Supplementation of Micro- and Macronutrients-A Role of Nutritional Status in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a condition in which the pathological cumulation of fat with coexisting inflammation and damage of hepatic cells leads to progressive dysfunctions of the liver. Except for the commonly well-known major causes of NAFLD such as obesity, dyslipidemia, insulin resistance, or diabetes, an unbalanced diet and imbalanced nutritional status should also be taken into consideration. In this narrative review, we summarized the current knowledge regarding the micro- and macronutrient status of patients suffering from NAFLD considering various diets and supplementation of chosen supplements. We aimed to summarize the knowledge indicating which nutritional impairments may be associated with the onset and progression of NAFLD at the same time evaluating the potential therapy targets that could facilitate the healing process. Except for the above-mentioned objectives, one of the most important aspects of this review was to highlight the possible strategies for taking care of NAFLD patients taking into account the challenges and opportunities associated with the micronutrient status of the patients. The current research indicates that a supplementation of chosen vitamins (e.g., vitamin A, B complex, C, or D) as well as chosen elements such as zinc may alleviate the symptoms of NAFLD. However, there is still a lack of sufficient data regarding healthy ranges of dosages; thus, further research is of high importance in this matter.

Micronutrient Status and Breast Cancer: A Narrative Review.

Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women's death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and progression. Another important factor in breast cancer onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients and their possible influence on breast cancer onset and progression. Further, the aim of this study was to investigate the impact of micronutrient status on the prevention of breast cancer and its possible influence on various therapeutic pathways. We researched meta-analyses, systemic and narrative reviews, retrospective studies, as well as original studies on human and animal models. The results of these studies indicate a possible correlation between the different levels of micronutrients and a decreased risk of breast cancer as well as a better survival rate. However, further studies are necessary to establish adequate doses of supplementation of the chosen micronutrients and the exact mechanisms of micronutrient impact on breast cancer therapy.

An Overview of the Spices Used for the Prevention and Potential Treatment of Gastric Cancer.

Gastric cancer (GC) ranks third in terms of cancer-related deaths and is the fifth most commonly diagnosed type of cancer. Its risk factors include Helicobacter pylori infection, Epstein-Barr virus infection, the consumption of broiled and charbroiled animal meats, salt-preserved and smoke-enhanced foods, alcohol drinking, tobacco smoking, exposure to ionizing radiation, and positive family history. The limited effectiveness of conventional therapies and the widespread risk factors of GC encourage the search for new methods of treatment and prevention. In the quest for cheap and commonly available medications, numerous studies focus on herbal medicine, traditional brews, and spices. In this review, we outline the potential use of spices, including turmeric, ginger, garlic, black cumin, chili pepper, saffron, black pepper, rosemary, galangal, coriander, wasabi, cinnamon, oregano, cardamom, fenugreek, caraway, clove, dill, thyme, Piper sarmentosum, basil, as well as the compounds they contain, in the prevention and treatment of GC. We present the potential molecular mechanisms responsible for the effectivity of a given seasoning substance and their impact on GC cells. We discuss their potential effects on proliferation, apoptosis, and migration. For most of the spices discussed, we also outline the unavailability and side effects of their use.

Trace Elements in Alzheimer's Disease and Dementia: The Current State of Knowledge.

Changes in trace element concentrations are being wildly considered when it comes to neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. This study aims to present the role that trace elements play in the central nervous system. Moreover, we reviewed the mechanisms involved in their neurotoxicity. Low zinc concentrations, as well as high levels of copper, manganese, and iron, activate the signalling pathways of the inflammatory, oxidative and nitrosative stress response. Neurodegeneration occurs due to the association between metals and proteins, which is then followed by aggregate formation, mitochondrial disorder, and, ultimately, cell death. In Alzheimer's disease, low Zn levels suppress the neurotoxicity induced by ß-amyloid through the selective precipitation of aggregation intermediates. High concentrations of copper, iron and manganese cause the aggregation of intracellular α-synuclein, which results in synaptic dysfunction and axonal transport disruption. Parkinson's disease is caused by the accumulation of Fe in the midbrain dopaminergic nucleus, and the pathogenesis of multiple sclerosis derives from Zn deficiency, leading to an imbalance between T cell functions. Aluminium disturbs the homeostasis of other metals through a rise in the production of oxygen reactive forms, which then leads to cellular death. Selenium, in association with iron, plays a distinct role in the process of ferroptosis. Outlining the influence that metals have on oxidoreduction processes is crucial to recognising the pathophysiology of neurodegenerative diseases and may provide possible new methods for both their avoidance and therapy.

