Malaria-induced acute kidney injury (MAKI) is a life-threatening complication of severe malaria. Here, we investigated the potential role of the angiotensin II (Ang II)/AT1 receptor pathway in the ...development of MAKI. We used C57BL/6 mice infected by Plasmodium berghei ANKA (PbA-infected mice), a well-known murine model of severe malaria. The animals were treated with 20 mg/kg/day losartan, an antagonist of AT1 receptor, or captopril, an angiotensin-converting enzyme inhibitor. We observed an increase in the levels of plasma creatinine and blood urea nitrogen associated with a significant decrease in creatinine clearance, a marker of glomerular flow rate, and glomerular hypercellularity, indicating glomerular injury. PbA-infected mice also presented proteinuria and a high level of urinary γ-glutamyltransferase activity associated with an increase in collagen deposition and interstitial space, showing tubule-interstitial injury. PbA-infected mice were also found to have increased fractional excretion of sodium (FENa+) coupled with decreased cortical (Na++K+)ATPase activity. These injuries were associated with an increase in pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, interleukin-17, and interferon gamma, in the renal cortex of PbA-infected mice. All modifications of these structural, biochemical, and functional parameters observed in PbA-infected mice were avoided with simultaneous treatment with losartan or captopril. Our data allow us to postulate that the Ang II/AT1 receptor pathway mediates an increase in renal pro-inflammatory cytokines, which in turn leads to the glomerular and tubular injuries observed in MAKI.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cryopreservation of ovarian tissue followed by transplantation represents a strategy to restore ovarian function and fertility. Stress from cryopreservation-thawing processes can lead to alterations ...and/or damage to mitochondrial structure and functionality. High resolution respirometry and histological analysis were used to evaluate the effect of cryopreservation and transplantation on ovarian tissue. Four different conditions were performed: Fresh non-transplanted tissue, Fresh transplanted tissue, Cryopreserved non-transplanted tissue and Cryopreserved transplanted tissue. All groups were able to respond to the substrates-uncoupler-inhibitor protocol. We found a dramatic decrease in general oxygen consumption in hemi-ovaries submitted to cryopreservation and/or transplantation. The effect of cryopreservation on mitochondrial metabolism was less intense than effect of transplantation, since the transplantation affected all of the mitochondrial states. A total of 2644 follicles were analyzed. Of these, 2198 were classified as morphologically normal. The percentage of morphologically normal follicles was significantly lower in the Cryopreserved transplanted group when compared to the Cryopreserved non-transplanted group and the Fresh transplanted group (p-value < 0.05). Despite decreased follicular viability and mitochondrial activity, the cryopreservation followed by transplantation of ovarian tissue proved feasible for attempts to restore ovarian function.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Is the optimal timing for administering erythropoietin to minimize ischaemic injury in ovarian tissue transplantation before ovary removal for cryopreservation and subsequent transplantation or after ...transplantation?
Thirty Swiss mice (nu/nu) were divided into three groups: treatment control group (n = 10); erythropoietin before harvesting group (EPO-BH) (n = 10) and erythropoietin after transplantation group (EPO-AT) (n = 10). Animals underwent bilateral ovariohysterectomy and their hemiovaries were cryopreserved by slow freezing. At the same time, previously cryopreserved hemiovaries were transplanted subcutaneously in the dorsal region. Erythropoietin (250 IU/kg) and sterile 0.9% saline solution were administered every 12/12 h over 5 consecutive days in the EPO-AT and EPO-BH groups, respectively.
Administration of erythropoietin in the EPO-AT group improved the viability of ovarian follicles, reducing degeneration and increasing the number of morphologically normal growing follicles at 14 days after transplantation compared with the EPO-BH group (P = 0.002). This group also showed higher percentages of proliferative follicles at 7 days after transplantation (P ≤ 0.03), increased blood vessel count (P ≤ 0.03) and greater tissue area occupied by blood vessels at days 7 and 14 after transplantation (P ≤ 0.03), compared with hormone administration before cryopreservation (EPO-BH group) and the treatment control group. Additionally, treatment with erythropoietin before or after transplantation reduced fibrotic areas at 7 days after transplantation (P = 0.004).
