Apoptosis In Children Research Articles

Auraptene alleviates inflammatory injury and cell apoptosis in children with pneumonia in vitro

Objective: The aim of the present study is to investigate the effects of auraptene on inflammation and apoptosis of pneumonia cell model and uncover the mechanism. Methods: WI-38 cells were treated with lipopolysaccharide (LPS) to construct a pneumonia model. Cell counting kit-8 assay, enzyme-linked-immunosorbent serologic assay, and quantitative polymerase chain reaction assay were conducted to confirm the effects of auraptene on the viability and inflammation of WI-38 cells. Flow cytometry (FCM) and immunoblot assays were conducted to detect the effects of auraptene on the apoptosis of WI-38 cells. Immunoblot assay was performed to confirm the mechanism. Results: We found that auraptene stimulated cell viability in WI-38 cells upon LPS treatment. Auraptene also inhibited cellular inflammation. Furthermore, auraptene inhibited cell apoptosis of WI-38 cells upon LPS treatment. Mechanically, auraptene inhibited the nuclear factor kappa B signaling pathway, thereby suppressing the pneumonia. Conclusion: Auraptene alleviates inflammatory injury and cell apoptosis in pneumonia, thus has the potential to act as a pneumonia drug.

Auraptene alleviates inflammatory injury and cell apoptosis in children with pneumonia in vitro

Objective: The aim of the present study is to investigate the effects of auraptene on inflammation and apoptosis of pneumonia cell model and uncover the mechanism. Methods: WI-38 cells were treated with lipopolysaccharide (LPS) to construct a pneumonia model. Cell counting kit-8 assay, enzyme-linked-immunosorbent serologic assay, and quantitative polymerase chain reaction assay were conducted to confirm the effects of auraptene on the viability and inflammation of WI-38 cells. Flow cytometry (FCM) and immunoblot assays were conducted to detect the effects of auraptene on the apoptosis of WI-38 cells. Immunoblot assay was performed to confirm the mechanism. Results: We found that auraptene stimulated cell viability in WI-38 cells upon LPS treatment. Auraptene also inhibited cellular inflammation. Furthermore, auraptene inhibited cell apoptosis of WI-38 cells upon LPS treatment. Mechanically, auraptene inhibited the nuclear factor kappa B signaling pathway, thereby suppressing the pneumonia. Conclusion: Auraptene alleviates inflammatory injury and cell apoptosis in pneumonia, thus has the potential to act as a pneumonia drug.

Auraptene alleviates inflammatory injury and cell apoptosis in children with pneumonia in vitro.

The aim of the present study is to investigate the effects of auraptene on inflammation and apoptosis of pneumonia cell model and uncover the mechanism. WI-38 cells were treated with lipopolysaccharide (LPS) to construct a pneumonia model. Cell counting kit-8 assay, enzyme-linked-immunosorbent serologic assay, and quantitative polymerase chain reaction assay were conducted to confirm the effects of auraptene on the viability and inflammation of WI-38 cells. Flow cytometry (FCM) and immunoblot assays were conducted to detect the effects of auraptene on the apoptosis of WI-38 cells. Immunoblot assay was performed to confirm the mechanism. We found that auraptene stimulated cell viability in WI-38 cells upon LPS treatment. Auraptene also inhibited cellular inflammation. Furthermore, auraptene inhibited cell apoptosis of WI-38 cells upon LPS treatment. Mechanically, auraptene inhibited the nuclear factor kappa B signaling pathway, thereby suppressing the pneumonia. Auraptene alleviates inflammatory injury and cell apoptosis in pneumonia, thus has the potential to act as a pneumonia drug.

