower risk (OR = 0.44, 95% CI = 0.27-0.72), especially in the 1930-1938 birth cohort (OR = 0.16, 95% CI = 0.04-0.62). Among ever smokers, participants with higher prenatal smoking scores had higher risk, irrespective of adult packyears (low: OR = 2.81, 95% CI = 1.38-5.72, high: OR = 2.67, 95% CI = 1.03-6.95). This prospective study suggests a positive association between prenatal smoking exposure and adult lung cancer risk, especially in the 1930-1938 birth cohort, independent of active smoking. Future studies with multiple birth cohorts are needed.

Low-grade systemic inflammation and peripheral airway function

BackgroundLow-grade systemic inflammation is linked to abnormal spirometry. Impulse oscillometry (IOS) is sensitive in detecting peripheral airway dysfunction, but inflammation in relation to IOS is poorly studied.ObjectivesTo analyse associations between C-reactive protein (CRP), blood eosinophils (B-Eos), blood neutrophils (B-Neu), blood lymphocytes (B-Lym), blood leukocytes (B-Leu), blood monocytes (B-Mono) and IOS.MethodsBlood biomarkers and IOS were assessed in 10 602 adults (aged 50–65 years) within the Swedish CardioPulmonary bioImage Study (SCAPIS). Upper tertiles for CRP (>1.80 mg·L−1), B-Eos (>0.20 109·L−1), B-Neu (>3.40 109·L−1), B-Lym (>2.00 109·L−1), B-Leu (>6.10 109·L−1) and B-Mono (>0.50 109·L−1) were analysed in relation to the following abnormal IOS indices: resistance at 5 Hz, resistance at 20 Hz, area of reactance, resonant frequency (>95th percentile) and reactance at 5 Hz (<5th percentile), based on healthy, never-smoking SCAPIS participants.ResultsAbnormal IOS was observed in 1715 (16.2%), of which 580 (33.8%) also had abnormal spirometry. Having several blood biomarkers in the upper tertile (1, 2–3 or 4–6versus0) was overall associated with abnormal IOS; adjusted odds ratios (OR) and 95% confidence intervals (CI) ranging from 1.19 (1.02, 1.38) to 2.27 (1.79, 2.89). Furthermore, having 2–3 or more blood biomarkersversus0 in the upper tertile was overall linked to abnormal IOS in participants with normal spirometry; adjusted OR (95% CI) ranging from 1.43 (1.17, 1.75) to 1.75 (1.29, 2.38).ConclusionsLow-grade systemic inflammation was related to abnormal IOS, and appeared consistent even when participants had normal spirometry.

Streptococcus suis 5’-nucleotidases contribute to adenosine-mediated immune evasion and virulence in a mouse model

ABSTRACT Streptococcus suis (S. suis) is an important swine bacterial pathogen and causes human infections, leading to a wide range of diseases. However, the role of 5’-nucleotidases in its virulence remains to be fully elucidated. Herein, we identified four cell wall-anchored 5’-nucleotidases (Snts) within S. suis, named SntA, SntB, SntC, and SntD, each displaying similar domains yet exhibiting low sequence homology. The malachite green reagent and HPLC assays demonstrated that these recombinant enzymes are capable of hydrolysing ATP, ADP, and AMP into adenosine (Ado), with the hierarchy of catalytic efficiency being SntC>SntB>SntA>SntD. Moreover, comprehensive enzymatic activity assays illustrated slight variances in substrate specificity, pH tolerance, and metal ion requirements, yet highlighted a conserved substrate-binding pocket, His–Asp catalytic dyad, metal, and phosphate-binding sites across Snts, with the exception of SntA. Through bactericidal assays and murine infection assays involving in site-mutagenesis strains, it was demonstrated that SntB and SntC collaboratively enhance bacterial survivability within whole blood and polymorphonuclear leukocytes (PMNs) via the Ado-A2aR pathway in vitro, and within murine blood and organs in vivo. This suggests a direct correlation between enzymatic activity and enhancement of bacterial survival and virulence. Collectively, S. suis 5’-nucleotidases additively contribute to the generation of adenosine, influencing susceptibility within blood and PMNs, and enhancing survival within blood and organs in vivo. This elucidation of their integral functions in the pathogenic process of S. suis not only enhances our comprehension of bacterial virulence mechanisms, but also illuminates new avenues for therapeutic intervention aimed at curbing S. suis infections.

Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy.

Peripheral immune cells critically contribute to the clinical-pathological progression of neurodegenerative diseases and also represent a reliable frame for translational applications. However, data on progressive supranuclear palsy (PSP) are almost scarce in this regard. Our goal is to provide a broad biological characterization of peripheral immune cells in a selected PSP cohort. Seventy-one PSP patients scored on the PSP Rating Scale (PSPRS), and 59 controls were enrolled. The blood cell count was collected, together with the neutrophil-to-lymphocyte ratio (NLR) calculation. In a subgroup of patients and controls, the peripheral blood mononuclear cells (PBMCs) were analyzed by the mitochondrial bioenergetic performance and the western blot assay of the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase 1 (HO-1) pathway and the total tau (t-tau) and phosphorylated tau (p-tau) proteins. Case-control comparison and correlation analyses were performed. PSP patients had a NLR higher than controls, with increased circulating neutrophils. The leukocyte metabolism was also globally increased and the NRF2/HO-1 pathway activated in patients. P-tau, but not t-tau, significantly accumulated in PSP PBMCs and inversely correlated with the PSPRS. PSP displays a systemic inflammatory shift of the peripheral immunity, which may justify a metabolic reprogramming of the blood leukocytes. Consistently, the NRF2/HO-1 pathway, a master regulator of inflammatory and metabolic response, was activated. PBMCs also engulf tau proteins, especially p-tau, in a way inverse to the disease severity, allowing for a peripheral tracking of tauopathy in patients. Immunometabolic targets may, therefore, gain relevance to PSP in biomarker or therapeutic purposes. © 2024 International Parkinson and Movement Disorder Society.

Recurrent pericarditis in older adults: Clinical and laboratory features and outcome.

Current guidelines for the diagnosis and treatment of pericarditis refer to the general adult population. Few and fragmentary data regarding recurrent pericarditis in older adults exist. Given the absence of specific data in scientific literature, we hypothesized that there might be clinical, laboratory and outcome differences between young adults and older adults affected by idiopathic recurrent pericarditis. We performed an international multicentric retrospective cohort study analyzing data from patients affected by recurrent pericarditis (idiopathic or post-cardiac injury) and referring to tertiary referral centers. Clinical, laboratory, and outcome data were compared between patients younger than 65 years (controls) and patients aged 65 or older. One hundred and thirty-three older adults and 142 young adult controls were enrolled. Comorbidities, including chronic kidney diseases, atrial fibrillation, and diabetes, were more present in older adults. The presenting symptom was dyspnea in 54.1% of the older adults versus 10.6% in controls (p < 0.001); pain in 32.3% of the older adults versus 80.3% of the controls (p < 0.001). Fever higher than 38°C was present in 33.8% versus 53.5% (p = 0.001). Pleural effusion was more prevalent in the older adults (55.6% vs 34.5%, p < 0.001), as well as severe pericardial effusion (>20 mm) (24.1% vs 12.7%, p = 0.016) and pericardiocentesis (16.5% vs 8.5%, p = 0.042). Blood leukocyte counts were significantly lower in the older adults (mean + SE: 10,227 + 289/mm3 vs 11,208 + 285/mm3, p = 0.016). Concerning therapies, NSAIDS were used in 63.9% of the older adults versus 80.3% in the younger (p = 0.003), colchicine in 76.7% versus 87.3% (p = 0.023), corticosteroids in 49.6% versus 26.8% (p < 0.001), and anakinra in 14.3% versus 23.9% (p = 0.044). Older adults affected by recurrent pericarditis show a different clinical pattern, with more frequent dyspnea, pleural effusion, severe pericardial effusion, and lower fever and lower leukocyte count, making the diagnosis sometimes challenging. They received significantly less NSAIDs and colchicine, likely due to comorbidities; they were also treated less commonly with anti-IL1 agents, and more frequently with corticosteroids.

