Search Results (18)

Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

This study investigated the prevalence of cystic fibrosis-related diabetes (CFRD) in the Croatian cystic fibrosis (CF) population, the age at diagnosis, insulin requirements, and the relationship between age at diagnosis and other clinical parameters. Medical records from 152 patients with genetically and laboratory-confirmed CF were reviewed through to 2025. The American Diabetes Association criteria were used to diagnose CFRD. Anthropometric and clinical data were collected from the latest medical records. A total of 17 out of 152 patients had CFRD, with a prevalence of 4.8% in the paediatric population (4/84) and 19.1% in adults (13/68). The median age of CFRD diagnosis was 14 years (range 9–22 years, SD = 3.95). Thirteen patients used insulin: one used bolus only, seven used basal-bolus multiple daily injections, and five used insulin pumps. The average total daily insulin (TDI) per kilogram (kg) body weight was 0.447 U/kg (SD = 0.429). The age at CFRD diagnosis was positively correlated with the body mass index (BMI) (p = 0.029). Patients requiring insulin by age 15 had higher TDI and were more likely to have CF liver disease (p = 0.027, p = 0.037, respectively). The prevalence of CFRD and age at diagnosis aligned with previous studies. Patients diagnosed at a younger age and requiring insulin earlier had lower BMIs, likely due to a faster decline in beta cell function and earlier onset of insulinopenia. Full article

Cystic fibrosis (CF) is a monogenic syndrome caused by variants in the CF Transmembrane Conductance Regulator (CFTR) gene, affecting various organ and systems, in particular the lung, pancreas, sweat glands, liver, gastrointestinal tract, vas deferens, and vascular system. While for some organs, e.g., the pancreas, a strict genotype-phenotype occurs, others, such as the lung, display a different pathophysiologic outcome in the presence of the same mutational asset, arguing for genetic and environmental modifiers influencing severity and clinical trajectory. CFTR variants trigger a pathophysiological cascade of events responsible for chronic inflammatory responses, many aspects of which, especially related to immunity, are not ascertained yet. Although clock genes expression and function are known modulators of the innate and adaptive immunity, their involvement in CF has been only observed in relation to sleep abnormalities. The aim of this review is to present current evidence on the clock genes role in immune-inflammatory responses at the lung level. While information on this topic is known in other chronic airway diseases (chronic obstructive pulmonary disease and asthma), CF lung disease (CFLD) is lacking in this knowledge. We will present the bidirectional effect between clock genes and inflammatory factors that could possibly be implicated in the CFLD. It must be stressed that besides sleep disturbance and its mechanisms, there are not studies directly addressing the exact nature of clock genes’ involvement in inflammation and immunity in CF, pointing out the directions of new and deepened studies in this monogenic affection. Importantly, clock genes have been found to be druggable by means of genetic tools or pharmacological agents, and this could have therapeutic implications in CFLD. Full article

Acute inflammation is the body’s first defense in response to pathogens or injury that is partially governed by a novel genus of endogenous lipid mediators that orchestrate the resolution of inflammation, coined specialized pro-resolving mediators (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs), include the eicosapentaenoic acid-derived and docosahexaenoic acid-derived Resolvins, Protectins, and Maresins. Herein, we review their biosynthesis, structural characteristics, and therapeutic effectiveness in various diseases such as ischemia, viral infections, periodontitis, neuroinflammatory diseases, cystic fibrosis, lung inflammation, herpes virus, and cancer, especially focusing on therapeutic effectiveness in respiratory inflammation and ischemia-related injuries. Resolvins are sub-nanomolar potent agonists that accelerate the resolution of inflammation by reducing excessive neutrophil infiltration, stimulating macrophage functions including phagocytosis, efferocytosis, and tissue repair. In addition to regulating neutrophils and macrophages, Resolvins control dendritic cell migration and T cell responses, and they also reduce the pro-inflammatory cytokines, proliferation, and metastasis of cancer cells. Importantly, several lines of evidence have demonstrated that Resolvins reduce tumor progression in melanoma, oral squamous cell carcinoma, lung cancer, and liver cancer. In addition, Resolvins enhance tumor cell debris clearance by macrophages in the tumor’s microenvironment. Resolvins, with their unique stereochemical structure, receptors, and biosynthetic pathways, provide a novel therapeutical approach to activating resolution mechanisms during cancer progression. Full article

