Chemerin Stimulates the Secretory Activity of BME-UV1 Bovine Mammary Epithelial Cells.

Adipose tissue is an active endocrine gland, synthesizing and secreting multiple signaling molecules termed adipokines. Following the detection of adipokines and their receptors in the mammary tissue of various species, it is indicated that adipokines play a role in the development of the mammary gland. The aim of the present study was to determine the concentration-dependent influence of three adipokines, leptin, adiponectin, and chemerin, on the viability, apoptosis, and secretory activity of BME-UV1 bovine mammary epithelial cells. The study confirmed that BME-UV1 cells contain the leptin receptor (Ob-R) protein, and express transcripts of adiponectin (ADIPOR1 and ADIPOR2) and chemerin (CMLKR1 and GPR1) receptors. Regardless of the administered dose, none of the three tested adipokines had an effect on the viability of BME-UV1 cells, and the number of apoptotic cells remained unchanged. However, chemerin (100 ng/mL) stimulated BME-UV1 cells to synthesize and secrete αS1-casein, the major protein component of milk. These results indicate that chemerin may be a potent regulator of the bovine mammary epithelial cells' functional differentiation, contributing, along with the major systemic hormones and local growth factors, to the development of the bovine mammary gland.

Oat Beta-Glucan as a Metabolic Regulator in Early Stage of Colorectal Cancer-A Model Study on Azoxymethane-Treated Rats.

Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1ß, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms.

Effect of Allergen-Specific Immunotherapy on Transcriptomic Changes in Canine Atopic Dermatitis.

Canine atopic dermatitis (cAD) is a genetic, chronic, and recurrent inflammatory and pruritic skin disorder. Allergen-specific immunotherapy (ASIT) is presently recognized as the only clinically effective disease-modifying treatment for allergies. The aim of our study was to analyze the changes in gene expression observed in the peripheral blood nuclear cells of cAD patients subjected to ASIT. Blood samples designated for transcriptomic analyses were collected from AD dogs twice, before and six months after ASIT, and also from healthy dogs. Statistical analysis revealed 521 differentially expressed transcripts, among which 241 transcripts represented genes with well-described functions. Based on the available literature, we chose nine differentially expressed genes (RARRES2, DPP10, SLPI, PLSCR4, MMP9, NTSR1, CBD103, DEFB122, and IL36G) which may be important in the context of the dysregulated immune response observed in cAD patients. The expressions of five out of the nine described genes (DPP10, PLSCR4, NTSR1, DEFB122, and IL36G) changed after the application of ASIT. The expressions of three of these genes returned to the level observed in the healthy control group. The genes listed above need further investigation to determine details of their role in the molecular mechanism of immune tolerance induction in response to allergen-specific immunotherapy.

Adipocyte-Derived Paracrine Factors Regulate the In Vitro Development of Bovine Mammary Epithelial Cells.

The mammary gland is composed of epithelial tissue forming ducts and lobules, and the stroma, composed of adipocytes, connective tissue, and other cell types. The stromal microenvironment regulates mammary gland development by paracrine and cell-cell interactions. In the present study, primary cultures of bovine mammary epithelial cells (bMEC) and bovine adipose-derived stem cells (bASC) subjected to adipogenic differentiation were used to investigate the influence of paracrine factors secreted by preadipocytes and adipocytes on bMEC development. Four types of conditioned media (CM) were collected from undifferentiated preadipocytes (preA) and adipocytes on days: 8, 12, 14 of differentiation. Next, bMEC were cultured for 24 h in CM and cell viability, apoptosis, migratory activity, ability to form spheroids on Matrigel, and secretory activity (alpha S1-casein concentration) were evaluated. CM derived from fully differentiated adipocytes (12 d and 14 d) significantly decreased the number of apoptotic cells in bMEC population and increased the size of spheroids formed by bMEC on Matrigel. CM collected from preadipocytes significantly enhanced bMEC's migration, and stimulated bMEC to produce alpha S1-casein, but only in the presence of prolactin. These results confirm that preadipocytes and adipocytes are important components of the stroma, providing paracrine factors that actively regulate the development of bovine mammary epithelium.

Interleukin-6 mimics insulin-dependent cellular distribution of some cytoskeletal proteins and Glut4 transporter without effect on glucose uptake in 3T3-L1 adipocytes.

