Genetic, Immunological, Dietary, Gut Microbiota, and Environmental Determinants of Osteoporosis in the Course of Celiac Disease: Which Factor Plays the First Violin in This Orchestra?

Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The worldwide prevalence of CD is estimated to be 0.7-1.4% of the general population. Etiopathology of this disease is multifactorial, with genetic determinants being a major contributing player to CD susceptibility. Its manifestation embraces different organs, including the musculoskeletal apparat. Patients with CD have increased risk of bone disorders. According to data, bone disorders - osteopenia and osteoporosis - can affect up to 70% of patients with CD at diagnosis, and it decreases after the initiation of a gluten-free diet. Gluten consumption in patients with CD triggers an inflammatory reaction followed by tissue damage, and both; local and systemic inflammation can increase the risk of bone mass deterioration. Other theory assumes shortages of vitamin D and an impaired calcium absorption mechanism leading to secondary hyperparathyroidism. Taking into account the increasing prevalence of CD and osteoporosis, we broadly discuss genetic, immunological, dietary, gut microbiota, and environmental factors that could increase the risk of osteoporosis in CD. Furthermore, we discuss lifestyle and pharmacological preventing and treatment measures.

Physical activity, quality of diet and bone mineral density in patients with inflammatory bowel disease.

BACKGROUND: The aim of this study was to find an association between moderate, vigorous and total physical activity (PA); diet quality; and bone mineral density (BMD) among patients suffering from inflammatory bowel disease (IBD). METHODS: We enrolled 54 IBD patients, including those with Crohn's disease (CD) and ulcerative colitis (UC), and 24 healthy adults. All subjects completed the Questionnaire of Eating Behaviour based on which prohealthy and nonhealthy diet indexes were calculated, and the questionnaire included questions from the International Physical Activity Questionnaire. Prohealthy and nonhealthy diet indexes were divided into low-, medium- and high scores. BMD and T- and Z-scores of the lumbar spine (L1-L4) and femoral neck (FN) were assessed using dual-energy X-ray absorptiometry method. RESULTS: BMD, T- and Z-scores of the FN and the Z-score of L1-L4 were significantly lower among patients with CD and UC than healthy controls. We did not find any differences in the time of PA among CD, UC and control groups (CG). The prohealthy diet index was higher among healthy subjects than the CD and UC groups. The nonhealthy diet index was lower among UC patients compared with the CG or CD patients. Prohealthy diet index positively correlated with BMD and T- and Z-scores of L1-L4 and FN in IBD. The prohealthy diet index correlated negatively with C-reactive protein and positively with body mass index. The prohealthy diet index correlated only with total PA in the CD group. CONCLUSION: A well-balanced diet and proper PA may decrease the risk of osteoporosis in IBD, so education of patients referring to nutrition and PA is needed.

Immunogenetic, Molecular and Microbiotic Determinants of Eosinophilic Esophagitis and Clinical Practice-A New Perspective of an Old Disease.

Eosinophilic oesophagitis (EoE) is a chronic, allergic disease associated with a T-lymphocyte response inducing esophageal eosinophilic infiltration in the esophagus. Inflammation and tissue fibrosis are responsible for the main clinical symptoms such as food impaction and dysphagia. The etiopathogenesis is multifactorial in which genetic and environmental factors coexist. The most common trigger is a non-IgE-mediated food allergy to milk, wheat, egg, soybean, nuts, fish, and seafood. The second factor we focus on is the contribution of genetic variation to the risk of EoE, describing the expression profile of selected genes associated with eosinophilic oesophagitis. We raise the topic of treatment, aiming to eliminate inflammation through an elimination diet and/or use of pharmacologic therapy with the use of proton pump inhibitors or steroids and endoscopic procedures to dilate the esophagus. We demonstrate that early diagnosis and effective treatment prevent the development of food impaction and decreased quality of life. The increasing presence of EoE requires bigger awareness among medical specialists concerning clinical features, the course of EoE, diagnostic tools, and management strategies.

