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BACKGROUND AND OBJECTIVES: Genome-scale metabolic networks (GEMs) represent a valuable modeling and computational tool in the broad field of systems biology. Their ability to integrate constraints and high-throughput biological data enables the study of intricate metabolic aspects and processes of different cell types and conditions. The past decade has witnessed an increasing number and variety of applications of GEMs for the study of human diseases, along with a huge effort aimed at the reconstruction, integration and analysis of a high number of organisms. This paper presents a systematic review of the scientific literature, to pursue several important questions about the application of constraint-based modeling in the investigation of human diseases. Hopefully, this paper will provide a useful reference for researchers interested in the application of modeling and computational tools for the investigation of metabolic-related human diseases. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Elsevier Scopus®, National Library of Medicine PubMed® and Clarivate Web of Science™ databases were enquired, resulting in 566 scientific articles. After applying exclusion and eligibility criteria, a total of 169 papers were selected and individually examined. RESULTS: The reviewed papers offer a thorough and up-to-date picture of the latest modeling and computational approaches, based on genome-scale metabolic models, that can be leveraged for the investigation of a large variety of human diseases. The numerous studies have been categorized according to the clinical research area involved in the examined disease. Furthermore, the paper discusses the most typical approaches employed to derive clinically-relevant information using the computational models. CONCLUSIONS: The number of scientific papers, utilizing GEM-based approaches for the investigation of human diseases, suggests an increasing interest in these types of approaches; hopefully, the present review will represent a useful reference for scientists interested in applying computational modeling approaches to investigate the aetiopathology of human diseases; we also hope that this work will foster the development of novel applications and methods for the discovery of clinically-relevant insights on metabolic-related diseases.
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Redes y Vías Metabólicas , Humanos , Modelos Biológicos , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/genética , Biología de Sistemas , Genoma Humano , Biología Computacional/métodosRESUMEN
Zoonoses have rapidly spread globally, necessitating the implementation of vaccination strategies as a control measure. Emerging and re-emerging vector-borne diseases are among the major global public health concerns. Dengue, a zoonotic viral infection transmitted to humans by a vector, the Aedes mosquito, is a severe global health problem. Dengue is a serious tropical infectious disease, second only to malaria, causing around 25,000 deaths each year. The resurgence of Dengue is mainly due to climate change, demographic transitions and evolving social dynamics. The development of an effective vaccine against Dengue has proven to be a complex undertaking due to four different viral serotypes with distinct antigenic profiles. This review highlights the urgent need to address the dengue threat by exploring the application of biotechnological and -OMICS sciences.
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The high frequency and complexity of mandibular third molar (M3M) surgery have led several authors to the development of classification systems for better evaluation and management in oral surgery. This study compared the classifications of Juodzabalys and Daugela et al. (JD), Sammartino et al., Chang et al., Jhamb et al., Maglione et al., and Nemsi et al. to understand the concordance between the scores of M3M surgery. Two types of analysis were conducted: the relationship between the M3M and the inferior alveolar nerve (IAN), and the overall difficulty score based on the tooth's angulation and its spatial position with the adjacent structure. The analysis of the classifications on the relationship between M3M and IAN resulted in a concordance of 26.1%. In the pairwise comparisons, the classifications of Nemsi et al. and Jhamb et al. showed the highest concordance of 59.5%. Analyzing the total scores difficulty, the JD et al., Chang et al., and Sammartino et al. classifications demonstrated a concordance level of 25.5%. A pairwise assessment revealed a higher concordance degree between the classifications of Sammartino et al. and Chang et al. (57.4%). The results highlight the limits in establishing a comprehensive and objective classification for the surgical difficulty of M3M, possibly attributed to variations in the methodology for computing total scores. An objective, automated, and non-operator-dependent classification method for assessing the surgical difficulty of M3M is still needed.
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Embryonic stem cells (ESCs) are defined as stem cells with self-renewing and differentiation capabilities. These unique properties are tightly regulated and controlled by complex genetic and molecular mechanisms, whose understanding is essential for both basic and translational research. A large number of studies have mostly focused on understanding the molecular mechanisms governing pluripotency and differentiation of ESCs, while the regulation of proliferation has received comparably less attention. Here, we investigate the role of ZZZ3 (zinc finger ZZ-type containing 3) in human ESCs homeostasis. We found that knockdown of ZZZ3 negatively impacts ribosome biogenesis, translation, and mTOR signaling, leading to a significant reduction in cell proliferation. This process occurs without affecting pluripotency, suggesting that ZZZ3-depleted ESCs enter a "dormant-like" state and that proliferation and pluripotency can be uncoupled also in human ESCs.
