Assessing the quantity of neuropeptide Y in the serum of patients referred to Baqiyatallah Hospital with covid-19 concerning inflammatory factors following steroid therapy.

PURPOSE: With the extensive presence of Covid-19, it is imperative to find compounds that can obstruct the virus's inflammatory activity and perhaps even stop the inflammatory phase from occurring. Several neuropeptides act as immune system regulators, which nerve terminals release as co-transmitters. It has been suggested that Neuropeptide Y (NPY) may be involved in inflammatory diseases through its ability to regulate the function of inflammatory cells. Consequently, the present study was designed to examine the changes in this neuropeptide in the serum of patients with Covid-19 disease, particularly following anti-inflammatory treatment, and its relationship with other inflammatory factors such as TNF-α. METHODS: The demographic information, vital and clinical signs (blood oxygen saturation level, blood pressure, heart rate, and body temperature), laboratory factors such as blood factors, inflammation, and blood electrolytes, as well as the use of steroids, were collected before and after steroid treatment the patient files. As part of the study, serum samples from patients were used to measure levels of NPY and TNF-α inflammatory factors using an ELISA kit. Additionally, the correlation between NPY values, other inflammatory factors, and other variables was examined before and after treatment. RESULTS: NPY, TNF-α, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels were significantly reduced after steroid treatment. But the blood urea nitrogen (BUN) factor level increased after treatment compared to the initial evaluation. Lymphocytes and neutrophils also changed after drug treatment. Results indicated a high correlation between NPY and TNF-α. In addition to TNF-α, NPY, creatinine, and BUN presented a direct and significant relationship. ESR and BUN factors showed a positive and significant correlation regarding the length of hospitalization. However, the correlation between NPY and TNF-α with hospitalization length was insignificant. CONCLUSION: Since the current study had a significant association between NPY and TNF-α, the regulating function of this peptide in Covid-19 inflammatory processes may be validated. Enough that it is crucial to consider NPY as a marker and its antagonist as a potential Covid-19 therapy. Also, the considerable reduction in NPY levels after steroid therapy to lower inflammatory variables supports the regulatory function of this peptide in inflammatory processes.

Electrophysiological analysis of ENG signals in patients with Covid-19.

Background: Currently, there is an increasing number of patients reporting dizziness, which has resulted in a positive COVID-19 PCR test. In this paper, we analyzed the ENG signals recorded from patients with a positive COVID-19 PCR test. Methods: In this paper, both linear and nonlinear analyses of time series were employed to determine the regularity and complexity of a recorded ENG signal. Results: The Wilcoxon rank-sum test indicated that the COVID-19 and non-COVID groups have significant differences based on different extracted features. Various machine learning methods including Linear Discriminant Analysis (LDA), Naïve Base (NB), K-nearest Neighbours (KNN), and Support Vector Machines (SVM) were used to classify COVID-19 and non-COVID groups. The best accuracy, precision and FCR achieved by SVM are 86%, 91% and 0.13. Conclusion: In this study, ENG signals were recorded from COVID-19 and control groups. Linear and non-linear features were extracted from the recorded signals to identify significantly different features. Subjects were classified based on SVM and different classifiers. The SVM (polynomial kernel) classifier showed the best result. The proposed method had not been used for the classification of COVID-19 and non-COVID-19 subjects before. This work helps other researchers conduct more research on the development of machine learning methods to diagnose the COVID-19 virus using ENG and other physiological signals.

Amelioration of pain and anxiety in sleep-deprived rats by intra-amygdala injection of cinnamaldehyde.

