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Saloniemi T.,University of Turku | Jarvensivu P.,University of Turku | Koskimies P.,QuatRx Pharmaceuticals | Jokela H.,University of Turku | And 10 more authors.
American Journal of Pathology | Year: 2010

Local estrogen production plays a key role in proliferative endometrial disorders, such as endometrial hyperplasia and cancer. Hydroxysteroid (17β) dehydrogenase 1 (HSD17B1) is an enzyme that catalyzes with high efficiency the conversion of weakly active estrone into highly potent estradiol. Here we report that female transgenic mice expressing human HSD17B1 invariably develop endometrial hyperplasia in adulthood. These mice also fail to ovulate and have enhanced peripheral conversion of estrone into estradiol in a variety of target tissues, including the uterus. As in humans, endometrial hyperplasia in HSD17B1 transgenic female mice was reversible on ovulation induction, which triggers a rise in circulating progesterone levels , and in response to exogenous progestins. Strikingly , a treatment with an HSD17B1 inhibitor failed to restore ovulation yet completely reversed the hyperplastic morphology of epithelial cells in the glandular compartment, although less so in the luminal epithelium. The data indicate that human HSD17B1 expression enhances endometrial estrogen production, and consequently, estrogen-dependent proliferation. Therefore, HSD17B1 is a promising new therapeutic target in the management of estrogen-dependent endometrial diseases. Copyright © American Society for Investigative Pathology. Source


Makinen S.,Natural Resources Institute Finland Luke | Streng T.,Turku Center for Disease Modeling | Streng T.,University of Turku | Larsen L.B.,University of Aarhus | And 2 more authors.
Journal of Functional Foods | Year: 2016

The angiotensin I-converting enzyme (ACE) inhibitory and antihypertensive properties of potato and rapeseed protein-derived peptides were investigated. Proteins from potato tubers were digested by autolysis and rapeseed meal proteins were hydrolysed with Alcalase. The digestions were followed by ultra filtration and solid phase extraction to concentrate the ACE inhibitory peptides. The effects of potato peptides (PP) and rapeseed peptides (RP) on blood pressure were measured in vivo in Goldblatt rat model of hypertension. The maximum difference in mean arterial pressure was approximately -60 mmHg induced by PP and -50 mmHg by RP in comparison to vehicle treated rats. Peptide analysis with LC and MS/MS showed a diverse peptide composition for the PP and RP. The results of the present study indicate first time the preventive potential of potato and rapeseed protein-derived peptides against the progression of hypertension in vivo. © 2016 Elsevier Ltd. Source


Asghar M.N.,Abo Akademi University | Emani R.,University of Turku | Alam C.,Abo Akademi University | Helenius T.O.,Abo Akademi University | And 9 more authors.
Inflammatory Bowel Diseases | Year: 2014

Background: Traditional techniques analyzing mouse colitis are invasive, laborious, or indirect. Development of in vivo imaging techniques for specific colitis processes would be useful for monitoring disease progression and/or treatment effectiveness. The aim was to evaluate the applicability of the chemiluminescent probe L-012, which detects reactive oxygen and nitrogen species, for in vivo colitis imaging. Methods: Two genetic colitis mouse models were used; K8 knockout (K8-/-) mice, which develop early colitis and the nonobese diabetic mice, which develop a transient subclinical colitis. Dextran sulphate sodium was used as a chemical colitis model. Mice were anesthetized, injected intraperitoneally with L-012, imaged, and quantified for chemiluminescent signal in the abdominal region using an IVIS camera system. Results: K8-/- and nonobese diabetic mice showed increased L-012-mediated chemiluminescence from the abdominal region compared with control mice. L-012 signals correlated with the colitis phenotype assessed by histology and myeloperoxidase staining. Although L-012 chemiluminescence enabled detection of dextran sulphate sodium-induced colitis at an earlier time point compared with traditional methods, large mouse-to-mouse variations were noted. In situ and ex vivo L-012 imaging as well as [18F]FDG-PET imaging of K8-/- mice confirmed that the in vivo signals originated from the distal colon. L-012 in vivo imaging showed a wide variation in reactive oxygen and nitrogen species in young mice, irrespective of K8 genotype. In aging mice L-012 signals were consistently higher in K8-/- as compared to K8+/+ mice. Conclusions: In vivo imaging using L-012 is a useful, simple, and cost-effective tool to study the level and longitudinal progression of genetic and possibly chemical murine colitis. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc. Source


Karaman D.S.,Abo Akademi University | Desai D.,Abo Akademi University | Desai D.,M. S. University of Baroda | Senthilkumar R.,Abo Akademi University | And 8 more authors.
Nanoscale Research Letters | Year: 2012

In nanomedicine, physicochemical properties of the nanocarrier affect the nanoparticle's pharmacokinetics and biodistribution, which are also decisive for the passive targeting and nonspecific cellular uptake of nanoparticles. Size and surface charge are, consequently, two main determining factors in nanomedicine applications. Another important parameter which has received much less attention is the morphology (shape) of the nanocarrier. In order to investigate the morphology effect on the extent of cellular internalization, two similarly sized but differently shaped rod-like and spherical mesoporous silica nanoparticles were synthesized, characterized and functionalized to yield different surface charges. The uptake in two different cancer cell lines was investigated as a function of particle shape, coating (organic modification), surface charge and dose. According to the presented results, particle morphology is a decisive property regardless of both the different surface charges and doses tested, whereby rod-like particles internalized more efficiently in both cell lines. At lower doses whereby the shape-induced advantage is less dominant, charge-induced effects can, however, be used to fine-tune the cellular uptake as a prospective 'secondary' uptake regulator for tight dose control in nanoparticle-based drug formulations. © 2012 Sen Karaman et al. Source


Turunen H.T.,University of Turku | Sipila P.,University of Turku | Sipila P.,Turku Center for Disease Modeling | Sipila P.,University of Helsinki | And 7 more authors.
Reproduction | Year: 2012

Bmyc is a member of the Myc family of transcriptional regulators in the mouse and the rat. It is predominantly expressed in hormonally controlled tissues, with highest level of expression in the epididymis. The BMYC protein has been shown to function as a transcription factor in vitro and to inhibit MYC. To study the significance of BMYC in vivo, a Bmyc knockout (KO) mouse model was generated by homologous recombination. The KO mice were viable and fertile and did not display gross morphological or histological changes compared to the WT mice. However, the testes and the epididymides of the KO mice were smaller than those of the WT mice. Correspondingly, a tendency for a lower sperm concentration in the cauda epididymides of the KO mice was detected. The testosterone produced/testis was significantly reduced, and accordingly, the LH levels were increased in the KO mice. Also, the expression levels of Myc and several of its target genes were elevated in the testes of prepubertal KO mice, whereas no differences in gene expression levels were detected in adult mice. Associated with the increased Myc expression, more apoptotic spermatogenic cells were detected in the seminiferous tubules of the KO mice. In conclusion, our data suggest that Bmyc is a regulator of Myc in vivo and that overexpression of Myc in the developing testis leads to increased apoptosis of spermatogenic cells. © 2012 Society for Reproduction and Fertility. Source

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