Cell Death Markers in Children with Immune Thrombocytopenic Purpura: A Preliminary Study

Immune thrombocytopenic purpura (ITP) is an autoimmune disease with possible dysregulation of the apoptotic pathways. We aimed to evaluate the possible role of some apoptotic markers (caspase 3, caspase 8 and BCL2) in the pathogenesis and course of ITP. We investigated some apoptotic markers (caspase 3, caspase 8 and BCL2) using the flow cytometry in 60 children with newly diagnosed ITP, 20 children with chemotherapy-related thrombocytopenia (CRT) and 20 healthy children. We also assessed the effects of intravenous immunoglobulin (IVIG) and methyl prednisolone therapies on the platelet apoptosis in children with newly diagnosed ITP. We demonstrated significantly higher values of caspase 3 in the newly diagnosed ITP group than control and CRT groups, and non-significantly higher values of caspase 8 in the ITP group than the healthy group. After IVIG treatment, the platelet count increased in all patients, and there was a significant decrease in caspase 3 and caspase 8 levels while BCL2 level increased. Regarding methylprednisolone treatment, there was a significant decrease in BCL2 and caspase 8 levels while caspase 3 levels did not significantly decrease. There is a possible role of the caspase dependent cell death pathway of the platelets in the occurrence of newly diagnosed ITP. There is heterogeneity in the apoptotic changes of newly diagnosed ITP children who received IVIG versus those who received methylprednisolone.

Disequilibrium in the Thioredoxin Reductase-1/Thioredoxin-1 Redox Couple Is Associated with Increased T-Cell Apoptosis in Children with Autism

Autism spectrum disorder (ASD) is a neuropsychiatric childhood disorder that affects social skill and language development, and is characterized by persistent stereotypic behaviors, restricted social interests, and impaired language/social skills. ASD subjects have dysregulated immune responses due to impairment in inflammatory and antioxidant signaling in immune cells, such as T cells. Thioredoxin reductase-1 (TrxR1) and thioredoxin-1 (Trx1) play a crucial role in the maintenance of redox equilibrium in several immune cells, including T cells. T-cell apoptosis plays a crucial role in the pathogenesis of several inflammatory diseases. However, it remains to be explored how the TrxR1/Trx1 redox couple affects T-cells apoptosis in ASD and typically developing control (TDC) groups. Therefore, this single-center cross-sectional study explored the expression/activity of TrxR1/Trx1, and Bcl2, 7-AAD/annexin V immunostaining in T cells of ASD (n = 25) and TDC (n = 22) groups. Further, effects of the LPS were determined on apoptosis in TDC and ASD T cells. Our data show that T cells have increased TrxR1 expression, while having decreased Trx1 expression in the ASD group. Further, TrxR enzymatic activity was also elevated in T cells of the ASD group. Furthermore, T cells of the ASD group had a decreased Bcl2 expression and an increased % of annexin V immunostaining. Treatment of T cells with LPS caused greater apoptosis in the ASD group than the TDC group, with same treatment. These data reveal that the redox couple TrxR1/Trx1 is dysregulated in T cells of ASD subjects, which is associated with decreased Bcl2 expression and increased apoptosis. This may lead to decreased survival of T cells in ASD subjects during chronic inflammation. Future studies should investigate environmental factors, such as gut dysbiosis and pollutants, that may cause abnormal immune responses in the T cells of ASD subjects due to chronic inflammation.

Increased serum levels of tumour necrosis factor-like weak inducer of apoptosis in children with autism spectrum disorder

Introduction: A previous study has evaluated the association between serum tumour necrosis factor-like weak apoptosis inducer (TWEAK) levels and autism spectrum disorder (ASD). In line with this investigation, the present study aimed to measure serum TWEAK levels to determine whether their eventual alteration might have etiopathogenetic significance in children with ASD. Methods: A total of 40 treatment-naive children with ASD and 40 healthy children as controls were included in the present study. The Schedule for Affective Disorders and Schizophrenia for School-Aged Children—Present and Lifetime Version, DSM-5 was used by a psychiatrist to screen the healthy controls for psychiatric disorders after a physical examination by a paediatrician. The clinical severity of the ASD symptoms was assessed by the Childhood Autism Rating Scale. Venous blood samples were collected, and serum TWEAK levels were measured. Results: This study included 80 children in total, with 40 (50.0%) in the patient group and 40 (50.0%) in the healthy control group. Thirty four (85.0%) of the participants in the patient group, and 31 (77.5%) in the healthy control group, were male, and the remainder were female. The distribution of the gender ratio was statistically similar between groups (p = 0.568). The volunteers were between 36 and 59 months old. The average age in the patient group was 46.0 ± 6.5, while that in the healthy control group was 45.2 ± 6.7. The ages were also statistically similar between groups (p = 0.615). The TWEAK values of the patient group were found to be statistically higher than those of the healthy control group (p < 0.001). Discussion: This study examined whether serum TWEAK levels were related to ASD in childhood. Our findings indicate that children with ASD have higher TWEAK levels when compared to other children. The findings further indicate that serum TWEAK levels could be related to ASD etiopathogenesis independent of ASD symptom severity.

