Obesity is a global health problem with high prevalence and defined by a high body mass index (BMI). Several comorbidities affecting the central nervous system (CNS) are associated with obesity ...(e.g., neurodegenerative diseases, cognitive deficit, and psychobehavioral disturbs). The zebrafish (Danio rerio) has been considered a suitable model organism to investigate the neurobehavioral features of various human diseases. Here, we verify the impact of a high-fat diet (HFD) on the CNS by specifically assessing the effects of short-term HFD on anxiety-like responses, aggression, social preference, and memory, which are essential behaviors for survival and reproduction. Animals were separated in three experimental groups. The standard diet group (SD) received 7.5 mg/fish of dry food, while HFD groups received 5 mg/fish dry food plus 7.5 (HFD-7.5) or 15 mg/fish (HFD-15) of chicken egg yolk daily. Dietary fat content (w/w) was approximately 6.5%, 16.9%, and 21.1%, respectively. We performed behavioral tests and morphometric analyses after two weeks of HFD. In comparison to SD animals, HFD groups showed typical obesogenic responses with increases in BMI, abdominal length, and body weight. HFD individuals also showed increased aggression and anxiety-like behaviors in the mirror-induced aggression and novel tank diving tests, respectively. Interestingly, HFD did not change the social preference behavior, mean swimming speed or spontaneous activity levels, while the HFD-15 group showed cognitive deficits in the inhibitory avoidance test. Collectively, this “proof-of-concept” study is the first report to characterize the effects of short-term HFD on different behavioral domains of zebrafish with high degree of face validity. Moreover, our data reinforce the growing utility of zebrafish to explore the neurobehavioral basis of obesity, providing clinically translatable data, complementing the existing rodent models and supporting future mechanistic studies.
•Short-term high-fat diet induces obesity in adult zebrafish.•High-fat diet affects different neurobehavioral domains in zebrafish.•High-fat diet impairs memory acquisition in the inhibitory avoidance test.•High-fat diet positively modulates aggression and anxiety-like behavior.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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
Animal venoms are rich sources of neuroactive compounds, including anti-inflammatory, antiepileptic, and antinociceptive molecules. Our study identified a protonectin peptide from the wasp ...Parachartergus fraternus' venom using mass spectrometry and cDNA library construction. Using this peptide as a template, we designed a new peptide, protonectin-F, which exhibited higher antinociceptive activity and less motor impairment compared to protonectin. In drug interaction experiments with naloxone and AM251, Protonectin-F's activity was decreased by opioid and cannabinoid antagonism, two critical antinociception pathways. Further experiments revealed that this effect is most likely not induced by direct action on receptors but by activation of the descending pain control pathway. We noted that protonectin-F induced less tolerance in mice after repeated administration than morphine. Protonectin-F was also able to decrease TNF-α production in vitro and modulate the inflammatory response, which can further contribute to its antinociceptive activity. These findings suggest that protonectin-F may be a potential molecule for developing drugs to treat pain disorders with fewer adverse effects. Our results reinforce the biotechnological importance of animal venom for developing new molecules of clinical interest.
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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
Considering the clinical importance of the ventricular fibrillation and that the most used therapy to reverse it has a critical side effect on the cardiac tissue, it is desirable to optimize ...defibrillation parameters to increase its efficiency. In this study, we investigated the influence of stimuli duration on the relationship between pacing threshold and defibrillation probability.
We found out that 0.5-ms-long pulses had a lower ratio of defibrillation probability to the pacing threshold, although the higher the pulse duration the lower is the electric field intensity required to defibrillate the hearts.
