Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.

Neurodegenerative diseases are characterized by progressive deterioration of the nervous system. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are prominently life-threatening examples of neurodegenerative diseases. The complexity of the pathophysiology in neurodegenerative diseases causes difficulties in diagnosing. Although the drugs temporarily help to correct specific symptoms including memory loss and degeneration, a complete treatment has not been found yet. New therapeutic approaches have been developed to understand and treat the underlying pathogenesis of neurodegenerative diseases. With this purpose, clustered-regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) technology has recently suggested a new treatment option. Editing of the genome is carried out by insertion and deletion processes on DNA. Safe delivery of the CRISPR/Cas system to the targeted cells without affecting surrounding cells is frequently investigated. Extracellular vesicles (EVs), that is exosomes, have recently been used in CRISPR/Cas studies. In this review, CRISPR/Cas and EV approaches used for diagnosis and/or treatment in AD, PD, ALS, and HD are reviewed. CRISPR/Cas and EV technologies, which stand out as new therapeutic approaches, may offer a definitive treatment option in neurodegenerative diseases.

Gender-related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model.

Epileptic seizures are seen as a result of changing excitability balance depending on the deterioration in synaptic plasticity in the brain. Neuroplastin, and its related molecules which are known to play a role in synaptic plasticity, neurotransmitter activities that provide balance of excitability and, different neurological diseases, have not been studied before in epilepsy. In this study, a total of 34 Sprague-Dawley male and female rats, 2 months old, weighing 250-300 g were used. The epilepsy model in rats was made via pentylenetetrazole (PTZ). After the completion of the experimental procedure, the brain tissue of the rats were taken and the histopathological changes in the hippocampus and cortex parts and the brain stem were investigated, as well as the immunoreactivity of the proteins related to the immunohistochemical methods. As a result of the histopathological evaluation, it was determined that neuron degeneration and the number of dilated blood vessels in the hippocampus, frontal cortex, and brain stem were higher in the PTZ status epilepticus (SE) groups than in the control groups. It was observed that neuroplastin and related proteins TNF receptor-associated factor 6 (TRAF6), Gamma amino butyric acid type A receptors [(GABA(A)], and plasma membrane Ca2+ ATPase (PMCA) protein immunoreactivity levels increased especially in the male hippocampus, and only AMPA receptor subunit type 1 (GluA1) immunoreactivity decreased, unlike other proteins. We believe this may be caused by a problem in the mechanisms regulating the interaction of neuroplastin and GluA1 and may cause problems in synaptic plasticity in the experimental epilepsy model. It may be useful to elucidate this mechanism and target GluA1 when determining treatment strategies.

Tauroursodeoxycholic Acid (TUDCA) Regulates Inflammation and Hypoxia in Autonomic Tissues of Rats with Seizures.

Inflammation and hypoxia have an effect on the molecular mechanism of cardiovascular and respiratory pathologies accompanying seizures. Against this, Tauroursodeoxycholic Acid (TUDCA) can regulate oxidative stress, inflammation and cellular survival by suppressing endoplasmic reticulum (ER) stress. We evaluated the expression changes of NF-κB p65, TNF-α, HIF1α and Kir6.2 proteins associated with seizures in brain stem, heart and lung tissues representing the autonomous network. Additionally, we examined the protective effects of TUDCA administration against damage caused by seizures in terms of immunohistochemistry and pathology. 4 groups of Wistar Albino male rats (250-300 g, n=32) were formed as control, pentylenetetrazole (PTZ), TUDCA and PTZ+TUDCA. The epilepsy kindling model was created by intraperitoneal (i.p.) injection of PTZ chemical (35 mg/kg, every 2 days) for one month. TUDCA (500 mg/kg; every 2 days) treatment was given intraperitoneally 30 minutes before seizures for 1 month. Brain stem, heart (atria, ventricle) and lung tissues of rats were isolated. NF-κB p65, TNF-α, HIF1α and Kir6.2 proteins in the obtained tissues were evaluated by immunohistochemical staining. The immunoreactivity of the investigated proteins in the brainstem heart and lung tissues of rats with chronic PTZ administration was significantly increased. Recurrent seizures led to accumulation of inflammatory cells in tissues, hemorrhage, vasodilation, and apoptosis. Following TUDCA administration, expression of NF-κB p65, TNF-α and Kir6.2 was significantly reduced in all tissues (except the atrium of the heart) compared to control rats. HIF-1α levels were significantly suppressed in ventricular and lung tissues of epileptic rats given TUDCA. However, TUDCA pretreatment improved histopathological changes due to chronic seizures and partially reduced apoptosis. We showed that epileptic seizures may cause tissue damage with the development of inflammatory and hypoxic conditions in the brainstem and organs that represent the autonomic network. TUDCA therapy could be an effective agent in the treatment of cardiac and respiratory problems associated with seizures.

