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Topic Review
The Global Medicines Agency Charter
The charter of the Global Medicines Agency (GMA) is based on learning from the working of these agencies to enable reaching the goal by bringing clarity, rationality, and practicality to the registration of drugs to overcome their accessibility issues.
  • 224
  • 25 Jul 2023
Topic Review
Role of Melatonin in Fibromyalgia
Fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome that is accompanied by fatigue, sleep disturbances, anxiety, depression, lack of concentration, and neurocognitive impairment. Melatonin is a low-molecular-weight indolamine (N-acetyl-5-methoxytryptamine) synthesized from the amino acid L-tryptophan, which is present in animals, plants, and even unicellular organisms. Melatonin is produced in the main cell of the pineal gland, the pinealocyte, and is controlled in mammals via ambient light.
  • 418
  • 24 Jul 2023
Topic Review
Therapies for Chronic Kidney Disease-Related Protein Energy Wasting
Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, “sterile” muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering “sterile” tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1β and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle.
  • 285
  • 12 Jul 2023
Topic Review
Possible Evolutionary Origin of Alzheimer’s Disease
The enormous, 2–3-million-year evolutionary expansion of hominin neocortices to the current enormity enabled humans to take over the planet. However, there appears to have been a glitch, and it occurred without a compensatory expansion of the entorhinal cortical (EC) gateway to the hippocampal memory-encoding system needed to manage the processing of the increasing volume of neocortical data converging on it. The resulting age-dependent connectopathic glitch was unnoticed by the early short-lived populations. It has now surfaced as Alzheimer’s disease (AD) in today’s long-lived populations. With advancing age, processing of the converging neocortical data by the neurons of the relatively small lateral entorhinal cortex (LEC) inflicts persistent strain and high energy costs on these cells. This may result in their hyper-release of harmless Aβ1–42 monomers into the interstitial fluid, where they seed the formation of toxic amyloid-β oligomers (AβOs) that initiate AD. At the core of connectopathic AD are the postsynaptic cellular prion protein (PrPC). Electrostatic binding of the negatively charged AβOs to the positively charged N-terminus of PrPC induces hyperphosphorylation of tau that destroys synapses. The spread of these accumulating AβOs from ground zero is supported by Aβ’s own production mediated by target cells’ Ca2+-sensing receptors (CaSRs).
  • 177
  • 05 Jul 2023
Topic Review
Effects of Tirzepatide in Spectrum of Metabolic Diseases
The prevalence of metabolic diseases including type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD) increases globally. This highlights an unmet need for identifying optimal therapies for the management of these conditions. Tirzepatide is a novel dual incretin receptor agonist (twincretin) that activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.
  • 316
  • 05 Jul 2023
Topic Review
Neuro-Inflammaging and Psychopatological Distress
Inflammaging is a low degree of chronic and systemic tissue inflammation associated with aging, and is intimately linked to pro-inflammatory mediators. These substances are involved in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms. Aging and inflammation have been defined in their interplay since the 1991 New York Academy of Sciences conference by a group of researchers. It ihas been suggested that  biological, chemical, and physics damage led to a chronic inflammatory process. The link between the molecular and cellular balance capable of permitting a physiological healthy aging or a cognitive impairment is still unclear. The innate immune system plays a crucial role in the inflammatory processes, usually reduced at advanced ages. In the elderly, senescent microglia augment the production of proinflammatory mediators with reduced chemotaxis and phagocytosis capacities, particularly of amyloid-β fibrils. The raised systemic inflammatory state and peripheral immunosenescence interfere with neuronal immune cell activity and reactivity.
  • 294
  • 28 Jun 2023
Topic Review
T2D Risk in Women with Polycystic Ovary Syndrome
Women with polycystic ovary syndrome (PCOS) are at increased risk for dysglycemia and type 2 diabetes compared to healthy BMI-matched women of reproductive age.
  • 314
  • 25 Jun 2023
Topic Review
Sodium–Glucose Cotransporter 2 and Kidney Function
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a relatively novel class of molecules named gliflozines that were originally designed to control glycemia, but over and above their effect on the glycemic metabolism, they unexpectedly improved the management of clinical conditions involving the function of the heart and kidneys. Importantly, the benefits of SGLT2i go beyond guideline-directed medical therapy, in that the drug’s metabolic effects on the kidneys and heart ameliorate the entire cardio–circulatory outcome.
  • 240
  • 20 Jun 2023
Topic Review
Hepatitis B Virus-Associated Polyarteritis Nodosa
Classic polyarteritis nodosa (PAN) is a vasculitis with systemic manifestations that is characterized by inflammatory and necrotizing lesions affecting medium and small muscular arteries, most frequently at the bifurcation of the vessels.
  • 513
  • 19 Jun 2023
Topic Review
The Metabolomics
Metabolomics is a combined set of strategies to identify and quantify cellular metabolites using advanced analytical tools. This is typically achieved through the use of liquid or gas chromatography, which allows for the detection of individual metabolites through their specific mass-to-charge ratio (m/z) and their fragmentation in a mass spectrometer. By matching detected metabolites against databases of known metabolites, it is possible to identify the specific metabolites altered by exercise in a biological sample.
  • 296
  • 19 Jun 2023
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