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Work-related musculoskeletal disorders are among the most common disorders of the musculoskeletal system. The aim of this paper is to determine the prevalence of the musculoskeletal disorders (MSD) for the teachers in higher education. Examinees and methods: 100 teachers (66% men and 34% women with average age of 38.8 ± 13.1) were included in the prospective study. The information about the state of the teachers’ musculoskeletal system was gathered using a questionnaire for the MSD analysis. Potential risk factors for MSD were analyzed. MSD was observed in 74 (74%) teachers and associates (68.9% male and 31.1% female, p˂0.05). 32% Teachers had pain within the first five years of teaching work, while the rest of MSD occurred after that period. 73% of teachers were diagnosed with rigor in the lower back, 62% were diagnosed with neck pain, 45.9% were diagnosed with upper back pain, while 27% had pain in their ankles/feet. Lower pain prevalence was noticed in wrist, hands, hips and elbows. The prevalence of the musculoskeletal disorders for teachers is 74% and it is higher for men than for women. MSD, whose samples are multifactorial, are the most common in the lower back, neck, upper back and shoulders. Ergonomics and ergonomic education are the primary factors in the prevalence and treatment of MSD.

Introduction. Musculoskeletal pain is one of the most common types of pain affecting muscles, bones, joints, ligaments and tendons. The aim of this study was to determine the differences in the prevalence of musculoskeletal pain between students of sports and physical education and health care students. Material and Methods. The cross-sectional study included a total of 50 students, of whom 25 (50%) were students of sports and physical education, and 25 (50%) were students of health care. Data on the musculoskeletal system of students were collected through a questionnaire for the analysis of musculoskeletal symptoms. Results. The results showed that the neck and upper back pain was not negligible (14 respondents, 28%) as well as the lower back pain (27, 54%). Based on the Chi-square test, it was concluded that low back pain was significantly more common in students of health care (c2 = 3.945; p = 0.047 < 0.05) than in students of sports and physical education. Also, neck pain was significantly more common in health care students (c2 = 6.349; p = 0.012 < 0.05). Conclusion. Based on the obtained results, it can be concluded that students mostly presented with low back pain, followed by the neck and upper back pain. Engaging in proper exercises on weekly basis and excess weight reduction can prevent low back pain.

Objectives: Globally, child mortality from external causes is in decline, but it is still among the leading causes of child deaths. The aim of this first national study was to determine trends of mortality rates from external causes among children aged 1-14 years in Serbia. Methods: Mortality data were collected from the database of the Statistical Office of Serbia. Joinpoint analysis was used to assess the average annual percentage change (APC) and the corresponding 95% confidence interval (CI) in mortality from 1997 to 2016. Results: In the 1997-2016 period, there were 1,388 child deaths from external causes. They contributed to 29.4% of child mortality in total, from 34.8% in 1997 to 21.8% in 2016. Mortality rate was two times higher among boys (8.1 per 100,000) than girls (4.1 per 100,000). Transport accidents (37.6%), followed by drowning and submersion (18.2%), represented more than half of all deaths due to external causes. Since 1997, mortality rate showed a significant downward trend in boys by -5.4% (95% CI -6.8 to -3.9) yearly for unintentional injuries and significantly by -10% (95% CI -19.0 to 0.1) yearly for intentional injuries. Among girls, death rate for unintentional injuries decreased significantly by -7.1% (95% CI -9.0 to -5.1) yearly and decreased insignificantly for intentional injuries by -2.1% (95% CI -15.3 to 13.1) yearly. Conclusions: The external causes of death, despite the substantial decline in mortality, are still present among children aged 1-14 years in Serbia. Therefore, implementation of nationwide programmes for prevention of external causes of death is urgent.