Oxidative response of sheep to transcervical applications.

This study aimed to investigate the stress-related changes that may occur in sheep following non-surgical cervical line passage. A total of 20 sheep underwent transcervical transition, and their heart rate, respiratory rate, body temperature, and blood samples were collected at specific time points: 1 h prior to the procedure, immediately after the procedure, and at 1, 2, 3, 4 and 5 h post-procedure. The study found that there was a statistically significant decrease in body temperature immediately after the procedure (p < .05); however, there were no significant differences in body temperature at other time points (p > .05). Respiratory rate remained similar throughout the study, and no significant differences were observed (p > .05). On the other hand, there was a significant increase in heart rate at the 1-h mark after the procedure (p < .05), which subsequently decreased to a similar level as the control group at the 4-h mark after the procedure (p > .05). The cortisol levels increased significantly after the application (p < .05) but decreased to a level similar to the control after 1 h (p > .05). The level of nitric oxide increased significantly in the first hour (p < .05) and decreased by the 5th hour (p < .05). There was a significant increase in malondialdehyde (MDA) and total oxidant capacity (TOC) levels 2 h after the application (p < .05), but this increase ceased at the 4th and 5th hours for MDA (p > .05) and at the 3rd, 4th and 5th hours for TOC (p > .05). The total antioxidant capacity decreased after the 2nd hour of application (p < .05) but remained similar at the fourth and 5th hours (p > .05). In conclusion, based on the cortisol data, transcervical manipulations create short-term stress. Therefore, it may be necessary to use various antioxidants before such procedures to reduce the effects of oxidative stress.

Functional characterization of KCNMA1 mutation associated with dyskinesia, seizure, developmental delay, and cerebellar atrophy.

KCNMA1 located on chromosome 10q22.3, encodes the pore-forming α subunit of the 'Big K+' (BK) large conductance calcium and voltage-activated K + channel. Numerous evidence suggests the functional BK channel alterations produced by different KCNMA1 alleles may associate with different symptoms, such as paroxysmal non kinesigenic dyskinesia with gain of function and ataxia with loss of function. Functional classifications revealed two major patterns, gain of function and loss of function effects on channel properties in different cell lines. In the literature, two mutations have been shown to confer gain of function properties to BK channels: D434G and N995S. In this study, we report the functional characterization of a variant which was previously reported the whole exome sequencing revealed bi-allelic nonsense variation of the cytoplasmic domain of calcium-activated potassium channel subunit alpha-1 protein. To detect functional consequences of the variation, we parallely conducted two independent approaches. One is immunostaining using and the other one is electrophysiological recording using patch-clamp on wild-type and R458X mutant cells to detect the differences between wild-type and the mutant cells. We detected the gain of function effect for the mutation (NM_001161352.1 (ENST00000286628.8):c.1372C > T;Arg458*) using two parallel approaches. According to the result we found, the reported mutation causes the loss of function in the cell. It should be noted that in future studies, it can be thought that the functions of genes associated with channelopathies may have a dual effect such as loss and gain.

