Human Wharton's jelly-derived mesenchymal stromal stem cells preconditioned with valproic acid promote cell migration and reduce renal inflammation in ischemia/reperfusion injury by activating the AKT/P13K and SDF1/CXCR4 pathways.

OBJECTIVE: To determine whether WJ-MSCs pretreated with VPA would enhance their migration to improve functional recovery of renal IRI in rats. METHODS: 150 Sprague-Dawley rats were distributed into 5 groups; Sham, IRI, WJ-MSC, VPA, and WJ-MSCs + VPA. 10 rats were sacrificed after 3, 5, and 7 days. Role of WJ-MSCs pretreated with VPA was evaluated by assessment of renal function, antioxidant enzymes together with renal histopathological and immunohistopathological analyses and finally by molecular studies. RESULTS: WJ-MSCs and VPA significantly improved renal function and increased antioxidants compared to IRI group. Regarding gene expression, WJ-MSCs and VPA decreased BAX and TGF-ß1, up-regulated Akt, PI3K, BCL2, SDF1α, and CXCR4 related to IRI. Additionally, WJ-MSCs pretreated with VPA improved the measured parameters more than either treatment alone. CONCLUSION: WJ-MSCs isolated from the umbilical cord and pretreated with VPA defended the kidney against IRI by more easily homing to the site of injury.

Bee venom enhances performance and immune function in thinlip mullet: A promising approach for sustainable aquaculture.

As an environmentally friendly alternative to antibiotics, bee venom holds promise for aquaculture due to its diverse health advantages, including immune-amplifying and anti-inflammatory features. This study investigated the effects of dietary bee venom (BV) on the growth and physiological performance of Thinlip mullet (Liza ramada) with an initial body weight of 40.04 ± 0.11 g for 60 days. Fish were distributed to five dietary treatments (0, 2, 4, 6, and 8 mg BV/kg diet) with three replicates. Growth traits, gut enzyme ability (lipase, protease, amylase), intestinal and liver histology, blood biochemistry, immune responses [lysozyme activity (LYZ), bactericidal activity (BA), nitroblue tetrazolium (NBT%)], and antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA)] were evaluated. BV supplementation significantly improved growth performance, digestive enzyme activity, histological integrity of organs, immune responses (LYZ, BA), and antioxidant status (SOD, CAT, GPx), while declining MDA levels. Optimal BV levels were identified between 4.2 and 5.8 mg/kg diet for different parameters. Overall, the findings suggest that BV supplementation can enhance growth and physiological performance in Thinlip mullet, highlighting its potential as a beneficial dietary supplement for fish health and aquaculture management.

Lactational performance and nutrients digestibility response of dairy buffaloes fed diets supplemented with probiotic (Streptococcus spp.) and fibrolytic enzymes.

The current study was conducted to explore the productive performance and health status of lactating buffaloes fed diets supplemented with probiotic and/or fibrolytic enzymes. Forty multiparous lactating Egyptian buffaloes (body weight 451 ± 8.5 kg) were equally assigned to four experimental groups: (1) the first group fed control diet, (2) second experimental group fed control diet plus 4 g of probiotic/kg dry matter (DM) (probiotic), (3) third experimental group fed control diet plus 4 g of fibrolytic enzymes/kg DM (enzymes) and (4) fourth experimental group fed control diet plus 2 g of probiotic + 2 g fibrolytic enzymes/kg DM (Mix), The experiment was extended for 63 days. Nutrients digestibility was estimated, daily milk yield was recorded and milk samples were analyzed for total solids, fat protein, lactose and ash. Blood serum samples were analyzed for glucose, total protein, albumin, urea-N, aspartate transaminase, alanine transaminase and cholesterol concentrations. Results showed that adding probiotic and/or fibrolytic enzymes improved nutrients digestibility (p < 0.05). The probiotic, enzymes and mix groups did not affect (p > 0.05) concentrations of serum total protein, albumin (A), globulin (G), albumin/globulin (A/G) ratio and urea-N concentrations. An improvement in daily milk yield (p < 0.0001) and energy-corrected milk (p = 0.0146) were observed with the probiotic and mix groups compared with the control. In conclusion, this study suggests that supplementing lactating buffaloes' diets with probiotic alone or in combination with fibrolytic enzymes would improve their productive performance without adversely impacting their health.

