The Role of Endoplasmic Reticulum Stress in Metabolic Diseases.

The endoplasmic reticulum (ER), the center of protein folding, also controls the cell's life-and-death signaling mechanisms. ER stress caused by unfolded or misfolded proteins leads to the activation of the unfolded protein response (UPR) in the cell. The UPR utilizes three main signaling pathways to restore disrupted ER homeostasis. These signaling pathways are protein kinase R-like endoplasmic reticulum kinase, inositol-requiring enzyme 1, and activating transcription factor 6. Studies have reported that ER stress (ERS) plays a role in the pathogenesis of metabolic disorders such as diabetes, obesity, atherosclerosis, and nonalcoholic liver disease. This review will briefly discuss the ERS response in these metabolic diseases.

Investigation of serum trimethylamine-N-oxide levels in missed abortion: A prospective study.

OBJECTIVE: The aim of our study was to investigate the relationship between missed abortion and serum trimethylamine N-oxide (TMAO) levels. METHODS: A total of 129 patients with 56 missed abortions and 73 healthy pregnancies were included in our study. Patients who had more than one pregnancy loss, had systemic disease (hypertension, diabetes, rheumatologic disease, hematologic disease, and so forth) and did not accept to participate in the study were excluded. Pregnant women who did not have a fetal heartbeat in the first 20th week of pregnancy were considered as missed abortion. Demographic characteristics of the patients were recorded. The serum TMAO levels of these patients were compared with the serum TMAO levels of healthy pregnant women with the same gestational week between the two groups. RESULTS: The median (IQR) serum level of TMAO was significantly higher in woman with missed abortus compared to the healthy controls (201.5 [IQR, 129.75-345] vs 150 [IQR, 86.9-273], U = 1534, P = 0.015, rrb = 0.25 [95% CI: 0.05-0.43]). We observed a positive and significant relationship between serum TMAO levels and age of the patients (Spearman's rho = 0.272 [95% CI: 0.01-0.50], P = 0.043). However, no significant relationship was found between serum TMAO levels and BMI (Spearman's rho = 0.093 [95% CI: -0.18 to 0.35], P = 0.496). CONCLUSION: In our study, we found that the serum TMAO level was higher in patients with missed abortion compared to healthy pregnancies. Serum TMAO levels measured at early gestational weeks can provide information about the course of pregnancy.

Investigation the effects of bee venom and H-dental-derived mesenchymal stem cells on non-small cell lung cancer cells (A549).

BACKGROUND: Lung cancer, one of the most common oncological diseases worldwide, continues to be the leading cause of cancer-related deaths. The development of new approaches for lung cancer, which still has a low survival rate despite medical advances, is of great importance. METHODS AND RESULTS: In this study, bee venom (BV), conditioned medium of MSCs isolated from dental follicles (MSC-CM) and cisplatin were applied at different doses and their effects on A549 cell line were evaluated. Dental follicles were used as a source of MSCs source and differentiation kits, and characterization studies (flow cytometry) were performed. Cell viability was measured by the MTT method and apoptosis was measured by an Annexin V-FITC/PI kit on flow cytometer. IC50 dose values were determined according to the 24th hour and were determined as 15.8 µg/mL for BV, 10.78% for MSC-CM and 5.77 µg/mL for cisplatin. IC50 values found for BV and MSC-CM were also given in combination and the effects were observed. It was found that the applied substances caused BV to decrease in cell viability and induced apoptosis in cells. In addition to the induction of apoptosis in BV, MSC-CM, and combined use, all three applications led to an increase in Bax protein expression and a decrease in Bcl-2 protein expression. The molecular mechanism of anticancer activity through inhibition of Bax and Bcl-2 proteins and the NF-κB signaling pathway may be suggested. CONCLUSION: Isolated MSCs in our study showed anticancer activity and BV and MSC-CM showed synergistic antiproliferative and apoptotic effects.

An evaluation of matrix metalloproteinase-9 (Mmp-9) and tissue inhibitor metalloproteinase-1 (Timp-1) Serum levels and the Mmp-9/Timp-1 Ratio in Covid-19 patients.

