Expression of Basal Compartment and Superficial Markers in Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy, a Worldwide Disease.

The aim of this study was to determine the association of basal compartment and superficial markers, comprising CK5/6, CD44, CK20, and the pathological characteristics of upper tract urothelial carcinoma (UTUC) associated with Balkan endemic nephropathy (BEN). Comparing the expression of the investigated markers in 54 tumors from the BEN region and 73 control UTUC, no significant difference between them was detected. In regression analysis, CK20 expression was not determined with expression of CK5/6, CD44, and the phenotypic characteristics of BEN and control UTUC. Parameters with predictive influence on the expression of CD44 in BEN UTUC included growth pattern (p = 0.010), necrosis (p = 0.019); differentiation (p = 0.001), and lymphovascular invasion (p = 0.021) in control UTUC. Divergent squamous differentiation in BEN tumors (p = 0.026) and stage in control tumors (p = 0.049) had a predictive influence on the expression of CK5/6. This investigation detected a predictive influence of the phenotypic characteristics of UTUC on the expression of basal compartment and superficial markers, with a significant influence of necrosis in BEN tumors (p = 0.006) and differentiation in control UTUC (p = 0.036).

Coumarin N-Acylhydrazone Derivatives: Green Synthesis and Antioxidant Potential-Experimental and Theoretical Study.

Coumarin N-acylhydrazone derivatives were synthesized in the reaction of 3-acetylcoumarin and different benzohydrazides in the presence of molecular iodine as catalyst and at room temperature. All reactions were rapidly completed, and products were obtained in good to excellent yields. It is important to emphasize that four products were reported for the first time in this study. The obtained compounds were subjected to evaluation of their in vitro antioxidative activity using DPPH, ABTS, and FRAP methods. It was shown that products with a catechol moiety in their structure are the most potent antioxidant agents. The thermodynamic parameters and Gibbs free energies of reactions were used to determine the most probable mechanism of action. The results of in silico examination emphasize the need to take solvent polarity and free radical species into account when examining antiradical action. It was discovered by using computational approaches that HAT and SPLET are competitive molecular pathways for the radical scavenging activity of all compounds in polar mediums, while the HAT is the dominant mechanism in non-polar environments.

Diclofenac and metformin synergistic dose dependent inhibition of hamster fibrosarcoma, rescued with mebendazole.

We examined whether combinig diclofenac and metformin in doses equivalent to human doses would synergize their anticancer activity on fibrosarcoma inoculated to hamsters and in vitro. Rescue experiment was performed to examine whether the prosurvival NF-κB stimulation by mebendazole can reverse anticancer effects of the treatment. BHK-21/C13 cell culture was subcutaneously inoculated to Syrian golden hamsters randomly divided into groups (6 animals per group): 1) untreated control; treated daily with 2) diclofenac; 3) metformin; 4) combinations of diclofenac and metformin at various doses; 5) combination of diclofenac, metformin and mebendazole; 6) mebendazole. Dose response curves were made for diclofenac and metformin combination. Tumor growth kinetics, biophysical, pathological, histological and immunohistochemical characteristics of excised tumors and hamster organs as well as biochemical and hematological blood tests were compared among the groups. Single treatments had no anticancer effects. Diclofenac (60 mg/kg/day) exhibited significant (P < 0.05) synergistic inhibitory effect with metformin (500 mg/kg/day) on all tumor growth parameters, without toxicity and influence on biochemical and hematological blood tests. The same results were obtained with double doses of diclofenac and metformin combination. The addition of mebendazole to the diclofenac and metformin combination rescued tumor expansion. Furthermore, diclofenac with metformin demonstrated antiproliferative effects in hamster fibrosarcoma BHK-21/C13, human lung carcinoma A549 (CCL-185), colon carcinoma HT-29 (HTB-38) and cervical carcinoma HeLa (CCL-2) cell cultures, with markedly lower cytotoxicity in the normal fetal lung MRC-5 cells. In conclusion, diclofenac and metformin combination may be recommended for potential use in oncology, due to synergistic anticancer effect in doses achievable in humans.

In silico evaluation of pharmacokinetic parameters, delivery, distribution and anticoagulative effects of new 4,7-dihydroxycoumarin derivative.