Background: Sleep disorders are accompanied by increased anxiety and somatic pain. In addition, it has been observed that anxiety and pain have a boosting effect on each other, resulting in continued sleep disturbances. Amygdala's (CeA) central nucleus plays a crucial role in these processes. Cinnamaldehyde (Cinn) is an aromatic compound with anti-anxiety, antioxidant, and sleep-promoting properties. The present study uses sleep-deprived rats to examine the effects of an intra-CeA injection of Cinn on pain and anxiety. Methods: Sleep deprivation (SD) was induced using the platform technique. 35 male Wistar rats were divided into five groups. Anxiety state and nociception were evaluated among groups using formalin test (F.T.), open field test (OFT), and elevated plus maze (EPM). Anxiety tests (OFT and EPM) were conducted in all groups. The first group was undergone FT without induction of SD (SD-FT+). The second group received SD without FT(SD+FT-). The third group received both SD and FT(SD+FT+). The treatment and vehicle groups have undergone both SD and FT in addition to the respectively intra-CeA injection of Cinn (SD+FT+ Cinn) and Cinn vehicle (SD+FT+ VC). The recorded behaviors were analyzed between groups using IBM SPSS 24th version. Results: SD did not lead to any significant difference in nociceptive behaviors in FT between groups SD-FT+ and SD+FT+ (P ≥ 0.05). At the same time, there was a considerable discrepancy in rearing behaviors (P < 0.006) and the number of fecal boli (P < 0.004) recorded in OFM between these groups. Treatment with Cinn led to decreased nociception (P < 0.038), decreased rearing behaviors (P < 0.01), and reduced defecation (P < 0.004) in group SD + FT+ Cinn in comparison to the group SD+FT+. There were no differences in anxiety test results between the first and second groups (P ≥ 0.05). Conclusion: SD can lead to elevated anxiety, while intra-CeA injection of Cinn ameliorated both perceptions of acute pain and anxiety. Besides, the conduction of FT before the anxiety test led to no disturbance in the results of anxiety tests.

Interaction effects of intracerebroventricular injection of crocin with the α2-adrenoceptors on memory deficit and hippocampal synaptic plasticity following chronic pain in rat.

Patients with chronic pain exhibit anxiety and deficits in memory. Additionally, α2-adrenoceptors that are wildly expressed in the brain have an important role in modulating both pain and memory formation. In the present study, we investigated the interaction effects of crocin with central α2-adrenoceptors on pain comorbidity and hippocampal synaptic plasticity changes following chronic constriction injury (CCI) of the sciatic nerve in rats. All the drugs (crocin, an antagonist (yohimbine) and agonist (clonidine) of α2-adrenergic receptors) were injected (via intracerebroventricular injection) from the day of CCI operation (day 0) and continued daily (once per day) until the 14th day post-CCI. The effects of drugs on the cold allodynia (using acetone test) and anxiety-like behaviors (using elevated plus maze, EPM and open field tests) were assessed. Spatial memory (using Barnes maze) was assessed on day 14 post-CCI operation. Hippocampal synaptic plasticity (using in-vivo extracellular field potential recording) was performed on day 14 post-CCI operation. We observed that crocin induced analgesic, anxiolytic and memory enhancer action following CCI surgery. Furthermore, crocin significantly increased long-term potentiation (LTP) (increased fEPSP slope and population spike amplitude). Furthermore, the co-injection of yohimbine effectively decreased analgesic, anxiolytic and enhancer action of crocin on the LTP parameters (fEPSP slope and population spike amplitude). Our study provided information that protective effects of crocin on pain/anxiety responses and synaptic plasticity were possibly mediated by central α2-adrenoceptor in the rats with chronic pain.

Investigation of how stimulation intensity of rTMS affects magneto permeabilization of the Blood-Brain Barrier (BBB).

The present study aimed to assess the effect of the rTMS (repetitive Transcranial Magnetic Stimulation) intensity on the permeability of the BBB for brain-targeted drug delivery. For this purpose, different rTMS intensities including 70%, 100%, and 130% of Resting Motor Threshold (RMT) assessed in three groups of rats (three groups of 5 rats). Stimulation applied over the right hemisphere of the animals. The first phase of the study was composed of intravenous administration of Evans Blue Dye (EBD), rTMS stimulation and EBD uptake measurement in both brain hemispheres. The second examination was included rTMS stimulation, injection of the MRI Contrast Agent (CA), and signal intensity measurement in post-contrast images. Each exam also included five rats in a sham group. Thus, the total of 40 male Wistar rats enrolled in this study. There was no significant difference in the amount of EBD accumulated between the right hemisphere of the brain in the sham group and the group with 70% RMT magnetic stimulation, while this figure was significantly higher than the sham group for both 100 and 130% RMT groups. There was also a significant difference in this index between 100 and 130% groups. All of the results from the first phase of the study were consistent with the second assessment representing an upward trend of induced permeability by rising rTMS intensity. The results of this study imply that to cause an effective temporary disruption in the BBB the intensity of 100% RMT or above should be used for stimulation.

