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Topic Review
Kynurenine Pathway of Tryptophan Metabolism
Migraine, the leading cause of disability in the population aged below 50, is frequently associated with functional gastrointestinal (GI) disorders (FGIDs) such as functional nausea, cyclic vomiting syndrome, and irritable bowel syndrome (IBS). Conversely, changes in intestinal GI transit may cause diarrhea or constipation and are a component of the autonomic symptoms associated with pre- and post-dorsal phases of migraine attack. 
  • 732
  • 28 Sep 2021
Topic Review
Small Molecular TKIs for EGFR Mutation in NSCLC
Molecular targeted therapy was reported to have fewer adverse effects and offer a more convenient route of administration compared with conventional chemotherapy. With the development of sequencing technology and research on the molecular biology of lung cancer, especially whole-genome information on non-small-cell lung cancer (NSCLC), various therapeutic targets have been unveiled. Among the NSCLC-driving gene mutations, epidermal growth factor receptor (EGFR) mutations are the most common driver gene, and approximately 10% of Caucasian and more than 50% of Asian NSCLC patients have been found to have sensitive EGFR mutations. A variety of targeted therapeutic agents for EGFR mutations have been approved for clinical applications or are undergoing clinical trials around the world. This review is focused on the indications of approved small molecular kinase inhibitors for EGFR mutation-positive NSCLC, the mechanisms of drug resistance and the corresponding therapeutic strategies, as well as the principle of reasonable and precision molecular structure for drug development discovery of next-generation inhibitors for EGFR, which would accelerate anticancer drug discovery.
  • 731
  • 09 Oct 2021
Topic Review
AML Diagnosis and Prognosis
The development of molecular studies to define the somatic genetic alterations has revolutionized the diagnostic and therapeutic management of acute myeloid leukemia (AML). AML is a highly heterogenous disease that includes many molecular subtypes; each subtype is heterogeneous both for the presence of variable co-mutations and complex combinations of clones and subclones, changing during disease evolution and in response to treatment. The treatment of AML is changing from standardized schemes of induction and consolidation chemotherapy to tailored approaches according to molecular and genetic profiles and to targeted therapy. Several molecularly targeted therapies have been approved for the treatment of some AML patients, including mutation-specific targeted drugs such as FLT3, IDH1 and IDH2 inhibitors, mutation-independent targeted drugs such as the Bcl2 inhibitor venetoclax, the hedgehog inhibitor glasdegib and the CD33-targeted drug gemtuzumab ozogamicin. Furthermore, recent studies have shown the feasibility of a personalized medicine approach for the treatment of AML patients, where the therapy decisions are guided by the results of genomic studies. 
  • 728
  • 07 Apr 2021
Topic Review
Extrapulmonary Tuberculosis
Pathogenic Mycobacterium tuberculosis complex organisms (MTBC) primarily cause pulmonary tuberculosis (PTB); however, MTBC are also capable of causing disease in extrapulmonary (EP) organs, which pose a significant threat to human health worldwide. Extrapulmonary tuberculosis (EPTB) accounts for about 20–30% of all active TB cases and affects mainly children and adults with compromised immune systems. EPTB can occur through hematogenous, lymphatic, or localized bacillary dissemination from a primary source, such as PTB, and affects the brain, eye, mouth, tongue, lymph nodes of neck, spine, bones, muscles, skin, pleura, pericardium, gastrointestinal, peritoneum, and the genitourinary system as primary and/or disseminated disease. EPTB diagnosis involves clinical, radiological, microbiological, histopathological, biochemical/immunological, and molecular methods. However, only culture and molecular techniques are considered confirmatory to differentiate MTBC from any non-tuberculous mycobacteria (NTM) species. While EPTB due to MTBC responds to first-line anti-TB drugs (ATD), drug susceptibility profiling is an essential criterion for addressing drug-resistant EPTB cases (DR-EPTB). Besides antibiotics, adjuvant therapy with corticosteroids has also been used to treat specific EPTB cases. Occasionally, surgical intervention is recommended, mainly when organ damage is debilitating to the patient. 
  • 727
  • 03 Jun 2021
Topic Review
Capsule-Based Dry Powder Inhalers
Capsule-based dry powder inhalers (cDPIs) are widely utilized in the delivery of pharmaceutical powders to the lungs. In these systems, the fundamental nature of the interactions between the drug/formulation powder, the capsules, the inhaler device, and the patient must be fully elucidated in order to develop robust manufacturing procedures and provide reproducible lung deposition of the drug payload. 