Micromorphology of Root Canal Walls After Laser Activated Irrigation.

This study aims to investigate the effects of laser-activated irrigation on root canal dentin using different laser wavelengths. Sixty-six roots were prepared and split longitudinally. First, lasers with different power settings were tested on 34 samples, pre-etched with phosphoric acid, or remaining with a smear-layer to determine the test parameters. Selected parameters were then applied on thirty roots (9 groups) covered with smear layer: 1. Smear-layer removed; 2. Smear-layer untouched; 3. Conventional needle irrigation with NaOCl and EDTA; 4. ER:YAG laser; 5. 9.3 µm CO2 laser; 6-9. Diode lasers. All lasers were applied in ultra-pure water as an irrigant. Root halves were examined by scanning electron microscope to analyze the intracanal dentin micromorphology on 9 consequent photos per specimen @ a magnification of 1000X. The results showed that conventional needle irrigation was effective in removing the smear-layer from coronal and middle root parts, while laser-activated irrigation had two main mechanisms: cleaning and opening of the dentinal tubules by removing the smear layer (Er:YAG laser) and melting of dentin (CO2 and diode lasers) in all root parts. The study concluded that laseractivated irrigation with different wavelengths impacted the smear layer and root canal dentin differently through pure physical/mechanical effects.

Association of glutamine synthetase polymorphisms rs2296521, rs10911021 and rs12136955 with plasma ammonia concentration in valproic acid-treated Egyptian epilepsy patients.

INTRODUCTION: The use of valproic acid (VPA) in the treatment of some psychiatric and neurological disorders such as bipolar disorder, migraines, and epilepsy is associated with hyperammonemia. However, the mechanism of this negative effect of VPA is unclear. In this study, we investigate gene glutamate-ammonia ligase (GLUL) polymorphisms for the glutamine synthetase (GS) enzyme, a key enzyme that catalyzes the removal of ammonia by incorporating it with glutamate to form glutamine, and we investigate whether it has a relationship with the emergence of hyperammonemia during VPA-based therapy. PATIENTS AND METHODS: We enrolled 180 Egyptian epilepsy patients in this study. Patient history, general and neurological examination and blood samples from arm veins were taken. Real time TaqMan PCR polymorphism for three polymorphism SNPs (rs2296521, rs10911021 and rs12136955) of GLUL was done. We assessed the relationship between the patient features, including three GLUL polymorphisms, and the development of hyperammonemia during VPA-based therapy. RESULTS: We found that the ammonia levels showed a positive correlation with VPA treatment duration (p = 0.015) and a negative correlation with carbamazepine total dose per day (p = 0.027) and with WBCs count (p = 0.026). Also, female patients having rs2296521 SNPs with the A allele and patients having rs10911021 SNPs with the C allele were at high risk for elevated plasma ammonia levels. Moreover, patients having rs12136955 SNPs with the A allele or associated hypertension as a co-morbidity were at high risk for elevated plasma ammonia levels. CONCLUSION: Female patients who have rs2296521 with the A allele, rs10911021 with the C allele, or rs12136955 with the A allele, are independent risk factors for elevated plasma ammonia levels during VPA-based therapy. Moreover, carbamazepine combined therapy may protect against the development of hyperammonemia in VPA-treated patients.

Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats.

The current study aimed to determine how palm date aqueous fruit extracts (AFE) affected the autistic-like behaviors brought on by valproic acid (VPA) injection, as well as any potential contributions from Sirt-1, oxidative stress, apoptosis, and autophagy. The pregnant Sprague Dawley females were treated with VPA at 12.5th gestation day and pregnant females and their offspring were treated with AFE orally at doses of 4 mg/Kg by gastric gavage for 45 days after birth. The elevated plus-T maze, water maze, and rotarod tests were used to examine autism-like behaviors. At the end of the study, the expression of Nrf2, heme oxygenase (HO-1), Sirt-1, caspase-3 (a marker of apoptosis), LC3 (a marker of autophagy), and NFκB (inflammatory cytokines) were evaluated along with the oxidative stress in brain tissues and the histological changes in the cerebellum and hippocampus. The neurobehavioral assessments significantly declined due to VPA, which also significantly increased oxidative stress in the brain tissues and significantly decreased Nrf2 and HO-1 expression. Additionally, VPA administration caused significant increase in the expression of caspase-3 in the cerebellar cortex, not in the hippocampus; LC3 and NFκB in the hippocampus, not in the cerebellar cortex; and significant reduction in the expression of Sirt-1 in the hippocampus, not in the cerebellum. On the other hand, AFE treatment significantly improved the neurobehavioral changes as well as it improved significantly the oxidative stress and the expression of LC3, NFκB, NrF2, HO-1, and Sirt-1 in the cerebellum and hippocampus. Conclusions: AFE administration might improve the autistic-like symptoms induced by VPA in rats via attenuation of the oxidative stress, upregulation of Nrf2 and HO-1, Sirt-1 and LC3 expression with downregulation of caspase-3, and NFκB expression in the cerebellum and hippocampus.

