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Gastrointestinal bacteria are known to have an impact on local and systemic immunity, and consequently either promote or suppress cancer development. Following the notion that perinatal bacterial exposure might confer immune system competency for life, we investigated whether early-life administration of cholera-toxin (CT), a protein exotoxin of the small intestine pathogenic bacterium Vibrio cholerae, may shape local and systemic immunity to impart a protective effect against tumor development in epithelia distantly located from the gut. For that, newborn mice were orally treated with low non-pathogenic doses of CT and later challenged with the carcinogen 7,12-dimethylbenzanthracene (DMBA), known to cause mainly mammary, but also skin, lung and stomach cancer. Our results revealed that CT suppressed the overall incidence and multiplicity of tumors, with varying efficiencies among cancer types, and promoted survival. Harvesting mouse tissues at an earlier time-point (105 instead of 294 days), showed that CT does not prevent preneoplastic lesions per se but it rather hinders their evolution into tumors. CT pretreatment universally increased apoptosis in the cancer-prone mammary, lung and nonglandular stomach, and altered the expression of several cancer-related molecules. Moreover, CT had a long-term effect on immune system cells and factors, the most prominent being the systemic neutrophil decrease. Finally, CT treatment significantly affected gut bacterial flora composition, leading among others to a major shift from Clostridia to Bacilli class abundance. Overall, these results support the notion that early-life CT consumption is able to affect host's immune, microbiome and gene expression profiles toward the prevention of cancer., (© 2023 UICC.)

Neutrophil and T-cell recruitment contribute to hepatic ischemia/reperfusion injury. The initial inflammatory response is orchestrated by Kupffer cells and liver sinusoid endothelial cells. However, other cell types, including γδ-Τ cells, seem to be key mediators in further inflammatory cell recruitment and proinflammatory cytokine release, including IL17a. In this study, we used an in vivo model of partial hepatic ischemia/reperfusion injury (IRI) to investigate the role of the γδ-Τ-cell receptor (γδTcR) and the role of IL17a in the pathogenesis of liver injury. Forty C57BL6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion (RN 6339/2/2016). Pretreatment with either anti-γδΤcR antibodies or anti-IL17a antibodies resulted in a reduction in histological and biochemical markers of liver injury as well as neutrophil and T-cell infiltration, inflammatory cytokine production and the downregulation of c-Jun and NF-κΒ. Overall, neutralizing either γδTcR or IL17a seems to have a protective role in liver IRI.

The impact of dietary inclusion of Spirulina platensis on the immune system, intestinal microbiome and skin of mink was investigated. Forty-eight animals were equally separated into four groups. Groups B and D were control animals, while groups A and C had their feed supplemented daily with 100 mg/kg of body weight Spirulina. Mink in groups A and B were descended from dams supplemented with spirulina during their reproductive period, while those in groups C and D were descended from dams fed the control diets. Fur growth rate and quality were graded semi-quantitatively. Fecal microbiome analysis, skin thickness histomorphometry, immunohistochemical labeling and counts of immune cells in the colon, mesenteric lymph nodes and spleen and quantitative gene expression analysis of cytokines in the colon were performed. Skin thickness, fur growth rate and skin quality were similar among groups (p > 0.05). However, differences were observed among groups concerning the relative and differential abundance of bacterial species. Tgf-β expression was lower in group A, whereas IL-β1 was lower in group C compared to group B (p < 0.05). Group D had significantly lower numbers of inflammatory cells in the colon and mesenteric lymph nodes. The results revealed that Spirulina decreased indices of subclinical inflammation in mink gut, while differences in the bacterial communities among groups were observed., Competing Interests: The authors declare no conflicts of interest.

