Effects of white wine and the role of wine polyphenols on weight gain in rats of different age were examined in the 4-week-voluntary-consumption trial.

We report the establishment of B6CaP, an allograft tumor line from a Hi-Myc transgenic mouse that had been backcrossed onto C57BL/6J background. This tumor line grows subcutaneously in wildtype C57BL/6J immunocompetent mice, expresses AR, and has a luminal cytokeratin profile. When digested into single cells and injected via intracardiac injection, B6CaP produces metastatic widespread metastases including frequent bone lesions. Metastatic lesions occur most often in the femur, spine, and skull, and have a mixed osteolytic/osteoblastic phenotype. B6CaP allografts are androgen dependent, and regress after castration. However, castration resistant tumors regrow after 4-6 months and can be maintained as androgen-independent clones. This is the first example of a prostate-derived tumor line that shows frequent metastasis to bone and grows in an immunocompetent host, making this model useful for studying mechanisms of bone metastasis and tumor immune response.

Hip osteoarthritis (HOA) is characterized by degradation of the cartilage and synovitis. However, the pathohistological effects of synovial tissue inflammation on HOA are not clear. The aim of this study was to evaluate the expression of iNOS, BCL-2 and MMP-9 markers in different synovial cell populations. A total of 32 patients were evaluated retrospectively. Age, sex, height, weight, body mass index were recorded and lymphocyte, fibrocytes and macrophages were analysed in tissue sections. Osteoarthritis cartilage histopathology assessment system (OARSI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Krenn score, Harris Hip Score (HHS) and Kellgren-Lawrence (K-L) grading of the hip joints were performed. Total hip arthroplasty was performed on 32 patients and controls. Patients were divided into two groups according to their disease severity. The tissues were immunohistochemically analysed. K-L grade and Krenn score differ between all three groups, but also between moderate and severe OA. Synovial lining cell layer, resident cells in stroma and especially inflammatory infiltration were increasing with severity of OA. iNOS expression in both intima and subintima was positively correlated with Krenn score in moderate and severe osteoarthritis (OA) groups. Expression of BCL-2 in intima of severe OA patients was positively correlated with Krenn score. In conclusion, iNOS, BCL-2 and MMP-9 are involved in the regulation of HOA. Our study indicates a relationship between the pathohistological features, the synovial inflammation and the cartilage condition at the time of hip replacement due to OA or femoral neck fracture.

Cells in every epithelium can be roughly divided in three compartments: stem cell (SC) compartment, transient amplifying cell (TA) compartment and terminally differentiated (TD) compartment. Maturation of stem cells is characterized by epithelial stromal interaction and sequential maturational movement of stem cell's progeny through those compartments. In this work we hypothesize that providing an artificial stroma, which murine breast cancer metastatic cells can infiltrate, will induce their differentiation.

Our study analyzed the expression pattern of different connexins (Cxs) and renin positive cells in the juxtaglomerular apparatus (JGA) of developing, postnatal healthy human kidneys and in nephrotic syndrome of the Finnish type (CNF), by using double immunofluorescence, electron microscopy and statistical measuring. The JGA contained several cell types connected by Cxs, and consisting of macula densa, extraglomerular mesangium (EM) and juxtaglomerular cells (JC), which release renin involved in renin-angiotensin- aldosteron system (RAS) of arterial blood pressure control. During JGA development, strong Cx40 expression gradually decreased, while expression of Cx37, Cx43 and Cx45 increased, postnatally showing more equalized expression patterning. In parallel, initially dispersed renin cells localized to JGA, and greatly increased expression in postnatal kidneys. In CNF kidneys, increased levels of Cx43, Cx37 and Cx45 co-localized with accumulations of renin cells in JGA. Additionally, they reappeared in extraglomerular mesangial cells, indicating association between return to embryonic Cxs patterning and pathologically changed kidney tissue. Based on the described Cxs and renin expression patterning, we suggest involvement of Cx40 primarily in the formation of JGA in developing kidneys, while Cx37, Cx43 and Cx45 might participate in JGA signal transfer important for postnatal maintenance of kidney function and blood pressure control.

In glomerular injury dendrin translocates from the slit diaphragm to the podocyte nucleus, inducing apoptosis. We analyzed dendrin expression in IgA glomerulonephritis and Henoch Schönlein purpura (IgAN/HSP) versus in podocytopathies minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), and compared it to pathohistological findings and renal function at the time of biopsy and the last follow-up.