The pro-convulsant effects of diazinon low dose in male rats under amygdala kindling.

Organophosphates can damage the brain in systemic intoxication. In this study, the effects of a minimum toxic dose (MTD) of diazinon (DZ) on amygdala afterdischarge threshold (ADT), kindling acquisition and kindled seizure parameters were evaluated. Intact male rats were stereotactically implanted with a tripolar and two monopolar electrodes in the amygdala and dura respectively. After recovery, animals received daily either, olive oil (control), 15 or 30 mg/kg (MTD) of DZ intraperitoneally, and ADT, afterdischarge duration (ADD) at each stage (S1 to S5) of kindling and number of trials for kindling acquisition were determined daily. Also, the effect of DZ on stage 4 latency (S4L), ADD, stage 5 duration (S5D) and the activity of the red blood cholinesterase (ChE) were evaluated. The ADT was lower and the ADD was longer significantly in DZ treated group in comparison to control (p < 0.01) and the number of trials to reach each stage of kindling acquisition was reduced (p < 0.001). The total amount of ADDs during the kindling procedure increased significantly 5 days after DZ treatment. While the S4L was reduced, the S5D increased significantly after DZ treatment. The ChE activity was inhibited significantly after 20 min of DZ treatment and continued till 24 h (p < 0.01). Data indicate that even half of the MTD of DZ could increase the sensitivity and excitability of the CNS to the epileptic activity at least via reduction of stimulation threshold and AD prolongation. Furthermore, repeated exposure to the low concentrations of organophosphates may be pro-convulsant and should be restricted.

Intracerebroventricular injection of propranolol blocked analgesic and neuroprotective effects of resveratrol following L5 spinal nerve ligation in rat.

OBJECTIVES: Resveratrol as a natural polyphenolic agent can alleviate neuropathic pain symptoms. The mechanism of analgesic activity of resveratrol is far from clear. The current study examine whether analgesic activity of resveratrol is mediated by its neuroprotective and anti-oxidant activity in the neuropathic pain. We further examine whether analgesic activity of resveratrol is mediated by ß-adrenoceptors in the brain. METHODS: Neuropathic pain induced by L5 spinal nerve ligation (SNL). Male Wistar rats assigned into sham, SNL, SNL + resveratrol (40 µg/5 µL), and SNL + resveratrol + propranolol (a non-selective ß-adrenoceptor antagonist, 30 µg/5 µL) groups. Drugs injected intracerebroventricular (ICV) at day SNL surgery and daily for 6 days following SNL. Thermal allodynia and anxiety examined on days of -1, 2, 4, and 6 following SNL. Electrophysiological study performed on day 6 following SNL for evaluation of resveratrol effects on sciatic nerve conduction velocity (NCV). The activity of catalase (Cat) and superoxide dismutase (SOD) enzymes in the brain assessed on days 6 following SNL. RESULTS: Resveratrol significantly decreased thermal allodynia (and not anxiety) in all experimental days. Additionally, resveratrol significantly increased NCV, and also normalized the disrupted Cat and SOD activities following neuropathic pain. Furthermore, propranolol significantly blocked the analgesic and neuroprotective effects of resveratrol. CONCLUSIONS: It is suggested that the analgesic effects of resveratrol is mediated by its neuroprotective and antioxidant activities in the neuropathic rats. Furthermore, propranolol blocked the analgesic and neuroprotective effects of resveratrol.