Background: The progression of COVID-19 has different clinical presentations, which raises a number of immunological questions. Objectives: This study aimed to investigate MMP-9 and TIMP-1 levels in patients diagnosed with COVID-19 and whether the MMP-9/TIMP-1 ratio is associated with lung involvement in COVID-19. Methods: This study was conducted with 192 patients and 45 healthy controls. ELISA was used to measure the MMP-9 and TIMP-1. Results: The MMP-9 and TIMP-1 levels of the patients were found to be higher than those of the controls. MMP-9 and TIMP-1 were detected more in patients with lung involvement on chest CT scans than in those with no lung involvement on chest CT scans. A comparison of lung involvement levels revealed no difference was found between the groups. The MMP-9/TIMP-1 ratio was 5.8 in the group with lung involvement on chest CT scans and 6.1 in the group without lung involvement on chest CT scans. No difference was found between the two groups. A comparison with respect to lung involvement levels showed that the MMP-9/TIMP-1 ratio difference was found between the groups. Conclusion: Diagnostic and treatment methods targeting MMP-9 activity or neutrophil activation may be important in predicting lung involvement in COVID-19 and directing clinical outcomes.

The effect of quercetin on bone healing in an experimental rat model.

OBJECTIVES: This study aims to evaluate the effect of quercetin on fracture healing in an open fracture model in rats. MATERIALS AND METHODS: A total of 80 Wistar-Albino male rats were used in this study. The rats were divided into 10 groups. Daily oral treatment of 100 mg/kg of quercetin dissolved in corn oil were given to four groups, whereas the other four group of control rats were treated with corn oil only. Histopathological and radiological examinations of fracture healing were performed at the end of Weeks 2 and 4 in these rats, while biomechanical and biochemical examinations were performed at the end of Weeks 4 and 6, since harder callus was required. Among the rats in the last two group that were not subjected to the open fracture model, one group was given only quercetin for three weeks and the other for six weeks, and the biochemical markers in the blood were compared between these two groups. Computed tomography images were taken for radiological evaluation. The modified Lane and Sandhu scoring system was used for histological evaluation. The 3-point bending test was performed for biomechanical evaluation. For biochemical evaluation, plasma alkaline phosphatase (ALP), acid phosphatase (AP), total antioxidant status (TAS) and total oxidant status (TOS) levels were measured. RESULTS: Radiologically, there was no significant difference between the early-stage results of quercetin and control groups (p=0.247), while quercetin caused a significant increase in callus tissue in terms of latestage results (p=0.012). Histopathologically, there was no significant difference in the early stage (p=0.584); however, in the late stage, a borderline significant increase was observed in the quercetin group compared to the control group (p=0.091). Biomechanical analysis showed that quercetin significantly increased the fracture strength in the healing bone both in the early period (p=0.036) and in the late period (p=0.027). Among biochemical markers, TOS and AP were found to be significantly decreased in the quercetin group. In the non-operated and quercetin given groups, TAS levels was significantly higher (p=0.001) and AP levels were borderline significantly lower at the end of Week 6 (p=0.063). CONCLUSION: Quercetin did not have a significant effect on bone healing in the early period, but significantly promoted bone healing in the late period in rats. We recommend the use of quercetin, a strong antioxidant, in cases with high oxidative stress and conditions such as diabetes, smoking, and malnutrition which may inhibit fracture union, although further clinical studies are needed to confirm these findings.

Early assessment of extremity compartment syndrome by biochemical markers in a rat model.