The increase in c-fos expression in epileptic seizures is inhibited by magnetic field application, but not KCa1.1 channel expression.

The aim of this study was to understand the expression of big potassium (BK, KCa1.1) channels in epileptic seizures under magnetic field application. Forty Wistar albino adult male rats were divided into five groups (n = 8). First group rats were control group. Pentylenetetrazole (PTZ) administrated to second group rats to induce the seizures with 35 mg/kg intraperitoneally injection every two days. Levetiracetam (LEV) i.p. at a dose of 108 mg/kg was given to third group rats as positive control group (PC) before 20 minutes PTZ administration. Pulsed magnetic field with 1.5 mT was exposed to the fourth group rats for 3 hours a day for 1 month as magnetic field (MF) group. 1.5 mT pulsed magnetic field was exposed to the fifth group rats for 3 hours a day for 1 month in addition to PTZ administration (PTZ+MF). KCa1.1 not changed in hippocampus of PTZ rats while increased in frontal cortex and pons for PTZ group but not changed with magnetic field exposure. KCa1.1 increased in heart of PTZ animals and turned back to mean control values with magnetic field exposure. Suppressing the expected increase of c-fos protein expression in seizures with magnetic field application but not being able to change the KCa1.1 expression shows that new studies can be done by increasing the frequency of 1.5 mT magnetic field.

Sepsis-induced cardiomyopathy in animals: From experimental studies to echocardiography-based clinical research.

The term "sepsis-induced cardiomyopathy" (SIC) is used to describe transient cardiac dysfunction in septic patients. However, there is no universally accepted definition of SIC; a reduction in left ventricular ejection fraction (LVEF) is often used. In addition to systolic dysfunction, diastolic dysfunction is now recognized as an essential component of SIC. It can be emphasized that previous animal experiments played an essential role in revealing SIC and hemodynamic instability in sepsis and septic shock. The diagnostic and prognostic capabilities of echocardiography for the assessment of SIC have been extensively studied since its introduction into intensive care clinical practice. Recent studies in dogs, calves, and horses have shown that left and right ventricular systolic dysfunction, left ventricular diastolic dysfunction, and circulatory dysfunction can occur in sepsis, severe sepsis, and septic shock in animals. Echocardiographic variables have also shown that indices of left and right ventricular dysfunction and circulatory failure are valuable indicators of mortality in septic animals.

Cardiomyopathie induite par la septicémie chez l'animal : des études expérimentales à la recherche clinique basée sur l'échocardiographie. Le terme « cardiomyopathie induite par la septicémie ¼ (SIC) est utilisé pour décrire un dysfonctionnement cardiaque transitoire chez les patients septiques. Cependant, il n'y a pas de définition universellement acceptée du SIC; une réduction de la fraction d'éjection ventriculaire gauche (FEVG) est souvent utilisée. En plus de la dysfonction systolique, la dysfonction diastolique est maintenant reconnue comme une composante essentielle du SIC. On peut souligner que les expérimentations animales antérieures ont joué un rôle essentiel dans la révélation du SIC et de l'instabilité hémodynamique dans la septicémie et le choc septique. Les capacités diagnostiques et pronostiques de l'échocardiographie pour l'évaluation du SIC ont été largement étudiées depuis son introduction dans la pratique clinique des soins intensifs. Des études récentes sur des chiens, des veaux et des chevaux ont révélé qu'un dysfonctionnement systolique ventriculaire gauche et droit, un dysfonctionnement diastolique ventriculaire gauche et un dysfonctionnement circulatoire peuvent survenir dans la septicémie, la septicémie sévère et le choc septique chez les animaux. Les variables échocardiographiques ont également démontré que les indices de dysfonctionnement ventriculaire gauche et droit et d'insuffisance circulatoire sont des indicateurs précieux de la mortalité chez les animaux septiques.(Traduit par Dr Serge Messier).

Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy.

Epilepsy is a devastating neurological disorder characterized by recurrent seizures attributed to the disruption of the dynamic excitatory and inhibitory balance in the brain. Epilepsy has emerged as a global health concern affecting about 70 million people worldwide. Despite recent advances in pre-clinical and clinical research, its etiopathogenesis remains obscure, and there are still no treatment strategies modifying disease progression. Although the precise molecular mechanisms underlying epileptogenesis have not been clarified yet, the role of ion channels as regulators of cellular excitability has increasingly gained attention. In this regard, emerging evidence highlights the potential implication of inwardly rectifying potassium (Kir) channels in epileptogenesis. Kir channels consist of seven different subfamilies (Kir1-Kir7), and they are highly expressed in both neuronal and glial cells in the central nervous system. These channels control the cell volume and excitability. In this review, we discuss preclinical and clinical evidence on the role of the several subfamilies of Kir channels in epileptogenesis, aiming to shed more light on the pathogenesis of this disorder and pave the way for future novel therapeutic approaches.

Cardiorespiratory findings in epilepsy: A recent review on outcomes and pathophysiology.

Epilepsy is a debilitating disorder of uncontrollable recurrent seizures that occurs as a result of imbalances in the brain excitatory and inhibitory neuronal signals, that could stem from a range of functional and structural neuronal impairments. Globally, nearly 70 million people are negatively impacted by epilepsy and its comorbidities. One such comorbidity is the effect epilepsy has on the autonomic nervous system (ANS), which plays a role in the control of blood circulation, respiration and gastrointestinal function. These epilepsy-induced impairments in the circulatory and respiratory systems may contribute toward sudden unexpected death in epilepsy (SUDEP). Although, various hypotheses have been proposed regarding the role of epilepsy on ANS, the linking pathological mechanism still remains unclear. Channelopathies and seizure-induced damages in ANS-control brain structures were some of the causal/pathological candidates of cardiorespiratory comorbidities in epilepsy patients, especially in those who were drug resistant. However, emerging preclinical research suggest that neurotransmitter/receptor dysfunction and synaptic changes in the ANS may also contribute to the epilepsy-related autonomic disorders. Thus, pathological mechanisms of cardiorespiratory dysfunction should be elucidated by considering the modifications in anatomy and physiology of the autonomic system caused by seizures. In this regard, we present a comprehensive review of the current literature, both clinical and preclinical animal studies, on the cardiorespiratory findings in epilepsy and elucidate the possible pathological mechanisms of these findings, in hopes to prevent SUDEP especially in patients who are drug resistant.

Envisioning the crosstalk between environmental enrichment and epilepsy: A novel perspective.

Epilepsies are a diverse group of neurological disorders characterized by an unprovoked seizure and a brain that has an enduring predisposition to seizures. The lack of disease-modifying treatment strategies against the same has led to the exploration of novel treatment strategies that could halt epileptic seizures. In this regard, environmental enrichment (EE) has gained increased attention in recent days. EE modulates the effects of interactions between the genes and the environment on the structure and function of the brain. EE therapy can improve seizure-related symptoms in neurological diseases such as epilepsy. EE therapy can have a significant effect on cognitive disorders such as learning and memory impairments associated with seizures. EE therapy in epileptic hippocampus tissue can improve seizure-related symptoms by inducing enhanced neurogenesis and neuroprotective mechanisms. In this context, the efficiency of EE is regulated in the epilepsy by the brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase (ERK) signaling pathway regulated by extracellular signaling. Herein, we provide experimental evidence supporting the beneficial effects of EE in epileptic seizures and its underlying mechanism.

The role of P-glycoprotein (P-gp) and inwardly rectifying potassium (Kir) channels in sudden unexpected death in epilepsy (SUDEP).