Suppression of the DNA repair enzyme NEIL2 promotes persistent inflammation and genomic damage in subjects with stable COPD and during severe exacerbations.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that is an independent risk factor for lung cancer. NEIL2, a DNA glycolase involved in DNA repair during transcription, has also been associated with an increased incidence of malignancies in humans. NEIL2 knockout mouse models have demonstrated increased inflammation and oxidative DNA damage in the lungs after exposure to an inflammatory insult, but data are lacking regarding NEIL2 function in individuals with stable COPD and during severe acute exacerbations of COPD (AECOPD). We investigated whether NEIL2 levels and oxidative DNA damage to the transcribed genome are altered in individuals with stable COPD and AECOPD. The study was conducted at a single center in the US. Eligible subjects underwent a one-time 30 cc venous blood draw. The population consisted of 50 adults: 16 with stable COPD, 11 hospitalized for AECOPD, and 23 volunteers. We analyzed blood leukocytes for NEIL2 mRNA and DNA damage by RT-qPCR and LA-qPCR, respectively, in all groups. Plasma levels of seven biomarkers, CXCL1, CXCL8, CXCL9, CXCL10, CCL2, CCL11 and IL-6, were analyzed in the COPD groups using a magnetic bead panel (Millipore®). The NEIL2 mRNA levels were lower in individuals with stable COPD and AECOPD than in controls (0.72 for COPD, p = 0.0289; 0.407 for AECOPD, p = 0.0002). The difference in NEIL2 mRNA expression between the stable COPD group and AECOPD group was also statistically significant (p < 0.001). The fold change in DNA lesions per 10 kb of DNA was greater in the stable COPD (9.38, p < 0.0008) and AECOPD (15.81, p < 0.0004) groups than in the control group. The difference in fold change was also greater in the AECOPD group versus stable COPD p < 0.0236). Biomarker levels were not significantly different between the COPD groups. NEIL2 levels were correlated with plasma eosinophil levels in the stable COPD group (r = 0.737, p < 0.0027). NEIL2 mRNA levels are significantly reduced in COPD subjects and are associated with increased DNA damage and inflammation. These results reveal a mechanism that promotes persistent airway inflammation and oxidative genomic damage and increases the risk of malignancy in this population.

PoIL8-L, a teleost interleukin-8 like, enhances leukocyte cellular vitality and host defense against bacterial infections in Japanese flounder (Paralichthys olivaceus)

Interleukin-8 (IL-8), a CXC chemokine, exerts pivotal effect on cell migration, inflammatory response, and immune regulation. In this study, we examined the immunological characteristics of an IL-8 like homologue (PoIL8-L) in Japanese flounder (Paralichthys olivaceus). PoIL8-L contains a conserved chemokine CXC domain and 105 amino acid residues. PoIL8-L expression in tissues was constitutive, and significantly regulated by V. havieri or E. tarda infection. In vitro, rPoIL8-L could bind to eight tested bacteria, exhibited bacteriostatic and bactericidal effects against certain bacteria, and could bind to the targeted bacterial Ⅳ pilin protein rPilA of E. tarda. Furthermore, rPoIL8-L could attach to peripheral blood leukocytes, and enhance their immune genes expression, respiratory burst, chemotaxis, proliferation, acid phosphatase activity, and phagocytic activity. Additionally, rPoIL8-L induce neutrophils to extrude neutrophil extracellular traps. In vivo, rPoIL8-L could promote host resistance to E. tarda infection. In summary, these findings provide fresh perspectives on the immunological antibacterial properties of IL-8 in teleost.

Development and Validation of a Clinical Prediction Model for Diagnosing Mycoplasma Infections in Gynecological Patients.

In adult females, mycoplasma infection is common and challenging to diagnose. This study aimed to use retrospective laboratory data to construct a nomogram for predicting the mycoplasma infection of individuals with probable urogenital tract mycoplasma infection. A total of 2,859 patients with suspected urogenital tract mycoplasma infection were retrospectively enrolled in this study. Demographics and routine examinations of leucorrhea were used to develop a nomogram for predicting mycoplasma infection. The least absolute shrinkage and selection operator (LASSO) method was applied to filter variables and select predictors, and multivariable logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). The performance and clinical utility of the nomogram were generated by using Harrell's concordance index, calibration curve, and decision curve analysis (DCA). By using the LASSO regression method, seven variables (age, white blood cell, epithetical cell, cleanliness, candidiasis vaginalis, sialidases, and leukocyte esterase) were chosen, and a nomogram was constructed using these variables. The prediction nomogram (0.676, 95% CI: 0.611 - 0.744) demonstrated a satisfactory performance. The prediction model's AUC was 0.679 (95% CI: 0.660 - 0.691). Furthermore, the DCA showed a good clinical net benefit based on the mycoplasma infection nomogram. A nomogram was created in this study, which included seven demographic and clinical characteristics of female patients. The nomogram could be of great value for the diagnosis of mycoplasma infection.

