Disease In Western Countries Research Articles

Overview of Cellular and Soluble Mediators in Systemic Inflammation Associated with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease in Western countries, affecting approximately 25% of the adult population. This condition encompasses a spectrum of liver diseases characterized by abnormal accumulation of fat in liver tissue (non-alcoholic fatty liver, NAFL) that can progress to non-alcoholic steatohepatitis (NASH), characterized by the presence of liver inflammation and damage. The latter form often coexists with liver fibrosis which, in turn, may progress to a state of cirrhosis and, potentially, hepatocarcinoma, both irreversible processes that often lead to the patient's death and/or the need for liver transplantation. Along with the high associated economic burden, the high mortality rate among NAFLD patients raises interest, not only in the search for novel therapeutic approaches, but also in early diagnosis and prevention to reduce the incidence of NAFLD-related complications. In this line, an exhaustive characterization of the immune status of patients with NAFLD is mandatory. Herein, we attempted to gather and compare the current and relevant scientific evidence on this matter, mainly on human reports. We addressed the current knowledge related to circulating cellular and soluble mediators, particularly platelets, different leukocyte subsets and relevant inflammatory soluble mediators.

Genetic Interference of FGFR3 Impedes Invasion of Upper Tract Urothelial Carcinoma Cells by Alleviating RAS/MAPK Signal Activity.

Upper tract urothelial cancer (UTUC) is a less common disease in Western countries but has a high level of prevalence in Asian populations. Compared to bladder cancer, unique etiologic and genomic factors are involved in UTUC. Fibroblast growth factor receptor 3 (FGFR3) up-regulation has been proposed as a promising target for bladder cancer therapy. In this study, we aimed to profile the expression of FGFR3 in Asian and Caucasian UTUC tissues and to evaluate the in vitro therapeutic efficacy of small interference RNA (siRNA)-mediated FGFR3 silencing in UTUC treatment. The FGFR3 expression levels in renal pelvis tissues and microarray sections from Asian and Caucasian patients with UTUC, respectively, were measured via immunohistochemistry. The BFTC-909 and UM-UC-14 UTUC cell lines were used to examine the effects of FGFR3 silencing on proliferation, migration, epithelial-mesenchymal transition (EMT) marker expression, and signaling machinery. FGFR3 expression increased as the TNM stage increased in both Asian and Caucasian UTUC tumors, and no statistical difference was identified between the two groups. In vitro studies demonstrated that FGFR3 siRNA delivery significantly inhibited proliferation and migration and suppressed the expression of EMT markers and transcription factors in UTUC cells. Mechanistically, FGFR3 silencing alleviated the constitutive expression of RAS and the phosphorylation of MAPK signaling mediators, including ERK1/2 and JNK1/2. FGFR3 silencing elicited an apoptosis-inducing effect similar to that of FGFR inhibition. Conclusion: siRNA-targeted FGFR3 expression may impede the expansion and invasion of UTUC cells by alleviating the RAS/MAPK signaling pathway. The genetic interference of FGFR3 expression via siRNA in UTUC cells may constitute a useful therapeutic strategy.

Engineered Fenofibrate as Oxidation-Sensitive Nanoparticles with ROS Scavenging and PPARα-Activating Bioactivity to Ameliorate Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries and China. Fenofibrate (FNB) can activate peroxisome proliferator-activated receptor α (PPARα) to increase fatty acid oxidation and ameliorate NAFLD. However, the application of FNB is limited in clinic due to its poor water solubility and low oral bioavailability. In this study, FNB-loaded nanoparticles (FNB-NP) based on a reactive oxygen species (ROS)-responsive peroxalate ester derived from vitamin E (OVE) and an amphiphilic conjugate 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG) were developed to enhance the preventive effects of FNB against NAFLD. In in vitro studies, FNB-NP displayed a high encapsulation efficiency of 97.25 ± 0.6% and a drug loading efficiency of 29.67 ± 0.1%, with a size of 197.0 ± 0.2 nm. FNB released from FNB-NP was dramatically accelerated in the medium with high H2O2 concentrations. Moreover, FNB-NP exhibited well storage stability and plasma stability. In pharmacokinetic (PK) studies, FNB-NP, compared with FNB crude drug, significantly increased the AUC0→t and AUC0→∞ of the plasma FNB acid by 3.3- and 3.4-fold, respectively. In pharmacodynamics (PD) studies, compared with an equal dose of FNB crude drug, FNB-NP more significantly reduced hepatic lipid deposition via facilitating FNB release in the liver and further upregulating PPARα expression in NAFLD mice. Meanwhile, oxidative stress in NAFLD was significantly suppressed after FNB-NP administration, suggesting that OVE plays a synergistic effect on antioxidation. Therefore, ROS-sensitive FNB delivery formulations FNB-NP enhance the preventive effects of FNB against NAFLD and could be further studied as a promising drug for the treatment of NAFLD in clinic.

