Promjene u RF-amidu srodnom peptidu-3 hipotalamusa i ekspresijama gena Kiss1 tijekom spermatogeneze kod štakora u uvjetima kroničnog stresa.

The effects were evaluated of chronic stress and the glucocorticoid receptor antagonist (RU486) on mRNA expressions of RF-amide related peptide-3 (RFRP-3) in the dorsomedial hypothalamic nucleus (DMH) and Kiss1 in the arcuate nucleus (ARC) of male rats. Twenty-four male rats were allocated to four equal sized groups: the stress, RU486, stress/RU486, and control groups. In the stress group the rats were restrained 1 hour/day for 12 days. In the RU486 group, the rats were injected with RU486 for 12 days. In the stress/RU486 group, the rats were injected with RU486 1 hour before the stress process for 12 days. Relative expressions of RFRP-3 and Kiss1 mRNAs were determined using real-time PCR. The relative expression of RFRP-3 mRNA in the stress group was higher than that in the RU486 and control rats. The relative expression of RFRP-3 mRNA did not differ between the stress group and the stress/RU486 rats. Furthermore, the relative expressions of Kiss1 mRNA in the stress, RU486, and stress/RU486 groups were less than that of the control rats. The relative expression of Kiss1 mRNA did not differ between the stress, RU486, and stress/RU486 groups. In conclusion, dysfunction in male rat fertility caused by the chronic stress may be the result of the increase in REFP-3 and the decrease in Kiss1 mRNA expression.Istražen je učinak kroničnog stresa i antagonista glukokortikoidnog receptora (RU486) na ekspresiju mRNA RF-amidu srodnog peptida-3 (RFRP-3) u dorzomedijalnoj jezgri hipotalamusa (DMH), te na ekspresije gena Kiss1 u arkuatnom nukleusu (ARC) štakora. Dvadeset i četiri štakora bila su raspodijeljena u četiri jednake skupine: stresna skupina, RU486 skupina, stresna/RU486 skupina i kontrolna skupina. U stresnoj skupini štakori su 12 dana bili obuzdani tijekom jednog sata dnevno. U skupini RU486, štakorima je tijekom 12 dana bio primijenjivan RU486. U skupini stres/RU486, štakorima je tijekom 12 dana apliciran RU486 jedan sat prije postupka obuzdavanja. Relativne ekspresije RFRP-3 i Kiss1 mRNA određene su lančanom reakcijom polimerazom u stvarnom vremenu. Relativna ekspresija RFRP-3 mRNA u stresnoj skupini bila je veća nego u skupini RU486 i kontrolnoj skupini. Relativna ekspresija RFRP-3 mRNA nije bila različita između stresne skupine i stres/RU486 skupine. Nadalje, relativne ekspresije Kiss1 mRNA u stresnoj skupini, skupini RU486, i stresnoj skupini/RU486 bile su manje u odnosu na kontrolnu skupinu. Relativna ekspresija Kiss1 mRNA nije se razlikovala između stresne skupine, skupineRU486 i stresne skupine/RU486. Zaključno, disfunkcija plodnosti kod štakora izloženih kroničnom stresu može biti uzrokovana putem povećane ekspresije RFRP-3 i smanjene ekspresije Kiss1 mRNA

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study

Objectives: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). Materials and methods: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. Results: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients \u3e 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P\u3c0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. Conclusion: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended

Dysregulated Expression of MiR-19b, MiR-25, MiR-17, WT1, and CEBPA in Patients with Acute Myeloid Leukemia and Association with Graft versus Host Disease after Hematopoietic Stem Cell Transplantation

Objectives Acute myeloid leukemia (AML) is a blood malignancy characterized by the proliferation of aberrant cells in the bone marrow and blood that interfere with normal blood cells. We have investigated whether changes in the level of micro-ribonucleic acid (miR)-19b, miR-17, and miR-25, Wilms' tumor (WT1), and CCAAT enhancer-binding protein α (CEBPA) genes expression affect disease prognosis and clinical outcome in AML patients. Materials and Methods The expression level of miR-19-b, miR-17, and miR-25, as well as WT1 and CEBPA genes in a group of patients and controls as well as different risk groups (high, intermediate, and favorite risk), M3 versus non-M3, and graft-versus-host disease (GvHD) versus non-GvHD patients were assessed using a quantitative SYBR Green real-time polymerase chain reaction method. Results When compared with the baseline level at the period of diagnosis before chemotherapy, the expression of miR-19b and miR-17 in AML patients increased significantly after chemotherapy. The level of miR-19b and miR-25 expression in AML patients with M3 and non-M3 French–American–British subgroups differ significantly. MiR-19b and miR-25 expression was elevated in GvHD patients, while miR-19b and miR-25 expression was somewhat decreased in GvHD patients compared with non-GvHD patients, albeit the difference was not statistically significant. Also, patients with different cytogenetic aberrations had similar levels of miR-19-b and miR-25 expression. Conclusion MiR-19b, miR-17, and miR-25 are aberrantly expressed in AML patients' peripheral blood leukocytes, which may play a role in the development of acute GvHD following hematopoietic stem cell transplantation

The Effect of Prolonged Exposure to Extremely Low Frequency Electromagnetic Fields on the β2 Adrenergic System Activity in the Small Intestine of Male Rats

