Pathological Phenomena Research Articles

#2724 Renal amyloidosis cohort registry in our health area

Abstract Background and Aims Renal amyloidosis is the pathological phenomenon of amyloid deposition in the kidney with marked differences in renal function impairment, proteinuria, need for renal replacement therapy (RRT) and exitus, depending on the protein involved. Light chain amyloidosis (AL) and serum protein A (AA) amyloidosis are the most common. Typical symptoms are severe proteinuria, nephrotic syndrome, and end-stage chronic kidney disease (ESRD). Method Retrospective study of a cohort of patients with renal amyloidosis. Data extracted from the biopsy registry of the HUVM Nephrology Service (2013-2022). We collected demographic, clinical, analytical, histological and clinical outcome variables (RTT, Exitus). Results are analyzed using Mayo Clinic staging criteria. Results 19 patients with a mean age of 63.4a; 57.9% male. Mean laboratory values at diagnosis: creatinine (Cr) 1.56 mg/dl and proteinuria 3.9 g/24 h. Abdominal fat biopsy in 13 cases; 3 (23%) tested positive. Comparative analysis of AL vs non-AL forms, Cr values (1.14 vs 2.27 mg/dl respectively) (p=0.57) differed. Proteinuria according to the histological location of the amyloid: 4.6 g/24 h in glomerular involvement vs. 0.3 g/24 h in those who did not present it (p<0.05). 31.6% required RTT with a mean onset time of 250.6 d from biopsy. Exitus of 21.1%: average time of 426.5 d. (See analysis in attached table). Conclusion We did not observe significant deterioration of renal function, which is greater in non-AL forms of amyloidosis. Fat biopsy was less cost-effective than reported in the literature. Significantly lower levels of proteinuria were found in the amyloidosis group without glomerular involvement. In our series, the prognostic capacity associated with the MAYO staging was confirmed.

Approaches to nutritional research using organoids; fructose treatment induces epigenetic changes in liver organoids

Nutritional researches have successfully used animal models to gain new insights into nutrient action. However, comprehensive descriptions of their molecular mechanisms of action remain elusive as appropriate in vitro evaluation systems are lacking. Organoid models can mimic physiological structures and reproduce in vivo functions, making them increasingly utilized in biomedical research for a better understand physiological and pathological phenomena. Therefore, organoid modeling can be a powerful approach for to understand the molecular mechanisms of nutrient action. The present study aims to demonstrate the utility of organoids in nutritional research by further investigating the molecular mechanisms responsible for the negative effects of fructose intake using liver organoids. Here, we treated liver organoids with fructose and analyzed their gene expression profiles and DNA methylation levels. Microarray analysis demonstrated that fructose-treated organoids exhibited increased selenoprotein p (Sepp1) gene expression, whereas pyrosequencing assays revealed reduced DNA methylation levels in the Sepp1 region. These results were consistent with observations using hepatic tissues from fructose-fed rats. Conversely, no differences in Sepp1 mRNA and DNA methylation levels were observed in two-dimensional cells. These results suggest that organoids serve as an ideal in vitro model to recapitulate in vivo tissue responses and help to validate the molecular mechanisms of nutrient action compared to conventional cellular models.

Causal Relationships Between Physical Activity and Arthrokinematic Integrity of the Ankle Joint-Foot Complex Across Normal and Pathological Phenomena: A Case-Control Analysis.

Introduction Muscles, ligaments, tendons, bones, and cartilage undergo age-related changes, affecting the foot-ankle joint complex biomechanics in both genders. While international studies have extensively researched these dynamics, Indian studies are limited. Our study aims to fill this gap by analyzing the anthropometric and biomechanical function of the foot-ankle joint complex in normal individuals and those with painful pathologies at All India Institute of Medical Sciences (AIIMS) Rajkot's OPD. Methods In a two-year case-control study of the cross-sectional type conducted at AIIMS Rajkot's OPD, 158 patients with similar pain intensity on the Numeric Pain Rating Scale were examined. Anthropometric and biomechanical measurements were taken for both affected and non-affected foot and ankle joints. Cases comprised patients with foot and ankle joint pain, while controls were selected based on predefined criteria and were without such pain. Ethical approval was acquired from the Institutional Ethical Committee of AIIMS Rajkot. Results The sprain of the ankle joint and foot was the most common musculoskeletal pathology (65 out of 158 cases, i.e., 41.13%) affecting the ankle joint-foot complex. Patients involved in occupations requiring higher physical inactivity suffer more commonly from ankle joint-foot pathologies. The mean difference in the range of motion, i.e., dorsiflexion, plantar flexion, inversion, and eversion, between affected and non-affected feet was found to be lower in the patients who belonged to occupations involving low physical activity compared to those patients having occupations with high physical activity. Conclusion Reduced physical activity increases the stiffness and reduces the flexibility of the tendons, muscles, and ligaments of any joint (the ankle joint-foot complex in this study) and is associated with a higher incidence of musculoskeletal pathologies.

Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK

The accumulation of lipid droplets (LDs) in aging and Alzheimer's disease brains is considered a pathological phenomenon with unresolved cellular and molecular mechanisms. Utilizing stimulated Raman scattering (SRS) microscopy, we observed significant in situ LD accumulation in microglia of tauopathy mouse brains. SRS imaging, combined with deuterium oxide (D2O) labeling, revealed heightened lipogenesis and impaired lipid turnover within LDs in tauopathy fly brains and human neurons derived from induced pluripotent stem cells (iPSCs). Transfer of unsaturated lipids from tauopathy iPSC neurons to microglia induced LD accumulation, oxidative stress, inflammation, and impaired phagocytosis. Neuronal AMP-activated protein kinase (AMPK) inhibits lipogenesis and promotes lipophagy in neurons, thereby reducing lipid flux to microglia. AMPK depletion in prodromal tauopathy mice increased LD accumulation, exacerbated pro-inflammatory microgliosis, and promoted neuropathology. Our findings provide direct evidence of native, aberrant LD accumulation in tauopathy brains and underscore the critical role of AMPK in regulating brain lipid homeostasis.

Analytical Modeling of Breast Elastography

The purpose of the research is to develop a method for assessing the level of nonspecific protection of the body. Тhe purpose of the research. Тo develop an analytical method based on micromechanics to determine the location, size and modulus of elasticity of a tumor mass embedded in symmetrical double-dimensional breast tissue and obtain a closed solution for deformation elastograms.Methods. Changes in tissue elasticity usually correlate with pathological phenomena. Many cancers, such as scirrhous carcinoma of the breast, appear as extremely hard nodules that result from increased stromal density. Other diseases include deposits that increase or decrease tissue elasticity. Complex fluid-filled cysts may not be visible on standard ultrasound, but may be much softer than the embedded tissue. Тhe elastic moduli of tumors change during their pathological evolution. Еlastographic imaging has the potential to detect and characterize cancers by mapping tissue stiffness distribution. Тhe work developed a model of the mammary gland in the form of a two-dimensional layer of unit thickness with a round tumor, taking into account boundary conditions. Local elastic responses were obtained when an acoustic field was applied.Results. Тo evaluate the possibilities of determining the quantitative values of the elastic modules of the medium, we proposed a model of the process of deformation of heterogeneity under the conditions of ultrasonic static elastography and investigated the influence of elastic moduli and deformation of heterogeneity in the direction of applied pressure. Conclusion. Тhe developed technique made it possible to obtain an analytical solution for the field of deformations and stresses of two-dimensional models of mammary glands containing inhomogeneities. Тhe model makes it possible to use the developed methodology for constructing medical elastographic devices and conducting research in the field of elastography.

Abstract LB197: Methylation patterns at adjacent CpG sites within enhancers are part of cell identity and are disrupted during malignant transformation

Abstract Background: Following the principles of physiology of DNA methylation, it is generally accepted that methylation status of CpG sites spaced up to 50 bp is correlated and accumulation of locally disordered methylation at CpG sites is a part of neoplastic transformation, acting in similar way as stochastic accumulation of mutations during malignant transformation. Methods: We developed a new algorithm allowing to analyze methylation status at the adjacent CpG sites. We then, used EPIC microarray data to analyze genome wide methylation patterns at the adjacent CpG sites in almost 600 samples, representing 12 healthy tissues and cell types as well as 572 cancer specimens. We also used bisulfite next generation sequencing data and Sanger sequencing to validate our findings. Results: Our analysis, identified in human genome a subset of loci with adjacent CpG sites spaced less than 50bp (average 28bp), harboring one cytosine methylated and the other devoid of methyl group. These loci are enriched in enhancers that are targeted by families of transcription factors involved in cell differentiation. The methylation patterns at these loci can differ between alleles within a cell, what allows for remarkable level of heterogeneity of methylation patterns. However, our analysis also showed that, different types of specialized cells, acquire during differentiation only one specific and remarkably stable pattern of methylation at each of these loci and that pattern is to a large extent lost during neoplastic transformation. Conclusions: Contrary to generally accepted principle of identical methylation status of the adjacent CpG sites being essential for regulatory function of DNA methylation. We have shown that methylation at a subset of adjacent CpG sites in human genome located within important functional genomic elements differs in healthy cells. These CpG sites acquire remarkably stable and tissue specific patterns of methylation during cell differentiation. Moreover, the methylation patterns at these CpG sites, are lost during malignant transformation suggesting the involvement of identified phenomenon in cancer pathology. Funding: This work was funded by grant OPUS22 from Polish National Science Centre (grant number: 2021/43/B/NZ2/02979) and Polish National Agency for Academic Exchange (grant number: PPN/PPO/2018/1/00088/U). Citation Format: Olga Taryma-Leśniak, Jan Bińkowski, Patrycja K. Przybylowicz, Katarzyna E. Sokolowska, Konrad Borowski, Tomasz K. Wojdacz. Methylation patterns at adjacent CpG sites within enhancers are part of cell identity and are disrupted during malignant transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB197.

Abstract SY03-03: Thinking outside the chromosome: Interrogating epigenetic mechanisms in noncanonical chromatin species

Abstract The epigenetic regulation of DNA-templated processes is intricately tied to numerous events that determine cell phenotype and fate. The abrogation of epigenetic cascades drives various disease states, including cancer. Many of these pathological phenomena involve major chromosomal arrangements that can include the generation of non-canonical chromatin structures existing in the primary nuclei or encapsulated in spatially distinct micronuclei. Recently, we undertook a mechanistic approach to investigate the properties of unique non-chromosomal structures, revealing significant epigenetic contributions to their regulation. We found that micronuclei, the result of chromosomal instability in cancer, assume altered epigenetic landscapes upon departure from the nucleus. Moreover, chromosomes sequestered in micronuclei retain the epigenetic "scars" after reintegration into the primary nucleus, contributing to epigenetic reprogramming and heterogeneity in cancer. Additionally, we turned our attention to the Hepatitis B Virus' (HBV) covalently closed circular DNA (cccDNA) minichromosome, which forms from viral DNA and human histones following infection. We found that chromatinization drives the expression of the key viral oncogene, HBx, and thus promotes viral infection. Elucidating this new mechanism enabled us to halt infection by inhibiting histone remodeling, creating a potential first-in-class therapy for HBV. These exciting findings demonstrate the key role of chromatin in biomedical events and how a fundamental understanding of these processes can lead to the identification of new therapeutic avenues. Citation Format: Yael David. Thinking outside the chromosome: Interrogating epigenetic mechanisms in noncanonical chromatin species [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr SY03-03.

Berger and the Breakthrough: A Centennial Celebration of the Human Electroencephalogram

ABSTRACT A century ago, it was a challenge for neuroscientists to decipher the mysteries of human brain functioning until German psychiatrist Hans Berger discovered what is now one of the most well-known electrophysiological recording techniques to examine brain function, EEG. He is rightly regarded as the Father of The Electroencephalogram (EEG), since he performed the first human electroencephalogram in 1924. Berger attempted to investigate the connection between psychology and physiology and to solve the “psychic energy” enigma. Despite turbulence in his professional life and slow progress in his research, he persevered and succeeded in giving humankind an indispensable technique that is now widely used in clinical and research practice. His publications on EEG provide valuable insight into our current understanding of several of the brain’s responses to physiological and pathological phenomena. In July 2024, it will be 100 years since Berger recorded the first human EEG, and that calls for a celebration among EEG researchers, neuroscientists, psychiatrists, and neurologists. This article presents a brief account of his journey and commemorates Hans Berger’s contributions to the field of neurodiagnostics.

Construction of curcumin-loaded macrophage and HUVECs membrane-derived vesicles for drug delivery in cardiovascular inflammatory

In the progression of cardiovascular disease (CVD), myocardial inflammation and vascular endothelial inflammation are prevalent pathological phenomena. However, the development of drug delivery platform with high specificity against these inflammatory injury sites remains a challenge. To overcome this, we fused RAW264.7 macrophage membranes with human umbilical vein endothelial cell (HUVEC) membranes to prepare hybrid extracellular vesicles (RAW-HEVs) consisted of both types of cell membrane proteins. This hybrid EVs exhibited high uptake ratio towards LPS-induced inflammatory HUVECs and H9C2 cells. By leveraging the stealth properties of HUVEC membranes in the bloodstream and the innate inflammation-targeting ability of RAW264.7 macrophage membranes, RAW-HEVs actively accumulated at inflammatory sites of the heart and thoracic aorta in vivo. By loading curcumin (Cur) with anti-inflammatory activity to prepare Cur-loaded hybrid extracellular vesicles (RAW-H/Cur). RAW-H/Cur significantly reduced the expression of pro-inflammatory cytokines in cell supernatants and mice serum as compared to free Cur, as determined by ELISA. In addition, a significant reduction in LPS-induced organ damage in the heart and thoracic aorta was observed with RAW-H/Cur treatment, determined by Hematoxylin-eosin staining and immunohistochemistry. In conclusion, RAW-H/Cur, as a promising bionic delivery system for cardiovascular inflammatory diseases, is expected to help deliver Cur to inflamed regions of the heart and blood vessels and alleviate inflammatory symptoms.

Inhaled nintedanib nanoparticles for enhanced efficacy in idiopathic pulmonary fibrosis (IPF) treatment – Evidence in disease-relevant in-vitro models

Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive interstitial lung disease with a high mortality rate due to limited prognosis. According to the National Institutes of Health (NIH), approximately 100,000 people in the United States suffer from IPF, and around 50% likelihood of dying within 2–3 years. Currently, nintedanib (Nint) is one of the only 2 FDA-approved drugs for the treatment of IPF, with anti-fibrotic and anti-inflammatory activities. However, Nint oral capsules have some undesirable limitations such as low bioavailability and high dose requirement for sufficient therapeutic efficacy, leading to various side effects associated with oral delivery. To address these shortcomings and enhance the therapeutic potential, Nint was loaded into PLGA nanoparticles (Nint NPs) for localized pulmonary delivery. In-vitro cell culture studies indicated that nano-sized particles (179 ± 3 nm) of Nint NPs enhanced cellular uptake in airway epithelial cells and normal human lung fibroblasts, while readily avoiding macrophage phagocytosis. Transforming growth factor-beta (TGF-β) (10 ng/mL) was selected to establish IPF in cells, which resulted in proliferation and rapid wound healing, whereas Nint NPs showed superior ability in inhibiting these pathological phenomena compared to free Nint. Upon further evaluation of pathological mechanisms of IPF, Nint NPs remarkably attenuated epithelial-to-mesenchymal transition (EMT) by elevating epithelial marker E-cadherin level and reducing extracellular matrix (ECM) deposition by evidence of reduced collagen production and fibroblast-to-myofibroblast differentiation marker, α-SMA. Nint NPs also decreased expression of inflammatory cytokine IL-17A and indicated autophagy as a separate anti-fibrotic mechanism. Finally, Nint NPs proved their superior efficacy in a novel IPF cell model using diseased lung ECM substrates. Hence, inhalation therapy of Nint NPs is a promising alternative tool for oral capsules in IPF therapy.

