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Topic Review
Ulcerative Colitis
The worldwide epidemiology of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), still shows an increasing trend in Asia and Iran. Despite an improvement in the treatment landscape focused on symptomatic control, long-term colectomies have not decreased over the last 10-year period. Thus, novel therapies are urgently needed in clinics to supplement the existing treatments. Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunosuppressive effects, targeting IBD as a new treatment strategy. They have recently received global attention for their use in cell transplantation due to their easy expansion and wide range of activities to be engrafted, and because they are home to the mucosa of the intestine. Moreover, MSCs are able to differentiate into epithelial and other cells that can directly promote repair in the mucosal damages in UC. It seems that there is a need to deepen our understanding to target MSCs as a promising treatment option for UC patients who are refractory to conventional therapies. Here, we overviewed the therapeutic effects of MSCs in UC and discussed the achievements and challenges in the cell transplantation of UC.
  • 544
  • 14 Dec 2020
Topic Review
Dabigatran in Alzheimer’s Disease
Alzheimer’s disease (AD) is caused by neurodegenerative, but also vascular and hemostatic changes in the brain. The oral thrombin inhibitor dabigatran, which has been used for over a decade in preventing thromboembolism and has a well-known pharmacokinetic, safety and antidote profile, can be an option to treat vascular dysfunction in early AD, a condition known as cerebral amyloid angiopathy (CAA). Dabigatran blocks soluble thrombin, thrombin-mediated formation of fibrin and amyloid-ß protein (Aβ)-containing fibrin clots. These clots are deposited in brain parenchyma and blood vessels in areas of CAA, leading to vascular and blood-brain barrier dysfunction, hypoperfusion and chronically reduced oxygen (hypoxia) and nutrient supply, mainly in hippocampal and neocortical brain areas. Dabigatran has the potential to preserve perfusion and oxygen delivery to the brain, and to prevent parenchymal Aß-, thrombin- and fibrin-triggered inflammatory and neurodegenerative processes, leading to synapse and neuron death, and cognitive decline. 
  • 544
  • 06 Jul 2021
Topic Review
Fexinidazole: All-Oral Therapy for Human African Trypanosomiasis
Human African trypanosomiasis (HAT or ‘sleeping sickness’) is a neglected tropical disease. If untreated, it is always fatal and leads to death. A few treatments are available for HAT, but most of them require a skilled professional, which increases the financial burden on the patient. Recently, fexinidazole (FEX) has been approved by the European Medicine Agency (EMA) and the United States Food and Drug Administration (USFDA) as the first all-oral therapy for the treatment of stage-1 (hemolymphatic) as well as stage-2 (meningoencephalitic) of HAT. Before the FEX approval, there were separate treatments for stage-1 and stage-2 of HAT. 
  • 543
  • 25 Jan 2022
Topic Review
Transient Receptor Potential
The superfamily of ion channels named transient receptor potential (TRP) acts as sensors of oxidative compounds at the plasma membrane and can amplify several signaling. The TRP superfamily is a non-selective cation channel initially identified in the Drosophila fly species. These channels are presented in different cell types and tissues, such as epithelial, immune, and neuronal cells.
  • 543
  • 12 Jan 2023
Topic Review
Ovarian Cancer Stem Cell Niche
Ovarian cancer is an aggressive gynaecological cancer with extremely poor prognosis, due to late diagnosis as well as the development of chemoresistance after first-line therapy.
  • 541
  • 05 May 2021
Topic Review
Critically Ill Patients Antimicrobial Dosing
In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. 
  • 541
  • 13 Jul 2021
Topic Review
Fenretinide in Cancer and Neurological Disease
Cancer and neurodegeneration share leadership as causes of morbidity and death worldwide. They can be thought as disease mechanisms at opposite ends: while in neurodegeneration, induction of inflammatory genes and suppression of cell-cycle genes are the prominent signals; the opposite happens in cancer. Fenretinide (all-trans-N-(4-hydroxyphenyl) retinamide, 4-HPR) is a synthetic derivative of all-trans-retinoic acid initially proposed in anticancer therapy for its antitumor effects combined with limited toxicity. It is also studied in many other diseases for its ability to influence several biological pathways and provide a broad spectrum of pharmacological effects.
  • 540
  • 18 Jul 2022
Topic Review
Intranasal Insulin in Ischemia, Brain Injuries and Diabetes
A decrease in the activity of the insulin signaling system of the brain leads to neurodegeneration and impaired regulation of appetite, metabolism, and endocrine functions. This is due to the neuroprotective properties of brain insulin, its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine and other systems. One of the approaches to restore the brain insulin system is the use of intranasally administered insulin (INI). INI is being considered as a promising drug to treat Alzheimer's disease and mild cognitive impairment. Clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. It has been shown that INI can be used for the treatment of cerebral ischemia, traumatic brain injuries, postoperative delirium, as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes.
  • 539
  • 20 Apr 2023
Topic Review
α-Synuclein Phosphorylation and Its Kinases
α-Synuclein is a protein with a molecular weight of 14.5 kDa and consists of 140 amino acids encoded by the SNCA gene. Missense mutations and gene duplications in the SNCA gene cause hereditary Parkinson’s disease. Highly phosphorylated and abnormally aggregated α-synuclein is a major component of Lewy bodies found in neuronal cells of patients with sporadic Parkinson’s disease, dementia with Lewy bodies, and glial cytoplasmic inclusion bodies in oligodendrocytes with multiple system atrophy. Aggregated α-synuclein is cytotoxic and plays a central role in the pathogenesis of the above-mentioned synucleinopathies. In a healthy brain, most α-synuclein is unphosphorylated; however, more than 90% of abnormally aggregated α-synuclein in Lewy bodies of patients with Parkinson’s disease is phosphorylated at Ser129, which is presumed to be of pathological significance. Several kinases catalyze Ser129 phosphorylation, but the role of phosphorylation enzymes in disease pathogenesis and their relationship to cellular toxicity from phosphorylation are not fully understood in α-synucleinopathy. G-protein-coupled receptor kinases, casein kinase II, and polo-like kinase possess the ability to phosphorylate α-synuclein protein. On this point, inhibition of these kinases is able to prevent α-synuclein phosphorylation, which indicates the potential therapeutic targets and availability of drug development for α-synucleinopathies. α-Synuclein phosphorylation can clinically be an accompanying event in the brains of patients with Parkinson’s disease rather than the critical factor for α-synuclein aggregation and toxicity. Nevertheless, increasing phosphorylated α-synuclein and the accumulation with disease progression is useful as a therapeutic target and biomarker.
  • 538
  • 08 Jun 2022
Topic Review
Antifungal Drugs against Paracoccidioidomycosis
Paracoccidioidomycosis is a neglected disease that causes economic and social impacts, mainly affecting people of certain social segments, such as rural workers. The limitations of antifungals, such as toxicity, drug interactions, restricted routes of administration, and the reduced bioavailability in target tissues, have become evident in clinical settings. These factors, added to the fact that Paracoccidioidomycosis (PCM) therapy is a long process, lasting from months to years, emphasize the need for the research and development of new molecules.
  • 537
  • 16 Dec 2020
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