The Potential of Lamiaceae Herbs for Mitigation of Overweight, Obesity, and Fatty Liver: Studies and Perspectives.

Numerous plants, plant extracts, and plant-derived compounds are being explored for their beneficial effects against overweight and liver diseases. Obesity is associated with the increased prevalence of non-alcoholic fatty liver disease (NAFLD), becoming the most common liver disease in Western countries. Obesity and NAFLD are closely associated with many other metabolic alternations such as insulin resistance, diabetes mellitus, and cardiovascular diseases. Many herbs of the Lamiaceae family are widely employed as food and spices in the Mediterranean area, but also in folk medicine, and their use for the management of metabolic disorders is well documented. Hereby, we summarized the scientific results of the medicinal and nutraceutical potential of plants from the Lamiaceae family for prevention and mitigation of overweight and fatty liver. The evidence indicates that Lamiaceae plants may be a cost-effective source of nutraceuticals and/or phytochemicals to be used in the management of metabolic-related conditions such as obesity and NAFLD. PubMed, Google Scholar, Scopus, and SciFinder were accessed to collect data on traditional medicinal plants, compounds derived from plants, their reported anti-obesity mechanisms, and therapeutic targets.

Inflammaging, a Common Factor in the Development of Sarcopenia and Metabolic-Associated Liver Disease (MAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, with its prevalence increasing annually [...]

Protocolo de prevención y tratamiento de la diarrea del viajero

The increase in travel to tropical and subtropical areas has caused an increase in imported disease in Western countries. Traveler's diarrhea is one of the main imported diseases. Though normally mild and self-limited, it is the principal cause for a medical consultation after an international trip. It has a big impact on the normal course of the trip. Give that the intake of contaminated food and drinks is the origin of most cases, prevention is the fundamental pillar. Likewise, due to its high incidence, travelers should be advised about the possibility of self-treatment.

Pulmonary Hypertension in Adult Congenital Heart Disease in Asia: A Distinctive Feature of Complex Congenital Heart Disease.

BackgroundThe epidemiology of pulmonary hypertension (PH) in patients with adult congenital heart disease in Western countries is already known. We investigate clinical characteristics of PH in adult congenital heart disease with emphasis on complex congenital heart disease (CHD) from an Asian cohort in Taiwan.Methods and ResultsAll adult patients (aged >18 years) diagnosed with CHD between January 2007 and July 2018 qualified for the study. PH was determined by cardiac catheterization data or echocardiography reports. In accord with the World Symposia on Pulmonary Hypertension, CHD was further categorized as simple, severe, or complex CHD (including pulmonary atresia‐ventricular septal defect and single‐ventricle anomalies).There were 4301 patients (55.6% women), 15.7% with severe and 3.9% with complex CHD. The cumulative incidence of PH was 4.4% (95% CI, 3.8–5.0). Our multivariable regression model indicated 4.2‐fold mortality increase (95% CI, 3.0–5.9) in the presence of PH, with age, female sex, and severe or complex CHD linked to higher incidence of PH. Only 49% of patients received PH‐specific therapy. Five‐ and 10‐year survival rates of patients with PH (n=190) were 72.3% (95% CI, 65.1%–78.4%) and 58.8% (95% CI, 50.1%–66.5%), respectively. Survival rates in those with Eisenmenger syndrome, PH after defect correction, and complex CHD were similar. Low oxygen saturation and high uric acid levels were associated with increased mortality.ConclusionsIn this sizable Asian adult CHD cohort, the cumulative incidence of PH was aligned with that of Western countries. Mortality proved higher in patients with PH versus without PH. Although complex CHD carried greater risk of PH compared with other adult CHD subsets, survival rate was similar.

Mediterranean Diet and Fatty Liver Risk in a Population of Overweight Older Italians: A Propensity Score-Matched Case-Cohort Study.

