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Topic Review
Hypomethylating Agents Failure
Hypomethylating agents (HMA) such as azacitidine and decitabine are a mainstay in the current management of patients with myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML) as either single agents or in multidrug combinations. Resistance to HMA is not uncommon, and it can result due to several tumor cellular adaptations. Several clinical and genomic factors have been identified as predictors of HMA resistance. However, the management of MDS/AML patients after the failure of HMA remains challenging in the absence of standardized guidelines.
  • 296
  • 05 May 2023
Topic Review
The Activity of Substance P on Corneal Epithelium
In 1931, Von Euler and Gaddum isolated substance P (SP), an undecapeptide from the tachykinin family, from equine brain and intestine tissue extracts. Numerous types of cells, including neurons, astrocytes, microglia, epithelial, and endothelial cells, as well as immune cells including T-cells, dendritic cells, and eosinophils, are responsible for its production. The corneal epithelium, immune cells, keratocytes, and neurons all express the two isoforms of NK1R, which has the highest affinity for SP. 
  • 251
  • 05 May 2023
Topic Review
Zonulin Pathway as a Therapeutic Target
The integrity and thus the function of blood–brain barrier (BBB) TJs play a crucial role in the pathomechanism of neuroinflammatory and neurodegenerative diseases. Previously, it has been suggested that targeting different elements of the zonulin pathway, including actin filaments, TJs, or NF-κB, have potential therapeutic effects on CNS diseases. Indeed, encouraging results are accumulating from a recent preclinical study, using myosin light chain kinase (MLCK) inhibitor ML-7, which attenuates BBB disruption by preventing the disintegration of actin cytoskeletal microfilaments. Similarly, blocking the cleavage of TJ proteins by matrix metalloproteases (MMP) inhibitors, using either direct (broad-spectrum or selective MMP-2 and MMP-9) or indirect inhibitors (COX) has been shown to protect BBB. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, such as rosiglitazone, pioglitazone, or D-allose, also prevented BBB integrity by inhibiting NF-κB activation. Therefore, the use of zonulin inhibitors seems to be justified in the treatment of CNS diseases.
  • 683
  • 04 May 2023
Topic Review
Implementation of Lutetium-177 Therapy
Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) based radiopharmaceuticals has emerged as a therapeutic area in the field of nuclear medicine and oncology, allowing for personalized medicine. Since the first market authorization in 2018 of [¹⁷⁷Lu]Lu-DOTATATE (Lutathera®) targeting somatostatin receptor type 2 in the treatment of gastroenteropancreatic neuroendocrine tumors, intensive research has led to transfer innovative 177Lu containing pharmaceuticals to the clinic.
  • 886
  • 04 May 2023
Topic Review
Platelet-Rich Plasma Applications in Foot and Ankle
Platelet-rich plasma can be beneficial in treating various conditions, such as chronic foot ulcers, osteoarthritis, Achilles tendinopathy, etc. The platelet-rich plasma (PRP) therapy technique is still relatively new, yet it has already seen widespread application in the orthopedic field. Positive effects of PRP on various musculoskeletal conditions. PRP can be beneficial in treating various conditions, such as chronic foot ulcers, osteoarthritis, Achilles tendinopathy, etc. 
  • 271
  • 04 May 2023
Topic Review Video
The Link between Cardiovascular Disease and Exosomes
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent decades, clinical research has made significant advances, resulting in improved survival and recovery rates for patients with CVD. Despite this progress, there is substantial residual CVD risk and an unmet need for better treatment. The complex and multifaceted pathophysiological mechanisms underlying the development of CVD pose a challenge for researchers seeking effective therapeutic interventions. Consequently, exosomes have emerged as a new focus for CVD research because their role as intercellular communicators gives them the potential to act as noninvasive diagnostic biomarkers and therapeutic nanocarriers. In the heart and vasculature, cell types such as cardiomyocytes, endothelial cells, vascular smooth muscle, cardiac fibroblasts, inflammatory cells, and resident stem cells are involved in cardiac homeostasis via the release of exosomes. Exosomes encapsulate cell-type specific miRNAs, and this miRNA content fluctuates in response to the pathophysiological setting of the heart, indicating that the pathways affected by these differentially expressed miRNAs may be targets for new treatments.