Introduction. Poor muscle development, accompanied by insuffcient physical activity and non-physiological forces which act on the bone and joint system, often causes improper body posture. Objectives. To examine whether performing corrective exercises which stretch shortened and strengthen weakened muscles regularly can improve body posture in preschool and school-aged children. Methods. The prospective study included 110 children, 63 (57.2%) boys and 47 (42.8%) girls (the average age being 6.6 ± 2.4). Corrective exercises were performed four times a week for six months, in periods of 90 minutes. We used somatoscopy and somatometry methods to assess body posture. Results. On the initial checkup it was found that 18 children (16.4%) had some kind of spine deformity; 11 of them (10%) had scoliosis, six (5.5%) had kyphosis and 1(0.9%) had lordotic body posture. The first follow-up checkup was performed 3 months later when we found a decrease in the number of children with a bad body posture. The second follow-up checkup was repeated 6 months later. Out of 18 children (16.4%) who had been registered at the beginning, 4 (3.6%) had scoliotic, 2 (1.8%) had kyphotic and 1 (0.9%) had lordotic posture 6 months later. Conclusion. Based on the obtained results, it can be said that regular performance of corrective exercises (strengthening weakened and stretching shortened muscles) for six months had a positive effect on certain spine deformities. Kyphosis correction was visible after only three months, scoliosis correction was visible after six months, while lordosis correction was not achieved by corrective exercises in the only registered case. Uvod: Slaba razvijenost mišića, praćena nedovoljnom fzičkom aktivnošću i nefziološkim silama koje deluju na koštano-zglobni sistem, često uzrokuje nepravilno držanje tela. Cilj: Ispitati da li se redovnim izvođenjem korektivnih vežbi kojima se isteže skraćena, a jača oslabljena muskulatura, može popraviti držanje tela kod dece predškolskog i školskog uzrasta. Ispitanici i metode: Prospektivna studija obuhvatila je uzorak od 110 dece, od kojih je 63 (57.2%) dečaka i 47 (42.8%) devojčica (prosečne starosti 6.6 ± 2.4 godina). Korektivne vežbe su izvođene u periodu od šest meseci, četiri puta nedeljno, u trajanju od 90 minuta. Za procenu držanja primenjivane su metode somatoskopije i somatometrije. Rezultati: Na inicijalnom pregledu utvrđeno je da 18 (16.4%) dece ima neki od deformiteta kičme. Njih 11 (10%) imalo je skoliozu, šest (5.5%) kifozu i jedno (0.9%) lordozu. Prvi kontrolni pregled obavljen je posle tri meseca, kada je zabeležen pad broja dece s lošim držanjem. Drugi kontrolni pregled ponovljen je nakon šest meseci. Od ukupno 18 (16.4%) registrovanih na početku, nakon šest meseci njih četvoro (3.6%) imalo je skoliozu, dvoje (1.8%) kifozu i jedno (0.9%) lordozu. Zaključak: Na osnovu dobijenih rezultata može se reći da je redovnim izvođenjem korektivnih vežbi (jačanjem oslabljenih i istezanjem skraćenih mišića) u trajanju od šest meseci ostvaren pozitivan efekat na određene deformitete kičmenog stuba. Korekcija kifoze je bila vidljiva već nakon tri meseca, skolioze nakon šest meseci, dok korekcija lordoze u jedinom zabeleženom slučaju nije postignuta korektivnim vežbama.

The literature data show that thrombophilia and maternal dysfunction of thyroid gland during pregnancy are associated with an increased risk of miscarriage, placental abruption, hypertensive disorders and fetal growth retardation. It was shown that thyroid hormones and hypercoagulable states influence onto a leucocyte activity. The aim of this study has been to investigate maternal leucocytes changes and their correlation with frequency of fetal cells micronuclei in pregnant women with thrombophilia and hypothyroidism. The samples of blood and amniotic fluid were collected from healthy pregnant women and pregnant women with inherited thrombophilia and hypothyroidism (16 - 18 weeks of gestation). Hematological characteristics were determined by using standard hematological methods. The frequency of micronuclei was determined in fetal cells after amniocentesis by using standard cytogenetic methods. The results of this study showed significant higher levels of β-hCG, number of monocytes and eosinophils in blood of pregnant women with thrombophilia. A large number of eosinophils was documented in blood of pregnant women with hypothyroidism. Increased percentage distribution of eosinophils and basophils is shown in both investigated groups of pregnant women. The increased fetal cells micronuclei frequency and their correlation with percentage distribution of eosinophils and basophils were indicated in pregnant women with hypothyroidism. The obtained results suggest that an increased percentage of eosinophils and basophils in pregnant women with hypothyroidism contribute to a formation of micronuclei in fetal cells.