BACKGROUND: This experimental study aimed to define a biochemical marker that will enable early diagnosis of acute compartment syndrome (ACS) of extremities, a mortal condition that occurs due to trauma. METHODS: A total of 15 Wistar rats were included in the study in which saline infusion technique, a clinically compatible ACS model, was applied. After the rats were anesthetized with ketamine-xylazine, the in-compartment pressure of the hind limb was slowly increased with saline delivered through the angiocatheter, and after reaching the target compartment pressure, the pressure level was kept with a rubber tourniquet. The in-compartment pressure level was continuously monitored with a pressure transducer. The rats were divided into three groups. No intervention was applied to the control group (CG) (n = 3). In study group 1 (SG1) (n = 6), ACS was created using the saline infusion technique, keeping the in-compartment pressure between 30 and 40 mmHg for 45 min. In study group 2 (SG2) (n = 6), ACS was created using the saline infusion technique, keeping the in-compartment pressure between 30 and 40 mmHg for 90 min. Fasciotomy was performed on all rats. Tissue samples were obtained for histopathological examination and blood samples for biochemical analysis. RESULTS: Total oxidant status (TOS) (p = 0.004), ischemia-modified albumin (IMA) (p = 0.030), aspartate transferase (AST) (p = 0.003) and neopterin (p = 0.012) levels differed significantly between groups in the early period of muscle ischemia. In fact, TOS levels differed significantly between the groups even in the cellular phase where signs of ischemia were not observed (p = 0.048, p = 0.024). According to histopathological evaluation, there was no significant difference between the groups. DISCUSSION: TOS can be detected in the early reversible stage of ischemia, when the histopathological findings of ACS do not occur.

The role of CD8+ regulatory T cells and B cell subsets in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a wide clinical spectrum from asymptomatic to mild, moderate, and severe cases. There are still many unknowns about the role of immunoregulatory mechanisms in COVID-19. We aimed to study regulatory T cells (Tregs) and B cell subsets and evaluate their correlations with severity of COVID-19. METHODS: In total, 50 patients with COVID-19 confirmed by PCR (mean age = 49.9 ± 12.8 years) and 40 healthy control (mean age = 47.9 ± 14.7 years) were included in this study. The patients were classified as 14 mild (median age = 35.5 [24-73] years), 22 moderate (median age = 51.5 [28-67] years) and 14 severe (median age = 55.5 [42-67] years). Within 24 h of admission, flow cytometry was used to assess the lymphocyte subsets, Tregs and Bregs without receiving any relevant medication. RESULTS: In all patients with COVID-19, the proportion of CD3+CD8+ T cells was reduced (p = 0.004) and the CD8+ Tregs were increased compared with control (p = 0.001). While the levels of regulatory B cells, plasmablasts, and mature naive B cells were found to be significantly high, primarily memory B-cell levels were low in all patients compared with controls (p < 0.05). Total CD3+ T cells were negatively correlated with the length of stay in the hospital (r = -0.286, p = 0.044). DISCUSSION: The changes in T and B cell subsets may show the dysregulation in the immunity of patients with COVID-19. In this context, the association between CD8+ Tregs and COVID-19 severity may help clinicians to predict severe and fatal COVID-19 in hospitalized patients.

Increased uncoupling protein 1 levels are associated with attention deficit and hyperactivity disorder in medication-free children.

OBJECTIVE: This study aimed to investigate serum visfatin, irisin, and uncoupling protein 1 (UCP1) levels between children with attention deficit and hyperactivity disorder (ADHD) and healthy controls and to discuss how performance on the Stroop Color Test and Serial Digit Learning Test changes with these adipokines. METHODS: A total of 45 medication-free children with ADHD and 43 controls aged 8-12 years were enrolled in this study. The serum levels of visfatin, UCP1, and irisin were measured using enzyme-linked immunosorbent assay kits. RESULTS: As a result, in our study, a statistically significant difference was found in UCP1 in the ADHD group compared with the control group, but no significant difference was found in visfatin and irisin levels. An analysis of covariance was also performed for the whole sample, and when controlling for potential confounders, including body mass index, age, and gender, the results did not change. In addition, it was determined that adipokines did not correlate with neuropsychological tests. CONCLUSION: These findings suggest that UCP1 might be associated with childhood ADHD.

Clinical Utility of Total Oxidative Stress and Total Antioxidant Capacity in Childhood Febrile Neutropenia.

