Obesity and sarcopenia, i.e., decreased skeletal muscle mass and function, are global health challenges. Moreover, people with obesity and sedentary lifestyles often have sleep disorders. Despite the potential associations, metabolic disturbances linking obesity, sarcopenia, and sleep disorders with cancer are neither well-defined nor understood fully. Abnormal levels of adipokines and adipomyokines originating from both adipose tissue and skeletal muscles are observed in some patients with obesity, sarcopenia and sleep disorders, as well as in cancer patients. This warrants investigation with respect to carcinogenesis. Adipokines and adipomyokines may exert either pro-carcinogenic or anti-carcinogenic effects. These factors, acting independently or together, may significantly modulate the incidence and progression of cancer. This review indicates that one of the possible pathways influencing the development of cancer may be the mutual relationship between obesity and/or sarcopenia, sleep quantity and quality, and adipokines/adipomyokines excretion. Taking into account the high proportion of persons with obesity and sedentary lifestyles, as well as the associations of these conditions with sleep disturbances, more attention should be paid to the individual and combined effects on cancer pathophysiology.

Exposure to environmental toxicants such as Arsenic (As) can result in As-induced alterations in immune regulators. Consequently, people who are more prone to viral infections like influenza A or B, H1N1, SARS CoV (Severe Acute Respiratory Syndrome Coronavirus), and SARS CoV2 may develop a susceptibility to immune responses in their lungs because our previous reports delineated the ability of QIAPI 1®, a melanin precursor, to dissociate water molecules with simultaneous therapeutic efficacy against central nervous system (CNS) diseases, retinopathy, and As-induced renal toxicity. Considering the commonalitie of lung pathology of SARS CoV and As-induced toxicity, the aim of this study is to decipher the efficacy of QIAPI 1® against pentavalent As-induced lung toxicity by examining the pulmonary pathology. Hematoxylin & Eosin (H&E) staining was used for ascertaining the lung pathology in Wistar rat models. Animals were divided into 3 groups: control group, group treated with pentavalent As, and a group treated with pentavalent As and QIAPI 1®. There were no significant changes in lung histopathology in the control group as indicated by intact morphology. The As-treated group revealed damage to the histoarchitecture with pulmonary edema, interstitial fibrosis, diffuse alveolar damage, Bronchiolitis obliterans organizing pneumonia (BOOP)-lesions, formation of hyaline membrane, multinucleated giant pneumocytes, atypical pneumocytes, inflammatory cell infiltration, and interstitial edema. The group treated with As and QIAPI 1® significantly associated with mitigated histological signs of lung inflammation induced by Arsenic. Therefore, QIAPI 1® can be recommended as antagonistic to Asinduced lung toxicity. In conclusion, this model could be preferred as a hypothetical model to examine the efficacy of QIAPI 1® in SARS CoV2-induced pulmonary damage. Future studies are warranted to delineate the efficacy of QIAPI 1® against SARS CoV and SARS CoV2 lung pathology.

Background: Stroke is a major challenge in neurology due to its multifactorial genesis and irreversible consequences. Processes of endogenous post-stroke neurogenesis, although insufficient, may indicate possible direction of future therapy. Multiple research considers stem-cell-based approaches in order to maximize neuroregeneration and minimize post-stroke deficits. Objective: Aim of this study is to review current literature considering post-stroke stem-cell-based therapy and possibilities of inducing neuroregeneration after brain vascular damage. Methods: Papers included in this article were obtained from PubMed and MEDLINE databases. The following medical subject headings (MeSH) were used: "stem cell therapy", "post-stroke neurogenesis", "stem-cells stroke", "stroke neurogenesis", "stroke stem cells", "stroke", "cell therapy", "neuroregeneration", "neurogenesis", "stem-cell human", "cell therapy in human". Ultimate inclusion was made after manual review of the obtained reference list. Results: Attempts of stimulating neuroregeneration after stroke found in current literature include supporting endogenous neurogenesis, different routes of exogenous stem cells supplying and extracellular vesicles used as a method of particle transport. Conclusion: Although further research in this field is required, post stroke brain recovery supported by exogenous stem cells seems to be promising future therapy revolutionizing modern neurology.