Background & Objective: Electromagnetic waves with the frequencies of 0–300 Hz and the intensity of 0.1–100 millitesla can affect several cellular activities. Therefore, the purpose of this study is to investigate the effect of prolonged exposure to extremely low frequency electromagnetic fields (ELF) on the adrenergic system in the small intestine. Materials & Methods: 21 adult male rats were divided into three groups. The first group was experimental group which exposed to ELF (50Hz, 1mT) for 75 days in powered on solenoid. The second group was sham group which was kept in similar conditions as the first group but in powered off solenoid. The third group or the control group was kept in animal house condition. The isolated strips of the colon were inserted into organ bath and were linked to power lab A to D system force transducer and their mechanical activity were recorded in response to different doses of Isoproterenol (10-4 M and10-5 M). The data were analyzed using one-way ANOVA test. Result: The results showed a significant increase (p≤0.05) of ileum basal contractions in experimental group compared to control and sham groups. While the relaxation changes of ileum in response to the different doses of isoproterenol (β2 adrenergic receptors agonist) in the experimental group compared to the sham and control groups was not statistically significant. Conclusion: It can be concluded that prolonged exposure to extremely low frequency electromagnetic fields may not affect β2 -adrenergic receptors activity

Low frequency electromagnetic fields long-term exposure effects on testicular histology, sperm quality and testosterone levels of male rats

Objective: To evaluate the effects of long-term exposure to low frequency EMF on the testicular function and structure. Methods: Fourteen adult male rats were randomly and equally divided into sham and experimental groups. Experimental group was exposed to 1 mT, 50 Hz EMF, continuously for 85 days in a solenoid. Sham group was kept under conditions same as experimental group, without EMF. At the end of the exposure period, weight and size of testes, sperm evaluation (sperm counts, motility and viability), histological testicular sections and serum total testosterone were determined. Results: Long-term exposure to low frequency EMF significantly decreased the diameter of the seminiferous tubules and increased number of seminiferous tubules per unit area of testes. In addition, low frequency EMF significantly reduced sperm motility and testosterone levels. However, it had no effect on the weight and size of testes, sperm concentration, and viability. Conclusions: Prolonged exposure to 50 Hz EMF has an adverse effect on male fertility

Therapeutic Effects of Dimethyl Fumarate on the Rat Model of Brain Ischemia

Blood-brain barrier (BBB) disruption, inflammation, and cell death are major pathogenic mechanisms in ischemic stroke. Dimethyl fumarate (DMF) has anti-inflammatory and immune-modulatory effects. So, this study aimed to elucidate the effects of DMF on brain ischemia in the middle cerebral artery occlusion (MCAO) model. 69 Sprague-Dawley male rats were allocated into a sham group that was just subjected to surgery stress; vehicle and DMF groups, after MCAO, received vehicle or 30 mg/kg DMF for three days. Neurological scores were evaluated every day. BBB disruption was evaluated by the extravasation of Evans blue. In addition to the measurement of brain water content, the total and infarct volume, numerical density, and the total number of neurons, non-neurons, and dead neurons in the right cortex were estimated by stereological methods. RT-PCR was done to analyze the expression levels of NF-κB and Nrf2. Although brain ischemia treatment with DMF did not have a significant effect on the infarction size, it improved neurobehavioral function, BBB disruption, cerebral edema, increased number of neurons, and expression of Nrf2. It also decreased the number of dead neurons and the expression of NF-κB. DMF beneficial effects on stroke may be mediated through both increase of the Nrf2 and decrease of NF-κB expression

Testicular germ cells apoptosis following exposure to chronic stress in rats

Objective: To evaluate the effects of chronic stress on testosterone hormone level and germ cells apoptosis in testes and the inhibitory role of glucocorticoid receptor antagonist, RU486. Methods: Adult male Sprague–Dawley rats were randomly assigned to four groups (n = 6): control; stress; RU486; stress/RU486. Animals in RU486 and stress/RU486 subjected to subcutaneous injections of 2.5 mg RU486/kg 1 h before stress session. Rats were submitted to chronic restraint stress (1 h daily for 12 consecutive days) whereas control animals were not subjected to stress. Serum testosterone assay was performed and the occurrence of DNA fragmentation in the testis sections was examined using TUNEL staining. Results: Chronic restraint stress significantly induced a decrease in serum testosterone level with increase in apoptosis in spermatogonia. Systemic administration of RU486 significantly restored serum testosterone levels and attenuates stress-induced apoptosis in spermatogonia. Conclusion: The restraint stress-induced change in serum testosterone levels and seminiferous tubules apoptosis closely associated with the glucocorticoid receptor

Therapeutic potential of hair follicle-derived stem cell intranasal transplantation in a rat model of ischemic stroke

Background Stem cell-based therapy has received considerable attention as a potential candidate in the treatment of ischemic stroke; however, employing an appropriate type of stem cells and an effective delivery route are still challenging. In the present study, we investigated the therapeutic effect of safe, noninvasive, and brain-targeted intranasal administration of hair follicle-derived stem cells (HFSCs) in a rat model of ischemic stroke. Methods Stem cells were obtained from the adult rat hair follicles. In experiment 1, stroke was induced by 30 min middle cerebral artery occlusion (MCAO) and stem cells were intranasally transplanted immediately after ischemia. In experiment 2, stroke was induced by 120 min MCAO and stem cells were administered 24 h after cerebral ischemia. In all experimental groups, neurological performance, short-term spatial working memory and infarct volume were assessed. Moreover, relative expression of major trophic factors in the striatum and cortex was evaluated by the quantitative PCR technique. The end point of experiment 1 was day 3 and the end point of experiment 2 was day 15. Results In both experiments, intranasal administration of HFSCs improved functional performance and decreased infarct volume compared to the MCAO rats. Furthermore, NeuN and VEGF expression were higher in the transplanted group and stem cell therapy partially prevented BDNF and neurotrophin-3 over-expression induced by cerebral ischemia. Conclusions These findings highlight the curative potential of HFSCs following intranasal transplantation in a rat model of ischemic stroke.UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study

Objectives: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). Materials and methods: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. Results: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P<0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. Conclusion: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended