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Topic Review
Peptide Human Neutrophil Elastase Inhibitors
Elastases are a broad group of enzymes involved in the lysis of elastin, the main component of elastic fibres. They are produced and released in the human body, mainly by neutrophils and the pancreas.
  • 1.5K
  • 06 Apr 2022
Topic Review
Angiotensin II
Cardiovascular disease is the leading cause of morbidity and mortality in the western and developing world, and the incidence of cardiovascular disease is increasing with the longer lifespan afforded by our modern lifestyle.  Vascular diseases including coronary heart disease, high blood pressure, and stroke comprise the majority of cardiovascular disease and therefore represent a significant medical and socioeconomic burden on our society.  It is not be surprising that these conditions overlap and potentiate each other when we consider the many cellular and molecular similarities between them. At the molecular level, the vascular smooth muscle cell (VSMC) is the target, integrator, and effector cell of both atherogenic and the major effector protein of the hypertensive signal, Angiotensin II (Ang II).  Together, these signals can potentiate each other and prime the artery and exacerbate hypertension and atherosclerosis. Therefore, VSMC are the fulcrum in progression of these diseases and therefore, understanding the effects of atherogenic stimuli and Ang II on VSMC is  key to understanding and treating  atherosclerosis and hypertension.  In this review, we will examine studies in which hypertension and atherosclerosis intersect on the VSMC, and illustrate common pathways between these two diseases and vascular aging.
  • 1.5K
  • 07 Jul 2020
Topic Review
Mitochondrial microRNAs
Mitochondrial microRNAs (mitomiRs) are endogenous small, single-stranded molecules of noncoding RNA (19–23 nucleotides) present in mitochondria that represent a new level of control of gene expression. These sequences can be either encoded in the nuclei - however the importing mechanism is still not fully established - or may be originated straight inside mitochondria, from mitochondrial genome-derived mRNA. Undeniably, mitomiRs typically act by regulating gene expression inside mitochondria at the post-transcriptional level with a significant role both in physiology and in pathology. Unveiling mitochondrial microRNAs biological function and their targets will propel the development of innovative therapeutic and diagnostic tools.
  • 1.5K
  • 11 Jan 2021
Topic Review
Forkhead Box Protein O1 (FOXO1)
Forkhead box protein O1 (FOXO1) also known as forkhead in rhabdomyosarcoma (FKHR) is a protein that in humans is encoded by the FOXO1 gene. FOXO1 is a transcription factor that plays important roles in regulation of gluconeogenesis and glycogenolysis by insulin signaling, and is also central to the decision for a preadipocyte to commit to adipogenesis. It is primarily regulated through phosphorylation on multiple residues; its transcriptional activity is dependent on its phosphorylation state.
  • 1.5K
  • 30 Nov 2022
Topic Review
Terpenoid Lactones
Terpenoids with lactone moieties have been indicated to possess various biological activities. Certain terpenoid lactones exist in nature, in plants and animals, but they can also be obtained by chemical synthesis. Terpenoids possessing lactone moieties are known for their cytotoxic, anti-inflammatory, antimicrobial, anticancer, and antimalarial activities. 
  • 1.5K
  • 31 May 2021
Topic Review
FTO Intronic SNP
Browning of white adipose tissue shifts adipocytes from energy storage white to energy expenditure beige types. The balance between the two adipocyte populations in white adipose tissue is highly determined by noncoding variants of the Fat mass and obesity-associated (FTO) locus which has the strongest association with obesity. The rs1421085 FTO risk allele results in a loss of ARID5B repression of IRX3 and IRX5 which promotes excess white adipocyte formation. Recent studies have revealed the presence of brown adipose tissues at several anatomical sites in humans including the deep-neck (DN).  We found that the characteristic gene expression profile and associated pathways of DN brown adipocytes were determined by partially overlapping effects of tissue site specific commitments of the stem cells, PPARγ stimulation and the FTO status of donors. The presence of FTO rs1421085 risk alleles had a strong influence, manifested during differentiation, on browning resulting in compromised expression of metabolic and mitochondrial genes as well as pathways which are decisive in thermogenesis.
  • 1.5K
  • 30 Oct 2020
Topic Review
Disordered Proteins and Dynamic Interactions
Intrinsically disordered proteins (IDPs) or regions (IDRs), compared to the well-structural proteins, do not have stable tertiary structures under physiological conditions, and even remain dynamic in specific complexes and functional assemblies. It is now recognized that they are highly prevalent and play important roles in biology and human diseases due to the presence of many representative conformational states and potential dynamic interactions, which requires computer simulations for describing disordered protein ensembles and dynamic interactions involved in biological functions, diseases, and therapeutics.