UPR-Activated IRE1 Signaling Pathway Promotes Malignant Growth of Breast Cancer

Initially, it was believed that the unfolded protein response (UPR) was a network signal that synchronized apoptotic and adaptive responses to the buildup of unfolded proteins in the endoplasmic reticulum (ER). The endoplasmic reticulum stress sensor IRE1 is a major player in the UPR, and overactivation of IRE1 can promote a variety of pathological phenomena, such as diabetes, neurodegenerative diseases, and cancer. Under endoplasmic reticulum stress, IRE1 is activated through autophosphorylation and oligomerization, leading to conformational changes in the RNase domain, thereby promoting two signaling pathways: 1) unconventional splicing of XBP1 and 2) regulated IRE1 dependence Decay (RIDD). Research has revealed that aggressive B-type breast cancer cells typically have an overexpressed and amplified IRE1 gene. Through the RIDD mechanism, IRE1 processes and regulates the breakdown of a fraction of tumor-suppressing micro-RNA, which in breast cancer cells results in the Ras oncogene GTPase. RAB3B is elevated. This article reveals the mechanism of action of the IRE1 signaling pathway and the RIE1-RIDD-miRNA pathway in promoting the malignant development of luminal breast cancer.

Rapid FRET Assay for the Early Detection of Alpha-Synuclein Aggregation in Parkinson's Disease.

Alpha-synuclein (α-Syn) is a key protein of Parkinson's disease (PD). Oligomers formed by misfolding and aggregation of α-Syn can cause many pathological phenomena and aggravate the development of PD. Therefore, sensitive and accurate detection of oligomers is essential to understanding the pathology of PD and beneficial to screening and developing new drugs against PD. Here, we demonstrated a simple and sensitive method to detect the early aggregation of α-Syn via Förster resonance energy transfer (FRET) technology. We performed systematic investigations of the FRET sensitizations, efficiencies, and donor-to-acceptor distances during α-Syn aggregation, which was proved to be more sensitive to reflect small distance changes in the early stage of α-Syn aggregation, especially for α-Syn oligomers. The FRET assays were also applied to study the influence of Ser129 phosphorylation (pS129) on the aggregation rate of α-Syn. Our results showed that pS129 modification promotes α-Syn aggregation and enhances the ability of preformed fibrils to induce monomer aggregation. pS129 also increased the cytotoxicity of α-Syn. These results are of great significance for a better understanding of the pathological mechanisms of PD and future PD drug development.

Gaudin model modulo p, Tango structures, and dormant Miura opers

In the present paper, we study the Bethe ansatz equations for Gaudin model and Miura opers in characteristic p>0. Our study is based on a work by E. Frenkel, in which solutions to the Bethe ansatz equations are described in terms of Miura opers on the complex projective line. The main result of the present paper provides a positive characteristic analogue of this description. We pay particular attention to the case of Miura PGL2-opers because dormant generic Miura PGL2-opers correspond bijectively to Tango structures, which bring various sorts of pathological phenomena in positive characteristic, e.g., counter-examples to the Kodaira vanishing theorem. As a consequence, we construct new examples of Tango structures by means of solutions to the Bethe ansatz equations modulo p.