The aim is to determine the oxidative status of children with febrile neutropenia (FEN). Blood samples were collected to determine the total antioxidant capacity (TAC) and total oxidative status (TOS) of healthy children (once) and children with FEN after 0, 48, and 96 hours. Eighteen patients with FEN were evaluated. The baseline TAC level of patients was significantly higher than that of the controls (P<0.0001). The TAC levels of patients with FEN with and without antibiotic modification were higher than those of the controls (P=0.002 and 0.02, respectively). The TAC levels of the patients with FEN with antibiotic modification were lower than those of the patients without antibiotic modification (P=0.0224). The oxidative stress index (OSI), calculated TOS/TAS, value of the children with FEN was lower than that of the controls (P<0.0001). The OSI values of the patients with FEN with and without antibiotic modification were lower than those of the control group (P=0.001 and <0.0001, respectively). The TAC values of the patients with antibiotic modification were higher than those of the patients without antibiotic modification (P=0.02). In conclusion, the oxidative status of the children with FEN was affected, and it can give information about the follow-up of FEN.

[Evaluation of Annexin-1 (ANXA-1), Annexin-2 (ANXA-2) and Bone Morphogenetic Protein-7 (BMP-7) Serum Levels in Patients Followed Up With A Diagnosis of COVID-19]. / COVID-19 Tanisiyla Takip Edilen Hastalarda Annexin-1 (ANXA-1), Annexin-2 (ANXA-2) ve Kemik Morfogenetik Protein-7 (BMP-7) Serum Düzeyinin Degerlendirilmesi.

Coronavirus disease 2019 (COVID-19) is a global health problem caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 infection may present with clinical pictures ranging from asymptomatic or mild forms to respiratory failure requiring intensive care follow-up and mechanical ventilation. The course of this disease with different clinical presentations raises many immunological questions. This study aimed to evaluate the serum levels of Annexin-1 (ANXA-1), Annexin-2 (ANXA-2) and bone morphogenetic protein-7 (BMP-7) in patients diagnosed with COVID-19 and to investigate whether these markers are associated with lung involvement. The study was conducted in 173 patients who were followed and treated with the diagnosis of COVID-19 and 51 healthy control group. Patients were primarily divided into two groups based on the presence of typical lung involvement (ground glass opacities, consolidation, and both) in the thoracic computed tomography (CT) scans for COVID-19. Those who found to have involvement in thoracic CT scans were divided into three groups as mild (< 33%), moderate (34-66%), and severe (> 67%) according to the extent of their lesions. Of the 173 patients included in the study, 130 had typical thoracic CT involvement for COVID-19, while 43 did not. ANXA-1, ANXA-2 and BMP-7 values were found to be higher in the patients than the control group (p= 0.001, p= 0.001, p= 0.001). ANXA-2 levels were higher in patients with thoracic CT involvement than those without thoracic CT involvement (p= 0.023). In addition, when the patients were evaluated according to their thorax CT involvement levels, it was found that as the lung involvement levels increased, ANXA-2 increased, ANXA-1 decreased, and BMP-7 levels did not change. While the increase in ANXA-2 was statistically significant, the decrease in ANXA-1 was not found statistically significant. When the relationship between the laboratory parameters and the thorax CT involvement level was evaluated; it was found that , the lymphocyte and thrombocyte counts decreased as the thorax CT involvement increased, and lactate dehydrogenase (LDH), ferritin, procalcitonin (PCT), C-reactive protein (CRP), D-dimer and troponin levels were increased. While no significant correlation was found between ANXA-1 and BMP-7 and laboratory parameters, a positive correlation was found between ANXA-2 and leukocyte count, LDH, troponin, PCT, ferritin, D-dimer, and CRP. The data obtained in our study suggest that the ANXA-2 level at the time of admission was related with the lung involvement and the level of involvement of the disease. As a result, molecular studies are needed today to understand the pathogenesis of COVID-19 and to investigate new treatment targets. Evaluation of ANXA-2 level may be important in predicting the level of lung involvement due to COVID-19.

Correlation of myeloid-derived suppressor cells with C-reactive protein, ferritin and lactate dehydrogenase levels in patients with severe COVID-19.

