Acute lymphoblastic leukemia (ALL), a leading cause of childhood cancer, targets immune system B and T cells. While understanding its causes is crucial, predicting susceptibility holds immense power for early diagnosis and intervention. This study explored the potential of interleukin 10 (IL-10), a key immune regulator, as a predictive tool in Egyptian children. Investigating 100 ALL patients and 100 healthy controls, we analyzed the IL10 gene polymorphism (-1082 A/G) and serum levels. Strikingly, both the G allele and higher serum IL-10 levels were significantly associated with increased ALL risk (p < 0.05, OR > 1). Moreover, IL-10 emerged as a remarkably accurate predictor, boasting an AUC of 0.995, with a sensitivity of 97% and specificity of 96%. These findings unveil the potential of IL-10 as a powerful predictive tool for pediatric ALL in the studied Egyptian population. Identifying individuals with the GG/AG haplotype and elevated IL-10 levels could enable early intervention and potentially improve outcomes. While further validation in larger and more diverse populations is needed, this study paves the way for personalized risk assessment and potentially revolutionizes how we combat this childhood killer.

Tuberculosis (TB) is a leading cause of death caused by Mycobacterium tuberculosis (M tb) and about one-third of the world\'s population is infected with TB. The household contacts of TB patients are at higher risk towards TB than general population. During the initial stages of infection, pro and anti-inflammatory cytokines are induced by innate immune cells, and the course of infection is influenced by general cytokine environment. These cytokines play an important role in the regulation of host immune responses against M tb. Therefore, it is necessary to understand the cytokines role in the immune mechanism to evaluate the correlation between the disease and the immune responses involved in TB. Our current study has focused on recombinant cytokines to understand their effects on cell proliferation and cytokine levels in culture supernatants. We observed that the mean proliferative responses to recombinant rhTNF-α were high and TNF-α levels were significantly low in APTB patients compared to their HHC and HC with p < 0.0375 and p < 0.0051 respectively. The mean proliferative responses to recombinant rhTGF-β were significantly low in APTB when compared to HHC and HC with p < 0.0376, p < 0.0247 respectively, and TGF-β levels were also significantly low in APTB and HHC compared to HC with p < 0.0468 and p < 0.0001 respectively. The lower cytokine secretions in culture supernatants might be due the autocrine signaling by recombinant cytokines towards the inflammatory response. Further, to validate these recombinant cytokines, a larger sample size could aid in identifying individuals at high risk for TB.

The prevalence of prenatal alcohol exposure (PAE) is increasing, with evidence suggesting that PAE is linked to an increased risk of infections. PAE is hypothesized to affect the innate immune system, which identifies pathogens through pattern recognition receptors, of which toll-like receptors (TLRs) are key components. We hypothesized that light-to-moderate PAE would impair immune responses, as measured by a heightened response in cytokine levels following TLR stimulation. Umbilical cord samples (10 controls and 8 PAE) from a subset of the Ethanol, Neurodevelopment, Infant and Child Health Study-2 cohort were included. Peripheral blood mononuclear cells (PMBCs) were stimulated with one agonist (TLR2, TLR3, TLR4, or TLR9). TLR2 agonist stimulation significantly increased pro-inflammatory interleukin-1-beta in the PAE group after 24 h. Pro- and anti-inflammatory cytokines were increased following stimulation with the TLR2 agonists. Stimulation with TLR3 or TLR9 agonists displayed minimal impact overall, but there were significant increases in the percent change of the control compared to PAE after 24 h. The results of this pilot investigation support further work into the impact on TLR2 and TLR4 response following PAE to delineate if alterations in levels of pro- and anti-inflammatory cytokines have clinical significance that could be used in patient management and/or attention to follow-up.

BACKGROUND: Recurrent pregnancy loss (RPL) is a complicated reproductive disorder with underlying genetic and immunological causes. RPL may be influenced by hereditary thrombophilia, a class of blood clotting-related genetic abnormalities, via the vascular and immune systems. This study examines the immunological characteristics that hereditary thrombophilia patients have in common with RPL.
METHODS: A prospective cohort study included 300 patients split into two groups: a control group without hereditary thrombophilia and a group with the condition. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) levels were measured, along with demographic specifics, antiphospholipid antibodies, natural killer (NK) cell counts, and other cytokines. Group differences were found using statistical analysis.
RESULTS: Antiphospholipid antibodies were significantly more common in the thrombophilia group (42% testing positive, p=0.001) compared to the control group (12% testing positive), despite demographic factors being similar between groups (p=0.372 and p=0.093). When body mass index (BMI) was taken into account, the study found a statistically significant difference (p=0.046), with the thrombophilia group having a higher mean BMI (26.3 kg/m2, standard deviation (SD): 2.8) than the control group (24.7 kg/m2, SD: 3.1). IL-6 (14.8 pg/mL, SD: 3.2, p=0.029) were higher than the control group (12.4 pg/mL, SD: 2.1), and TNF-α levels were higher in the thrombophilia group (10.5 pg/mL, SD: 2.0, p=0.012) compared to the control group (8.9 pg/mL, SD: 1.5), but NK cell counts did not differ significantly (p=0.213).
CONCLUSIONS: This study emphasizes the role of elevated pro-inflammatory cytokines (IL-6 and TNF-α) and antiphospholipid antibodies in RPL among people with hereditary thrombophilia. In this population, early detection and immunomodulatory interventions may improve pregnancy outcomes. To fully comprehend these mechanisms and create customized treatments, collaborative research is required.