Effect of vanillic acid on pentylenetetrazole-kindled rats: Nrf2/HO-1, IGF-1 signaling pathways cross talk.

Vanillic acid (VA) exhibited antioxidant and neuroprotective properties in some neurodegenerative disorders. So, the current study examined the neuroprotective potential of VA as an antiepileptic agent in pentylenetetrazole (PTZ)-induced epileptic rats and the prospective role of Insulin like growth factor-1 (IGF-1) and nuclear factor-2 erythroid-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in this respect. Thirty male albino rats were equally subdivided into 3 groups; (1) normal control (NC) group, (2) PTZ-group: received PTZ (50 mg/Kg, i.p. every other day) for 14 days, and (3) PTZ + VA group: received PTZ and VA (50 mg/Kg daily for 2 weeks). The seizure score and latency were evaluated after PTZ injection. Also, the markers of oxidative stress (malondialdehyde (MDA), catalase, and reduced glutathione (GSH)), histopathological examination, the expression of glial fibrillary acidic protein (GFAP) (a marker of astrocytes) IGF-1, Nrf2, and HO-1 were assessed in the brain tissues by the end of the experiment. PTZ caused significant decrease in seizure latency and significant increase in seizure score by the end of the experiment (p < 0.01). This was associated with significant increase in MDA and GFAP with significant decrease in GSH, total antioxidant capacity (TAC) and IGF-1 in brain tissues compared to normal group (p < 0.01). On the other hand, treatment with VA caused significant attenuation in PTZ-induced seizures which was associated with significant improvement in oxidative stress markers and downregulation in GFAP and upregulation of Nrf2, HO-1 and IGF-1 in CA3 hippocampal region (p < 0.01). VA showed neuroprotective and anti-epileptic effects against PTZ-induced epilepsy which probably might be due to its antioxidant properties and upregulation of Nrf2/HO-1 pathway and IGF-1.

Effects of Stevia rebaudiana Bertoni extracts in the rat model of epilepsy induced by pentylenetetrazol: Sirt-1, at the crossroads between inflammation and apoptosis.

The current study investigated the effects of stevia extracts on a PTZ-induced epileptic rat model and its potential mechanism. Thirty male Sprague-Dawley rats were equally subdivided into 3 groups; (1) normal control (NC) group, (2) PTZ-group: received PTZ (50 mg/kg, i.p. every other day) for 2 weeks, and (3) PTZ+ Stevia group: received PTZ and stevia (200 mg/kg orally daily) for 4 weeks (2 weeks before the start of PTZ treatment and 2 weeks with PTZ administration). The first jerk latency and the seizure score were assessed in rats. Also, brain tissue samples were collected by the end of the experiment, and oxidative stress markers (catalase, MDA, and total antioxidant capacity (TAC)) were measured by biochemical analysis in hippocampal brain homogenates. Also, in the hippocampus, the expression of IL6 and Bcl-2 at the mRNA level and expression of Sirt-1, P53, caspase-3, GFAP, and NF-kB in CA3 hippocampal region by immunohistochemistry was investigated. PTZ substantially increased the seizure score and decreased the seizure latency. Also, PTZ significantly increased MDA, GFAP, IL-6, NF-kB, caspase-3, and p53 and significantly reduced Sirt-1, TAC, and Bcl-2 in hippocampal tissues compared to the control group (p < 0.01). However, Stevia Rebaudiana Bertoni (Stevia R.) significantly attenuated the PTZ-induced seizures, improved oxidative stress markers, downregulated GFAP, IL-6, NF-kB, caspase-3, and p53, and upregulated Sirt-1 and Bcl-2 in the CA3 hippocampal region (p < 0.01). In conclusion, Stevia R. exhibits neuroprotective and antiepileptic actions in PTZ-induced epilepsy due to its antioxidant, anti-apoptotic, and anti-inflammatory effects. Additionally, the Sirt-1 pathway might be involved in the antiepileptic and neuroprotective effects of stevia in PTZ-kindled epileptic rat model.

