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Topic Review
Multiple Sclerosis
Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS), caused by genetic and environmental factors. It is characterized by intermittent and recurrent episodes of inflammation that result in the demyelination and subsequent damage of the underlying axons present in the brain, optic nerve and spinal cord [1][2][3].
  • 1.6K
  • 22 Apr 2021
Topic Review
The uPA/uPAR System in Fibrosis Progression
Urokinase plasminogen activator (uPA) is a single-chain serine protease that can cleave and activate Plg into plasmin by binding to urokinase plasminogen activator receptor (uPAR). uPA is secreted as a single-chain glycosylated zymogen called pro-uPA, and pro-uPA is activated by several proteinases, such as kallikrein, stromelysin, and plasmin. uPAR is a glycosyl-phosphatidyl-inositol anchored (GPI) membrane protein that consists of three domains: D1 (residues 1–92), D2 (residues 93–191) and D3 (residues 192–283). uPAR is cleaved between the D1 and D2 domains (linker region) and the GPI-anchor domain by several proteases, such as uPA, plasmin, MMPs, and GPI-specific phospholipase D, and then forms soluble uPAR (suPAR; full length D1-D3, D2D3, and D1).
  • 1.6K
  • 01 Feb 2023
Topic Review
Dipeptidyl Peptidase 4 Inhibitors in Antidiabetic Treatment
Dipeptidyl peptidase 4 (DPP4) enzyme is a type II transmembrane glycoprotein, expressed ubiquitously in many tissues, including the immune cells, kidney, liver, pancreas, fat cells, and presents as a soluble form in the circulation. Dipeptidyl peptidase 4 is a serine protease, can cleave and inactivate incretin hormones, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), neuropeptides, and chemokines. In addition, DPP4 has been shown to have a direct pro-inflammatory role in lymphocytes, macrophages, and smooth muscle cell.
  • 1.6K
  • 25 May 2022
Topic Review
OTOF-Associated Hearing Impairment
Otoferlin, an essential synaptic protein in the auditory sensory inner hair cells, is encoded by the gene OTOF. Biallelic variants in OTOF are associated with autosomal recessive auditory neuropathy or synaptopathy (DFNB9). Since its discovery in 1996, roughly 220 causally-associated variants have been uncovered. The prevalence of OTOF-associated hearing loss varies according to population. A higher molecular genetic diagnostic yield has been reported in patients with prelingual auditory synaptopathy, making this very specific clinical feature a useful criterion for OTOF diagnostic testing. Apart from this clinical hallmark, genotype-phenotype correlations are rather complex and include a variant that causes temperature-sensitive auditory neuropathy (p.Ile515Thr) and three variants that have so far been associated with progressive hearing impairment. Several founder variants have been reported in the Asian and European populations. A complete landscape of genomic variation at the DFNB9 locus remains to be determined and improvements in genomics technologies may eventually uncover novel insights into possible missing variants. A complete understanding of OTOF variants is essential for the success of current and future therapies.
  • 1.6K
  • 13 Jan 2021
Topic Review
Respiratory System Related Organ-on-a-Chip Models
The development of microfluidic chip technology provides a technical platform for better research on respiratory diseases. The size of its microchannel can be similar to the space for cell growthin vivo. In addition, organ-on-a-chip can achieve long-term co-cultivation of multiple cells and produce precisely controllable fluid shear force, periodically changing mechanical force, and perfusate with varying solute concentration gradient. To sum up, the chip can be used to analyze the specific pathophysiological changes of organs meticulously, and it is widely used in scientific research on respiratory diseases.
  • 1.6K
  • 27 Oct 2021
Topic Review
Pulmonary Arterial Hypertension: Therapeutic Pathways
Pulmonary arterial hypertension (PAH) is a severe disease characterized by the loss and obstructive remodeling of the pulmonary arterial wall, causing a rise in pulmonary arterial pressure and pulmonary vascular resistance, which is responsible for right heart failure, functional decline, and death. The main molecular pathways involved in drugs are available for the treatment PAH involve nitric oxide, endothelin 1 and prostacyclin. Although, this condition continues to be life-threatening, and its long-term treatment is expensive.
  • 1.6K
  • 21 Jul 2020
Topic Review
RNA Deregulation in ALS
RNA metabolism is central to cellular physiopathology. Almost all the molecular pathways underpinning biological processes are affected by the events governing the RNA life cycle, ranging from transcription to degradation. The deregulation of these processes contributes to the onset and progression of human diseases.