The effects of Valerian on sleep spindles in a model of neuropathic pain.

INTRODUCTION: Valeriana officinalis is known to be one of the most famous herbal supplements for the treatment of anxiety and insomnia. Despite its widespread use in most countries all around the world, there is little scientific information and research on how this medication affects sleep patterns, and there are almost no studies on its effects on the characteristics of sleep spindles. MATERIAL AND METHODS: The present study was conducted to investigate the effects of Valerian extract (VAL) on sleep spindles and induced anxiety in chronic neuropathic pain model in rats. 24 male rats were divided into three groups: neuropathic group (n=9) in which the rats underwent chronic constriction injury (CCI), sham group (n=7) in which the sciatic nerves of the animals were exposed without any constriction and also fed with the vehicle, and the third group was under CCI condition and treated with Valerian (n=8). All the rats underwent electrode implant surgery so that we could record electroencephalogram and electromyography waves. In all the three groups, EEG and EMG recordings were recorded three times (150min each time). The initial recording was just prior to the CCI surgery and the rest were 3 and 6 days following CCI surgery. Moreover, cold allodynia and elevated plus maze tests were performed 3 and 6 days following the CCI surgery. RESULTS: Valerian treatment could repair the allodynia induced by neuropathy. On the other hand, by Valerian treatment (400mg/kg) during neuropathy, the REM sleep, decreased and the non-REM sleep increased. Moreover, there was an increment in sleep spindle density and spindle frequency even in neuropathic condition. DISCUSSION: This herbal supplement improves the quality of sleep in neuropathy conditions.

Peroxisome Proliferator-activated Receptor (PPAR)-γ Modifies Aß Neurotoxin-induced Electrophysiological Alterations in Rat Primary Cultured Hippocampal Neurons.

Alzheimer's disease (AD) is undoubtedly one of the serious and growing public health challenges in the world today. There is an unmet need for new and effective preventative and therapeutic treatment approaches for AD, particularly at early stages of the disease. However, the underlying mechanism against Aß-induced electrophysiological alteration in cultured hippocampal pyramidal neurons is still not fully understood. This study investigated the impacts of activation and inhibition of PPAR-γ/δ on the Aß-induced functional toxicity, which occured before cell death, using patch clamp technique. Findings demonstrated that Aß treatment alone altered the normal electrophysiological properties and reduced the Ca2+ channel currents in primary cultured hippocampal pyramidal neurons without any major changes either in cell structure, as evidenced by electron microscope examination, or cell viability. Rosiglitazone (30 µM), a potent PPAR-γ activator, when co-treated with Aß (100 nM) prevented almost completely the induction of function toxicity of Aß, as evidentiated by restored normal appearing electrophysiological properties. Inhibition of PPAR- γ/δ by FH535 (15 µM), an inhibitor of both Wnt/beta-catenin signaling and PPAR- γ and δ activity, when applied in combination of Aß not only worsen the toxic electrophysiological effects of Aß on firing frequency, membrane resistance and cell viability, but also even preserved the suppressive effect of Aß on Ca2+ channel current when compared to control condition. Overall, these findings suggest that PPAR-γ activation could be a potential candidate to prevent the functional changes induced by low concentration of Aß which may possibly occur in neurons during early stages of AD.

Stretch Induces Invasive Phenotypes in Breast Cells Due to Activation of Aerobic-Glycolysis-Related Pathways.

It is increasingly being accepted that cells' physiological functions are substantially dependent on the mechanical characteristics of their surrounding tissue. This is mainly due to the key role of biomechanical forces on cells and their nucleus' shapes, which have the capacity to regulate chromatin conformation and thus gene regulations. Therefore, it is reasonable to postulate that altering the biomechanical properties of tissue may have the capacity to change cell functions. Here, the role of cell stretching (as a model of biomechanical variations) is probed in cell migration and invasion capacity using human normal and cancerous breast cells. By several analyses (i.e., scratch assay, invasion to endothelial barrier, real-time RNA sequencing, confocal imaging, patch clamp, etc.), it is revealed that the cell-stretching process could increase the migration and invasion capabilities of normal and cancerous cells, respectively. More specifically, it is found that poststretched breast cancer cells are found in low grades of invasion; they substantially upregulate the expression of manganese-dependent superoxide dismutase (MnSOD) through activation of H-Ras proteins, which subsequently induce aerobic glycolysis followed by an overproduction of matrix metalloproteinases (MMP)-reinforced filopodias. Presence of such invadopodias facilitates targeting of the endothelial layer, and increased invasive behaviors in breast cells are observed.