  • 693
  • 04 May 2023
Topic Review
Metabolic Syndrome According to the Circadian Rhythm
Physiological processes occur in accordance with a rhythm regulated by the endogenous biological clock. This clock is programmed at the molecular level and synchronized with the daily light–dark cycle, as well as activities such as feeding, exercise, and social interactions. It consists of the core clock genes, Circadian Locomotor Output Cycles Protein Kaput (CLOCK) and Brain and Muscle Arnt-Like protein 1 (BMAL1), and their products, the period (PER) and cryptochrome (CRY) proteins, as well as an interlocked feedback loop which includes reverse-strand avian erythroblastic leukemia (ERBA) oncogene receptors (REV-ERBs) and retinoic acid-related orphan receptors (RORs). These genes are involved in the regulation of metabolic pathways and hormone release. Therefore, circadian rhythm disruption leads to development of metabolic syndrome (MetS). MetS refers to a cluster of risk factors (RFs), which are not only associated with the development of cardiovascular (CV) disease (CVD), but also with increased all-cause mortality.
  • 245
  • 04 May 2023
Topic Review
Nanoparticles as Delivery Systems via the Nasal Cavity
Microorganisms can produce nanoparticles through both intracellular and intercellular biosynthesis. This process can occur in a variety of different microorganisms, making it a versatile method for nanoparticle production. Different types of microbes can control the synthesis of various metallic nanoparticles. 
  • 344
  • 04 May 2023
Topic Review
Stress and Glucocorticoids Favor Metastatic Spread of Melanoma
Circulating glucocorticoids increase during stress. Chronic stress, characterized by a sustained increase in serum levels of cortisol, has been associated in different cases with an increased risk of cancer and a worse prognosis. Glucocorticoids can promote gluconeogenesis, mobilization of amino acids, fat breakdown, and impair the body's immune response. Therefore, conditions that may favor cancer growth and the acquisition of radio- and chemo-resistance. Glucocorticoid receptor knockdown diminishes the antioxidant protection of murine B16-F10 (highly metastatic) melanoma cells are found, thus leading to a drastic decrease in their survival during interaction with the vascular endothelium. The BRAFV600E mutation is the most commonly observed in melanoma patients. Studies revealed that VMF/PLX40-32 (vemurafenib, a selective inhibitor of mutant BRAFV600E) increases mitochondrial respiration and reactive oxygen species (ROS) production in BRAFV600E human melanoma cell lines. Early-stage cancer cells lacking Nrf2 generate high ROS levels and exhibit a senescence-like growth arrest. Thus, it is likely that a glucocorticoid receptor antagonist (RU486) could increase the efficacy of BRAF-related therapy in BRAFV600E-mutated melanoma. In fact, during early progression of skin melanoma metastases, RU486 and VMF induced metastases regression. However, treatment at an advanced stage of growth found resistance to RU486 and VMF. This resistance was mechanistically linked to overexpression of proteins of the Bcl-2 family (Bcl-xL and Mcl-1 in different human models). Moreover, melanoma resistance was decreased if AKT and NF-κB signaling pathways were blocked. These findings highlight mechanisms by which metastatic melanoma cells adapt to survive and could help in the development of most effective therapeutic strategies.  
  • 246
  • 04 May 2023
Topic Review
C-X-C Motif Chemokine Ligand 1 in Breast Cancer
C-X-C motif chemokine ligand 1 (CXCL1) is a member of the CXC chemokine subfamily and a ligand for CXCR2. Its main function in the immune system is the chemoattraction of neutrophils. Female breast cancer is the most commonly diagnosed cancer. In 2020, 2.26 million new cases of this cancer were diagnosed, accounting for 11.7% of all cancer diagnoses
  • 261
  • 04 May 2023
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