Venom-derived peptides are important sources for the development of new therapeutic molecules, especially due to their broad pharmacological activity. Previously, our research group identified a novel natural peptide, named fraternine, with promising effects for the treatment of Parkinson\'s disease. In the present paper, we synthesized three peptides bioinspired in fraternine: fra-10, fra-14, and fra-24. They were tested in the 6-OHDA-induced model of parkinsonism, quantifying motor coordination, levels of TH+ neurons in the substantia nigra pars compacta (SN), and inflammation mediators TNF-α, IL-6, and IL-1ß in the cortex. Peptides fra-14 and fra-10 improved the motor coordination in relation to 6-OHDA lesioned animals. However, most of the peptides were toxic in the doses applied. All three peptides reduced the intensity of the lesion induced rotations in the apomorphine test. Fra-24 higher dose increased the number of TH+ neurons in SN and reduced the concentration of TNF-α in the cortex of 6-OHDA lesioned mice. Overall, only the peptide fra-24 presented a neuroprotection effect on dopaminergic neurons of SN and a reduction of cytokine TNF-α levels, making it worthy of consideration for the treatment of PD.

UNASSIGNED: Although studies have associated elevated prenatal obesity with increased risk of various diseases in offspring, little is known regarding the immune system. The aim of this study was to evaluate the relationship between prenatal obesity and levels of cytokines in umbilical cord blood and development of allergic disease during the first 10 years of life in an offspring.
UNASSIGNED: A cohort of term infants born at the ShaoXing Women and Children Hospitals in China in 2011 was enrolled in this study. Flow cytometry was performed to measure levels of various cord blood cytokines, namely IL1β, IL2, IL10, IL6, IL8, IL17, IL12, TNF-α and IFN-γ. Next, logistic regression was used to explore the association of prenatal BMI with the development of allergic disease. The relationship between levels of each cord blood cytokine with prenatal BMI, and allergic disease development was tested using linear and logistic regression analyses, respectively.
UNASSIGNED: After 10 years of follow-up, higher prenatal BMI was significantly associated with development of allergic disease in children (HR = 2.45, 95% CI:1.08-5.57, P = 0.033). We also adjusted for maternal age, education and infant gender, and found that prenatal BMI was significantly associated with higher levels of IL12 (P = 0.023) and IL1β (P = 0.049) in cord blood. Moreover, we adjusted for maternal age, education, allergic dermatitis, gestation age and infant gender, and found that increase in each unit (1.26 pg/ml) in IL17 was associated with a 55.5% higher risk of allergic disease in 10-year-old children (HR = 1.55, 95%Cl: 0.99-2.45, P = 0.056). Meanwhile, after adjusting for maternal age, education level, gestation age, prenatal BMI, gestational weight gain, infant gender and birthweight, we found that for every unit increase in IL10, IL6 and IL1β, the risk of overweight/obesity in children after 10-year follow-up increased by 18.7% (HR = 1.19, 95%Cl: 1.01-1.40, P = 0.042), 13.9% (HR = 1.14, 95%Cl: 1.02-1.27, P = 0.021) and 41.3% (HR = 1.41, 95%Cl: 1.02-1.95, P = 0.036), respectively.
UNASSIGNED: Prenatal obesity was positively correlated with allergic diseases in offspring. Cord blood cytokine may play mediating roles in the associations of prenatal obesity with offspring allergic diseases.

UNASSIGNED: Clostridioides difficile is the most common infectious agent of nosocomial diarrhea. C. difficile infection (CDI) pathogenesis and disease severity depend on its toxins (toxins A, B and binary) and on the host\'s immune response, especially the innate immune system. The current study examined the efficacy of macrophage activity, macrophages viability and cytokine secretion levelsin response to different sequence type (ST) strains of C. difficile.
UNASSIGNED: RAW 264.7 macrophages were exposed to six different strains of C. difficile as well as to both toxins A and B and macrophage viability was measured. The levels of four secreted cytokines were determined by RT-PCR and ELISA. Morphological changes to the macrophages were investigated by fluorescent microscopy.
UNASSIGNED: Strains ST37 and ST42 affected macrophages\' vitality the most. Toxins A and B led to a significant reduction in macrophages\' vitality at most time points. In addition, starting at 30-min post-exposure to 5 ng/μl of both toxins led to significant differences in macrophage viability versus at lower concentrations. Furthermore, cytokine secretion levels, including IL-12, IL-6 and TNF-α, increased dramatically when macrophages were exposed to strains ST42 or ST104. Finally, gene expression surveys point to increases in IL-12 gene expression in response to both ST42 and ST104.
UNASSIGNED: C. difficile strains with higher toxins levels induced an increased activation of the innate immune system and may activate macrophages more profoundly resulting in secretion of higher levels of pro-inflammatory cytokines. However, higher toxin levels may also damage macrophages\' normal skeletal structure, reducing macrophage viability.