MORPHOLOGICAL CHANGES OF RAT PERIODONTIUM IN SUPRAOCCLUSAL RELATIONS OF INDIVIDUAL TEETH IN THE AGE ASPECT

Although the issue of the occlusal load influence on the occurrence of pathological phenomena in the body has been discussed for decades, it is still a subject of debate. Pathogenic occlusion is defined as excessive occlusal forces (premature contacts and interference) that can cause injuries to the dentition, including teeth and periodontal tissues. Changes in occlusal dimensions, if not properly performed or treated, can lead to dysfunctions of the dentition, such as joint clicking, difficulty in chewing, occlusal discomfort, muscle fatigue, and pain.
 Aim: to determine the morphological changes of periodontium in rats of different age groups in the supraocclusal relationship of individual teeth in the age aspect.
 Materials and methods of the study. The study was conducted on 60 white laboratory rats aged 4 to 22 months and weighing 90 to 330 g. The rats were divided into control (30 animals) and experimental (30 animals) groups. Each group was divided into 3 subgroups (10 animals each) depending on the age of the rats: young, mature and senile. Young animals included rats aged 3 4 months with a weight of 90 100 g; mature animals aged 6-8 months with a weight of 150 170 g; senile rats 20 22 months and weighing 200 220 g. In the experimental group, the state of supraocclusion was modeled by increasing the height of the lower right second molars by placing 1 mm high filling. For the placement of the filling, 37% orthophosphorus etching gel for enamel and dentin (Latus, Ukraine), microapplicators (Latus, Ukraine), the fifth generation Prime&Bond NT adhesive system (Dentsply Sirona, Germany), the universal microhybrid light-curing composite material Latelux (Latus, Ukraine) and the photopolymerizer LED.D (WOODPECKER, China) were used according to the manufacturer's instructions. The experimental animals were withdrawn from the experiment on the 15th day by decapitation under general anesthesia with sodium thiopental. The lower jaws were skeletonized, and dental blocks were cut out in the area of the molars. For histological examination, the dental blocks were fixed in a 10% solution of neutral formalin for two days, dehydrated in alcohols of increasing concentration and embedded in paraffin. Then, sections were made from the obtained preparations on a Shandon Finesse 325 rotary microtome with a section thickness of 4-6 μm. The histological sections were fixed on degreased slides and dried. Van Gieson staining was performed. The width of the periodontal gap was determined using the ZEISS ZEN 3.7 program by Carl Zeiss Microscopy.
 Results of the study. Histometric analysis has showed significant morphological changes in the experimental group of all age categories. In young rats, the fibrinoid edema phenomena of the periodontal ligament collagen fibers were observed. In mature rats, there was a picture of mucoid edema of collagen fibers of the periodontal ligament. In senile rats, fibrinoid necrosis of collagen fibers of the periodontal ligament were discovered, an inflammatory infiltrate, macrophages and neutrophils, with a predominance of neutrophilic inflammatory microenvironment, and initial hyaline tissue changes were found. In all age groups, there was cement resorption on the lateral surfaces of the tooth root, lacunar resorption of alveolar bone tissue and the presence of a large number of osteoclasts. In senile rats, hypercementosis was determined in the apical part of the root. In the control group of all age categories, neither resorption nor disorganization of connective tissue, nor hypercementosis was detected.
 Conclusions. The study shows that traumatic occlusion leads to resorption of root and alveolar cementum in all age groups. In young rats, traumatic occlusion causes fibrinoid edema of collagen fibers of the periodontal ligament. In mature rats, traumatic occlusion causes mucoid edema of collagen fibers of the periodontal ligament. In senile rats, traumatic occlusion causes fibrinoid necrosis of collagen fibers of the periodontal ligament, initial hyaline tissue changes and hypercementosis.

Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury.

Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model. Our results demonstrated that exposure to Pb caused inflammatory damage in cerebellums and thalami, evidenced by the characteristics of inflammation, the decrease in anti-inflammatory factors (interleukin (IL)-2 and interferon-γ (INF-γ)), and the increase in pro-inflammatory factors (IL-4, IL-6, IL-12β, IL-17, and nitric oxide (NO)). Moreover, we found that the IL-2/IL-17-NO pathway took part in Pb-caused inflammatory injury. The above findings were reversed by the supplementation of dietary Se, meaning that Se relieved inflammatory damage caused by Pb via the IL-2/IL-17-NO pathway. In addition, an up-regulated oxidative index malondialdehyde (MDA) and two down-regulated antioxidant indices (glutathione (GSH) and total antioxidant capacity (TAC)) were recorded after the chickens received Pb stimulation, indicating that excess Pb caused an oxidant/antioxidant imbalance and oxidative stress, and the oxidative stress mediated inflammatory damage via the GSH-IL-2 axis. Interestingly, exposure to Pb inhibited four glutathione peroxidase (GPx) family members (GPx1, GPx2, GPx3, and GPx4), three deiodinase (Dio) family members (Dio1, Dio2, and Dio3), and fifteen other selenoproteins (selenophosphate synthetase 2 (SPS2), selenoprotein (Sel)H, SelI, SelK, SelM, SelO, SelP1, SelPb, SelS, SelT, SelU, and selenoprotein (Sep)n1, Sepw1, Sepx1, and Sep15), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the SPS2-GPx1-GSH pathway. Se supplementation, as expected, reversed the changes mentioned above, indicating that Se supplementation improved antioxidant capacity and mitigated oxidative stress in chickens. For the first time, we discovered that the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway is involved in the complex inflammatory damage mechanism caused by Pb in chickens. In conclusion, this study demonstrated that Se relieved Pb-induced oxidative stress and inflammatory damage via the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway in the chicken nervous system. This study offers novel insights into environmental pollutant-caused animal poisoning and provides a novel theoretical basis for the detoxification effect of Se against oxidative stress and inflammation caused by toxic pollutants.

Problematic Behaviour Among Students in Secondary Schools and the Role of Educational Counsellors

Nowadays it is very important to focus on selecting a topic. Students begin to adopt various types of problematic behaviours in the education system. They engage in problematic behaviour in interactions not only with their peers, but also their teachers. Compared to the situation in other countries, the prevalence of such behaviour is still low in our country. Nevertheless, the present study is aimed at addressing those issues. Humiliation, bullying, truancy and similar behaviour constitute a problem that occurs at an increasing frequency and might transform into major pathological phenomena.

The etiology, diagnostics, and treatment of the spasm of the near reflex - a narrative review.

Physiological adaptation of the eye to the visual perception of near objects consists of the "near triad": convergence, accommodation, and pupil miosis. Normally, these tend to revert when one stops fixating on a near object. Spasm of the near reflex (SNR) is a pathological phenomenon, which manifests itself by the persistence of the above-mentioned adjustments, which prevents the eye from returning to its relaxed state. In this narrative review, we aim to summarize the etiology, diagnostics, treatment, and prevention of SNR. The literature review was performed by searching online databases. The clinical presentation of SNR is diverse; it presents as isolated accommodative spasm more frequently than impairment of all three components of the near triad. Patients usually present with fluctuations in visual acuity, blurred vision, diplopia, and asthenopia. The etiology is not fully understood. Potential causes include neuroanatomic, organic, and psychogenic disorders. The diagnosis is clinical, based on the constellation of symptoms and assessment of the near triad. The diagnostic golden standard is a cycloplegic examination of refraction, preferably using cyclopentolate hydrochloride (1%, 0.5%, or 0.1% solution). The first-line treatment requires the administration of a cycloplegic drug in combination with plus lenses, flipper lenses, optical fogging, or miotics. For secondary cases, causal treatment should be implemented. Prevention of SNR should be based on eliminating modifiable risk factors. We propose including screening for SNR symptoms in every ophthalmic examination, especially among patients with psychogenic or neural disorders, after brain trauma, or young adults spending much time in front of computer screens.

