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Topic Review
Transient Receptor Potential Cation 6
Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates the cAMP (adenosine 3’,5’-cyclic monophosphate) response element-binding protein (CREB), an important transcription factor linked to neuronal survival.
  • 1.0K
  • 03 Mar 2021
Topic Review
EWSR1
EWSR1 belongs to the FET family of RNA-binding proteins including also Fused in Sarcoma (FUS), and TATA-box binding protein Associated Factor 15 (TAF15).
  • 1.0K
  • 07 Jul 2021
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.
  • 1.0K
  • 28 Sep 2021
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).
  • 1.0K
  • 25 Dec 2020
Topic Review
Cortical Hyperexcitability in the Driver’s Seat in ALS
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the degeneration of cortical and spinal motor neurons. With no effective treatment available to date, patients face progressive paralysis and eventually succumb to the disease due to respiratory failure within only a few years. Intriguingly, a key feature present in both ALS patients and rodent models of the disease is cortical hyperexcitability and hyperconnectivity, the mechanisms of which still remain incompletely understood. 
  • 1.0K
  • 28 Feb 2022
Topic Review
Molecular Pathology of Skin Melanoma
Skin melanoma is traditionally considered one of the most immunogenic tumor types, based in part on its long-known feature of frequently containing a characteristic lymphoid infiltrate; furthermore, it may be the only tumor type for which spontaneous regression can occur in the primary tumor; this regression is assumed to be the consequence of antitumor immune response. More recent research and therapy results supported the unique immunological features of cutaneous melanoma from other aspects. It belongs to tumors with the highest tumor mutational burden (TMB), caused by high mutagen exposure (UV radiation).
  • 1.0K
  • 26 May 2022
Topic Review
Hsrω lncRNAs
The lncRNAs produced by the hsrω gene are known to modulate neurotoxicity in polyQ and amyotrophic lateral sclerosis disease models of Drosophila. Elevated expression of hsrω lncRNAs exaggerates, while their genetic depletion through hsrω-RNAi or in an hsrω-null mutant background suppresses, the disease pathogenicity.
  • 1.0K
  • 12 Jan 2023
Topic Review
Tularemia
Francisella tularensis (Ft) is the etiological agent of tularemia, a disease known for over 100 years in the northern hemisphere. Ft includes four subspecies, of which two are the etiologic agents of tularemia: Ft subsp. tularensis (Ftt) and Ft subsp. holarctica (Fth), mainly distributed in North America and the whole northern hemisphere, respectively.
  • 1.0K
  • 27 Jan 2021
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.
  • 1.0K
  • 15 May 2023
Topic Review
Extracellular Vesicles as a Biomarker in Liver Disease
Extracellular vesicles (EVs) are membrane-derived vesicles released by a variety of cell types, including hepatocytes, hepatic stellate cells, and immune cells in normal and pathological conditions. Depending on their biogenesis, there is a complex repertoire of EVs that differ in size and origin. EVs can carry lipids, proteins, coding and non-coding RNAs, and mitochondrial DNA causing alterations to the recipient cells, functioning as intercellular mediators of cell–cell communication (auto-, para-, juxta-, or even endocrine). The use of EVs as biomarkers in liver disease development are described. 
  • 1.0K
  • 11 Jan 2023
Topic Review
Drug Delivery Across Blood-Brain Barrier
Brain tumors are characterized by very high mortality and, despite the continuous research on new pharmacological interventions, little therapeutic progress has been made. One of the main obstacles to improve current treatments is represented by the impermeability of the blood vessels residing within nervous tissue as well as of the new vascular net generating from the tumor, commonly referred to as blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), respectively.
  • 1.0K
  • 06 Feb 2021
Topic Review
Inflammasome and Pyroptosis in Hypertension
Inflammasomes are components of the innate immune response that have recently emerged as crucial controllers of tissue homeostasis. In particular, the nucleotide-binding domain, leucine-rich-containing (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a complex platform involved in the activation of caspase-1 and the maturation of interleukin (IL)-1β and IL-18, which are mainly released via pyroptosis. Pyroptosis is a caspase-1-dependent type of cell death that is mediated by the cleavage of gasdermin D and the subsequent formation of structurally stable pores in the cell membrane.
  • 1.0K
  • 18 Mar 2021
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.
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  • 18 Jan 2022
Topic Review
Immune-Checkpoint Inhibitors(ICI)
Recently, the introduction of immunotherapy radically changed the therapeutic algorithm of non-small-cell lung cancer as upfront or secondary strategy. Unfortunately, the small number of patient who benefits from immune-checkpoint inhibitors (ICI) and the prognostic role of concomitant treatments are a burning open issue. The use of steroids was associated with poor outcomes during ICI. We investigated the impact of intercurrent steroids, according to clinical indication, which is actually unclear. Interestingly, the use of intercurrent steroids given for cancer-unrelated symptoms has no survival impact on our study cohort. 