  • 1.5K
  • 27 Oct 2021
Topic Review
Structural and Regulation Aspects of IGF2
Insulin-like growth factor two (IGF-II) is a key protein regulating growth, particularly during normal fetal development, but it is also often dysregulated during tumorigenesis. IGF-II belongs to a larger system including several different regulatory factors and generally referred to as the “IGF system”. IGF-I and IGF-II are the main ligands of the type 1 IGF receptor (IGF-1R).
  • 1.5K
  • 28 Jun 2022
Topic Review
Cell Cycle Checkpoints
Studies have shown that during early embryogenesis, preimplantation embryos exhibit higher levels of chromosomal abnormalities in the initial stages of cleavage compared to the late morula stage or blastocysts. Thus, preimplantation embryos can acquire an aneuploidy phenotype already in early developmental stages, which points to the fact that these first mitotic cycles are more susceptible to chromosomal aberrations. The monitoring of chromatin damage, the so-called cell cycle checkpoint, is therefore an essential aspect of the cell cycle.
  • 1.5K
  • 12 May 2023
Topic Review
Vascularization and Cancer Biology
Vascularization is another hallmark of cancer, whereby cancer cells promote the formation of blood vessels to deliver nutrients for fast-growing solid tumors. The most well-known process of vascularization is angiogenesis. In normal cells and tissues, the angiogenesis is a controlled process that is turned on or off depending on the needs of the cells; however, in cancerous cells and tumors, the angiogenesis process is continuous and there is a dysregulation of pro- and antiangiogenesis factors . This continuous activation of angiogenesis allows the cancer cells to form blood vessels to obtain sufficient nutrients for continuous growth and proliferation. There are other ways tumors can achieve vascularization, such as vascular co-option, intussusceptive microvascular growth and vasculogenic mimicry.
  • 1.5K
  • 22 Apr 2022
Topic Review
KRAS
The RAS family consists of membrane-associated small GTPases which play essential roles in cell survival, proliferation, and differentiation. There are four RAS protein isoforms in humans: HRAS, NRAS, and two splice variants, KRAS4A and KRAS4B. 
  • 1.5K
  • 12 Oct 2021
Topic Review
Mitochondrial Processing Peptidases
Mitochondrial proteins are encoded by both nuclear and mitochondrial DNA. While some of the essential subunits of the oxidative phosphorylation (OXPHOS) complexes responsible for cellular ATP production are synthesized directly in the mitochondria, most mitochondrial proteins are first translated in the cytosol and then imported into the organelle using a sophisticated transport system. These proteins are directed mainly by targeting presequences at their N-termini. These presequences need to be cleaved to allow the proper folding and assembly of the pre-proteins into functional protein complexes. In the mitochondria, the presequences are removed by several processing peptidases, including the mitochondrial processing peptidase (MPP), the inner membrane processing peptidase (IMP), the inter-membrane processing peptidase (MIP), and the mitochondrial rhomboid protease (Pcp1/PARL). Their proper functioning is essential for mitochondrial homeostasis as the disruption of any of them is lethal in yeast and severely impacts the lifespan and survival in humans.
  • 1.5K
  • 16 Feb 2022
Topic Review
The HMOX1 Pathway
Heme oxygenase (HMOX1) is a key enzyme that catalyzes the rate-limiting first step in the heme degradation process, generating carbon monoxide, ferrous, and biliverdin, and therefore HMOX1 has a cytoprotective role as excess free heme has been shown to induce apoptosis. HMOX1 is expressed at high levels in the lungs and has been shown to mediate the anti-inflammatory effect of interleukin-10 (IL-10) in mice. Given these functions of HMOX1, it has been implicated in a variety of pathological states, including myocardial infarction, diabetes, chronic obstructive pulmonary disease (COPD). The upregulation of HMOX1 has been shown to have a protective role against the oxidative stress produced upon HIV, DENV, HCV, and IAV infections.