Thyroid volume of Hashimoto's thyroiditis (HT) patients varies in size over the course of disease and it may reflect changes in biological function of thyroid gland. Patients with subclinical hypothyroidism predominantly have increased thyroid volume whereas patients with more pronounced hypothyroidism have smaller thyroid volumes. Suggested mechanism for thyroid atrophy is thyrocyte death due to apoptosis. We performed the first genome-wide association study (GWAS) of thyroid volume in two groups of HT patients, depending on levothyroxine (LT4) therapy, and then meta-analysed across. Study included 345 HT patients in total and 6 007 322 common autosomal genetic variants. Underlying hypothesis was that genetic components that are involved in regulation of thyroid volume display their effect in specific pathophysiologic conditions of thyroid gland of HT patients. We additionally performed immunohistochemical analysis using thyroid tissues and analysed differences in expression levels of identified proteins and apoptotic marker between HT patients and controls. We found genome-wide significant association of two loci, both involved in apoptosis, with thyroid volume of HT patients: rs7212416 inside apoptosis-antagonizing transcription factor AATF (P = 8.95 × 10-9) and rs10738556 near chromatin-remodeling SMARCA2 (P = 2.83 × 10-8). In immunohistochemical analysis we observed that HT patients with homozygous AATF risk genotypes have decreased AATF expression (0.46-fold, P < 0.0001) and increased apoptosis (3.99-fold, P = 0.0001) in comparison to controls. HT patients with heterozygous SMARCA2 genotypes have decreased SMARCA2 expression, albeit without reaching statistical significance (1.07-fold, P = 0.5876), and significantly increased apoptosis (4.11-fold, P < 0.0001). By two lines of evidence we show that two highly plausible genetic loci, AATF and SMARCA2, may be involved in determining the thyroid volume of HT patients. The results of our study significantly add to the current knowledge of disturbed biological mechanisms in thyroid gland of HT patients.

Monotherapy with immune checkpoint inhibitors has generally been unsuccessful in men with advanced prostate cancer. Preclinical data support the notion that cryotherapy may improve immune-mediated and anti-tumor responses. The objective of this study was to assess the safety and feasibility of whole-prostate gland cryotherapy combined with pembrolizumab and androgen deprivation in men with oligometastatic hormone-sensitive prostate cancer.

Numerous evidence corroborates roles of gap junctions/hemichannels in proper kidney development. We analyzed how Dab1 gene functional silencing influences expression and localization of Cx37, Cx40, Cx43, Cx45, Panx1 and renin in postnatal kidneys of yotari mice, by using immunohistochemistry and electron microscopy. Dab1 Δ102/221 might lead to the activation of c-Src tyrosine kinase, causing the upregulation of Cx43 in the medulla of yotari mice. The expression of renin was more prominent in yotari mice (p < 0.001). Renin granules were unusually present inside the vascular walls of glomeruli capillaries, in proximal and distal convoluted tubules and in the medulla. Disfunction of Cx40 is likely responsible for increased atypically positioned renin cells which release renin in an uncontrolled fashion, but this doesn't rule out simultaneous involvement of other Cxs, such as Cx45 which was significantly increased in the yotari cortex. The decreased Cx37 expression in yotari medulla might contribute to hypertension reduction provoked by high renin expression. These findings imply the relevance of Cxs/Panx1 as markers of impaired kidney function (high renin) in yotari mice and that they have a role in the preservation of intercellular signaling and implicate connexopathies as the cause of premature death of yotari mice.

Thyroid cancer is the predominant endocrine-related malignancy. ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.

To assess the effect of liver damage on methadone metabolism in opiate addicts undergoing methadone maintenance treatment (MMT).

To test the association of NOS3 gene with hypoxic-ischemic encephalopathy (HIE).

To investigate the association of cerebral palsy motor disorders, perinatal factors, and related disabilities with brain magnetic resonance imaging classification score (MRICS)-based groups in a population-based sample.

We studied the influence of experimentally induced DM1, in combination with different dietary n6:n3 polyunsaturated fatty acid (PUFA) ratios on different types of nerve fibers in rat myocardium, in order to reveal whether protective/unfavorable effects of different PUFAs on myocardial function in diabetic patients could be a (partial) repercussion of their effect on the changes in cardiac innervation. The control group (c) and diabetic group (stz) were fed with an n6/n3 ratio of ≈7; the diet of the stz+n6 group had an n6/n3 ratio ≈60, while the diet for the stz+DHA group contained 2.5% of fish oil (containing 16% eicosapentaenoic acid-EPA and 19% docosahexaenoic acid-DHA), n6/n3 ratio of ≈1. DM1 was induced by i.p. injection of streptozotocin (55 mg/kg) and rats were euthanized 30 days after induction. Immunohistochemistry was used for the detection and quantification of different types of neuronal fibers in the cardiac septum. We found changes in cardiac innervations characteristics for the initial phase of experimental DM1, which manifested as an increase in total number and area density of all neuronal fibers, measured by Pgp9.5 immunoreactivity. By detailed analysis, we found that this increase consisted mostly of heavy myelinated NF200 immunoreactive fibers and TH immunoreactive sympathetic fibers, while the density of ChAT immunoreactive parasympathetic fibers decreased. In the deep (middle) part of the myocardium, where rare fibers (of all studied types) were found, significant differences were not found. Surprisingly, we found a more consistent protective effect of n6 PUFAs, in comparison to n3 PUFAs supplementation. These results may provide a better understanding of the potential impacts of different PUFA ratios in the diet of diabetic patients on cardiac innervation and genesis and outcome of diabetic autonomic cardiomyopathy.