Sudden unexpected death in epilepsy (SUDEP) is the major cause of death that affects patients with epilepsy. The risk of SUDEP increases according to the frequency and severity of uncontrolled seizures; therefore, SUDEP risk is higher in patients with refractory epilepsy (RE), in whom most antiepileptic drugs (AEDs) are ineffective for both seizure control and SUDEP prevention. Consequently, RE and SUDEP share a multidrug resistance (MDR) phenotype, which is mainly associated with brain overexpression of ABC-transporters such as P-glycoprotein (P-gp). The activity of P-gp can also contribute to membrane depolarization and affect the normal function of neurons and cardiomyocytes. Other molecular regulators of membrane potential are the inwardly rectifying potassium channels (Kir), whose genetic variants have been related to both epilepsy and heart dysfunctions. Although it has been suggested that dysfunctions of the cardiac, respiratory, and brainstem arousal systems are the causes of SUDEP, the molecular basis for explaining its dysfunctions remain unknown. In rats, repetitive seizures or status epilepticus induced high expression of P-gp and loss Kir expression in the brain and heart, and promoted membrane depolarization, malignant bradycardia, and the high rate of mortality. Here we reviewed clinical and experimental evidences suggesting that abnormal expression of depolarizing/repolarizing factors as P-gp and Kir could favor persistent depolarization of membranes without any rapid functional recovery capacity. This condition induced by convulsive stress could be the molecular mechanism leading to acquired severe bradycardia, as an ineffective heart response generating the appropriate scenario for SUDEP development. This article is part of the Special Issue "NEWroscience 2018".

Enlightening the neuroprotective effect of quercetin in epilepsy: From mechanism to therapeutic opportunities.

Epilepsy is a devastating neurological disorder characterized by the repeated occurrence of epileptic seizures. Epilepsy stands as a global health concern affecting around 70 million people worldwide. The mainstream antiepileptic drugs (AEDs) only exert symptomatic relief and drug-resistant epilepsy occurs in up to 33 percent of patients. Hence, the investigation of novel therapeutic strategies against epileptic seizures that could exert disease modifying effects is of paramount importance. In this context, compounds of natural origin with potential antiepileptic properties have recently gained increasing attention. Quercetin is a plant-derived flavonoid with several pharmacological activities. Emerging evidence has demonstrated the antiepileptic potential of quercetin as well. Herein, based on the available evidence, we discuss the neuroprotective effects of quercetin against epileptic seizures and further analyze the plausible underlying molecular mechanisms. Our review suggests that quercetin might be a potential therapeutic candidate against epilepsy that deserves further investigation, and paves the way for the development of plant-derived antiepileptic treatment approaches.

Neopterin, procalcitonin, clinical biochemistry, and hematology in calves with neonatal sepsis.

This study aims to determine how neopterin, procalcitonin, biochemical and hematological parameters change during treatment of calves with neonatal sepsis. A total of 25 calves divided into two groups. Sepsis group was composed of 15 newborn calves aged 0-10 days which met neonatal sepsis criteria, but did not receive any treatment. Control group included 10 healthy calves aged 0-10 days. Clinical examinations (respiratory rate, rectal temperature, heart rate, capillary refill time, sucking reflex) were performed at certain times before (0th h) and during (12th, 24th, 48th, and 72th h) the treatment. The blood was taken from the jugular vein from the sepsis group before (0th h) and during the treatment (12th, 24th, 48th, and 72nd h) and once from the control group. Procalcitonin pretreatment (0th h) and control group concentrations were found as 178.08 ± 2.4 (pg/mL) and 42.78 ± 1.25 (pg/mL), respectively (p < 0.001). Neopterin pretreatment (0th h) and control group concentrations were determined as 14.44 ± 0.30 (ng/mL) and 3.63 ± 0.29 (ng/mL), respectively (p < 0.001). As a result, neopterin and procalcitonin concentration decreased along with the treatment, confirming the presence of sepsis in calves and suggesting that sepsis could be a prognostic indicator. Therefore, both procalcitonin and neopterin can be prognostic and diagnostic in calves with sepsis.