Long-term histopathological changes of the nasal mucosa after total laryngectomy: a prospective cohort study.

BACKGROUND: Changes in the nasal function following total laryngectomy resulted in histopathological alterations of the nasal mucosa. We aimed to evaluate the long-term histopathological changes and the mucociliary clearance (MCC) of the nasal mucosa after total laryngectomy. METHODS: We performed a histological examination of inferior turbinate biopsy, and saccharine test to assess the MCC time for patients who were candidates for total laryngectomy before the procedure, 6-12 months after surgery, and at least two years postoperatively. RESULTS: Seventy-five patients scheduled for total laryngectomy were initially enrolled in our study. We excluded patients who received postoperative radiotherapy or were lost during the follow-up period. Eventually, 63 and 54 patients were available for assessment 6-12 months after surgery and at least two years postoperatively, respectively. Except for ciliary and goblet cell destruction, which were significantly reduced 6-12 months postoperatively, there were no statistically significant differences in the histopathological findings of the nasal mucosa before surgery and 6-12 months postoperatively. After two years, the histopathological alterations of the nasal mucosa were statistically more evident than those before surgery and 6-12 months postoperatively; the most common histopathological findings were mononuclear cell infiltration and stromal fibrosis. The mean MCC time preoperatively was 12.56 minutes that statistically significantly decreased to 11.81 minutes 6-12 months after surgery; then, it significantly increased to 20.98 minutes at least two years postoperatively. CONCLUSIONS: After total laryngectomy, the nasal mucosa showed histopathological alterations and early enhancement of the MCC, which was later impaired due to nasal mucosal atrophy and the saprophytic infection.

Designing Low-Cost Capacitive-Based Soil Moisture Sensor and Smart Monitoring Unit Operated by Solar Cells for Greenhouse Irrigation Management.

Precise and quick estimates of soil moisture content for the purpose of irrigation scheduling are fundamentally important. They can be accomplished through the continuous monitoring of moisture content in the root zone area, which can be accomplished through automatic soil moisture sensors. Commercial soil moisture sensors are still expensive to be used by famers, particularly in developing countries, such as Egypt. This research aimed to design and calibrate a locally manufactured low-cost soil moisture sensor attached to a smart monitoring unit operated by Solar Photo Voltaic Cells (SPVC). The designed sensor was evaluated on clay textured soils in both lab and controlled greenhouse environments. The calibration results demonstrated a strong correlation between sensor readings and soil volumetric water content (θV). Higher soil moisture content was associated with decreased sensor output voltage with an average determination coefficient (R2) of 0.967 and a root-mean-square error (RMSE) of 0.014. A sensor-to-sensor variability test was performed yielding a 0.045 coefficient of variation. The results obtained from the real conditions demonstrated that the monitoring system for real-time sensing of soil moisture and environmental conditions inside the greenhouse could be a robust, accurate, and cost-effective tool for irrigation management.

Pre-symptomatic and asymptomatic transmission of COVID-19: Implications for control measures in Qatar.

Public health control measures for communicable diseases are often based on the identification of symptomatic cases. However, emerging epidemiological evidence demonstrates the role of pre-symptomatic and asymptomatic transmissions of coronavirus disease 2019 (COVID-19). Understanding high-risk settings where transmissions can occur from infected individuals without symptoms has become critical for improving the response to the pandemic. In this review, we discussed the evidence on the transmission of severe acute respiratory syndrome coronavirus-2, its effect on control strategies, and lessons that can be applied in Qatar. Although Qatar has a small population, it has a distinct setting for COVID-19 control. It has a largely young population and is mostly composed of expatriates particularly from the Middle East and Asia that reside in Qatar for work. Further key considerations for Qatar and travel include population movement during extended religious holiday periods, screening and tracing of visitors and residents at entry points into the country, and expatriates living and working in high-density settings. We also consider how its international airport serves as a major transit destination for the region, as Qatar is expected to experience a rapid expansion of visitors while preparing to host the FIFA World Cup in 2022.

