Dynamic indicators of acute respiratory diseases treatment in children after correction.

OBJECTIVE: Aim: To study the Respiratory pathology of the upper respiratory tract, markers of the inflammatory response of the organism, Oxidative stress, Metabolic adaptation and possibilities of correction. PATIENTS AND METHODS: Materials and Methods: The study group (n=111) included school-aged children (10-14 years old). The general group of inflammatory diseases of the respiratory tract (J000-J06) was considered, with a diagnosis of acute respiratory infection (ARI) of viral and bacterial origin and included local inflammationof the upper respiratory tract with presentation of acute pharyngitis (68.0%), acute bronchitis (22,0%), acute tonsillitis (10,0%). RESULTS: Results: Dynamic observation of groups of children who received optimized (group 1, n=60) and basic (group 2, n=51) treatment was carried out. The level of the erythrocyte pool correlated with IL-1 (r=-0,29, p=0,03), IL-4 (r=0,32, p=0,01), TNF-α (r=-0,35 , p=0,006). Creatinine value correlated with IL-10 (r=0,3, p=0,005), γ-IFN (r=0,42, p=0,001), TNF-α (r=0,25, p=0,05). Correlations of ferritin presented positive correlation values with the level of total protein (r=0,26, p=0,04) and TNF-α (r=0,41, p=0,001). CONCLUSION: Conclusions: After the optimized treatment, there was a significant decrease in the reliable levels of CRP and γ-IFN by 7 and 4,4 times (by groups) and 5,8 and 3,2 times (by groups), respectively. Correlation relationships of urea levels with IL-2,4 were detected. The level of the erythrocyte pool correlated with IL-1,4, TNF-α, Ferritin presented positive correlation values with the level of total protein,TNF-α .

In vivo determination of the anti-inflammatory and antioxidant effects of the aqueous extract of Syzygium aromaticum (clove) in an asthmatic rat model.

Asthma is a chronic inflammatory disease of the airways strongly associated with interleukin-4 (IL-4), a cytokine that mediates and regulates various immune responses, including allergic reactions. This study aimed to evaluate the anti-inflammatory and antioxidant effects of an Aqueous Extract of Clove (AEC) Syzygium aromaticum on the lungs and erythrocytes of an experimental asthma model in Wistar rats. For this purpose, four groups of male rats were examined: control, sensitized with ovalbumin (OVA), treated with AEC, and treated with a combination of OVA/AEC. After treatment, the antioxidant effect was determined by measuring the malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione (GSH), and catalase (CAT) levels. The anti-inflammatory effect was determined by measuring IL-4 levels by performing enzyme-linked immunosorbent assay (ELISA) using serum, lung, and bronchoalveolar lavage fluid (BALF) samples. A significant reduction (p ≤ 0.05) in the MDA levels and a significant increase (p ≤ 0.05) in the levels of GPx and CAT were observed in the lungs of rats treated with cloves. However, no statistically significant variation was observed in GSH levels. In erythrocytes, no statistically significant differences were observed between the experimental batches. Regarding the anti-inflammatory effect, the administration of S. aromaticum extract to sensitized rats resulted in a recovery in the levels of total proteins and IL-4 and a decrease in the three compartments studied (lungs, serum, and bronchoalveolar liquid). These results were confirmed by microscopic examination of lung histological sections. Overall, these findings confirmed that the AEC has anti-inflammatory and antioxidant effects.

