Evaluation of In Vivo Biological Activity Profiles of Isoindole-1,3-dione Derivatives: Cytotoxicity, Toxicology, and Histopathology Studies.

The anticancer activity of N-benzylisoindole-1,3-dione derivatives was evaluated against adenocarcinoma (A549-Luc). First, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide activity assay studies of two isoindole-1,3-dione derivatives were performed against A549 cell lines. Both compounds showed inhibitory effects on the viability of A549 cells. Then, we explored the potential of these compounds as active ingredients by in vivo studies. Nude mice were given A549-luc lung cancer cells, and tumor growth was induced with a xenograft model. Then, nude mice were divided into three groups: the control group, compound 3 group, and compound 4 group. After application of each compound to the mice, tumor sizes, their survival, and weight were determined for 60 days. Furthermore, toxicological studies were performed to examine the effects of the drugs in mice. In addition to toxicological studies, histopathological analyses of organs taken from mice were performed, and the results were evaluated. The obtained results showed that both N-benzylisoindole derivatives are potential anticancer agents.

Effects of creative dance on functional capacity, pulmonary function, balance, and cognition in COPD patients: A randomized controlled trial.

BACKGROUND: Exercise training is key to the comprehensive management of patients with chronic obstructive pulmonary disease (COPD). Creative dance can be an innovative approach as effective as traditional exercise training. OBJECTIVES: This study aimed to investigate effect of creative dance-based exercise (CDE) training on functional capacity, postural stability and balance, pulmonary and cognitive functions, respiratory and peripheral muscle strength in COPD patients. METHODS: Twenty-four patients with COPD were randomly allocated to either "chest physiotherapy and home-based walking program" (PT) or "CDE alongside home-based chest physiotherapy group" (PT+CDE). Both groups performed chest PT program twice a day for 5 days per week for 8 weeks. PT+CDE group received CDE training 2 days a week for 8 weeks. Primary outcome was six minute walk test (6MWT). Secondary outcomes were postural stability and balance, pulmonary function, maximum inspiratory (MIP) and expiratory (MEP) pressure, peripheral muscle strength, Montreal Cognitive Assessment (MoCA), COPD Assessment Test (CAT), and BODE index. Outcome measures were assessed at baseline and after 8 weeks of training. RESULTS: Both groups showed statistically significant improvements in 6MWT distance, MIP, MEP, MoCA score, CAT, and BODE index (p < 0.05). Only with CDE training was achieved improvements in postural stability and balance scores, pulmonary function, and peripheral muscle strength (p < 0.05). The improvements in 6 MWT distance, MEP, MoCA score, and CAT were greater in PT+CDE group (p < 0.05). CONCLUSION: Use of creative dance training in addition to home-based chest PT program was more effective than chest PT program regarding primary and secondary outcomes in COPD patients.

Effect of thoracic mobilization exercises on hamstring flexibility: a randomized controlled trial.

Background and aim: The aim was to investigate the effect of thoracic mobilization exercises on hamstring flexibility. Materials and methods: One hundred twenty individuals with hamstring tightness were included in the study. The participants were randomized into two groups: the experimental group (EG) (n = 60) or the control group (CG) (n = 60). The EG performed a home-based thoracic mobilization exercise program comprising 2 sets with 10 repetitions, once a day, 3 days a week, for 4 weeks. The CG performed active-assisted stretching of the hamstring comprising 3 sets with 10 repetitions for 15 seconds. The active knee extension (AKE) test was used to measure hamstring flexibility, and self-reported hamstring pain intensity was evaluated with a visual analog scale (VAS). All evaluations were conducted at the beginning and end of the intervention. Results: Both groups showed significant improvement in AKE (p<0.05). Pain intensity during the stretching exercises was significantly decreased only in the EG. The improvements in AKE and VAS score were greater in the EG than in the CG (p < 0.05). Between-group effect sizes were large for AKE (d = 1.075) and VAS score (d = 1.077). Conclusion: The current study showed that thoracic mobilization exercises may increase hamstring flexibility and reduce pain intensity during hamstring stretch exercises.