Assessing the effectiveness of CoQ10 dietary supplementation on growth performance, digestive enzymes, blood health, immune response, and oxidative-related genes expression of Nile tilapia (Oreochromis niloticus).

The present study was conducted to investigate the effects of CoQ10 dietary supplementation on growth performance, feed utilization, blood profile, immune response, and oxidative status of Nile tilapia (12.4 ± 0.11 g, initial body weight). Five experimental diets were formulated containing CoQ10 at levels of 0, 10, 20, 30, 40 mg kg-1 diet (D1, D2, D3, D4, and D5, respectively). The results of a 56-days feeding trial showed that, significantly higher weight gain % (WG %), specific growth rate (SGR), feed intake (FI), and feed efficiency ratio (FER) were recorded in fish groups fed diets supplemented with different levels of CoQ10 than fish fed the control diet, while survival rate (SR%), condition factor (CF), hepatosomatic index (HSI) and viscerasomatic index (VSI) showed no obvious differences (P > 0.05) among all experimental groups. The highest activities of digestive enzymes (protease, amylase, and lipase) were recorded in D3, D4, and D5 groups. Moreover, blood status of all experimental fish was within normal rates and significant alterations were only in the case of glucose, cortisol, total cholesterol (T-Chol), triglycerides, and total protein (TP), where fish fed on D3, D4 and D5 diets exhibited lower values of glucose, cortisol, T-Chol, and triglycerides and higher values of TP. Furthermore, the lowest values of immune response [lysozyme, bactericidal, respiratory burst (NBT), and alternative complement pathway activities (ACP)], antioxidant capacity and oxidative related genes expressions [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)] resulted from feeding on the basal diet (D1) compared to CoQ10 diets, especially with its high levels {≥20 mg kg-1 diet (D3, D4, and D5)} in most cases. In conclusion, our results suggest that the use of ≥20 mg CoQ10 kg-1 diet improves the growth and health being of Nile tilapia.

The enhanced photocatalytic performance of SnS2@MoS2 QDs with highly-efficient charge transfer and visible light utilization for selective reduction of mythlen-blue.

Molybdenum disulfide (MoS2) has recently been considered as an effective material for potential photocatalytic applications; however, its photocatalytic activity was limited due to the low density of active sites. In this work, MoS2 Quantum dots (QDs) were synthesized via the ultrasonication technique to construct heterostructure with SnS2 nanosheets (SnS2@MoS2 QDs) and the prepared materials were tested for photocatalytic applications for Methylene blue (MB). Pristine SnS2 and SnS2@MoS2 QDs nanocomposite were analyzed by XRD, TEM, PL, and Uv-Vis. Both SnS2 and SnS2@MoS2 QDs exhibited a single trigonal phase with the P-3m1 space group. The TEM analysis confirmed the coupling between the pristine SnS2 and SnS2@MoS2 QDs. The results of photocatalytic activity toward MB indicated that SnS2@MoS2 QDs material exhibits much superior photocatalytic performance compared to pristine SnS2. The excellent photodegradation performance of SnS2@MoS2 QDs is due in the main to the formation of heterojunction between SnS2 and MoS2 QDs with narrow bandgap formation, which results in a facile carriers transfer and thus high photocatalytic efficiency. A representative mechanism of the photodegradation for SnS2@MoS2 QDs photocatalyst was proposed. Such an ultrasonic technique is capable of producing small metallic particle size that can be used to construct new heterostructures for water remediation applications.

Melatonin Improves Memory Deficits in Rats with Cerebral Hypoperfusion, Possibly, Through Decreasing the Expression of Small-Conductance Ca2+-Activated K+ Channels.