Epigenetic regulation of mitochondrial DNA (mtDNA) is an emerging and fast-developing field of research. Compared to regulation of nucler DNA, mechanisms of mtDNA epigenetic regulation (mitoepigenetics) remain less investigated. However, mitochondrial signaling directs various vital intracellular processes including aerobic respiration, apoptosis, cell proliferation and survival, nucleic acid synthesis, and oxidative stress. The later process and associated mismanagement of reactive oxygen species (ROS) cascade were associated with cancer progression. It has been demonstrated that cancer cells contain ROS/oxidative stress-mediated defects in mtDNA repair system and mitochondrial nucleoid protection. Furthermore, mtDNA is vulnerable to damage caused by somatic mutations, resulting in the dysfunction of the mitochondrial respiratory chain and energy production, which fosters further generation of ROS and promotes oncogenicity. Mitochondrial proteins are encoded by the collective mitochondrial genome that comprises both nuclear and mitochondrial genomes coupled by crosstalk. Recent reports determined the defects in the collective mitochondrial genome that are conducive to breast cancer initiation and progression. Mutational damage to mtDNA, as well as its overproliferation and deletions, were reported to alter the nuclear epigenetic landscape. Unbalanced mitoepigenetics and adverse regulation of oxidative phosphorylation (OXPHOS) can efficiently facilitate cancer cell survival. Accordingly, several mitochondria-targeting therapeutic agents (biguanides, OXPHOS inhibitors, vitamin-E analogues, and antibiotic bedaquiline) were suggested for future clinical trials in breast cancer patients. However, crosstalk mechanisms between altered mitoepigenetics and cancer-associated mtDNA mutations remain largely unclear. Hence, mtDNA mutations and epigenetic modifications could be considered as potential molecular markers for early diagnosis and targeted therapy of breast cancer. This review discusses the role of mitoepigenetic regulation in cancer cells and potential employment of mtDNA modifications as novel anti-cancer targets.

BACKGROUND:Ionizing Radiation (IR) is one of the major limiting factors for human deep-space missions. Preventing IR-induced cognitive alterations in astronauts is a critical success factor. It has been shown that cognitive alterations in rodents can be inferred by alterations of a psycho- emotional balance, primarily an anxiogenic effect of IR. In our recent work, we hypothesized that the neurokinin-1 (NK1) receptor might be instrumental for such alterations.OBJECTIVE:The NK1 receptor antagonist rolapitant and the classic anxiolytic diazepam (as a comparison drug) were selected to test this hypothesis on Wistar rats.METHODS:Pharmacological substances were administered through intragastric probes. We used a battery of tests for a comprehensive ethological analysis. High-performance liquid chromatography was applied to quantify monoamines content. An analysis of mRNA expression was performed by real-time PCR. Protein content was studied by the Western blotting technique.RESULTS:Our salient finding includes no substantial changes in anxiety, locomotor activity and cognitive abilities of treated rats under irradiation. No differences were found in the content of monoamines. We discovered a synchronous effect on mRNA expression and protein content of 5- HT2a and 5-HT4 receptors in the prefrontal cortex, as well as decreased content of serotonin transporter and increased content of tryptophan hydroxylase in the hypothalamus of irradiated rats. Rolapitant affected the protein amount of a number of serotonin receptors in the amygdala of irradiated rats.CONCLUSION:Rolapitant may be the first atypical radioprotector, providing symptomatic treatment of CNS functional disorders in astronauts caused by IR.