Video game-based exercise in children and adolescents with non-cystic fibrosis bronchiectasis: A randomized comparative study of aerobic and breathing exercises.

BACKGROUND: Video game-based systems have been proposed to improve effectiveness and compliance with exercise training in children and adolescents with noncystic fibrosis bronchiectasis (NCFB). This study aimed to investigate the effects of aerobic and breathing video game-based exercises (VGE) on pulmonary function, respiratory and peripheral muscle strength, functional capacity, and balance in children and adolescents with NCFB. METHOD: Thirty-nine children and adolescents aged between 8 and 18 years with NCFB were randomly allocated into three groups as "home-based chest physiotherapy group" (CP), "aerobic VGE given in addition to home-based chest physiotherapy group" (CP + aerobic VGE), and "breathing VGE given in addition to home-based chest physiotherapy group" (CP + breathing VGE). All three groups performed chest physiotherapy program twice a day for 7 days per week for 8 weeks. Pulmonary function, respiratory and peripheral muscle strength, functional capacity, and balance were assessed at baseline and after 8 weeks of training. RESULTS: The improvement in maximum expiratory pressure and balance scores were significantly higher in both CP + aerobic and CP + breathing VGE groups. The significant improvement in maximum inspiratory pressure was greater in the CP + breathing VGE group. The changes in peripheral muscle strength and functional capacity were significantly higher in the CP + aerobic VGE group. CONCLUSIONS: The present study showed that aerobic VGE provides additional benefits in improving peripheral muscle strength and functional capacity, while breathing VGE provides further increase in improving respiratory muscle strength. In addition, both aerobic and breathing VGE were effective in improving balance, but they were not superior to each other.

Synthesis and biological evaluation of new chloro/acetoxy substituted isoindole analogues as new tyrosine kinase inhibitors.

We have developed a versatile synthetic approach for the synthesis of new isoindole derivatives via the cleavage of ethers from tricyclic imide skeleton compounds. An exo-cycloadduct prepared from the Diels-Alder reaction of furan and maleic anhydride furnished imide derivatives. The epoxide ring was opened with Ac2O or Ac2O/AcCl in the presence of a catalytic amount of H2SO4 in order to yield new isoindole derivatives 8a-d and 9a-d. The anticancer activity of these compounds was evaluated against the HeLa cell lines. The synthesized compounds showed inhibitory effects on the viability of HeLa cells and the degree of cytotoxicity was increased with the level of bigger branched isoindole derivatives. To better understand the acting mechanism of these molecules, western blot analysis was performed with using mTOR and its downstream substrates. In addition, human mTOR and ribozomal S6 kinase ß1 (RS6Kß1) have been investigated with molecular modelling studies as possible targets for compound series 8 and 9.

Environmental distribution of Cryptococcus neoformans and C. gattii around the Mediterranean basin.

In order to elucidate the distribution of Cryptococcus neoformans and C. gattii in the Mediterranean basin, an extensive environmental survey was carried out during 2012-2015. A total of 302 sites located in 12 countries were sampled, 6436 samples from 3765 trees were collected and 5% of trees were found to be colonized by cryptococcal yeasts. Cryptococcus neoformans was isolated from 177 trees and C. gattii from 13. Cryptococcus neoformans colonized 27% of Ceratonia, 10% of Olea, Platanus and Prunus trees and a lower percentage of other tree genera. The 13 C. gattii isolates were collected from five Eucalyptus, four Ceratonia, two Pinus and two Olea trees. Cryptococcus neoformans was distributed all around the Mediterranean basin, whereas C. gattii was isolated in Greece, Southern Italy and Spain, in agreement with previous findings from both clinical and environmental sources. Among C. neoformans isolates, VNI was the prevalent molecular type but VNII, VNIV and VNIII hybrid strains were also isolated. With the exception of a single VGIV isolate, all C. gattii isolates were VGI. The results confirmed the presence of both Cryptococcus species in the Mediterranean environment, and showed that both carob and olive trees represent an important niche for these yeasts.