Selective Removal of Chlorophyll and Isolation of Lutein from Plant Extracts Using Magnetic Solid Phase Extraction with Iron Oxide Nanoparticles.

In recent years, there has been a growing interest in plant pigments as readily available nutraceuticals. Photosynthetic pigments, specifically chlorophylls and carotenoids, renowned for their non-toxic antioxidant properties, are increasingly finding applications beyond their health-promoting attributes. Consequently, there is an ongoing need for cost-effective methods of isolation. This study employs a co-precipitation method to synthesize magnetic iron oxide nanoparticles. Scanning electron microscopy (SEM) coupled with energy dispersive spectrometry (EDS) confirms that an aqueous environment and oxidizing conditions yield nanosized iron oxide with particle sizes ranging from 80 to 140 nm. X-ray photoelectron spectroscopy (XPS) spectra indicate the presence of hydrous iron oxide FeO(OH) on the surface of the nanosized iron oxide. The Brunauer-Emmett-Teller (BET) surface area of obtained nanomaterial was 151.4 m2 g-1, with total pore volumes of pores 0.25 cm3 g-1 STP. The material, designated as iron oxide nanoparticles (IONPs), serves as an adsorbent for magnetic solid phase extraction (MSPE) and isolation of photosynthetic pigments (chlorophyll a, lutein) from extracts of higher green plants (Mentha piperita L., Urtica dioica L.). Sorption of chlorophyll a onto the nanoparticles is confirmed using UV-vis spectroscopy, Fourier transform infrared photoacoustic spectroscopy (FT-IR/PAS), and high-performance liquid chromatography (HPLC). Selective sorption of chlorophyll a requires a minimum of 3 g of IONPs per 12 mg of chlorophyll a, with acetone as the solvent, and is dependent on a storage time of 48 h. Extended contact time of IONPs with the acetone extract, i.e., 72 h, ensures the elimination of remaining components except lutein, with a spectral purity of 98%, recovered with over 90% efficiency. The mechanism of chlorophyll removal using IONPs relies on the interaction of the pigment's carbonyl (C=O) groups with the adsorbent surface hydroxyl (-OH) groups. Based on molecular dynamics (MD) simulations, it has been proven that the selective adsorption of pigments is also influenced by more favorable dispersion interactions between acetone and chlorophyll in comparison with other solutes. An aqueous environment significantly promotes the removal of pigments; however, it results in a complete loss of selectivity.

Common fibular nerve palsy due to the Fabella: A review.

One of the most common nerve palsies - common fibular nerve palsy - can be caused by the variant small sesamoid bone in the posterolateral compartment of the knee joint known as the fabella. We compared and reviewed all reported cases of common fibular nerve palsy due to fabellae in the English literature. Compression can develop spontaneously or post-surgically (total knee arthroplasty). Symptoms progress rapidly to complete foot drop. Among all the cases reviewed, 68.42% were males with a median age of 39.39 years. Fabella compression was more common in the left common fibular nerve (CFN) (63.16%). Both big (23 × 20 × 16 mm) and small (5 × 5 mm) fabellae can be responsible for compression. While diagnosis can be problematic, the treatment (either surgical fabellectomy or conservative) is relatively easy and brings quick improvement.

Consequences of Disturbing Manganese Homeostasis.

Manganese (Mn) is an essential trace element with unique functions in the body; it acts as a cofactor for many enzymes involved in energy metabolism, the endogenous antioxidant enzyme systems, neurotransmitter production, and the regulation of reproductive hormones. However, overexposure to Mn is toxic, particularly to the central nervous system (CNS) due to it causing the progressive destruction of nerve cells. Exposure to manganese is widespread and occurs by inhalation, ingestion, or dermal contact. Associations have been observed between Mn accumulation and neurodegenerative diseases such as manganism, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. People with genetic diseases associated with a mutation in the gene associated with impaired Mn excretion, kidney disease, iron deficiency, or a vegetarian diet are at particular risk of excessive exposure to Mn. This review has collected data on the current knowledge of the source of Mn exposure, the experimental data supporting the dispersive accumulation of Mn in the brain, the controversies surrounding the reference values of biomarkers related to Mn status in different matrices, and the competitiveness of Mn with other metals, such as iron (Fe), magnesium (Mg), zinc (Zn), copper (Cu), lead (Pb), calcium (Ca). The disturbed homeostasis of Mn in the body has been connected with susceptibility to neurodegenerative diseases, fertility, and infectious diseases. The current evidence on the involvement of Mn in metabolic diseases, such as type 2 diabetes mellitus/insulin resistance, osteoporosis, obesity, atherosclerosis, and non-alcoholic fatty liver disease, was collected and discussed.