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Proliferación Celular , Proteínas de Unión al ADN , Células Madre Embrionarias Humanas , Serina-Treonina Quinasas TOR , Factores de Transcripción , Humanos , Diferenciación Celular/genética , Homeostasis , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/citología , Biosíntesis de Proteínas , Ribosomas/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
A sedentary lifestyle associated with unregulated diets rich in high-calorie foods have contributed to the great prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) latterly, with up to 60% in the high-risk population and 25% in the general population. The absence of specific pharmacological strategies for this syndrome represents one of the major problems in the management of MASLD patients. Lifestyle interventions and adherence to a healthy diet are the main cornerstones of current therapies. The identification of nutraceuticals useful in the treatment of MASLD appears to be one of the most promising strategies for the development of new effective and safe treatments for this disease. The onion, one of the most widely studied foods in the field of nutraceuticals, serves as an inexhaustible reservoir of potent compounds with various beneficial effects. The following preliminary study analyzes, mediating in silico studies, the iteration of a library of typical onion compounds with 3-hydroxy-3-methylglutaryl-coenzyme A reductase, liver receptors X α and ß, as well as peroxisome proliferator-activated receptors α and γ. In this study, for the first time promising smart molecules from the onion that could have a beneficial action in MASLD patients were identified.
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Simulación del Acoplamiento Molecular , Cebollas , Polifenoles , Cebollas/química , Polifenoles/farmacología , Humanos , Ligandos , Suplementos Dietéticos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismoRESUMEN
Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune disease, characterized by destruction of bile ducts. PBC predominantly affects women between 40 and 60 years of age. The presence of antimitochondrial antibodies (AMA) is a serological feature of PBC. These highly specific antibodies are found in about 95% of patients with the disease. The family of enzymes located in the inner membrane of the mitochondria, called the 2-oxo-acid dehydrogenase complex represents the target of the AMA. Ursodeoxycholic acid (UDCA) is a synthetic bile acid capable of protecting cholangiocytes from cholestatic damage caused by the accumulation of bile acids with a mechanism of action not yet well clarified. UDCA represents the gold standard therapy for PBC patients with recommended dose of 13-15 mg/kg/day. However, not every patient responds to therapy. On the other hand, the gut microbiota plays a key role in the onset of PBC through still unclear biochemical pathways. Less is known about its role as a potential biomarker after drug treatment. Actually, few studies analyzed the changes in gut microbiota composition before and after UDCA treatment. For this reason, this review represents an examination of the studies carried out on changes in gut microbiota composition in patients affected by PBC before and after treatment.
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Emerging evidence shows that oral squamous cell carcinoma (OSCC) invasiveness can be attributed to a small subpopulation of cancer stem cells (CSCs) in the bulk of the tumor. However, the presence of CSCs in the OSCC close resection margins is still poorly unexplored. Here, we found that BMI1, CD44, SOX2, OCT4, UBE2C, CXCR4 CSCs marker genes are significantly upregulated, while IGF1-R, KLF4, ALDH1A1, CD133, FAM3C are downregulated in the tumor core vs healthy mucosa of 24 patients with OSCC. Among these, SOX2 appears also upregulated in the tumor close margin vs healthy mucosa and this significantly correlates with tumor size and lymph node compromise. In vitro analyses in CAL27 and SCC15 tongue squamous cell carcinoma cell lines, show that SOX2 transient knockdown i) promotes the mesenchymal-to-epithelial transition, ii) smooths the invasiveness, iii) attenuates the 3D tumor sphere-forming capacity, and iv) partially increases the sensitivity to cisplatin treatment. Overall, our study highlights that the OSCC close margins can retain CSC-specific markers. Notably, SOX2 may represent a useful CSCs marker to predict a more aggressive phenotype and a suitable target to prevent local invasiveness.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Neoplasias de la Lengua , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de la Boca/patología , Neoplasias de la Lengua/patología , Neoplasias de Cabeza y Cuello/patología , Células Madre Neoplásicas/metabolismo , Fenotipo , Línea Celular Tumoral , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Proteínas de Neoplasias/genética , Citocinas/metabolismoRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the scientific community wonders if liver injury in patients suffering from severe forms is a direct consequence of the virus or secondary manifestations of systemic inflammation. The liver plays an essential role in the development of the inflammatory storm typical of this disease, and its involvement is associated with worse clinical outcomes and a higher risk of morbidity and mortality from Coronavirus disease 2019 (COVID-19). METHODS: Ten patients suffering from severe COVID-19 disease who died between January 2020 and December 2021 were included in the present analysis. These subjects underwent a post mortem examination with a focused evaluation of the hepatic