Clinical validation of circulating GDF15/MIC-1 as a marker of response to docetaxel and survival in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC. METHODS: IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (n = 430). IL4, IL6, and GDF15 levels were measured by ELISA. Monocytes and dendritic cells were treated with 10% plasma from men with high or low GDF15 or recombinant GDF15. RESULTS: IntVal: Higher GDF15 levels at BL and Day 21 were associated with shorter overall survival (OS) (BL; p = 0.03 and Day 21; p = 0.004). IL4 and IL6 were not associated with outcomes. ExtVal: Higher GDF15 levels at BL and Day 42 predicted shorter OS (BL; p < 0.0001 and Day 42; p < 0.0001). Plasma from men with high GDF15 caused an increase in CD86 expression on monocytes (p = 0.03), but was not replicated by recombinant GDF15. CONCLUSIONS: Elevated circulating GDF15 is associated with poor prognosis in men with mCRPC receiving docetaxel and may be a marker of changes in the innate immune system in response to docetaxel resistance. These findings provide a strong rationale to consider GDF15 as a biomarker to guide a therapeutic trial of drugs targeting the innate immune system in combination with docetaxel in mCRPC.

Serum Levels of Interleukins in Endometriosis Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: The aims of this systematic review and meta-analysis were to produce a comprehensive survey of the serum levels of interleukins (ILs) in untreated people with endometriosis compared with people without endometriosis. DATA SOURCES: A systematic literature search of English language studies within Cinahl, Medline Complete, PubMed, and Scopus from inception to May 2023 was performed. METHODS OF STUDY SELECTION: We included studies that compared IL serum levels in people with endometriosis to those without endometriosis. Meta-analysis was performed on IL-1RA, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IL-18, IL-23, and IL-37. TABULATION, INTEGRATION, AND RESULTS: The systematic search retrieved 651 studies, of which 77 underwent a full-text review. A total of 30 studies met inclusion criteria for the meta-analysis. IL-1Ra, IL-6, and IL-37 serum levels were 2.56 (95% CI 2.20-2.92, p <.001), 1.38 (95% CI 0.58-2.17, p <.001), and 1.77 (95% CI 1.33-2.20, p <.001) standard deviations higher in the patients with endometriosis compared with patients without endometriosis while IL-23 serum levels 0.40 (95% CI -0.73 to -0.07, p = .02) standard deviations lower, respectively. CONCLUSION: There is mounting evidence that ILs, especially IL-6, may be good candidates for unique noninvasive diagnostic tools and/or treatment pathways for endometriosis.

Prenatal exposure to RSV season influences first-year risk of RSV lower respiratory illness and RSV-specific immune responses assessed at birth.

Maternal-to-fetal transmission of respiratory syncytial virus (RSV) has been shown to occur but whether late prenatal exposure to RSV season influences offspring postnatal RSV-lower respiratory illness (LRI) risk in early life or RSV immune status at birth is unclear. In this study, the duration of third trimester RSV season exposure was determined for 1,094 newborns of the Tucson Children's Respiratory Study (TCRS) and found to show an inverse relation to risk for first RSV-LRI in the first year. Cord blood anti-RSV antibody is related to third trimester RSV season exposure but not to first year RSV-LRI risk. In a separate birth cohort (the Infant Immune Study), supernatants from cord blood mononuclear cells stimulated with the recall antigen, UV-inactivated RSV, were assayed for IFN-γ and IL-4. The frequency of detectable IFN-γ (but not IL-4) was increased for those with at least 2 mo of third trimester RSV season exposure, suggestive of a fetal immune response to RSV. IMPORTANCE Our study found that duration of third trimester exposure to RSV season related inversely to subsequent risk of postnatal RSV-LRI in the first year, thus implicating this exposure as an important factor in reducing risk of postnatal RSV-LRIs, a risk reduction that appears to be independent of maternally transferred anti-RSV antibody level. The increase in frequency of detectable IFN-γ and not IL-4 in response to UV-inactivated RSV in cord blood immune cells for infants with greater third trimester exposure to RSV season is suggestive of a Type-1 immune response to RSV occurring in utero.

Aqueous humor cytokine levels are associated with the severity of visual field defects in patients with primary open-angle glaucoma.