Is the Retinol-Binding Protein 4 a Possible Risk Factor for Cardiovascular Diseases in Obesity?

Although many preventive and treatment approaches have been proposed, cardiovascular disease (CVD) remains one of the leading causes of deaths worldwide. Current epidemiological data require the specification of new causative factors, as well as the development of improved diagnostic tools to provide better cardiovascular management. Excessive accumulation of adipose tissue among patients suffering from obesity not only constitutes one of the main risk factors of CVD development but also alters adipokines. Increased attention is devoted to bioactive adipokines, which are also produced by the adipose tissue. The retinol-binding protein 4 (RBP4) has been associated with numerous CVDs and is presumably associated with an increased cardiovascular risk. With this in mind, exploring the role of RBP4, particularly among patients with obesity, could be a promising direction and could lead to better CVD prevention and management in this patient group. In our review, we summarized the current knowledge about RBP4 and its association with essential aspects of cardiovascular disease-lipid profile, intima-media thickness, atherosclerotic process, and diet. We also discussed the RBP4 gene polymorphisms essential from a cardiovascular perspective.

Short-term ammonium supply induces cellular defence to prevent oxidative stress in Arabidopsis leaves.

Plants can assimilate nitrogen from soil pools of both ammonium and nitrate, and the relative levels of these two nitrogen sources are highly variable in soil. Long-term ammonium nutrition is known to cause damage to Arabidopsis that has been linked to mitochondrial oxidative stress. Using hydroponic cultures, we analysed the consequences of rapid shifts between nitrate and ammonium nutrition. This did not induce growth retardation, showing that Arabidopsis can compensate for the changes in redox metabolism associated with the variations in nitrogen redox status. During the first 3 h of ammonium treatment, we observed distinct transient shifts in reactive oxygen species (ROS), low-mass antioxidants, ROS-scavenging enzymes, and mitochondrial alternative electron transport pathways, indicating rapid but temporally separated changes in chloroplastic, mitochondrial and cytosolic ROS metabolism. The fast induction of antioxidant defences significantly lowered intracellular H2 O2 levels, and thus protected Arabidopsis leaves from oxidative stress. On the other hand elevated extracellular ROS production in response to ammonium supply may be involved in signalling. The response pattern displays an intricate plasticity of Arabidopsis redox metabolism to minimise stress in responses to nutrient changes.

[Alternative oxidase - never ending story]. / Oksydaza alternatywna - niedokonczona opowiesc.

Investigations of plant cyanide resistant respiration lead to the discovery in mitochondrial respiratory chain of the second terminal oxidase, alternative oxidase (AOX). AOX transfers electrons from reduced ubiquinone to oxygen omitting two coupling places thus lowering energetic efficiency of respiration. The presence of AOX was shown in all plants and also in some fungi, mollusca and protista. In termogenic plants the activity of AOX is connected with heat production. In other organisms AOX activity is important for maintaining metabolic homeostasis (carbon metabolism, cell redox state and energy demand) and ROS homeostasis. In this article structure of plant AOX protein and the regulation on molecular levels was described. Possible role of AOX as stress marker was pointed and the possibility of using AOX in human gene therapy was discussed.

[Importance of physician-patient relations in therapeutic process of patients with hematological neoplasms]. / Znaczenie relacji lekarz-pacjent dla procesu terapeutycznego chorych na nowotwory ukladu krwiotwórczego.

A cancer diagnosis provides significantly level of emotional distress and discomfort both for patient and his family. They must confront themselves with the new, difficult reality. A cancer-related distress may promote the serious psychic disturbances and influenced negatively the therapeutic process. The good interpersonal relationship between physician and patient clearly decreased the level of fear and depression, improved patient's physical and psychical state. Patients who have good communication with their physician are more prone to good adherence and compliance which are essential for the effective therapeutic process. This article discusses the role of relationship between physician and patient regarding its influence on compliance and provides a review of different types of therapeutic contact and the principles of building the physician-patient relationship.

