Intermediate filament proteins are reliable immunohistological biomarkers to help diagnose multiple tissue-specific diseases.

Cytoskeletal networks are proteins that effectively maintain cell integrity and provide mechanical support to cells by actively transmitting mechanical signals. Intermediate filaments, which are from the cytoskeleton family and are 10 nanometres in diameter, are unlike actin and microtubules, which are highly dynamic cytoskeletal elements. Intermediate filaments are flexible at low strain, harden at high strain and resist breaking. For this reason, these filaments fulfil structural functions by providing mechanical support to the cells through their different strain-hardening properties. Intermediate filaments are suitable in that cells both cope with mechanical forces and modulate signal transmission. These filaments are composed of fibrous proteins that exhibit a central α-helical rod domain with a conserved substructure. Intermediate filament proteins are divided into six groups. Type I and type II include acidic and basic keratins, type III, vimentin, desmin, peripheralin and glial fibrillary acidic protein (GFAP), respectively. Type IV intermediate filament group includes neurofilament proteins and a fourth neurofilament subunit, α-internexin proteins. Type V consists of lamins located in the nucleus, and the type VI group consists of lens-specific intermediate filaments, CP49/phakinin and filen. Intermediate filament proteins show specific immunoreactivity in differentiating cells and mature cells of various types. Various carcinomas such as colorectal, urothelial and ovarian, diseases such as chronic pancreatitis, cirrhosis, hepatitis and cataract have been associated with intermediate filaments. Accordingly, this section reviews available immunohistochemical antibodies to intermediate filament proteins. Identification of intermediate filament proteins by methodological methods may contribute to the understanding of complex diseases.

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.

Inflammatory mediators of cytokines and chemokines in sepsis: From bench to bedside.

Background: Sepsis is a serious clinical condition characterized by damage to the immune system as a result of an uncontrolled response to infection. Septic patients show complications such as fever, cardiovascular shock, and/or systemic organ failure. Acute organ failure formed in sepsis mostly affects the respiratory and cardiovascular systems. In sepsis, responses including pro-inflammatory and anti-inflammatory processes in addition to the Toll-Like Receptor 4 (TLR4) signals leading to the release of inflammatory mediators have been suggested to be fundamental pathways in the pathophysiology of sepsis. Purpose: In this context, unregulated levels of sepsis-associated inflammatory mediators may increase the risk of mortality. In sepsis, infection-induced pathogens lead to a systemic inflammatory response. These systemic responses may contribute to septic shock and organ dysfunction. In the unfavorable clinical course of sepsis, an uncontrolled inflammatory response is observed. Accordingly, the mechanism of inflammatory mediators such as cytokines and chemokines in sepsis might increase. Neurotransmitters and gene regulators affect inflammatory mediators and control the inflammatory response. In this review, we aimed to show the new therapeutic targets in sepsis treatment with current studies. New clinical implications targeting inflammatory mediators in high mortality affected by the uncontrolled inflammatory response in sepsis can contribute to the understanding of the symptoms.

The effect of antioxidants in Ehrlich Ascites Cancer.

A fundamental goal in molecular oncology is to unravel the underlying mechanisms which cause the cell transformation. In line with this approach, genome-wide functional screening approaches have revealed exciting insights into heterogeneous nature of cancer. Rapidly expanding horizons of research have unraveled myriad of pathways which play instrumental role in carcinogenesis and metastasis. Oxidative stress has also been reported to be significantly involved in cancer onset and progression. In line with this approach, oxidative stress modulating chemicals have always been sharply divided into antioxidants and oxidative stress-inducing agents. Conceptual and experimental advancements have enabled us to critically analyze full potential of these two different groups of chemicals in cancer chemoprevention. Different antioxidants are currently being analyzed in different phases of clinical trials. Although it has been reported in the literature that antioxidant supplements reduce tumor cells in some tumors or cause volume reduction in solid tumor sizes, there is no definite consensus. Therefore, an antioxidant supplement guideline based on more detailed clinical research and as a result of these is needed to achieve the best care for cancer patients and to avoid risky treatments for cancer patients.

Myocardial Iron Overload in an Experimental Model of Sudden Unexpected Death in Epilepsy.