BACKGROUND: To evaluate the aqueous humor (AH) levels of cytokines in primary open-angle glaucoma (POAG) patients and cataract patients. METHODS: Thirty-eight POAG patients and 26 cataract patients were recruited. Peripheral blood (PB) was collected from each subject. The POAG group was divided into 2 subgroups according to the severity of visual field defects. The cutoff point of the mean deviation (MD) of the visual field was -12 dB. AH was obtained at the time of anterior chamber puncture during cataract or glaucoma surgery by using a 27-gauge needle attached to a microsyringe. AH and PB levels of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta2 (TGF-ß2) and IL-4 were assayed by enzyme-linked immunosorbent assay. Postoperative intraocular pressures (IOPs) of POAG patients were recorded during the follow-up period. RESULTS: TNF-α and TGF-ß2 showed significantly higher AH levels in the POAG group than in the cataract group (P < 0.001 and P = 0.001, respectively). For the POAG group, preoperative IOPs were significantly positively correlated with AH levels of TNF-α (r2 = 0.129, P = 0.027) and TGF-ß2 (r2 = 0.273, P = 0.001). AH levels of TGF-ß2 were significantly different among cataract patients, POAG patients with MD> -12 dB and POAG patients with MD≤ -12 dB (P = 0.001). AH levels of TNF-α were significantly positively associated with IOP reduction after trabeculectomy (P = 0.025). AH and PB levels of cytokines were not related to the long-term success of trabeculectomy. CONCLUSION: The levels of TNF-α and TGF-ß2 showed different profiles in POAG patients and cataract patients. AH levels of TGF-ß2 were correlated with the severity of glaucomatous neuropathy in POAG patients. The findings suggest possible roles for cytokines in the pathogenesis and development of POAG.

Role of IL4 and GMCSF in Predicting Survival in Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study's objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients. STUDY DESIGN: A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma). RESULTS: Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p < 0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040). CONCLUSIONS: These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.

[Long noncoding RNA LOC102640791 alleviates sepsis inflammation in mice by sponging miR-320-5p].

Objective To investigate the role and mechanism of long noncoding RNA (lncRNA) LOC102640791 in sepsis inflammatory response. Methods The mice model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS). The cell model of sepsis was established by treating of RAW264.7 macrophages with LPS. Mice or cells were randomly divided into the control group and the LPS group. The levels of lncRNA and miRNA in serum were detected by microarrays. The levels of LOC102640791 and miR-320-3p were tested by the real time quantitative PCR. The levels of TNF-α, IL-6, IL-8, IL-4 and IL-10 in serum and cell culture supernatant of RAW264.7 were detected by the ELISA. Luciferase reporter gene technology was used to verify the relationship between LOC102640791 and miR-320-3p. Results Compared with the control group, the LPS group had lower expression of LOC102640791 and higher expression of miR-320-3p. Compared with the LPS group, the LPS group with high expression of LOC102640791 and the LPS group with low expression of miR-320-3p had higher expression of pro-inflammatory factors (TNF-α, IL-6 and IL-8) and lower expression of anti-inflammatory factors (IL-4 and IL-10). Wild type LOC102640791 can inhibit the luciferase activity of miR-320-3p. Conclusion LOC102640791 alleviates sepsis inflammatory response by sponging miR-320-5p.

Monocyte subsets, T cell activation profiles, and stroke in men and women: The Multi-Ethnic Study of Atherosclerosis and Cardiovascular Health Study.

BACKGROUND AND AIMS: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke. METHODS: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models. RESULTS: We observed associations of intermediate monocytes, early-activated CD4+ T cells, and both CD4+ and CD8+ T cells producing interleukin-4 after cytokine stimulation (Th2 and Tc2, respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women. CONCLUSIONS: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention.

Analysis of Serum Th2 Cytokines in Infants with Non-IgE Mediated Food Allergy Compared to Healthy Infants.