Trace Elements Levels in Major Depressive Disorder-Evaluation of Potential Threats and Possible Therapeutic Approaches.

The multifactorial etiology of major depressive disorder (MDD) includes biological, environmental, genetic, and psychological aspects. Recently, there has been an increasing interest in metallomic studies in psychiatry, aiming to evaluate the role of chosen trace elements in the MDD etiology as well as the progression of symptoms. This narrative review aims to summarize the available literature on the relationship between the concentration of chosen elements in the serum of patients with MDD and the onset and progression of this psychiatric condition. The authors reviewed PubMed, Web of Science, and Scopus databases searching for elements that had been investigated so far and further evaluated them in this paper. Ultimately, 15 elements were evaluated, namely, zinc, magnesium, selenium, iron, copper, aluminium, cadmium, lead, mercury, arsenic, calcium, manganese, chromium, nickel, and phosphorus. The association between metallomic studies and psychiatry has been developing dynamically recently. According to the results of current research, metallomics might act as a potential screening tool for patients with MDD while at the same time providing an assessment of the severity of symptoms. Either deficiencies or excessive amounts of chosen elements might be associated with the progression of depressive symptoms or even the onset of the disease among people predisposed to MDD.

Technological Advances in a Therapy of Primary Open-Angle Glaucoma: Insights into Current Nanotechnologies.

Glaucoma is a leading cause of irreversible blindness and is characterized by increased intraocular pressure (IOP) and progressive optic nerve damage. The current therapeutic approaches for glaucoma management, such as eye drops and oral medications, face challenges including poor bioavailability, low patient compliance, and limited efficacy. In recent years, nanotechnology has emerged as a promising approach to overcome these limitations and revolutionize glaucoma treatment. In this narrative review, we present an overview of the novel nanotechnologies employed in the treatment of primary open-angle glaucoma. Various nanosystems, including liposomes, niosomes, nanoparticles, and other nanostructured carriers, have been developed to enhance the delivery and bioavailability of antiglaucoma drugs. They offer advantages such as a high drug loading capacity, sustained release, improved corneal permeability, and targeted drug delivery to the ocular tissues. The application of nanotechnologies in glaucoma treatment represents a transformative approach that addresses the limitations of conventional therapies. However, further research is needed to optimize the formulations, evaluate long-term safety, and implement these nanotechnologies into clinical practice. With continued advancements in nanotechnology, the future holds great potential for improving the management and outcomes of glaucoma, ultimately preserving vision and improving the lives of millions affected by this debilitating disease.

Linking Metallic Micronutrients and Toxic Xenobiotics to Atherosclerosis and Fatty Liver Disease-Postmortem ICP-MS Analysis of Selected Human Tissues.

Dyslipidaemia is a disorder of the lipid metabolism, caused mainly by poor eating habits. The most severe consequence of an inappropriate diet is the development of atherosclerosis and hepatic steatosis. It is generally believed that a change in nutrition, and increased physical activity can eliminate these health problems. The contemporary research and therapies used to treat dyslipidemia mainly focus on lowering the triglyceride and cholesterol levels. However, disturbances in trace element homeostasis or the accumulation of toxic elements can also affect physiological processes, and be involved in the development of metabolically mediated diseases. The present study aimed to determine the mineral profiles of liver and brain tissues collected at autopsy (n = 39) in groups of people with hepatic steatosis (n = 5), atherosclerosis (n = 9), hepatic steatosis, and atherosclerosis (n = 16), and others without the selected disorders (n = 9). Concentrations of 51 elements were analysed via inductively coupled plasma mass spectrometry (ICP-MS) after the initial wet mineralisation of the samples with nitric acid. The results obtained allow us to conclude that the hepatic steatosis group suffers from a deficiency of important trace elements, such as copper, zinc, and molybdenum (p < 0.05), whereas the group with atherosclerosis is characterised by elevated levels of cadmium in the liver tissue (p = 0.01). Analysing the mean values of the element concentrations measured in 11 brain areas, statistically significant higher levels of calcium and copper (p < 0.001) were found in the atherosclerosis group, compared to the hepatic steatosis group, confirming the involvement of these elements in the pathogenesis of atherosclerosis. In addition, an accumulation of cadmium, lead, titanium, and strontium in the brain tissue was observed in the atherosclerosis group. While the accumulation of individual elements differs in different parts of the brain, the differences in the cadmium content (p < 0.05) between the study groups apply to the whole brain, except for the nucleus accumbens septi area, where a statistically significant titanium accumulation occurs in the atherosclerosis and steatosis groups, compared to the others (p < 0.05). In addition, the disruption of elemental homeostasis in the brain of a single case with bipolar disorder, and a case with hip replacement was observed. Our results confirm the involvement of chemical elements in the pathogenesis of selected metabolic diseases, and the need for further studies in larger populations.

Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis.

Current views show that an impaired balance partly explains the fat accumulation leading to obesity. Fetal malnutrition and early exposure to endocrine-disrupting compounds also contribute to obesity and impaired insulin secretion and/or sensitivity. The liver plays a major role in systemic glucose homeostasis through hepatokines secreted by hepatocytes. Hepatokines influence metabolism through autocrine, paracrine, and endocrine signaling and mediate the crosstalk between the liver, non-hepatic target tissues, and the brain. The liver also synthetizes bile acids (BAs) from cholesterol and secretes them into the bile. After food consumption, BAs mediate the digestion and absorption of fat-soluble vitamins and lipids in the duodenum. In recent studies, BAs act not simply as fat emulsifiers but represent endocrine molecules regulating key metabolic pathways. The liver is also the main site of the production of ketone bodies (KBs). In prolonged fasting, the brain utilizes KBs as an alternative to CHO. In the last few years, the ketogenic diet (KD) became a promising dietary intervention. Studies on subjects undergoing KD show that KBs are important mediators of inflammation and oxidative stress. The present review will focus on the role played by hepatokines, BAs, and KBs in obesity, and diabetes prevention and management and analyze the positive effects of BAs, KD, and hepatokine receptor analogs, which might justify their use as new therapeutic approaches for metabolic and aging-related diseases.

Assessment of the Concentration of 51 Elements in the Liver and in Various Parts of the Human Brain-Profiling of the Mineral Status.

The anthropogenic environment and diet introduce many metals into the human body, both essential and toxic. Absorption leads to systemic exposure and accumulation in body fluids and tissues. Both excess and deficiency of trace elements are health hazards. The primary aim of the present study was to evaluate the concentration of 51 elements in liver samples and 11 selected brain regions obtained at post-mortem examination from a population of adults living in south-eastern Poland (n = 15). A total of 180 analyses were performed by inductively coupled plasma mass spectrometry in two independent replicates. The collected data show very high individual variability in the content of the investigated elements. Macroelements such as sodium, magnesium, phosphorus, potassium, calcium, iron, and zinc occurred in the highest concentrations and with the greatest statistically significant variations. Although the elemental content of the brain and liver differed significantly, the strongest positive correlation between liver and polus frontalis was observed for the essential element selenium (0.9338) and the strongest negative one for manganese (-0.4316) and lanthanum (-0.5110). The brain areas studied have different requirements for phosphorus, manganese, iron, and molybdenum. In addition, males had a significantly (p < 0.05) higher brain content of lanthanides and actinides than females. The results of this study show that the inhabitants of south-eastern Poland are exposed to a fairly uniform accumulation of aluminum and vanadium in the brain, which have the highest affinity to the thalamus dorsalis. This result proves that there is environmental exposure to these elements.

The Future of Morphological Science Education: Learning and Teaching Anatomy in the Wake of the COVID-19 Pandemic.

