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Topic Review
Oxidative Stress and Thyroid Diseases
Thyroid diseases, including neoplasms, autoimmune diseases and thyroid dysfunctions, are becoming a serious social problem with rapidly increasing prevalence. The latter is increasingly linked to oxidative stress. There are many methods for determining the biomarkers of oxidative stress, making it possible to evaluate the oxidative profile in patients with thyroid diseases compared to the healthy population. This opens up a new perspective for investigating the role of elevated parameters of oxidative stress and damage in people with thyroid diseases, especially of neoplastic nature. An imbalance between oxidants and antioxidants is observed at different stages and in different types of thyroid diseases. The organ, which is part of the endocrine system, uses free radicals (reactive oxygen species, ROS) to produce hormones. Thyroid cells release enzymes that catalyse ROS generation; therefore, a key role is played by the internal defence system and non-enzymatic antioxidants that counteract excess ROS not utilised to produce thyroid hormones, acting as a buffer to neutralise free radicals and ensure whole-body homeostasis. An excess of free radicals causes structural cell damage, undermining genomic stability. Looking at the negative effects of ROS accumulation, oxidative stress appears to be implicated in both the initiation and progression of carcinogenesis.
  • 584
  • 18 Oct 2021
Topic Review
Pentosan Polysulphate as a Potential Xylan based Prebiotic
In animal husbandry, prebiotic xylans aid in the maintenance of a healthy gut microbiome. This prevents the colonization of the gut by pathogenic organisms obviating the need for dietary antibiotic supplementation, a practice which has been used to maintain animal productivity but which has led to the emergence of antibiotic resistant bacteria that are passed up the food chain to humans. Seaweed xylan-based animal foodstuffs have been developed to eliminate ruminant green-house gas emissions by gut methanogens in ruminant animals, contributing to atmospheric pollution. Biotransformation of pentosan polysulfate by the gut microbiome converts this semi-synthetic sulfated disease-modifying anti-osteoarthritic heparinoid drug to a prebiotic metabolite that promotes gut health, further extending the therapeutic profile and utility of this therapeutic molecule. Xylans are prominent dietary cereal components of the human diet which travel through the gastrointestinal tract as non-digested dietary fibre since the human genome does not contain xylanolytic enzymes. The gut microbiota however digest xylans as a food source. Xylo-oligosaccharides generated in this digestive process have prebiotic health-promoting properties. Engineered commensal probiotic bacteria also have been developed which have been engineered to produce growth factors and other bioactive factors. A xylan protein induction system controls the secretion of these compounds by the commensal bacteria which can promote gut health or, if these prebiotic compounds are transported by the vagal nervous system, may also regulate the health of linked organ systems via the gut–brain, gut–lung and gut–stomach axes. Dietary xylans are thus emerging therapeutic compounds warranting further study in novel disease prevention protocols.
  • 584
  • 12 Oct 2022
Topic Review
Ultrastructure in Transthyretin Amyloidosis
Transthyretin (TTR) amyloidosis is caused by systemic deposition of wild-type or variant amyloidogenic TTR (ATTRwt and ATTRv, respectively). ATTRwt amyloidosis has traditionally been termed senile systemic amyloidosis, while ATTRv amyloidosis has been called familial amyloid polyneuropathy. Although ATTRwt amyloidosis has classically been regarded as one of the causes of cardiomyopathy occurring in the elderly population, recent developments in diagnostic techniques have significantly expanded the concept of this disease. For example, this disease is now considered an important cause of carpal tunnel syndrome in the elderly population. The phenotypes of ATTRv amyloidosis also vary depending on the mutation and age of onset. Peripheral neuropathy usually predominates in patients from the conventional endemic foci, while cardiomyopathy or oculoleptomeningeal involvement may also become major problems in other patients. Electron microscopic studies indicate that the direct impact of amyloid fibrils on surrounding tissues leads to organ damage, whereas accumulating evidence suggests that nonfibrillar TTR, such as oligomeric TTR, is toxic, inducing neurodegeneration. Microangiopathy has been suggested to act as an initial lesion, increasing the leakage of circulating TTR. Regarding treatments, the efficacy of liver transplantation has been established for ATTRv amyloidosis patients, particularly patients with early-onset amyloidosis. Recent phase III clinical trials have shown the efficacy of TTR stabilizers, such as tafamidis and diflunisal, for both ATTRwt and ATTRv amyloidosis patients. 