Many studies have shown the effect of dance to the brain. It seems that long-term practice modulates brain plasticity and visuomotor skills, as it activates the Action Observation Network (AON). The aim of this systematic review was to evaluate potential differences in the brain activity (visuomotor skills) between professional dancers and non-dancer adults, measured by electroencephalography (EEG), during the observation of an individual who is dancing (video dance stimuli). This literature search was conducted from February to June 2022, according to the PRISMA guidelines, in the PubMed database using advanced search, mesh terms, and extensive manual search. The included articles were published in English. Specifically, case-control studies were selected, which used healthy adults, professional dancers, and non-dancers as participants, who were exposed to video dance clips and measured by EEG. The articles were excluded if they were based on different type of study, unhealthy population, control group with athletic background, different type of stimuli (rhythmic), or different type of task and procedure. The ratings of quality of evidence were conducted using the Joanna Briggs Institute's (JBI) critical appraisal tool. Five case-control studies were included with 193 participants in total, 87% females. The participating groups of professional dancers (n = 12-25) had mean age 25.14 years, with at least 9-19 years of professional training, whereas control groups had the same sample size, mean age of 24.14 years, and no experience in dancing. Most of the studies presented high methodological quality. All studies showed significant differences in dancers' brain activity, especially regarding the visuomotor skills. The results showed faster activation of AON demonstrated by higher P300 at the frontocentral regions and increased sensitivity of the occipital temporal cortex. Dancers could cope easier with familiar-unfamiliar and effortful-effortless movements. They also demonstrated faster alpha band peak frequency, stronger synchrony over the bands theta, beta, gamma during the audiovisual stimuli, and the ability to encode faster the visual information. The results demonstrate that dancers had better visuomotor skills suggesting dance-enhanced neuroplasticity, as professional dancers processed their actions easier. Dance, which includes visuomotor tasks, could help in prevention, therapy, and rehabilitation of neurodegenerative diseases or movement disorders., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Stress is associated with unhealthy habits and non-communicable diseases. It is also linked to communicable diseases due to its impact on immune function. These can be prevented through intervention programs in schools. The aim of this study was to examine the effect of the simplified Pythagorean Self-Awareness Intervention on heart rate variability (HRV) parameters, perceived stress and behaviors of preschool children. The sample of the study consisted of 45 preschool students. A “one group (double) pretest—posttest design” was used, to allow for comparisons of the measurements before and after the intervention. Students were assessed via two questionnaires (“Perceived Stress Scale for Children” (PSS-C) and “Checklist for Screening Behavioral Problems in Preschool Children”) and a photoplethysmographic (PPG) device. The intervention lasted 9 weeks and included practicing of the Pythagorean Self-awareness techniques and the adoption of healthy behaviors. The results showed no statistically significant differences between the two pretests (p > 0.05 for all comparisons) and statistically significant differences between the second pretest and posttest (“Perceived Stress Scale for Children”, (PSS-C) p < 0.0001, “Checklist for Screening Behavioral Problems in Preschool Children” p < 0.0001 and two indices of PPG device: heart rate mean, p < 0.0001, low frequency/very low frequency, p = 0.034). In conclusion, the Pythagorean Self-Awareness Intervention had a beneficial effect on the sample of preschool students examined, as the results showed an improvement in the perceived stress and the HRV parameters tested, and in engaging healthier behaviors, findings that indicate a relaxed psychologic state and a healthier lifestyle.

Recently, our group showed that Romidepsin, a histone deacetylase inhibitor (HDACi), suppressed diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in mice. In the present study, we investigated the effect of Romidepsin-treatment on gene expression levels of components of Bmp and Notch signaling pathways, which are both known to be aberrantly regulated in hepatocarcinogenesis. Total RNA from liver tissue samples and paraffin-embedded livers were retrieved from a recent experiment where C57BL/6 mice were treated with Romidepsin 10 months after DEN challenge and sacrificed 2 months later. RT qPCR was used for quantification of gene expression and immunohistochemistry for in situ protein detection. Regarding Bmp pathway, Romidepsin HCC-suppression was found to correlate significantly with Bmp2 and Bmp7 ligand up- and down-regulation, respectively. Intracellularly, Romidepsin-treated HCC mice exhibited a significant elevation of Bmp-inhibitor Smurf2 and Bmp-target gene Id3, as compared to the HCC untreated controls. Concerning Notch signaling, higher expression levels of ligands Jag1/Dll4, accompanied by a decreased expression of receptor Notch2, were identified in the Romidepsin-treated group. Τhe anti-oncogenic effect of Romidepsin, also correlated significantly with an increased expression of Hes1 target, as well as an up- and down-regulation of Klf4 and Sox9 transcription factors, respectively. Moreover, the cancer-related genes Snai2 and p21, known to be involved in many signaling pathways, including Bmp and Notch, were also found to be downregulated in Romidepsin-treated mice. Romidepsin HCC suppression is associated with gene expression deregulation of selective components of both Bmp and Notch signaling cascades.