Background A new virus from the group of coronaviruses was identified as the cause of atypical pneumonia and called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and disease called Corona Virus Disease (COVID-19). During the cytokine storm, the main cause of the death, proinflammatory cytokines are released which stimulate further tissue destruction. Galectin-1 is pleiotropic cytokine involved in many immune and inflammatory processes and its role in COVID-19 is still unknown. Objective The aim of this study was to determine systemic values of galectin-1 and correlations between gal-1 and proinflammatory cytokines and clinical parameters during COVID-19 progression. Design Observational and cross-sectional study. Patients 210 COVID-19 patients were included and divided into mild, severe or critical group according to COVID-19 severity. Main Measures Serum levels of IL-1β, IL-6, IL-10, IL-23, IL-33 and galectin-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Key Results Systemic levels of IL-1β, IL-6, IL-10, IL-23, IL-33 and galectin-1 were significantly higher in stage III of COVID-19 patients compared to stage I and II. There were no significant differences in ratio between Galectin-1 and IL-10 with proinflammatory cytokines. Positive correlation was detected between Gal-1 and IL-1β, IL6, IL-10, IL-23 and IL-33. Gal-1 positively correlated with chest radiographic finding, dry cough and headache and negatively correlated with normal breathing sound. Conclusions Linear regression model and ROC curve analysis point on Gal-1 as significant predictors for COVID-19 severity. Presented results implicate on Gal-1 and IL-10 dependent immunomodulation. The precise mechanism of Gal-1 effect in COVID-19 and its potential as a stage marker of disease severity is still to be clarified.

In the past few years, intensive research has focused on corneal stem cells as an unlimited source for cell-based therapy in regenerative ophthalmology. Today, it is known that the cornea has at least two types of stem cells: limbal epithelial stem cells (LESCs) and corneal stromal stem cells (CSSCs). LESCs are used for regeneration of corneal surface, while CSSCs are used for regeneration of corneal stroma. Until now, various approaches and methods for isolation of LESCs and CSSCs and their successful transplantation have been described and tested in several preclinical studies and clinical trials. This review describes in detail phenotypic characteristics of LESCs and CSSCs and discusses their therapeutic potential in corneal regeneration. Since efficient and safe corneal stem cell-based therapy is still a challenging issue that requires continuous cooperation between researchers, clinicians, and patients, this review addresses the important limitations and suggests possible strategies for improvement of corneal stem cell-based therapy.

In this study the leaves and fruits of wild raspberry (Rubus idaeus L.) populations from the central Balkan region were examined to determine the level of secondary metabolites and related antioxidant activity, as well as biological activity, upon existing ethnobotanical evidence, primarily linked to gastrointestinal disorders. The values obtained for total phenols ranged from 59.68 to 96.83 mg GA g-1 and 24.29 to 38.71 mg GA g-1 in leaf and fruit extracts, respectively. The highest values of tannins and anthocyanins were determined for leaf extracts from a population of east Serbia at a level of 1.27 mg mL-1 and 9.00 mg mL-1. Antioxidant activity was evaluated by measuring the scavenging capacity of the extracts on DPPH. Higher antioxidant activity was detected in the leaf extracts than in the fruit extracts. Leaf and fruit extract were the most effective against Escherichia coli (ATCC 8739). Anticancer activity was studied on a human colorectal cancer cell line HCT-116. Leaf extracts exhibited anticancer activity with IC50/24 h 162.38 μg mL-1 and IC50/48 h 95.69 μg mL-1. Wild raspberry leaf and fruit extracts contain numerous secondary metabolites providing marked antioxidant, antimicrobial and anticancer activity.

Introduction/Objective. The quality of life (QL) is a modern concept of observing the outcome of the disease and the success of the therapeutic procedure in all fields of medicine. The aim was to assess the QL of surgically treated patients with lumbar radiculopathy (LR) at the beginning of treatment and three and six months after the initiation of prescribed and applied medical rehabilitation. Methods. The study group included randomized and stratified sample of 50 patients treated with lumbar microdiscectomy (LM). Conservative treatment was carried out using physical therapy procedures, and kinetic and ergonomic therapeutic procedures and educational training program in ergonomics were carried out in all the patients. To assess the condition of the patients, the QL and the efficacy of the rehabilitation treatment, we used two standardized questionnaires, the Short Form Survey Instrument (SF-36) and the Oswestry Disability Index (ODI). Results. The lowest values of the SF-36 ? PCS, SF-36 ? MCS, and of the ODI were recorded at the beginning of the rehabilitation (PCS: 28.8; MCS: 37.8; ODI: 56.1%). The most significant improvements of the scores were observed three months after the treatment initiation (PCS: 42.8; MCS: 45.2; ODI: 38.9%). At six months of treatment, the scores were slightly higher (PCS: 49.2; MCS: 52.5; ODI: 23.7%) (p < 0.001). Conclusion. The QL and the functional status of patients after LM are significantly better after three and six months in comparison with the beginning of rehabilitation, and the state for six months compared to the state for three months.

