Systematic-Narrative Hybrid Literature Review: Crosstalk between Gastrointestinal Renin-Angiotensin and Dopaminergic Systems in the Regulation of Intestinal Permeability by Tight Junctions.

In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin-angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin-angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both renin-angiotensin and dopaminergic systems influence intestinal Na+/K+-ATPase activity, thus maintaining electrolyte and nutritional homeostasis. The colocalization of B0AT1 and ACE2 indicates the direct role of the renin-angiotensin system in amino acid absorption. Yet, more studies are needed to thoroughly define the structural and functional interaction between TJ-associated proteins and GI renin-angiotensin and dopaminergic systems.

Salsolinol Protects SH-SY5Y Cells Against MPP+ Damage and Increases Enteric S100-Immunoreactivity in Wistar Rats.

A dopamine derivative, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, known as salsolinol (SAL), has increasingly gained attention since its first detection in the urine of Parkinson's disease patients treated with levodopa, and has been proposed as a possible neurotoxic contributor to the disease. Yet, so far, the neurobiological role of SAL remains unclear. Thus, the main aims of our study were to compare the neurotoxic potential of SAL with MPP+ (1-methyl-4-phenylpyridinium ion) in vitro, and to examine intestinal and metabolic alterations following intraperitoneal SAL administration in vivo. In vitro, SH-SY5Y neuroblastoma cell line was monitored following MPP+ and SAL treatment. In vivo, Wistar rats were subjected to SAL administration by either osmotic intraperitoneal mini-pumps or a single intraperitoneal injection, and after two weeks, biochemical and morphological parameters were assessed. SH-SY5Y cells treated with MPP+ (1000 µM) and SAL (50 µM) showed increase in cell viability and fluorescence intensity in comparison with the cells treated with MPP+ alone. In vivo, we predominantly observed decreased collagen content in the submucosal layer, decreased neuronal density with comparable ganglionic area in the jejunal myenteric plexus, and increased glial S100 expression in both enteric plexuses, yet with no obvious signs of inflammation. Besides, glucose and triglycerides levels were lower after single SAL-treatment (200 mg/kg), and low- to high-density lipoprotein (LDL/HDL) ratio and aspartate to alanine aminotransferases (AST/ALT) ratio levels were higher after continuous SAL-treatment (200 mg/kg in total over 2 weeks). Low doses of SAL were non-toxic and exhibited pronounced neuroprotective properties against MPP+ in SH-SY5Y cell line, which supports the use of SAL as a reference compound for in vitro studies. In vivo results give insight into our understanding of gastrointestinal remodeling following intraperitoneal SAL administration, and might represent morphological correlates of a microglial-related enteric neurodegeneration and dopaminergic dysregulation.

The autonomic nervous system in anorexia nervosa - an implication for the fat tissue.

Eating disorders are a heterogeneous group of diseases affecting mainly young people in developed countries. Among them, anorexia nervosa (AN) is the one with the highest mortality, up to five times higher compared to healthy individuals. The etiology of this medical condition is complex and still un- certain. However, disturbances of the autonomic nervous system (ANS) and increased lipolysis resulting in a decrease of the adipose tissue volume are common findings among AN patients. Since ANS is directly connected to adipocyte tissue, thus significantly affecting the body's metabolic homeostasis, we suspect that this relationship may be a potential pathophysiological underpinning for the development of AN. In this narrative review, we have analyzed scientific reports on ANS activity in AN considering different phases of the disease in humans as well as animal models. Due to the different effects of the disease itself on the ANS as well as specific variations within animal models, the common feature seems to be dysregulation of its function without the identification of one universal pattern. Nonetheless, higher norepinephrine concentrations have been reported in adipocyte tissue, suggesting local dominance of the sym- pathetic nervous system. Further studies should explore in depth the modulation of sympathetic in adipose tissue factor and help answer key questions that arise during this brief narrative review.

Expanded insights into the neural component of the activity-based anorexia animal model - morphological changes in the enteric nervous system and altered pain perception.