Interleukin (IL)-6, a known proinflammatory cytokine, is released in both visceral adipose tissue and contracting skeletal muscle. In this study, we used microRNA profiling as a screening method to identify miRNA species modified by IL-6 treatment in mouse 3T3-L1 adipocytes. miRNA microarray analysis and qRT-PCR revealed increased expression of miR-146b-3p in adipocytes exposed to IL-6 (1 ng/ml) during 8-day differentiation. On the basis of ontological analysis of potential targets, selected proteins associated with cytoskeleton and transport were examined in the context of adipocyte response to insulin, using immunofluorescence and confocal microscopy. We concluded that IL-6: (i) does not affect insulin action on actin cellular distribution; (ii) modulates the effect of insulin on myosin light chain kinase (Mylk) distribution by preventing its shift toward cytoplasm; (iii) mimics the effect of insulin on dynein distribution by increasing its near-nuclear accumulation; (iv) mimics the effect of insulin on glucose transporter Glut4 distribution, especially by increasing its near-nuclear accumulation; (v) supports insulin action on early endosome marker Rab4A near-nuclear accumulation. Moreover, as IL-6 did not disturb insulin-dependent glucose uptake, our results do not confirm the IL-6-induced impairment of insulin action observed in some in vitro studies, suggesting that the effect of IL-6 is dose dependent.

AgNOR patterns and configurations in adult acute leukemia patients.

The number of argyrophilic nucleolus organizer regions (AgNOR) is related to the proliferative activity of cells and the degree of neoplastic transformation. The surface area of AgNOR depending on nuclear structure may be a predictor of tumor recurrence, while research into acute leukemias is scarce. The aim of the study was to determine whether the assessment of AgNOR parameters is useful in the differentiation of acute leukemias and, together with cytogenetic changes, would allow for a quick evaluation of the risk group. The AgNOR structures were analyzed in terms of the shape, surface area and distribution in bone marrow blast cells in patients with acute leukemias. We observed significant differences in the AgNOR structures, simple, compound and complex patterns between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Complex structures were more numerous in ALL than in AML patients. There were significant differences in the distribution of AgNOR configuration among various cytogenetic AML risk groups. We observed a significant difference in the mean number of AgNOR between ALL-T and ALL-B. We detected diversity in the AgNOR structures and pattern map in AML and ALL. Thus, presentation of a variety of AgNOR configurations is innovative and can be a useful method of differentiating patients with acute leukemia types and cytogenetic risk.

Primary cutaneous indolent B-cell lymphomas - a retrospective multicenter analysis and a review of literature.

Introduction: Primary cutaneous indolent B-cell lymphomas (PCBCLs) are not well characterized due to their rarity and indolent character.Methods: We retrospectively reviewed the data from 52 patients with primary cutaneous follicular lymphoma (PCFL) (n = 26), marginal zone lymphoma (PCMZL) (n = 25) or undefined PCBCL (n = 1) treated in 10 hematology centers in 1999-2019.Results: Patients characteristics and diagnostic approach: In almost half of the patients, pruritus or pain were present at diagnosis. The lesions were predominantly located on the head and trunk. The disease was present in a form of solitary infiltration or disseminated lesions with a similar frequency.Treatment details and outcomes: Surgery, radiotherapy, rituximab alone or combined with chemotherapy were applied as first-line treatment in 33%, 25%, 21% and 21% of patients, with complete response (CR) achieved by 94%, 83%, 50% and 70% of patients, respectively (p = 0.28). The median duration of response (DoR) was 65 months (95%CI 35-155).Survival: After the median follow-up time of 46 months (range: 3-225), the estimated 5-year overall survival (OS) and progression-free survival (PFS) were 93% and 54%, respectively.Discussion: Clinical presentation was largely consistent with the literature data, however, we observed some differences, including higher predilection to affect upper extremities (25%) and more frequent multifocal appearance in PCFCL (64%) and unifocal in PCMZL (70%).A high proportion of patients with indolent PCBCL achieved CR after the first-line therapy (77%), regardless of treatment mode. We did not find any impact of clinical features on treatment outcomes.Conclusions: All treatment modalities resulted in a high overall response rate. Surgery and/or radiotherapy are the optimal therapeutic options for patients with localized disease. The decision to treat systemically should rather be limited to the generalized form of the disease. High response rate, long duration of remission and excellent long-term survival confirm the truly indolent character of PCFCL and PCMZL.

Voice Multilateration System.