  • 1.5K
  • 26 Oct 2020
Topic Review
Brillouin Spectroscopy
Brillouin spectroscopy has recently gained considerable interest within the biomedical field as an innovative tool to study mechanical properties in biology. The Brillouin effect is based on the inelastic scattering of photons caused by their interaction with thermodynamically driven acoustic modes or phonons and it is highly dependent on the material’s elasticity. Therefore, Brillouin is a contactless, label-free optic approach to elastic and viscoelastic analysis that has enabled unprecedented analysis of ex vivo and in vivo mechanical behavior of several tissues with a micrometric resolution, paving the way to a promising future in clinical diagnosis.
  • 1.5K
  • 20 Aug 2021
Topic Review
Exposome
The “exposome” is the cumulative exposures (diet, exercise, environmental exposure, vaccination, genetics, etc.) an individual has experienced and provides a mechanism for the establishment of immune training or immunotolerance. It is becoming increasingly clear that trained immunity constitutes a delicate balance between the dose, duration, and order of exposures. Upon innate stimuli, trained immunity or tolerance is shaped by epigenetic and metabolic changes that alter hematopoietic stem cell lineage commitment and responses to infection. Due to the immunomodulatory role of the exposome, understanding innate immune training is critical for understanding why some individuals exhibit protective phenotypes while closely related individuals may experience immunotolerant effects (e.g., the order of exposure can result in completely divergent immune responses). Research on the exposome and trained immunity may be leveraged to identify key factors for improving vaccination development, altering inflammatory disease development, and introducing potential new prophylactic treatments, especially for diseases such as COVID-19, which is currently a major health issue for the world. Furthermore, continued exposome research may prevent many deleterious effects caused by immunotolerance that frequently result in host morbidity or mortality. 
  • 1.5K
  • 09 Dec 2020
Topic Review
Necroptosis in Intestinal Inflammation
Necroptosis is a caspases-independent programmed cell death displaying intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development such tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis plays a role in many disease conditions and inhibiting necroptosis is currently considered a promising therapeutic strategy.
  • 1.5K
  • 20 Oct 2020
Topic Review
UFM1
Post-translational modification with Ubiquitin-like proteins represents a complex signaling language regulating virtually every cellular process. Among these post-translational modifiers is Ubiquitin-fold modifier (UFM1), which is covalently attached to its substrates through the orchestrated action of a dedicated enzymatic cascade. Originally identified to be involved embryonic development, its biological function remains enigmatic. Recent research reveals that UFM1 regulates a variety of cellular events ranging from DNA repair to autophagy and ER stress response implicating its involvement in a variety of diseases. Given the contribution of UFM1 to numerous pathologies, the enzymes of the UFM1 cascade represent attractive targets for pharmacological inhibition.
  • 1.5K
  • 26 Feb 2021
Topic Review
Treatment of Galactosemia
Galactosemia is an inborn disorder of carbohydrate metabolism characterized by the inability to metabolize galactose, a sugar contained in milk (the main source of nourishment for infants), and convert it into glucose, the sugar used by the body as the primary source of energy. Galactosemia is an autosomal recessive genetic disease that can be diagnosed at birth, even in the absence of symptoms, with newborn screening by assessing the level of galactose and the GALT enzyme activity, as GALT defect constitutes the most frequent cause of galactosemia. Currently, galactosemia cannot be cured, but only treated by means of a diet with a reduced content of galactose and lactose. Although the diet is able to reverse the neonatal clinical picture, it does not prevent the development of long-term complications. 
  • 1.5K
  • 29 Jul 2022
Topic Review
γ-Hydroxybutyric Acid
γ-Hydroxybutyric acid (GHB) is an endogenous short chain fatty acid that acts as a neurotransmitter and neuromodulator in the mammalian brain. It has often been illegally abused or misused due to its strong anesthetic effect, particularly in drug-facilitated crimes worldwide. However, proving its ingestion is not straightforward because of the difficulty in distinguishing between endogenous and exogenous GHB, as well as its rapid metabolism. Metabolomics and metabolism studies have recently been used to identify potential biomarkers of GHB exposure. 
  • 1.5K
  • 04 Mar 2021
Topic Review
Chemical Chaperones
Chemical chaperones are well known as inhibitors of protein and peptide self-assembly, as well as structural stabilizers of misfolded enzymes. We discovered that chemical chaperones inhibit adenine self-assembly both in a yeast model and in vitro. According to our study, chemical chaperones might have a dual function as enhancers of enzyme stability and as inhibitors of toxic metabolite self-assembly. This novel approach could be implemented for the rational design of inhibitors that target metabolite self-assembly as therapeutics for inborn errors of metabolism.
  • 1.5K
  • 15 Sep 2021
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