The novel coronavirus disease 2019 (COVID-19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid-derived suppressor cells (MDSCs) in COVID-19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID-19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings-aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C-reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty-one patients with COVID-19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets-polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs-by flow cytometric immunophenotyping, and PMN-MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID-19. Total MDSCs, PMN-MDSCs, mature PMN-MDSCs and monocytic MDSCs were significantly higher in patients with COVID-19 compared with the healthy controls (P < .05). Only PMN-MDSCs and their immature PMN-MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C-reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID-19. These findings suggest that MDSCs play a role in the pathogenesis of COVID-19, while PMN-MDSCs, especially immature PMN-MDSCs, are associated with the severity of the disease.

Evaluation of hematological parameters and inflammatory markers in children with COVID-19.

BACKGROUND: The aim of this study was to evaluate hematological parameters in children with COVID-19 and determine the effects of inflammatory biomarkers on the assessment of hospitalization. METHODS: This retrospective single-center study was performed on 633 children with COVID-19 between March 2020 and January 2021. The study population was separated into two groups: inpatients (n = 83) and outpatients (n = 550). Univariate and multivariate logistic regression was applied to identify risk factors for hospitalization. RESULTS: Lymphopenia (n = 228, 36%) was found mainly to be a hematological abnormality in all cases. Compared with outpatients, inpatients had significantly higher white blood cell (WBC) (p = 0.005), lymphocyte (p < 0.001), and platelet counts (p = 0.036), and significantly higher red cell distribution width (p = 0.001), C-reactive protein (CRP) (p = 0.003), procalcitonin (p = 0.001), D-dimer (p < 0.001), and lymphocyte to monocyte ratio values (p = 0.004). On the other hand, they had significantly lower values of hemoglobin (p < 0.001), neutrophil to lymphocyte ratio (p = 0.024), platelet lymphocyte ratio (p = 0.001), derivated neutrophil to lymphocyte ratio (p = 0.037), and mean platelet volume to lymphocyte ratio (p < 0.001). ROC analysis showed that WBC, CRP, and procalcitonin cutoff values were the best discriminated between inpatients and outpatients. The results for the areas under the curve of WBC, CRP, and procalcitonin used to assess patients' hospitalization were 0.595 (95% CI 0.519-0.670, p = 0.005), 0.599 (95% CI 0.527-0.672, p = 0.003), and 0.599 (95% CI 0.525-0.673, p = 0.004), respectively. CONCLUSION: We suggest that high WBC and procalcitonin levels can be used as independent predictors of hospitalization in children with COVID-19.

Effects of amantadine and topiramate on neuronal damage in rats with experimental cerebral ischemia-reperfusion.

BACKGROUND: Ischemia-reperfusion models are used to evaluate treatment options that may minimize cellular damage after ischemia. OBJECTIVES: To investigate the effects of amantadine and topiramate on apoptosis and cellular oxidative damage. MATERIAL AND METHODS: This experiment was performed using 30 male Wistar albino rats. The right internal carotid artery was identified and clamped with an aneurysm clip under general anesthesia, except for animals in the control group. After 10 min of occlusion, the aneurysm clip was removed, allowing reperfusion. After reperfusion and a waiting period of 12 h, the test and control groups were intraperitoneally administered the following solutions: the sham group received 10 mg/kg of isotonic solution, the amantadine group received 20 mg/kg of amantadine, the topiramate group received 40 mg/kg of topiramate, and the amantadine-topiramate group received 20 mg/kg of amantadine and 40 mg/kg of topiramate. After 24 h, the rats were euthanized. RESULTS: Apoptosis was evaluated using the TUNEL method. Total antioxidant status (TAS), total oxidant status (TOS), total thiol, and ischemia-modified albumin (IMA) levels were measured in both brain tissue and serum samples. The rate of apoptosis in the sham and amantadine groups increased significantly compared to the control group and the non-ischemic counter hemisphere. In the amantadine-topiramate group, both serum TAS and tissue thiol levels decreased. Tissue TOS levels were significantly higher in the topiramate group compared to all other test groups. Tissue TAS levels were significantly higher in the amantadine group compared to all other test groups. CONCLUSIONS: This experimental ischemia-reperfusion model revealed that topiramate reduces apoptosis in the early period after ischemia and that its combination with amantadine does not provide additional benefits against cell death. However, topiramate did not have an inhibitory effect on the oxidative stress biomarkers used in our study (TAS, TOS, IMA, and thiol). Studies that reveal the neuroprotective mechanism of action and long-term effects of topiramate are needed to complement this study.

