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Topic Review
Aryl Hydrocarbon Receptor
The aryl hydrocarbon receptor (AhR) was first identified as the intracellular protein that 14 bound and mediated the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and 15 dioxin-like compounds (DLCs). Subsequent studies show that the AhR plays an important role in 16 maintaining cellular homeostasis and in pathophysiology and there is increasing evidence that the 17 AhR is a important drug target. The AhR binds structurally diverse compounds including 18 pharmaceuticals, phytochemicals, endogenous biochemicals some of which may serve as 19 endogenous ligands. Classification of DLCs and non-DLCs based on their persistence (metabolism), 20 toxicities, binding to wild-type/mutant AhR and structural similarities have been reported. This 21 review provides data suggesting that ligands for the AhR are selective AhR modulators (SAhRMs) 22 which exhibit tissue/cell-specific AhR agonist and antagonist activities and their functional diversity 23 is similar to selective receptor modulators that target steroid hormone and other nuclear receptors.
  • 929
  • 10 Feb 2021
Topic Review
Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis
The aryl hydrocarbon receptor (AHR)/AHR-nuclear translocator (ARNT) system is a sensitive sensor for small molecular, xenobiotic chemicals of exogenous and endogenous origin, including dioxins, phytochemicals, microbial bioproducts, and tryptophan photoproducts. AHR/ARNT are abundantly expressed in the skin. Once activated, the AHR/ARNT axis strengthens skin barrier functions and accelerates epidermal terminal differentiation by upregulating filaggrin expression. In addition, AHR activation induces oxidative stress. However, some AHR ligands simultaneously activate the nuclear factor-erythroid 2-related factor-2 (NRF2) transcription factor, which is a master switch of antioxidative enzymes that neutralizes oxidative stress. 
  • 751
  • 18 Oct 2021
Topic Review
AS-OCT in Corneal Disorders
Anterior segment optical coherence tomography (AS-OCT) is a non-contact method of in vivo ocular imaging technology. It uses low coherence interferometry that measures the echo time delay of light backscattered from tissue structures and combines multiple axial scans into a composite B-scan image. Earlier ultrasound bio microscopy was used for anterior segment imaging, but with time AS-OCT has become a popular imaging tool for anterior segment imaging. AS-OCT is faster and provides more in-depth assessment of the anterior chamber and is repeatable and reproducible. For AS imaging, longer wavelengths (1050–1310 nm) are preferred than retinal OCT (800–900 nm) due to higher penetration and less scattering.
  • 482
  • 15 Apr 2022
Topic Review
Ascorbate in Cancer Therapy
Cancer is a disease of high mortality, and its prevalence has increased steadily in the last few years. Ascorbate (ascorbic acid or vitamin C) is a potent water-soluble antioxidant that is produced in most mammals but is not synthesised endogenously in humans, which lack enzymes for its synthesis. Ascorbate has antioxidant effects that correspond closely to the dose administered. Interestingly, this natural antioxidant induces oxidative stress when given intravenously at a high dose, a paradoxical effect due to its interactions with iron. Importantly, this deleterious property of ascorbate can result in increased cell death. Although, historically, ascorbate has been reported to exhibit anti-tumour properties, this effect has been questioned due to the lack of available mechanistic detail. Recently, new evidence has emerged implicating ferroptosis in several types of oxidative stress-mediated cell death, such as those associated with ischemia–reperfusion. This effect could be positively modulated by the interaction of iron and high ascorbate dosing, particularly in cell systems having a high mitotic index. In addition, it has been reported that ascorbate may behave as an adjuvant of favourable anti-tumour effects in cancer therapies such as radiotherapy, radio-chemotherapy, chemotherapy, immunotherapy, or even in monotherapy, as it facilitates tumour cell death through the generation of reactive oxygen species and ferroptosis.
  • 357
  • 28 Jun 2022
Topic Review
Ascorbic Acid against Chronic Diseases
Ascorbic acid (ASC) is a key nutrient that serves as an antioxidant and a cofactor for numerous enzymatic reactions. However, humans, unlike most mammals, are unable to synthesize it. Consequently, ASC must be obtained through dietary sources, especially fresh fruit and vegetables. The value of administering exogenous micronutrients, to reestablish antioxidant concentrations in patients with severe disease, has been recognized for decades. Despite the suggestion that ASC supplementation may reduce oxidative stress and prevent several chronic conditions, few large, randomized clinical trials have tested it in patients with severe illness. This article reviews the recent literature on the pharmacological profile of ASC and the role of its supplementation in critically ill patients.
  • 648
  • 11 Dec 2020
Topic Review
ASIC1/2, TRPV1/4 in skin Tumors
The acid-sensing ion channels ASIC1 and ASIC2, as well as the transient receptor potential vanilloid channels TRPV1 and TRPV4, are proton-gated cation channels that can be activated by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear.
  • 464
  • 22 Sep 2021
Topic Review
Aspartate in Cell Proliferation and Survival
Aspartate is a precursor for nucleotide synthesis and  is indispensable for cell proliferation. Moreover, the malate–aspartate shuttle plays a key role in redox balance, and a deficit in aspartate can lead to oxidative stress. It is now recognized that aspartate biosynthesis is largely governed by mitochondrial metabolism, including respiration and glutaminolysis in cancer cells. Therefore, under conditions that suppress mitochondrial metabolism, including mutations, hypoxia, or chemical inhibitors, aspartate can become a limiting factor for tumor growth and cancer cell survival.
  • 1.5K
  • 15 Jul 2022
Topic Review
Aspiration Pneumonia and Dysphagia in the Elderly
Pneumonia in the elderly has been increasing on an annual basis. To a greater or lesser extent, aspiration is a major contributor to the development of pneumonia in the elderly. Antimicrobials alone are not sufficient for the treatment of pneumonia, and the condition may become intractable or even recur repeatedly. In addition, some patients with pneumonia may have no problems with eating, while others are unable to receive the necessary nutrition due to severe dysphagia. It has been found that pneumonia decreases both the muscle mass and strength of the swallowing and respiratory muscles, a condition named pneumonia-associated sarcopenia. This contributes to a pathophysiological time-axis of aspiration pneumonia and dysphagia in the elderly, in which silent aspiration leads to the development of pneumonia, and further to dysphagia, malnutrition, and low immunity. 
  • 662
  • 09 Oct 2022
Topic Review
Aspirin and Colorectal Cancer Prevention in Lynch Syndrome
Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. 
  • 460
  • 20 Apr 2022
Topic Review
Aspirin and Infection
Aspirin (acetylsalicylic acid) is one of the most commonly used drugs in the world. It derives from the extract of white willow (Salix alba) bark. The first evidence of the therapeutic use of salix (now known as willow) dates back to 1534 BC from the Egyptian Ebers Papyrus, considered the most comprehensive medical papyrus ever recovered. Then, the use of willow bark continued through ancient Greece and through to Roman times. In the 19th century, scientists were able to produce a compound from the crystals isolated from willow bark which was named salicylic acid and in 1852, salicylic acid was acetylated for the first time to reduce its irritant properties. In 1899, aspirin was coined.
  • 319
  • 09 Feb 2022
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