Anorexia nervosa (AN) is an eating disorder characterized by distinct etiopathogenetic concepts that are gradually being linked together to unravel the dominant pathophysiological pathways underlying the disease. Excessive food restrictions, often accompanied by over-exercise and undertaken to lose weight, lead to the development of numerous complications. The biological concept of neurohormonal dysfunction in AN seems incomplete without demonstrating or excluding the role of the enteric nervous system (ENS). Using an animal model of activity-based anorexia (ABA), we conducted the preliminary assessment of the ENS structure. Here we show, in preparations stained by immunohistochemistry with anti- ChAT, anti-NOS, anti-PGP 9.5, anti-c-fos, and anti-TH antibodies, a lower density of cholinergic and nitrergic nerve fibers as well as reduced neuronal activity in myenteric plexus. Such structural and functional damage to the ENS may be responsible for a number of gastrointestinal symptoms that worsen the course of the disease. In addition, we expanded the study to address the unresolved issue of mechanical and thermal pain sensitivity in AN. The Von Frey and hot plate tests revealed, that in ABA animals, the pain threshold for mechanical stimulus decreases while for thermal increases. In this way, we have significantly supplemented the background of AN with potentially observable nervous system changes which may influence the evolution of the therapeutic approach in the future.

The Inhibitory Effect of Human Plasma Albumin and Haptoglobin on Platelet Aggregation and 5-HT Release.

Platelet aggregation contributes to the pathogenesis of cardiovascular diseases. After activation it leads to dense granule secretion and 5-HT release. The question arises; how platelet aggregation is endogenously controlled during blood circulation. In preliminary studies, we observed that human platelets aggregate more rapidly when suspended in buffer as compared to those suspended in plasma (PRP). These observations point to the presence of an endogenous substance that may inhibit arachidonic acid- induced platelet aggregation. An analysis of plasma Cohn fractions demonstrated that most of the plasma inhibitory activity was associated with albumin-rich and α-globulin rich protein fractions. The identity of plasma endogenous inhibitors of platelet aggregation (EIPA) was established by affinity chromatography on Cibacron Blue F3G-A for specific removal of albumin. The association of α-globulins to EIPA activity was recognized as due to haptoglobin by affinity chromatography on a column of hemoglobin-sepharose. In addition, we also found that the distribution of EIPA activity varies according to sex and physiological state. These findings reveal that EIPA may act by modulation of arachidonic acid metabolism or sequestering the fatty acid substrate.

Retrospective analysis of a case report of a left ovarian ectopic pregnancy after the former tubal.

Up to 2% of pregnancies may be extrauterine. Despite reproductive problems, they might increase the risk of serious complications. We present a case report of a 31-year-old woman with two extrauterine pregnancies - tubal and ovarian, which occurred at the same side with little time difference. In addition, we aimed to examine possible reasons underlying this rare pathology. Thus, surgically removed tissue specimens were morphologically assessed and further compared with specimens from healthy control patients. Telocytes were analysed in detail due to their pivotal role in the female reproductive system. Our study had observational character and obvious limitations typical for a clinical case. Yet, such a clinical case of two ectopic pregnancies has not been previously reported in the literature.

Gastrointestinal Dopamine in Inflammatory Bowel Diseases: A Systematic Review.

BACKGROUND: an increased prevalence of gastro-duodenal ulceration was described almost sixty years ago as prodromal to idiopathic Parkinson's disease, while duodenal ulcers have been rarely diagnosed in patients with schizophrenia. The cytoprotective role of dopamine in animal models of gastrointestinal ulcerations has also been described. Interestingly, Parkinson's disease (PD) might share common pathophysiological links with inflammatory bowel disease (IBD) as epidemiological and genetic links already suggest. Thus, the aim of our study was to review the existing literature on the role of the gastrointestinal dopaminergic system in IBD pathogenesis and progression. METHODS: a systematic search was conducted according to the PRISMA methodology. RESULTS: twenty-four studies satisfied the predetermined criteria and were included in our qualitative analysis. Due to different observations (cross-sectional studies) as well as experimental setups and applied methodologies (in vivo and in vitro studies) a meta-analysis could not be performed. No ongoing clinical trials with dopaminergic compounds in IBD patients were found. CONCLUSIONS: the impairment of the dopaminergic system seems to be a significant, yet underestimated, feature of IBD, and more in-depth observational studies are needed to further support the existing preclinical data.