The COVID-19 Pandemic has conveyed an unprecedented worldwide challenge. Although there is much emphasis on caring for patients and communities, the high incidence of SARS-CoV-2 had seriously disturbed education and calls for prompt as well as serious consideration from educators in medical schools. The necessity to teach and prepare prospective medics, as well as clinicians, has certainly not been as intense as it is currently. The global effects of coronavirus disease 2019 may cause a permanent change in the education of future clinicians. The COVID-19 era presented logistical and practical obstacles and fears for the patients' well-being, taking into consideration the fact that students may be potential channels for the spread of the virus when asymptomatic and may get infected while being in training and attending lectures. This paper discusses the present state of morphological science education, depicting the effect of COVID-19 on learning environments, as well as highlights the probable effects of COVID-19 on medical instruction in the future.

Aluminium in the Human Brain: Routes of Penetration, Toxicity, and Resulting Complications.

Aluminium (Al) is the most ubiquitous metal in the Earth's crust. Even though its toxicity is well-documented, the role of Al in the pathogenesis of several neurological diseases remains debatable. To establish the basic framework for future studies, we review literature reports on Al toxicokinetics and its role in Alzheimer's disease (AD), autism spectrum disorder (ASD), alcohol use disorder (AUD), multiple sclerosis (MS), Parkinson's disease (PD), and dialysis encephalopathy (DE) from 1976 to 2022. Despite poor absorption via mucosa, the biggest amount of Al comes with food, drinking water, and inhalation. Vaccines introduce negligible amounts of Al, while the data on skin absorption (which might be linked with carcinogenesis) is limited and requires further investigation. In the above-mentioned diseases, the literature shows excessive Al accumulation in the central nervous system (AD, AUD, MS, PD, DE) and epidemiological links between greater Al exposition and their increased prevalence (AD, PD, DE). Moreover, the literature suggests that Al has the potential as a marker of disease (AD, PD) and beneficial results of Al chelator use (such as cognitive improvement in AD, AUD, MS, and DE cases).

Niacin Skin Flush Backs-From the Roots of the Test to Nowadays Hope.

The niacin skin flush test (NSFT) is a simple method used to assess the content of fatty acids in cell membranes and is a possible indicator of factors hidden behind various outcomes in patients. The purpose of this paper is to determine the potential usefulness of NSFT in mental disorder diagnostics along with the determination of factors that may affect its results. The authors reviewed articles from 1977 onwards, focusing on the history, variety of methodologies, influencing factors, and proposed mechanisms underlying its performance. Research indicated that NSFT could be applicable in early intervention, staging in psychiatry, and the search for new therapeutic methods and drugs based on the mechanisms of NSFT action. The NSFT can contribute to defining an individualized diet for patients and prevent the development of damaging disease effects at an early stage. There is promising evidence for supplementation with polyunsaturated fatty acids, which have a beneficial influence on the metabolic profile and are effective even in the subclinical phase of the disease. NSFT can contribute to the new classification of diseases and a better understanding of certain mental disorders' pathophysiology. However, there is a need to establish a validated method for assessing the NSFT results.

Application of 3D Printing in Bone Grafts.

The application of 3D printing in bone grafts is gaining in importance and is becoming more and more popular. The choice of the method has a direct impact on the preparation of the patient for surgery, the probability of rejection of the transplant, and many other complications. The aim of the article is to discuss methods of bone grafting and to compare these methods. This review of literature is based on a selective literature search of the PubMed and Web of Science databases from 2001 to 2022 using the search terms "bone graft", "bone transplant", and "3D printing". In addition, we also reviewed non-medical literature related to materials used for 3D printing. There are several methods of bone grafting, such as a demineralized bone matrix, cancellous allograft, nonvascular cortical allograft, osteoarticular allograft, osteochondral allograft, vascularized allograft, and an autogenic transplant using a bone substitute. Currently, autogenous grafting, which involves removing the patient's bone from an area of low aesthetic importance, is referred to as the gold standard. 3D printing enables using a variety of materials. 3D technology is being applied to bone tissue engineering much more often. It allows for the treatment of bone defects thanks to the creation of a porous scaffold with adequate mechanical strength and favorable macro- and microstructures. Bone tissue engineering is an innovative approach that can be used to repair multiple bone defects in the process of transplantation. In this process, biomaterials are a very important factor in supporting regenerative cells and the regeneration of tissue. We have years of research ahead of us; however, it is certain that 3D printing is the future of transplant medicine.

Clinical significance of Left-Sided Gallbladder for laparoscopic cholecystectomy and hepatectomy.