  • 583
  • 19 Jul 2021
Topic Review
Metabolic Obesity in People with Normal Body Weight
The term Metabolic Obesity in People with Normal Body Weight (MONW) is used to describe people who, despite having a healthy body weight - usually defined by the body index (BMI), and more and more often also the percentage of adipose tissue - show metabolic disorders characteristic of obese people. 
  • 581
  • 29 Mar 2022
Topic Review
The Role of Annexin A1 in the Kidney
Renal disorders are very prevalent and associated with significant morbidity and mortality. Among diverse pathogenic mechanisms, the dysregulation of immune and inflammatory responses plays an essential role in such disorders. Consequently, the discovery of Annexin A1, as a glucocorticoid-inducible anti-inflammatory protein, has fueled investigation of its role in kidney pathologies. Thus, its role has been examined in diverse renal pathologies, including acute kidney injury, diabetic nephropathy, immune-mediated nephropathy, drug-induced kidney injury, kidney stone formation, and renal cancer.
  • 581
  • 03 Mar 2022
Topic Review
Proprotein Convertase Subtilisin/Kexin Type 9 and Atherosclerosis
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, which leads to an increase in the level of cholesterol in the blood. The main anti-atherosclerotic effect of PCSK9 inhibitors results from their lipid-lowering efficiency.
  • 579
  • 01 Apr 2022
Topic Review
Cartilage Conduction Hearing
Cartilage conduction (CC) is a form of conduction that allows a relatively loud sound to be audible when a transducer is placed on the aural cartilage. The CC transmission mechanism has gradually been elucidated, allowing for the development of CC hearing aids (CC-HAs), which are clinically available in Japan. However, CC is still not fully understood.
  • 578
  • 09 Jun 2021
Topic Review
Antioxidants and Male Fertility
Spermatozoa are physiologically exposed to reactive oxygen species (ROS) that play a pivotal role on several sperm functions through activation of different intracellular mechanisms involved in physiological functions such as sperm capacitation associated-events. However, ROS overproduction depletes sperm antioxidant system, which leads to a condition of oxidative stress (OS). Subfertile and infertile men are known to present higher amount of ROS in the reproductive tract which causes sperm DNA damage and results in lower fertility and pregnancy rates. Thus, there is a growing number of couples seeking fertility treatment and assisted reproductive technologies (ART) due to OS-related problems in the male partner. Interestingly, although ART can be successfully used, it is also related with an increase in ROS production. This has led to a debate if antioxidants should be proposed as part of a fertility treatment in an attempt to decrease non-physiological elevated levels of ROS. However, the rationale behind oral antioxidants intake and positive effects on male reproduction outcome is only supported by few studies. 
  • 576
  • 16 Aug 2021
Topic Review
Reporting Thyroid Cytology
The Italian SIAPEC-AIT 2014 classification, the 2017 Bethesda System for Reporting Thyroid Cytology (TBSRTC), the 2016 UK Royal College of Pathologists (RCPath) thyroid reporting system, and the 2019 Japanese reporting system for thyroid aspiration cytology (JRSTAC2019) represent the most widely used reporting systems among clinicians and pathologists for the purpose of cytologically diagnosing, estimating the potential risk of malignancy (ROM), and defining the most appropriate treatment for a patient with a thyroid nodule. Although all the systems use overlapping diagnostic categories and morphologic criteria, they differ on the basis of the criteria for inclusion in the cytologic categories, which may, in turn, affect the ROM of a given category and the clinical management of the patient, particularly with regard to the “indeterminate” categories. 
