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Topic Review
Diarylureas
The diarylurea is a scaffold of great importance in medicinal chemistry as it is present in numerous heterocyclic compounds with antithrombotic, antimalarial, antibacterial, and anti-inflammatory properties.
  • 795
  • 25 Jan 2021
Topic Review
Novel Selective RET Inhibitors
RET-selective tyrosine kinase inhibitors (TKIs) pralsetinib and selpercatinib, are effective against the RET V804L/M gatekeeper mutants. However, adaptive mutations that cause resistance at the solvent front RET G810 residue have been found, pointing to the need for the development of the next-generation of RET-specific TKIs. 
  • 795
  • 29 Apr 2021
Topic Review
Mitochondrial Bioenergetics in the Brain
Oxidative phosphorylation (OxPhos) is the basic function of mitochondria, although the landscape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of -omics technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding details to the mitochondrial proteome and defining novel metabolic cellular interrelations, especially in the human brain. We focussed on the diversity of bioenergetics demand and different aspects of mitochondrial structure, functions, and dysfunction in the brain. Definition such as ‘mitoexome’, ‘mitoproteome’ and ‘mitointeractome’ have entered the field of ‘mitochondrial medicine’.
  • 795
  • 22 Sep 2021
Topic Review
The Structure and Function of Integrins
Integrins are heterodimeric transmembrane proteins that mediate adhesive connections between cells and their surroundings, including surrounding cells and the extracellular matrix (ECM). They modulate tissue mechanics and regulate intracellular signaling, including cell generation, survival, proliferation, and differentiation, and the up-regulation of integrins in tumor cells has been confirmed to be associated with tumor development, invasion, angiogenesis, metastasis, and therapeutic resistance. Thus, integrins are expected to be an effective target to improve the efficacy of tumor therapy. A variety of integrin-targeting nanodrugs have been developed to improve the distribution and penetration of drugs in tumors, thereby, improving the efficiency of clinical tumor diagnosis and treatment. 
  • 795
  • 29 Jun 2023
Topic Review
Medicinal Plants with Anti-Leukemic Effects
Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient’s survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half of the drugs utilized nowadays in treating cancer are from natural products and their derivatives. Medicinal plants have proven to be an effective natural source of anti-leukemic drugs. The cytotoxicity and the mechanisms underlying the toxicity of these plants to leukemic cells and their isolated compounds were investigated.
  • 795
  • 18 May 2021
Topic Review
DNA-Repair Pathways: Links to Neurodegeneration
Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). A possible causative role for DNA damage and DNA repair in the pathogenesis of common, late-onset NDDs is less well established, although DDR defects are emerging as possible culprits in diseases like AD, PD, and ALS. Whether targeting DNA repair or the DDR may be developed into therapeutic options against NDDs remains to be clarified.
  • 795
  • 18 Jun 2021
Topic Review
In Vitro Maturation of Oocytes
In vitro maturation (IVM) of transvaginally aspirated immature oocytes is an effective and safe assisted reproductive treatment for predicted or high responder patients. Currently, immature oocytes are also being collected from the contralateral ovary during laparoscopy/laparotomy and even ex vivo from the excised ovary or the spent media during ovarian tissue preparation prior to ovarian cortex cryopreservation. The first live births from in vitro-matured ovarian tissue oocytes (OTO-IVM) were reported after monophasic OTO-IVM, showing the ability to achieve mature OTO-IVM oocytes. However, fertilisations rates and further embryological developmental capacity appeared impaired. The introduction of a biphasic IVM, also called capacitation (CAPA)-IVM, has been a significant improvement of the oocytes maturation protocol. However, evidence on OTO-IVM is still scarce and validation of the first results is of utmost importance to confirm reproducibility, including the follow-up of OTO-IVM children. Differences between IVM and OTO-IVM should be well understood to provide realistic expectations to patients.
  • 795
  • 20 Oct 2021
Topic Review
The Interventricular Septum
Vertebrates developed pulmonary circulation and septated the heart into venous and arterial compartments, as the adaptation from aquatic to terrestrial life requires more oxygen and energy. The interventricular septum (IVS) accommodates the ventricular portion of the conduction system and contributes to the mechanical function of both ventricles. Conditions or diseases that affect IVS structure and function (e.g., hypertrophy, defects, other) may lead to ventricular pump failure and/or ventricular arrhythmias with grave consequences. IVS structure and function can be evaluated today using current imaging techniques. Effective therapies can be provided in most cases, although definitions of underlying etiologies may not always be easy, particularly in the elderly due to overlap between genetic and acquired causes of IVS hypertrophy, the most common being IVS abnormality.
  • 795
  • 24 Jun 2022
Topic Review
Cerebral Small Vessel Disease
Cerebral small vessel disease (CSVD) represents a cluster of various vascular disorders with different pathological backgrounds. The advanced vasculature net of cerebral vessels, including small arteries, capillaries, arterioles and venules, is usually affected. Processes of oxidation underlie the pathology of CSVD, promoting the degenerative status of the epithelial layer. There are several classifications of cerebral small vessel diseases; some of them include diseases such as Binswanger’s disease, leukoaraiosis, cerebral microbleeds (CMBs) and lacunar strokes.
  • 794
  • 07 Jan 2021
Topic Review
CXCL1 in Noncancerous Diseases of the Nervous System
Chemokines are chemotactic cytokines, whose most important function is the chemoattraction of immune cells. CXC motif chemokine ligand 1 (CXCL1), a CXC chemokine, is also known as growth-regulated (or -related) oncogene-α (Gro-α) and melanoma growth-stimulatory activity (MGSA). The role CXCL1 plays in the physiology of the nervous system is described. 
  • 794
  • 10 Jun 2022
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