Membranes and Synaptosomes Used to Investigate Synaptic GABAergic Currents in Epileptic Patients.

Among the most prevalent neurological disorders, epilepsy affects about 1% of the population worldwide. We previously found, using human epileptic tissues, that GABAergic neurotransmission impairment is a key mechanism that drives the pathological phenomena that ultimately lead to generation and recurrence of seizures. Using both a "microtransplantation technique" and synaptosomes preparations from drug-resistant temporal lobe epilepsies (TLEs), we used the technique of two-electrode voltage clamp to record GABA-evoked currents, focusing selectively on the synaptic "fast inhibition" mediated by low-affinity GABAA receptors. Here, we report that the use-dependent GABA current desensitization (i.e., GABA rundown, which is evoked by applying to the cells consecutive pulses of GABA, at high concentration), which is a distinguishing mark of TLE, is mainly dependent on a dysfunction that affects synaptic GABAA receptors. In addition, using the same approaches, we recorded a depolarized GABA reversal potential in synaptosomes samples from the human epileptic subicula of TLE patients. These results, which confirm previous experiments using total membranes, suggest an altered chloride homeostasis in the synaptic area. Finally, the lack of a Zn2+ block of GABA-evoked currents using the synaptosomes supports the enrichment of "synaptic fast inhibitory" GABAA receptors in this preparation. Altogether, our findings suggest a pathophysiological role of low-affinity GABAA receptors at the synapse, especially during the fast and repetitive GABA release underlying recurrent seizures.

MiR-378a-5p represses Barrett's esophagus cells proliferation, migration and invasion through targeting TSPAN8.

Barrett's esophagus (BE) belongs to a pathological phenomenon occurring in the esophagus, this paper intended to unveil the underlying function of miR-378a-5p and its target TSPAN8 in BE progression. GEO analysis was conducted to determine differentially expressed genes in BE samples. Non-dysplastic metaplasia BE samples, high-grade dysplastic BE samples and controls were collected from subjects. CP-A and CP-B cells were exposed to bile acids (BA) to mimic gastroesophageal reflux in BE cells. RT-qPCR as well as western blot were applied for verifying expressions of miR-378a-5p, TSPAN8, CDX2 and SOX9. CCK-8, wound scratch together with Transwell assays were exploited for ascertaining cell proliferation, migration as well as invasion. The targeted relationship of miR-378a-5p and TSPAN8 could be verified by correlation analysis, dual-luciferase reporter experiment, and rescue experiments. Through analyzing GSE26886 dataset, we screened the most abundantly expressed gene TSPAN8 in BE samples. miR-378a-5p was reduced whereas TSPAN8 was elevated in CP-A as well as CP-B cells after triggering with BA. Knocking down TSPAN8 could counteract BA-triggered enhancement in BE cell proliferation, migration along with invasion. miR-378a-5p could suppress BE cell proliferation, and migration along with invasion via targeting TSPAN8. In BE, miR-378a-5p targeted TSPAN8 to inhibit BE cell proliferation, and migration along invasion. miR-378a-5p deletion or elevation of TSPAN8 may be key point in regulating CDX2 and SOX9 levels, thereby promoting BE formation.

Patologie w środowisku pracy zagrożeniem dla zdrowia i rozwoju osobistego

The work environment pathologies as a health and personal development threat In the time of dynamic socio-cultural, economic and technological changes, human functioning in the work environment becomes an important individual and social problem. The dynamics of the work environment force the individual to quickly adapt to the changing situation, which often causes serious adaptation difficulties. The complexity and ambiguity of the modern world of work result in dysfunctional or pathological phenomena in the work environment, which significantly affect professional career and personal development. The study presents, against the background of statistics, the most common pathological phenomena in the work environment that negatively affect the work process and the employee himself, undermining his dignity and sense of security.