Background: The aim of this study is to assess the serum values of IL-4, IL-5, IL-10, and IL-13 in a group of infants with non-IgE mediated food allergies treated with a hydrolyzed formula and compare them with a group of healthy peers. Methods: A total of 53 infants aged 1 to 4 months, of which 34 with non-IgE mediated food allergies and 19 healthy infants were enrolled in this study. Infants were eligible if they had gastrointestinal symptoms of food allergy and needed to switch from their initial formula to hydrolyzed formulas with an improvement of symptoms. Controls were fed with either breastmilk or standard formula. Blood samples were taken within one week of a special diet for cases. Interleukinsin in peripheral blood was detected and analyzed using the real-time PCR MAMA method. Fecal calprotectin was evaluated using a quantitative assay. Results: Values of IL-4 and IL-13 were significantly higher in the non-IgE food allergy group compared to the control group (p < 0.05), while IL-5 and IL-10 were significantly lower than the control group (p < 0.05). Fecal calprotectin in the non-IgE food allergy group was significantly higher compared to the control group (p < 0.05). Conclusion: This study provides a theoretical basis that Th2 cytokine expression in infants with a non-IgE mediated food allergy is significantly different than in healthy infants; this finding supports the use of early dietetic treatment with hydrolyzed formulas.

Analysis of Serum Levels of IFN-γ, IL-4, and TNF-α in Patients with Cervicitis Complicated by HPV Infection and Their Clinical Significance.

In order to investigate the expression levels of serum IFN-γ, IL-4, and tumor necrosis TNF-α in patients with cervicitis complicated with human papillomavirus (HPV) infection and clinical significance, a retrospective study was conducted on 90 patients with chronic cervicitis complicated by HP V infection who visited our hospital from June 2020 to June 2021, and they are included in the research group. According to the degree of HPV infection, the patients are divided into low-risk HPV type group (n = 65 cases) and high-risk HPV type group (n = 25 cases); 50 patients with cervicitis (without HPV infection) who received treatment in our hospital are selected as control group 1. Fifty healthy women who underwent physical examination are selected as the control group 2. The general data of the two groups of patients during hospitalization are collected, and HPV-DNA, IFN-γ, IL-4, and TNF-α are detected in all patients. For patients with cervicitis complicated by HPV infection, the IFN-indexes in the body are significantly decreased, IL-4 and TNF-αare significantly increased, and with the degree of HPV infection, IFN-γ, IL-4, and TNF-α have high diagnostic performance with HPV infection, and there is a significant correlation between the three, which can be used in cervicitis complicated with HPV infection. It is widely used in the early diagnosis and screening of infected patients.

Functionally distinct T-helper cell phenotypes predict resistance to different types of parasites in a wild mammal.

The adaptive immune system is critical to an effective response to infection in vertebrates, with T-helper (Th) cells pivotal in orchestrating these responses. In natural populations where co-infections are the norm, different Th responses are likely to play an important role in maintaining host health and fitness, a relationship which remains poorly understood in wild animals. In this study, we characterised variation in functionally distinct Th responses in a wild population of Soay sheep by enumerating cells expressing Th-subset specific transcription factors and quantifying Th-associated cytokines. We tested the prediction that raised Th1 and Th2 responses should predict reduced apicomplexan and helminth parasite burdens, respectively. All measures of Th-associated cytokine production increased with age, while Th17- and regulatory Th-associated cytokine production increased more rapidly with age in males than females. Independent of age, sex, and each other, IL-4 and Gata3 negatively predicted gastro-intestinal nematode faecal egg count, while IFN-γ negatively predicted coccidian faecal oocyst count. Our results provide important support from outside the laboratory that Th1 and Th2 responses predict resistance to different kinds of parasites, and illustrate how harnessing specific reagents and tools from laboratory immunology will illuminate our understanding of host-parasite interactions in the wild.

Phasic firing of dopaminergic neurons in the ventral tegmental area triggers peripheral immune responses.

