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Topic Review
Cerebellar Ataxias
The terminology of cerebellar ataxias (CAs) embraces a ubiquitous deficit in 3 elemental domains: (a) limbs’ motor symptoms, (b) oculomotor symptoms, and (c) cognitive/emotional symptoms occurring in patients showing cerebellar dysfunction. Patients with CAs develop inaccuracy and clumsiness limb movements, characterized by dysmetria, tremor and adiadochokinesis. Posture is irregular and gait is unstable. Ocular movements lack accuracy. Cerebellar patients also show similar deficits in executive functions, linguistic processing, spatial cognition and affect regulation. Recent physiological studies have clarified that cerebellar outputs are modified by the release or facilitation of Purkinje cell-mediated inhibition on the cerebellar nucleus neurons. Thus, impairments in the formation of output signals elicit asthenia and adventitious movements, described by Holmes. These output signals are formed under controls of the internal forward model, embedded in the cerebellum. The deficits in the predictive computation for voluntary movements explains a range of characteristics accompanied by dysmetria. We argue that the impairments in the cerebellar outputs signals and the dysfunction in the internal forward model are fundamental mechanisms explaining the deficits in the 3 domains.
  • 1.4K
  • 02 Jul 2021
Topic Review
IFN-γ and Intracellular Protozoan Parasites
IFN-γ is an important cytokine in both innate and adaptive immune responses during intracellular parasite infections. Elevated levels of IFN-γ is detected in both experimental animals and human patients following intracellular protozoal infections. An extensive number of studies support a protective role for IFN-γ against the infection of intracellular protozoan parasites, including Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma, Leishmania, while a few studies also indicated that IFN-γ contributes to the pathogenesis of parasite infection.
  • 1.4K
  • 24 Feb 2023
Topic Review
CDKs in Sarcoma
Sarcomas represent one of the most challenging tumor types to treat due to their diverse nature and our incomplete understanding of their underlying biology. Recent work suggests cyclin-dependent kinase (CDK) pathway activation is a powerful driver of sarcomagenesis. CDK proteins participate in numerous cellular processes required for normal cell function, but their dysregulation is a hallmark of many pathologies including cancer. The contributions and significance of aberrant CDK activity to sarcoma development, however, is only partly understood. Here, we describe what is known about CDK-related alterations in the most common subtypes of sarcoma and highlight areas that warrant further investigation. As disruptions in CDK pathways appear in most, if not all, subtypes of sarcoma, we discuss the history and value of pharmacologically targeting CDKs to combat these tumors. The goals of this review are to (1) assess the prevalence and importance of CDK pathway alterations in sarcomas, (2) highlight the gap in knowledge for certain CDKs in these tumors, and (3) provide insight into studies focused on CDK inhibition for sarcoma treatment. Overall, growing evidence demonstrates a crucial role for activated CDKs in sarcoma development and as important targets for sarcoma therapy.
  • 1.4K
  • 29 Oct 2020
Topic Review
Nipah Virus Disease
Nipah virus (NiV) infection is a viral disease caused by a Henipavirus, belonging to the Paramyxoviridae family, responsible for a zoonosis. The course of the disease can be very serious and lead to death. NiV natural hosts are fruit bats (also known as megabats) belonging to the Pteropodidae family, especially those of the Pteropus genus. Natural infection in domestic animals has been described in farming pigs, horses, domestic and feral dogs and cats. Natural NiV transmission is possible intra-species (pig-to-pig, human-to-human) and inter-species (flying bat-to-human, pig-to-human, horse-to-human).
  • 1.4K
  • 11 Jan 2023
Topic Review
Pruritus Pathogenesis in Psoriasis
Psoriasis is a chronic, systemic inflammatory disease with a genetic background that involves almost 3% of the general population worldwide. About 70-80% of psoriatic patients suffer from pruritus. Despite its high prevalence in psoriasis, its pathogenesis still remains unclear. 
  • 1.4K
  • 22 Sep 2021
Topic Review
Hypophosphatasia: a Rare Bone Disease
Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5′-phosphate (PLP).