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca2+-activated K+ (SK) channels in memory deficits after cerebral hypoperfusion (CHP) with or without melatonin treatment, in rats. Adults male Wistar rats (n = 20/group) were divided into (1) a sham (2) a sham + melatonin (3) a two-vessel occlusion (2-VO) model, and (4) a 2-VO + melatonin. Melatonin was administered (i.p.) to all rats at a daily dose of 10 mg kg-1 for 7 days starting at the time of 2-VO-induction. In contrast to 2-VO rats, melatonin increased the latency of the passive avoidance learning test and decreased time to find the hidden platform in Water Morris Test in all tested rats. In addition, it concomitantly downregulated SK1, SK2, and SK3 channels, downregulated mRNA levels of TNFα and IL-1ß, enhanced BDNF levels and activity of PKA levels, and restored the levels of cholinergic markers in the hippocampi of the treated-rats. Mechanistically, melatonin significantly prevented CHP-induced activation of ERK1/2, JNK, and P38 MAPK at least by inhibiting ROS generation and enhancing the total antioxidant potential. In cultured hypoxic hippocampal neurons, individual blockage of MAPK signaling by the MEK1/2 inhibitor (U0126), but not by the P38 inhibitor (SB203580) or JNK inhibitor (SP600125), completely prevented the upregulation of all three kinds of SK channels. These data clearly confirm that upregulation of SK channels plays a role in CHP-induced memory loss and indicate that melatonin reverses memory deficits after CHP in rats, at least by, downregulation of SK1, SK2, and SK3 channels in their hippocampi.

Effects of metformin on apoptosis and α-synuclein in a rat model of pentylenetetrazole-induced epilepsy.

The present study was designed to examine the possible neuroprotective and antiepileptic effects of metformin (Metf) in a rat model of pentylenetetrazole (PTZ)-induced epilepsy and its possible underlying mechanisms. Forty male albino rats were assigned to 4 groups of equal size: (1) normal control (NC) group, (2) Metf group: daily treatment with Metf (200 mg/kg, i.p.) for 2 weeks, (3) PTZ group: treatment with PTZ (50 mg/kg, i.p.) every other day for 2 weeks, and (4) Metf + PTZ group: daily treatment with PTZ and metformin (200 mg/kg, i.p.) for 2 weeks. Administration of PTZ caused a significant increase in seizure score and duration, induced a state of oxidative stress (high malondialdehyde, low reduced glutathione and catalase activity), and led to the upregulation of ß-catenin, caspase-3, and its cleavage products, Hsp70 and α-synuclein, in hippocampal regions as well as a significant reduction in seizure latency. While Metf treatment significantly ameliorated PTZ-induced seizures, attenuated oxidative stress, and upregulated α-synuclein and ß-catenin expression, it also inhibited caspase-3 activation and the release of the cleavage product and caused more upregulation in Hsp70 expression in hippocampal regions (p < 0.05). In conclusion, the antiepileptic and neuroprotective effects of Metf in PTZ-induced epilepsy might be due to the inhibition of apoptosis, attenuation of oxidative stress and α-synuclein expression, and upregulation of Hsp70.

Effects of nicorandil on vascular and renal dysfunctions in adenine-induced nephropathy: Possible underlying mechanisms.

Vascular dysfunctions in chronic kidney disease (CKD) include endothelial dysfunctions and vascular calcification (VC). In the present study, we examined the possible protective effect of nicorandil (potassium channel opener) on renal and vascular dysfunctions in a rat model of adenine-induced nephropathy and its underlying mechanisms. Thirty-four male Sprague-Dawley rats were randomly allocated into 3 groups: Control group, Adenine group (animals received high-adenine diet for 4 weeks), and Nicorandil group (animals received adenine for 4 weeks and nicorandil 1 mg/kg per oral for 4 weeks). The results showed significant reduction in the body weight, heart rate (HR), hemoglobin contents, serum Ca2+ and reduction in the expression of mRNA of endothelial nitric oxide synthase (eNOS) and nuclear factor erythroid related factor 2 (nrf2) genes in aortic tissues with significant increase in arterial blood pressure (ABP), serum creatinine, blood urea nitrogen (BUN), plasma renin activity (PRA), K+ and phosphate (PO43-), urinary albumin excretion (UAE) and aortic VC in Adenine group compared to normal group (p < 0.05). On the other hand, coadminsitration of nicorandil caused significant improvement in the studied parameters compared to Adenine group (p < 0.05). We concluded that nicorandil has a potential protective effect against the vascular and renal impairment induced by adenine, which might be due to attenuation of vascular calcifications, activation of Nrf2 and eNOS genes in aortic tissues.

Effects of heme oxygenase-1 upregulation on isoproterenol-induced myocardial infarction.

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).

Upregulation of heme oxygenase 1 (HO-1) attenuates kidney damage, oxidative stress and inflammatory reaction during renal ischemia/ reperfusion injury.