Dopaminergic neurons in the ventral tegmental area (VTA) play a crucial role in the processing of reward-related information. Recent studies with pharmacological manipulations of VTA neuronal activity demonstrated a VTA-induced immunoenhancement in peripheral organs. Here, to examine the detailed physiological dynamics, we took an optogenetic approach in which VTA dopaminergic neurons were selectively activated with millisecond precision. Optogenetic phasic, rather than tonic, stimulation of VTA dopaminergic neurons increased serum cytokine levels, such as IL-2, IL-4 and TNF-α. These results provide direct evidence to link dopaminergic neuronal phasic firing to peripheral immunity. Next, we tested whether cytokine induction in male mice was boosted by female encounters, a natural condition that induces increased active VTA neurons and gamma power. Female encounters increased serum IL-2 levels, which were abolished by pharmacological inhibition of VTA neuronal activity. Taken together, our results highlight the importance of the brain reward system in the treatment and management of immune-related disorders.

Correlation of Physiological Parameters in Rats after Stress Exposure under Conditions of Antigenic Stimulation with Lipopolysaccharide Administration.

We studied correlation dependences between physiological parameters in rats in 3 h, 1 day, and 8 days after administration of LPS (100 µg/kg) at the end of 24-h immobilization stress. In 3 h after LPS administration against the background of stress exposure, significant correlations of metabolic parameters with the relative weight of the adrenal glands and the perceptual component of nociception in rats were revealed. A direct relationship between the concentration of the proinflammatory cytokine TNFα and anti-inflammatory IL-4 was also found in these animals. On the first day after LPS injection, correlations were revealed, predominantly positive, only between the indicators of the cytokine blood profile. In the late post-stress period after antigenic exposure, no correlations between the studied physiological parameters were found. It can be hypothesized that immune modulation through systemic administration of LPS prevents persistent excessive stress of physiological functions at the later stages after stress exposure.

The role and correlation of IL-35 and type II intrinsic lymphocytes in children with allergic rhinitis.

To investigate the role and correlation of IL-35 and ILC2 in children with allergic rhinitis. 50 cases of children with allergic rhinitis admitted to our hospital from February 2018 to March 2020 were selected as the research subjects and set as the study group. During the same period, 50 cases of normal children admitted to our hospital for physical examination were selected as the control group. The differences in the expression of IL-35 and ILC2 between the two groups and the correlation with the severity of allergic rhinitis were compared. In BMI, the study group was significantly lower than the control group, and the difference was statistically significant (P<0.05). IL-35 in the study group was significantly lower than that in the control group, while ILC2, IL4+ILC2, IL-5+ILC2, IL-13+ILC2, IgE and ECP in the study group were significantly higher than those in the control group, the difference was statistically significant (P<0.05). Pearson correlation analysis showed a moderate negative correlation between TNSS score and IL-35 (r =-0.642, P<0.05), was positively correlated with ILC2, IL4+ILC2, IL-5+ILC2, IL-13+ILC2, ECP (r =0.745, 0.713, 0.725, 0.769, 0.746, P<0.05), and was strongly correlated with IgE (r =0.952, P<0.05). Also, It was positively correlated with TGF-?1 (r =0.513, P<0.05). IL-35 was strongly negatively correlated with ILC2, IL4+ILC2, IL-5+ILC2, IL-13+ILC2 (r =-0.845, -0.812, -0.805, 0.823, -0.854, P<0.05). Was negatively correlated with ECP and TGF-?1 (r =-0.795, -0.543, P<0.05). ILC2 was strongly correlated with IgE (r =0.812, P<0.05), and moderately positively correlated with ECP and TGF-?1 (r =0.642, 0.541, P<0.05). ROC curve was used to evaluate the diagnostic value. The results showed that among the five indicators, IgE had the highest sensitivity of 92.23%, while IL-35 had the highest specificity of 92.56%. However, the combined area, sensitivity and specificity of the five indicators were the highest, 0.962, 95.18% and 94.25%, respectively (P<0.05). Both IL-35 and type II intrinsic lymphocytes are highly correlated with the severity of allergic rhinitis in children, the former is negatively correlated with the latter is positively correlated. The detection of these indexes in clinical practice can be helpful for clinical diagnosis.

Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis.

Interleukin (IL)-4 and IL-13 belong to the T helper 2 (Th2) cytokine family, along with IL-3, IL-5, and IL-9. These cytokines are key mediators of allergic inflammation. They have important immunomodulatory activities and exert influence on a wide variety of immune cells, such as B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes. Recent studies have implicated IL-4 and IL-13 in the development of various autoimmune diseases. Additionally, these cytokines have emerged as potential players in pathogenesis of inflammatory arthritis. Recent findings suggest that the IL-4 and IL-13 might play a significant role in the downregulation of inflammatory processes underlying RA pathology, and beneficially modulate the course of the disease. This review summarizes the biological features of the IL-4 and IL-13 and provides current knowledge regarding the role of these cytokines in inflammatory arthritis.

Association of reduced maternal sHLA-G5 isoform levels and elevated TNF-α/IL-4 cytokine ratio with Recurrent Pregnancy Loss: A study on South Indian women.

Inflammation is of critical importance in successful implantation during pregnancy. However, the establishment of maternal immune tolerance towards semi-allograft foetus is more exigent and is achieved predominantly by human leukocyte antigen-G (HLA-G) isoforms with a special emphasis on soluble HLA-G5 (sHLA-G5). Constant inflammation and lack of resolution by anti-inflammatory milieu, due to aberrant expression of critical immunoregulatory molecules such as sHLA-G5 and dysfunctional T helper cells 1 and 2 (Th1-Th2) cytokine shift, can lead to adverse pregnancy outcomes including recurrent pregnancy loss (RPL). Serum samples of 270 pregnant women (135 healthy parous and 135 with a history of RPL) were evaluated for the concentrations of sHLA-G5, interleukin-4 (IL-4) and tumour necrosis factor-alpha (TNF-α) using sandwich enzyme-linked immunosorbent assay (ELISA) and found elevated levels of sHLA-G5 and IL-4 in controls and higher TNF-α levels and TNF-α:IL-4 ratio in patients (P < .05). Stratified data analysis based on the time of sample collection, that is the first and second trimesters exhibited higher sHLA-G5 and IL-4 in both first and second trimesters in controls than patients, while they displayed lower levels concerning TNF-α and TNF-α:IL-4 ratio (P < .05). However, within patients and controls in the first or second trimesters, there was a significant variation concerning sHLA-G5 alone. Further, the outcome of pregnancies studied in the present investigation revealed a significant elevation in sHLA-G5 levels among women with successful pregnancies compared with women who experienced pregnancy loss, therefore, concluding the potential application of sHLA-G5 isoform as a marker in assisting improved pregnancy outcomes.

Evaluation of several serum interleukins as markers for treatment effectiveness in naïve HIV infected patients: A pilot study.

In this observational pilot study, we investigated the impact of Dolutegravir, Raltegravir, Elvitegravir (Integrase Strand Transfer Inhibitors, INSTIs), or boosted Darunavir (a Protease Inhibitor, PI) in combination with two nucleoside reverstranscriptase inhibitors (Emtricitabine/Tenofovir disoproxil or Lamivudine/Tenofovir disoproxil, NRTI) on four interleukins (IL-4, IL-10, IL-13, and IL-21) as immune activation markers in naïve HIV(Human Immunodeficiency Virus)-infected patients during the first six months of combined standard-of-care antiretroviral therapy (cART). Newly diagnosed with HIV-infected subjects and without any disease that could affect the immune activation markers were evaluated. The patients' physicians recommended the cART as standard-of-care and the ILs were measured before cART and six months of cART. The levels of CD4+ T-cells count and CD4+/CD8+ ratio significantly increased at six months (P-value<0.02) regardless of the drugs, INSTIs or PI. However, a CD4+/CD8+ >1 was observed in 25% of patients treated with Raltegravir and half of those treated with Dolutegravir. At six months of cART, viral load was detectable in only 6/31 individuals. IL-21 had an undetectable level in 30/31 patients after six months of cART. Our results suggest the potency in restoring immune markers in HIV-infected patients with all investigated drugs. Dolutegravir showed a tendency to statistically significant changes in IL-4 and IL-10. A clinical trial with random allocation of medication and an extensive follow-up is needed to replicate this research and validate the usefulness of evaluated ILs as markers of cART effectiveness.