injury. Also, several laboratory parameters have been evaluated, with a primary focus on prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers to detect coagulative changes. RESULTS: The main cause of death was represented by pulmonary thromboembolism events (50%). The analysis of coagulation laboratory parameters and liver biomarkers revealed a statistically significant rise in aPTT and ALP, and a decrease in albumin, when comparing the blood value at admission and death. We also found high levels of D-dimers in most of the subjects at the time of hospitalization. Interestingly, the post mortem analysis of the liver showed ample morphologic variability, with several disease features. In detail, the liver histology revealed the following: the presence of a variable degree of micro- and macrovacuolar steatosis, inflammation (also, hepato-cholangitis), and variable fibrosis. Of mention, we were also able to detect organized fibrinous material. CONCLUSIONS: Our results indicate that in subjects with a severe form of COVID-19, liver disease is related to changes in coagulative and fibrinolytic pathways. In particular, we noted low fibrinogen levels and high D-dimer levels with histological liver findings. Our data suggest that fibrinogen and D-dimers may be used as prognostic markers to detect the severity of liver disease in patients with COVID-19. Finally, we underline the crucial role of coagulation balance in subjects with severe forms of COVID-19.
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BACKGROUND AND OBJECTIVE: Mechanistic-based Model simulations (MM) are an effective approach commonly employed, for research and learning purposes, to better investigate and understand the inherent behavior of biological systems. Recent advancements in modern technologies and the large availability of omics data allowed the application of Machine Learning (ML) techniques to different research fields, including systems biology. However, the availability of information regarding the analyzed biological context, sufficient experimental data, as well as the degree of computational complexity, represent some of the issues that both MMs and ML techniques could present individually. For this reason, recently, several studies suggest overcoming or significantly reducing these drawbacks by combining the above-mentioned two methods. In the wake of the growing interest in this hybrid analysis approach, with the present review, we want to systematically investigate the studies available in the scientific literature in which both MMs and ML have been combined to explain biological processes at genomics, proteomics, and metabolomics levels, or the behavior of entire cellular populations. METHODS: Elsevier Scopus®, Clarivate Web of Science™ and National Library of Medicine PubMed® databases were enquired using the queries reported in Table 1, resulting in 350 scientific articles. RESULTS: Only 14 of the 350 documents returned by the comprehensive search conducted on the three major online databases met our search criteria, i.e. present a hybrid approach consisting of the synergistic combination of MMs and ML to treat a particular aspect of systems biology. CONCLUSIONS: Despite the recent interest in this methodology, from a careful analysis of the selected papers, it emerged how examples of integration between MMs and ML are already present in systems biology, highlighting the great potential of this hybrid approach to both at micro and macro biological scales.
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Aprendizaje Automático , Humanos , Biología de Sistemas/métodos , Genómica , MetabolómicaRESUMEN
BACKGROUND: Liver steatosis in patients with chronic infection of hepatitis C virus (HCV) is important from multiple standpoints: faster disease progression, more frequent hepatocellular carcinoma and cirrhosis development or worse therapy response. Liver biopsy as diagnostic method, is in recent years more and more challenged due to its well-known flaws. Hepatic steatosis index (HSI) and triglyceride-glucose (TyG) Index, are surrogate scores developed in the first place for noninvasive assessment of steatosis in patients with nonalcoholic fatty liver disease (NAFLD). However, their use in the context of chronic hepatitis C (CHC) virus infection is still unclear. Aim of our study was to assess the accuracy of both HSI and TyG index in patients with CHC. METHODS: The cohort included 814 patients with CHC infection in whom liver biopsy was performed. After implementing strict criteria for sample adequacy and necessary data, 424 patients were finally enrolled in our study. Histological findings were used as a reference point, and surrogate scores HSI and TyG index were expressed through receiver operating characteristic (ROC) curves in order to assess their ability in determining patients without (<5%) or with steatosis (>5%), but also to address their ability in assessing between different degrees of steatosis. RESULTS: The average age of study population was 37.09 years and the majority of patients were men (67%). Liver steatosis was detected in approximately half of the liver biopsy samples (50.4%). About 5% of them had severe steatosis. The area under the ROC curve values for HSI and TyG index when detecting liver steatosis were 0.76 and 0.629, respectively. Similar values were obtained comparing between absence of steatosis and mild steatosis (5-30%). CONCLUSIONS: Non-invasive surrogate scores HSI and TyG index in CHC patients, have good performance to detect the presence of steatosis. In this context, these tools are cheap, widely available and could be valuable asset in liver steatosis assessment outside liver biopsy.