Crocin improved amyloid beta induced long-term potentiation and memory deficits in the hippocampal CA1 neurons in freely moving rats.

Extracellular beta-amyloid (Aß) accumulation and deposition is the main factor, which causes synaptic loss and eventually cells death in Alzheimer's disease (AD). Memory loss and long-term potentiation (LTP) dysfunction in the hippocampus are involved in the AD. The involvement of crocin, as the main and active constituent of saffron extract in learning and memory processes, has been proposed. Here we investigated the probable therapeutic effect of crocin on memory, LTP, and neuronal apoptosis using in vivo Aß models of the AD. The Aß peptide (1-42) was bilaterally administered into the frontal-cortex using stereotaxic apparatus. Five hours after surgery, rats were given intraperitoneal crocin (30 mg/kg) daily, which repeated for 12 days. Barnes maze results showed that administration of crocin significantly improves spatial memory indicators such as latency time to achieving the target hole and the number of errors when compared to Aß-group. Passive avoidance test revealed that crocin significantly increased the step-through-latency compared to Aß-treated alone. These learning deficits in Aß-treated animals correlated with a reduction of LTP in hippocampal CA1 synapses in freely moving rats, which crocin improved population spike amplitude and mean field excitatory postsynaptic potentials (fEPSP) slope reduction induced by Aß. Neuronal apoptosis was detected by TUNEL assay and the expression levels of c-Fos proteins were examined by Western blotting. Crocin significantly reduced the number of TUNEL-positive cells in the CA1 region and decreased c-Fos in the hippocampus compared to Aß-group. In vivo Aß treatment altered significantly the electrophysiological properties of CA1 neurons and crocin further confirmed a neuroprotective action against Aß toxicity.

Assessing the relationship of paraoxonase-1 Q192R polymorphisms and the severity of lung disease in SM-exposed patients.

Late respiratory complications in patients suffering from pulmonary lesions due to sulfur mustard (SM) gas are asthma, chronic obstructive pulmonary disease and bronchiectasis. Recently PON1 antioxidant activity draws attention as the enzyme which prevents the oxidation of lipoproteins during oxidative stress. In this study we aimed to investigate PON1 192 polymorphisms and paraoxonase and arylesterase activity in the serum of SM-exposed lung disease patients. Also, we examined the detection of PON1 and apoA1 proteins in BAL fluid. 101 male patients were included who were categorized to three groups of mild, moderate and severe suffering from pulmonary lesions due to SM. Significant reduction in paraoxonase activity [Healthy: 412.46 ± 89.1 U/L, Severe: 89.66 ± 20.7 U/L] (p < 0.0001) and arylesterase activity [Healthy: 25826.4 ± 4425.23 U/L, Severe: 16760.43 ± 3814.9 U/L] (p < 0.0001) with increase in severity of disease was demonstrated statistically. With respect to the distribution of the PON1 polymorphism, the RR genotype was more frequent in severe patients [37.2%] than healthy group [10%] (p < 0.05) and no significant regression was found between genotype and PON1 activity. On the other hand, the results of PON1 and apoA1 detection illustrated that only apoA1 protein was found in BAL fluid. According to our findings it seems that increase in the stress oxidative in chemical injured veterans with pulmonary complications comes with reduction in PON1 enzyme activity and appearance of RR genotype rises up with the increase in disease severity. Since a significant correlation between enzyme activity and genotype was not observed altering these two variables with each other requires more studies.