The current study investigated the effect of upregulation of heme oxygenase 1 (HO-1) by cobalt protoporphyrin (CoPP) on renal dysfunctions in renal ischemia/reperfusion (I/R) injury and its underlying mechanisms. 72 male Sprague Dawley rats were divided into 4 groups: sham group, ischemic group (left 45-min renal ischemia), CoPP-before group (as ischemic group with CoPP 20 mg/kg 30 min before ischemia) and CoPP-after group (as ischemic group with CoPP 20 mg/kg 20 min after ischemia). Serum creatinine, urea and TGF-ß1 and markers of redox state (MDA, SOD, GSH and CAT), nitric oxide (NO), TGF-ß1 and HO-1 in kidney tissues were measured. Serum creatinine and urea levels were significantly increased in ischemic group and attenuated in CoPP-treated groups (p < 0.05). Also, markers of redox state showed significant deteriorations in ischemic group which were improved significantly in CoPP-treated groups (p < 0.05). HO-1 expression in kidney tissues showed significant increase in ischemic group and showed more significant increase in CoPP-treated groups (p < 0.05). Moreover, serum and renal TGF-ß1 levels were significantly increased in ischemic group and attenuated in CoPP-treated groups (p ≶ 0.05). We concluded that up-regulation of HO-1 by CoPP treatment before and after renal I/R injury improved the kidney function and morphology and this might be due to impairment of oxidative stress and inflammatory cytokines in kidney tissues.

Drivers of genetic differentiation in a generalist insect-pollinated herb across spatial scales.

The isolation-by-distance model (IBD) predicts that genetic differentiation among populations increases with geographic distance. Yet, empirical studies show that a variety of ecological, topographic and historical factors may override the effect of geographic distance on genetic variation. This may particularly apply to species with narrow but highly heterogeneous distribution ranges, such as those occurring along elevational gradients. Using nine SSR markers, we study the genetic differentiation of the montane pollination-generalist herb, Erysimum mediohispanicum. Because the effects of any given factor may depend on the geographic scale considered, we investigate the contribution of different environmental and historical factors at three different spatial scales. We evaluate five competing models that put forward the role of geographic distance, local environmental factors [biotic interactions (IBEb) and climatic variables (IBEa)], landscape resistance (IBR) and phylogeographic patterns (IBP), respectively. We find significant IBD regardless of the spatial scale and the genetic distance estimator considered. However, IBEa and IBP also play a prominent role in shaping genetic differentiation patterns at the larger spatial scales, and IBR is significant at the fine spatial scale. Overall, our results highlight the importance of combining different estimators, statistical approaches and spatial scales to disentangle the relative importance of the various ecological factors contributing to the shaping of genetic divergence patterns in natural populations.

Effects of ferulic acid on oxidative stress, heat shock protein 70, connexin 43, and monoamines in the hippocampus of pentylenetetrazole-kindled rats.

The present study investigated the effects of ferulic acid (FA) on pentylenetetrazole (PTZ)-induced seizures, oxidative stress markers (malondialdehyde (MDA), catalase, and reduced glutathione (GSH)), connexin (Cx) 43, heat shock protein 70 (Hsp 70), and monoamines (serotonin (5-HT) and norepinephrine (NE)) levels in a rat model of PTZ-induced kindling. Sixty Sprague Dawley rats were divided into 5 equal groups: (a) normal group; (b) FA group: normal rats received FA at a dose of 40 mg/kg daily; (c) PTZ group: normal rats received PTZ at a dose of 50 mg/kg i.p. on alternate days for 15 days; (d) FA-before group: treatment was the same as for the PTZ group, except rats received FA; and (e) FA-after group: rats received FA from sixth dose of PTZ. PTZ caused a significant increase in MDA, Cx43, and Hsp70 along with a significant decrease in GSH, 5-HT, and NE levels and CAT activity in the hippocampus (p < 0.05). Pre- and post-treatment with FA caused significant improvement in behavioral parameters, MDA, CAT, GSH, 5-HT, NE, Cx43 expression, and Hsp70 expression in the hippocampal region (p < 0.05). We conclude that FA has neuroprotective effects in PTZ-induced epilepsy, which might be due to attenuation of oxidative stress and Cx43 expression and upregulation of neuroprotective Hsp70 and neurotransmitters (5-HT and NE).