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Hepatitis C Crónica , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Masculino , Humanos , Femenino , Adulto , Hepacivirus , Triglicéridos , Glucosa , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/patología , Hepatitis C Crónica/complicacionesRESUMEN
BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causal agent of the coronavirus disease (COVID-19), has infected millions of people worldwide. Currently, the scientific community debates on the direct viral responsibility of liver damage or whether the observed changes are secondary manifestations of systemic inflammation triggered by COVID-19. The hepatic involvement is associated with worse clinical outcomes and higher risk of COVID-19 related morbidity and mortality. Furthermore, SARS-CoV-2 infection may predispose patients to thrombotic disease due to excessive inflammation, platelet activation, and endothelial dysfunction. METHODS: In this paper, we reported a cross-sectional analysis of five patients affected by a severe form of COVID-19, who died between April 11 and May 1, 2020. Each patient has been subjected to a medico-legal autopsy in which both gross and histological liver changes were evaluated, as well as the correlation with the related coagulation profile. RESULTS: In three cases of our cohort, the thromboembolism was recognized as cause of death. Furthermore, a significant statistical difference between D-dimer values at hospital admission and death among enrolled patients (P=0.033), was evaluated. No patient has recorded a pre-existing liver disease. CONCLUSIONS: Our results support the evidence that hepatic damage in subjects with severe form of COVID-19 is related to the changes in coagulative and fibrinolytic pathways. Hence, the evaluation of D-dimer blood levels may be useful in clinical practice to predict the involvement of the liver and the prognosis of these patients. This data highlights the fundamental role of coagulation balance in subjects with advanced form of COVID-19.
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COVID-19 , Hepatopatías , Humanos , COVID-19/complicaciones , SARS-CoV-2 , Estudios Transversales , Inflamación , Hepatopatías/etiologíaRESUMEN
The intestinal microbiota represents the microbial community that colonizes the gastrointestinal tract and constitutes the most complex ecosystem present in nature. The main intestinal microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucromicrobia, with a clear predominance of the two phyla Firmicutes and Bacteroidetes which account for about 90% of the intestinal phyla. Intestinal microbiota alteration, or dysbiosis, has been proven to be involved in the development of various syndromes, such as non-alcoholic fatty liver disease, Crohn's disease, and ulcerative colitis. The present review underlines the most recurrent changes in the intestinal microbiota of patients with NAFLD, Crohn's disease, and ulcerative colitis.
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Colitis Ulcerosa , Enfermedad de Crohn , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Microbiota , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad de Crohn/microbiología , Colitis Ulcerosa/microbiología , Firmicutes , Disbiosis/microbiologíaRESUMEN
Acute liver failure (ALF) presents with an acute abnormality of liver blood tests in an individual without underlying chronic liver disease. The clinical course leads to the development of coagulopathy and hepatic encephalopathy. The role of nutrition in its prevention and treatment remains uncertain. We aimed to review literature data on the concept of ALF and the role of nutrition in its treatment and prevention, considering the impact of gut microbiota dysbiosis and eubiosis. We conducted a review of the literature on the main medical databases using the following keywords and acronyms and their associations: liver failure, nutrition, branched-chain amino acids, gut microbiota, dysbiosis, and probiotics. Upon their arrival at the emergency department, an early, accurate nutritional assessment is crucial for individuals with ALF. Branched-chain amino acids (BCAAs), stable euglycemia maintenance, and moderate caloric support are crucial for this subset of patients. An excessive protein load must be avoided because it worsens hepatic encephalopathy. Preclinical evidence supports future probiotics use for ALF treatment/prevention. Nutritional support and treatment for ALF are crucial steps against patient morbidity and mortality. BCAAs and euglycemia remain the mainstay of nutritional treatment of ALF. Gut dysbiosis re-modulation has an emerging and natural-history changing impact on ALF.