Hypersensitivity to polyethylene glycol (PEG).

The need for mass population vaccination against Covid-19 poses a public health problem. Allergic symptoms occurring after the 1st dose of the vaccine may result in resignation from the administration of the 2nd dose. However, the majority of patients with mild and/or non-immediate symptoms may be safely vaccinated. The only absolute contraindication to administration of the vaccine is an anaphylactic reaction to any of its ingredients. Polyethylene glycol (PEG), widely used as an excipient in various vaccines, is considered the primary cause of allergic reactions associated with administration of Comirnaty (Pfizer/BioNTech) and Covid-19 Vaccine (Moderna) vaccines. However, hypersensitivity to PEG reported to date seems very rare, considering its widespread use in multiple everyday products, including medicines and cosmetics. In the paper, current literature data describing mechanisms of hypersensitivity reactions to PEG, their clinical symptoms and diagnostic capabilities are presented. Undoubtedly, the issue of hypersensitivity to PEG warrants further research, while patients with the diagnosis require individual diagnostic and therapeutic approach.

Neglected workforce: pharmacists and their health-related quality of life.

BACKGROUND: pharmacists remain on the frontline of public health around the globe and their performance directly impacts patients' safety. So far, to our knowledge, no European study has been dedicated to their heath-related quality of life (HQoL). Therefore, the primarily aim of our study was to evaluate HQoL of Polish pharmacists utilizing the SF-36 health survey with regard to anthropometric and lifestyle-related variables. METHODS: A total sample screened consisted of 1412 respondents, yet 765 pharmacists (mean age 40, 86.3% females) finally participated in the study. HQoL was assessed with the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS: The lowest median scores were noted for general health (GH, 50.0) and vitality (V, 60.0) domains. No gender differences regarding physical and mental summary scores were found. Significant difference of HQoL was found among the assessed age groups in several domains, especially physical functioning (PF) and GH (p <0.001) scores, and especially in the group of 51-60-year-old-respondents. Correlations were found between PF (r = -0.29, p <0.001), GH (r = -0.25, p <0.001) and age as well PF (r = -0.27, p <0.001), GH (r = -0.21, p <0.001) and BMI. Self-assessed dietary habits were correlated with PF (r = 0.22, p <0.001), mental health (r = 0.25, p <0.001), GH (r = 0.27, p <0.001) and V (r = 0.30, p <0.001) scores. CONCLUSIONS: The analysis indicates that pharmacists tend to have similar mental and physical burden according to SF-36, with age, BMI and dietary habits as predominant factors influencing their HQoL. The study presents unique values for future comparative analyses related, for instance, to the influence of the ongoing pandemic on HQoL of health-care providers.

Hypothalamic and brain stem neurochemical profile in anorectic rats after peripheral administration of kisspeptin-10 using 1 H-nmr spectroscopy in vivo.