Cystic fibrosis (CF) is a multifaceted disorder predominantly investigated for its pulmonary manifestations, yet patients with CF also exhibit a spectrum of extrapulmonary manifestations, notably those involving the hepatobiliary system. The latter constitutes the third leading cause of morbidity and mortality in individuals with CF. Cystic fibrosis-related liver disease (CFLD), with an escalating prevalence, manifests diverse clinical presentations ranging from hepatomegaly to cirrhosis and hepatopulmonary syndrome. Consequently, early detection and appropriate management are imperative for sustaining the health and influencing the quality of life of CF patients afflicted with CFLD. This review aims to consolidate existing knowledge by providing a comprehensive overview of hepatobiliary manifestations associated with CF. It delineates the clinical hepatobiliary manifestations, diagnostic methodologies, incorporating minimally invasive markers, and therapeutic approaches, encompassing the impact of novel CFTR modulators on CFLD. Given the exigency of early diagnosis and the intricate management of CFLD, a multidisciplinary team approach is essential to optimize care and enhance the quality of life for this subset of patients. In conclusion, recognizing CF as more than solely a pulmonary ailment, the authors underscore the imperative for further clinical investigations to establish a more robust evidence base for CFLD management within the continuum of this chronic disease. Full article

Cystic fibrosis (CF) is an autosomal recessive disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. With the advent of highly effective modulator therapy targeting the abnormal CFTR protein, people with CF (PwCF) are living more than 40 years longer than the pre-modulator therapy era. As a result, PwCF are facing new challenges of managing similar comorbidities affecting the average aging population. While CF is notoriously identified as a chronic respiratory disease, the multisystem presence of the CFTR gene can contribute to other organ-related complications acutely, but also heighten the likelihood of chronic conditions not routinely encountered in this cohort. In this overview, we will focus on risk factors and epidemiology for PwCF as they relate to cardiovascular disease, dyslipidemia, CF-related diabetes, pulmonary hypertension, obstructive sleep apnea, CF-liver disease, bone health and malignancy. With increased awareness of diseases affecting a newly aging CF population, a focus on primary and secondary prevention will be imperative to implementing a comprehensive care plan to improve long-term morbidity and mortality. Full article

(1) Background: Cystic echinococcosis is a zoonotic helminth disease that causes severe economic losses. The study aimed to assess the prevalence and viability of cystic echinococcosis in examined camels. In addition, assessing the histological, morphological, oxidative, and antioxidant state related to the cystic echinococcosis infection; (2) Methods: The study was performed on 152 slaughtered dromedary camels between March and September 2022 at El-Basatin abattoir in Cairo Governorate, Egypt; (3) Results: The results revealed that the prevalence of hydatidosis was 21.7% in slaughtered camel and the highest infection rate observed in lungs was 87.87%, while it was 9% in livers. Camels’ liver infections were rare, whereas their lung infections were more common. By comparing to non-infected camels, the level of MAD was significantly increased with hydatid cysts infection, while the level of GSH, SOD and CAT was significantly decreased. Histopathological section of camel cyst revealed layered membranes surrounded by a zone of cellular infiltration and an outermost fibrous tissue reaction. In addition, there was evidence of atelectasis, emphysema, hemorrhage, congestion, and fibrosis in the surrounding tissues. Nonetheless, the degeneration and necrosis of hepatocytes and other pathological alterations in liver cyst sections were remarkably comparable to those seen in the lungs. Furthermore, calcification was detected. Full article

