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Topic Review
Metformin Regulates Gluconeogenesis through Foxo1
Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus (T2D). Metformin exerts its glucose-lowering effect primarily through decreasing hepatic glucose production (HGP). However, the precise molecular mechanisms of metformin remain unclear due to supra-pharmacological concentration of metformin used in the study. 
  • 1.0K
  • 28 Sep 2021
Topic Review
Aromatase in Breast Cancer Treatment
The current therapeutic approach for the treatment of hormone dependent breast cancer includes interference with estrogen receptors via either selective modulators or estrogens deprivation, by preventing their biosynthesis with aromatase inhibitors. Severe side effects and acquired resistance are drawbacks of both drug classes, and the efforts to overcome these issues still allow for research in this field to be animated. This review reports on recent findings that have opened new avenues for reconsidering the role of aromatase enzyme (and estrogen receptors) leading to the possibility of looking at well-known targets in a new perspective.
  • 1.0K
  • 14 Dec 2020
Topic Review
MS-Based Proteomics for Bipolar Disorder Potential Biomarkers Assessment
Bipolar disorder (BD) is a clinically heterogeneous condition, presenting a complex underlying etiopathogenesis that is not sufficiently characterized. Without molecular biomarkers being used in the clinical environment, several large screen proteomics studies have been conducted to provide valuable molecular information. Mass spectrometry (MS)-based techniques can be a powerful tool for the identification of disease biomarkers, improving prediction and diagnosis ability.
  • 1.0K
  • 27 May 2022
Topic Review
INK4a/ARF
Genetic alterations in the INK4a/ARF (or CDKN2A) locus have been reported in many cancer types, including melanoma, head and neck squamous cell carcinomas, lung, breast and pancreatic cancers.  The CDKN2A locus encodes two critical tumor suppressor proteins, the cyclin-dependent kinase inhibitor p16INK4a and the p53 regulator p14ARF. The majority of CDKN2A alterations in melanoma selectively target p16INK4a or affect the coding sequence of both p16INK4a and p14ARF. There is also a subset of less common somatic and germline INK4a/ARF alterations that affect p14ARF, while not altering the syntenic p16INK4a coding regions. This review describes the frequency and types of somatic and germline alterations affecting the CDKN2A locus and their functional consequences in melanoma development. The clinical implications of CDKN2A inactivating alterations and their influence on treatment response and resistance are also described. 
  • 1.0K
  • 21 Oct 2020
Topic Review
Human Mitochondrial Pyruvate Carrier
Human mitochondrial pyruvate carriers (hMPCs), which are required for the uptake of pyruvate into mitochondria, are associated with several metabolic diseases, including type 2 diabetes and various cancers. Yeast MPC was recently demonstrated to form a functional unit of heterodimers. However, human MPC-1 (hMPC-1) and MPC-2 (hMPC-2) have not yet been individually isolated for their detailed characterization, in particular in terms of their structural and functional properties, namely, whether they exist as homo- or heterodimers. In this study, hMPC-1 and hMPC-2 were successfully isolated in micelles and they formed stable homodimers. However, the heterodimer state was found to be dominant when both hMPC-1 and hMPC-2 were present. In addition, as heterodimers, the molecules exhibited a higher binding capacity to both substrates and inhibitors, together with a larger structural stability than when they existed as homodimers. Taken together, our results demonstrated that the hetero-dimerization of hMPCs is the main functional unit of the pyruvate metabolism, providing a structural insight into the transport mechanisms of hMPCs.
  • 1.0K
  • 24 Mar 2021
Topic Review
Skeletal Muscle and Stress Proteins
All organisms and cells respond to various stress conditions by up-regulating the expression and/or activation of a group of proteins called heat shock proteins (HSPs). Although their expression is induced by several stimuli, they are commonly recognized as HSPs due to the first experiments showing their increased transcription after application of heat shock. These proteins are molecular chaperones mainly involved in assisting protein transport and folding, assembling multimolecular complexes, and triggering protein degradation by proteasome. In addition, they play a crucial role in gene expression regulation, DNA replication, signal transduction, cell differentiation, apoptosis, cellular senescence or immortalization, and intercellular communications. Heat shock proteins are classified according to their molecular weight in super heavy, 100, 90, 70, 60, 40, and small HSPs. Although they are the most highly conserved, ubiquitous, and abundant proteins in all organisms, their cellular stress response can depend on the class and stimulus.
  • 1.0K
  • 16 Apr 2021
Topic Review
Vimentin-Binding Aptamer Motifs for Ovarian Cancer
The application of aptamers in biomedicine is emerging as an essential technology in the field of cancer research. As small single-stranded DNA or RNA ligands with high specificity and low immunogenicity for their targets, aptamers provide many advantages in cancer therapeutics over protein-based molecules, such as antibodies. Vimentin is an intermediate filament protein that is overexpressed in endothelial cells of cancerous tissue. High expression levels of vimentin have been associated with increased capacity for migration and invasion of the tumor cells. We have selected and identified thioated aptamers with high specificity for vimentin using human ovarian cancer tissues. Tentative binding motifs were chosen for two vimentin aptamers based on predicted secondary structures. Each of these shorter, tentative binding motifs was synthesized, purified, and characterized via cell binding assays. Two vimentin binding motifs with high fidelity binding were selected and further characterized via cell and tissue binding assays, as well as flow cytometric analysis. The equilibrium binding constants of these small thioated aptamer constructs were also determined. Future applications for the vimentin binding aptamer motifs include conjugation of the aptamers to synthetic dyes for use in targeted imaging and therapy, and ultimately more detailed and precise monitoring of treatment response and tumor progression in ovarian pathology. 