Hepatic steatosis, often known as fatty liver, is the most common hepatic disease in Western countries. The latest guidelines for the treatment of nonalcoholic fatty liver disease emphasize lifestyle measures, such as changing unhealthy eating patterns. Using a propensity score-matching approach, this study investigated the effect of adhering to a Mediterranean diet (MedDiet) on fatty liver risk in an older population (≥65 years) from Southern Italy. We recruited 1.403 subjects (53.6% men, ≥65 years) who completed a food frequency questionnaire (FFQ) and underwent clinical assessment between 2015 and 2018. For the assessment of the liver fat content, we applied the Fatty Liver Index (FLI). To evaluate the treatment effect of the MedDiet, propensity score matching was performed on patients with and without FLI > 60. After propensity score-matching with the MedDiet pattern as treatment, we found a higher consumption of red meat (p = 0.04) and wine (p = 0.04) in subjects with FLI > 60. Based on the FLI, the inverse association shown between adherence to the MedDiet and the risk of hepatic steatosis shows that the MedDiet can help to prevent hepatic steatosis. Consuming less red and processed meat, as well as alcoholic beverages, may be part of these healthy lifestyle recommendations.

The role of MLKL in Hepatic Ischemia-Reperfusion Injury of Alcoholic Steatotic Livers.

Alcohol-related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the primary causes of chronic liver disease in western countries. Liver transplantation is currently one of the most efficient approaches to save patients with liver failure, which is often associated with hepatic ischemia-reperfusion (IR) injury. IR injury is exacerbated by hepatic steatosis, yet the mechanism remains elusive. Necroptosis is a form of regulated cell death mediated by receptor-interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like (MLKL) protein, which has been implicated in the pathogenesis of ALD and NAFLD. Though necroptosis plays an important role in IR injury of high fat diet - induced steatotic livers, the role of necroptosis in IR injury of ethanol - induced steototic livers has not been investigated. In the present study, we used chronic plus binge alcohol (Gao-binge) feeding followed by IR surgery to investigate IR liver injury with ethanol-associated steatosis. We found that the levels of key necroptotic proteins MLKL and RIP3 increased in alcohol-fed mouse livers. Moreover, we observed increased liver injury after IR in control diet-fed mice, which was further exacerbated by alcohol feeding based on serum alanine aminotransferase (ALT) levels and TUNEL staining of necrotic cells. Hepatic neutrophil infiltration also increased in alcohol-fed mice after IR surgery. However, deletion of Mlkl did not protect against IR liver injury in alcohol-fed mice compared with matched wild-type mice. In conclusion, alcoholic steatosis promotes IR injury, which seems to be independent of MLKL-mediated necroptosis.

Cell Models and Omics Techniques for the Study of Nonalcoholic Fatty Liver Disease: Focusing on Stem Cell-Derived Cell Models.

Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease in western countries. The molecular mechanisms leading to NAFLD are only partially understood, and effective therapeutic interventions are clearly needed. Therefore, preclinical research is required to improve knowledge about NAFLD physiopathology and to identify new therapeutic targets. Primary human hepatocytes, human hepatic cell lines, and human stem cell-derived hepatocyte-like cells exhibit different hepatic phenotypes and have been widely used for studying NAFLD pathogenesis. In this paper, apart from employing the different in vitro cell models for the in vitro assessment of NAFLD, we also reviewed other approaches (metabolomics, transcriptomics, and high-content screening). We aimed to summarize the characteristics of different cell types and methods and to discuss their major advantages and disadvantages for NAFLD modeling.

CFTR mutational screening by next-generation sequencing reveals novel variants and a high carrier rate in a Middle Eastern population.

Cystic fibrosis is the most common life-limiting autosomal recessive disease in western countries with an incidence of 1:2500 in United States and 1:1000 in some European countries. Similar incidences were noted for the Middle East with variations from 1 in 2560 to 1 in 15,876 according to the degree of consanguinity. This is a preliminary systematic study that aims to assess the incidence and carrier rate of cystic fibrosis in the Middle Eastern Lebanese population; known for a high frequency of consanguinity. One hundred thirteen DNA samples were collected from neonatal blood cards obtained from newborns to healthy unrelated families with no previous history of Cystic fibrosis. Screening for Cystic Fibrosis-causing pathogenic variants was performed using next generation sequencing, and 17 different single nucleotide variants were detected, including six pathogenic and likely pathogenic. 5.5%-7% newborns were found to be carriers of a variant strongly suggestive of pathogenicity and comparable to published literature worldwide. This pilot analysis highlights the challenging interpretation of CFTR variants in a country underrepresented by large ethnic population analyses, and stresses the importance of premarital screening programs for Cystic fibrosis.