Adequate intake of nutrients such as essential fatty acids (EFA) are critical in cystic fibrosis (CF). The clinical course of deterioration of lung function in people with CF has been shown to relate to nutrition. Independent of the higher energy consumption and malabsorption due to pancreatic insufficiency, EFA deficiency is closely associated with the risk of pulmonary infection, the most significant pathology in CF. This review will focus on the EFA deficiency identified in people with CF, as well as the limited progress made in deciphering the exact metabolic pathways that are dysfunctional in CF. Specifically, people with CF are deficient in linoleic acid, an omega 6 fatty acid, and the ratio of arachidonic acid (omega 6 metabolite) and docosahexaenoic acid (omega 3 metabolite) is increased. Analysis of the molecular pathways in bronchial cells has identified changes in the enzymes that metabolise EFA. However, fatty acid metabolism primarily occurs in the liver, with EFA metabolism in CF liver not yet investigated, indicating that further research is required. Despite limited understanding in this area, it is well known that adequate EFA concentrations are critical to normal membrane structure and function, and thus are important to consider in disease processes. Novel insights into the relationship between CF genotype and EFA phenotype will be discussed, in addition to sex differences in EFA concentrations in people with CF. Collectively, investigating the specific effects of genotype and sex on fatty acid metabolism may provide support for the management of people with CF via personalised genotype- and sex-specific nutritional therapies. Full article

Hepatobiliary involvement is a hallmark in cystic fibrosis (CF), as the causative CF Transmembrane Conductance Regulator (CFTR) defect is expressed in the biliary tree. However, bile acid (BA) compositions in regard to pancreatic insufficiency, which is present at an early stage in about 85% of CF patients, have not been satisfactorily understood. We assess the pattern of serum BAs in people with CF (pwCF) without CFTR modulator therapy in regard to pancreatic insufficiency and the CFTR genotype. In 47 pwCF, 10 free and 12 taurine- and glycine-conjugated BAs in serum were prospectively assessed. Findings were related to genotype, pancreatic insufficiency prevalence (PIP)-score, and hepatic involvement indicated by serum liver enzymes, as well as clinical and ultrasound criteria for CF-related liver disease. Serum concentrations of total primary BAs and free cholic acid (CA) were significantly higher in pwCF with higher PIP-scores (p = 0.025, p = 0.009, respectively). Higher total BAs were seen in pwCF with PIP-scores ≥0.88 (p = 0.033) and with pancreatic insufficiency (p = 0.034). Free CA was higher in patients with CF-related liver involvement without cirrhosis, compared to pwCF without liver disease (2.3-fold, p = 0.036). pwCF with severe CFTR genotypes, as assessed by the PIP-score, reveals more toxic BA compositions in serum. Subsequent studies assessing changes in BA homeostasis during new highly effective CFTR-modulating therapies are of high interest. Full article

Vitamin D is a cyclopentane polyhydrophenanthrene compound involved mainly in bone health and calcium metabolism but also autophagy, modulation of the gut microbiota, cell proliferation, immune functions and intestinal barrier integrity. The sources of vitamin D include sunlight, diet and vitamin D supplements. Vitamin D3, the most effective vitamin D isoform is produced in the human epidermis as a result of sunlight exposure. Vitamin D undergoes two hydroxylation reactions in the liver and kidney to reach its active form, 1,25-dihydroxyvitamin D. Recent studies highlighted a complex spectrum of roles regarding the wellbeing of the gastrointestinal tract. Based on its antimicrobial effect, it was recently indicated that vitamin D supplementation in addition to standard eradication therapy might enhance H. pylori eradication rates. Moreover, it was suggested that low levels of vitamin D might also be involved in the acquisition of H. pylori infection. In terms of celiac disease, the negative effects of vitamin D deficiency might begin even during intrauterine life in the setting of maternal deficiency. Moreover, vitamin D is strongly related to the integrity of the gut barrier, which represents the core of the pathophysiology of celiac disease onset, in addition to being correlated with the histological findings of disease severity. The relationship between vitamin D and cystic fibrosis is supported by the involvement of this micronutrient in preserving lung function by clearing airway inflammation and preventing pathogen airway colonization. Moreover, this micronutrient might exert anticatabolic effects in CF patients. Inflammatory bowel disease patients also experience major benefits if they have a sufficient level of circulating vitamin D, proving its involvement in both induction and remission in these patients. The findings regarding the relationship between vitamin D, food allergies, diarrhea and constipation remain controversial, but vitamin D levels should be monitored in these patients in order to avoid hypo- and hypervitaminosis. Further studies are required to fill the remaining gaps in term of the complex impact of vitamin D on gastrointestinal homeostasis. Full article