  • 576
  • 17 Sep 2021
Topic Review
Heart Disease and Metabolic Steatosis
The liver-heart axis is a growing field of interest owing to rising evidence of complex bidirectional interplay between the two organs. Recent data suggest non-alcoholic fatty liver disease (NAFLD) has a significant, independent association with a wide spectrum of structural and functional cardiac diseases, and seems to worsen cardiovascular disease (CVD) prognosis.
  • 575
  • 28 Apr 2021
Topic Review
Premature Aging in CKD
The characteristics of CKD (chronic kidney disease) are similar to those of the aging process; therefore, it has been hypothesized that CKD promotes premature aging associated with related diseases. Furthermore, chronic diseases usually observed in aging, such as CVD, inflammation, vascular calcification, mineral, and bone disorders, and chronodisruption (chronic alteration of circadian rhythms), are markedly frequent in patients with CKD.
  • 573
  • 04 Aug 2021
Topic Review
Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease
Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease, which classically includes a spectrum of progressive pathological conditions, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) with different grades of fibrosis and cirrhosis. NAFLD is also a “multisystemic” disease, NAFLD is independently associated with serious hepatic complications (e.g., hepatic decompensation, hepatocellular carcinoma [HCC]), but also with an increased risk of developing cardiovascular disease (CVD).
  • 572
  • 17 Feb 2022
Topic Review
TRPM4 in Disease
Transient receptor potential melastatin 4 (TRPM4) is a unique member of the TRPM protein family and, similarly to TRPM5, is Ca2+ sensitive and permeable for monovalent but not divalent cations. It is widely expressed in many organs and is involved in several functions; it regulates membrane potential and Ca2+ homeostasis in both excitable and non-excitable cells. 
  • 569
  • 25 Jul 2024
Topic Review
Coronary Atherosclerosis Imaging
Identifying patients at increased risk of coronary artery disease, before the atherosclerotic complications become clinically evident, is the aim of cardiovascular prevention. Imaging techniques provide direct assessment of coronary atherosclerotic burden and pathological characteristics of atherosclerotic lesions which may predict the progression of disease. Atherosclerosis imaging has been traditionally based on the evaluation of coronary luminal narrowing and stenosis. However, the degree of arterial obstruction is a poor predictor of subsequent acute events. More recent techniques focus on the high-resolution visualization of the arterial wall and the coronary plaques. Most acute coronary events are triggered by plaque rupture or erosion. Hence, atherosclerotic plaque imaging has generally focused on the detection of vulnerable plaque prone to rupture. 
  • 568
  • 14 Jul 2021
Topic Review Peer Reviewed
The Effects of SARS-CoV-2 on the Angiopoietin/Tie Axis and the Vascular Endothelium
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyperinflammation, vasculitis, and multi-organ failure. SARS-CoV-2 causes the deterioration of numerous systems, with increasing evidence implying that COVID-19 affects the endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietin/Tie balance affects the vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects the Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically on the Angiopoietin/Tie pathway.
  • 567
  • 21 Mar 2024
Topic Review
Non-Pharmacological Interventions for Pain Management in Hemodialysis
Acupuncture demonstrated considerable promise as a benign and efficacious supplementary therapy for managing pain, enhancing functional capacity and muscular strength, lessening symptoms of restless leg syndrome and uremic pruritus, and bettering the quality of life (QOL) of patients on hemodialysis. Additional investigations are imperative to confirm these results and define the ideal parameters for treatment. Cognitive behavioral therapy also exhibited the potential to ameliorate diverse facets of wellness in hemodialysis patients, including social support, QOL, and mental health outcomes. Cognitive behavioral therapy (CBT) proved successful in attenuating depressive symptom severity, enhancing therapy adherence, and diminishing depression. Internet-based CBT could potentially enhance the accessibility and effectiveness of these interventions for this patient population. Relaxation techniques, encompassing progressive muscle relaxation, guided imagery, deep breathing exercises, and mindfulness meditation, appear to hold potential in managing pain, fatigue, stress, and sleep patterns, as well as in promoting well-being and QOL for hemodialysis patients. Emerging as an innovative immersive technology, virtual reality has demonstrated potential benefits in pain management for individuals undergoing hemodialysis.
