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Topic Review
Moonlighting Metalloproteinase
Protein moonlighting a.k.a. gene sharing has been defined as the concept that one protein processes multiple tasks and plays multiple roles [1]. Thus, multifunctional proteins are designated as moonlighting proteins. Matrix metalloproteinases play multiple roles in extracellular proteolysis and intracellular gene regulation [2,3], prompting us to propose a new definition of Moonlighting Metalloproteinase (MMP).
  • 979
  • 16 Nov 2020
Topic Review
Monoclonal Antibodies and Airway Diseases
Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS).
  • 979
  • 25 Dec 2020
Topic Review
Neonatal Screening for MPS Disorders
Newborn screening enables the diagnosis of treatable disorders at the early stages, and because of its countless benefits, conditions have been continuously added to screening panels, allowing early intervention, aiming for the prevention of irreversible manifestations and even premature death. Mucopolysaccharidoses (MPS) are lysosomal storage disorders than can benefit from an early diagnosis, and thus are being recommended for newborn screening. They are multisystemic progressive disorders, with treatment options already available for several MPS types. MPS I was the first MPS disorder enrolled in the newborn screening (NBS) panel in the USA and a few other countries, and other MPS types are expected to be added. Very few studies about NBS for MPS in Latin America have been published so far.
  • 978
  • 27 Nov 2020
Topic Review
Exercise Mitigates Pathological Liver Changes
Exercise attenuates pathological changes in the liver induced by high-fat diets. The underlying mechanisms might be related to Nuclear factor erythroid-2-related factor 2 (NRF2) and mediated by SIRT1/AMPK signaling. 
  • 976
  • 29 Mar 2022
Topic Review
Precision Treatment in ACS–Role Fibrinolysis
Despite advancements in pharmacotherapy and interventional strategies, patients with acute coronary syndrome (ACS) remain at risk of recurrent thrombotic events. In addition to an enhanced tendency to thrombus formation, impairment in the ability to naturally dissolve or lyse a developing thrombus, namely impaired endogenous fibrinolysis, is responsible for a major part of this residual risk regardless of optimal antiplatelet medication.
  • 974
  • 23 Mar 2021
Topic Review
Biomarker for Thyroid Cancer
Thyroid cancer has the most rapidly increasing incidence rate among all major cancers, with a triple increase from 4.5 to 14.4 per 100,000 population during 1974–2013. It was estimated 52,890 new cases in the United States in 2020 and contributed to 0.36% of all cancer deaths. Most primary thyroid cancers are follicular cell-derived epithelial tumors, making up four main pathological carcinoma types: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).
  • 974
  • 29 Mar 2022
Topic Review
Metabolomics in Thyroid Cancer
There is still a lack of reliable and specific markers for the detection and staging of thyroid cancer. Fine needle aspiration biopsy is the current diagnostic gold standard but indeterminate results or an inability to discriminate different carcinomas, requires additional surgical procedures to obtain a final diagnosis. Metabolomics has the potential to identify molecular markers of thyroid cancer and identify novel metabolic profiles of the disease, which can, in turn, help in the classification of pathological conditions and lead to a more personalised therapy, assisting in the diagnosis and in the prediction of cancer behaviour. This review considers the current results in thyroid cancer biomarker research with a focus on metabolomics.
  • 971
  • 15 Feb 2021
Topic Review
ESBL/AmpC
Extended-spectrum beta-lactamase (ESBL) and AmpC beta-lactamase (AmpC) producing Enterobacteriaceae occur frequently in livestock animals and the subsequent stages of the meat production chain and are therefore considered a risk for human health. Therefore, biosecurity and specific intervention measures shall prevent the entry and the spread of ESBL/AmpC producing E. coli in animal farms. Our review presents data from fourteen studies about the effectiveness of intervention studies on the occurrence of commensal, pathogenic and ESBL/AmpC producing E. coli in broiler fattening farms. The intervention measures were competitive exclusion, cleaning and disinfection and feed additives. The measured effects varied from "no effect" to a reduction of up to 6.6 log10 CFU/g.
  • 971
  • 26 May 2021
Topic Review
Airway Structural Changes in Asthma
Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n=47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.