Self-care behaviours and related cultural factors among Chinese immigrants with cardiovascular disease in western countries: an integrative review.

This review aimed to demonstrate the self-care behaviours of first-generation Chinese immigrants with cardiovascular disease in western countries and identify related cultural factors. Self-care is the cornerstone to mitigate disease symptoms and maintain health status. Chinese immigrants to western countries, operating within a cross-cultural context, may find self-care to manage their cardiovascular disease challenging. An integrative review was conducted. Seven databases were searched Scopus, ProQuest Health & Medicine, Medline (Ovid), Embase (Ovid), AMED (Ovid), PsycINFO and CINAHL, with output limited to peer-reviewed studies published from 2000 to 2020 in English or Chinese. Initially, 2037 papers were screened. Six papers were retained and critiqued using the Joanna Briggs Institute critical appraisal tools. Deductive and inductive approaches were utilised to analyse the findings. The PRISMA 2020 checklist informed review reportage. In general, Chinese immigrants with cardiovascular disease took an active role in management of their cardiovascular disease, including through diet and activity adaptation and adherence to western medication. Families also played a significant role in disease decision-making and management. However, language and cultural barriers impeded their access to health information and resources in host countries. Understanding self-care behaviours and associated cultural factors among Chinese immigrants with cardiovascular disease is important to improve nurses' culturally sensitive practices and provide tailored health education interventions to promote self-care behaviours among immigrant populations. The scarcity of literature on self-care behaviours among Chinese first-generation immigrants with cardiovascular disease indicates the need for further research in this area. Development of culturally and linguistically sensitive health resources and education programs is urgently needed.

S1156 Hypothyroidism-Related Development of Non-Alcoholic Fatty Liver Disease - Is Levothyroxine the Answer?

Introduction: Non-alcoholic fatty liver disease (NAFLD) refers to fatty infiltration of the liver, with or without inflammation and fibrosis. NAFLD is the most common cause of liver disease in Western countries. Numerous studies have demonstrated a positive association between hypothyroidism and the development of non-alcoholic fatty liver disease. It has been proposed that treatment with thyroid hormone could reduce the risk of developing liver disease. Our aim is to determine if hypothyroidism patients treated with levothyroxine, a thyroid hormone analogue, are at lower risk of developing NAFLD and cirrhosis. Methods: We performed a retrospective analysis in the IBM Explorys database (1999-2021), a pooled, de-identified clinical database of over 75 million unique patients across the United States. Patient populations were identified using SNOMED and ICD codes. Inclusion criteria were patients with hypothyroidism and patients taking levothyroxine. Adverse events included a diagnosis of NAFLD, non-alcoholic steatohepatitis (NASH), or cirrhosis. Odds ratios (OR) with a 95% confidence interval (CI) were calculated for NAFLD/NASH and cirrhosis in hypothyroidism and patients on levothyroxine. Results: 3,720,320 patients with hypothyroidism were included in this study. Patients with hypothyroidism were at increased risk of developing NAFLD/NASH (OR 7.8058, 95% CI 7.6617 to 7.9527, P-value < 0.0001) or cirrhosis (OR 5.7648, 95% CI 5.7176 – 5.8124, P-value < 0.0001). Patients taking levothyroxine were not at lower risk of developing NASH/NAFLD (OR 6.7248, 95% CI 6.5265 to 6.9291, P-value < 0.0001) or cirrhosis (OR 4.3715, 95% CI 4.3069 to 4.4371, P-value < 0.0001). Conclusion: Our study confirmed a positive clinical association between hypothyroidism and the development of liver disease such as NAFLD/NASH and cirrhosis. Treatment of hypothyroidism with levothyroxine did not positively impact the progression of liver disease to NAFLD/NASH or cirrhosis. Further research is needed to understand how to modulate thyroid hormone to decrease the progression of liver disease in hypothyroid patients.