Background: Diabetes is regarded as an epidemiological threat for the twenty-first century. Phytochemicals with known pharmaceutical properties have gained interest in the field of alleviating secondary complications of diseases. Such a substance is crocin, a basic constituent of saffron ( Crocus sativus ). The present study aimed at examining the beneficial effects of per os crocin administration on the antioxidant status, blood biochemical profile, hepatic gene expression and plasminogen activator inhibitor-1 activity (PAI-1) in the liver, kidney and plasma (an important marker of pre-diabetic status and major factor of thrombosis in diabetes) of healthy rats, as well as of rats with nicotinamide-streptozotocin-induced diabetes., Results: Diabetes disrupted the oxidation-antioxidation balance, while crocin improved the antioxidant state in the liver by significantly affecting SOD1 gene expression and/or by restoring SOD and total antioxidant capacity (TAC) levels. In the kidney, crocin improved hydrogen peroxide decomposing activity and TAC. In blood, hepatic transaminases ALT and AST decreased significantly, while there was a trend of decrease regarding blood urea nitrogen (BUN) levels. The expression of PAI-1 gene was affected in the liver by the dose of 50 mg kg -1 ., Conclusions: Crocin treatment contributed in restoring some parameters after diabetes induction, primarily by affecting significantly hepatic transaminases ALT and AST, SOD1 and PAI-1 gene expression and nephric H 2 O 2 decomposing activity. In conclusion, crocin did contribute to the alleviation of some complications of diabetes., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Notch is an evolutionarily conserved signaling pathway with an important role in development and cell fate determination. Deregulation of Notch signaling has been associated with several pathological conditions, including cancer. Acting as an oncogene in some types of cancers and as a tumor suppressor in other, Notch effects seem to be highly context-dependent in solid tumors. In the present study, we aimed to investigate gene expression levels of Notch pathway constituents, including ligands, receptors, and target genes, during the early stages of inflammation-associated intestinal carcinogenesis. To achieve so, we used our recently developed mouse model, in which colon cancer arises in the absence of urokinase-type plasminogen activator (uPA) due to colitis induced by dextran sodium sulfate (DSS) treatment. Among the cell surface components, ligands Jag1/Jag2 and receptors Notch1/Notch2 were found to be significantly upregulated in the uPA-deficient protumorigenic inflammatory microenvironment. Moreover, several intracellular Notch modulators, i.e. Hes1, Hey1, and Klf4, were also shown to be deregulated with inflammation, yet irrespective of uPA status. Sox9 transcription factor, however, was significantly downregulated in the uPA-deficient/DSS-treated mice that developed colon adenomas as compared to the wild-type/DSS-treated group with no neoplasia identified. The latter finding supports a tumor suppressive role of Sox9 in intestinal carcinogenesis. Our results point towards an early activation of Notch signaling pathway at the receptor-ligand level in inflammation-associated colon neoplasmatogenesis developed in the absence of uPA. Interestingly, such activation may not be accompanied by deregulation of downstream Notch-target genes, possibly due to the effects of other inter-related signaling pathways.

Greece is an endemic country for human and canine leishmaniosis. Studies about the role of lagomorphs and minks in the epidemiology of the diseases are, so far, limited. The aim of the present study was to investigate the prevalence of Leishmania infection in these animals, in different areas of the country. Samples from 393 domestic and wild rabbits, 90 hares and 200 minks were collected and examined by cytology (spleen imprints) and serology (ELISA), while spleen samples of 116, 56 and 95 of the rabbits, hares and minks, respectively, were examined by a PCR assay targeting the ITS1 region. For every animal examined a form was created, recording information like date, area, animal species, sex, etc. All imprint smears examined were negative, while serology revealed infection in 7.6% (C.I. 5.0-10.3%) rabbits, 6.7% (C.I. 1.5-11.8%) hares and 20% (C.I. 14.5-25.5%) minks. Infection was confirmed by molecular methods in 2.6% (C.I. 0.0-5.5%), 3.6% (C.I. 0.0-8.4%) and 2.1% (C.I. 0.0-5.0%) of the animals, respectively. The statistical analysis showed that minks are most likely to be seropositive and that in rabbits, the breeding method (i.e. homestead reared animals) was associated with infection. Because of the proximity of lagomorphs and minks to humans and dogs it is necessary to further elucidate their role in the epidemiology of leishmaniosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A 25-year-old male college student reported an immediate sharp pain in the lateral aspect of his left knee while playing recreational basketball. He sought a direct-access consultation by a physical therapist. Due to the superficial nature of the fibular (lateral) collateral ligament (FCL), static and dynamic ultrasound imaging was used to visualize the FCL. Complementing the clinical examination findings, use of dynamic imaging strengthened the differential diagnosis of multidirectional laxity and supported the clinical decision of referral. Subsequent follow-up magnetic resonance imaging confirmed tears of the anterior cruciate ligament and FCL.J Orthop Sports Phys Ther 2019;49(3):210. doi:10.2519/jospt.2019.8460.