Socioeconomic inequalities influence the development of inequalities in healthcare-morbidity, treatment, survival, care and quality of life of the patients. Gastric cancer is the 4th most frequent and the 3rd deadliest malignant disease in the world, while approximately 70%. of gastric cancer cases occur in the undeveloped countries. The purpose of this paper is to review the published literature on the influence of socioeconomic inequalities on gastric cancer development, its early detection, treatment and survival rates. The results indicate that in persons of lower socioeconomic status there is a higher risk for development of gastric cancer which is usually detected in an advanced phase and the survival time is shorter. Preventive measures within national, social and economic policies aiming to reduce inequality will result in reducing gastric cancer morbidity and mortality and consequent economic burden to society imposed by this disease.

In recent years, the progress of science and medicine greatly has influenced human life span and health. However, lifestyle habits, like physical activity, smoking cessation, moderate alcohol consumption, diet, and maintaining a normal body weight represent measures that greatly reduce the risk of various diseases. The type of diet is very important for disease development. Numerous epidemiological clinical data confirm that longevity is linked to predominantly plant-based diets and it is related to a long life; whereas the western diet, rich in red meat and fats, increases the risk of oxidative stress and thus the risk of developing various diseases and pre-aging. This review is focused on the bioavailability of polyphenols and the use of polyphenols for the prevention of prostate diseases. Special focus in this paper is placed on the isoflavonoids and flavan-3-ols, subgroups of polyphenols, and their protective effects against the development of prostate diseases.

Introduction. Lumbar spine pain is among the most common conditions affecting daily activities in modern-day societies, as well as the second most common cause of absenteeism from work. The aim of the paper was to determine the incidence of lumbar spine pain in dental professionals of the Dental Clinic of Vojvodina, the effects of lumbar spine pain on their general health and work ability, their attitude to treatment options, as well as potential etiological factors for the appearance of lumbar spine pain. Material and Methods. A prospective study included 45 employees of the Dental Clinic of Vojvodina. We investigated the association between the appearance of lumbar spine pain and the work of dental professionals. The data were gathered via a questionnaire analyzing musculoskeletal disorders, and the probable risk factors for their appearance. Results. There were 75.6% (34/45) of women and 24.4% (11/45) of men, aged from 22 to 64 years, with a total work experience of 13?9.6 years. Lumbar spine pain was recorded in 60% of examinees. They were mostly localized in the lower back (52.2%), but also spreading down along both legs (17.4%) and into the right hip (13%) (p < 0.01). The incidence of low back pain was higher in dentists (72.4%) than in dental assistants (45.5%) and dental technicians (20%) (p < 0.05). Conclusion. Lumbar spine disorders are among the most frequent occupational diseases in dental practice, associated with multifactorial causes. Ergonomics and ergonomic education are primary factors in the prevention and therapy of lumbar spine conditions.

Trout production represents a major agricultural activity in Serbia. Organic compounds are drained into the environment, usually without previous sedimentation, thus affecting the stream biota. Considering that biological monitoring is commonly based on aquatic macroinvertebrates as target organisms, the authors used larvae of Dinocras megacephala to estimate trout farm effects on the mass of the larvae and their antioxidative defense in pollution stress conditions. Four locations were chosen along the channel of the Raska River, 2 upstream (L1, L2) and 2 downstream (L3, L4) from the trout farm outlet. Basic physical and chemical water parameters were measured. Superoxide dismutase (SOD) and catalase (CAT) activity changes were analyzed to determine the level of oxidative stress caused by the increase of organic compounds originating from the trout farm. Dissolved oxygen concentration decreased from the upstream to downstream locations. Furthermore, the concentration of ionized ammonia was almost 10 times higher at the downstream locations than at the upstream locations. Larval mass, as well as CAT activity, was significantly higher at L3 compared with the other 3 locations. Activity of SOD was significantly higher at L3 than at L1. The results indicate that higher concentrations of organic compounds from the trout farm induce clear changes in the status of the antioxidant defense of D. megacephala larvae. Environ Toxicol Chem 2016;35:1775-1782. © 2015 SETAC.