Survival in Patients with Uveal Melanoma Is Linked to Genetic Variation at HERC2 Single Nucleotide Polymorphism rs12913832

Uveal melanoma (UM) is a rare disease, with the highest incidence in people with fair skin and light eyes. Eye color is largely genetically determined and is defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP related to prognosis. We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of 6 common eye color-related SNPs. Clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival were compared among patients with different genotypes. Three hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands. We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using 6 eye color SNPs from the HIrisPlex-S assay (Erasmus MC, Walsh lab). The genotypes extracted from the sequencing data were uploaded onto the HIrisPlexwebtool (https://hirisplex.erasmusmc.nl/) for eye color prediction. We tested the association of eye color SNPs with tumor characteristics and chromosome aberrations using Pearson's chi-square test and the Mann-Whitney U test and evaluated survival with Kaplan-Meier curves with the log-rank test and Cox regression. Uveal melanoma-related survival. Of 392 patients with analyzable genotype data, 307 patients (78%) were assigned blue eyes, 74 patients (19%) were assigned brown eyes, and 11 patients (3%) could not be assigned to either blue or brown. Patients with a genetically blue eye color showed worse survival (P= 0.04). This was related to 1 genotype: patients with the G/G genotype of rs12913832 (HERC2), which codes for blue eye color showed a worse prognosis (P= 0.017) and more often had high-risk tumors (monosomy of chromosome 3; P= 0.04) than in patients with an A/G or A/A genotype. The G/G genotype of rs12913832 (HERC2), which is related to blue eye color, not only is a genetic factor related to the risk of UM develop, but also is linked to a worse prognosis because of an association with a higher risk of a high-risk UM developing (carrying monosomy of chromosome 3). The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Interactions between rumen epithelium-associated microbiota and host immunological and metabolic adaptations in response to different milk replacer feeding intensities in dairy calves

The milk replacer feeding regime in dairy calves has a great impact on metabolic and immunological functioning and affects animal welfare and lifetime performance. The feeding regime influences the rumen microbial composition, and epithelium-associated microbes may interact with the immune system of the host. We examined the correlations between blood leukocyte counts and the rumen epithelium-associated microbiome in dairy calves fed 2 different milk replacer feeding intensities and if these factors related to metabolic traits. Fourteen newborn female dairy calves were allocated to a group receiving either 10% (n = 7) or 20% (n = 7) milk replacer of their body weight (on average 41 kg) and provided ad libitum access to grass hay and concentrate pellets. At 3 weeks of life, all calves were fitted with a rumen cannula. Calves were weaned at 12 weeks of life and received a total mixed ration for ad libitum intake. Pre- (8 to 10 weeks of life) and post-weaning (21 to 23 weeks of life), methane production was measured in respiration chambers, and rumen epithelium and blood were sampled for 16S rRNA sequencing and leukocyte analyses, respectively. Pre-weaning, the reduced milk replacer feeding intensity was accompanied with higher concentrate intake but lower growth performance (P < 0.001), a higher abundance of amylolytic and lower abundance of cellulolytic epimural microbes. The group fed a low milk replacer intensity had also greater portions of monocytes (P = 0.031), CD8+ (P < 0.001), and CD14+ (P = 0.044) leukocytes, suggesting elevated inflammatory conditions. Correlations between CD8+ T cells and rumen methanogens, Ruminococcaceae, and Lachnospiraceae were recorded, but these were not consistent throughout maturation. Post-weaning, differences in feed intake and rumen microbial composition converged among milk replacer groups, while differences in growth performance (P = 0.040) and CD8+ cells (P < 0.001) were still present. In conclusion, a reduced milk replacer feeding intensity in dairy calves compromised growth performance and immunity and this effect persisted in the long-term. Significant correlations between the proportion of leukocytes and distinct epimural microbe taxa indicated an interplay between rumen epimural colonization and immune functioning of the host. However, further research is required addressing this interplay between rumen epimural microbes and immune functioning in dairy calves.