PURPOSE: Although anorexia nervosa is classified as a psychiatric disorder associated with socio-environmental and psychological factors, a deeper insight into the dominant neurobiological basis is needed to develop a more effective approach of treatment. Given the high contribution of genetic predisposition and the underlying pathophysiology of neurohormonal circuits, it seems that pharmacological targeting of these mechanisms may provide us with better therapeutic outcomes. METHODS: 1 H-NMR spectroscopy was used to measure concentrations of the hypothalamus and brain stem metabolites in an activity-based rodent model (ABA) after subcutaneous administration of kisspeptin-10. Because anorexia mainly affects young women and often leads to hypogonadotropic-hypogonadism, we investigated the influence of this neuropeptide, which is involved in reproductive function by regulating the hypothalamic-pituitary-gonadal axis, on the ABA model development. RESULTS: Kisspeptin reinforced food consumption in an activity-based rodent model of anorexia changing a pattern of weight loss. 1 H-NMR spectroscopy of the hypothalamus and brain stem of ABA rats revealed a statistically significant change in the concentration of creatine (Cr; decreased, P = 0.030), phosphocreatine (PCr; increased, P = 0.030), γ-aminobutyric acid (GABA; decreased, P = 0.011), glutathione (GSH; increased, P = 0.011) and inositol (INS; increased, P = 0.047) compared to the control group. Subcutaneous administration of kisspeptin reversed the decrease in GABA (P = 0.018) and Cr (P = 0.030) levels in the hypothalamus as well as restored glutamate (GLU; P = 0.040) level in the brain stem. CONCLUSIONS: We suspect that kisspeptin through modulation of hypothalamic GABAergic signaling increases food intake, and thus positively alters brain metabolism.

Aberrations in the female reproductive organs and a role of telocytes in a rat model of anorexia nervosa.

BACKGROUND: Anorexia nervosa is a widely prevalent eating disorder that o en leads to life-threatening complications. Since it mostly concerns females, many authors have focused on studying the reproductive system in anorexic women. Recently discovered telocytes may give a new insight into the pathophysiology of gynecological complications in these patients. MATERIAL AND METHODS: We adopted an animal model of anorexia nervosa induced by voluntary physical activity. Sixteen female Wistar rats were divided into two groups: control and activity-based anorexia. When the weight loss of activity-based anorexia (ABA) rats reached 25% animals were euthanized. Size and weight measurements as well as histopathological analysis of the reproductive organs were performed. Additionally, we used immunohistochemical staining for detection of telocytes. RESULTS: Telocytes were identified in uteri of anorectic rats but no differences were observed when compared to the control group. Nevertheless, in the ABA group the weight of the uteri and the number of follicles in the ovaries decreased significantly. CONCLUSIONS: Our rat model of anorexia nervosa mimics the effects of this eating disorder that occur in the female reproductive system since we reported ovarian dysfunction and uterine involution in the experimental animals. It supports its potential role in the further studies of anorexia pathophysiology and treatment possibilities.

Nutritional parameters and carbohydrate and fat metabolism after prolonged salsolinol administration in rats fed normal or high-fat diets.

OBJECTIVES: Previous studies have reported that exogenous salsolinol might contribute to myenteric cell death and altered gastrointestinal motility. Because the entire gut mucosal, entero-endocrine and motor functions are integrated by the enteric nervous system, the aim of the present study was to investigate if prolonged intraperitoneal salsolinol administration alters basic metabolism and nutritional parameters in adult Wistar rats fed normal or high-fat diets. METHODS: Male Wistar rats were subjected to continuous intraperitoneal low dosing of salsolinol with ALZET osmotic mini-pumps for 2 or 4 weeks and fed either a normal or high-fat diet. Appropriate groups served as the controls. Nutritional status (food intake, body weight, and epididymal fat pads weight), residual solid food in the stomach and biochemical parameters (GIP, GLP-1, CRF, glucose, TG, LDL, HDL) were assessed. RESULTS: Prolonged salsolinol treatment significantly reduced total body mass and adipose tissue accumulation. The effects were more pronounced in the salsolinol-treated rats fed a high-fat diet. In salsolinol-treated rats, serum postprandial GIP levels were elevated, and serum postprandial GLP-1 levels were lower compared with the appropriate controls. CONCLUSIONS: Salsolinol might influence the regulatory mechanisms of body weight and epididymal fat pad accumulation through neurohormonal pathways.

The Impact of Prenatal Alcohol Exposure on the Autonomic Nervous System and Cardiovascular System in Rats in a Sex-Specific Manner.

BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is a consequence of prenatal alcohol exposure (PAE) associated with a range of effects, including dysmorphic features, prenatal and/or postnatal growth problems, and neurodevelopmental difficulties. Despite advances in treatment methods, there are still gaps in knowledge that highlight the need for further research. The study investigates the effect of PAE on the autonomic system, including sex differences that may aid in early FASD diagnosis, which is essential for effective interventions. METHODS: During gestational days 5 to 20, five pregnant female Wistar rats were orally administered either glucose or ethanol. After 22 days, 26 offspring were born and kept with their mothers for 21 days before being isolated. Electrocardiographic recordings were taken on the 29th and 64th day. Heart rate variability (HRV) parameters were collected, including heart rate (HR), standard deviation (SD), standard deviation of normal-to-normal intervals (SDNN), and the root mean square of successive differences between normal heartbeats (RMSSD). Additionally, a biochemical analysis of basic serum parameters was performed on day 68 of the study. RESULTS: The study found that PAE had a significant impact on HRV. While electrolyte homeostasis remained mostly unaffected, sex differences were observed across various parameters in both control and PAE groups, highlighting the sex-specific effects of PAE. Specifically, the PAE group had lower mean heart rates, particularly among females, and higher SDNN and RMSSD values. Additionally, there was a shift towards parasympathetic activity and a reduction in heart rate entropy in the PAE group. Biochemical changes induced by PAE were also observed, including elevated levels of alanine transaminase (ALT) and aspartate aminotransferase (AST), especially in males, increased creatinine concentration in females, and alterations in lipid metabolism. CONCLUSIONS: PAE negatively affects the development of the autonomic nervous system, resulting in decreased heart rate and altered sympathetic activity. PAE also induces cardiovascular abnormalities with sex-specific effects, highlighting a relationship between PAE consequences and sex. Elevated liver enzymes in the PAE group may indicate direct toxic effects, while increased creatinine levels, particularly in females, may suggest an influence on nephrogenesis and vascular function. The reduced potassium content may be linked to hypothalamus-pituitary-adrenal axis overactivity.

Neuroprotective Activity of Enantiomers of Salsolinol and N-Methyl-(R)-salsolinol: In Vitro and In Silico Studies.

Salsolinol (1-methyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol) is a close structural analogue of dopamine with an asymmetric center at the C1 position, and its presence in vivo, both in humans and rodents, has already been proven. Yet, given the fact that salsolinol colocalizes with dopamine-rich regions and was first detected in the urine of Parkinson's disease patients, its direct role in the process of neurodegeneration has been proposed. Here, we report that R and S enantiomers of salsolinol, which we purified from commercially available racemic mixture by means of high-performance liquid chromatography, exhibited neuroprotective properties (at the concentration of 50 µM) toward the human dopaminergic SH-SY5Y neuroblastoma cell line. Furthermore, within the study, we observed no toxic effect of N-methyl-(R)-salsolinol on SH-SY5Y neuroblastoma cells up to the concentration of 750 µM, either. Additionally, our molecular docking analysis showed that enantiomers of salsolinol should exhibit a distinct ability to interact with dopamine D2 receptors. Thus, we postulate that our results highlight the need to acknowledge salsolinol as an active dopamine metabolite and to further explore the neuroregulatory role of enantiomers of salsolinol.

Health-Related Quality of Life in Relation to Fruit and Vegetable Intake among Polish Pharmacists.

A direct association between health-related quality of life (HQoL) and nutrition remains unclear, although lifestyle habits are known to impact on human health. Thus, the aim of this study was to estimate an association between dietary habits, such as vegetable and fruit consumption, in particular, and HQoL. SF-36 (RAND-SF-36) and the Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN) were addressed to Polish pharmacists with a valid professional license. After the preliminary verification, 667 pharmacists were included into the study, and altogether, 11 questions from the KomPAN questionnaire and all RAND-SF-36 multiple choice questions were processed for statistical analysis. All HQoL scores, excluding physical functioning and role-physical, were significantly higher in the group declaring fruit consumption ≥1 time per day (p < 0.005), while physical functioning (p = 0.008) and general health (p = 0.03) were significantly higher in the group declaring vegetable consumption ≥1 time per day. Thus, there is indeed a positive association between vegetable and fruit consumption and HQoL. Increased fruit intake could certainly impact on the health-related quality of life of Polish pharmacists, primarily in terms of mental functioning, while increased vegetable intake could impact in terms of physical functioning.