This paper presents an innovative method of locating airplanes, which uses only voice communication between an air traffic controller and the pilot of an aircraft. The proposed method is described in detail along with its practical implementation in the form of a technology demonstrator (proof of concept), included in the voice communication system (VCS). A complete analysis of the performance of the developed method is presented, including the results of simulation and measurement tests in real conditions. The obtained results are very optimistic and indicate that the proposed solution may constitute an alternative method of locating aircraft in emergency conditions, i.e., a backup solution in the case of failure of other positioning systems.

Magnesium and Morphine in the Treatment of Chronic Neuropathic Pain-A Biomedical Mechanism of Action.

The effectiveness of opioids in the treatment of neuropathic pain is limited. It was demonstrated that magnesium ions (Mg2+), physiological antagonists of N-methyl-D-aspartate receptor (NMDAR), increase opioid analgesia in chronic pain. Our study aimed to determine the molecular mechanism of this action. Early data indicate the cross-regulation of µ opioid receptor (MOR) and NMDAR in pain control. Morphine acting on MOR stimulates protein kinase C (PKC), while induction of NMDAR recruits protein kinase A (PKA), leading to a disruption of the MOR-NMDAR complex and promoting functional changes in receptors. The mechanical Randall-Selitto test was used to assess the effect of chronic Mg2+ and morphine cotreatment on streptozotocin-induced hyperalgesia in Wistar rats. The level of phosphorylated NMDAR NR1 subunit (pNR1) and phosphorylated MOR (pMOR) in the periaqueductal gray matter was determined with the Western blot method. The activity of PKA and PKC was examined by standard enzyme immunoassays. The experiments showed a reduction in hyperalgesia after coadministration of morphine (5 mg/kg intraperitoneally) and Mg2+ (40 mg/kg intraperitoneally). Mg2+ administered alone significantly decreased the level of pNR1, pMOR, and activity of both tested kinases. The results suggest that blocking NMDAR signaling by Mg2+ restores the MOR-NMDAR complex and thus enables morphine analgesia in neuropathic rats.

Interleukin-6 affects pacsin3, ephrinA4 expression and cytoskeletal proteins in differentiating primary skeletal myoblasts through transcriptional and post-transcriptional mechanisms.

Interleukin (IL)-6 is a proinflammatory cytokine released in injured and contracting skeletal muscles. In this study, we examined cellular expression of proteins associated with cytoskeleton organization and cell migration, chosen on the basis of microRNA profiling, in rat primary skeletal muscle cells (RSkMC) treated with IL-6 (1 ng/ml) for 11 days. MiRNA microarray analysis and qRT-PCR revealed increased expression of miR-154-3p and miR-338-3p in muscle cells treated with IL-6. Pacsin3 was downregulated post-transcriptionally by IL-6, but not by IGF-I. Ephrin4A protein was increased both in IL-6- and IGF-I-treated myocytes. IL-6, but not IGF-I, stimulated migratory ability of RSkMC, examined in wound healing assay. Alpha-actinin protein was slightly augmented in RSKMC treated with IL-6, similarly to IGF-I. IL-6, but not IGF-I, upregulated desmin in differentiating RSkMC. IL-6 supplementation caused accumulation of alpha-actinin and desmin in near-nuclear area of muscle cells, which was manifested by increased ratio: mean near-nuclear fluorescence/mean peripheral cytoplasm fluorescence of these proteins. We concluded that IL-6, a known proinflammatory cytokine and a physical activity-associated myokine, acting during differentiation of primary skeletal muscle cells, alters expression of nonmuscle-specific miRNAs. This cytokine causes differential effects on pacsin-3 and ephrinA4, through post-transcriptional inhibition and stimulation, respectively. IL-6-exerted modifications of cytoskeletal proteins in muscle cells include both transcriptional (desmin and dynein heavy chain 5) and post-transcriptional activation (alpha-actinin). Moreover, IL-6 augments near-nuclear distribution of cytoskeletal proteins, alpha-actinin and desmin and promotes migration of myocytes. Such effects suggest that IL-6 plays a role during skeletal muscle regeneration, acting through mechanisms independent of regulation of myogenic program.

Interleukin-8 enhances myocilin expression, Akt-FoxO3 signaling and myogenic differentiation in rat skeletal muscle cells.