The appropriate choice of defibrillatory shock parameters is able to increase the efficiency of the defibrillation improving the survival chances after the occurrence of a severe arrhythmia. The relationship between pulse duration and the probability of reversal of fibrillation shows that this parameter cannot be underestimated in defibrillator design since different pulse durations have different levels of safety.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ContHeart is a software designed to analyze cardiomyocyte contractile dynamics using Canny’s method for edge detection in recorded videos. It is a tool that allows researchers (users) to post-analyze ...video usually captured in their work routine, without special capture apparatus. The software has a user-friendly graphical interface in which the user can apply filters and modify parameters to optimize edge detection and shortening measurement. Therefore, the software quickly generates reliable data on the variation of cell dimensions over time, which can be interpreted by the researcher. We believe researchers will find here a powerful tool to enhance the reach of their basic cardiovascular research, allowing them to include the cardiomyocytes shortening analysis on their work. That might increase the scope of knowledge within the field, as the effect of different pathophysiological conditions may be analyzed on cardiomyocyte contraction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although high-intensity electric fields (HEF) application is currently the only effective therapy available to terminate ventricular fibrillation, it may cause injury to cardiac cells. In this study ...we determined the relation between HEF pulse length and cardiomyocyte lethal injury. We obtained lethality curves by survival analysis, which were used to determine the value of HEF necessary to kill 50% of cells (E50) and plotted a strength-duration (SxD) curve for lethality with 10 different durations: 0.1, 0.2, 0.5, 1, 3, 5, 10, 20, 35 and 70 ms. For the same durations we also obtained an SxD curve for excitation and established an indicator for stimulatory safeness (stimulation safety factor - SSF) as the ratio between the SxD curve for lethality and one for excitation. We found that the lower the pulse duration, the higher the HEF intensity required to cell death. Contrary to expectations, the highest SSF value does not correspond to the lowest pulse duration but to the one of 0.5 ms. As defibrillation threshold has been described as duration-dependent, our results imply that the use of shorter stimulus duration - instead of the one typically used in the clinic (10 ms) - might increase defibrillation safeness.
Human reproduction presents a challenge for our species, as evidenced by the escalating rates of infertility. This trend has prompted inquiries into diverse strategies aimed at mitigating infertility ...and enhancing conception rates. Despite the extensive research on advanced maternal age as a risk factor for reproductive outcomes, paternal age has historically garnered comparatively less attention. The aim of this study was to assess the impact of paternal age on embryos and its subsequent repercussions on fertilization rate, biochemical pregnancy, clinical pregnancy, and live birth rate in individuals undergoing assisted reproductive treatment in a public reproductive center located in Brazil.OBJECTIVEHuman reproduction presents a challenge for our species, as evidenced by the escalating rates of infertility. This trend has prompted inquiries into diverse strategies aimed at mitigating infertility and enhancing conception rates. Despite the extensive research on advanced maternal age as a risk factor for reproductive outcomes, paternal age has historically garnered comparatively less attention. The aim of this study was to assess the impact of paternal age on embryos and its subsequent repercussions on fertilization rate, biochemical pregnancy, clinical pregnancy, and live birth rate in individuals undergoing assisted reproductive treatment in a public reproductive center located in Brazil.This investigation adopted a retrospective cohort, cross-sectional, analytical design, utilizing the analysis of secondary data, covering the period from July 2015 to July 2021.METHODSThis investigation adopted a retrospective cohort, cross-sectional, analytical design, utilizing the analysis of secondary data, covering the period from July 2015 to July 2021.A total of 350 couples grappling with infertility and undergoing intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) were included in the analysis. Examination of age groups revealed a notable correlation between the ages of women and men (correlation coefficient R=0.12, p<0.0001). In the analysis of IVF techniques, a discernible trend towards a negative correlation with paternal age was observed, signifying that higher paternal age was linked to lower fertilization rates (p=0.004).RESULTSA total of 350 couples grappling with infertility and undergoing intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) were included in the analysis. Examination of age groups revealed a notable correlation between the ages of women and men (correlation coefficient R=0.12, p<0.0001). In the analysis of IVF techniques, a discernible trend towards a negative correlation with paternal age was observed, signifying that higher paternal age was linked to lower fertilization rates (p=0.004).Advanced paternal age significantly impacts full-term birth rates in IVF procedures, emphasizing the need for preconception public health advisories that underscore the risks associated with delaying parenthood for both men and women, particularly among those necessitating assisted reproductive techniques.CONCLUSIONSAdvanced paternal age significantly impacts full-term birth rates in IVF procedures, emphasizing the need for preconception public health advisories that underscore the risks associated with delaying parenthood for both men and women, particularly among those necessitating assisted reproductive techniques.
The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to ...evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, associated with two low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioenergetic impairment in the hippocampus, characterized by a decrease in both O2 consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by the two-hit protocol, here verified through the absence of a decrease in O2 consumption after uncoupled protein-1 inhibition and an increase in the reserve respiratory capacity. Impaired mitochondrial function was also observed in the liver of HFD+STZ juvenile mice, but not in their heart. These results indicate that exposure to HFD+STZ early in life has a detrimental impact on the bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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