Herein we report the synthesis of new trans-bis(2-phenylselenylmethyl)oxolane)dichloroplatinum(II) complex Pt1. Newly synthetized complex, together with two, structurally related trans-Pd(II) complexes (trans-bis(2-(phenylselenylmethyl)oxolane)dichloropalladium(II) Pd1 and trans-bis(2-(phenylselenylmethyl)oxane)dichloropalladium(II)) Pd2, were screened for cytotoxic activity through in vitro study on the HCT-116 colorectal carcinoma cell line and on the MRC-5 healthy lung pleura cell line. Activity of complexes was assessed by comparing it to the cisplatin. The cells viability and proliferation were determined using MTT assay.

Background: Dendritic cell (DC)-derived indolamine 2,3-dioxygenase (IDO) degrades tryptophan to kynurenine, which promotes conversion of inflammatory T cells in immunosuppressive regulatory T cells (Tregs). We analyzed the significance of the IDO:Treg axis for inducing and maintaining mucosal healing in ulcerative colitis (UC). Methods: Dextran sodium sulphate (DSS)-induced colitis in BALB/c mice (model for mucosal healing) and C57BL/6 mice (model for persistent disease) was used. Serum, fecal samples and colon-infiltrating immune cells of 65 patients with UC with mucosal healing or persistent colitis were analyzed. Results: Significantly higher serum levels of kynurenine and downregulated inflammatory cytokines were noticed in DSS-treated BALB/c mice compared with C57BL/6 mice. Increased IDO activity and attenuated capacity for antigen presentation and production of inflammatory cytokines, observed in BALB/c DCs, was followed by a significantly lower number of inflammatory T helper 1 (Th1) and Th17 cells and a notably increased number of Tregs in the colons of DSS-treated BALB/c mice. DCs and Tregs were crucially important for the maintenance of mucosal healing since their depletion aggravated colitis. Mucosal healing, followed by an increase in kynurenine and intestinal Tregs, was re-established when BALB/c DCs were transferred into DC-depleted or Treg-depleted DSS-treated BALB/c mice. This phenomenon was completely abrogated by the IDO inhibitor. Significantly higher serum and fecal levels of kynurenine, accompanied by an increased presence of intestinal Tregs, were noticed in patients with UC with mucosal healing and negatively correlated with disease severity, fecal calprotectin, colon-infiltrating interferon γ and interleukin-17-producing cells, serum and fecal levels of inflammatory cytokines. Conclusion: IDO-dependent expansion of endogenous Tregs should be further explored as a new approach for the induction and maintenance of mucosal healing in patients with UC.

[Purpose] Trochanteric bursitis is a disease for which there are no effective standardized therapy protocols. Very often pain persists in spite of applying all therapeutic treatments. The purpose of this study was to determine whether treatment of trochanteric bursitis with a local injection of bicomponent corticosteroid and 2% lidocaine would improve patients’ conditions and relieve pain symptoms in the trochanteric area. [Subjects and Methods] A retrospective observational study was conducted of 2,217 patients in a 6 year follow-up period at the Special Hospital “Agens”, Mataruska Banja, Serbia. [Results] Of 2,217 examined patients, 58 (2.6%) patients were found to suffer from trochanteritis associated with low back pain, and 157 (7%) were found to suffer from trochanteric pains without low back pains. Local corticosteroid therapy followed by physical therapy was effective in 77 (49%) of these patients, and only corticosteroid injection in 61 (39%) patients. A single injection was given to 47 (29.9%) of the patients. Two injections were given to 9 (5.7%) patients, and from 3 to 5 injections were given repeatedly every 4–6 weeks to 7 (4.5%) patients. [Conclusion] For most patients, local injections of corticosteroids with lidocaine alone or followed by physical therapy gave satisfactory results.

[Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient’s medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future.