  • 1.0K
  • 27 Oct 2020
Topic Review
Autophagy Induction: Host-Directed Therapeutic Strategy
Tuberculosis (TB), a bacterial infectious disease caused by Mycobacterium tuberculosis (M.tb), causes significant mortality in humans worldwide. The current treatment regimen involves the administration of multiple antibiotics over the course of several months that contributes to patient non-compliance leading to relapse and the development of drug-resistant M.tb (MDR and XDR) strains. Together, these facts highlight the need for the development of shorter TB treatment regimens. Host-directed therapy (HDT) is a new and emerging concept that aims to augment host immune response using drugs/compounds with or without adjunct antibiotics against M.tb infection. Autophagy is a natural catabolic mechanism of the cell that involves delivering the cytosolic constituents to the lysosomes for degradation and recycling the components; thereby maintaining the cellular and energy homeostasis of a cell. However, over the past decade, an improved understanding of the role of autophagy in immunity has led to autophagy activation by using drugs or agents. This autophagy manipulation may represent a promising host-directed therapeutic strategy for human TB. 
  • 1.0K
  • 02 Jun 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).
  • 1.0K
  • 29 Mar 2022
Topic Review
Translation of Ferroptosis into Clinical Hepatocellular Carcinoma Practice
Ferroptosis, an iron and reactive oxygen species (ROS)-dependent non-apoptotic type of regulated cell death, is characterized by a massive iron overload and peroxidation of polyunsaturated fatty acids (PUFAs), which finally results in cell death. Recent studies suggest that ferroptosis can influence carcinogenesis negatively and therefore may be used as a novel anti-cancer strategy. Hepatocellular carcinoma (HCC) is a deadly malignancy with poor chances of survival and is the second leading cause of cancer deaths worldwide. Diagnosis at an already late stage and general resistance to current therapies may be responsible for the dismal outcome. As the liver acts as a key factor in iron metabolism, ferroptosis is shown to play an important role in HCC carcinogenesis and, more importantly, may hold the potential to eradicate HCC.
  • 1.0K
  • 05 May 2022
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.
  • 1.0K
  • 30 Jun 2022
Topic Review
New Perspectives on Polycythemia Vera
Polycythemia vera (PV) is mainly characterized by elevated blood cell counts, thrombotic as well as hemorrhagic predisposition, a variety of symptoms, and cumulative risks of fibrotic progression and/or leukemic evolution over time. Major changes to its diagnostic criteria were made in the 2016 revision of the World Health Organization (WHO) classification, with both hemoglobin and hematocrit diagnostic thresholds lowered to 16.5 g/dl and 49% for men, and 16 g/dl and 48% for women, respectively. The main reason leading to these changes was represented by the recognition of a new entity, namely the so-called “masked PV”, as individuals suffering from this condition have a worse outcome, possibly owing to missed or delayed diagnoses and lower intensity of treatment. Thrombotic risk stratification is of crucial importance to evaluate patients’ prognosis at diagnosis. Currently, patients are stratified into a low-risk group, in the case of younger age (<60 years) and no previous thromboses, and a high-risk group, in the case of patients older than 60 years and/or with a previous thrombotic complication. Furthermore, even though they have not yet been formally included in a scoring system, generic cardiovascular risk factors, particularly hypertension, smoking, and leukocytosis, contribute to the thrombotic overall risk. In the absence of agents proven to modify its natural history and prevent progression, PV management has primarily been focused on minimizing the thrombotic risk, representing the main cause of morbidity and mortality. When cytoreduction is necessary, conventional therapies include hydroxyurea as a first-line treatment and ruxolitinib and interferon in resistant/intolerant cases. Each therapy, however, is burdened by specific drawbacks, underlying the need for improved strategies. Currently, the therapeutic landscape for PV is still expanding, and includes several molecules that are under investigation, like long-acting pegylated interferon alpha-2b, histone deacetylase inhibitors, and murine double minute 2 (MDM2) inhibitors.
  • 1.0K
  • 24 Aug 2020
Topic Review
Vascular Smooth Muscle Cell Phenotype Switching in Arteriogenesis
Vascular smooth muscle cells in the adult vasculature are not terminally differentiated cells. They possess extensive plasticity such that it can be stimulated to undergo a structural and functional transition into proliferative/migratory/synthetic phenotype or undergo an extreme phenotypic change into osteochondrocyte-like cells, foam-like cells, and myofibroblastsas detected in atherosclerotic lesions. Nevertheless, SMC plasticity enables de-differentiated SMCs to re-differentiate back to a quiescent and contractile state according to their microenvironment. SMCs are the predominant cell type in collateral arteries that restores blood flow after significant arterial occlusion in peripheral arterial disease patients. They respond to altered blood flow and inflammatory conditions after an arterial occlusion by switching their phenotype between quiescent contractile and proliferative synthetic states.
  • 1.0K
  • 13 Feb 2023
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