The role of genetic risk factors, diet, and gut microbiota in type 1 diabetes mellitus, pancreas and pancreatic islet transplantation.

Despite advances in insulin delivery and glucose monitoring technology, prevention of the progression of secondary complications in patients with type 1 diabetes (T1DM) remains a challenge. Beta cell replacement therapy in the form of islet or pancreas transplantation can restore long-term normoglycaemia with sustained periods of insulin independence among T1DM patients. However, the same genetic, behavioural, or gut microbiota-related factors that promoted autoimmunity and primary islet destruction may also affect the function of transplanted islets and the ultimate results of transplant procedures. In such cases, identifying genetic risk factors and modifying behavioural factors and those related to gut microbiota may be beneficial for the outcomes of transplant procedures. Herein, we review related literature to the identified current gap in knowledge to be addressed in future clinical trials.

From an understanding of etiopathogenesis to novel therapies-what is new in the treatment of celiac disease?

Celiac disease, a chronic autoimmune disorder caused by genetic factors and exposure to gluten, is increasingly being recognized and diagnosed in both children and adults. Scientists have been searching for a cure for this disease for many years, but despite the impressive development of knowledge in this field, a gluten-free diet remains the only recommended therapy for all patients. At the same time, the increasing diagnosis of celiac disease in adults, which was considered a childhood disease in the 20th century, has opened a discussion on the etiopathology of the disease, which is proven to be very complex and involves genetic, immunological, nutritional, environmental and gut microbiota-related factors. In this review, we extensively discuss these factors and summarize the knowledge of the proposed state-of-the-art treatments for celiac disease to address the question of whether a better understanding of the etiopathogenesis of celiac disease has opened new directions for therapy.

A high consumption of ultra-processed foods is associated with higher total mortality in an adult Mediterranean population.

BACKGROUND & AIMS: The consumption of ultra-processed foods (UPF) has been associated with higher all-cause and cardiovascular disease (CVD) mortality, although this association has not been sufficiently investigated in Mediterranean populations. We aimed to evaluate the association between UPF consumption and all-cause, CVD and cancer mortality in an adult population in Spain. METHODS: We analysed data from 1,538 participants aged 20 years and above in the Valencia Nutrition Survey in 1995. Diet was assessed at baseline using a validated food frequency questionnaire and the consumption of UPF was calculated using the NOVA system. Information on socio-demographic characteristics, lifestyles, and presence of diseases was also collected at baseline. Cause of death was ascertained during an 18-year follow-up period. We used Cox regression and competing risk models as proposed by Fine and Gray's to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (95 %CI). RESULTS: After 18 years of follow-up, we documented 312 deaths (36.5 % of CVD and 25.6 % of cancer). Compared with participants in the lowest tertile of UPF consumption, those in the highest tertile showed 40 % higher risk of all-cause mortality, HR 1.40 (95 %CI: 1.04-1.90), and evidence of a higher CVD mortality, HR 1.39 (95 %CI: 0.80-2.41) and of cancer mortality, HR 1.53 (95 %CI: 0.83-2.82). CONCLUSIONS: This study suggests that a high UPF consumption is associated with a higher all-cause mortality in a Mediterranean population after a long follow-up period. Considering the increase in UPF consumption and their detrimental health effects on mortality, these results should be confirmed by other studies in other populations.

Are variants of the RBP4 gene associated with serum retinol-binding protein 4 concentrations and carotid intima-media thickness values in women with obesity?

