Biotech World: December 2017

Sunday, December 31, 2017

To my readers -

Wish you and your family a very Happy and Prosperous New Year!

Selenium as an antioxidant and protector of brain

Selenium (Se) is a trace element, a powerful antioxidant and an important micronutrient that’s absolutely essential for human health. Selenium plays an important role in human cell function - it strengthens and protects cell structure and supports cellular metabolism. As an antioxidant, selenium helps fight free radical damage and moderates reactive oxygen species (ROS), which cause cellular oxidative stress. In addition to acting as an essential nutrient for the immune system and overall body function, selenium also plays a critical role in the operation of the nervous system and in human brain function.The functions of selenium are carried out by selenoproteins, in which selenium is specifically incorporated as the amino acid, selenocysteine (21st amino acid).

Human beings have 25 selenoproteins in their genome and majority of these are relative to the antioxidant defence of the body. The three well-studied subfamilies of selenoproteins include thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and iodothyronine deiodinases (DIO). Three of these TrxR selenoproteins have been identified in mammals that includes TrxR1, which functions in the cytosol and nucleus, TrxR2, which functions in the mitochondria, and TrxR3, which functions in testis. The TrxRs are also important components of the mechanism to reduce peroxide. This group of selenoproteins is required for reduction of thioredoxin (Trx), which uses a cysteine thiol-disulfide exchange for reduction of thiol groups in protein residues. Trx can inhibit apoptosis signaling regulating kinase1 (ASK1) and prevent apoptosis to control cell division, longevity, and cell death. The Trx–TrxR systems are also important for reducing proteins that have cysteine in DNA-binding domains, which include NF-kB, AP-1, p53, and glucocorticoid receptors [1]. Also Selenoprotein P has been reported to possess antioxidant activities and the ability to promote neuronal cell survival according to recent research. Selenium and selenoproteins are also involved in brain metabolism and brain signalling pathways. Selenoproteins have special importance to the neuronal cells, which utilise γ-aminobutyric acid (GABA) as their signalling molecule (GABAergic neurons). In both selenium deficient organisms and organism with genetic impairment of selenoprotein biosynthesis this kind of neurons are affected most heavily [2]. Severe selenium deficiency or malfunction of selenium transporting protein, selenoprotein P, causes degeneration of special group of GABAergic neurons leading to impaired neuronal function that results in motor function disorders, including seizures, and cognitive impairments like affected learning. This is because of the abundance of the GABA-utilising neurons in the corresponding brain regions – hippocampus, cerebral cortex and cerebellum.

Through selenoproteins selenium is involved in the diverse functions of the brain including motor performance, coordination, memory and cognition. Selenoproteins are important for normal brain function, and decreased function of selenoproteins can lead to impaired cognitive function and neurological disorders such as Alzheimer's disease, Parkinson's disease (impaired function of glutathione peroxidase selenoenzymes), Huntington's disease (here selenium deters lipid peroxidation by increasing specific glutathione peroxidases/GPX), amyotrophic lateral sclerosis and epilepsy [3]. Since the human body cannot produce selenium, it must be consumed from an external source and generally an adult human requires a minimum of 55 micrograms per day. Women who are pregnant or breastfeeding require slightly more.

References:

Pillai, R., Uyehara-Lock, J. H. and Bellinger, F. P. (2014), Selenium and selenoprotein function in brain disorders. IUBMB Life, 66: 229–239. doi:10.1002/iub.1262
https://atlasofscience.org/importance-of-selenium-for-brain-function/
https://www.ncbi.nlm.nih.gov/pubmed/12807419

Sunday, December 17, 2017

Dengue virus pathogenesis

Dengue virus (DENV) is a mosquito-transmitted (primarily from the female mosquitoes of genus Aedes) RNA virus that infects an estimated 390 million humans each year. DENV is a member of the Flavivirus genus of single-stranded positive-sense RNA viruses that cause visceral and central nervous system disease in humans. Dengue is currently the most prevalent arthropod-borne viral disease of humans that is caused by four antigenically distinct serotypes of dengue virus (DENV 1–4) that are genetically similar and share approximately 65% of their genomes. Infection with any of the DENV serotypes may result in a wide spectrum of clinical symptoms, ranging from a mild flu-like syndrome (known as dengue fever [DF]) to the most severe forms of the disease, which are characterized by coagulopathy, increased vascular permeability (increased hemoconcentration or fluid effusion in chest or abdominal cavities), fragility (dengue hemorrhagic fever [DHF]) and dengue shock syndrome [DSS]. Severe dengue is a potentially deadly complication due to plasma leaking, fluid accumulation, respiratory distress, severe bleeding and organ impairment [1]. The World Health Organization (WHO) classifies DHF in four grades (I to IV). DHF grades I and II represent relatively mild cases without shock, whereas grade III and IV cases are more severe and accompanied by shock. Recovery from infection by one serotype provides lifelong immunity against that particular serotype, and does not provide cross-immunity against other serotypes.

The primary vector of dengue is Aedes aegypti mosquito that lives in urban habitats and breeds mostly in man-made containers. Ae. aegypti is a day-time feeder and its peak biting periods are early in the morning and in the evening before dusk. Aedes albopictus is the secondary dengue vector in Asia, has spread to North America and more than 25 countries in the European Region. During the feeding of mosquitoes on humans, DENV is presumably injected into the bloodstream, with spillover in the epidermis and dermis, resulting in infection of immature Langerhans cells (epidermal dendritic cells [DC]) and keratinocytes. Infected cells then migrate from site of infection to lymph nodes, where monocytes and macrophages are recruited, which become targets of infection. Consequently the infection is amplified and virus is disseminated through the lymphatic system. As a result of this primary viremia, several cells of the mononuclear lineage, including blood-derived monocytes, myeloid DC, and splenic and liver macrophages are infected [2]. There are several immune cells associated with the pathogenesis of DENV infection and systemic spread, including dendritic cells, macrophages, and mast cells (MCs). MCs are widely recognized for their immune functions and as cellular regulators of vascular integrity in human skin [3].

Several genetic factors have been shown to be associated with the development of DHF/DSS and some have been shown to be protective. Certain HLA- class I and class II allele polymorphisms in the tumor necrosis factor alpha (TNF-α), Vitamin D receptor, CTLA-4 and transforming growth factor ß (TGF-β) have been shown to be associated with development of DHF/DSS. Several studies have shown that concentrations of multiple cytokines and other mediators, as well as soluble receptors, are significantly increased during severe dengue infections. Higher plasma levels of IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-13, IL-18, TGF-1β, TNF-α, and IFN-γ have been found in patients with severe DENV infections, in particular in patients with DSS [4].

There is no specific treatment for dengue fever. Maintenance of the patient's body fluid volume is critical to severe dengue care. In late 2015 and early 2016, the first dengue vaccine, Dengvaxia (CYD-TDV) by Sanofi Pasteur, was registered in several countries for use in individuals 9-45 years of age living in endemic areas. WHO recommends that countries should consider introduction of the dengue vaccine CYD-TDV only in geographic settings (national or subnational) where epidemiological data indicate a high burden of disease.