Role of Innate Immune Receptor TLR4 and its endogenous ligands in epileptogenesis.

Understanding the interplay between the innate immune system, neuroinflammation, and epilepsy might offer a novel perspective in the quest of exploring new treatment strategies. Due to the complex pathology underlying epileptogenesis, no disease-modifying treatment is currently available that might prevent epilepsy after a plausible epileptogenic insult despite the advances in pre-clinical and clinical research. Neuroinflammation underlies the etiopathogenesis of epilepsy and convulsive disorders with Toll-like receptor (TLR) signal transduction being highly involved. Among TLR family members, TLR4 is an innate immune system receptor and lipopolysaccharide (LPS) sensor that has been reported to contribute to epileptogenesis by regulating neuronal excitability. Herein, we discuss available evidence on the role of TLR4 and its endogenous ligands, the high mobility group box 1 (HMGB1) protein, the heat shock proteins (HSPs) and the myeloid related protein 8 (MRP8), in epileptogenesis and post-traumatic epilepsy (PTE). Moreover, we provide an account of the promising findings of TLR4 modulation/inhibition in experimental animal models with therapeutic impact on seizures.

The protective role of melatonin against the effects of different doses of caffeine on the fetus.

Skeletal system and some organs development changes in rat fetuses with 30 and 60 mg/kg caffeine and melatonin's (10 mg/kg) protective role against rat fetuses were investigated. Groups (n = 4) were formed as Control, LDC, HDC, LDC+melatonin, HDC+melatonin and melatonin. Fetuses were taken by cesarean section and stained using dual skeletal staining method and FESEM. TRAP and AP immune-reactivity concentrations were calculated.  Oxidative stress and inflammatory markers were also measured by liver, bone and placenta samples.  TNF-α, IL-1ß, IL-6, VEGF-A, SOST and Fetuin-A levels were measured in tissue by using ELISA. TBARS, SOD, GSH, GSSG, TOS, TAS, measured by spectrophotometric assay method.  The mRNA levels of Agtr2 gene expressed in placental tissues of control rats and in placental tissues of rats exposed to HDC, LDC, MEL, HDC+MEL, LDC+MEL were analyzed by Real-time PCR. The gene expressions of Agtr2 were significantly upregulated in the placentas exposed to HDC, MEL, HDC+MEL and LDC+MEL (P<0,001). No significant difference in samples of the LDC group (P>0,05). According to these data, caffeine used during pregnancy delayed ossification; melatonin, a powerful antioxidant, was found to eliminate this effect. Besides, changes in angiotensin receptor expression observed in response to a caffeine and melatonin exposure result from high dose and join effect.

Expression of cardiac inwardly rectifying potassium channels in pentylenetetrazole kindling model of epilepsy in rats.

Clinical and experimental studies show that epilepsy affects cardiac function; however, the underlying molecular mechanism has not been fully elucidated. Inwardly-rectifying potassium (Kir) channels transport K+ ions into excitable cells such as neurons and cardiomyocytes; they control the cell excitability by acting towards the repolarization phase of cardiac action potential. Kir channel expression has been previously shown to vary in epileptic brains, at the same time seizures are known to affect the autonomic nervous system. Kir channel expression in cardiac tissue is a possible mechanism for the explanation of cardiac pathology in epilepsy. We investigate the expression of Kir channels in epileptic cardiac tissue by using pentylenetetrazole (PTZ)-kindling model in rats. Our molecular analyses showed significant decrease in cardiac Kir channel mRNA and protein expression of PTZ-kindled rats. Interestingly, both Kir2.x, which directs IK1 flux in ventricular tissue and Kir3.x, which is responsible for IKACh in the atria, were observed to decrease significantly. Kir channel expression also differs between females and males. This is the first study to our knowledge in epileptic cardiac tissue showing the expression of Kir channels. Our results show that Kir channels may play a role in cardiac pathology associated with epilepsy.