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Introduction: Gut microbiota is not only a taxonomic biologic ecosystem but is also involved in human intestinal and extra-intestinal functions such as immune system modulation, nutrient absorption and digestion, as well as metabolism regulation. The latter is strictly linked to non-alcoholic fatty liver disease (NAFLD) pathophysiology. Materials and methods: We reviewed the literature on the definition of gut microbiota, the concepts of "dysbiosis" and "eubiosis", their role in NAFLD pathogenesis, and the data on fecal microbiota transplantation (FMT) in these patients. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, eubiosis, dysbiosis, bile acids, NAFLD, and FMT. Results: Gut microbiota qualitative and quantitative composition is different in healthy subjects vs. NALFD patients. This dysbiosis is associated with and involved in NAFLD pathogenesis and evolution to non-acoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). In detail, microbial-driven metabolism of bile acids (BAs) and interaction with hepatic and intestinal farnesoid nuclear X receptor (FXR) have shown a determinant role in liver fat deposition and the development of fibrosis. Over the use of pre- or probiotics, FMT has shown preclinical and initial clinical promising results in NAFLD treatment through re-modulation of microbial dysbiosis. Conclusions: Promising clinical data support a larger investigation of gut microbiota dysbiosis reversion through FMT in NAFLD using randomized clinical trials to design precision-medicine treatments for these patients at different disease stages.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Trasplante de Microbiota Fecal , Ecosistema , Disbiosis/terapia , Disbiosis/complicaciones , Ácidos y Sales BiliaresRESUMEN
BACKGROUND: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive destruction of the intrahepatic bile ducts, followed by fibrous substitution of the ducts and potential evolution in cirrhosis. The geographical disparity in the prevalence of PBC suggests a possible role of environmental factors in developing the disease. We analyzed two groups of patients with different geographical prevalence. METHODS: This study concerned the analysis of 14 Caucasian patients in two groups: ten patients enrolled in the Digestive Diseases Unit, University of Catanzaro (Italy), and four patients enrolled in the Department of Hepatology, University Hospital Kràlovskè Vinohrady of Prague (Czech Republic). The statistical analysis was performed using the software IBM SPSS (v. 20, Windows). RESULTS: The Italian group showed a statistically significant difference in the total bilirubin values at diagnosis and during the last control (0.74±0.267 vs. 0.56±0.246; p-value: 0.013). Moreover, the comparison between the two groups showed a statistically significant difference in the serum albumin values at the time of the last control (4.6±0.231 vs. 4.15±0.532; p-value: 0.048). CONCLUSION: Our data indicate an effective difference in the onset and clinical presentation between our two groups. More epidemiologic, prospective, and multicenter research projects are warranted to advance PBC knowledge in Europe.
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Cirrosis Hepática Biliar , Humanos , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/epidemiología , Ácido Ursodesoxicólico , Estudios Prospectivos , Bilirrubina , Albúmina SéricaRESUMEN
BACKGROUND: Hepatic encephalopathy is defined as a spectrum of neuropsychiatric disorders in patients with liver dysfunction, usually cirrhosis, after exclusion of brain disease. This study reports the role of manganese in brain alterations and therefore in clinical manifestations of hepatic encephalopathy. CASE PRESENTATION: Male patient, 67 years old, suffering from alcoholic liver cirrhosis and two previous episodes of hepatic encephalopathy, developed drowsiness, asterixis, amnesia, disorientation in time and space, and psychomotor retardation. Brain MRI without contrast showed: initial signs of cerebral atrophy, a hyperintense signal of globi pallidi and bilateral substantia nigra. The hyperintense signal of globi pallidi is the result of manganese deposition in the brain. CONCLUSION: The case report presented supports the data reported in the literature indicating that the increase in plasma manganese levels in subjects with liver dysfunction is correlated with the onset of extrapyramidal symptoms.