  • 565
  • 23 Aug 2023
Topic Review
Vitamin D in Oral Diseases Development
Vitamin D is a fat-soluble secosteroid that plays a significant role in the whole body, including the maxillofacial region. The discovery of its receptors in many cells and organs made it possible to reveal the participation of vitamin D not only in the regulation of calcium phosphate metabolism, but also in immune processes, in providing anti-inflammatory and antimicrobial effects, slowing down cell proliferation and stimulating differentiation. In this literature review, we demonstrate the association between low vitamin D levels and the development of recurrent aphthous stomatitis, the course and response to treatment of squamous cell carcinoma of the oral cavity, the severity of periodontal diseases, and the processes of osseointegration and bone remodeling during dental implantation and guided tissue regeneration. 
  • 565
  • 17 Nov 2021
Topic Review
Targeted Therapeutic Approach for AML
Acute myeloid leukemia (AML) is a heterogenous hematopoietic neoplasm with various genetic abnormalities in myeloid stem cells leading to differentiation arrest and accumulation of leukemic cells in bone marrow (BM). The multiple genetic alterations identified in leukemic cells at diagnosis are the mainstay of World Health Organization classification for AML and have important prognostic implications. Recently, understanding of heterogeneous and complicated molecular abnormalities of the disease could lead to the development of novel targeted therapeutic agents. In the past years, gemtuzumab ozogamicin, BCL-2 inhibitors (venetovlax), IDH 1/2 inhibitors (ivosidenib and enasidenib) FLT3 inhibitors (midostaurin, gilteritinib, and enasidenib), and hedgehog signaling pathway inhibitors (gladegib) have received US Food and Drug Administration (FDA) approval for the treatment of AML. Especially, AML patients with elderly age and/or significant comorbidities are not currently suitable for intensive chemotherapy. Thus, novel therapeutic planning including the abovementioned target therapies could lead to improve clinical outcomes in the patients.
  • 562
  • 01 Jun 2021
Topic Review
Hyperthermic Intraperitoneal Chemotherapy
With increasing awareness amongst physicians and improved radiological imaging techniques, the peritoneal cavity is increasingly recognized as an important metastatic site in various malignancies. Prognosis of these patients is usually poor as traditional treatment including surgical resection or systemic treatment is relatively ineffective. Intraperitoneal delivery of chemotherapeutic agents is thought to be an attractive alternative as this results in high tumor tissue concentrations with limited systemic exposure. The addition of hyperthermia aims to potentiate the anti-tumor effects of chemotherapy, resulting in the concept of heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal metastases as it was developed about 3 decades ago. With increasing experience, HIPEC has become a safe and accepted treatment offered in many centers around the world. However, standardization of the technique has been poor and results from clinical trials have been equivocal.
  • 562
  • 07 Jul 2021
Topic Review
Molecular Mechanisms of Colistin Resistance in Acinetobacter baumannii
Colistin, as a positively charged peptide, exerts its antibacterial effect via electrostatic interactions with negatively charged lipid A, a component of lipopolysaccharide (LPS). Accordingly, two main mechanisms of colistin resistance have been described in Acinetobacter baumannii (A. baumannii): the complete loss or modifications of the target LPS, leading to abolishing or reducing its negative charge. The complete loss of LPS results from inactivation of the first three genes of the lipid A biosynthetic pathway (lpxA, lpxC, and lpxD genes), whereas the modification of LPS occurs through the addition of phosphoethanolamine (PEtN) moieties to lipid A by the pmrCAB operon-encoded enzymes. Although 4-amino-4-deoxy-L-arabinose (L-Ara4N) modification of LPS has been described as a more common and effective colistin resistance mechanism compared to PEtN LPS modification in diverse Gram-negative pathogens (Salmonella enterica, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa), it was absent in A. baumannii. In addition to chromosome-mediated mechanisms, plasmid-mediated colistin resistance encoded by mcr genes has been recognized as a major driver of rapid dissemination by horizontal gene transfer among pathogenic Gram-negative bacteria, including A. baumannii.
  • 560
  • 21 Mar 2023
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