Uncontrolled repetitive generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). GTCS can be observed in models such as Pentylenetetrazole kindling (PTZ-K) or pilocarpine-induced Status Epilepticus (SE-P), which share similar alterations in cardiac function, with a high risk of SUDEP. Terminal cardiac arrhythmia in SUDEP can develop as a result of a high rate of hypoxic stress-induced by convulsions with excessive sympathetic overstimulation that triggers a neurocardiogenic injury, recently defined as "Epileptic Heart" and characterized by heart rhythm disturbances, such as bradycardia and lengthening of the QT interval. Recently, an iron overload-dependent form of non-apoptotic cell death called ferroptosis was described at the brain level in both the PTZ-K and SE-P experimental models. However, seizure-related cardiac ferroptosis has not yet been reported. Iron overload cardiomyopathy (IOC) results from the accumulation of iron in the myocardium, with high production of reactive oxygen species (ROS), lipid peroxidation, and accumulation of hemosiderin as the final biomarker related to cardiomyocyte ferroptosis. Iron overload cardiomyopathy is the leading cause of death in patients with iron overload secondary to chronic blood transfusion therapy; it is also described in hereditary hemochromatosis. GTCS, through repeated hypoxic stress, can increase ROS production in the heart and cause cardiomyocyte ferroptosis. We hypothesized that iron accumulation in the "Epileptic Heart" could be associated with a terminal cardiac arrhythmia described in the IOC and the development of state-potentially in the development of SUDEP. Using the aforementioned PTZ-K and SE-P experimental models, after SUDEP-related repetitive GTCS, we observed an increase in the cardiac expression of hypoxic inducible factor 1α, indicating hypoxic-ischemic damage, and both necrotic cells and hemorrhagic areas were related to the possible hemosiderin production in the PTZ-K model. Furthermore, we demonstrated for the first time an accumulation of hemosiderin in the heart in the SE-P model. These results suggest that uncontrolled recurrent seizures, as described in refractory epilepsy, can give rise to high hypoxic stress in the heart, thus inducing hemosiderin accumulation as in IOC, and can act as an underlying hidden mechanism contributing to the development of a terminal cardiac arrhythmia in SUDEP. Because iron accumulation in tissues can be detected by non-invasive imaging methods, cardiac iron overload in refractory epilepsy patients could be treated with chelation therapy to reduce the risk of SUDEP.

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.

Revisiting the role of neurotransmitters in epilepsy: An updated review.

Epilepsy is a neurologicaldisorder characterized by persistent predisposition to recurrent seizurescaused by abnormal neuronal activity in the brain. Epileptic seizures maydevelop due to a relative imbalance of excitatory and inhibitory neurotransmitters. Expressional alterations of receptors and ion channelsactivated by neurotransmitters can lead to epilepsy pathogenesis. AIMS: In this updated comprehensive review, we discuss the emerging implication of mutations in neurotransmitter-mediated receptors and ion channels. We aim to provide critical findings of the current literature about the role of neurotransmitters in epilepsy. MATERIALS AND METHODS: A comprehensive literature review was conducted to identify and critically evaluate studies analyzing the possible relationship between epilepsy and neurotransmitters. The PubMed database was searched for related research articles. KEY FINDINGS: Glutamate and gamma-aminobutyric acid (GABA) are the main neurotransmitters playing a critical role in the pathophysiology of this balance, and irreversible neuronal damage may occur as a result of abnormal changes in these molecules. Acetylcholine (ACh), the main stimulant of the autonomic nervous system, mediates signal transmission through cholinergic and nicotinic receptors. Accumulating evidence indicates that dysfunction of nicotinic ACh receptors, which are widely expressed in hippocampal and cortical neurons, may be significantly implicated in the pathogenesis of epilepsy. The dopamine-norepinephrine-epinephrine cycle activates hormonal and neuronal pathways; serotonin, norepinephrine, histamine, and melatonin can act as both hormones and neurotransmitters. Recent reports have demonstrated that nitric oxide mediates cognitive and memory-related functions via stimulating neuronal transmission. SIGNIFICANCE: The elucidation of the role of the main mediators and receptors in epilepsy is crucial for developing new diagnostic and therapeutic approaches.

The prevalence of intestinal parasites in the province of Izmir, Turkey.

Stool samples of a total of 2,047 people in Izmir province were examined by wet mount, formalin ethyl acetate concentration, and trichrome staining methods with an aim to reveal the prevalence of intestinal parasites in Izmir together with related personal and environmental risk factors. Geographical mapping showing the density and variation of the species of intestinal parasites in Izmir was done after all maps were scaled, and the coordinates were determined with GeoMedia5.0. The prevalence of the intestinal parasites was found to be 25.6% in Izmir, with a variation between the districts. Blastocystis hominis was the leading parasite, and the prevalence of parasites was higher in children compared to adults; however, the difference was statistically insignificant. There was also no significant difference between the parasite prevalence and sex, marital status, education, income, frequent eating outside, and habitual raw meat eating. Significant differences were found between the parasite prevalence and crowded families, early immigrants, individuals with no social security, and people living in close contact with their livestock. The parasites were found to be less common among individuals who had been drinking bottled water and living in a house with a sewage system. The results demonstrated a correlation between the intestinal parasites and environmental conditions in our study group. We further plan to expand the study group to cover all regions of Turkey.