Interleukin (IL)-8 is released both in visceral adipose tissue and in contracting skeletal muscles. In this study, we examined cellular pathways associated with muscle hypertrophy, chosen on the basis of microRNA profiling, in differentiating rat primary skeletal muscle cells (RSkMC) treated with IL-8 (1 ng/ml) for 11 days. IL-8 increased myocilin expression, Akt phosphorylation, FoxO3 dispersion throughout the cytoplasm, and reduced FoxO3 level. IL-8 decreased the expression of atrogin and MuRF1 and increased myotube length and diameter. We concluded that IL-8 present in extracellular environment of myoblasts induced to differentiation stimulates expression of myocilin, a protein important for skeletal muscle hypertrophy. This phenomenon was associated with: (a) activation of myogenic transcription, (b) increased phosphorylation and activation of PKB/Akt, leading to (c) cytoplasm distribution and degradation of a transcription factor FoxO3, (d) decreased expression of gene markers of proteolysis, atrogin and Murf1, and (e) increased myotube length and diameter. In this regard, IL-8 affects skeletal muscle cells similarly to IGF-I and can be considered as a potent anticatabolic factor for skeletal muscle.

Oral administration of oat beta-glucan preparations of different molecular weight results in regulation of genes connected with immune response in peripheral blood of rats with LPS-induced enteritis.

PURPOSE: Beta-glucans are biologically active polysaccharides having antioxidant, immunomodulatory, and antiinflammatory properties. This study investigated the transcriptomic profile in peripheral blood of rats with LPS-induced enteritis, which were fed a diet supplemented with high- (G1) and low- (G2) molecular-weight oat beta-glucans. METHODS: Two-color rat gene expression microarrays were applied and the analysis was performed using a common reference design to provide easy means of comparing samples from various experimental conditions against one another. Common reference sample was labeled with cyanine 3 (Cy3) and investigated samples from each experimental group: C-G0 (control group fed semi-synthetic diet), LPS-G0 (LPS-challenged group fed semi-synthetic diet), LPS-G1 (LPS-challenged group fed G1 beta-glucan enriched diet), and LPS-G2 (LPS-challenged group fed G2 beta-glucan enriched diet) were labeled with cyanine 5 (Cy5). Each microarray was performed in quadruplicate. Statistical analysis was performed using one-way ANOVA and Tukey's HSD post-hoc test (p < 0.05). A multiple testing correction was performed using Benjamini and Hochberg False Discovery Rate < 5%. A quantitative real-time RT-PCR was performed to verify the expression of chosen transcripts. RESULTS: The microarray analyses revealed differentially expressed transcripts between: the LPS-G0 and the control groups: C-G0 (138 genes), the LPS-G1 and LPS-G0 groups (533 genes), and the LPS-G2 and LPS-G0 groups (97 genes). Several differentially expressed genes in the beta-glucan-supplemented groups encoded proteins belonging to TLR and NLR signaling pathways, as well as prostaglandin synthesis and regulation pathways. Both beta-glucans up-regulated the expression of Atg10, which belongs to the family of autophagy-related genes, suggesting a possible link between autophagy induction and beta-glucan supplementation. CONCLUSION: The changes in gene expression observed in the peripheral blood indicate that oat beta-glucans exerted a protective effect in rats with an induced inflammatory state caused by LPS challenge. The greater number of differentially expressed genes was observed in group supplemented with G1 beta-glucan, pointing at the differences in the mode of action of high- and low-molecular-weight beta-glucans in the organism.

Beneficial Effects of Oat Beta-Glucan Dietary Supplementation in Colitis Depend on its Molecular Weight.

BACKGROUND: Inflammatory bowel diseases are an important health problem. Therefore, the aim of the present study was to compare the impact of isolated oat beta-glucan fractions of low and high molecular weight, taken as dietary supplementation, on inflammatory markers in the colitis model. METHODS: Two groups of Sprague-Dawley rats-control and with experimentally induced colitis-were subsequently divided into three subgroups and fed over 21 days feed supplemented with 1% of low (ßGl) or high (ßGh) molecular weight oat beta-glucan fraction or feed without supplementation. The level of colon inflammatory markers, cytokines, and their receptors' genes expressions and immune cells numbers were measured by ELISA, RT-PCR, and by flow cytometry methods, respectively. RESULTS: The results showed moderate inflammation affecting the colon mucosa and submucosa, with significant changes in the number of lymphocytes in the colon tissue, elevated cytokines and eicosanoid levels, as well as disruption of the main cytokine and chemokine cell signaling pathways in colitis rats. Beta-glucans supplementation caused a reverse in the percentage of lymphocytes with stronger effects of ßGh and reduction of the levels of the inflammatory markers, and improvement of cytokine and chemokine signaling pathways with stronger effects of ßGl supplementation. CONCLUSIONS: The results indicate the therapeutic effect of dietary oat beta-glucan supplementation in the colitis in evident relation to the molecular weight of polymer.

Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212-2 in renal cell carcinoma.

BACKGROUND: The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB1 and CB2), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB1 and CB2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212-2 (WIN-55)] in RCC cell lines. METHODS: Human RCC cell lines were used for this study. The CB 1 and CB 2 gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB1 and CB2 receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB1 and CB2 receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells. RESULTS: The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB2 receptor as compared to CB1 in RCC cells. Immunocytochemical staining also confirmed the expression of the CB1 and CB2 proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB2 agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis. CONCLUSIONS: This study elucidated the involvement of CB2 in the in vitro inhibition of RCC cells, and future applications of CB2 agonists in the prevention and management of RCC are discussed.

Gene expression changes in rat brain regions after 7- and 28 days inhalation exposure to exhaust emissions from 1st and 2nd generation biodiesel fuels - The FuelHealth project.

While the impact of emissions from combustion of fossil fuel on human health has been extensively studied, current knowledge of exhaust exposure from combustion of biofuels provides limited and inconsistent information about its neurotoxicity. The objective of the present work was to compare the gene expression patterns in rat frontal cortex and hippocampus after exposure to diesel exhaust emissions (DEE) from combustion of two 1st generation fuels, 7% fatty acid methyl esters (FAME) (B7) and 20% FAME (B20), and a 2nd generation 20% FAME/hydrotreated vegetable oil (SHB20: synthetic hydrocarbon biofuel), with and without diesel particulate filter (DPF). The Fisher 344 rats (n = 7/treatment) were exposed to DEE for 7 days (6h/day), and for 28 days (6h/day, 5 days/week) in whole body exposure chambers. The controls were breathing room air. Brain histological examinations did not reveal any adverse exposure-related effects of DEE in frontal cortex or in hippocampus. Gene expression analysis showed that several genes associated with antioxidant defenses and inflammation were statistically differently expressed in DEE exposed animals versus control. In addition, the gene expression changes between the exposure groups were compared, where the observed rank order in frontal cortex was B7 > B20 > SHB20 after 7 days of exposure, and SHB20 > B7 = B20 after 28 days of exposure. In the hippocampus, the rank order was B7 > SHB20 > B20. Effect of DPF treatment was observed for Tnf only. Overall, moderate increases in bio-components in diesel blends do not appear to result in dramatic alterations in gene expression or adverse histopathological effects.

Evaluation of the effectiveness of treatment of vulvar lichen sclerosus et atrophicus. Analysis of own material and review of the literature.

MATERIAL AND METHODS: The study group included eleven female patients aged 18-77 years with a diagnosis of lichen sclerosus. Basic therapy consisted in the application of clobetasol in the first month and then once a day for the following two months. Then, clobetasol was recommended once a week until full resolution of the symptoms. RESULTS: In nine patients with three-month basic therapy with clobetasol we observed a reduction of symptoms. Improvement of skin lesions was obtained in seven patients. After maintenance therapy lasting from four to twelve months the relapse of symptoms was observed in four women. Five women did not experience a relapse of the disease. The ointment with testosterone was applied in five women. Two women had poor tolerance of this drug. Two patients stopped the treatment after one month and after 11 months of using testosterone due to the relapse of the disease. One patient with good tolerance is currently continuing the therapy. CONCLUSIONS: Vulvar lichen sclerosus et atrophicus is a chronic condition requiring long-term treatment. Topical use of steroids as first-line drugs bring a good local control of lesions in most women, yet further search of other possible causes of LSA is necessary.

Insulin-dependent cytoplasmic distribution of Rab4a in mouse adipocytes is inhibited by interleukin-6, -8, and -15.