The Relationship between COVID-19 Severity and Bacillus Calmette-Guérin (BCG)/ Mycobacterium tuberculosis exposure history in healthcare workers: a multi-center study.

The COVID-19 pandemic has brought countries' health services into sharp focus. It was drawn to our group's attention that healthcare workers (HCWs) had a lower mortality rate against higher COVID-19 incidence compared to the general population in Turkey. Since risk of exposure to tuberculosis bacillus among healthcare workers are higher than the population, we aimed to investigate if there is a relationship between BCG and Mycobacterium tuberculosis exposure history with COVID-19 severity in infected HCWs. This study was conducted with 465 infected HCWs from thirty-three hospitals to assess the relationship between COVID-19 severity (according to their hospitalization status and the presence of radiological pneumonia) and BCG and Mycobacterium tuberculosis exposure history. HCWs who required hospital admission had significantly higher rates of chronic diseases, radiological pneumonia, and longer working hours in the clinics. Higher rates of history of contact and care to tuberculosis patients, history of tuberculosis, and BCG vaccine were observed in hospitalized HCWs. HCWs who had radiological pneumonia had a significantly increased ratio of history of care to tuberculosis patients and a higher family history of tuberculosis. The findings from our study suggest that the lower mortality rate despite the more severe disease course seen in infected HCWs might be due to frequent exposure to tuberculosis bacillus and the mortality-reducing effects of the BCG vaccine.

Growth Differentiation Factor-15 Level and Tissue Doppler Echocardiography as a Tool in Identification of Cardiac Effects in the Children with Type 1 Diabetes Mellitus.

OBJECTIVE: The aim of this study was to evaluate the importance of growth-differentiation factor-15 level and tissue Doppler imaging in the detection of cardiomyopathy in children who have type 1 diabetes mellitus. MATERIALS AND METHODS: Thirty-eight patients (11 males and 27 females) with type 1 diabetes mellitus were included in this study. The control group consisted of 40 age- and gender-matched healthy volunteers. All children underwent a detailed echocardiography, which contained an m-mode, pulse Doppler and tissue Doppler imaging; and growth-differentiation factor-15 level was measured. RESULTS: In this study, there were significant differences between diastolic function parameters of the heart. The mitral isovolumic contraction time, contraction time, and isovolumic relaxation time values were different in the patients than in the controls (p<0.01, p<0.01, p<0.01, respectively). Also, the tricuspid isovolumic contraction time, contraction time, and isovolumic relaxation time values were different in the patients than in the controls (p<0.01, p=0.01, p<0.01, respectively). No statistically significant difference was found between the other M-mode parameters. Mean plasma growth-differentiation factor-15 level was significantly higher in patients than in healthy controls (p<0.01). CONCLUSION: The follow-up of children with type 1 diabetes mellitus in terms of cardiomyopathy and the use of tissue Doppler imaging and growth differentiation factor-15 levels may be useful.

Mesenchymal stem cell therapy for COVID-19.

The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) started in December 2019 and affected the whole world in a short time. The course of the disease depends on the person's immune system, physical properties, health status, etc. as it varies according to its characteristics while it is asymptomatic in some people, it causes fatal processes that start with flu-like symptoms such as cough, fever, respiratory distress in some people and progress to acute respiratory distress syndrome (ARDS), severe pneumonia and multi-organ dysfunction, and the basic mechanism underlying these effects known as a cytokine storm. There is no specific effective antiviral drug or vaccine in treatment yet. Supportive/alternative treatment methods are needed as both the desired effect cannot be achieved and undesirable side effects are seen with the current treatments used in the clinic. Mesenchymal stem cells (MSCs) are frequently preferred recently from basic studies to clinical studies and are effective and safe in immune-mediated inflammatory diseases such as Systemic Lupus Erythematosus, Graft-versus-Host disease. MSCs can secrete many types of cytokines through paracrine secretion or directly interact with immune cells leading to immunomodulation. According to the results of the completed studies; it has been stated that the cytokine storm caused by the overstimulation of the immune system decreases and even damage of the cytokine storm on organs decreases, respiratory distress is relieved and contributes to the healing process by repairing damaged tissues. In this review, clinical trials completed/ongoing on MSCs recommended for treating COVID-19, a global problem, are reviewed and the review is prepared to specify the existence of such a route to clinicians.