Advancing European nutrition - are pharmacists eligible partners in the process?

BACKGROUND/OBJECTIVES: Pharmacists may play an important role in disease prevention through the public education about dietary and lifestyle behaviors, however their expertise is constantly ignored. The study primarily aimed to identify nutrition knowledge and dietary habits among Polish pharmacists. SUBJECTS: A total sample screened consisted of 1412 respondents, yet 667 (573 females and 94 males) pharmacists finally participated in the study. A validated questionnaire for Polish population, the Dietary Habits and Nutrition Beliefs Questionnaire, was used for the evaluation. RESULTS: The majority of pharmacists (94%) were current non-smokers with BMI levels below 25 kg/m2 (66.5%). Female pharmacists had higher the Pro-Healthy (pHDI-10) score (p < 0.001) and lower the Non-Healthy (nHDI-14) score (p = 0.004) compared to the males. In the self-assessment of nutritional habits, the pHDI-10 was significantly higher in the "very good" group compared to the "poor" (p < 0.001) and the "very poor" (p = 0.015) group, and the "poor group" had higher nHDI-14 when compared to "very good" (p < 0.001) and "good" (p < 0.001) groups. The nutrition knowledge test score was above average in over 72% of respondents, was correlated with the pHDI-10 (r = 0.16), yet the score decreased with age (r = -0.19). CONCLUSIONS: We believe that our analysis justifies the inevitability to benefit from pharmacists' expertise. Pharmacists with around-the-clock accessibility should be eligible partners, as members of an interdisciplinary team, in the process of advancing population-based nutrition.

Cardiotoxicity of Fluoropyrimidines: Epidemiology, Mechanisms, Diagnosis, and Management.

Cancer is a growing public health problem; it is responsible annually for millions of deaths worldwide. Fluoropyrimidines are highly effective and commonly prescribed anti-neoplastic drugs used in a wide range of chemotherapy regimens against several types of malignancies. 5-fluorouracil and its prodrugs affect neoplastic cells in multiple ways by impairing their proliferation, principally through the inhibition of thymidylate synthase. Fluoropyrimidine-induced cardiotoxicity was described more than 50 years ago, but many details such as incidence, mechanisms, and treatment are unclear and remain disputed. Severe cardiotoxicity is not only life-threatening, but also leads to withdrawal from an optimal chemotherapy regimen and decreases survival rate. Differences in the frequency of cardiotoxicity are explained by different chemotherapy schedules, doses, criteria, and populations. Proposed pathophysiological mechanisms include coronary vasospasm, endothelial damage, oxidative stress, Krebs cycle disturbances, and toxic metabolites. Such varied pathophysiology of the cardiotoxicity phenomenon makes prevention and treatment more difficult. Cardiovascular disturbances, including chest pain, arrhythmias, and myocardial infarction, are among the most common side effects of this class of anti-neoplastic medication. This study aims to summarize the available data on fluoropyrimidine cardiotoxicity with respect to symptoms, incidence, metabolism, pathophysiological mechanism, diagnosis, management, and resistance.

Is the Activity-Based Anorexia Model a Reliable Method of Presenting Peripheral Clinical Features of Anorexia Nervosa?

Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.

Backstage of Eating Disorder-About the Biological Mechanisms behind the Symptoms of Anorexia Nervosa.

Anorexia nervosa (AN) represents a disorder with the highest mortality rate among all psychiatric diseases, yet our understanding of its pathophysiological components continues to be fragmentary. This article reviews the current concepts regarding AN pathomechanisms that focus on the main biological aspects involving central and peripheral neurohormonal pathways, endocrine function, as well as the microbiome-gut-brain axis. It emerged from the unique complexity of constantly accumulating new discoveries, which hamper the ability to look at the disease in a more comprehensive way. The emphasis is placed on the mechanisms underlying the main symptoms and potential new directions that require further investigation in clinical settings.