To determine mortality trends and premature mortality due to stroke in Serbia in 1992–2013 period. We obtained mortality database from the Statistical Office of Serbia. From 1992 to 2005, age-standardized mortality rates (ASRs) per 100,000 for all stroke increased, with annual percentage change (APC) of 1.01 % in men and 1.05 % in women. From 2005 to 2013, ASRs decreased, with APC of −4.93 % in men, and −5.63 % in women. In men, years of life lost (YLLs) for all stroke deaths were 21,710 in 1992; 22,193 in 2003 and 17,464 in 2013, with average years of life lost (AYLLs) of 3.46, 2.89 and 3.00, respectively. In women, YLLs were 33,508 in 1992; 35,130 in 2003 and 21,676 in 2013, with AYLLs of 4.65; 3.57 and 2.97. From 1992 to 2013, ASRs and YLLs for all stroke showed two segment trends in Serbia, with increase in the first, and decrease in the second period. Due to the shorter AYLLs and longer life tables, in 2013 stroke deaths occurred at >4 years older age in both sexes than in 1992.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease occurring in people living in along the tributaries of the Danube River. The aim of the study was to determine serum level and urinary excretion of placental growth factor (PlGF) and placental protein 13 (PP13) in patients with BEN.Thirty patients with BEN from the South Morava River region of Serbia and 18 controls were studied. Age of patients was 74 yr (53-87) and 73 yr (66-83) in controls.In patients with BEN, serum creatinine was significantly higher than in controls (129.7 vs. 83.2 µmol/L, respectively), but GFR was lower in patients than in controls (40.7 vs. 54.6 mL/min). Serum PlGF was significantly higher in BEN patients than in controls (9.90 vs. 6.80 pg/mL), urinary excretion being significantly lower in patients (0.20 vs. 0.90 pg/mmol creat.). Serum PP13 was significantly lower in BEN patients (208.2 vs. 291.0 pg/mL). Urinary excretion of PP13 was also significantly lower in BEN patients than in controls (32.5 vs. 182.5 pg/mmol creat). In multivariate regression analysis BEN, sex and age were significant determinants of the observed changes in PlGF and PP13.Important changes of PlGF and PP13 in patients with BEN were demonstrated, where kidney disease, female sex, and the age have been significant determinants.

In this study, we researched the effects of maternal subclinical hypothyroidism on the amniotic fluid cells oxidative metabolism during the first trimester of pregnancy. Oxidative stress and damage biomarkers were assayed in the amniotic fluid cells of healthy and pregnant women with subclinical hypothyroidism. Obtained results show that amniotic fluid cells of pregnant women with subclinical hypothyroidism have significantly higher concentrations of oxidative stress biomarkers (superoxide anion, nitric oxide, peroxynitrite) and oxidative damage (lipid peroxide and micronuclei frequency), but lower concentrations of hydrogen peroxide and oxidized glutathione in comparison to healthy pregnant women. We also showed that oxidative stress biomarkers were positively correlated with micronuclei frequency and lipid peroxide concentration in amniotic fluid cells of pregnant women with subclinical hypothyroidism. The present study provides the first evidence for prooxidative effects of maternal subclinical hypothyroidism on the fetus obtained by the estimating oxidative metabolism in the amniotic fluid cells.

Purpose: Hypothyroidism in pregnancy is the serious state that may lead to fetal morbidity and mortality. Oxidative stress biomarkers in the amniotic fluid can provide important information on the health, development and maturation of the fetus during pregnancy. In this study, we examined whether maternal hypothyroidism contributes to increased oxidative stress biomarkers in the amniotic fluid during the first trimester of pregnancy. Materials and methods: The study was conducted on healthy pregnant women and pregnant women with hypothyroidism (gestational age: 16-18 weeks). Oxidative stress biomarkers, such as superoxide anion (O2•-), hydrogen peroxide (H2O2), nitric oxide (NO), peroxynitrite (ONOO-), lipid peroxide (LPO), reduced glutathione (GSH) and oxidized glutathione (GSSG) were assayed in the amniotic fluid. Results: The results of this study indicated that concentrations of O2•- and NO are significantly higher, while the concentration of H2O2 is significantly lower in the amniotic fluid of pregnant women with hypothyroidism in comparison to healthy pregnant women. There were no differences in concentrations of LPO, GSH and GSSG among tested groups. Also, we found that amniotic fluid concentration of O2•- is negatively correlated with the body weight and Apgar score values of the newborns. Conclusion: These results suggest that pregnancy hypothyroidism is characterized by the amniotic fluid oxidative stress. Incorporation of the oxidative stress biomarkers measurement in the amniotic fluid may be of clinical importance in the management of pregnancy hypothyroidism.