INTRODUCTION: Several studies showed the correlation of retinol-binding protein 4 (RBP4) with increased cardiovascular risk - including higher values of carotid intima-media thickness (cIMT) - particularly in individuals with obesity. OBJECTIVES: Our study aimed to investigate the impact of rs10882273; rs3758538; rs3758539, and rs7094671 RBP4 gene variants on RBP4 serum concentrations as well as cIMT values (a marker of subclinical atherosclerosis) among female patients with obesity. PATIENTS AND METHODS: We recruited 74 women with obesity and 24 women without obesity as a study and control group, respectively. The genotypic and allelic frequencies of RBP4 gene variants were evaluated for associations with serum RBP4 and cIMT. RESULTS: The median serum RBP4 concentrations were 20.30 µg/mL and 19.80 µg/mL in the patients and control group, respectively (p = 0.740). No significant differences were seen in cIMT values between the two studied groups (0.60 [0.50-1.00] vs. 0.60 ± 0.10 in the patient and control group, respectively); however, the results were close to reaching significance (p = 0.071), similar as in observed association of the minor haplotype AA for rs7084671 and rs375839 with female obesity (p = 0.0559). The correlation analysis showed no significant differences between RBP4 gene variants with serum RBP4 and cIMT. CONCLUSIONS: According to our knowledge, this is the first study investigating the association between RBP4 gene variants and serum RBP4 and cIMT among Polish female patients with obesity. However, our results show that genetic variants rs10882273, rs3758538, rs3758539, and rs7094671 of the RBP4 gene are not associated with RBP4 serum concentrations or cIMT values among women with obesity.

Personality traits favourable for non-adherence to treatment in patients with chronic myeloid leukaemia: role of type A and D personality.

BACKGROUND: The introduction of BCR-ABL tyrosine kinase inhibitors (TKIs) to chronic myeloid leukemia (CML) therapy has revolutionized the treatment of this disease. Although regular TKI intake is a prerequisite for successful therapy, it has been shown that a significant proportion of patients are non-compliant. Recently there is growing evidence that personality traits may influenced the tendency for non-adherence to treatment in patients with chronic diseases. As far as we know, such a relationship in patients with CML has not been examined, yet. The aim of our study was to determine if personality traits favor non-adherence to treatment recommendations. We investigated the relationship between five-factor model personality factors (conscientiousness, neuroticism, agreeableness, extraversion, and openness) and medication non-adherence. We also checked if the patients with type A and type D personality, were at higher risk of poor medication adherence. METHODS: The following tools were used: self-constructed survey, the NEO-Five Factor Inventory, the Framingham Type A Scale, the D-Scale 14. The study included 140 CML patients treated with imatinib, dasatinib, or nilotinib. RESULTS: 39% of patients reported skipping at least one dose of medication in the month prior to follow-up visit. 51% admitted to skipping such doses from the start of their treatment to the time at which our assessment was performed. We did not find any relationship between the mean values of the analyzed factors of the Big Five (neuroticism, extraversion, openness, agreeableness, conscientiousness) and adherence. However, our analysis revealed that CML patients who admitted to missing doses of drugs during the entire course of treatment demonstrated greater intensity of type A personality traits (p = 0.020). Regarding both factors of type D personality, it was revealed that higher level of negative affectivity significantly decreased the adherence (p = 0.020). CONCLUSION: The results of our study indicate that screening for type D and A personalities may help to identify patients who are at higher risk of poor medication adherence.

Why Does Obesity as an Inflammatory Condition Predispose to Colorectal Cancer?

Obesity is a complex and multifactorial problem of global importance. Additionally, obesity causes chronic inflammation, upregulates cell growth, disturbs the immune system, and causes genomic instability, increasing the risk of carcinogenesis. Colorectal cancer is one of the most common cancers, and it has become a global problem. In 2018, there were around 1.8 million new cases and around 881,000 deaths worldwide. Another risk factor of colorectal cancer associated with obesity is poor diet. A Western diet, including a high intake of red and processed meat and a low consumption of whole grains, fruits, vegetables, and fiber, may increase the risk of both colorectal cancer and obesity. Moreover, the Western diet is associated with a proinflammatory profile diet, which may also affect chronic low-grade inflammation. In fact, people with obesity often present gut dysbiosis, increased inflammation, and risk of colorectal cancer. In this article, the association between obesity and colorectal cancer is discussed, including the most important mechanisms, such as low-grade chronic inflammation, gut dysbiosis, and poor diet.