  • 1.4K
  • 10 May 2021
Topic Review
Duchenne Muscular Dystrophy
In Duchenne muscular dystrophy (DMD), the activation of proinflammatory and metabolic cellular pathways in skeletal muscle cells is an inherent characteristic. Synthetic glucocorticoid intake counteracts the majority of these mechanisms. However, glucocorticoids induce burdensome secondary effects, including hypertension, arrhythmias, hyperglycemia, osteoporosis, weight gain, growth delay, skin thinning, cushingoid appearance, and tissue-specific glucocorticoid resistance. Hence, lowering the glucocorticoid dosage could be beneficial for DMD patients. A more profound insight into the major cellular pathways that are stabilized after synthetic glucocorticoid administration in DMD is needed when searching for the molecules able to achieve similar pathway stabilization. This review provides a concise overview of the major anti-inflammatory pathways, as well as the metabolic effects of glucocorticoids in the skeletal muscle affected in DMD. The known drugs able to stabilize these pathways, and which could potentially be combined with glucocorticoid therapy as steroid-sparing agents, are described. This could create new opportunities for testing in DMD animal models and/or clinical trials, possibly leading to smaller glucocorticoids dosage regimens for DMD patients.
  • 1.4K
  • 10 Nov 2020
Topic Review
Benign Prostatic Hyperplasia (BPH)
Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate and can cause obstructive and irritating lower urinary tract symptoms (LUTS); this proliferative change affects smooth muscle and epithelial cells within the transition zone of the prostate.
  • 1.4K
  • 03 Mar 2021
Topic Review
Potential Biochemical Properties and Genetics of C-Reactive Protein
C-Reactive Protein (CRP) is supposed to be an accredited benchmark for physicians, to reveal or rule out inflammation, and multifarious scientific endeavors have been made so as to detect the direct pleiotropic functions of this protein. The use of CRP as the most important and critical immunochemical marker of several medical conditions, including infections such as sepsis, physiological organ diseases, various autoimmune disorders, malignancies and other health conditions, has become widely popular.
  • 1.4K
  • 14 Nov 2023
Topic Review
Polyphenols and Ischemic Stroke
Stroke is now the second leading cause of death worldwide, and is defined as an impairment in blood supply to the brain, and is linked to different cardiovascular dysfunctions. Two main types of stroke exist: ischemic stroke (due to clot-mediated blood vessel occlusion), which accounts for about 85% of all stroke cases, and hemorrhagic stroke (caused by blood vessel rupture), which accounts for 15% of total cases. Following the stroke, while the core region undergoes sudden death, the surrounding injured regions (called penumbra) may be able to recover their functions.
  • 1.4K
  • 23 Jun 2021
Topic Review
Biomaterials Applied to Bone Regeneration
Bone loss raises great concern in numerous situations, such as ageing and many diseases and in both orthopedic and dentistry fields of application, with an extensive impact on health care. Therefore, it is crucial to understand the mechanisms and the determinants that can regulate osteogenesis and ensure bone balance. In particular, new strategies for the improvement of the ability of biomaterials to trigger and sustain osteogenesis need to be developed. Autophagy is a well conserved lysosomal degradation pathway, which is known to be highly active during differentiation and development. An extensive revision of the literature on biomaterials, both for orthopedic and dentistry applications, enhancing osteogenesis by modulation of the autophagic process is here presented. Already investigated conditions regulating bone regeneration via autophagy need to be better understood for designing novel biomaterials with improved bioactivity.
  • 1.4K
  • 28 Oct 2020
Topic Review
Nonalcoholic fatty liver disease (NAFLD)
Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability.
  • 1.4K
  • 19 Aug 2020
Topic Review
Atrioventricular Septal Defect
Robert Anderson has made a huge contribution to almost all aspects of morphology and under-standing of congenital cardiac malformations, none more so than the group of anomalies that many of those in the practice of paediatric cardiology and adult congenital heart disease now call ‘Atrioventricular Septal Defect’ (AVSD). In 1982, with Anton Becker working in Amsterdam, their hallmark ‘What’s in a name?’ editorial was published in the Journal of Thoracic and Cardio-vascular Surgery. At that time most described the group of lesions as ‘atrioventricular canal mal-formation’ or ‘endocardial cushion defect’. Perhaps more significantly, the so-called ostium pri-mum defect was thought to represent a partial variant. It was also universally thought, at that time, that the left atrioventricular valve was no more than a mitral valve with a cleft in the aortic leaflet. In addition to this, lesions such as isolated cleft of the mitral valve, large ventricular septal defects opening to the inlet of the right and hearts with straddling or overriding tricuspid valve were variations of the atrioventricular canal malformation. Anderson and Becker emphasised the differences between the atrioventricular junction in the normal heart and those with a common junction for which they recommended the generic name, ‘atrioventricular septal defect’.