  • 971
  • 30 Sep 2021
Topic Review
Oxidative Stress in AD
Alzheimer’s disease (AD) is the most common cause of dementia and the sixth cause of death in the world, constituting a major health problem for aging societies. This disease is a neurodegenerative continuum with well-established pathology hallmarks, namely the deposition of amyloid-β (Aβ) peptides in extracellular plaques and intracellular hyperphosphorylated forms of the microtubule associated protein tau forming neurofibrillary tangles (NFTs), accompanied by neuronal and synaptic loss. Interestingly, patients who will eventually develop AD manifest brain pathology decades before clinical symptoms appear. Among all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. 
  • 971
  • 06 Jul 2021
Topic Review
Electronic Cigarettes
Electronic cigarettes (EC) are a novel product, marketed as an alternative to tobacco cigarette. Its effects on human health have not been investigated widely yet, especially in specific populations such as patients with asthma.
  • 971
  • 18 Aug 2021
Topic Review
The Primary Microglial Leukodystrophies
Primary microglial leukodystrophy or leukoencephalopathy are disorders in which a genetic defect linked to microglia causes cerebral white matter damage. Pigmented orthochromatic leukodystrophy, adult-onset orthochromatic leukodystrophy associated with pigmented macrophages, hereditary diffuse leukoencephalopathy with (axonal) spheroids, and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) are different terms apparently used to designate the same disease. However, ALSP linked to dominantly inherited mutations in CSF1R (colony-stimulating factor receptor 1) causes CSF-1R-related leukoencephalopathy (CRP). Yet, recessive ALSP with ovarian failure linked to AARS2 (alanyl-transfer (t)RNA synthase 2) mutations (LKENP) is a mitochondrial disease and not a primary microglial leukoencephalopathy. Polycystic membranous lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; Nasu–Hakola disease: NHD) is a systemic disease affecting bones, cerebral white matter, selected grey nuclei, and adipose tissue The disease is caused by mutations of one of the two genes TYROBP or TREM2, identified as PLOSL1 and PLOSL2, respectively.
  • 971
  • 30 Jun 2022
Topic Review
Toll-Like Receptors and Alpha-Synuclein Proteotoxicity
The misfolding and subsequent abnormal accumulation and aggregation of α-Synuclein (αSyn) as insoluble fibrils in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson’s disease (PD) and several neurodegenerative disorders. A combination of environmental and genetic factors is linked to αSyn misfolding, among which neuroinflammation is recognized to play an important role. Indeed, a number of studies indicate that a Toll-like receptor (TLR)-mediated neuroinflammation might lead to a dopaminergic neural loss, suggesting that TLRs could participate in the pathogenesis of PD as promoters of immune/neuroinflammatory responses.
  • 971
  • 15 May 2023
Topic Review
Obstructive Sleep Apnea
The aim of this study was to assess the current scientific data and to summarize systematically the evidence of efficiency of adenotonsillectomy (AT) and orthodontic treatment (i.e.: rapid maxillary expansion (RME) and mandibular advancement (MA)) in the treatment of pediatric OSA. AT and orthodontic treatment were more effective together than separately to cure OSA in pediatric patients. There was a higher decrease of Apnea Hypoapnea Index (AHI) and Respiratory Disturbance Index (RDI), a major increase of the lowest oxygen saturation and the oxygen desaturation index (ODI) after undergoing both treatments. Nevertheless, reappearance of OSA could occur several years after reporting adequate treatment. In order to avoid recurrence, myofunctional therapy (MT) could be recommended as follow-up. However, further studies with good clinical evidence are required to confirm this finding.
  • 970
  • 18 Jan 2022
Topic Review
Bone Vascularization
As vascularization is an integral part of bone repair process, the analysis of the preventive and/or curative effects of physical exercise is currently very undeveloped. Angiogenesis–osteogenesis coupling may constitute a new way for understanding the role of physical activity, especially in fracturing or in the integration of bone biomaterials.