Suicides on railway tracks are one of the most drastic ones. No research concerning this phenomenon has been done to this date in Poland. This article focuses on the connection between suicidal behaviors on Polish railway tracks and sociodemographic traits and presents risk factors.BACKGROUND:The suicide behavior is largely spread among many European countries. Of these, Poland ranks 22nd in terms of suicide attempts. This study aims to highlight the suicide attempts rates on Polish railways lines and their main risk factors.LIMITATIONS:Limited number of available statistical data before 2013.METHOD:Statistical review of the available Central Police headquarters database and analyses of the influence of the risk factors on people's awareness during the suicide attempts and their geographical distribution in Poland during the years 2013 - 2016. The prevalence of railway suicides in individual voivodeships (provinces) in Poland have been indicated in a 3D map.RESULTS:There were 834 cases of railway suicide fatalities across the entire country. Of the total suicide statistics by any means, 3.75% are railway related. The average known age of those committing railway suicides were: 37.9 years for men (n = 627) and 34.6 for women (n = 155). In most cases, suicides were committed by bachelors (54.3%). The largest group of people who committed suicide had a primary level of education (42.0%). Among the suicides, a significant group are unemployed (45.2%). Alcohol intoxication have been established as responsible for a person's lower awareness of his actions in 70.9% of cases. Almost 63.3% of people had a higher propensity for suicidal ideation and behavior, resulting in their being treated for mental health issues.CONCLUSION:Alcohol intoxication, illegal narcotics and psychotropic medication are responsible for a person's lower awareness during his ore her actions, in most of the cases of suicide on Polish railway lines.

: The root cause of non-inherited Alzheimer’s disease (AD) remains unknown despite hundreds of research studies performed to attempt to solve this problem. Since proper prophylaxis remains the best strategy, many scientists have studied the risk factors that may affect AD development. There is robust evidence supporting the hypothesis that cardiovascular diseases (CVD) may contribute to AD progression, as the diseases often coexist. Therefore, a lack of well-defined diagnostic criteria makes studying the relationship between AD and CVD complicated. Additionally, inflammation accompanies the pathogenesis of AD and CVD, and is not only a consequence but also implicated as a significant contributor to the course of the diseases. Of note, АроЕε4 is found to be one of the major risk factors affecting both the cardiovascular and nervous systems. According to genome wide association and epidemiological studies, numerous common risk factors have been associated with the development of AD-related pathology. Furthermore, the risk of developing AD and CVDs appears to be increased by a wide range of conditions and lifestyle factors: hypertension, dyslipidemia, hypercholesterolemia, hyperhomocysteinemia, gut/oral microbiota, physical activity, and diet. This review summarizes the literature and provides possible mechanistic links between CVDs and AD.

Background: Given the evidence of little or no therapeutic benefit of injection-based growth factor therapies, it has been proposed that a naturally triggered uninterrupted blood circulation of the growth factors would be superior. Objective: We seek to stimulate discussions and more research about the possibility of using the already available growth factors found in the prostate gland and endometrium by starting novel educable physiology, known as biological transformations controlled by the mind. Methods: We summarized the stretch-gated ion channel mechanism of the cell membrane and offer several practical methods that can be applied by anyone, in order to stimulate and enhance the blood circulation of the growth factors from the seminal fluid to sites throughout the body. This study describes, in detail, the practical application of our earlier published studies about biological transformations. Results: A previously reported single-patient case study has been extended, adding more from his personal experiences to continually improve this novel physiological training and extending the ideas from our earlier findings in detail. Conclusion: The biological transformation findings demonstrate the need for additional research to establish the benefits of these natural therapies to repair and rejuvenate tissues affected by various chronic diseases or aging processes.

Background: A patient was evaluated with respect to the effects and results of a complex treatment plan for complete dental rehabilitation. Several steps were required. Each step included immunological tests of salivary biomarkers. Clinical and immunological assessments were evaluated on Day 3, Week 2, Month 3, and Month 6 post-surgery. These evaluations guided the decision-making process with regard to preparation of a permanent prosthesis. Objective: The aim of the study is to evaluate the response of tissues and organs of the maxillofacial region in patients during dental rehabilitation after maxillofacial surgery. Methods: Complex treatment and rehabilitation involving cooperation between the specialists in maxillofacial surgery, prosthetic dentistry, and cancer immunology. Results: Long-term monitoring and clinical examination showed a direct relationship between the patient's clinical and dental status and the changes in oral fluid biomarkers. Conclusion: The data revealed that the oral fluid biomarkers reflected the patient's adaptation to prosthodontic rehabilitation. Treatment and monitoring of a maxillofacial tumor patient could use biomarkers as a non-invasive indicator.

