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Topic Review
HDAC Inhibitors and Prostate Cancer
Novel treatment regimens are required for castration-resistant prostate cancers (CRPCs) that become unresponsive to standard treatments, such as docetaxel and enzalutamide. Histone deacetylase (HDAC) inhibitors showed promising results in hematological malignancies, but they failed in solid tumors such as prostate cancer, despite the overexpression of HDACs in CRPC. Four HDAC inhibitors, vorinostat, pracinostat, panobinostat and romidepsin, underwent phase II clinical trials for prostate cancers; however, phase III trials were not recommended due to a majority of patients exhibiting either toxicity or disease progression. In this entry, the pharmacodynamic reasons for the failure of HDAC inhibitors were assessed and placed in the context of the advancements in the understanding of CRPCs, HDACs and resistance mechanisms. 
  • 525
  • 01 Jul 2021
Topic Review
Hypoxia (Medical)
Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during hypoventilation training or strenuous physical exercise. Hypoxia differs from hypoxemia and anoxemia in that hypoxia refers to a state in which oxygen supply is insufficient, whereas hypoxemia and anoxemia refer specifically to states that have low or zero arterial oxygen supply. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia. Generalized hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness leading to potentially fatal complications: high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content, e.g. while diving underwater especially when using closed-circuit rebreather systems that control the amount of oxygen in the supplied air. Mild, non-damaging intermittent hypoxia is used intentionally during altitude training to develop an athletic performance adaptation at both the systemic and cellular level. In acute or silent hypoxia, a person's oxygen level in blood cells and tissue can drop without any initial warning, even though the individual's chest x-ray shows diffuse pneumonia with an oxygen level below normal. Doctors report cases of silent hypoxia with COVID-19 patients who did not experience shortness of breath or coughing until their oxygen levels had plummeted to such a degree that the patients risked acute respiratory distress (ARDS) and organ failure. In a The New York Times opinion piece (April 20, 2020), emergency room doctor Richard Levitan reports: "A vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at triage—seemingly incompatible with life—but they were using their cellphones as we put them on monitors." Hypoxia is a common complication of preterm birth in newborn infants. Because the lungs develop late in pregnancy, premature infants frequently possess underdeveloped lungs. To improve lung function, doctors frequently place infants at risk of hypoxia inside incubators (also known as humidicribs) that provide warmth, humidity, and oxygen. More serious cases are treated with CPAP. The 2019 Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza in recognition of their discovery of cellular mechanisms to sense and adapt to different oxygen concentrations, establishing a basis for how oxygen levels affect physiological function.
  • 524
  • 01 Dec 2022
Topic Review
Remission in Type 2 Diabetes
Type 2 diabetes mellitus (T2DM) is a progressive disease with a growing prevalence, associated with an increased risk of complications. The introduction of new classes of antidiabetic drugs into clinical practice has dramatically changed the landscape of diabetes therapy. However, despite the progress made in the pharmacotherapy of T2DM, mitigating the burden of the disease on individuals, societies and health care systems remains a challenge. Remission has emerged as a therapeutic target in T2DM, achievable through a wide range of interventions. Studies have shown that extensive lifestyle changes, such as weight reduction, bariatric surgery, and intensive glucose lowering therapy, can prompt the remission of diabetes, but some unanswered questions remain regarding its long-term effects on diabetic complications. Metabolic surgery and novel classes of glucose-lowering medications are the most effective interventions to induce weight loss and by extension remission in patients with diabetes.
  • 523
  • 02 Dec 2022
Topic Review
Palonosetron in Cisplatin-Induced Nephrotoxicity
Cisplatin is widely used to treat various types of cancers, but it is often limited by nephrotoxicity. In this study, we employed an integrated in silico and in vivo approach to identify potential treatments for cisplatin-induced nephrotoxicity (CIN). We were able to find that palonosetron, a serotonin type 3 receptor (5-HT3R) antagonist, can suppress CIN. This study supports the use of in silico and in vivo approaches in drug repositioning studies. 
  • 521
  • 02 Apr 2021
Topic Review
Eating Disorders in Women with Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) is a heterogeneous, multifactorial disease that leads to menstrual and ovulatory irregularities, infertility, hyperandrogenism, and metabolic disturbances. It is recognized as the most prevalent endocrine/metabolic disorder in reproductive-aged women. Despite continuous research efforts, the unifying pathophysiological mechanisms that could explain the etiology of this complex disorder are still not fully understood. The interplay between genetic and epigenetic factors, mitochondrial dysfunction, altered protein and miRNA profiles, and environmental factors that also contribute to obesity lead to exaggerated gonadotropin-releasing hormone (GnRH) pulsatility with hypersecretion of luteinizing hormone (LH) and insulin resistance (IR). Compensatory hyperinsulinemia adds to increased ovarian androgen production and impaired oocyte development. The essential role of the frequent coexistence of mental disorders and polycystic ovary syndrome (PCOS) is being increasingly recognized in the management of PCOS patients since it influences the success of weight loss interventions. Patients frequently experience disrupted eating behaviors, evidenced by the high prevalence of eating disorders in this population. Therefore, assessment and potential modification of eating disorders and eating-related behavior might be especially relevant to improve obesity treatment outcomes in this population, which remains the most efficient causal treatment in PCOS patients with high metabolic risk. 
  • 521
  • 26 Dec 2022
Topic Review
Intrinsic Kidney Pathology Following COVID-19 Infection in Children
COVID-19 infections resulting in pathological kidney manifestations have frequently been reported in adults since the onset of the global COVID-19 pandemic in December 2019. Gradually, there have been an increased number of COVID-19-associated intrinsic kidney pathologies in children and adolescents reported as well. The pathophysiological mechanisms between COVID-19 and the onset of kidney pathology are not fully known in children; it remains a challenge to distinguish between intrinsic kidney pathologies that were caused directly by COVID-19 viral invasion, and cases which occurred as a result of multisystem inflammatory syndrome due to the infection. 
  • 520
  • 20 Jan 2022
Topic Review
Maternal Selenium and Developmental Programming
Selenium (Se) is an essential trace element of fundamental importance to health due to its antioxidant, anti-inflammatory, and chemopreventive properties, attributed to its presence within at least 25 selenoproteins (Sel).
  • 519
  • 11 Aug 2021
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.
  • 517
  • 19 Jun 2023
Topic Review
Multifunctional Magnetic Nanowires
Traditional cancer therapeutics are limited by factors such as multi-drug resistance and a plethora of adverse effect. These limitations need to be overcome for the progression of cancer treatment. In order to overcome these limitations, multifunctional nanosystems have recently been introduced into the market. The employment of multifunctional nanosystems provide for the enhancement of treatment efficacy and therapeutic effect as well as a decrease in drug toxicity.
  • 515
  • 26 Sep 2021
Topic Review
Isocitrate Dehydrogenase Mutations in Glioma
Mutations in isocitrate dehydrogenase (IDH) are commonly observed in lower-grade glioma and secondary glioblastomas. IDH mutants confer a neomorphic enzyme activity that converts α-ketoglutarate to an oncometabolite D-2-hydroxyglutarate, which impacts cellular epigenetics and metabolism. IDH mutation establishes distinctive patterns in metabolism, cancer biology, and the therapeutic sensitivity of glioma. Thus, a deeper understanding of the roles of IDH mutations is of great value to improve the therapeutic efficacy of glioma and other malignancies that share similar genetic characteristics.
  • 514
  • 25 Jun 2021
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