  • 1.6K
  • 29 Sep 2021
Topic Review
Factors influence skin barrier dysfunction
Atopic dermatitis (AD) is an eczematous, pruritic skin disorder with extensive barrier dysfunction and elevated interleukin (IL)-4 and IL-13 signatures. The barrier dysfunction correlates with the downregulation of barrier-related molecules such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL). IL-4 and IL-13 potently inhibit the expression of these molecules by activating signal transducer and activator of transcription (STAT)6 and STAT3. In addition to IL-4 and IL-13, IL-22 and IL-17A are probably involved in the barrier dysfunction by inhibiting the expression of these barrier-related molecules. In contrast, natural or medicinal ligands for aryl hydrocarbon receptor (AHR) are potent upregulators of FLG, LOR, and IVL expression. As IL-4, IL-13, IL-22, and IL-17A are all capable of inducing oxidative stress, antioxidative AHR agonists such as coal tar, glyteer, and tapinarof exert particular therapeutic efficacy for AD. These antioxidative AHR ligands are known to activate an antioxidative transcription factor, nuclear factor E2-related factor 2 (NRF2). This article focuses on the mechanisms by which FLG, LOR, and IVL expression is regulated by IL-4, IL-13, IL-22, and IL-17A. The author also summarizes how AHR and NRF2 dual activators exert their beneficial effects in the treatment of AD.
  • 1.6K
  • 11 Aug 2020
Topic Review
Coronavirus Disease 2019
Review of the effect of COVID-19 on pulmonary circulation
  • 1.6K
  • 20 Aug 2020
Topic Review
Apical Periodontitis
Apical periodontitis is the inflammation and destruction of periradicular tissues, mediated by microbial factors originating from the infected pulp space. This bacteria-mediated inflammatory disease is known to interfere with root development in immature permanent teeth.
  • 1.6K
  • 20 Jun 2023
Topic Review
Flavonoids in Skin Senescence Prevention
Skin aging is associated with the accumulation of senescent cells and is related to many pathological changes, including decreased protection against pathogens, increased susceptibility to irritation, delayed wound healing, and increased cancer susceptibility. Senescent cells secrete a specific set of pro-inflammatory mediators, referred to as a senescence-associated secretory phenotype (SASP), which can cause profound changes in tissue structure and function. Thus, drugs that selectively eliminate senescent cells (senolytics) or neutralize SASP (senostatics) represent an attractive therapeutic strategy for age-associated skin deterioration. There is growing evidence that plant-derived compounds (flavonoids) can slow down or even prevent aging-associated deterioration of skin appearance and function by targeting cellular pathways crucial for regulating cellular senescence and SASP. This review summarizes the senostatic and senolytic potential of flavonoids in the context of preventing skin aging.
  • 1.6K
  • 22 Sep 2021
Topic Review
Vitamin D in Multiple Sclerosis
Multiple sclerosis (MS) is a chronic demyelinating disease of central nervous system and is caused by an aberrant immune response to myelin sheath. Disease-modifying medications, which mainly aim to suppress such aberrant immune response, have significantly improved MS treatment. However, the disease severity continues to worsen. In contrast, progressively more data suggest that 1,25-dihydroxyvitamin D or 1,25(OH)2D, i.e., the active vitamin D, suppresses the differentiation of potentially pathogenic T cells associated with MS, enhances the differentiation of regulatory T cells that suppress the pathogenic T cells, and promotes remyelination. These novel 1,25(OH)2D functions have encouraged investigators to develop vitamin D as a potential therapy for MS. However, because of the hypercalcemia that is associated with high 1,25(OH)2D concentrations, supplementation of native vitamin D has been a major focus in clinical trials for the treatment of MS, but such trials have produced mixed data. In this article, we will review current progress in the supplementation of different vitamin D forms for the treatment of experimental autoimmune encephalomyelitis (i.e., an MS animal model) as well as MS.
  • 1.6K
  • 28 Oct 2020
Topic Review
Tauopathies
Tauopathies are neurodegenerative diseases characterized by the pathological accumulation of microtubule associated protein Tau (MAPT) in the form of neurofibrillary tangles and paired helical filaments in neurons and glia, leading to brain cell death. These diseases include frontotemporal dementia (FTD) and Alzheimer’s disease (AD) and can be sporadic or inherited when caused by mutations in the MAPT gene. Despite an incredibly high socio-economic burden worldwide, there are still no effective disease-modifying therapies and few Tau-focused experimental drugs have reached clinical trials. One major hindrance for therapeutic development is the knowledge gap in molecular mechanisms of Tau-mediated neuronal toxicity and death. For the promise of precision medicine for brain disorders to be fulfilled, it is necessary to integrate known genetic causes of disease, i.e., MAPT mutations, with understanding of the dysregulated molecular pathways that constitute potential therapeutic targets. Here, the growing understanding of known and proposed mechanisms of disease etiology will be reviewed, together with promising experimental Tau-directed therapeutics, such as recently developed Tau degraders. A particular focus will be given to the application of patient-specific stem cell models to study disease, and a number ofCurrent challenges faced by the fields of Tau research and drug discovery will alsobe addressed, including Tau pathophysiology unanswered questions, limitations of model systems and current challenges faced in developing cell-permeable small molecules that target Tau in disease.