The evaluation of antioxidant and anticancer effects of Lepidium Sativum Subsp Spinescens L. methanol extract on cancer cells.

In recent years, there is an increased research interest for plants which are natural sources of antioxidants. Lepidium sativum Subsp spinescens L., commonly found in South West Asia, is a plant known as a healthy nutritional source containing bio-molecules that carry anti-hypertensive, hypoglycemic, anti-asthmatic, antispasmodic, hepato-protective, chemoprotective, anti-inflammatory and anti-oxidant effects. In this study, we aimed to investigate the antioxidant content and activity of Lepidium sativum Subsp spinescens L. methanol extract on cancer cells. Methanol extract of dried Lepidium sativum Subsp spinescens L. was prepared. Total amount of phenolic compounds was determined by Slinkard and Singleton method using Folin-Ciocalteu reagent. Total flavonoid amount was determined according to Zhishen method. Antioxidant activity of the extract was evaluated by CUPRAC and ABTS radical scavenging activity assays. Cytotoxic effects of the plant extract on colon and endometrium cancer cells, and human peripheral lymphocyte cells were investigated in vitro by MTT and neutral red assays. Furthermore, the plant extract was investigated for necrotic effects by LDH assay; apoptotic activity by DNA ladder fragmentation, ELISA and acridine orange/ethidium bromide staining; and genotoxic effect by comet assay methods. Methanol extract of Lepidium sativum Subsp spinescens L. was found to have a high content of phenolic and flavonoid compounds. The extract showed significant antioxidant activity and also cytotoxic activity on colon and endometrium cancer cells in a concentration-dependent manner. Apoptotic activity and genotoxic effects were significantly increased, especially with 200 µg/ml concentrations at 48 hours incubation. In conclusion, it was determined that the extract evaluated in this study could be a natural source of antioxidants. Further molecular studies explaining chemo-preventive and chemotherapeutic effects on cancer cells are required to support anticancer efficacy of the plant.

Attitudes toward COVID-19 vaccines during pregnancy and breastfeeding.

Background: Although vaccination is one of the most effective means of controlling the spread of COVID-19, public concerns and indecision about vaccination still continue. Because pregnant and breastfeeding individuals are at high risk for severe outcomes in case of infections, determining their level of hesitation and attitude toward COVID-19 vaccines will guide the management of the disease. This study aimed to determine pregnant and breastfeeding women's levels of hesitation and attitude toward COVID-19 vaccines as well as their related factors. Methods: The sample of this descriptive research consisted of 103 pregnant or breastfeeding individuals who were seen at the obstetrics and gynecology outpatients clinic of a state hospital in Istanbul, Turkey. The data were collected using a 'demographic data form', the 'Vaccine Hesitancy Scale in Pandemic', and the 'Attitudes toward COVID-19 Vaccine Scale'. The research data were analyzed with appropriate statistical methods. Results: The mean age of the participants was 29.71 ± 4.75, 51% were pregnant, and 74.8% had received the COVID-19 vaccine. The mean score of the 'Vaccination Hesitancy Scale in Pandemic' was 30.83 ± 6.91, and the mean score for the 'Attitude Scale toward the COVID-19 Vaccine' was 25.50 ± 5.20. A significant difference was found between the total score of the 'Vaccine Hesitation Scale in the Pandemic' and the mean score of the 'Lack of Confidence' sub-dimension between the 'working status' and the 'influenza vaccination' status. In terms of the mean score of the 'Risk' sub-dimension, a significant difference was found between the 'period of vaccination' (p < 0.05). According to the mean total score of the 'Attitude Towards COVID-19 Vaccine Scale', there was a significant difference between the 'smoking' status. There was a significant difference in the 'Positive Attitude' sub-dimension in terms of the 'flu vaccination' status. There was a significant difference in the 'Negative Attitude' sub-dimension in terms of the 'chronic disease' status. A positive correlation was found between the total scores of the scales. Conclusion: It was concluded that although the participants had a high level of hesitation toward the COVID-19 vaccine, they had a positive attitude. The results obtained will be guided in determining the strategies to be developed for these specific groups in future pandemics.