Background : To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. Methods : Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC) included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, β-catenin. Hepatocyte growth factor receptor (C-MET/HGFR) and Bcl-2 antagonist of cell death (BAD) serum levels were determined using a quantitative sandwich enzyme immunoassay technique. Results : Inhibition of AURK reduced the number of DEN-induced liver tumours. Apoptosis and proliferation was very low in both DEN-induced and anti- AURK groups respectively. The hepatocellular adenoma cells of DEN-treated mice uniformly had ample nuclear INCENP whereas in anti- AURK markedly decreased. Expression of β-catenin, NF-kB and c-Jun did not differ in liver tumors of both AURK -depleted and non-depleted mice. Conclusions: Depletion of AURK reduced the number of DEN-induced hepatic tumours. However, their size did not differ significantly between the groups., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Recent evidence has suggested that downregulation of the Wnt/β-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days. At that time, DEN-treated mice had multiple variably-sized hepatic cell adenomas. Anti-Wnt-1 was particularly potent in suppressing the expression of critical elements of the Wnt/β-catenin signaling pathway, such as β-catenin and Frizzled-1 receptor, however, not Dickkopf-related protein 1. This effect co-existed with the suppression of Cyclin D1, FOXM1, NF-κΒ and c-Jun commensurate with proliferation and apoptosis blockade in hepatocellular adenomas, and reduced Bcl-2 and c-Met in the serum of mice. Nonetheless, tumor size and multiplicity were found to be unaffected, suggesting that apoptosis may be equally important to proliferation in the context of counteracting DEN induced hepatocellular adenomas of mice.

Deregulation of the bone morphogenetic protein (BMP) pathway has been documented in colorectal cancer (CRC). Previously, we investigated possible associations between urokinase-type plasminogen activator (uPA) deficiency and expression of extracellular constituents of BMP signaling in a newly developed mouse model of inflammation-driven intestinal neoplasmatogenesis, in which chronic colitis and CRC are induced using dextran sodium sulfate (DSS). In this report, we explored the contribution of intracellular components of Smad-mediated BMP signal transduction using the same model. Interestingly, upon DSS treatment, we noticed an overexpression of Runx1/2/3 transcription factors in both wild-type and uPA-deficient mice. Moreover, Runx1 and Runx2 expression levels exhibited an even higher increase in DSS-treated/uPA-deficient mice as compared to DSS-treated/wild-type animals. In all experimental conditions, in situ investigation of Runx-expressing cell types, revealed detection of all three Runx in the immune cells, yet in the DSS-treated/uPA-deficient mice Runx1 and Runx2 were also identified in the preneoplastic epithelium of advanced high-grade dysplasia and carcinoma in-situ colonic lesions. Finally, the uPA-deficient pro-tumorigenic colitic microenvironment exhibited increased levels of the Runx-induced target genes Snai2, Bim and Claudin1, known to have a role in tumor development and progression. These findings suggest that the absence of uPA correlates with increased levels of Runx transcriptional regulators in a way that promotes inflammation-associated carcinogenesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the prevalence of Leishmania infection in rodents from various areas of northern Greece., Methods: Ninety-seven rodents (66 Mus musculus, 19 Rattus norvegicus and 12 R. rattus) were collected during pest control programmes and examined by cytology (spleen and liver smears), serology (ELISA) and PCR (real-time and gel-based) for Leishmania. Date, environment, sex, existence of dogs in the close environment were recorded for each rodent., Results: All cytological preparations were negative, whereas specific IgG was detected in 54.5% in total; 70% of R. norvegicus; 50% of R. rattus; and 50% of M. musculus. In at least one molecular method, 19.6% of the samples in total were positive: 25% of R. rattus, 24% of M. musculus, but no R. norvegicus was found positive. Environment (semi-urban areas, P = 0.037) and species (M. musculus, P = 0.032) were associated with positive PCR. All infected animals showed evidence of low parasite burden, demonstrated by the negative cytological examinations and the high Ct values observed in real-time PCR., Conclusion: Due to the proximity of rodents to humans and dogs, these animals may be important in the epidemiology of leishmaniosis, especially if proven that they can infect sand flies., (© 2017 John Wiley & Sons Ltd.)