The article has been withdrawn at the request of the co-authors due to the death of the corresponding author (Dr. Aliev). Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

It is with deep sadness that we offer our memorial on the unexpected demise of our dear colleague, Professor Gjumrakch Aliev [...]

OBJECTIVE Serrated colorectal lesions are a group of colonic lesions with a serrated (saw-tooth) profile of the surface epithelium and crypts, and peculiar molecular and genetic developmental mechanisms that are incompletely understood. These formations cause concern due to their premalignant potential. AIM The review is dedicated to serrated lesions of colon and appendix. We focused on modern classification, role in carcinogenesis, as well as new approaches to morphological diagnosis. METHODS A literature search was performed using PubMed, Scopus, ResearchGate, Google, MEDLINE, and ScienceDirect databases to find studies of serrated colorectal lesions related cancer published between 2000 and 2020 that address epidemiological risk factors, underlying pathophysiological mechanism and enable our review of these factors as well as molecular, genetics, and structural patterns. RESULTS Serrated colorectal lesions take one third of all benign neoplasms of the colon in the pathologist's practice. The active study of serrated lesions began in the 1900s. Terminology and diagnostic criteria changed in the updated classification in 2019. Morphological criteria, immunohistochemical and molecular profile, endoscopic and clinical characteristics are reviewed. CONCLUSION Although significant efforts were made in attempt to improve our understanding and diagnostic criteria of serrated polyps of colorectum, very little has changed since the original morphologic description of preneoplastic serrated lesions in early 2000s. There remains a need for more research in order to develop more definitive immuophenotypic and molecular biomarkers in order to distinguish between non-neoplastic and neoplastic serrated lesions.

Postpartum uterine diseases are associated with significant imbalance in the levels of biogenic amines (BAs) in rat uterus. Mast cells (MCs) are the main suppliers of BAs such as serotonin, catecholamines, and histamine in uterus. There is limited evidence of the BA-positive elements involved in the physiological regulation of uterus during postpartum involution. The aim of present study is to determine the concentration and distribution of biogenic amines (BAs) such as histamine, serotonin, and catecholamines in the uterine endometrium, myometrium, and peritoneal fluid (PF) during the postpartum uterine involution. A total of 110 nulliparous outbred female nonpregnant Wistar rats of mature age were divided into eleven groups (n=10 per group) according to days of postpartum involution. Tissue specimens of uterine segments, PF were prepared. Serotonin, catecholamines, and histamine concentrations were examined by fluorescence-histochemical techniques. The fluorescence of the BA-positive elements was detected and analyzed by microspectrofluorimetry. Results were analyzed using the Kruskal-Wallis chi-squared test and pairwise Mann-Whitney-Wilcoxon tests with "Benjamini-Hochberg correction" in R 3.6.3. Mast cells in uterine segments, PF exhibited characteristic yellowish-green fluorescence. The highest MCs number was reported in corpus uteri on the 15th day of postpartum involution. Serotonin, catecholamines, and histamine levels were significantly higher in BA-positive elements in the initial days. BA content was dynamic and relies on the time elapsed after parturition. There was statistically significant difference in the levels of BAs in the cornu and cervix uteri. A single morphofunctional complex of BA supply was noticed in the reproductive system of the rats. The coupled interactions of intra- and extra-organic BA-positive elements was associated with anabolic/catabolic equilibrium in uterus through the metabolism of serotonin, catecholamines, and histamine during postpartum involution.

The main purpose of our work is to assess the likewise of mentoring practices in the educational process of teaching the discipline "normal human anatomy" to medical students in full-time practical classes and in distance learning using interactive technologies. We present our version of best practices for tutoring students in normal human anatomy classes, which enables us to focus on the most difficult topics of this discipline. In particular, we analyzed teaching central nervous system anatomy to two groups of medical students under different learning conditions: during classical practical classes and, separately, during distance learning using interactive technologies. MATERIALS AND METHODS In the 2018-2019 academic year, a group of students in classical anatomy class was surveyed using a printed questionnaire and a the Google form. One of the research materials was the data obtained during the survey. The survey gathered opinion data regarding the quality of teaching and requested suggestions to improve teaching and learning. In March-May 2020, we implemented mentoring for a group of students using Zoom, Skype, and VK social network for conducting classes, sending materials, and receiving feedback. RESULTS We found that the electronic materials were rated positively by students, which we used to improve the teaching process for "Normal Human Anatomy." We found that mentoring directly improved students' academic performance. Mentoring provided flexibility that enabled students to have a measure of self-control of their engagement in their educational process. Sharing with classmates helped students reflect on their learning activities and allowed them to present their own ideas. Mentoring engaged students in their educational process in a meaningful and worthwhile say. CONCLUSION Properly formulated mentoring goals in anatomy studies improved students' motivation to learn and their interest in the subject matter.