Features of CD4+ lymphocytes apoptosis in children with cryptosporidiosis

The aim of this study was to identify the features of CD4+ lymphocytes apoptosis in children with cryptosporidiosis. Feces for the detection of cryptosporidium and venous blood for the study of lymphocytes apoptosis were the material of the study. Mononuclear leukocytes were isolated from venous whole blood and cultured in a complete culture medium. Cells were incubated for 24 hours with inducers of the receptor (TNFα) and mitochondrial pathways of apoptosis (dexamethasone).Cryptosporidia have been found in 35% of acute intestinal infections in children. The number of lymphocytes with cytoflurimetric signs of apoptosis in the group of cryptosporidiosis-positive patients did not differ from that in patients without cryptosporidiosis (p=0.421). There were no intergroup differences in the number of CD4+ lymphocytes expressing the Fas receptor on their surface (p=0.462). In cultures incubated in the presence of dexamethasone, a decrease in the number of apoptotically altered CD4+ lymphocytes was registered only in the group of cryptosporidiosispositive patients (p=0.028).The study showed that in cryptosporidiosis, the sensitivity of CD4+ cells to the induction of the mitochondrial pathway of apoptosis changes in favor of slowing down this variant of cell death.

Association of Prenatal Exposure to Endocrine-Disrupting Chemicals With Liver Injury in Children

Prenatal exposures to endocrine-disrupting chemicals (EDCs) may increase the risk for liver injury in children; however, human evidence is scarce, and previous studies have not considered potential EDC-mixture effects. Furthermore, the association between prenatal EDC exposure and hepatocellular apoptosis in children has not been studied previously. To investigate associations of prenatal exposure to EDC mixtures with liver injury risk and hepatocellular apoptosis in childhood. This prospective cohort study used data collected from April 1, 2003, to February 26, 2016, from mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort studies from 6 European countries (France, Greece, Lithuania, Norway, Spain, and the UK). Data were analyzed from April 1, 2021, to January 31, 2022. Three organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 3 phenols, 4 parabens, 10 phthalates, 4 organophosphate pesticides, 5 perfluoroalkyl substances, and 9 metals. Child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and CK-18 were measured at 6 to 11 years of age. Risk for liver injury was defined as having ALT, AST, and/or GGT levels above the 90th percentile. Associations of liver injury or cytokeratin 18 (CK-18) levels with each chemical group among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy were estimated using 2 complimentary exposure-mixture methods: bayesian weighted quantile sum (BWQS) and bayesian kernel machine regression. The study included 1108 mothers (mean [SD] age at birth, 31.0 [4.7] years) and their singleton children (mean [SD] age at liver assessment, 8.2 [1.6] years; 598 [54.0%] boys). Results of the BWQS method indicated increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (odds ratio [OR], 1.44 [95% credible interval (CrI), 1.21-1.71]), PBDEs (OR, 1.57 [95% CrI, 1.34-1.84]), perfluoroalkyl substances (OR, 1.73 [95% CrI, 1.45-2.09]), and metals (OR, 2.21 [95% CrI, 1.65-3.02]). Decreased odds of liver injury were associated with high-molecular-weight phthalates (OR, 0.74 [95% CrI, 0.60-0.91]) and phenols (OR, 0.66 [95% CrI, 0.54-0.78]). Higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (β, 5.84 [95% CrI, 1.69-10.08] IU/L) and PBDEs (β, 6.46 [95% CrI, 3.09-9.92] IU/L). Bayesian kernel machine regression showed associations in a similar direction as BWQS for all EDCs and a nonlinear association between phenols and CK-18 levels. With a combination of 2 state-of-the-art exposure-mixture approaches, consistent evidence suggests that prenatal exposures to EDCs are associated with higher risk for liver injury and CK-18 levels and constitute a potential risk factor for pediatric nonalcoholic fatty liver disease.