Evaluation of Plasma Asymmetric Dimethylarginine Levels and Abdominal Aortic Intima-Media Thickness in Infants of Smoker Mothers.

OBJECTIVE: Smoking during pregnancy has harmful effects on the fetus and infant. Although some studies suggest that exposure to fetal-maternal smoking adversely affects both fetal growth and cardiovascular development, the mechanisms and biochemical consequences of smoking in pregnancy and newborns are not yet fully understood. We aimed to investigate whether maternal smoking during pregnancy causes fetal cardiovascular effect by measuring serum asymmetric dimethylarginine (ADMA) level and abdominal aortic intima-media thickness (aIMT). STUDY DESIGN: This prospective study was conducted in newborns of smoking mothers and never-smoker control mothers during their pregnancies. The babies were evaluated echocardiographically on the first day following birth. In two-dimensional mode, abdominal aIMT measurements were performed. ADMA was measured in umbilical cord blood at birth. RESULTS: There were 25 mothers in the study group and 25 mothers in the control group. Serum ADMA levels were 0.459 ± 0.119 µmol/L in the study group and 0.374 ± 0.1127 µmol/L in the control group (p = 0.034). The aIMT value in the study group was 0.84 ± 0.026 mm and the aIMT value in the control group was 0.63 ± 0.011 mm (p = 0.005). CONCLUSION: We found that both the serum ADMA and the aIMT significantly increased in the group with newborns of smoker mothers compared with the group of the newborns of never-smoker mothers. It may also be suggested that exposure to fetal-maternal smoking adversely affects cardiovascular development. KEY POINTS: · It is a known fact that smoking during pregnancy has harmful effects on the development of the fetus and infant.. · We found that both the serum ADMA and aIMT were significantly higher in the group of infants of smoker mothers..

The clinical value of interleukins-8, -10, and -17 in idiopathic granulomatous mastitis.

INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is a rare, chronic inflammatory benign breast disease. Although the etiology of this disease is unknown, it has been suggested that hormonal disorders, autoimmunity, smoking, and α1-antitrypsin deficiency may play a role in the etiopathogenesis. The aim is to investigate the changes in cytokine profiles including interleukin (IL)-4, -8, -10, -17, and tumor necrosis factor (TNF)-alpha in patients with IGM. METHODS: Forty-seven patients with pathologically diagnosed IGM and 30 healthy women were included. The cytokines including IL-4, -8, 10, -17, and TNF-alpha were measured by human enzyme-linked immunosorbent assay. RESULTS: The IL-8, IL-10, and IL-17 levels were higher in IGM patients than control group (p = .002; p = .008; and p = .018, respectively). The IL-8 levels of patients with active lesions and in remission were statistically higher than the control group (p = .027 and p = .015, respectively). IL-10 levels of patients in remission were higher than the control group (p = .024). There was no difference in IL-4 and TNF-ɑ levels between all groups. CONCLUSION: These results showed that proinflammatory cytokines including IL-8 and IL-17 have role in pathogenesis of IGM. However, the increased levels of IL-10 in especially patients in remission suggest that it reduces the release of proinflamatory cytokines as well as suppressing their function and activation for controlling IGM. Although IGM is thought to be a surgical disease, these cytokine changes indicate the presence of serious immune dysregulation. This suggests that in the treatment of IGM, treatment needs to evolve from surgery to medical treatment.Key points• The IL-8, IL-10, and IL-17 levels were higher in IGM patients than in control group.• The IL-8 levels of both patients with active lesions and in remission were high.• There was no difference in IL-4 and TNF-ɑ levels between all groups.