VIABILITY OF BLOOD LEUKOCYTES OF RATS AFTER IMPLANTATION OF POLYPROPYLENE SURGICAL MESH WITH A TANTALUM-BASED COATING AND ITS DERIVATIVES

Aim. To investigate the viability and types of cell death of peripheral blood leukocytes in experimental animals after implantation of surgical meshes with a tantalum-based coating and its derivatives. Materials and methods. The experimental group included 40 male rats of the WAG population. Polypropylene surgical mesh was surgically implanted between the abdominal wall and sections of the large intestine with different types of coatings. After 28 days, collected blood was analyzed by a BD FACSCanto™ II flow cytometer. Results. It was determined that there were no significant changes in the viability of blood leukocytes between the animals of the intact group and the group of animals that underwent surgery without implantation. Analysis of leukocyte viability in groups of rats implanted with tantalum and tantalum oxide-coated meshes showed a slight decrease in viable cells compared with the results of the intact group. At the same time, the percentage of necrotic cells showed a slight increase. In the group of rats implanted with a mesh with tantalum nitride-coated, a decrease in viable leukocytes was determined in comparison with the results of the intact group by 12,9%, while the percentage of necrotic leukocytes was 3,8% higher. A 16,2% decrease in viable leukocytes was determined in the group of rats implanted with a non-coated mesh compared to the results of the intact group. At the same time, the percentage of necrotic cells was 6,9% higher. Conclusions. Implantation of uncoated and tantalum nitride-coated surgical meshes was found to decrease the percentage of viable blood leukocytes in rats compared to intact animals, while implantation of tantalum- and tantalum-oxide-coated surgical meshes did not significantly decrease viable white blood cells. leukocytes.

CLINICAL CASE OF RARE SMITH-MAGENIS SYNDROME IN NEWBORN CHILD

Aim. The purpose of the work is a comprehensive analysis of chromosomal pathology based on own detection of a rare clinical case of Smith-Magenis syndrome in a newborn child, the results of which may be useful for the detection and prevention of hereditary diseases. Materials and methods. Based on the analysis of literature data, it was found that clinical cases of rare (SMS) in newborns occur with a frequency of 1 in 25,000–1:15,000. This syndrome is caused by a chromosomal rearrangement that leads to the loss of significant segments of one chromosome from the 17th pair of chromosomes. There is a deletion of genetic material in the region of chromosome 17 (17p11.2), which is why SMS is sometimes called 17p syndrome. In this work, the analysis of clinical symptoms and laboratory-instrumental examinations, the main of which are cytogenetic (karyotyping) and molecular genetic methods, were used to confirm the diagnosis of the disease. The results were obtained during the study of the biological material of the lymphocyte culture of the peripheral blood of the child, mother and father. As a result of the cytogenetic study of the child, the karyotype 46, ХУ, del(17) (p11.2p11.2) was established, that is, a male karyotype with an interstitial deletion in the short arm of chromosome 17 within the band 17p11.2. The mother's karyotype is 46, XX, no chromosomal abnormalities were detected. The father's karyotype is 46, XU, no chromosomal abnormalities were detected. A molecular genetic study of blood leukocytes was conducted to establish the presence of microdeletions/microduplications in the corresponding loci. The result of the study is rsa17p11.2(P245)x1. Chromosome imbalance was established in the form of RAI1, DRC3, LLGL1 gene deletion in the 17p11.2 region, which verifies Smith-Magenis syndrome. Conclusions. In the work, a comprehensive analysis of chromosomal pathology was carried out based on the own detection of a clinical case of a rare Smith-Magenis syndrome in a newborn child. A detailed anamnesis, clinical manifestations, a set of laboratory-instrumental studies, the main ones of which are cytogenetic (karyotyping) and molecular genetic methods, are used for targeted examination, verification of the diagnosis and assessment of disease manifestations. The biological material of the peripheral blood culture (lymphocytes, leukocytes) of the child and parents was used. The results of a comprehensive analysis of chromosomal pathology based on one's own clinical case of the rare Smith-Magenis syndrome in a child of the neonatal period can draw the attention of primary care physicians to the study of syndromes of hereditary diseases and, in the differential diagnosis of patients, direct them to a medical-genetic consultation for cyto- and molecular-genetic studies.