In this study, pharmacological profiling and investigation of the anticoagulant activity of the newly synthesized coumarin derivative: (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (L) were performed. The obtained results were compared with the parameters obtained for Warfarin (WF), which is a standard good oral anticoagulant. The estimated high binding affinity of L toward plasma proteins (PPS% value is > 90%) justifies the investigation of binding affinity and comparative analysis of L and WF to Human Serum Albumin (HSA) using the spectrofluorimetric method (296, 303 and 310 K) as well as molecular docking and molecular dynamics simulations. Compound L shows a very good binding affinity especially to the active site of WF (the active site I -subdomain IIA), quenching HSA fluorescence by a static process. Also, the finite element smeared model (Kojic Transport Model, KTM), which includes blood vessels and tissue, was implemented to compute the convective-diffusion transport of L and WF within the liver. Finally, compound L shows a high degree of inhibitory activity toward the VKOR receptor comparable to the inhibitory activity of WF. Stabilization and limited flexibility of amino acid residues in the active site of the VKOR after binding of L and WF indicates a very good inhibitory potential of compound L. The high affinity of the L for the VKOR enzyme (Vitamin K antagonist), as well as the structural similarity to commercial anticoagulants (WF), provide a basis for further studies and potential application in the treatment of venous thrombosis, pulmonary embolism and ischemic heart disease.Communicated by Ramaswamy H. Sarma.

Unintentional Fall-Related Mortality among the Elderly in Serbia: Importance of Death Reporting Quality.

Background: Falls have been one of the leading causes of injury-related deaths among the elderly, having an increasing trend in many countries. We investigated trends of fall-related mortality among people aged ≥65 yr in Serbia. Methods: Based on official data, we calculated unintentional fall-related mortality rate (MR) from 1998 to 2017, using join point regression analysis to determine annual percentage changes (APC). Starting from 2005, doctors from Serbian Public Health Institute have been controlling the quality of death certificates. Results: In the 1998-2004 period, MR decreased in men and women aged 65-74 and men aged ≥85 (by -12.4; -13.0; and -15.1% yearly) followed by an upward trend in men and women aged 65-74 (by 76.3 vs.40.2%yearly) from 2004 to 2007 and men aged ≥85 (by 13.7% yearly) from 2004 to 2017. MR decreased among women aged ≥85 (by -9.8% yearly) from 1998 to 2008 and then increased (by 9.0% yearly) from 2008 to 2017. In men and women aged 75-84, an increase of MR (by 7.4 vs.3.1%) was observed during the entire study period. In all age groups, except women aged ≥85, significant negative correlation was found between fall-related deaths and ill-defined and unknown causes of deaths. Conclusion: Control of death certificates by physicians from the Institute of Public Health led to the better reporting of the increasing trend of fall-related mortality among the elderly. Policy makers must investigate risk factors for fall and then adopt national guidelines for prevention and treatment of fall-related injury.

Postacute Rehabilitation Impact on Functional Recovery Outcome and Quality of Life in Stroke Survivors: Six Month Follow-Up.

Background and Objectives: This study aimed to examine the impact of postacute rehabilitation duration on the outcome of the functional recovery and patients' quality of life after the stroke. Materials and Methods: One hundred patients (52 females, 48 males, mean age: 66.5 ± 7.3; range 53 to 79 years) who experienced a stroke (50 with ischemic stroke (IS) and 50 with intracranial hemorrhage (ICH)) took part in the study. Patients (treated with postacute rehabilitation measures for six months) were examined after one, three, and six months of postacute rehabilitation. Functional independence was measured using the functional independence measure (FIM) test, while the EQ-5D-3L questionnaire was used to assess the quality of life. Results: Patients with ICH had a slightly lower FIM score (FIM motor = 29.8 ± 11.8; FIM cognitive = 14.4 ± 4.6) on admission compared to patients with IS (FIM motor = 41.8 ± 18.8; FIM cognitive = 18.7 ± 6.3), but, after six months of postacute rehabilitation, patients with ICH reached an approximate level of functional independence (FIM motor = 53.8 ± 14.4; FIM cognitive = 25.8 ± 4.7), as did patients with IS (FIM motor = 67.6 ± 16.4; FIM cognitive = 29.2 ± 4.0). The motor and cognitive FIM, as well as quality of life, was statistically significantly increased at all four measurement points (p < 0.001). Furthermore, there is a statistically significant connection between functional independence and quality of life at all tested times. Conclusion: Patients achieved the highest degree of functional independence after six months. Furthermore, our findings point out that inpatient rehabilitation as well as outpatient rehabilitation are effective in functionality and quality of life improvement after a stroke; thus, both should be emphasized and regularly implemented.

Galectin-1 as the new player in staging and prognosis of COVID-19.

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 (Gal-1) is a pleiotropic cytokine involved in many immune and inflammatory processes and its role in COVID-19 is still unknown. The aim of this study was to determine systemic values of Gal-1 and correlations between Gal-1 and proinflammatory cytokines and clinical parameters during COVID-19 progression. This is observational and cross-sectional study. 210 COVID-19 patients were included and divided into mild, severe or critical group according to COVID-19 severity. Serum levels of IL-1ß, IL-6, IL-10, IL-23, IL-33 and Gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Systemic levels of IL-1ß, IL-6, IL-10, IL-23, IL-33 and Gal-1 were significantly higher in stage III of COVID-19 patients compared to stage I and II. There were no significant differences in the ratio between Gal-1 and IL-10 with proinflammatory cytokines. Positive correlation was detected between Gal-1 and IL-1ß, 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. Linear regression model and ROC curve analysis point on Gal-1 as significant predictor 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.