Metabolomic Predictors of Non-alcoholic Steatohepatitis and Advanced Fibrosis in Children.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in western countries both in children and adults. Metabolic dysregulation associated with gut microbial dysbiosis may influence disease progression from hepatic steatosis to inflammation and subsequent fibrosis. Using a multi-omics approach, we profiled the oral and fecal microbiome and plasma metabolites from 241 predominantly Latino children with non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFL), and controls. Children with more severe liver pathology were dysbiotic and had increased gene content associated with lipopolysaccharide biosynthesis and lipid, amino acid and carbohydrate metabolism. These changes were driven by increases in Bacteroides and concomitant decreases of Akkermansia, Anaerococcus, Corynebacterium, and Finegoldia. Non-targeted mass spectrometry revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. Random forests modeling of plasma metabolites was highly predictive of non-alcoholic steatohepatitis (NASH) (97% accuracy) and hepatic fibrosis, steatosis and lobular inflammation (93.8% accuracy), and can differentiate steatohepatitis from simple steatosis (90.0% accuracy). Multi-omics predictive models for disease and histology findings revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. These results highlight the promise of non-invasive biomarkers for the growing epidemic of fatty liver disease.

Review Article Drug Impairment and Liver Disease

Abstract Abstract: Liver disease is a major cause of morbidity and mortality and is rated as one of the top 5 commonest causes of premature death in the world. However, not all liver problems are related to an underlying liver disease. Many patients have liver dysfunction which may be secondary to drug therapy, infections or sepsis, gallstones or trauma. The liver helps purify the blood by changing potentially harmful chemicals into harmless ones, the sources of these chemicals can be outside the body, such as medications, or alcohol, or inside body, as ammonia and bilirubin. When drug injure the liver and disrupt its normal function, symptoms, signs. These drugs which called drug induced liver disease (DILI), leads to abnormal blood tests of liver disease, and also liver failure. Liver failure occurs when large parts of the liver become damaged beyond repair, and the liver is no longer able to function, drug-induced liver injury (DILI), is the 4th most important cause of liver disease in western countries, the incidence of DILI is between 1/10000 and 1/100000 patients-years. Aim of Study: Review the evidence regarding fundamental pharmacokinetics alterations caused by the liver disease as well as the potential foe liver toxicity with DILI. Analysis of the evidence of DILI and severe liver injury leading to death will be the aim, finally, provide recommendation and directions regarding drugs and how to minimize the risk of liver toxicity.

ATTD 2021 Invited Speaker Abstracts.

ATTD 2021 Invited Speaker Abstracts.

MO070NEW ASPECTS OF THE PATHOMORPHOLOGIC SEQUENCE OF NEPHRON LOSS IN DIABETIC NEPHROPATHY

Abstract Background and Aims Diabetic nephropathy (DN) is the leading cause of end-stage-renal disease in western countries. Despite of innumerable studies undertaken to elucidate the pathogenesis of DN the underlying morphologic alterations have been insufficiently analyzed. Method Re-evaluation of more than 800 biopsies was done showing several unknown features. Results: 1. Matrix accumulation in the mesangium: Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of DN, generally considered to emerge from different sites of overproduction: GBM components from podocytes and mesangial matrix from mesangial cells. We show, that the accumulation of matrix in the mesangium emerges from an overproduction of GBM material by podocytes and endothelial cells and an impaired degradation by mesangial cells. The progressing deposition of worn-out GBM material into the mesangium accounts for the advancement from diffuse mesangial sclerosis (DMS) to nodular sclerosis (NS) and to the herniation of the tuft through the glomerular vascular pole to the outside; the latter is associated with the outgrowth of glomerular capillaries into the peri-glomerular space leading to the destruction of the juxtaglomerular apparatus. 2.The role of podocytes Podocytes have frequently been accused to play a central role in DN. This is correct, but in another way than generally assumed. Damage to podocytes cannot be seen in DMS. The albuminuria regularly seen during this stage derives, as previously suggested by others, from an increased leakiness of the glomerular capillary endothelium based on a deranged glycocalyx. Podocyte detachments start at the transition from DMS to NS, based on the loss of cross talk signals with the capillary endothelium: the increasing deposition of matrix leads to the collapse of many capillaries. These podocytes contribute little to the further progression of the damage: they are lost into primary urine or they undergo cell lysis.In addition to their role in increased matrix production, podocytes take an active role in the formation of tuft adhesions to Bowman’s capsule (BC), starting the progression to NS. Expansion of the matrix within the mesangium has led to expansion of the tuft (frequently associated with nodules) towards Bowman’s capsule (BC) or towards the urinary orifice. Podocytes on the surface of these expansions are in their majority structurally intact, exhibiting an intact pattern of foot processes. These podocytes come into contact with parietal epithelial cells and initiate DN-specific tuft adhesions to BC allowing the proliferation of glomerular capillaries into BC. There they deliver an exudate into BC that spreads around the entire circumference of the glomerulus presenting as giant insudative spaces. Moreover, this process encroaches via the glomerulo-tubular junction onto the tubule constituting the major pathway of glomerular damage extending to the tubulointerstitium. 3. Tubulointerstitial fibrosisIt is current opinion that the tubulointerstitial fibrosis may start from tubular damage resulting in an own, glomerular-independent pathway to nephron loss. However, there is scant evidence for such a mechanism. Studying 162 glomerulo-tubular transitions, we did not see a tubular epithelial or interstitial damage in those biopsies without any evidence of a glomerulo-tubular damage transfer. The only exception consists of the well-known prominent thickening of the tubular basement membrane, which may result in functional loss but does not lead to structural epithelial damage. Conclusion We consistently found that tubulo-interstitial damage develops after encroachment of the glomerular damage onto the tubule, leading first to a gradual degeneration of tubules which subsequently initiate the process of interstitial fibrosis.