Effects of parity and early pregnancy on peripheral blood leukocytes in dairy cattle

Subfertility remains a major problem in the dairy industry. Only 35-40% of high-yielding dairy cows and 55-65% of nonlactating heifers become pregnant after their first service. The immune system plays a critical role in the establishment of pregnancy. However, it can also create challenges for embryo survival and contribute to reduced fertility. We conducted 2 separate experiments to characterize changes in subsets of peripheral blood leukocytes (PBL) and their phenotype over the estrous cycle and early pregnancy in heifers and cows. We used flow cytometry and RT-qPCR to assess protein and mRNA expression of molecules important for immune function. We observed that CD14+ monocytes and CD3+ T cells tended to be affected by pregnancy status in heifers, whereas CD8B+ lymphocytes and NCR1+ natural killer (NK) cells were affected during early pregnancy in cows. Changes in expression of immune function proteins appeared to be greater in heifers than cows. To compare the most striking differences between heifers and cows observed in the initial experiments, we conducted a third experiment where PBL sampled from heifers and cows were simultaneously collected and analyzed under the same experimental conditions. Our results indicate that, compared with heifers, cows had greater mRNA expression of proinflammatory cytokines (IFNG and IL6) and AHR protein along with greater percentage of MM20A+ neutrophils and myeloid cells expressing SIRPA, ITGAM and ITGAX. Moreover, animals that failed to become pregnant showed altered expression of anti-inflammatory molecules compared with cyclic and pregnant animals. Overall, these findings support the hypothesis that early pregnancy signaling alters the phenotype of immune cells in the peripheral blood and that there are differences in the peripheral immune response to pregnancy between cows and heifers. Because cows have lower conception rates than heifers, it is possible that a more proinflammatory immune status in peripheral blood may play a role in embryo loss.

Value analysis of preoperative peripheral blood LMR in predicting prognosis of serous papillary ovarian adenocarcinoma

ObjectiveTo analyze the predictive effect of preoperative peripheral blood leukocyte related inflammatory indicators on the prognosis of patients with serous papillary ovarian adenocarcinoma.MethodsA retrospective analysis was conducted on the case data of 83 patients with ovarian cancer undergoing tumor cell reduction surgery admitted to our hospital from January 2017 to December 2020. Pathological findings confirmed serous papillary ovarian adenocarcinoma. Kaplan–Meier method was used to analyze the relationship between lymphocyte to monocyte ratio (LMR) and the patients survival prognosis. Analyzing factors affecting patient prognosis which using a multivariable Cox risk.ResultsThe overall survival (OS) of the patients with serous papillary ovarian adenocarcinoma in high LMR group was higher than that in the low LMR group preoperative. The disease free survival (DFS) of ovarian adenocarcinoma patients in the high LMR group was higher than that in the low LMR group preoperative. That was the low LMR indicating a poor prognosis. Single factor analysis showed that age of onset was correlated with OS and DFS, and the body mass index (BMI) was only correlated with OS. Multivariable analysis showed that the age of onset (HR = 2.571, 95% CI 1.199–5.512, P = 0.015) and BMI (HR = 0.337, 95% CI 0.158–0.718, P = 0.005) were independent risk factors for OS.ConclusionsAlthough the serous papillary ovarian adenocarcinoma patients with preoperative peripheral blood LMR reduction have poor prognosis, the correlation between LMR values and prognosis is not significant. Therefore, it is not recommended to use preoperative peripheral leukocyte related inflammatory indicators as prognostic markers for serous papillary ovarian adenocarcinoma.

Tuberculosis in otherwise healthy adults with inherited TNF deficiency

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette–Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte–macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette–Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Two cases of Leukemoid reaction in premature infants caused by fetal inflammatory response syndrome

BackgroundFetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients’ hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts.Case presentationWe performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies’ alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal.Conclusions . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions.

Causal association between blood leukocyte counts and vascular dementia: a two-sample bidirectional Mendelian randomization study

While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis.

Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a mendelian randomization analysis

BackgroundPrevious observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD.MethodsFive TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk.ResultsModel association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk.ConclusionMultiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.