FML/QuilA-Vaccinated Dogs Naturally Infected with Leishmania infantum: Serum Cytokines, Clinicopathological Profile, and Parasitological Parameters.

Dogs are the main reservoir of Leishmania infantum in endemic regions. Canine leishmaniasis, caused by L. infantum, can progress to a chronic disease resulting in death. Vaccines have been developed with a certain degree of success. The pathogenesis of this disease is not completely understood, especially in previously vaccinated dogs. We herein described clinical data, parasite load, serum levels of cytokines, and the reservoir potential in vdogs vaccinated with the fucose-mannose ligand (FML)/QuilA saponin vaccine (Leishmune™) naturally infected (Vi) and compared to vaccinated not infected dogs (Vn). Thirty-four dogs from private owners were divided into two groups: vaccinated/infected and vaccinated/uninfected. Clinical evaluation, hematological and biochemical parameters, and serum levels of cytokines were measured by conventional methods. The parasite burden in the bone marrow was measured by quantitative real-time PCR, and the transmissibility of parasites to sand flies was assessed by xenodiagnosis. Clinical, biochemical, and hematological parameters of vaccinated infected dogs were mostly normal. Vi dogs developed mild disease with low clinical scores. Serum levels of IL-10 were higher in Vi dogs, and a strong correlation was observed in IL-4 levels and the A/G ratio in Vi dogs. These results suggest a role of TH2 response in Vi dogs, although more data is needed to better understand the disease in vaccinated dogs.

Characterization by Quantitative Serum Proteomics of Immune-Related Prognostic Biomarkers for COVID-19 Symptomatology.

The COVID-19 pandemic caused by SARS-CoV-2 challenges the understanding of factors affecting disease progression and severity. The identification of prognostic biomarkers and physiological processes associated with disease symptoms is relevant for the development of new diagnostic and therapeutic interventions to contribute to the control of this pandemic. To address this challenge, in this study, we used a quantitative proteomics together with multiple data analysis algorithms to characterize serum protein profiles in five cohorts from healthy to SARS-CoV-2-infected recovered (hospital discharge), nonsevere (hospitalized), and severe [at the intensive care unit (ICU)] cases with increasing systemic inflammation in comparison with healthy individuals sampled prior to the COVID-19 pandemic. The results showed significantly dysregulated proteins and associated biological processes and disorders associated to COVID-19. These results corroborated previous findings in COVID-19 studies and highlighted how the representation of dysregulated serum proteins and associated BPs increases with COVID-19 disease symptomatology from asymptomatic to severe cases. The analysis was then focused on novel disease processes and biomarkers that were correlated with disease symptomatology. To contribute to translational medicine, results corroborated the predictive value of selected immune-related biomarkers for disease recovery [Selenoprotein P (SELENOP) and Serum paraoxonase/arylesterase 1 (PON1)], severity [Carboxypeptidase B2 (CBP2)], and symptomatology [Pregnancy zone protein (PZP)] using protein-specific ELISA tests. Our results contributed to the characterization of SARS-CoV-2-host molecular interactions with potential contributions to the monitoring and control of this pandemic by using immune-related biomarkers associated with disease symptomatology.