This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSC)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl4 (1 μl/g intraperitoneally) twice/week for 1 month. MSCs (1 × 106 ), or MSC-conditioned medium (MSC-CM), were intravenously injected 24 h after CCl4 and on every 7th day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining, and RT-PCR. Serum levels of cytokines, indoleamine 2,3-dioxygenase (IDO), and kynurenine were determined by ELISA. Flow cytometry was performed to identify liver-infiltrated cells. In vitro, CD4+ T cells were stimulated and cultured with MSCs. 1-methyltryptophan was used for inhibition of IDO. MSCs significantly attenuated CCl4 -induced liver fibrosis by decreasing serum levels of inflammatory IL-17, increasing immunosuppressive IL-10, IDO, and kynurenine, reducing number of IL-17 producing Th17 cells, and increasing percentage of CD4+ IL-10+ T cells. Injection of MSC-CM resulted with attenuated fibrosis accompanied with the reduced number of Th17 cells in the liver and decreased serum levels of IL-17. MSC-CM promoted expansion of CD4+ FoxP3+ IL-10+ T regulatory cells and suppressed proliferation of Th17 cells. This phenomenon was completely abrogated in the presence of IDO inhibitor. MSCs, in IDO-dependent manner, suppress liver Th17 cells which lead to the attenuation of liver fibrosis.

Mesenchymal stem cells (MSCs) are, due to immunomodulatory characteristics, considered as novel agents in the treatment of immune-mediated acute liver failure. Although it is known that MSCs can regulate activation of T lymphocytes, their capacity to modulate function of neutrophils and natural killer T (NKT) cells, major interleukin (IL) 17-producing cells in acute liver injury, is still unknown. By using 2 well-established murine models of neutrophil and NKT cell-mediated acute liver failure (induced by carbon tetrachloride and α-galactoceramide), we investigated molecular and cellular mechanisms involved in MSC-mediated modulation of IL17 signaling during acute liver injury. Single intravenous injection of MSCs attenuate acute hepatitis and hepatotoxicity of NKT cells in a paracrine, indoleamine 2,3-dioxygenase (IDO)-dependent manner. Decreased levels of inflammatory IL17 and increased levels of immunosuppressive IL10 in serum, reduced number of interleukin 17-producing natural killer T (NKT17) cells, and increased presence of forkhead box P3 + IL10-producing natural killer T regulatory cells (NKTregs) were noticed in the injured livers of MSC-treated mice. MSCs did not significantly alter the total number of IL17-producing neutrophils, CD4+, and CD8 + T lymphocytes in the injured livers. Injection of mesenchymal stem cell-conditioned medium (MSC-CM) resulted with an increased NKTreg/NKT17 ratio in the liver and attenuated hepatitis in vivo and significantly reduced hepatotoxicity of NKT cells in vitro. This phenomenon was completely abrogated in the presence of IDO inhibitor, 1-methyltryptophan. In conclusion, the capacity of MSCs to alter NKT17/NKTreg ratio and suppress hepatotoxicity of NKT cells in an IDO-dependent manner may be used as a new therapeutic approach in IL17-driven liver inflammation. Liver Transplantation 23 1040-1050 2017 AASLD.

In recent years, electromagnetic field (EMF) and low-level laser (LLL) have been found to affect various biological processes, the growth and proliferation of cells, and especially that of stem cells. The aim of this study was to investigate the effects of EMF and LLL on proliferation of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and thus to examine the impact of these therapeutic physical modalities on stem cell engraftment. hAT-MSCs were isolated from subcutaneous adipose tissue of six persons ranging in age from 21 to 56 years. EMF was applied for a period of 7 days, once a day for 30 min, via a magnetic cushion surface at a frequency of 50 Hz and an intensity of 3 mT. LLL was applied also for 7 days, once a day for 5 min, at radiation energies of 3 J/cm(2), with a wavelength of 808 nm, power output of 200 mW, and power density of 0.2 W/cm(2). Nonexposed cells (control) were cultivated under the same culture conditions. Seven days after treatment, the cells were examined for cell viability, proliferation, and morphology. We found that after 7 days, the number of EMF-treated hAT-MSCs was significantly higher than the number of the untreated cells, LLL-treated hAT-MSCs were more numerous than EMF-treated cells, and hAT-MSCs that were treated with the combination of EMF and LLL were the most numerous. EMF and/or LLL treatment did not significantly affect hAT-MSC viability by itself. Changes in cell morphology were also observed, in terms of an increase in cell surface area and fractal dimension in hAT-MSCs treated with EMF and the combination of EMF and LLL. In conclusion, EMF and/or LLL treatment accelerated the proliferation of hAT-MSCs without compromising their viability, and therefore, they may be used in stem cell tissue engineering.