Mortality from external causes among 1-14 years old children in Serbia, 1997-2016.

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.

Violent deaths among adolescents in Serbia: past, present and future.

OBJECTIVES: The aim of the study was to determine the trend and methods of violent deaths (suicide and homicide) in adolescents aged 15-19 years in Serbia. METHODS: Mortality database was drawn from the Statistical Office of Serbia from the 1997-2019 period. To calculate the annual percentage change (APC) of mortality rate (MR) with corresponding 95% confidence interval we used join point regression analysis. Statistical analyses were also performed using the chi-square test and Spearman's rho correlation. RESULTS: The average suicide rate was 3.65 per 100,000 and homicide rate was 1.36 per 100,000 adolescents. The boys to girls ratio was 4.2 for suicides and 2.7 for homicides. Among girls, suicide rate significantly decreased (APC -20.7%; 95% CI -32.5 to -6.8) and homicide rate insignificantly decreased (APC -19.3%; 95% CI -37.8 to 5.1). Among boys, suicide rate significantly decreased (APC -4.6%; 95% CI -7.0 to -2.0) as well as homicide rate (APC -7.7%; 95% CI -11.5 to -4.3). The most common method of suicide was hanging (195, 44.3%) and nearly one third (198, 32.6%) of violent deaths were caused by firearms. Significantly negative correlation was observed between the Human Development Index (HDI), gross domestic product (GDP) per capita and MR due to suicides and homicides among both genders (p < 0.05). CONCLUSIONS: Increase of GDP and HDI, national preventive intervention and strict application of the provisions of the law regarding the possession and storage of weapons must be implemented in order to continue reducing violent deaths among adolescents.

Corneal Stem Cells as a Source of Regenerative Cell-Based Therapy.

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.

The Polyphenols as Potential Agents in Prevention and Therapy of Prostate Diseases.

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.

Production of Soluble Receptor Activator of Nuclear Factor Kappa-Β Ligand and Osteoprotegerin by Apical Periodontitis Cells in Culture and Their Modulation by Cytokines.

RANKL, a bone-destructive cytokine, and OPG, its osteoprotective counterpart, are expressed in periapical lesions (PLs), which represent hystopatological manifestations of apical periodontitis. However, their regulation in PLs has not been elucidated yet. Therefore, our aim was to study the production of RANKL and OPG and their modulation by pro- and anti-inflammatory cytokines in PL cell cultures. Isolated PL cells were cultured alone or with addition of TNF-α, IFN-ϒ, IL-17, IL-4, IL-10, and IL- 33, respectively. The levels of RANKL and OPG in supernatants were measured by ELISA. The proportion of CD3+ (T cells) and CD19+/CD138+ (B cells/plasma cells) within isolated PLs was determined by immunocytochemistry. The levels of RANKL were higher in cultures of symptomatic PLs compared to asymptomatic PLs and PLs with the dominance of T cells (T-type lesions) over B cells/plasma cells (B-type lesions). A higher proportion of osteodestructive processes (RANKL/OPG ratio > 1.0) were detected in symptomatic PLs. The production of RANKL was upregulated by IFN-ϒ and IL-17 and higher concentrations of IL-33. IL-10 and lower concentrations of IL-33 augmented the production of OPG. The addition of either RANKL or anti-RANKL antibody to the cultures did not modify significantly the production of OPG. In conclusion, this original PL cell culture model suggests that increased bone destruction through upregulated production of RANKL could be associated with exacerbation of inflammation in PLs with the predominance of Th1 and Th17 responses and increased secretion of IL-33. In contrast, IL-10 and lower levels of IL-33, through upregulation of OPG, may suppress osteolytic processes.

Oxidative stress biomarkers in amniotic fluid of pregnant women with hypothyroidism.

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.

Indoleamine 2,3-dioxygenase-dependent expansion of T-regulatory cells maintains mucosal healing in ulcerative colitis.

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.

Effects of maternal subclinical hypothyroidism on amniotic fluid cells oxidative status.

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.

Mesenchymal stem cells attenuate liver fibrosis by suppressing Th17 cells - an experimental study.

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 attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells.

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.

Combined effects of electromagnetic field and low-level laser increase proliferation and alter the morphology of human adipose tissue-derived mesenchymal stem cells.

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/cm2, with a wavelength of 808 nm, power output of 200 mW, and power density of 0.2 W/cm2. 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.

Treatment of trochanteric bursitis: our experience.

[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.

Mesenchymal stem cells in regenerative rehabilitation.

[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.