The suppression of the bone morphogenetic protein (BMP) signaling pathway has been recently shown to promote adenoma-to-carcinoma transition in sporadic colon cancer. However, its role in the evolution of early preneoplastic changes to neoplasia remains elusive. In the present study, we aimed to investigate the gene expression levels of multiple extracellular BMP family constituents, including BMP ligands/receptors and inhibitors, during the early stages of inflammation-associated colon carcinogenesis. For that, we used the recently developed urokinase-type plasminogen activator (uPA)-deficient mouse model of colonic polypoidogenesis, in which adenomatous polyps arise several months after the induction of dextran sodium sulfate (DSS) colitis. In DSS-treated wild-type mice, the preneoplastic lesions which did not eventually evolve to adenomas resided in a colitic microenvironment characterized by a balanced upregulation of both BMP ligands, i.e., Bmp4/7 and BMP inhibitors, such as chordin, noggin, and gremlin-1. In the uPA-deficient tumor-promoting inflammatory microenvironment, however, there was a clear evidence for BMP pathway suppression. By contrast to DSS-treated wild-type controls, the inflammation-associated Bmp4 upregulation was abolished, and the BMP signaling suppression was further enhanced by a particularly high increase of gremlin-1 expression. These findings propose that BMP pathway suppression in colon cancer could be associated with very early stages of the preneoplasia-to-neoplasia sequence of events.

Inflammation-associated oxidative stress contributes to hepatic ischemia/reperfusion injury (IRI). Detrimental inflammatory event cascades largely depend on activated Kupffer cells (KCs) and neutrophils, as well as proinflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL) 18. The aim of our study was to evaluate the effects of IL 18 binding protein (IL 18Bp) in hepatic IRI of mice. Thirty C57BL/6 mice were allocated into 3 groups: sham operation, ischemia/reperfusion (I/R), and I/R with intravenous administration of IL 18Bp. Hepatic ischemia was induced for 30 minutes by Pringle's maneuver. After 120 minutes of reperfusion, mice were euthanized, and the liver and blood samples were collected for histological, immunohistochemical, molecular, and biochemical analyses. I/R injury induced the typical liver pathology and upregulated IL-18 expression in the liver of mice. Binding of IL 18 with IL 18Bp significantly reduced the histopathological indices of I/R liver injury and KC apoptosis. The I/R-induced increase of TNF-α, malondialdehyde, aspartate aminotransferase, and alanine aminotransferase levels was prevented in statistically significant levels because of the pretreatment with IL 18Bp. Likewise, blocking of IL 18 ablated the I/R-associated elevation of nuclear factor kappa B, c-Jun, myeloperoxidase, and IL 32 and the up-regulation of neutrophils and T-helper lymphocytes. Administration of IL 18Bp protects the mice liver from I/R injury by intervening in critical inflammation-associated pathways and KC apoptosis., (© 2015 American Association for the Study of Liver Diseases.)

Our studies in mice have suggested that the immunological microenvironment of preneoplastic lesions could determine their fate toward neoplasia or regression. A role for gastrointestinal tract bacteria antigens in modulating cancer-related immune responses in the tumor micro- and macro-environment is emerging, thus opening new possibilities for colon cancer prevention.

Background/aim: Kallikrein-related peptidases (KLKs) comprise a serine protease family with prominent roles in tissue physiology and disease pathogenesis, including cancer. Previously, we have characterized canine Klk4-10 and -14. Herein, we continue our efforts by characterizing three novel members of the canine family, i.e. Klk11-13, and investigating their expression in mammary cancer., Materials and Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and DNA sequencing were used for investigating the expression and determining the nucleotide sequence of all transcripts identified, respectively., Results: It was demonstrated that (i) unlike other Klks, (CANFA)Klk12 probably possesses a non-AUG translation initiation codon, (ii) all three Klks undergo alternative splicing, with exon 2 and 3 concurrent elimination serving as the most prominent event, (iii) all transcripts identified were detected in both tumor and normal tissues, yet with different frequencies., Conclusion: Having completed this work, Klk15 is the only gene remaining to experimentally resolve the entire canine Klk family. Our data lay sufficient groundwork for validation studies and await further incorporation into genetic/evolutionary studies with translational impact., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)