  • 1.4K
  • 08 Mar 2021
Topic Review
Vascular Calcification
A variety of actively regulated processes on cellular and systemic level with various contributing and inhibiting factors can result in vascular calcification (VC). Currently, treatment is limited to management of risk factors including regulation of the calcium-phosphate metabolism. Due to the complex pathophysiology, the mechanisms underlying ectopic calcification are studied in various, distinctly different research models. Beside in vitro models using cells of different origin, ex vivo settings using aortic tissue are available. In addition, various in vivo disease-induced animal models are currently used in research. All of these experimental settings depict (patho)physiologic mechanisms within the vascular calcification process.
  • 1.3K
  • 29 Oct 2020
Topic Review
Zinc Dyshomeostasis and Parkinson’s Disease
Zinc and other heavy metals have received considerable attention in neurodegenerative diseases because of their cytotoxicity. The role of zinc in the pathogenesis of PD is not straightforward because of its numerous and complex function. Both deficiency and excess of zinc have been incriminated in the development of the disease, though overwhelming evidence favor the later mechanism.
  • 1.3K
  • 20 May 2021
Topic Review
Focal Adhesion Kinase Inhibitors
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kinase activity in the cytoplasm, mainly dependent on the integrin signaling, and a scaffolding activity into the nucleus by networking with different gene expression regulators. For this reason, FAK has to be considered a target with high therapeutic values. Indeed, evidence suggests that FAK targeting could be effective, either alone or in combination, with other already available treatments.
  • 1.3K
  • 25 Feb 2022
Topic Review
Cardiac Autonomic Neuropathy
Cardiac autonomic neuropathy (CAN) is one of the earliest manifestations of type 2 diabetes (T2D). It constitutes the major cause of silent cardiovascular events in patients without overt cardiac disease. The high prevalence of CAN in patients newly diagnosed with T2D suggests that its pathophysiology is rooted in an earlier stage of metabolic derangement, possibly being prediabetes.
  • 1.3K
  • 11 Dec 2020
Topic Review
Autophagy-ER Stress Axis in High Fat/Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease that can progress from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), and even further to liver cirrhosis or liver cancer. Overconsumption of high fat and/or carbohydrate are among the most common lifestyle factors that drive the development and progression of NAFLD. This review evaluates recent reports on the involvement of autophagy and endoplasmic reticulum (ER) stress in the pathogenesis of NAFLD. Here, we reveal a mechanism of an intrinsically linked axis of impaired autophagy and unresolved ER stress that mediates the development and progression of NAFLD resulting from the overconsumption of high fat and/or carbohydrate.
  • 1.3K
  • 05 Nov 2020
Topic Review
Multiple Myeloma
Multiple myeloma (MM), characterized by malicious clonal explanation of plasma cells in the bone marrow with creation of monoclonal gammopathy, is the second most prevalent hematologic malignancy in adults. It accounts for approximately 13% of all hematologic malignancies and 1% of all cancers in the world, with a median age of onset of 69 years [1][2]. 
  • 1.3K
  • 27 Oct 2020
Topic Review
Methanethiol: A Scent Mark of Cancer
Dysregulation of sulfur metabolism may result in elevated levels of volatile sulfur compounds (VSCs) in body fluids, breath, and/or excretions of cancer patients. Besides hydrogen sulfide (H2S), methanethiol is the predominant cancer-associated VSC and has been proposed as a promising biomarker for non-invasive cancer diagnosis. Gut bacteria are the major exogenous source of exposure to this foul-smelling toxic gas, with methanethiol-producing strains such as Fusobacterium nucleatum highly abundant in the gut microbiome of colorectal carcinoma (CRC) patients. Physiologically, methanethiol becomes rapidly degraded through the methanethiol oxidase (MTO) activity of selenium-binding protein 1 (SELENBP1). However, SELENBP1, which is considered a tumor suppressor, is often downregulated in tumor tissues, and this has been epidemiologically linked to poor clinical outcomes. In addition to impaired removal, an increase in methanethiol levels may derive from non-enzymatic reactions, such as a Maillard reaction between glucose and methionine, two metabolites enriched in cancer cells. High methionine concentrations in cancer cells may also result in enzymatic methanethiol production in mitochondria. Moreover, enzymatic endogenous methanethiol production may occur through methyltransferase-like protein 7B (METTL7B), which is present at elevated levels in some cancers, including CRC and hepatocellular carcinoma (HCC). In conclusion, methanethiol contributes to the "scent of cancer" as part of the cancer-associated signature combination of volatile organic compounds (VOCs).
  • 1.3K
  • 12 Oct 2023
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