BACKGROUND: Physical activity (PA) reduces the risk of developing breast cancer (BC) and mortality rate in BC patients starting PA after diagnosis. Immunomodulation is considered responsible for these effects. However, limited data exist on the immunomodulation induced by moderate PA (mPA) during neoadjuvant chemotherapy (NACT). We have investigated the longitudinal change of cytokines during NACT alone or combined with mPA.
METHODS: Twenty-three cytokines were analyzed in BC patients at consecutive timepoints: at baseline (T0), before starting mPA (T1), before surgery (T2), and after surgery (T3). mPA consisted of 3-weekly brisk-walking sessions for 9-10 consecutive weeks.
RESULTS: Ninety-two patients were assessed: 21 patients refused mPA (untrained) and 71 agreed (trained). At T1, NACT induced significant up-regulation of interleukin (IL)-5, IL-6, IL-15, chemokine ligand (CCL)-2, interferon-γ, and C-X-C motif ligand (CXCL)-10 and reduction of expression of IL-13 and CCL-22. At T2, NACT and mPA induced up-regulation of IL-21, CCL-2, and tumor necrosis factor-α and reduction of expression of IL-8, IL-15, vascular endothelial growth factor, and soluble interleukin 6 receptor. Only CXCL-10 increased in untrained patients. A cytokine score (CS) was created to analyze, all together, the changes between T1 and T2. At T2 the CS decreased in trained and increased in untrained patients. We clustered the patients using cytokines and predictive factors and identified two clusters. The cluster A, encompassing 90% of trained patients, showed more pathological complete response (pCR) compared to the cluster B: 78% versus 22%, respectively.
CONCLUSIONS: mPA interacts with NACT inducing CS reduction in trained patients not observed in untrained patients, suggesting a reduction of inflammation, notwithstanding chemotherapy. This effect may contribute to the higher rate of pCR observed in the cluster A, including most trained patients.

The cross-talk between the innate and adaptive immune response represents the first defense weapon against the threat of pathogens. Substantial evidence has shown a relationship between immune phenotype lymphocytes and COVID-19 disease severity and/or implication in susceptibility to SARS-CoV-2 infection. Recently, belonging to ABO blood groups has been investigated as a correlation factor to COVID-19 disease. This pilot study investigated lymphocyte typing in a cohort of blood donors to understand the underlying mechanism in SARS-CoV-2 infection linked to the blood group. The study cohort consisted of 20-64-year-old subjects, without comorbidities, from both sexes, who were COVID-19 vaccinated with previous or no infection history. Whole blood samples, collected at A.O.R.N. Sant\'Anna and San Sebastiano Hospital (Campania Region), were processed by multiparametric cytofluorimetric assay, to characterize CD4+ helper and CD8+ cytotoxic T cell CD3+ subpopulations. The CD45RA, CCR7, CD27, CD28, CD57 and PD-1 markers were investigated to delineate the peripheral T-cell maturation stages. Differences were detected in ABO blood types in CD3+, CD4+ gated on CD3+, CD8+ and CD8+ gated on CD3+ percentage. These results contribute to identifying a memory cell \"identikit\" profile in COVID-19 disease, thus leading to a useful tool in precision medicine.

Genital tract infections can cause a variety of harmful health outcomes, including endometritis, bacterial vaginosis, and pelvic inflammatory disease, in addition to infertility. Anaerobic bacteria, such as Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae, are more commonly identified in cases of bacterial vaginosis than lactobacilli. It is unknown how the microorganisms that cause pelvic inflammatory diseases and endometritis enter the uterus. Both prospective and retrospective research have connected pelvic inflammatory disorders, chronic endometritis, and bacterial vaginosis to infertility. Similar to bacterial vaginosis, endometritis-related infertility is probably caused by a variety of factors, such as inflammation, immune system recognition of sperm antigens, bacterial toxins, and a higher risk of STDs. Preconception care for symptomatic women may include diagnosing and treating pelvic inflammatory disease, chronic endometritis, and bacterial vaginosis before conception to optimize the results of both natural and assisted reproduction.