  • 970
  • 28 Sep 2021
Topic Review
FeNO analysis in IPF
Fractional exhaled nitric oxide is a non-invasive and reproducible biomarker that has demonstrated an interesting potential for differential diagnosis and prognostic estimation of patients affected by idiopathic pulmonary fibrosis. In particular, alveolar concentration of nitric oxide appeared to be a reliable indicator of severity of lung fibrosis and proved its efficacy in the early detection of patients with a fast progression of disease. Fractional exhaled nitric oxide (FeNO) is a well-known and widely accepted biomarker of airways inflammation in asthmatic patients. Recent evidences underlined the potential value of an extended analysis of FeNO, including a multiple-flows assessment, as a useful tool for the management of patients with interstitial lung However, the multiple-flows assessment of FeNO can provide a reliable measurement of bronchial and alveolar production of NO, supporting its potential value as biomarker also in peripheral lung diseases, such as interstitial lung diseases (ILD). The possibility to measure a biomarker of airway inflammation with a non-invasive, reproducible and economic technique led to the development of exhaled NO analyzers able to measure the NO burden in the airways. The procedure for the quantification of FeNO was standardized in 2005 [1]. To provide a more accurate evaluation of NO dynamics in distal airways and alveolar space, an extended analysis of FeNO has been proposed and the last technical standard document by ERS officially endorsed this procedure for future research[2]. Here, we performed a systematic review of literature in order to report all the available evidences concerning the rationale and the potential usefulness of extended FeNO analysis in the clinical management of idiopathic pulmonary fibrosis (IPF).
  • 969
  • 17 Sep 2020
Topic Review
Immunohistochemistry in Liver Tumors Diagnosis
Although radiological diagnostics have been progressing, pathological diagnosis remains the most reliable method for diagnosing liver tumors. In some cases, definite pathological diagnosis cannot be obtained by histological evaluation alone, especially when the sample is a small biopsy; in such cases, immunohistochemical staining is very useful. Immunohistochemistry is the most frequently used technique for molecular pathological diagnosis due to its broad application, ease of performance and evaluation, and reasonable cost. The results occasionally reflect specific genetic mutations. The immunohistochemical markers of hepatocellular carcinoma include those of hepatocellular differentiation—such as hepatocyte paraffin 1 and arginase-1—and those of malignant hepatocytes—such as glypican-3, heat shock protein 70, and glutamine synthetase (GS). To classify the subtypes of hepatocellular adenoma, examination of several immunohistochemical markers, such as liver fatty acid-binding protein, GS, and serum amyloid A, is indispensable. Immunohistochemical staining for GS is also important for the diagnosis of focal nodular hyperplasia. The representative immunohistochemical markers of intrahepatic cholangiocarcinoma include cytokeratin (CK) 7 and CK19.
  • 969
  • 15 Jun 2021
Topic Review
Immunomodulation in Cystic Fibrosis: Why and How?
Cystic fibrosis lung disease is characterized by unconventional mechanisms of inflammation, implicating a chronic immune response dominated by innate immune cells. Historically, therapeutic development has focused on the mutated cystic fibrosis transmembrane conductance regulator (CFTR), leading to the discovery of small molecules aiming at modulating and potentiating the presence and activity of CFTR at the plasma membrane. However, treatment burden sustained by CF patients, side effects of current medications, and recent advances in other therapeutic areas have highlighted the need to develop novel disease targeting of the inflammatory component driving CF lung damage. Furthermore, current issues with standard treatment emphasize the need for directed lung therapies that could minimize systemic side effects. Here, we summarize current treatment used to target immune cells in the lungs, and highlight potential benefits and caveats of novel therapeutic strategies.
  • 968
  • 13 May 2020
Topic Review
The HSC Niche in β-thalassemia and SCD
Hemoglobinopathies are inherited disorders affecting hemoglobin (Hb) production, estimated to be the most common monogenic diseases worldwide. In the last decade, research on pathophysiology and therapeutic solutions for β-thalassemia (BThal) and sickle cell disease (SCD) has been mostly focused on the primary erythroid defect, thus neglecting the study of hematopoietic stem cells (HSCs) and bone marrow (BM) microenvironment. The quality and engraftment of HSCs depend on the BM microenvironment, influencing the outcome of HSC transplantation (HSCT) both in allogeneic and in autologous gene therapy settings. In BThal and SCD, the consequences of severe anemia alter erythropoiesis and cause chronic stress in different organs, including the BM. 
  • 968
  • 07 Jul 2022
Topic Review
Early Sings in ASDs
Autism spectrum disorder (ASD) is neurodevelopmental pathology that manifest as deficits in certain fundamental areas.
  • 967
  • 10 Mar 2021
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