Effect of birth type and sex on growth performance, wither height, humerus-radius bone dimensions, humerus-ulna growth plate width and selected hormone profile in growing Gurcu goat kids.

OBJECTIVES: In this study, the effects of sex and birth type on growth performance, withers height (WH), radiographic measurements and selected hormone profiles in Gurcu goat kids were investigated. METHODS: Twenty kids (single female = 5, single male = 5, twin female = 5, twin male = 5) were included in the study. Body weight (BW), WH, radiographic measurements (humerus length [HL], radius length [RL], proximal humerus epiphyseal plate width [HEP] and distal ulna epiphyseal plate width [UEP]) and biochemical analysis (for serum calcitonin, free triiodothyronine [FT3], free thyroxine [FT4], growth hormone [GH] and insulin-like growth factor-I [IGF-I]) were performed at 1, 3, 5, 7, 9 and 12 months of age. RESULTS: BW was significantly higher in males starting from the seventh month compared to females (p < 0.05). HL was higher in males at seventh (p = 0.009) and ninth (p = 0.033) months, whereas RL was lower in twins at the third month (p = 0.021). UEP was wider in males at seventh (p = 0.008) and ninth (p = 0.036) months. Closure of HEP was observed in 65% of kids by the 12th month. Calcitonin was lower in twins at third (p = 0.045) and fifth (p = 0.006) months, with changes observed due to group and time effects (p < 0.05), whereas other hormones only changed with time (p < 0.05). Positive correlations were observed between BW, WH, HL, RL and IGF-I. There was a negative correlation between BW, WH, HL, RL, IGF-I and HEP, UEP, calcitonin, FT3, FT4, GH. CONCLUSION: Sex and birth type in Gurcu goat kids may have an impact on growth performance, radiographic measurements and certain hormonal profiles.

An Expanded Narrative Review of Neurotransmitters on Alzheimer's Disease: The Role of Therapeutic Interventions on Neurotransmission.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-ß (Aß) plaques and tau neurofibrillary tangles are the key players responsible for the pathogenesis of the disease. The accumulation of Aß plaques and tau affect the balance in chemical neurotransmitters in the brain. Thus, the current review examined the role of neurotransmitters in the pathogenesis of Alzheimer's disease and discusses the alterations in the neurochemical activity and cross talk with their receptors and transporters. In the presence of Aß plaques and neurofibrillary tangles, changes may occur in the expression of neuronal receptors which in turn triggers excessive release of glutamate into the synaptic cleft contributing to cell death and neuronal damage. The GABAergic system may also be affected by AD pathology in a similar way. In addition, decreased receptors in the cholinergic system and dysfunction in the dopamine neurotransmission of AD pathology may also contribute to the damage to cognitive function. Moreover, the presence of deficiencies in noradrenergic neurons within the locus coeruleus in AD suggests that noradrenergic stimulation could be useful in addressing its pathophysiology. The regulation of melatonin, known for its effectiveness in enhancing cognitive function and preventing Aß accumulation, along with the involvement of the serotonergic system and histaminergic system in cognition and memory, becomes remarkable for promoting neurotransmission in AD. Additionally, nitric oxide and adenosine-based therapeutic approaches play a protective role in AD by preventing neuroinflammation. Overall, neurotransmitter-based therapeutic strategies emerge as pivotal for addressing neurotransmitter homeostasis and neurotransmission in the context of AD. This review discussed the potential for neurotransmitter-based drugs to be effective in slowing and correcting the neurodegenerative processes in AD by targeting the neurochemical imbalance in the brain. Therefore, neurotransmitter-based drugs could serve as a future therapeutic strategy to tackle AD.