Non-alcoholic fatty liver diseases: current challenges and future directions.

Non-alcoholic fatty liver diseases (NAFLD) is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries within the next years. This review focusses on the definition of NAFLD and NASH, possible screening mechanisms and the question who should be screened. Still there is a need for non-invasive diagnostic tools and biomarkers for NASH that can quickly and easily diagnose the severity of NAFLD, monitor liver changes, and identify high risk patients. In addition, treatment strategies are discussed as well as the clientele, who should be treated. There are currently no drugs approved for NAFLD. Successful clinical studies with e.g., obeticholic acid and new substances (e.g., cenicriviroc with anti-inflammatory activity) have already been published. If weight-reducing diets and a change in lifestyle fail in the case of severe obesity, bariatric surgery (e.g., gastric bypass or stomach reduction) should be considered. In the case of manifest type 2 diabetes, metformin can be used as an oral antidiabetic of first choice, and GLP-1 agonists have shown beneficial effects on NAFLD. However, up to now the prevention of overweight and lack of exercise targets the most important risk factors. This review aims to identify therapy relevant risk factors, management strategies, and open questions concerning NAFLD patients.

MicroRNA-29c Acting on FOS Plays a Significant Role in Nonalcoholic Steatohepatitis Through the Interleukin-17 Signaling Pathway.

Nonalcoholic fatty liver disease is the most common hepatic disease in western countries and is even more ubiquitous in Asian countries. Our study determined that TH17/Treg cells were imbalanced in animal models. Based on our interest in the mechanism underlying TH17/Treg cell imbalance in nonalcoholic fatty liver mice, we conducted a joint bioinformatics analysis to further investigate this process. Common gene sequencing analysis was based on one trial from one sequencing platform, where gene expression analysis and enrichment analysis were the only analyses performed. We compared different sequencing results from different trials performed using different sequencing platforms, and we utilized the intersection of these analytical results to perform joint analysis. We used a bioinformatics analysis method to perform enrichment analysis and map interaction network analysis and predict potential microRNA sites. Animal experiments were also designed to validate the results of the data analysis based on quantitative polymerase chain reaction (qPCR) and western blotting. Our results revealed 8 coexisting differentially expressed genes (DEGs) and 7 hinge genes. The identified DEGs may influence nonalcoholic steatosis hepatitis through the interleukin-17 pathway. We found that microRNA-29c interacts with FOS and IGFBP1. Polymerase chain reaction analyses revealed both FOS and microRNA-29c expression in NASH mice, and western blot analyses indicated the same trend with regard to FOS protein levels. Based on these results, we suggest that microRNA-29c acts on FOS via the interleukin-17 signaling pathway to regulate TH17/Treg cells in NASH patients.

Heart Valve Critical Pathway and Heart Valve Clinic: Novel Benchmarks for Modern Management of Valvular Heart Disease.

The growing burden of valvular heart disease in Western countries represents a challenge for the daily clinical practice, especially in the light of the ever-increasing number of therapeutic options. The Euro Heart Survey showed that, among elderly subjects with severe, symptomatic valve dysfunction, surgery is denied for 33% of patients with aortic stenosis and for 50% of patients with mitral regurgitation. Current management (from diagnosis to follow-up) is often fragmented in multiple-sometimes unnecessary-steps. Such a "patchy" approach may translate into a suboptimal management, especially in the geriatric population. New healthcare models exist that can coordinate care, reduce fragmentation, limit costs and, ultimately, improve outcomes: the clinical pathways.