The root cause of non-inherited Alzheimer's disease (AD) remains unknown despite hundreds of research studies performed to attempt to solve this problem. Since proper prophylaxis remains the best strategy, many scientists have studied the risk factors that may affect AD development. There is robust evidence supporting the hypothesis that cardiovascular diseases (CVD) may contribute to AD progression, as the diseases often coexist. Therefore, a lack of well-defined diagnostic criteria makes studying the relationship between AD and CVD complicated. Additionally, inflammation accompanies the pathogenesis of AD and CVD, and is not only a consequence but also implicated as a significant contributor to the course of the diseases. Of note, АроЕε4 is found to be one of the major risk factors affecting both the cardiovascular and nervous systems. According to genome wide association and epidemiological studies, numerous common risk factors have been associated with the development of AD-related pathology. Furthermore, the risk of developing AD and CVDs appears to be increased by a wide range of conditions and lifestyle factors: hypertension, dyslipidemia, hypercholesterolemia, hyperhomocysteinemia, gut/oral microbiota, physical activity, and diet. This review summarizes the literature and provides possible mechanistic links between CVDs and AD.

Background: Psychosocial stress-induced depressive behavior is linked to the etiology of several neurological diseases viz., PTSD, and neurodegenerative disease like Alzheimer's Disease (AD). The repeated bouts of social stress defeat can be induced using Resident-Intruder- Paradigm (RIP) and Chronic Mild Social Stress (CMSS) animal models to assess the stress-induced depressive behavioral patterns. Objectives: The aim of this study to examine the anti-depressive efficacy of 3-methoxythietane- 1,1-dioxide (N-14) in RIP models of behavioral alterations. Methods: In this study, we have used Sprague-Dawley rats in Resident-Intruder-Paradigm (RIP), where intruders interacted with residents Day 0 to Day +5 for 10 minutes to invoke CMSS in intruders and became defeated/submissive rats due to the depressive-like behavioral alterations in social activity, explorations, grooming, defense, aggressive behavior, social interaction, freeze, rearing etc., with residents. Control intact animals are included in group I, group II received N-14 alone; group III received CMSS, and group IV received cotreatment of N14 with CMSS. N-14 (2 mg/kg) was administered intraperitoneally from Day 0 to Day +5 to intact animals and intruder animals under conditions of CMSS. Results: Several behavioral tests viz., forced swim test, open field test, and elevated-plus maze test were used to examine the above behavioral dynamic parameters. The dynamic interaction between Residents and Intruders during the study showed substantial alterations in exploratory activity, aggressiveness, defensive behavior, body weight, and thymus mass in stressed animals. N-14 cotreatment has mitigated sociability, exploratory activity, aggressiveness increased social adaptability and defensive behavior. An extensive rise in active forms of defense and submission latency indicates that N-14 has induced antidepressant activity with a psycho-sedative component of action. Conclusion: Serendipitously, we observed the ameliorative capability of N-14 cotreatment to mitigate depressive-behavioral symptoms in intruders.