Connexins (Cxs) are membrane-spanning proteins which enable flow of information important for kidney homeostasis. Changes in their spatiotemporal patterning characterize blood vessel abnormalities and chronic kidney diseases (CKD). We analysed spatiotemporal expression of Cx37, Cx40, Cx43 and Cx45 in nephron and glomerular cells of developing, postnatal kidneys, and nephrotic syndrome of the Finnish type (CNF) by using immunohistochemistry, statistical methods and electron microscopy. During kidney development, strong Cx45 expression in proximal tubules and decreasing expression in glomeruli was observed. In developing distal nephron, Cx37 and Cx40 showed moderate-to-strong expression, while weak Cx43 expression gradually increased. Cx45/Cx40 co-localized in mesangial and granular cells. Cx43 /Cx45 co-localized in podocytes, mesangial and parietal epithelial cells, and with podocyte markers (synaptopodin, nephrin). Different Cxs co-expressed with endothelial (CD31) and VSMC (α -SMA) markers in vascular walls. Peak signalling of Cx37, Cx43 and Cx40 accompanied kidney nephrogenesis, while strongest Cx45 signalling paralleled nephron maturation. Spatiotemporal Cxs patterning indicate participation of Cx45 in differentiation of proximal tubules, and Cx43, Cx37 and Cx40 in distal tubules differentiation. CNF characterized disorganized Cx45 expression in proximal tubules, increased Cx43 expression in distal tubules and overall elevation of Cx40 and Cx37, while Cx40 co-localized with increased number of interstitial myofibroblasts.

BACKGROUND Little is known about how vibrational stimuli applied to hand digits affect motor cortical excitability. The present transcranial magnetic stimulation (TMS) study investigated motor evoked potentials (MEPs) in the upper extremity muscle following high-frequency vibratory digit stimulation. MATERIAL AND METHODS High-frequency vibration was applied to the upper extremity digit II utilizing a miniature electromagnetic solenoid-type stimulator-tactor in 11 healthy study participants. The conditioning stimulation (C) preceded the test magnetic stimulation (T) by inter-stimulus intervals (ISIs) of 5-500 ms in 2 experimental sessions. The TMS was applied over the primary motor cortex for the hand abductor pollicis-brevis (APB) muscle. RESULTS Dunnett's multiple comparisons test indicated significant suppression of MEP amplitudes at ISIs of 200 ms (P=0.001), 300 ms (P=0.023), and 400 ms (P=0.029) compared to control. CONCLUSIONS MEP amplitude suppression was observed in the APB muscle at ISIs of 200-400 ms, applying afferent signaling that originates in skin receptors following the vibratory stimuli. The study provides novel insight on the time course and MEP modulation following cutaneous receptor vibration of the hand digit. The results of the study may have implications in neurology in the neurorehabilitation of patients with increased amplitude of MEPs.

Neutrophils and monocytes through their CD15s, CD11b and CD44 adhesion molecules are implicated in the initiation and resolution of cardiac inflammation as well as in healing processes after the myocardial infarction (MI). The aim of this study was to determine the effect of white wine consumption on granulocyte and monocyte CD15s, CD11b, and CD44 expression 24h after the surgically inflicted MI. Granulocytes and monocytes were analyzed by flow cytometry, using whole blood of male Sprague-Dawley rats that consumed white wine for 4 weeks. This group was compared with water only drinking controls, sham animals (subject to surgery without myocardial infarction) and baseline group (intact animals that received no intervention prior to being sacrificed). Sham animals did not differ from baseline animals in CD11b+CD44+ percentage and CD44+ median fluorescence intensity. Wine drinking was associated with striking increase in CD44 expression on monocyte subpopulations. Its expression was three and fourfold increased on monocytes and large monocytes, respectively, relative to the water only drinking controls. Because of known role of CD44 on suppression of post-infarction inflammation, its upregulation on granulocytes and monocytes may significantly contribute to the microenvironment favourable for the cardiac regeneration.