Immunopathogenetic significance of activation and apoptosis of immunocompetent cells in children with HIV infection

The purposeis to clarify the immunopathogenetic significance of immunocompetent cells activation and apoptosis in children with HIV-infection.Materials and methods. A clinical and immunological examination of 92 children aged 1 to 5 years old with HIVinfection in latent stage 3 (25), in the stage of secondary diseases 4A (21), 4B (22) and 4V (24) was conducted.Results.During the clinical examination, the consistent appearance of HIV-associated symptoms, opportunistic infections, and tumors was noted. Changes in the immune status included abnormalities in the T-cell component – a decrease in the number of CD4-, CD3-, increase of CD8-lymphocytes, inversion of the CD4/CD8 ratio, in the B-cell component – hyperimmunoglobulinemia, increase in the content of circulating immune complexes, in the part of innate immunity factors – a decrease in the intensity of the oxygen-dependent neutrophil metabolism and its reserve capabilities. Identified impaired positive activation of lymphocytes – a decrease in the number of CD25- and an increase in HLADR-cells. An increase in the expression of CD95-receptors on the lymphocyte membrane, an increase in the number of lymphocytes in the early (AnV) and late stages of apoptosis (AnV/Pr) was found. With the progression of HIV infection, there was a deepening of these shifts in immunological parameters, especially during the transition to the stage of secondary diseases 4V (AIDS).Conclusion.An immunological examination and correlation analysis showed that an important immunopathogenetic mechanism for reducing the number of CD4 lymphocytes in children with HIV infection is the activation of apoptosis involving the receptor and mitochondrial mechanisms. One of the reasons for the formation of depressed cellular immunity was the hyperactivation of immunocompetent cells. The findings provide a rationale for the timely prescription of antiretroviral therapy for children with HIV-infection, which will prevent hyperactivation and apoptosis of immune system cells.

MicroRNA-199 inhibits proliferation and promotes apoptosis in children with acute myeloid leukemia by mediating caspase-3.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MicroRNA-199 inhibits proliferation and promotes apoptosis in children with acute myeloid leukemia by mediating caspase-3, by F. Xue, Y. Zhu, F. Xu, L.-J. Zhou, F. Han, S.-C. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3584-3593-DOI: 10.26355/eurrev_201905_17780-PMID: 31114982" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17780.

Peculiarities of leukocyte apoptosis modulation in children with pyelonephritis

One of the leading places among inflammatory diseases of the urinary tract of children belongs to pyelonephritis, the course of which presents in most cases as a severe infectious disease threatening the patient’s life, which is the main reason for development of chronic kidney failure. This study was conducted to compare apoptosis stages in peripheral blood of children of different age categories with pyelonephritis depending on etiological factor and complications. The problem of mechanisms underlying immune system misregulation, especially functional activity of leukocytes in children with pyelonephritis, have not been explored in recent years. Assessment of leukocytes (neutrophils) apoptosis stages in peripheral blood of children of different age categories with pyelonephritis depending on complications and etiological factor was the aim of present study. The children's peripheral blood samples were analysed and assessed using a flow cytofluorimeter. The present study demonstrates an increase of the level of apoptotic cells at an early stage of apoptosis in children of all age categories with chronic pyelonephritis, which can be explained by associations of a wide range of pathogens and the presence of sequelae. An increase in the number of apoptotic cells in the late stage of apoptosis is observed in children aged 1 month – 8 years, in children 8–18 years, the amount of apoptotic cells is reduced by 1.5 times. The study of apoptosis stages allows complete characterization of the dynamics of the apoptotic process and supplementation of the pathogenesis of pyelonephritis in children. Such studies will make it possible to affect apoptosis modulation to regulate or correct it and encourage the finding of innovative solutions in the treatment related to influence on the immune response. We conclude that enhancement of peripheral blood leukocyte apoptosis in chronic form of pyelonephritis especially in young children is due to the polyetiology of this form of pyelonephritis and the development of complications.