A left-sided gallbladder (LSG) represents a rare anatomical variation defined by the location of the gallbladder to the left side of the liver falciform and round ligaments, which is often not discovered until surgery. The reported prevalence of this ectopia ranges from 0.2% to 1.1%, however, those values may be underestimated. It is mostly an asymptomatic condition, thus not causing the patient any harm, and being few reported cases in the current literature. Based on clinical presentation and standard diagnostic procedures, LSG can remain undetected and represent accidental intraoperative finding. The attempts to explain the cause of this anomaly have been different, but the numerous variations described do not allow a clear definition of its origin. Although this debate is still open, it is of considerable importance to know that LSG is frequently associated with alterations of both the portal branches and the intrahepatic biliary tree. The association of these anomalies, therefore, represents an important risk of complications in cases when surgical treatment is necessary. In this context, our literature review aimed to summarize possible anatomical anomalies coexisting with LSG and discuss the clinical significance of the LSG, when the patient requires cholecystectomy or hepatectomy.

The relation between the depth of pigment disposition and men's skin thickness, the age and tattoo locations on the body.

The most important function of the skin is to protect the body against harmful mechanical, physical and chemical factors. Its regenerative capacity is sufficient for self-repair in the event of damage, for example, during tattooing, which can be treated as an invasive procedure introducing pigment molecules into skin layers. In the present research on tattoo pigment deposition, the structure of the dermis and epidermis was evaluated using the standard histological technique with hematoxylin and eosin staining. In addition, statistically significant differences between the depth of pigment deposition on the one hand and age, dermis and epidermis thickness and tattoo location on the other were demonstrated.

Nutritional Supplements for Skin Health-A Review of What Should Be Chosen and Why.

Supplementation of micronutrients is considered to be crucial in the reinforcement of the skin's barrier. In this paper, 14 nutritional compounds commonly used in food or pharmaceutic industries were analyzed in terms of influencing skin conditions. The major objective of this paper was to provide a narrative review of the available literature regarding several chosen compounds that are currently widely recommended as supplements that aim to maintain proper and healthy skin conditions. We conducted a review of the literature from PubMed, Scopus, and Web of Science until September 2023 without any other restrictions regarding the year of the publication. Ultimately, we reviewed 238 articles, including them in this review. Each of the reviewed compounds, including vitamin A, vitamin C, vitamin D, vitamin E, curcumin, chlorella, Omega-3, biotin,Ppolypodium leucotomos, Simmondsia chinesis, gamma oryzanol, olive leaf extract, spirulina, and astaxanthin, was observed to present some possible effects with promising benefits for a skin condition, i.e., photoprotective radiation. Adding them to the diet or daily routine might have a positive influence on some skin inflammatory diseases such as atopic dermatitis or psoriasis. Further, UV radiation protection facilitated by some supplements and their impact on human cells might be helpful during chemotherapy or in preventing melanoma development. Further research is needed because of the lack of clear consensus regarding the doses of the described compounds that could provide desirable effects on the skin.

Recent Advances in the Digestive, Metabolic and Therapeutic Effects of Farnesoid X Receptor and Fibroblast Growth Factor 19: From Cholesterol to Bile Acid Signaling.

Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In the small intestine, BA act as strong detergents for emulsification, solubilization and absorption of dietary fat, cholesterol, and lipid-soluble vitamins. Primary BA escaping the active ileal re-absorption undergo the microbiota-dependent biotransformation to secondary BA in the colon, and passive diffusion into the portal vein towards the liver. BA also act as signaling molecules able to play a systemic role in a variety of metabolic functions, mainly through the activation of nuclear and membrane-associated receptors in the intestine, gallbladder, and liver. BA homeostasis is tightly controlled by a complex interplay with the nuclear receptor farnesoid X receptor (FXR), the enterokine hormone fibroblast growth factor 15 (FGF15) or the human ortholog FGF19 (FGF19). Circulating FGF19 to the FGFR4/ß-Klotho receptor causes smooth muscle relaxation and refilling of the gallbladder. In the liver the binding activates the FXR-small heterodimer partner (SHP) pathway. This step suppresses the unnecessary BA synthesis and promotes the continuous enterohepatic circulation of BAs. Besides BA homeostasis, the BA-FXR-FGF19 axis governs several metabolic processes, hepatic protein, and glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted in cholestasis, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Thus, targeting FXR activity can represent a novel therapeutic approach for the prevention and the treatment of liver and metabolic diseases.