Impact of Folate Intake on Bone Mineral Density in Patients with Inflammatory Bowel Disease.

BACKGROUND: Decreased bone mineral density (BMD) is a common problem among patients with inflammatory bowel disease (IBD). We hypothesised that an insufficient intake of folate might affect BMD. METHODS: The study subjects included 26 with Crohn's disease-CD, 30 with ulcerative colitis-UC, and 31 healthy adults (control group-CG) aged 18-50 years. Participants were asked to follow their usual diet, and dietary intake was assessed by a 4-day, 24 h dietary recall. All the participants filled in a questionnaire referring to folic acid supplementation. The BMD, T-score, and Z-score of the lumbar spine (L1-L4) and femoral neck (FN) were assessed. RESULTS: We found significant differences in the body mass, BMI (body mass index), CRP (C-reactive protein), BMD, Z-score, and T-score of the L1-L4 and FN between groups. There were no differences in energy and folate intake or the percentage coverage of recommended dietary allowances (RDA) of folate in all groups. Moreover, 70% of patients with UC, 92% of patients with CD, and 77% of CG patients showed insufficient folate intake. Folic acid was supplemented with a similar frequency in patients covering and not covering the RDA of folate. The intake of folate per 1000 kcal correlated positively with the CD group's BMD and T-score of L1-L4. CONCLUSIONS: Insufficient folate intake is common in patients with IBD and healthy individuals. The impact of folate on BMD in IBD is not clear. We need more studies on the association between folate intake, folic acid concentration, and BMD in IBD.

Oxidation-reduction and reactive oxygen species homeostasis in mutant plants with respiratory chain complex I dysfunction.

Mutations in a mitochondrial or nuclear gene encoding respiratory chain complex I subunits lead to decreased or a total absence of complex I activity. Plant mutants with altered or lost complex I activity adapt their respiratory metabolism by inducing alternative pathways of the respiratory chain and changing energy metabolism. Apparently, complex I is a crucial component of the oxidation-reduction (redox) regulatory system in photosynthetic cells, and alternative NAD(P)H dehydrogenases of the mitochondrial electron transport chain (mtETC) cannot fully compensate for its impairment. In most cases, dysfunction of complex I is associated with lowered or unchanged hydrogen peroxide (H(2)O(2)) concentrations, but increased superoxide (O(2)(-)) levels. Higher production of reactive oxygen species (ROS) by mitochondria in the mosaic (MSC16) cucumber mutant may be related to retrograde signalling. Different effects of complex I dysfunction on H(2)O(2) and O(2)(-) levels in described mutants might result from diverse regulation of processes involved in H(2)O(2) and O(2)(-) production. Often, dysfunction of complex I did not lead to oxidative stress, but increased the capacity of the antioxidative system and enhanced stress tolerance. The new cellular homeostasis in mutants with dysfunction of complex I allows growth and development, reflecting the plasticity of plant metabolism.

Treatment of Diabetes and Osteoporosis-A Reciprocal Risk?

Diabetes mellitus is a metabolic and systematic disorder that requires individualized therapy. The disease leads to various consequences, resulting in the destruction of tissues and organs. The aforementioned outcomes also include bone mineral disorders, caused by medications as well as diet therapy and physical activity. Some drugs may have a beneficial effect on both bone mineral density and the risk of fractures. Nevertheless, the impact of other medications remains unknown. Focusing on pharmacotherapy in diabetes may prevent bone mineral disorders and influence both the treatment and quality of life in patients suffering from diabetes mellitus. On the other hand, anti-osteoporosis drugs, such as antiresorptive or anabolic drugs, as well as drugs with a mixed mechanism of action, may affect carbohydrate metabolism, particularly in patients with diabetes. Therefore, the treatment of diabetes as well as osteoporosis prevention are vital for this group of patients.

Antioxidant effects of vitamin E and risk of cardiovascular disease in women with obesity - A narrative review.