MicroRNA-199 inhibits proliferation and promotes apoptosis in children with acute myeloid leukemia by mediating caspase-3.

The aim of this study was to detect the expression level of microRNA-199 in acute myeloid leukemia (AML). Meanwhile, we also investigated whether microRNA-199 could inhibit the proliferation and promote apoptosis of AML cells by regulating caspase-3. The expression level of microRNA-199 in peripheral blood samples of AML patients and healthy controls was determined using Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Similarly, microRNA-199 expression was also detected in AML cells and human medullary cells. The overexpression plasmid of microRNA-199 was constructed and transfected into cells. Subsequently, the regulatory effects of microRNA-199 on the proliferation, cell cycle, apoptosis, invasion and migration were accessed. The relationship between microRNA-199 and caspase-3 expression was further elucidated by Western blot and RT-qPCR. MicroRNA-199 was lowly expressed in peripheral blood of AML patients and AML cell lines than normal controls. The overexpression of microRNA-199 significantly decreased proliferative, invasive and migratory capacities of AML cells, whereas markedly increased apoptotic rate. Western blot results showed that microRNA-199 increased caspase-3 expression in AML cells. Rescue experiments demonstrated that microRNA-199 inhibited malignant progression of AML by targeting caspase-3. MicroRNA-199 is lowly expressed in AML patients. Furthermore, it inhibits the malignant progression of AML by targeting caspase-3.

Oxidative Stress Manifestation for Community-Acqiured Pneumonia in Children Living in Endemic Area of Iodine Deficiency

Objective: We aimed to evaluate the state of oxidative stress, level of molecular damage in relationship with the subcellular distribution of iodine in patients with community-acquired pneumonia from the iodine deficiency region. &#x0D; Materials and Methods: Our study involved 70 children, 4-14 years old, with CAP (moderate severity in 35 children (Group 1); severe - in 35 (Group 2)) and 35 healthy children of the control group (Group 3). The state of organificated/inorganic, antioxidant defense system, stress-dependent systems, apoptosis and the level of molecular damage were assessed in serum samples.&#x0D; Results: Lower concentration of organificated iodine (12% and 59%, respectively) and high concentration of inorganic iodine (21% and 48%, respectively) were found in Groups 1 and 2. Patients of Group 2 had an inverse relationship between the levels of iodine distribution for the organic and inorganic iodine (r = - 0.645, p&lt;0.05). In patients of Group 1, this relationship tends to decrease. The oxidative stress indicators correlated with disease severity. ROS generation indices in patients of Group 1 is 28.1 (24.2; 32.1) RFU/mg; (p &lt; 0.05); Group 2 – 40.2 (34.2; 42.5) RFU/mg (p &lt; 0.05); Caspase-3 is 25.77 (21.45–32.16) pmol/mg Group 1 and 39.42 (32.41–44.21) pmol/mg Group 2, (respectively, p &lt; 0.05). We found that children with a severe pneumonia have a prooxidant activation, manifested by a significant increase of oxidation-modified proteins [2.21 (1.88–2.53) nmol/mg)] and DNA fragmentation [13.42 (10.3–15.46) %], (p &lt; 0.05). The extent of DNA damage correlates with the extent of apoptosis. &#x0D; Conclusions: Increase in the concentration of inorganic iodine with a simultaneous decrease in the level of organic iodine in the blood, which leads to a more severe course of pneumonia. Fluctuations in the indices of oxidative stress, the level of molecular damage and the intensity of apoptosis in children with pneumonia correlate with the severity of the disease.