Toll-like receptor 21 in Labeo rohita recognizes double-stranded RNA and lipopolysaccharides by engaging the critical motifs in the LRR domain and gets activated against bacterial assaults

TLR (Toll-like receptor)-21 is a non-mammalian TLR and exhibits a unique function within the innate immune systems of fishes, birds, and amphibians. Despite its important role as PRR (pattern recognition receptor), research on TLR21 in many fish species, as well as in rohu (Labeo rohita), remains relatively limited. This article describes the molecular cloning of LrTLR21 (TLR21 in L. rohita), 3D (3-dimensional) modelling of its LRR (leucine-rich repeat)-regions, prediction of LRR18 to LRR20 as the LPS (lipopolysaccharide)-binding site, and LRR1 to LRR5 and LRR21 to LRR23 as the poly I:C (polyinosinic-polycytidylic acid) binding sites. It also describes the response of LrTLR21 in response to Aeromonas hydrophila and Edwardsiella tarda infections and PAMPs (pathogen-associated molecular patterns) (LPS and poly I:C)-stimulations. The ORF (open reading frame) of the LrTLR21 comprises 2955 nucleotides, encoding 984 aa (amino acid) residues with molecular weight and isoelectric point of 113.791 kDa and ∼8.79, respectively. Domain analysis of the deduced LrTLR21 displayed the existence of a signal peptide (residues 1–24), 26 LRR regions (residues 61–685), a TM (transmembrane) domain (residues 736–758), and a TIR (Toll/interleukin-1 receptor) domain (residues 790–937). The 3D model of LrTLR21-LRR regions has parallel β-sheets and few α-helices. Phylogenetically, LrTLR21 is closely related to the Onychostoma macrolepis and Carassius gibelio TLR21, and during ontogenesis, it is expressed in most of the developmental stages. In rohu fingerlings, it is consistently expressed in all examined tissues viz., skin, liver, heart, blood, eye, muscle, kidney, intestine, brain, gill, and spleen. Upon exposure to E. tarda and A. hydrophila infections, as well as LPS and poly I:C stimulations, the expression of LrTLR21 is significantly (p < 0.05) increased in the blood, kidney, liver, and gill. In the RBCs (red blood cells), PBLs (peripheral blood leukocytes), and kidney macrophages, LrTLR21 is also significantly induced following in-vivo and in-vitro LPS and poly I: C-stimulations. These findings on LrTLR21 are the first ones showing its structural insights and PAMPs binding motifs and its key role in recognizing pathogens and their PAMPs in RBCs, PBLs, and macrophages.

Hematological parameters of COVID-19 patients at Jakarta Pondok Kopi Islamic Hospital

Background: The 2019 Corona Virus Disease (Covid-19) has become a pandemic. As of 15 January 2021, 223 countries have been infected, with a total number of 92,262,621 confirmed cases, and 1,995,037 deaths. In Indonesia, as of the same date, there were 896,642 confirmed cases and 25,767 deaths.1 Diagnosis of COVID-19 is based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) results on oropharyngeal/nasopharyngeal swab samples.2 A basic hematological examination is also conducted on patients with suspected COVID-19. The results of baseline hematological examinations are thought to be a predictor of the patient being infected with COVID-19 before the RT-PCR results are released. The purpose of this study is to identify the hematological parameters of COVID-19 patients at Pondok Kopi Islamic Hospital in Jakarta (RSIJ PK) in order to provide an overview of the hematological parameters that can be used to predict the possibility of a patient being infected with COVID-19. Methods: The study adopted a cross-sectional approach, using the database on COVID-19 patients at Pondok Kopi Islamic Hospital. Data variables were categorized and described by frequency and percentage. Statistical analysis was conducted using the likelihood ratio test and SPSS (statistical package for the social sciences) version 26. Results: The number of research respondents was 250, with 142 males (56.8%). The majority of participants were between the ages of 40 and 59, at 127 (50.8%). Most patients exhibited a moderate level of clinical severity, at 215 (86%). The three most common comorbidities were hypertension in 82 patients (32.8%), diabetes in 68 patients (27.2%), and chronic kidney disease in 27 patients (10.8%). The dominant hematological parameters were normal blood leukocytes in 157 patients (62.8%), increased Neutrophil/Lymphocyte Ratio (NLR) (&gt;3.13) in 148 patients (59.2%), low Absolute Lymphocyte Count (ALC) (&lt;1500/µL) in 133 patients (53.2%), increased C-Reactive Proteins (CRP) (&gt;10 mg/L) in 171 patients (68.4%), and increased d-dimer (&gt;0.5 µg/mL) in 148 patients (59.2%). There was a significant correlation between age (p 0.028), comorbid hypertension (p 0.002), comorbid diabetes (p 0.011), leukocyte levels (p 0.045), and ALC levels (p 0.025), and the severity of the COVID-19 disease. Conclusions: The majority of COVID-19 patients had normal blood leukocyte levels, increased NLR, low ALC, and increased CRP and d-dimer.