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Non-alcoholic fatty liver disease (NAFLD) presents the most common chronic liver disease globally; it is estimated that 25.24% of the world's population has NAFLD. NAFLD is a multi-factorial disease whose development involves various processes, such as insulin resistance, lipotoxicity, inflammation, cytokine imbalance, the activation of innate immunity, microbiota and environmental and genetic factors. Numerous clinical studies have shown that the Mediterranean diet produces beneficial effects in NAFLD patients. The aim of this review is to summarize the beneficial effects of lycopene, a soluble pigment found in fruit and vegetables, in NAFLD.
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The histological features of nonalcoholic steatohepatitis (NASH) are the presence of hepatic steatosis with concomitant inflammation, ballooned hepatocytes, and potential fibrosis, which can lead to liver cirrhosis. To reduce the need for liver biopsy, that is still the gold standard for diagnosing NASH, various noninvasive biomarkers have been investigated. This narrative review summarizes the current knowledge about noninvasive diagnostic biomarkers and scores proposed for patients with NASH. A search was performed in the main medical literature databases. The following search terms were used: NASH, noninvasive biomarkers or NASH scores and panels. We focused only on studies assessing NASH diagnosis or predictive values for biomarkers, panels and scores. Data on their accuracy in predicting NASH were collected. Several panels such as NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4), and FibroMeter presented good predictive values of NASH, with novel proteomics panels such as the NAFLD Fibrosis Protein Panel (NFPP) using mainly the adisintegrin and metalloproteinase with thrombospondin motifs like 2 (ADAMTSL2) that showed an advantage in predicting NASH compared to NFS and FIB-4. Another novel panel, Index of NASH (ION) performed better than cytokeratin 18 (CK-18) in excluding severe fibrosis, but the overall accuracy of ION and CK-18 was modest compared to NFS and FIB-4 as it did not provide any significant advantage. Noninvasive biomarkers are currently unable to replace liver biopsy and histological assessment. However, they may play a key and vital role in triaging patients for liver biopsy, lowering the related financial burden. Future studies are needed to verify the predictive values of the newly emerging tests and panels as well as to find more affordable and reliable noninvasive early diagnostic tools.
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Proteínas ADAMTS , Proteómica , Humanos , FibrosisRESUMEN
The study of novel drug delivery systems represents one of the frontiers of the biomedical research area. Multi-disciplinary scientific approaches combining traditional or engineered technologies are used to provide major advances in improving drug bioavailability, rate of release, cell/tissue specificity and therapeutic index. Biodegradable and bio-absorbable polymers are usually the building blocks of these systems, and their copolymers are employed to create delivery components. For example, poly (lactic acid) or poly (glycolic acid) are often used as bricks for the production drug-based delivery systems as polymeric microparticles (MPs) or micron-scale needles. To avoid time-consuming empirical approaches for the optimization of these formulations, in silico-supported models have been developed. These methods can predict and tune the release of different drugs starting from designed combinations. Starting from these considerations, this review has the aim of investigating recent approaches to the production of polymeric carriers and the combination of in silico and experimental methods as promising platforms in the biomedical field.
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BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease characterized by erythematous plaques that can extend along the entire skin surface. In the latest years, it has been shown that serum calprotectin correlated strongly with several inflammatory biomarkers. Since high levels of calprotectin have been found in psoriatic lesions, it is of paramount importance to investigate the role of serum calprotectin as a possible novel diagnostic marker of psoriasis. Aim of our prospective pilot study was to assess the level of serum calprotectin in psoriatic patients. METHODS: Between January 2018 and July 2019, 45 subjects were enrolled at the Dermatology Unit of Magna Graecia University of Catanzaro, Italy. Thirty-two of them were psoriatic patients and 13 healthy controls. Psoriasis severity was assessed by the Psoriasis Area Severity Index. RESULTS: A statistically significant difference between the two groups (P=0.01) was found in terms of body mass index, higher among patients than in controls. By performing the Student's t-test for unpaired data, serum calprotectin resulted significantly higher (P=0.033) among psoriatic patients than in controls. Furthermore, performing the receiver operator characteristic curve analysis, serum calprotectin showed a significant area under the curve, implying its possible role in finding psoriatic patients. Our study aimed to evaluate the serum levels of calprotectin in a group of psoriatic patients and in a control group. The results showed that serum calprotectin levels were significantly higher in the patient group than in the control group. This result confirms the observations present in the literature. CONCLUSIONS: In this pilot study psoriatic patients had a significant high level of serum calprotectin than healthy subjects, and this biomarker had high accuracy in identifying patients. Further studies, with larger sample size will need to confirm our data.