Alginate (ALG) is a biocompatible and biodegradable polymer. Mechanical weakness is one of the main problems for the alginate-based scaffolds. Various plasticizer additives or modifications tested to improve the mechanical properties. In the presented study, ALG plasticized with triacetin (TA), and tributyl citrate (TBC) than tested on bone healing. In the presented study, the alginate modified with triacetin or tributyl citrate. In-vitro, and in-vivo efficiency of the scaffolds tested on bone tissue regeneration. Scaffolds fabricated by solvent casting, and physicochemical characterizations performed. Monocytes (THP-1) cultured with scaffolds, and macrophage-released cytokines was determined. In-vivo efficacy of the scaffolds was tested in the rat drill hole model. Alginate and tributyl citrate-modified scaffolds have no cytotoxic effect on osteoblastic cells (MC-3T3). Tributyl citrate modification increased tumor necrosis factor-alpha (TNF-alpha) level but did not increase interleukin -1 beta (IL-1 beta) level. In vivo studies showed that osteoblastic growth was significant in alginate and triacetin-modified scaffolds. However, the best values for osteoclastic activity and osteoid tissue formation seen in the triacetin modification. The results demonstrated that the modified alginate scaffolds were more successful than non-modified alginate scaffolds and can used as long-term bone repairing treatments.

OBJECTIVE: It is now well known that Bifidobacterium animalis subsp. lactis (B. lactis), an important early-life colonizer of the gut, provides immune-related benefits to infants. The aim of the work is to explore the intraspecific resistance to Salmonella infection of B. lactis isolated from neonatal feces, and to learn more insights into how B. lactis mediates beneficial roles in early-life infection resistance.
METHODS: Five strains of B. lactis (NFBAL11/NFBAL23/NFBAL44/NFBAL63/NFBAL92) were screened from fecal samples of neonates born within fifteen days and pretreated neonatal rats prior to infection with Salmonella typhimurium (S. typhimurium) SL1344. The survival rate, fecal occult blood, diarrhea and hepatosplenomegaly were detected to assess the ability of B. lactis to prevent S. typhimurium infection. Furthermore, the structure of mucus layer, gene expression, cytokine levels, antioxidant levels and intestinal microflora composition were detected to explore the mechanism.
RESULTS: All strains showed activity against S. typhimurium, with B. lactis NFBAL23 being the most active, followed by NFBAL63 and NFBAL92. And these advantages weren\'t attained by enhancing physical growth and development. Mechanistically, the neonatal rats treated with B. lactis (NFBAL23/NFBAL63/NFBAL92) had improved intestinal barrier function involving physical, chemical, immune and biological barriers in the face of challenges posed by S. typhimurium.
CONCLUSIONS: These findings revealed the intraspecific difference, beneficial roles and mechanisms of action of B. lactis against Salmonella infection early in life, which highlighted the necessity of supplementing appropriate B. lactis, and provided several potential B. lactis candidates for Salmonella infection treatment.

Cytokines are important immune-modulators and improper T-cell activation can lead to cytokine storms which are believed to result in endothelial permeability and leakage, a typical feature of Dengue disease progressing into a more severe stage. Many cytokines have been implied in causing severe Dengue manifestations among which IL-10 poses to be an important one. Inflammatory cytokines such as TNFα and IFN γ can be pointed out in Dengue pathogenesis and prognosis. Therefore, we sought to investigate the T cell activation of Dengue infected patients via these three markers and asses their levels and correlate cytokine levels with disease severity and clinical outcomes.
Samples using standard blood collection techniques were obtained from patients with clinical signs suggestive of dengue. A haematological was obtained subsequently. Serological markers including IgM and NS1 were assessed using ELISA following which ELISA will be done for immunological markers including TNFα, IFN γ (markers of pro-inflammatory response and IL-10 (marker for regulatory response).
There was a significant correlation between IL10 and clinical features. There was no significant correlation between TNF alpha and clinical features. IFN gamma had a positive correlation with the clinical features. There was a positive cumulative correlation between clinical features, platelet counts, IL10 and TNF alpha but not with IFN gamma contrary to its correlation as a separate entity with just the clinical features.
The present study clearly indicates that IL10 is a highly sensitive marker of Severe Dengue and can be used as a screening tool in Secondary Dengue patients or those with warning signs. TNF alpha as it correlates strongly with patients with warning signs can be used for prognosis is patients presenting with symptoms. However, interferon gamma correlates strongly with low platelet counts and can be a measure to screen patients presenting with fever with thrombocytopenia.