  • 723
  • 23 Sep 2021
Topic Review
Skeletal Muscle Damage in COVID-19
Muscle dystrophy in COVID-19 entails loss of muscle mass and muscle strength, as well as suboptimal physical performance same as in cachexia and sarcopenia, albeit the loss in COVID is exaggerated. It is most evident in hospitalized patients during the acute phase by myalgia/muscle pain and fatigue, and it is associated with poor prognosis. It manifests in remitting COVID-19 patients by poor physical performance, slowness, fatigue and dyspnea while performing activities of daily living.
  • 719
  • 02 Jul 2021
Topic Review
Metformin in Differentiated Thyroid Cancer
Metformin is a synthetic biguanide that improves insulin sensitivity and reduces hepatic gluconeogenesis. Aside being the first-line therapy for Type 2 Diabetes (T2D), many pleiotropic effects have been discovered in recent years, such as its capacity to reduce cancer risk and tumorigenesis.
  • 718
  • 25 Apr 2022
Topic Review
Placental Abruption
Placental abruption is the separation of the placenta from the lining of the uterus before childbirth. It is an infrequent perinatal complication with serious after-effects and a marked risk of maternal and fetal mortality. Despite the fact that numerous placental abruption risk factors are known, the pathophysiology of this issue is multifactorial and not entirely clear.
  • 716
  • 02 Jul 2021
Topic Review
Neurological Functions of Bile Acids
Bile acids (BA) are amphipathic steroid acids synthesized from cholesterol in the liver. They act as detergents to expedite the digestion and absorption of dietary lipids and lipophilic vitamins. BA are also considered to be signaling molecules, being ligands of nuclear and cell-surface receptors, including farnesoid X receptor and Takeda G-protein receptor 5. Moreover, BA also activate ion channels, including the bile acid-sensitive ion channel and epithelial Na+ channel. BA regulate glucose and lipid metabolism by activating these receptors in peripheral tissues, such as the liver and brown and white adipose tissue. Recently, 20 different BA have been identified in the central nervous system. Furthermore, BA affect the function of neurotransmitter receptors, such as the muscarinic acetylcholine receptor and γ-aminobutyric acid receptor. BA are also known to be protective against neurodegeneration. 
  • 716
  • 31 Aug 2021
Topic Review
Triazolo-Thiadiazole Derivatives
The fusion of 1,2,4-triazole and 1,3,4-thiadiazole rings results in a class of heterocycles compounds with an extensive range of pharmacological properties. A series of 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles was synthesized and tested for its enzyme inhibition potential and anticancer activity. The results show that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles display potent anticancer properties in vitro against a panel of cancer cells and in vivo efficacy in HT-29 human colon tumor xenograft in CB17 severe combined immunodeficient (SCID) mice.
  • 715
  • 20 Apr 2021
Topic Review
JDP2 in Cardiac Disease
Heart failure (HF) and atrial fibrillation (AF) are two major life-threatening diseases worldwide. Causes and mechanisms are incompletely understood, yet current therapies are unable to stop disease progression. In our study, we focus on the contribution of the transcriptional modulator, Jun dimerization protein 2 (JDP2), and on HF and AF development. In recent years, JDP2 has been identified as a potential prognostic marker for HF development after myocardial infarction. This close correlation to the disease development suggests that JDP2 may be involved in initiation and progression of HF as well as in cardiac dysfunction.
  • 713
  • 28 Apr 2021
Topic Review
Telomerase in Brain
Telomerase is an enzyme that in its canonical function extends and maintains telomeres, the ends of chromosomes. However, telomere-independent functions are known for the telomerase protein TERT like shuttling from the nucleus to mitochondria where it decreases oxidative stress, apoptosis sensitivity and DNA damage. Recently, a protective role of TERT was found in brain where it protects neurons from stress and toxic proteins connected to neurodegenerative diseases. Telomerase activators are able to boost this protection in brain. The entry summarises our current knowledge about telomerase in the brain and highlights possible therapeutic approaches.
  • 713
  • 31 May 2021
Topic Review
Metformin for Preeclampsia Prophylaxis
The possibility of prophylaxis of hypertensive disorders of pregnancy (HDPs) such as preeclampsia (PE) and pregnancy-induced hypertension (PIH) is of interest due to the unpredictable course of these diseases and the risks they carry for both mother and fetus. It has been proven that their development is associated with the presence of the placenta, and the processes that initiate it begin at the time of the abnormal invasion of the trophoblast in early pregnancy. The ideal HDPs prophylaxis should alleviate the influence of risk factors and, at the same time, promote physiological trophoblast invasion and maintain the physiologic endothelium function without any harm to both mother and fetus. So far, aspirin is the only effective and recommended pharmacological agent for the prevention of HDPs in high-risk groups. Metformin is a hypoglycemic drug with a proven protective effect on the cardiovascular system. Respecting the anti-inflammatory properties of metformin and its favorable impact on the endothelium, it seems to be an interesting option for HDPs prophylaxis. 