  • 1.6K
  • 07 Dec 2020
Topic Review
Platelets, Depression and its Co-Morbidities
Alongside their function in primary haemostasis and thrombo-inflammation, platelets are increasingly considered a bridge between mental, immunological and coagulation-related disorders. This review focuses on the link between platelets and the pathophysiology of major depressive disorder (MDD) and its most frequent comorbidities. Platelet- and neuron-shared proteins involved in MDD are functionally described. Platelet-related studies performed in the context of MDD, cardiovascular disease, and major neurodegenerative, neuropsychiatric and neurodevelopmental disorders are transversally presented from an epidemiological, genetic and functional point of view. To provide a complete scenario, we report the analysis of original data on the epidemiological link between platelets and depression symptoms suggesting moderating and interactive effects of sex on this association. Epidemiological and genetic studies discussed suggest that blood platelets might be relevant biomarkers of MDD prediction and occurrence also in the context of MDD comorbidities. Finally, this review has the ambition to formulate some directives and perspectives for future research on this topic.
  • 1.6K
  • 02 Dec 2020
Topic Review
miRNAs in Cancer
Scientific investigations have shown the involvement of microRNAs (miRNAs) as a new key factor for cancer development and progression. Owing to their role in the regulation of gene expression and their stability (resistance to endogenous RNase activity) in body fluids, miRNAs have been extensively shown to be of particular interest for diagnosis, recurrence, identification, and treatment of cancer metastasis.  Despite miRNAs being considered small conserved regulators with the limitation of target specificity, we outline the dual role of melanoma-associated miRNAs, as oncogenic and/or tumor suppressive factors, compared to other tumors. 
  • 1.6K
  • 27 Oct 2020
Topic Review
Neuroinflammation in Friedreich’s Ataxia
Friedreich’s ataxia (FRDA) is a rare genetic disorder caused by mutations in the gene frataxin, encoding for a mitochondrial protein involved in iron handling and in the biogenesis of iron−sulphur clusters, and leading to progressive nervous system damage.
  • 1.6K
  • 10 Jun 2022
Topic Review
Antioxidant Therapy in Cystic Fibrosis
Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by major lung pathology including excess mucous build-up, chronic inflammation, persistent bacterial infections and progressive lung dysfunction. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an ion channel protein responsible for transport of chloride ions (Cl-) across epithelial cell membranes and, hence, regulates fluid secretion and homeostasis. CFTR also facilitates the efflux of intracellular glutathione (GSH), one of the most predominant antioxidants in animal cells, with impaired function causing systemic deficiency in extracellular GSH. Excessive reactive oxygen species (ROS) produced by inflammatory immune cells and bacterial infection leads to a highly oxidative extracellular environment, which further contributes to lung damage.
  • 1.6K
  • 26 Nov 2020
Topic Review
Mycoplasma pneumoniae Infections
Mycoplasma pneumoniae is a major causative agent of community-acquired pneumonia which can lead to both acute upper and lower respiratory tract inflammation, and extrapulmonary syndromes. 
  • 1.6K
  • 28 Sep 2021
Topic Review
Innovative Therapies for Wound Healing
Wound healing is divided into four overlapping phases: hemostasis, inflammation, proliferation, and remodeling/maturation. During hemostasis, endothelial cells secrete the von Willebrand factor, favoring the adhesion of platelets, which release mediators. During the inflammatory phase mast cells promote vasodilation by the secretion of histamine or serotonin. During the proliferative phase, fibroblasts, in addition to being involved in the formation of granulation tissue, are involved both in the regulation of keratinocyte migration and proliferation other than in angiogenesis. The main processes that distinguish the maturation (or remodeling) phase are collagen restoration and wound contraction, the latter due to myofibroblasts originating from the fibroblasts.
  • 1.6K
  • 19 Sep 2023
Topic Review
Bleeding Disorders in Primary Fibrinolysis
Fibrinolysis is a complex enzymatic process aimed at dissolving blood clots to prevent vascular occlusions. The fibrinolytic system is composed of a number of cofactors that, by regulating fibrin degradation, maintain the hemostatic balance. A dysregulation of fibrinolysis is associated with various pathological processes that result, depending on the type of abnormality, in prothrombotic or hemorrhagic states. 
  • 1.6K
  • 14 Jul 2021
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