Background: Life expectancy has increased in cystic fibrosis (CF) patients; however, the rate of mortality is still high, and in a majority of cases, the cause of death is due to respiratory deterioration. Vitamin D plays an important role in immunity and infection prophylaxis, as its deficiency is associated with frequent infections. In CF patients, a deficit of liposoluble vitamins is common, despite daily supplementation. The aim of this study is to evaluate the relation between vitamin D status and lung function expressed by lung clearance index (LCI) in patients with CF. We also assessed the relation of factors such as nutritional status, genotype, and associated comorbidities such as Pseudomonas infection, cystic fibrosis-related diabetes (CFRD), and cystic fibrosis liver disease (CFLD) with vitamin D and LCI. Methods: A cross-sectional study was conducted at the National Cystic Fibrosis Center by analyzing patients with CF who presented in our center between November 2017 and November 2019. We enrolled in the study patients diagnosed with CF, who were followed up in our CF center and who were able to perform lung function tests. Patients in exacerbation were excluded. Results: A strong negative correlation was found between vitamin D and LCI (r = −0.69, p = 0.000). A lower vitamin D storage was found in patients with CFLD and CFRD. Higher LCI values were found among patients with chronic Pseudomonas infection, with BMI under the 25th percentile, or with associated CFLD. Conclusion: In CF patients, vitamin D plays an important role, and its deficit correlates with an impaired LCI. Vitamin D deficit is a risk factor in patients with associated comorbidities such as CFLD and CFRD. Chronic infection with Pseudomonas, the presence of impaired nutritional status, and CFLD are associated with a prolonged LCI. Full article

Nowadays, increasingly more attention is being paid to a holistic approach to health, in which diet contributes to disease prevention. There is growing interest in functional food that not only provides basic nutrition but has also been demonstrated to be an opportunity for the prevention of disorders. A promising functional food is soybean, which is the richest source of the isoflavone, genistein. Genistein may be useful in the prevention and treatment of such disorders as psoriasis, cataracts, cystic fibrosis, non-alcoholic fatty liver disease and type 2 diabetes. However, achievable concentrations of genistein in humans are low, and the use of soybean as a functional food is not devoid of concerns, which are related to genistein’s potential side effects resulting from its estrogenic and goitrogenic effects. Full article

Vitamin K2 activates vitamin K-dependent proteins that support many biological functions, such as bone mineralization, the inhibition of vascular stiffness, the improvement of endothelial function, the maintenance of strong teeth, brain development, joint health, and optimal body weight. Due to the transformation of food habits in developed countries over the last five decades, vitamin K and, specifically, vitamin K2 intakes among parents and their offspring have decreased significantly, resulting in serious health implications. The therapeutics used in pediatric practice (antibiotics and glucocorticoids) are also to blame for this situation. Low vitamin K status is much more frequent in newborns, due to both endogenous and exogenous insufficiencies. Just after birth vitamin K stores are low, and since human milk is relatively poor in this nutrient, breast-fed infants are at particular risk of a bleeding disorder called vitamin K deficiency bleeding. A pilot study showed that better vitamin K status is associated with lower rate of low-energy fracture incidence. An ongoing clinical trial is intended to address whether vitamin K2 and D3 supplementation might positively impact the biological process of bone healing. Vitamin K2 as menaquinone-7 (MK-7) has a documented history of safe and effective use. The lack of adverse effects of MK-7 makes it the ideal choice for supplementation by pregnant and nursing women and children, both healthy and suffering from various malabsorptions and health disorders, such as dyslipidemia, diabetes, thalassemia major (TM), cystic fibrosis (CF), inflammatory bowel diseases (IBD), and chronic liver diseases. Additionally, worthy of consideration is the use of vitamin K2 in obesity-related health outcomes. Full article

Cystic Fibrosis-related liver disease (CFLD) has become a leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF), and affects children and adults. The understanding of the pathogenesis of CFLD is key in order to develop efficacious treatments. However, it remains complex, and has not been clarified to the last. The search for a drug might be additionally complicated due to the diverse clinical picture and lack of a unified definition of CFLD. Although ursodeoxycholic acid has been used for decades, its efficacy in CFLD is controversial, and the potential of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators and targeted gene therapy in CFLD needs to be defined in the near future. This review focuses on the current knowledge on treatment strategies for CFLD based on pathomechanistic viewpoints. Full article