OBJECTIVE: Osteoporosis (OP) is a disease characterized by decreased bone mass, deteriorated microstructure, and increased fragility and fracture risk. The diagnosis and prevention of OP and its complications have become major public health challenges. Therefore, exploring the complex ecological connections between the immune and skeletal systems may provide new insights for clinical prevention and treatment strategies.
METHODS: First, we performed single-cell RNA sequencing on human lumbar lamina tissue and conducted clustering and subgroup analysis of quality-controlled single-cell transcriptome data to identify target subgroups. Subsequently, enrichment analysis and pseudotime analysis were performed. In addition, we conducted in-depth studies on the gene regulatory network between different cell subgroups and the communication between bone immune cells.
RESULTS: In this study, we identified several cell subgroups that may be involved in the progression of OP. For example, the CCL4+ NKT and CXCL8+ neutrophils subgroups promote OP progression by mediating an inflammatory environment that disrupts bone homeostasis, and the MNDA+ Mac subgroup promotes osteoclast differentiation to promote OP. Moreover, the TNFAIP6+ Obl, NR4A2+ B and HMGN2+ erythrocyte subgroups promoted the balance of bone metabolism and suppressed OP. In the cell communication network, Obl closely interacts with immune cell subgroups through the CXCR4-CXCL12, CTGF-ITGB2, and TNFSF14-TNFRSF14 axes.
CONCLUSIONS: Our research revealed specific subgroups and intercellular interactions that play crucial roles in the pathogenesis of OP, providing potential new insights for more precise therapeutic interventions for OP.

UNASSIGNED: Immune cells are dynamic in the inflammatory environment and play a key role in eradicating periodontal pathogens, modulating immune responses, and instigating tissue destruction. Identifying specific immune cell phenotypes associated with periodontitis risk is essential for targeted immunotherapeutic interventions. However, the role of certain specific immune cell phenotypes in the development of periodontitis is unknown. Mendelian randomization offers a novel approach to reveal causality and address potential confounding factors through genetic instruments.
UNASSIGNED: This two-sample Mendelian randomization study assessed the causal relationship between 731 immune cell phenotypes and periodontitis using the inverse variance weighting method with the GWAS catalog genetic database. Methodological robustness was ensured through Cochran\'s Q test, MR-Egger regression, MR-PRESSO, and Leave-One-Out analysis.
UNASSIGNED: 14 immune cell phenotypes showed potential positive causal associations with periodontitis risk (p < 0.05), suggesting an increased risk, while 11 immune cell phenotypes exhibited potential negative causal associations (p < 0.05), indicating a reduced risk. No significant heterogeneity or pleiotropy was observed.
UNASSIGNED: This study underscores certain immune cell types as potential periodontitis risk biomarkers, laying a theoretical foundation for future individualized treatment and precision medicine development.

The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line were found in terms of increased systemic IgM (primary immune responses), increased synthesis of IFN-gamma upon stimulation (Th1) and increased peripheral T cells (mainly \"naive\" CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 β and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.

OBJECTIVE: To examine the fetal thymic-thoracic ratio (TTR) in intrahepatic cholestasis of pregnancy (ICP).
METHODS: This prospective case-control study was conducted in a single tertiary center. The sample consisted of 86 pregnant women at 28-37 weeks of gestation, including 43 women with ICP and 43 healthy controls. TTR was calculated for each patient using the anterior-posterior measurements of the thymus and intrathoracic mediastinal measurements.
RESULTS: The median TTR value was found to be smaller in the ICP group compared to the control group (0.32 vs. 0.36, p<0.001). The ICP group had a greater rate of admission to the neonatal intensive care unit (NICU) (p<0.001). Univariate regression analysis revealed that lower TTR values increased the possibility of NICU admission six times (95 % confidence interval: 0.26-0.39, p=0.01). A statistically significant negative correlation was detected between TTR and the NICU requirement (r: -0.435, p=0.004). As a result of the receiver operating characteristic analysis, in predicting NICU admission, the optimal cut-off value of TTR was determined to be 0.31 with 78 % sensitivity and 67 % specificity (area under the curve=0.819; p<0.001).
CONCLUSIONS: We determined that the fetal TTR may be affected by the inflammatory process caused by the maternal-fetal immune system and increased serum bile acid levels in fetal organs in the presence of ICP. We consider that TTR can be used to predict adverse pregnancy outcomes in patients with ICP.