Erythropoietin treatment after transplantation reduced ischaemic damage in transplanted ovarian tissue, increased angiogenesis, maintenance of ovarian follicle proliferation and reduced fibrosis areas in the grafted tissue.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Many feline species are currently threatened with extinction. Therefore, germplasm bank establishment has become imperative. However, cryoinjury and ischemia-reperfusion injury pose significant ...obstacles to both cryopreservation and xenotransplantation. In this regard, erythropoietin (Epo) represents a potential alternative strategy due to its properties. This study aimed to assess the incubation of domestic cat ovarian tissue in Epo, both before and after cryopreservation, and investigate its effectiveness in promoting revascularization following xenotransplantation. Sixteen ovaries from 8 healthy cats were sliced following elective bilateral ovariohysterectomy (OHE). Subsequently, 8 fragments measuring 3 mm³ each were obtained from the cortical region of each ovary. The fragments were allocated into 3 treatment groups: Cryo group, fragments were cryopreserved, thawed and immediately transplanted; Cryo + Epo group, fragments were first cryopreserved in nitrogen, thawed, incubated in Epo (100 IU) for 2h and transplanted; and the Epo + Cryo group, in which fragments were first incubated in Epo (100 IU) for 2h, cryopreserved, thawed and immediately transplanted. The fragments were then xenotransplanted into the dorsal subcutaneous region of ovariectomized female nude mice and retrieved at 7, 14, 21, and 28 days post-transplantation. The results indicated that Epo effectively enhanced follicular survival, preservation of viability, and tissue revascularization. The Epo + Cryo group displayed better revascularization rates on D14 and D21 post-transplantation and an increase in primordial and growing follicles on D28, the Cryo + Epo group exhibited significantly more follicles on D14 and D21, with fewer degenerated follicles.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The objective of this study was to investigate the influence of Cladosporium cladosporioides during cocoa fermentation on the physico-chemical characteristics, phenolic compounds, free bioactive ...amines and volatile compounds. Two fermentation treatments were carried out: a spontaneous, control process and another one with the addition of C. cladosporioides starter culture. The use of this starter culture did not affect significantly the temperature and acidity (p > 0.05) of cocoa throughout fermentation. It led to decreased levels of total phenolic compounds, catechin and epicatechin. In addition, it caused an increase in the levels of reducing sugars (glucose and fructose), an increase in bioactive amines (cadaverine, putrescine, phenylethylamine and spermidine) and an increase in the levels and diversity of volatile compounds (2-phenethylacetate, benzaldehyde and acetophenone, responsible for floral, fruity and candy notes) in fermented and dried cocoa. Multivariate analysis (principal component analysis and hierarchical cluster analysis) emphasized the differences between the two treatments. Based on these results, the use of C. cladosporioides as a starter culture during cocoa fermentation seems to be promising. However, further studies are needed to ascertain their impact on the sensorial characteristic and acceptance of chocolate.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Dermcidin (DCD) is a candidate oncogene localized at 12q13.1. It is produced by benign melanocytic naevi and dark cells of eccrine sweat glands and proteolytic processed and transported via ...sweat to the epidermal surface to act as peptide antibotic, but it is not induced under inflammation. We have established the role of DCD in melanoma growth and survival by silencing DCD expression in human melanoma G361 cell line and overexpression in murine melanoma B16 cell line. Downregulation of DCD in G-361 cell line significantly reduced cellular resistance to cytotoxic agents. Balb/c Nude mice inoculated with 1x106 G-361 cells underwent a progressive increase in the tumor size and body weight loss, whereas animals inoculated with G-361-IBC I melanoma cells expressing DCD shRNA, we observed a significant difference in tumor volumes. Moreover, administration of rabbit polyclonal antibody against DCD in mice bearing G361 xenografts for four weeks delayed tumor growth. To examine tumor heterogeneity we isolated by FACS cell sorting specific cancer-stem cell populations based on cell size and enhanced tumorigenic capacity in Nude mice. In parallel, we are employing the microarray and exome methodologies to define genes that are up- and downregulated, patterns of genetic modifications and gene mutation in specific oncogenic pathways to evaluate the hypothesis that DCD control multiple oncogenic stimuli (EGFR/HER2, C-MYC, PI3K/AKT/mTOR, VEGF, BRAF/RAS, etc.). We will summarize these results and highlight genetic and biological mechanisms suggesting that DCD functions as tumor growth and cell survival factor.
Citation Format: Beatriz A. Sangiuliano, Marcela Nancy Perez, Aline Cadurin, Andrew Aguiar, Dayson F. Moreira, Jose E. Belizario. Role of Dermcidin in Tumorigenesis of Skin Cancers abstract. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr A26.
Resprouting is a functional trait in species which occur in fire-prone ecosystems. These plants can resprout from aerial buds and by recruiting belowground bud bank using carbohydrates allocated in ...roots as resource. In this study, we present morpho-anatomical features and chemical composition related to the resprouting potential of two species of Eugenia L. in an area of the Cerrado (Brazilian savanna) under regeneration, after the clear-cutting of Pinus sp. with the later burning of pine needles layer. We used standard histological techniques for belowground organs analysis and aerial buds protection degree. Belowground buds in layer from soil surface down to 10 depth were counted and the chemical analyses were performed on roots. In all aerial buds, there were relevant protection traits. The belowground organ is a sobole and the number of buds in its upper portion varied from 24 to 517 between individuals of both species. Phenolic compounds, flavonoids, starch and other carbohydrates were detected in roots. The protection of aerial buds, the large number of belowground buds and the storing and protective compounds may have favored the resprouting of the species in the area.
The use of continuous positive airway pressure (CPAP) in asthma has been a point of debate over the past several years. Various studies, including those on animals and humans have attempted to ...understand the role and pathophysiology of CPAP in patients with either well controlled or poorly controlled asthma. The aim of this manuscript is to review the currently available literature on the physiologic and clinical effects of CPAP in animal models of asthma and on humans with stable asthma.
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