Antibiotic supplements affect electrophysiological properties and excitability of rat hippocampal pyramidal neurons in primary culture.

INTRODUCTION: Antibiotic supplements are regularly used in neuronal culture media to control contamination; however, they can interfere with the neuronal excitability and affect electrophysiological properties. Therefore, in this study, the effect of penicillin/streptomycin supplements on the spontaneous electrophysiological activity of hippocampal pyramidal neurons was examined. METHODS: Electrophysiological whole-cell patch-clamp recordings from rat hippocampal pyramidal cells in primary culture were performed to investigate the effects of antibiotic supplements on the intrinsic excitability of cultured cells. RESULTS: The present findings indicated that presence of antibiotic supplements (penicillin/streptomycin) in the culture medium altered the intrinsic electrical activity of hippocampal pyramidal neurons in primary culture. These alterations included: 1) depolarized resting membrane potential; 2) a significant enhancement in the after-hyperpolarization amplitude; 3) a significant increase in the area under the action potential and in the decay and rise time of the action potential; 4) a significant broadening of action potential and 5) a significant reduction in the firing frequency. CONCLUSION: These findings suggest that addition of antibiotic supplements to culture media influences the neuronal excitability and alters the electrophysiological properties of cultured neurons, possibly through changing the ionic conductance underlying neuronal excitability.

The effects of dopaminergic drugs in the ventral hippocampus of rats in the nicotine-induced anxiogenic-like response.

Nicotine an active alkaloid of tobacco has dopaminergic properties. The drug alters anxiety-like behavior in rodents. Ventral hippocampus (VHC) may be a site for modulation of anxiety-like behaviors. The possible involvement of ventral hippocampal dopaminergic receptor mechanism in the nicotine influence on anxiogenic-like response has been investigated in the present study. The effects of apomorphine, sulpiride and SCH23390 on nicotine response in elevated plus maze in rats have been investigated. Intraperitoneal administration of nicotine (0.6mg/kg) decreased percentage of open arm time (%OAT) but not percentage of open arm entries (%OAE) and locomotor activity, indicating an anxiogenic-like response. Intra-hippocampal injection (intra-VHC) of apomorphine, a D(1)/D(2) dopamine receptor agonist (0.1 and 0.2microg/rat) also caused anxiogenic-like effects, but the drug blocked that of nicotine. Intra-VHC administration of the D(2) receptor antagonist, sulpiride (1, 2.5 and 5microg/rat) or the D(1) receptor antagonist, SCH23390 (0.01, 0.1 and 1microg/rat) did not elicit any response. However, pretreatment with sulpiride (1microg/rat) or SCH23390 (0.1microg/rat) decreased nicotine's effect. The results may indicate a modulatory effect for the D(1) and D(2) dopamine receptors of VHC in the anxiogenic-like response induced by nicotine.

Cannabinoid receptor agonist WIN-55,212-2 protects differentiated PC12 cells from organophosphorus- induced apoptosis.

Cannabinoid neuroprotection is usually greater in vivo than in neuronal cell culture systems. To the authors' knowledge, a good in vitro culture model for the neuroprotective effects of cannabinoids does not exist. Therefore, a 3-dimensional (3D) culture system was developed to investigate the neuroprotective effects of the cannabinoid receptor agonist WIN-55,212-2 on apoptosis of differentiated PC12 cells, caused by the organophosphorus compounds paraoxon and diazinon. Cells pretreated with WIN-55,212-2 were exposed to a proapoptotic concentration of paraoxon and diazinon. TUNEL was used to detect apoptosis, and neurite length was assessed by morphometry. Both paraoxon and diazinon induced apoptosis, although the latter was more potent. WIN-55,212-2 also protected cells from neurite retraction and DNA fragmentation induced by the OPs. The results suggest that WIN-55,212-2 protects PC12 cells cultured under 3D conditions from organophosphorus-induced apoptosis. This 3D culture system may prove to be a useful tool for investigating the neuroprotective effects of cannabinoids.