Proper dietary habits are a vital element of cardiovascular (CV) treatment, and - according to the current guidelines - a diet rich in antioxidants is generally recommended. It remains, however, inconclusive whether antioxidant nutrients should be supplemented for CV health, and if so, in which form and dosage. Currently available data suggest that vitamin E may be essential in preventing CVD, especially in coronary heart disease and atherosclerosis - nevertheless, vitamin E supplementation may be questionable and may even be associated with adverse outcomes. Further, current studies highlight a strong need for identifying sex-specific strategies, which could improve guidelines for both the prevention and management of cardiovascular disease (CVD). It should also be emphasized that understanding the role of genetic variants in genes involved in VE metabolism may also be crucial for more precise nutritional recommendations for patients suffering from CVD. Therefore, we summarize the current knowledge regarding vitamin E antioxidant properties, which could be essential from CV perspective, and aim to assess whether vitamin E supplementation can be beneficial in CV prevention, especially in the high-risk group of women with obesity.

Why are western diet and western lifestyle pro-inflammatory risk factors of celiac disease?

The prevalence of celiac disease increased in recent years. In addition to the genetic and immunological factors, it appears that environmental determinants are also involved in the pathophysiology of celiac disease. Gastrointestinal infections impact the development of celiac disease. Current research does not directly confirm the protective effect of natural childbirth and breastfeeding on celiac disease. However, it seems that in genetically predisposed children, the amount of gluten introduced into the diet may have an impact on celiac disease development. Also western lifestyle, including western dietary patterns high in fat, sugar, and gliadin, potentially may increase the risk of celiac disease due to changes in intestinal microbiota, intestinal permeability, or mucosal inflammation. Further research is needed to expand the knowledge of the relationship between environmental factors and the development of celiac disease to define evidence-based preventive interventions against the development of celiac disease. The manuscript summarizes current knowledge on factors predisposing to the development of celiac disease including factors associated with the western lifestyle.

Accumulation of Advanced Glycation End-Products in the Body and Dietary Habits.

The formation of advanced glycation end-products (AGE) in tissues is a physiological process; however, excessive production and storage are pathological and lead to inflammation. A sedentary lifestyle, hypercaloric and high-fructose diet and increased intake of processed food elements contribute to excessive production of compounds, which are created in the non-enzymatic multi-stage glycation process. The AGE's sources can be endogenous and exogenous, mainly due to processing food at high temperatures and low moisture, including grilling, roasting, and frying. Accumulation of AGE increases oxidative stress and initiates various disorders, leading to the progression of atherosclerosis, cardiovascular disease, diabetes and their complications. Inborn defensive mechanisms, recovery systems, and exogenous antioxidants (including polyphenols) protect from excessive AGE accumulation. Additionally, numerous products have anti-glycation properties, occurring mainly in fruits, vegetables, herbs, and spices. It confirms the role of diet in the prevention of civilization diseases.

Pleiotropic Effects of Vitamin D in Patients with Inflammatory Bowel Diseases.

The multifaceted activity of vitamin D in patients with inflammatory bowel disease (IBD) presents a challenge for further research in this area. Vitamin D is involved in the regulation of bone mineral metabolism, it participates in the regulation of the immune system, and it is an underlying factor in the pathogenesis of IBD. Additionally, vitamin D affects Th1 and Th2 lymphocytes, influencing the release of cytokines and inhibiting tumor necrosis factor (TNF) expression and the wnt/ß-catenin pathway. As far as IBDs are concerned, they are associated with microbiota dysbiosis, abnormal inflammatory response, and micronutrient deficiency, including vitamin D hypovitaminosis. In turn, the biological activity of active vitamin D is regulated by the vitamin D receptor (VDR) which is associated with several processes related to IBD. Therefore, in terms of research on vitamin D supplementation in IBD patients, it is essential to understand the metabolic pathways and genetic determinants of vitamin D, as well as to identify the environmental factors they are subject to, not only in view of osteoporosis prevention and therapy, but primarily concerning modulating the course and supplementation of IBD pharmacotherapy.