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Topic Review
Flavonoids as CYP3A4 Inhibitors In Vitro
CYP enzymes are a group of heme-containing enzymes that play important roles in the metabolism of many drugs and other xenobiotics. They are located in the endoplasmic reticulum of cells throughout the body, but they are most abundant in the liver.
  • 62
  • 22 Mar 2024
Topic Review
Treatment of Cisplatin/Platinum-Ineligible Metastatic Urothelial Carcinoma
Metastatic urothelial cancer (mUC) is an aggressive malignancy with limited treatment options. Cisplatin-based chemotherapy has been the standard of care in metastatic urothelial cancer (mUC). However, many patients with comorbidities cannot receive cisplatin or its alternative, carboplatin. ‘Cisplatin-ineligible’ and ‘platinum-ineligible’ patients lacked effective therapy options. However, the combination of enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, with pembrolizumab (P), an antibody targeting the programmed death-1 (PD-1) immune checkpoint, is changing the status quo of frontline mUC treatment, with potential synergy seen in the EV-103 and EV-302 clinical trials.
  • 91
  • 22 Mar 2024
Topic Review
Infections in Disorders of Immune Regulation
Primary immune regulatory disorders (PIRDs) constitute a spectrum of inborn errors of immunity (IEIs) that are primarily characterized by autoimmunity, lymphoproliferation, atopy, and malignancy. In PIRDs, infections are infrequent compared to other IEIs. While susceptibility to infection primarily stems from antibody deficiency, it is sometimes associated with additional innate immune and T or NK cell defects. The use of immunotherapy and chemotherapy further complicates the immune landscape, increasing the risk of diverse infections. Recurrent sinopulmonary infections, particularly bacterial infections such as those associated with staphylococcal and streptococcal organisms, are the most reported infectious manifestations. Predisposition to viral infections, especially Epstein–Barr virus (EBV)-inducing lymphoproliferation and malignancy, is also seen. Notably, mycobacterial and invasive fungal infections are rarely documented in these disorders. Knowledge about the spectrum of infections in these disorders would prevent diagnostic delays and prevent organ damage. 
  • 75
  • 22 Mar 2024
Topic Review
Classification and Hemodynamic Definitions of Pulmonary Hypertension
Pulmonary hypertension (PH) refers to a pathologic elevation of the mean pulmonary artery pressure (mPAP) and is associated with increased morbidity and mortality in a wide range of medical conditions. These conditions are classified according to similarities in pathophysiology and management in addition to their invasive hemodynamic profiles. The 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension present the newest clinical classification system and includes significant updates to the hemodynamic definitions. Pulmonary hypertension is now hemodynamically defined as an mPAP > 20 mmHg, reduced from the previous threshold of ≥25 mmHg, due to important insights from both normative and prognostic data. Pulmonary vascular resistance has been extended into the definition of pre-capillary pulmonary hypertension, with an updated threshold of >2 Wood Units (WU), to help differentiate pulmonary vascular disease from other causes of increased mPAP. Exercise pulmonary hypertension has been reintroduced into the hemodynamic definitions and is defined by an mPAP/cardiac output slope of >3 mmHg/L/min between rest and exercise. While these new hemodynamic thresholds will have a significant impact on the diagnosis of pulmonary hypertension, no evidence-based treatments are available for patients with mPAP between 21–24 mmHg and/or PVR between 2–3 WU or with exercise PH. 
  • 67
  • 21 Mar 2024
Topic Review Peer Reviewed
The Effects of SARS-CoV-2 on the Angiopoietin/Tie Axis and the Vascular Endothelium
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyperinflammation, vasculitis, and multi-organ failure. SARS-CoV-2 causes the deterioration of numerous systems, with increasing evidence implying that COVID-19 affects the endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietin/Tie balance affects the vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects the Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically on the Angiopoietin/Tie pathway.
  • 410
  • 21 Mar 2024
Topic Review
The Single Toxin Origin of Alzheimer’s Disease
New data suggest that the aggregation of misfolded native proteins initiates and drives the pathogenic cascade that leads to Alzheimer’s disease (AD) and other age-related neurodegenerative disorders. Researchers propose a unifying single toxin theory of brain neurodegeneration that identifies new targets and approaches to the development of disease-modifying treatments. An extensive body of genetic evidence suggests soluble aggregates of beta-amyloid (Aβ) as the primary neurotoxin in the pathogenesis of AD. New insights from fluid biomarkers, imaging, and clinical studies provide further evidence for the decisive impact of toxic Aβ species in the initiation and progression of AD.
  • 67
  • 21 Mar 2024
Topic Review
Development of Pre-Eclampsia
Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan dysfunction.
  • 94
  • 21 Mar 2024
Topic Review
Paraoxonase 1 and Its Implications in Various Diseases
Paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory pathways, especially paraoxonase 1 (PON1). PON1 is diminished in infectious diseases, it can be used as a marker, and it can lead to lower protection against the microorganism; therefore, it can play a part in the development of antibiotic resistance.
  • 44
  • 21 Mar 2024
Topic Review
Melatonin in Viral, Bacterial and Parasitic Infections
The current view of the origin of melatonin (MLT), chemically defined as N-acetyl-5-methoxytriptamine, suggests that MLT appeared on earth about 2.5 billion years ago. Indeed, it is proposed that at that time, anaerobic bacteria developed the ability to synthesize MLT as an adaptative response to increasing concentrations of oxygen in the atmosphere.
  • 172
  • 21 Mar 2024
Topic Review
Glutamine, a Versatile Precursor for Biosynthesis and Bioenergetics
Glutamine, one of the most abundant amino acids in the body, plays diverse roles in cellular metabolism, ranging from bioenergetics to the synthesis of nucleotides, glutathione (GSH), and various other non-essential amino acids.
  • 48
  • 21 Mar 2024
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