  • 707
  • 16 Jul 2021
Topic Review
Stem Cell-Derived Organoids in Disease
Organoids represent one of the most important advancements in the field of stem cells during the past decade. The earliest usage of the term goes back to 1946 when Smith and Cochrane described a cystic teratoma case by referring to it as “cystic organoid teratoma”. Organoids, or as the term literally signifies “resembling an organ”, are three-dimensional (3D) in vitro culturing systems that originate from self-organizing stem cells, capable of mimicking the in vivo structural and functional specificities of an organ.
  • 707
  • 28 Jul 2021
Topic Review
Role of Cytokine IL-37 in Modulating Inflammation
Inflammation constitutes an essential response of tissues to infection or injury. The cytokine IL-37 is a member of the IL-1 family of cytokines, otherwise known for its pivotal role in promoting inflammation. This cytokine (a former member 7 of the IL-1 family) was characterized by computational cloning, which revealed its role as a negative regulator of the cytokine IL-18, which in addition to IL-1β is the key proinflammatory cytokine of the IL-1 cytokine family. There is growing interest in the therapeutic potentials of IL-37.
  • 707
  • 20 Jun 2022
Topic Review
Exosome-Derived MicroRNAs of Human Milk
Multiple biologically active components of human milk support infant growth, health and development. Milk provides a wide spectrum of mammary epithelial cell-derived extracellular vesicles (MEVs) for the infant. Although the whole spectrum of MEVs appears to be of functional importance for the growing infant, the majority of recent studies report on the MEV subfraction of milk exosomes (MEX) and their miRNA cargo, which are in the focus of this entry.
  • 704
  • 23 Jun 2021
Topic Review
PIPAC
Theoretical considerations as well as comprehensive preclinical and clinical data suggest that optimizing physical parameters of intraperitoneal drug delivery might help to circumvent initial or acquired resistance of peritoneal metastasis (PM) to chemotherapy. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive drug delivery system systematically addressing the current limitations of intraperitoneal chemotherapy. The rationale behind PIPAC is: (1) optimizing homogeneity of drug distribution by applying an aerosol rather than a liquid solution; (2) applying increased intraperitoneal hydrostatic pressure to counteract elevated intratumoral interstitial fluid pressure; (3) limiting blood outflow during drug application; (4) steering environmental parameters (temperature, pH, electrostatic charge etc.) in the peritoneal cavity for best tissue target effect. In addition, PIPAC allows repeated application and objective assessment of tumor response by comparing biopsies between chemotherapy cycles. 
  • 703
  • 09 Aug 2021
Topic Review
Mineral Deficiency
Mineral deficiency is a lack of the dietary minerals, the micronutrients that are needed for an organism's proper health. The cause may be a poor diet, impaired uptake of the minerals that are consumed, or a dysfunction in the organism's use of the mineral after it is absorbed. These deficiencies can result in many disorders including anemia and goitre. Examples of mineral deficiency include, zinc deficiency, iron deficiency, and magnesium deficiency.
  • 703
  • 02 Dec 2022
Topic Review
SLC6A14 and SLC38A5
SLC6A14 and SLC38A5 are the two transporters that are upregulated in a variety of cancers to mediate the influx of glutamine, serine, glycine, and methionine into cancer cells. SLC6A14 is a Na+/Cl− -coupled transporter for multiple amino acids, including these four amino acids. In contrast, SLC38A5 is a Na+-coupled transporter with rather restricted specificity towards glutamine, serine, glycine, and methionine. Both transporters exhibit unique functional features that are ideal for the rapid proliferation of cancer cells.
  • 702
  • 14 Apr 2021
Topic Review
Endometriosis in Menopause
Endometriosis, an estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial tissue, has been the topic of renewed research and debate in recent years. The paradigm shift from the belief that endometriosis only affects women of reproductive age has drawn attention to endometriosis in both premenarchal and postmenopausal patients. There is still scarce information in literature regarding postmenopausal endometriosis, the mostly studied and reported being the prevalence in postmenopausal women. Yet, other important issues also need to be addressed concerning diagnosis, pathophysiology, and management.
  • 701
  • 13 Jul 2021
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