Gemfibrozil Pretreatment Affecting Antioxidant Defense System and Inflammatory, but not Nrf-2 Signaling Pathways Resulted in Female Neuroprotection and Male Neurotoxicity in the Rat Models of Global Cerebral Ischemia–Reperfusion

Two important pathophysiological mechanisms involved during cerebral ischemia are oxidative stress and inflammation. In pathological conditions such as brain ischemia the ability of free radicals production is greater than that of elimination by endogenous antioxidative systems, so brain is highly injured due to oxidation and neuroinflammation. Fibrates as peroxisome proliferator-activated receptor (PPAR)-α ligands, are reported to have antioxidant and anti-inflammatory actions. In this study, gemfibrozil, a fibrate is investigated for its therapeutic potential against global cerebral ischemia–reperfusion (I/R) injury of male and female rats. This study particularly has focused on inflammatory and antioxidant signaling pathways, such as nuclear factor erythroid-related factor (Nrf)-2, as well as the activity of some endogenous antioxidant agents. It was found that pretreatment of animals with gemfibrozil prior to I/R resulted in a sexually dimorphic outcome. Within females it proved to be protective, modulating inflammatory factors and inducing antioxidant defense system including superoxide dismutase (SOD), catalase, as well as glutathione level. However, Nrf-2 signaling pathway was not affected. It also decreased malondialdehyde level as an index of lipid peroxidation. In contrast, gemfibrozil pretreatment was toxic to males, enhancing the expression of inflammatory factors such as tumor necrosis factor-α, nuclear factor-κB, and cyclooxygenase-2, and decreasing Nrf-2 expression and SOD activity, leading to hippocampal neurodegeneration. Considering that gemfibrozil is a commonly used anti-hyperlipidemic agent in clinic, undoubtedly more investigations are crucial to exactly unravel its sex-dependent neuroprotective/neurodegenerative potential.     

Simultaneous Inhibition of COX-2 and Activation of PPAR-γ Resulted in the Same Level and Pattern of Neuroprotection as They were Targeted Separately

The inflammatory response is an immune response of the body when exposed to internal and external stimuli. Cyclooxygenases (COX) are major inflammatory mediators implicated in inflammation. COX-2 is reported to be involved in neuroinflammation. Moreover, 15-Deoxy-d ^12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPAR-γ), has been demonstrated to have anti-inflammatory actions. In this study, we investigated whether co-therapy of a selective COX-2 inhibitor NS-398 and 15d-PGJ2 as a PPAR-γ ligand could exert additional neuroprotective effects in rat pheochromocytoma (PC12) cells. Our findings showed that 15d-PGJ2 and NS-398 suppress the apoptotic pathway in PC12 cells exposed to H₂O₂ by attenuation of the Bax/Bcl-2 ratio. This effect was mediated through PPAR-γ, as it was reversed by GW9662 (a PPAR-γ inhibitor). Also, 15d-PGJ2 and NS-398 induced the Nrf2 signaling pathway and decreased NF-κB level in a PPAR-γ-dependent manner. We found that coadministration of a selective COX-2 inhibitor and a PPAR-γ ligand in PC12 cells has equal neuroprotective effect compared to their effects when used separately. Considering the higher affinity of 15d-PGJ2 for PPAR-γ than NS-398, it seems that the observed neuroprotection of this combination therapy was from 15d-PGJ2.     

Reversal of Prenatal Morphine Exposure-Induced Memory Deficit in Male But Not Female Rats

Impaired memory performance in offspring is one of the long-lasting neurobehavioral consequences of prenatal opiate exposure. Here, we studied the effects of prenatal morphine exposure on inhibitory avoidance memory performance in male and female offspring and also investigated whether these deficits are reversible during the postnatal development. Pregnant Wistar rats received morphine sulfate through drinking water, from the first day of gestation up to the day 13, M_1–13, or to the time of delivery, M_1–21. Four- and ten-week-old (adolescent and adult, respectively) male and female offspring were subjected to behavioral assays and then analysis of proteins involved in apoptosis or in synaptic plasticity. Results revealed that adolescent and adult female rats failed in passive avoidance retention task in both M_1–13 and M_1–21 groups. Adolescent and adult male offspring were similar to control animals in M_1–13 group. However M_1–21 impaired retention task in prepubertal male offspring, and this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2 ratio and cleaved caspase-3 were significantly increased in both M_1–13 and M_1–21 adolescent and adult female rats, but only in M_1–21 adolescent male rats. Furthermore, prenatal morphine exposure reduced the expression of brain-derived neurotrophic factor precursor protein in adolescent and adult female offspring and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin-dependent kinase II ratio in adolescent male and female rats. Altogether, the results show that prenatal morphine exposure, depending on the time or duration of exposure, has distinct effects on male and female rats, and postnatal development may reverse these deficits more likely in males.     

Rational design of yolk–shell nanostructures for drug delivery

Yolk–shell nanoparticles (YSNPs) are a new class of hollow nanostructures, and their unique properties can be utilized in drug delivery systems. The recent progress in YSNPs-based carriers is highlighted in drug delivery systems. Doxorubicin hydrochloride, ceftriaxone sodium, and methotrexate are three of the most common drugs that are used in this field. According to the reported studies, the materials used most often as yolk–shells are magnetic nanoparticles and polymers. The used methods for synthesizing a diverse array of YSNPs are classified based on their core structures. Various properties of YSNPs include their high drug-loading capacity, and their ability to decrease drug toxicity and satisfactorily and efficiently release drugs.

The recent progress in yolk–shell nanoparticles (YSNPs) as a new class of hollow nanostructures applied for drug delivery.     

Long-term effects of sprint interval training on expression of cardiac genes involved in energy efficiency

Purpose

The real mechanisms of intensive exercise training-induced energy efficiency have not yet been well examined. Therefore, the aim of the present study was to investigate the effects of sprint interval training (SIT) on gene expression of uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS).

Methods

For this purpose, 16 Albino Wistar rats (250–300 g) were randomly divided into equal groups of control and sprint training. The animals run on treadmill for 10 weeks, 5 days per week at intensity corresponding to 90–95% maximal oxygen consumption. The gene expression of UCP2, UCP3 and eNOS was analyzed by RT-PCR method in hearts. The data were analyzed by independent samples T test at P?<?0.05 level.

Results

Sprint interval training significantly decreased mRNA expression of UCP2 (t₁₄?=?4.818, P?=?0.001) and UCP3 (t₁₄?=?4.620, P?=?0.001) in cardiac muscle of rats. In contrast, mRNA expression of eNOS in cardiac muscle significantly increased following sprint interval training (t₁₄?=?7.967, P?=?0.001).

Conclusion

This study elucidates that SIT through reduction in gene expression of uncoupling proteins can improve energy efficiency. But, more studies are needed to confirm this hypothesis.

     

Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials

Journal of Neurology - The Present study was conducted to systematically review the effect of the melatonin on sleep quality. We summarized evidence from randomized clinical trials (RCTs) that...     

Hospital-acquired infections in a tertiary hospital in Iran before and during the COVID-19 pandemic

Wiener Medizinische Wochenschrift - Infection prevention protocols are the accepted standard to control nosocomial infections. These protective measures intensified after the coronavirus 2019...     

The effects of low-level laser irradiation on breast tumor in mice and the expression of Let-7a,miR-155, miR-21, miR125, and miR376b

Low-level laser therapy (LLLT) is a form of photon therapy which can be a non-invasive therapeutic procedure in cancer therapy using low-intensity light in the range of 450–800 nm. One of the main functional features of laser therapy is the photobiostimulation effects of low-level lasers on various biological systems including altering DNA synthesis and modifying gene expression, and stopping cellular proliferation. This study investigated the effects of LLLT on mice mammary tumor and the expression of Let-7a, miR155, miR21, miR125, and miR376b in the plasma and tumor samples. Sixteen mice were equally divided into four groups including control, and blue, green, and red lasers at wavelengths of 405, 532, and 632 nm, respectively. Weber Medical Applied Laser irradiation was carried out with a low power of 1–3 mW and a series of 10 treatments at three times a week after tumor establishment. Tumor volume was weekly measured by a digital vernier caliper, and qRT-PCR assays were performed to accomplish the study. Depending on the number of groups and the p value of the Kolmogorov-Smirnov test of normality, a t test, a one-way ANOVA, or a non-parametric test was used for data analyses, and p?<?0.05 was considered to be statistically significant. The average tumor volume was significantly less in the treated blue group than the control group on at days 21, 28, and 35 after cancerous cell injection. Our data also showed an increase of Let-7a and miR125a expression and a decrease of miR155, miR21, and miR376b expression after LLLT with the blue laser both the plasma and tumor samples compared to other groups. It seems that the non-invasive nature of laser bio-stimulation can make LLLT an attractive alternative therapeutic tool.