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Topic Review
Synthesis of Medicinally Relevant N-Heterocycles
N-heterocycles, both saturated and unsaturated, are ubiquitous biologically active molecules that are extremely appealing scaffolds in drug discovery programs. Although classical synthetic methods have been developed to access many relevant N-heterocyclic scaffolds, representing well-established and reliable routes, some do not meet the needs of sustainability. In this context, several advances have been made towards the sustainable synthesis of N-heterocycles.
  • 1.1K
  • 12 Oct 2021
Topic Review
Nuclear factor-κB in Psoriasis
Nuclear factor-κB (NF-κB) plays a central role in psoriasis and canonical Wnt/β-catenin pathway blunts the immune-mediated inflammatory cascade in psoriasis. Adenosine A2A receptor activation blocks NF-κB and boosts the Wnt/β-catenin signaling. PDRN (Polydeoxyribonucleotide) is a biologic agonist of the A2A receptor and its effects were studied in an experimental model of psoriasis. Psoriasis-like lesions were induced by a daily application of imiquimod (IMQ) on the shaved back skin of mice for 7 days. Animals were randomly assigned to the following groups: Sham psoriasis challenged with Vaseline; IMQ animals challenged with imiquimod; and IMQ animals treated with PDRN (8 mg/kg/ip). An additional arm of IMQ animals was treated with PDRN plus istradefylline (KW6002; 25 mg/kg/ip) as an A2A antagonist. PDRN restored a normal skin architecture, whereas istradefylline abrogated PDRN positive effects, thus pointing out the mechanistic role of the A2A receptor. PDRN decreased pro-inflammatory cytokines, prompted Wnt signaling, reduced IL-2 and increased IL-10. PDRN also reverted the LPS repressed Wnt-1/β-catenin in human keratinocytes and these effects were abolished by ZM241385, an A2A receptor antagonist. Finally, PDRN reduced CD3+ cells in superficial psoriatic dermis. PDRN anti-psoriasis potential may be linked to a “dual mode” of action: NF-κB inhibition and Wnt/β-catenin stimulation.
  • 1.1K
  • 03 Nov 2020
Topic Review
Probiotics and Oral Candidiasis
Oral candidiasis (OC) is an increasing health problem due to the introduction of new drugs, population aging, and increasing prevalence of chronic illness.  The intake of probiotics can have a beneficial effect on OC and that the effects could vary according to the patients’ characteristics.
  • 1.1K
  • 24 Aug 2021
Topic Review
Histone Monoubiquitination in Chromatin Remodelling
Chromatin remodelling is a major mechanism by which cells control fundamental processes including gene expression, the DNA damage response (DDR) and ensuring the genomic plasticity required by stem cells to enable differentiation. The post-translational modification of histone H2B resulting in addition of a single ubiquitin, in humans at lysine 120 (K120; H2Bub1) and in yeast at K123, has key roles in transcriptional elongation associated with the RNA polymerase II-associated factor 1 complex (PAF1C) and in the DDR. H2Bub1 itself has been described as having tumour suppressive roles and a number of cancer-related proteins and/or complexes are recognised as part of the H2Bub1 interactome. These include the RING finger E3 ubiquitin ligases RNF20, RNF40 and BRCA1, the guardian of the genome p53, the PAF1C member CDC73, subunits of the switch/sucrose non-fermenting (SWI/SNF) chromatin remodelling complex and histone methyltransferase complexes DOT1L and COMPASS, as well as multiple deubiquitinases including USP22 and USP44. While globally depleted in many primary human malignancies, including breast, lung and colorectal cancer, H2Bub1 is selectively enriched at the coding region of certain highly expressed genes, including at p53 target genes in response to DNA damage, functioning to exercise transcriptional control of these loci.
  • 1.1K
  • 16 Dec 2020
Topic Review
Flavonoids for Health and Longevity
Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits, vegetables, tea, wine, and Chinese herbal medicine. Flavonoids have a basic C6–C3–C6 15 carbon skeleton composed of two aromatic rings and one pyran ring. Flavonoid compounds are divided into six subclasses based on their carbon structure and level of oxidation, which are flavones, flavonols, flavanones, isoflavones, flavanol, and anthocyanins.
  • 1.1K
  • 23 Feb 2022
Topic Review
Tumor Microenvironment in melanoma
Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved the way for targeted and effective therapies. Melanoma was one of the first tumor types to benefit from this new care frontier by introducing specific inhibitors for v-Raf murine sarcoma viral oncogene homolog B (BRAF), mitogen-activated protein kinase (MEK), v-kit Hardy–Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and, recently, immunotherapy. However, despite the progress made in the melanoma treatment, primary and/or acquired drug resistance remains an unresolved problem. The molecular dynamics that promote this phenomenon are very complex but several studies have shown that the tumor microenvironment (TME) plays, certainly, a key role. In this review, we will describe the new melanoma treatment approaches and we will analyze the mechanisms by which TME promotes resistance to targeted therapy and immunotherapy.
  • 1.1K
  • 21 Oct 2020
Topic Review
Oxidative Stress in Periodontal Disease
Periodontal disease dominates as the most common inflammatory disease in the oral cavity. There is growing evidence on the involvement of oxidative stress, which is simply described as the imbalance between oxidants and antioxidants in favor of the former, in the initiation and progression of periodontal disease. Redox mechanistic insights that underlie immuno-inflammatory pathway may thus advance our understanding about periodontal pathogenesis, serving as the background for the development of efficient strategies for periodontal disease prevention and treatment.
  • 1.1K
  • 15 Jan 2021
Topic Review
First-and Second-Line Therapies for Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by the progressive destruction of the intrahepatic bile ducts. Currently, the first line drug for PBC is ursodeoxycholic acid characterized by anti-apoptotic, anti-inflammatory and protective actions on cholangiocytes. 
  • 1.1K
  • 21 Mar 2022
Topic Review
Influenza Hemagglutinin Vaccines
Hemagglutinin （HA） is the predominant antigenic protein of influenza viruses and antibodies directed at HA are correlated with protection against influenza virus infection
  • 1.1K
  • 12 May 2021
Topic Review
Single Use Medical Device Reprocessing
Single-use medical device reprocessing is the disinfection, cleaning, remanufacturing, testing, packaging and labeling, and sterilization among other steps, of a used, (or, in some cases, a device opened from its original packaging but unused), medical device to be put in service again. All reprocessed medical devices originally labeled for single use in the United States are subject to U.S. Food and Drug Administration (FDA) manufacturing requirements and must meet strict cleaning, functionality, and sterility specifications prior to use. Although first regulated in the U.S., the reprocessing of medical devices, particularly those that are labeled “Single Use Device” (SUDs), is a global practice with countries in Europe, Asia, Africa, and North America actively engaged in reprocessing. Currently, approximately 2% of all SUDs on the U.S. market are eligible for reprocessing by a qualified third-party vendor. The U.S. revenue for reprocessed devices (not SUDs) is estimated to be around $400 million annually.
  • 1.1K
  • 06 Oct 2022
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