IODINE STATUS AND PATTERNS OF OXIDATIVE METABOLISM DISORDERS IN CHILDREN WITH COMMUNITY-ACQIURED PNEUMONIA FROM THE IODINE DEFICIENCY REGION

Introduction.Community‒acquired pneumonia is one of the most frequent pathologies of childhood. The severity of the course of this disease in children is due to concomitant pathology, the state of the endocrine and immune systems of the body, especially among the population living in conditions of endemic iodine deficiency.The aim of the study.To evaluate the state of the system of antioxidant protection in children with community−acquired pneumonia with iodine deficiency in conjunction with the subcellular distribution of iodine in the body.Materials and Methods.70 children with pneumonia were examined. The iodine availability of patients was determined by determining the level of ioduria, studying the intracellular distribution of iodine in the blood, assessing the state of the antioxidant defense system, lipid peroxidation, glutathione, apoptosis and the level of molecular damage.Results and Discussion. The level of iodine deficiency varied according to the severity of pneumonia: from mild (63.8 μg/L) with moderate pneumonia, to moderate (36.2 μg/L‒ moderate iodine deficiency) in severe disease. A lower content of organic iodine (by 12% and 59%, respectively) and a high concentration in the blood of inorganic iodine (21% and 48%, respectively) with mild to severe course of pneumonia was established.The severe course of pneumonia contributed to decrease in the activity of superoxide dismutase and a decrease in the redox index of glutathione against the background of an increase in the content of oxyradicals, caspase-3, intensive formation of oxidative modification of proteins, and enhancement of DNA fragmentation. The revealed changes tend to decrease depending on the severity of pneumonia.Conclusions.Indicators of oxidative stress, molecular damage and the intensity of apoptosis in children with community-acquired pneumonia correlate with the severity of the disease combined with iodine deficiency. The degree of iodine deficiency is significantly higher in children with severe pneumonia.

PECULIARITIES OF THE REGULATION OF THE IMMUNE SYSTEM IN CHILDREN RESIDING IN CONDITIONS OF STRONTIUM GEOCHEMICAL PROVINCE

There was made a study of the features of apoptosis in children drinking potable water with an increased content of stable strontium of natural origin. The percentage of non-standard samples of strontium content in the water on the observation territory was 16.7%, which corresponded to the exceedance of the maximum permissible concentration of strontium in drinking water at the level of 1.2 MPC (up to 8.4 mg/l). In children living in the strontium geochemical province, the blood content of strontium (0.1 mg/dm3) was established statistically significant higher (p = 0.02) in comparison with the results obtained from children living in the territory of relative sanitary and hygienic well-being (0.028 mg/dm3). There was made an estimation of parameters of the dependence between the concentration of strontium in drinking water and the concentration of strontium in the blood was estimated, there was obtained a reliable dependence (b0 = 0.04, b1 = 0.012, R2 = 0.44, F = 310, p = 0.00001) of the increase in the blood content of strontium by the 1.3 times relative to the reference level from the concentration of strontium in water. In the exposure range of 7.84 ± 0.62 mg/L per 1 mg/L increase in strontium in water, its concentration in the blood was established to increase by 0.012 mg/dm3. In children living in the strontium geochemical province (1.5-0.8 times) by the method of flow cytometry, there were established to statistically significant decline the (relative and absolute values) number of CD95+ lymphocytes (p = 0.04-0.001) by 3.8 times, the expression of p53, bcl-2, Bax and the amount of Annexin V-FITC+PI- cells dying via the path of apoptosis, as well as the content of Annexin V-FITC+PI+ cells, dying via necrosis was statistically significantly (p = 0.001) elevated, in comparison with the control group. The obtained results prove the prolonged excessive effect on the children’s organism of stable strontium supplied with drinking water to lead to changes in the functioning of the immune system, characterized by a violation of the regulation of cell death - inhibition of apoptosis and activation of necrosis. The ranges of values of strontium in the blood corresponding to the ranges at the level of 0.1 [0.04-0.11] mg/dm3 are given in the ranges of apoptotic regulation (relative content,%): CD95+ - 17.50 [15.48; 22.03], p53 - 0.53 [0.22; 0.98], bcl-2 0.24 [0.21; 0.36], bax = 5.66 [4.67; 7.84], AnnexinV-FITC+PI- cells: 0.67 [0.56; 0.88], AnnexinV-FITC+ PI+ cells: 10.58 [9.54; 16.11]. The indices of apoptotic regulation of CD95+, p53, bcl-2, Annexin V-FITC+ PI- are recommended to be used as indices of early disorders of the immune status, and also for the monitoring the effectiveness of preventive measures in the territories of strontium geochemical provinces.

DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4+ (nTh) and CD8+ (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.

Regulation of apoptotic signal by strontium in immunocytes

Exposure to heavy metals can initiate the development of negative effects in different organs and systems, including the immune system, and can be manifested as dysfunction of receptor systems and intracellular signaling. The participation of stable strontium (Sr2+) in the regulation of apoptotic signals in immunocompetent cells was analyzed. Various mechanisms of strontium-induced modulation of the apoptotic lymphocyte reaction were described, and the formation of intracellular signal transduction involving Sr2+ was defined. The flow cytometry method was used to study changes in membrane and intracellular markers of apoptosis in children who consumed drinking water with the elevated levels of strontium. It was shown that the content of strontium in blood in the range of 0.0129–0.173 mg/dm3 affected different ways of apoptosis regulation (CD95-, p53-, and TNF-induced apoptosis) and their integration sites, thereby reducing the transmission of apoptotic signal in immunocompetent cells, and formed an alternative pathway of the cell elimination based on the mechanism of necrosis.

Activity index of lymphocyte apoptosis in children with neonatal sepsis

Activity index of lymphocyte apoptosis in children with neonatal sepsis

Enhanced Blood Lymphocytes Apoptosis in Children with Inflammatory Bowel Disease

The aim of this work was to measure peripheral lymphocyte apoptosis during IBD flare and remission. Subjects and Methods. Flow-cytometric assessment of apoptosis of peripheral blood lymphocytes (PBL) was assessed in 30 children with IBD (16 with ulcerative colitis and 14 with Crohn's disease) compared to 22, age and sex matched, healthy children. This was carried out during a flare, whether in newly diagnosed or relapsing patients, and after achievement of remission. Clinical findings, complete blood count, liver transaminases, and kidney functions were assessed. Results. Early apoptotic and late apoptotic/necrotic lymphocytes were significantly higher during IBD flare compared to controls (P ≤ 0.01 and <0.01, resp., in ulcerative colitis and P ≤ 0.01 and <0.01, resp., in Crohn's disease patients). Remission values were significantly decreased but did not come back to the control levels. Early apoptotic values were significantly related to joint involvement in IBD patients (P < 0.0001). Conclusions. We can speculate a systemic nature of IBD as evident by enhanced peripheral lymphocyte apoptosis. This is related, to a great extent, to the disease process as it is more deranged in flare than in remission. Relation of this derangement to extraintestinal manifestations needs a special attention.

New markers of apoptosis in children on chronic dialysis

Enhanced apoptosis is characteristic for chronic kidney disease (CKD). A specific type of apoptosis, anoikis, is connected with the extracellular matrix turnover and cell detachment. Although E-cadherin, extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP)-8 may play an important role in this process, they have not been analyzed in any nephrological aspect, either in CKD. The aim of study was to evaluate the serum concentrations of E-cadherin, EMMPRIN and their potential regulators (MMP-8, MMP-7, TIMP-1, TIMP-2), with relevance to apoptosis/cell damage markers (sFas, sFasL, Hsp27), in children with CKD. 39 CKD children stages 3–4, 26 CKD children stage 5 still on conservative treatment, 19 patients on hemodialysis (HD), 22 children on automated peritoneal dialysis (APD) and 30 controls were examined. Serum concentrations of those parameters were assessed by ELISA. Median E-cadherin, EMMPRIN and MMP-8 values were significantly increased in patients on dialysis versus those in pre-dialysis period and versus controls. The highest values were noticed in the HD subjects. Regression analysis revealed that EMMPRIN and MMP-8 predicted various apoptosis markers, whereas E-cadherin turned out the best predictor of both apoptosis (Hsp27, sFas, sFasL) and matrix turnover (MMP-7, TIMP-1, TIMP-2) indexes in dialyzed patients. Children with CKD are prone to E-cadherin, EMMPRIN and MMP-8 elevation, aggravated by the dialysis commencement and most evident on hemodialysis. Correlations between parameters suggest their role as indexes of apoptosis in children on dialysis. E-cadherin seems the most accurate marker of anoikis in this population.