The purpose of the study was to examine the effect of interleukins, IL-6, IL-8, and IL-15, on insulin-mediated redistribution of Rab4a, an early endosome marker, in mouse 3T3-L1 adipocytes. The interleukins did not affect cell viability; however, cell number was slightly but significantly higher in cultures exposed to IL-8 and IL-15. IL-8 and IL-15 decreased lipid storage in adipocytes, whereas IL-6 had no effect. Rab4A showed cytoplasmic localization, and in control unstimulated adipocytes it was found primarily nearby nucleus, that was supported by cellular fluorescence distribution profile, and by calculated indices, that is, high percentage of near-nuclear area fluorescence and a low mean peripheral cytoplasmic fluorescence/mean near-nuclear fluorescence ratio. Insulin stimulation (100 nmol/l, 30 min) altered the cytoplasmic localization of Rab4a in control adipocytes, which was manifested by its redistribution towards plasma membrane. This effect of insulin was prevented in adipocytes exposed to IL-6, IL-8, or IL-15. We concluded that insulin-dependent Rab4a redistribution, probably reflecting stimulation of vesicle-mediated transport, is inhibited in adipocytes subjected to differentiation in the presence of IL-6, IL-8, or IL-15. Such alterations may be involved in the mechanisms contributing to development of insulin resistance associated with inflammation; however, further studies in this field are required.

No adverse lung effects of 7- and 28-day inhalation exposure of rats to emissions from petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without particulate filter - the FuelHealth project.

Increased use of biofuels raises concerns about health effects of new emissions. We analyzed relative lung health effects, on Fisher 344 rats, of diesel engine exhausts emissions (DEE) from a Euro 5-classified diesel engine running on petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without diesel particulate filter (DPF). One group of animals was exposed to DEE for 7 days (6 h/day), and another group for 28 days (6 h/day, 5 days/week), both with and without DPF. The animals (n = 7/treatment) were exposed in whole body exposure chambers. Animals breathing clean air were used as controls. Genotoxic effects of the lungs by the Comet assay, histological examination of lung tissue, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury, and mRNA markers of inflammation and oxidative stress were analyzed. Our results showed that a minor number of genes related to inflammation were slightly differently expressed in the exposed animals compared to control. Histological analysis also revealed only minor effects on inflammatory tissue markers in the lungs, and this was supported by flow cytometry and ELISA analysis of cytokines in BALF. No exposure-related indications of genotoxicity were observed. Overall, exposure to DEE with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF. Overall, exposure to DEE from a modern Euro 5 light vehicle engine run on B20 fuel with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF.

Carcionoid of the appendix in pregnant woman - case report and literature review.

Neuroendocrine neoplasms are detected very rarely in pregnant women. The following is a case report of carcinoid tumor of the appendix diagnosed in 28 year-old woman at 25th week of gestation. The woman delivered spontaneously a healthy baby at the 38th week of gestation. She did not require adjuvant therapy with somatostatin analogues. The patient remained in remission. There are not established standards of care due to the very rare incidence of carcinoid tumors in pregnancy. A review of the literature related to management and prognosis in such cases was done.

The influence of eicosapentaenoic acid and docosahexaenoic acid on expression of genes connected with metabolism and secretory functions of ageing 3T3-L1 adipocytes.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 long chain polyunsaturated fatty acids. The purpose of our study was to evaluate the influence of EPA and DHA on expression of genes connected with metabolism and secretory functions of ageing adipocytes. Young, mature and old differentiated 3T3-L1 adipocytes were cultured for 48h in the presence of EPA, or DHA. Both fatty acids increased the expression of Pparg, FATP1, FATP4 and ATGL genes, but only in young 3T3-L1 adipocytes. Moreover, in young, mature and old cells DHA elevated the expression of CPT1 gene. In addition, EPA and DHA enhanced the expression of leptin, adiponectin and apelin genes only in young cells. Investigated fatty acids changed mRNA levels of IL6 and MCP1 in young, mature and old cells. EPA increased the expression of these two genes, whereas DHA decreased it. Furthermore, EPA and DHA treatment changed the expression of IRS1 and GLUT4 genes involved in insulin signalling pathway, but their effects were opposite. Expression of these genes was decreased by EPA and increased by DHA in young, mature and old cells. In summary, the investigated fatty acids are able to affect the expression of genes associated with lipid metabolism, secretory functions and insulin resistance in ageing 3T3-L1 adipocytes, but their impact is age-dependant. Young cells seem to be more sensitive to EPA and DHA than mature and old ones. Furthermore, the effect of these two fatty acids is not always identical, and therefore requires further investigation.