Background: Biogenic amines (BAs) secreted by the sympathetic neural apparatus of rat uterus are reported to be conducive to the uterine functional activity during postpartum involution; the imbalance in BAs ratio could confer postpartum reproductive disorders including improper postpartum involution. Objective: The objective of this study is to identify the changes in the density of uterine sympathetic nerves implicated in the pathology of endometriosis, adenomyosis, and delayed uterine involution. The present study aims to ascertain ‘serotonin’ and ‘catecholamine’ concentrations in mesenteric mast cells (MCs), and structural elements of nerve fibers across the perivascular plexuses (PPs) and single sympathetic nerve terminals (SST). Methods: Furthermore, the density of their spatial distribution (SDP and SDT) in the uterine body, cervix, and mesometrium was determined during postpartum involution. Tissue specimens of postpartum uterus were obtained from 55 nulliparous female Wistar outbred strain rats, which were grouped according to the days after parturition at the time of sacrifice. The nerve fibers of PP and SST exhibited emerald green fluorescence, which was detected by glyoxylic acid fluorescence technique; the fluorescence invoked by BAs was identified by microspectrofluorimetry. Results: Concentrations of BAs were extensive in the varicosities of PP and SST on the 10th day. However, the highest BA concentrations were found in structural elements of PP in the uterine mesometrium in the initial days of postpartum. In mesenteric MC, serotonin and catecholamines were at the highest concentration on the 10th day of postpartum. Histamines peaked on the 6th day. Conclusion: SDP and SDT were increased significantly in all structural elements of uterine nerve fibers in the uterine body and cervix compared to SDP in mesentery. Considering that catecholamines and serotonin are antagonists in many aspects of their biological action, the ratio of BAs should be well-balanced to maintain anabolic- catabolic equilibrium in the rat uterus.

Background: Renal cell carcinoma represents 3% of all adult malignancies. MicroRNAs exhibit specific functions in various biological processes through their interaction with cellular mRNA involved in apoptosis and cell cycle control. Recent studies have reported the potential association of single-nucleotide polymorphisms (SNPs) in miRNA-binding sites of VHL-HIF1α pathway genes with renal cancer development and progression. Objective: The objective of this study is to investigate the SNPs invoking an alteration in the nature of interaction with miRNA binding sites of VHL-HIF1α pathway genes. Methods: Total 450 cases of histologically and clinically verified ccRCC and 490 controls were included in our study. Genotyping was performed using a TaqMan PCR allelic discrimination method. Kaplan-Meier method of statistical analysis was implemented to analyze the overall patient survival rate. Results : Polymorphism rs10491534 in TSC1 gene was significantly associated with the risk of developing advanced ccRCC. Allele G of rs1642742 in VHL gene was significantly prevalent in ccRCC compared with the control group aged 55 and older (OR = 1.5566; CI [1.1532-2.1019]). Results from the dominant model combining individuals with AG or AA genotype showed that the A allele bearers of CDCP1 rs6773576 exhibited a higher risk of death compared to GG carriers (HR 3.93, 95% CI 1.76-17.21, log-rank P = 0.0033). Conclusion: The present study delineated the association of miRNA binding site variants in VHL- HIF1α pathway genes with the ccRCC risk, which may affect the clinical outcomes.

Objective: Serrated colorectal lesions are a group of colonic lesions with a serrated (saw-tooth) profile of the surface epithelium and crypts, and peculiar molecular and genetic developmental mechanisms that are incompletely understood. These formations cause concern due to their premalignant potential. Aim: The review is dedicated to serrated lesions of colon and appendix. We focused on modern classification, role in carcinogenesis, as well as new approaches to morphological diagnosis. Methods: A literature search was performed using PubMed, Scopus, ResearchGate, Google, MEDLINE, and ScienceDirect databases to find studies of serrated colorectal lesions related cancer published between 2000 and 2020 that address epidemiological risk factors, underlying pathophysiological mechanism and enable our review of these factors as well as molecular, genetics, and structural patterns. Results: Serrated colorectal lesions take one third of all benign neoplasms of the colon in the pathologist's practice. The active study of serrated lesions began in the 1900s. Terminology and diagnostic criteria changed in the updated classification in 2019. Morphological criteria, immunohistochemical and molecular profile, endoscopic and clinical characteristics are reviewed. Conclusion: Although significant efforts were made in attempt to improve our understanding and diagnostic criteria of serrated polyps of colorectum, very little has changed since the original morphologic description of preneoplastic serrated lesions in early 2000s. There remains a need for more research in order to develop more definitive immuophenotypic and molecular biomarkers in order to distinguish between non-neoplastic and neoplastic serrated lesions.