UNASSIGNED: Sleep is an important physiological process that is necessary for the normal functioning of the body. Sleep greatly affects all aspects of our body, including the immune pathways or immune response system of our body, which plays a determinant role in the development and progression of chronic inflammatory diseases. In this study, we worked to find the relation between sleep deprivation and levels of pro-inflammatory markers macrophage inflammatory protein 1-alpha (MIP-1α) and interferon gamma (IFN-γ). To find the relation between sleep deprivation and levels of pro-inflammatory markers MIP-1α and IFN-γ.
UNASSIGNED: To find the relation between sleep deprivation and levels of pro-inflammatory markers MIP-1α and IFN-γ.
UNASSIGNED: The study was conducted with 40 individuals as participants, of which 20 were sleep-deprived (SD), and 20 had adequate amounts of sleep. The sleep duration details of the individuals were obtained by questionnaire. Blood was withdrawn from all the subjects after due consent from them. Plasma was separated and was used to evaluate their MIP-1α levels and IFN-γ levels.
UNASSIGNED: The MIP-1α levels and levels of IFN-γ were found to be significantly elevated in the SD individuals than that of individuals who had adequate sleep.
UNASSIGNED: Sleep loss and sleep deprivation are associated with altered expressions of key regulatory factors and upregulation of pro-inflammatory cytokines production. Thus, sleep deprivation can be considered to be one of the major contributors to the development and progression of various chronic inflammatory diseases.

BACKGROUND: Global life expectancy is rising, with the 60 + age group projected to hit 2 billion by 2050. Aging impacts the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their importance, links between immune cell phenotypes including ARIPs and mortality are underexplored. We prospectively investigated 16 different immune cell phenotypes using flow cytometry and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998-2001).
RESULTS: Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the 19-year survival rate was 65%. Adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR: 0.86 [0.76-0.96], 0.84 [0.74-0.94], respectively), while higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3 +) were associated with increased all-cause mortality risk (HR = 1.17, [1.03-1.32]). Elevated IL-6 levels correlated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26-1.62], 1.70 [1.31-2.21], and 1.36 [1.18-1.57], respectively). However, after adjusting for cardiovascular risk factors and prevalent cancer alongside age, sex, and CMV, immune cell phenotypes were no longer associated with mortality in our cohort. Nonetheless, IL-6 remained significantly associated with all-cause and cardiovascular mortality (HRs: 1.3 [1.13-1.49], 1.5 [1.12-1.99], respectively).
CONCLUSIONS: In 19-year follow-up, higher Tc17/CD8 + Treg and CD4/CD8 ratios were associated with lower all-cause mortality, while the CD8 + CD25 + FoxP3 + (CD8 + Treg) phenotype showed increased risk. Elevated IL-6 levels consistently correlated with amplified mortality risks. These findings highlight the links between immune phenotypes and mortality, suggesting implications for future research and clinical considerations.

The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world\'s adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14-16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p < 0.001), interferon signaling (z-score = 2.464, p < 0.001), interferon alpha/beta signaling (z-score = 3.873, p < 0.001), and complement signaling (z-score = 2, p = 0.002) were upregulated in adolescents with MDD compared with adolescents without MDD independently from their level of risk. The up-regulation of such inflammation-related pathways was observed in females but not in males. Inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling were identified as key indicators of adolescent depression, and this effect was present only in females.