  • 1.0K
  • 11 Nov 2021
Topic Review
Impact of Ultraviolet Radiation on Cyanobacteria
Ultraviolet radiation (UVR) tends to damage key cellular machinery. Cells may adapt by developing several defence mechanisms as a response to such damage; otherwise, their destiny is cell death. Since cyanobacteria are primary biotic components and also important biomass producers, any drastic effects caused by UVR may imbalance the entire ecosystem. Cyanobacteria are exposed to UVR in their natural habitats. This exposure can cause oxidative stress which affects cellular morphology and vital processes such as cell growth and differentiation, pigmentation, photosynthesis, nitrogen metabolism, and enzyme activity, as well as alterations in the native structure of biomolecules such as proteins and DNA. The high resilience and several mitigation strategies adopted by a cyanobacterial community in the face of UV stress are attributed to the activation of several photo/dark repair mechanisms, avoidance, scavenging, screening, antioxidant systems, and the biosynthesis of UV photoprotectants, such as mycosporine-like amino acids (MAAs), scytonemin (Scy), carotenoids, and polyamines.
  • 1.0K
  • 08 Aug 2023
Topic Review
Nuclear P38
One of the hallmarks of MAPK signaling is the nuclear translocation of some of its components upon stimulation. This is important for the regulation of transcription, activation of enzymes and stabilisation of proteins that lead to the induced  processes involved in the response to the particular stimulation or pathologies. Here we describe the nuclear function regulation and mechanism of translocation of two central MAPKs, namely P38α/β that are involved in the regulation of a variety of processes including mainly stress response. 
  • 1.0K
  • 26 Oct 2020
Topic Review
Microfluidics on Assisted Reproductive Technology
Infertility is a state of the male or female reproductive system that is defined as the failure to achieve pregnancy even after 12 or more months of regular unprotected sexual intercourse. Assisted reproductive technology (ART) plays a crucial role in addressing infertility. Various ART are now available for infertile couples. Fertilization in vitro (IVF), intracytoplasmic sperm injection (ICSI) and intrauterine insemination (IUI) are the most common techniques in this regard. Various microfluidic technologies can incorporate various ART procedures such as embryo and gamete (sperm and oocyte) analysis, sorting, manipulation, culture and monitoring.
  • 1.0K
  • 09 Aug 2021
Topic Review
Nobiletin and Derivatives
The search for effective methods of cancer treatment and prevention has been a continuous effort since the disease was discovered. Recently, there has been increasing interest in exploring plants and fruits for molecules that may have potential as either adjuvants or as chemopreventive agents against cancer. One of the promising compounds under extensive research is nobiletin (NOB), a polymethoxyflavone (PMF) extracted exclusively from citrus peel. Not only does NOB itself exhibit anti-cancer properties, but its derivatives are also promising chemopreventive agents; examples of derivatives with anti-cancer activity include 3′-demethylnobiletin (3′-DMN), 4′-demethylnobiletin (4′-DMN), 3′,4′-didemethylnobiletin (3′,4′-DMN) and 5-demethylnobiletin (5-DMN). In vitro studies have demonstrated differential efficacies and mechanisms of NOB and its derivatives in inhibiting and killing of colon cancer cells. The chemopreventive potential of NOB has also been well demonstrated in several in vivo colon carcinogenesis animal models. NOB and its derivatives target multiple pathways in cancer progression and inhibit several of the hallmark features of colorectal cancer (CRC) pathophysiology, including arresting the cell cycle, inhibiting cell proliferation, inducing apoptosis, preventing tumour formation, reducing inflammatory effects and limiting angiogenesis. However, these substances have low oral bioavailability that limits their clinical utility, hence there have been numerous efforts exploring better drug delivery strategies for NOB and these are part of this review. We also reviewed data related to patents involving NOB to illustrate the extensiveness of each research area and its direction of commercialisation. Furthermore, this review also provides suggested directions for future research to advance NOB as the next promising candidate in CRC chemoprevention.
  • 1.0K
  • 31 Aug 2021
Topic Review
Entrectinib—An Inhibitor of SARS-CoV-2 Cell Entry
This entry describes entrectinib as an antiviral drug.
  • 1.0K
  • 20 Jan 2022
Topic Review
Immune Cell Type-Specific Metabolic Reprogramming
Immunometabolism is an emerging discipline in cancer immunotherapy. Tumor tissues are heterogeneous and influenced by metabolic reprogramming of the tumor immune microenvironment (TIME). In the TIME, multiple cell types interact, and the tumor and immune cells compete for limited nutrients, resulting in altered anticancer immunity. Therefore, metabolic reprogramming of individual cell types may influence the outcomes of immunotherapy. Understanding the metabolic competition for access to limited nutrients between tumor cells and immune cells could reveal the breadth and complexity of the TIME and aid in developing novel therapeutic approaches for cancer.
  • 1.0K
  • 18 Mar 2022
Topic Review
Diacylglycerol Kinase in the Amelioration of Diabetic Nephropathy
The drastic increase in the number of patients with diabetes and its complications is a global issue. Diabetic nephropathy, the leading cause of chronic kidney disease, significantly affects patients’ quality of life and medical expenses. Furthermore, there are limited drugs for treating diabetic nephropathy patients. Impaired lipid signaling, especially abnormal protein kinase C (PKC) activation by de novo-synthesized diacylglycerol (DG) under high blood glucose, is one of the causes of diabetic nephropathy. DG kinase (DGK) is an enzyme that phosphorylates DG and generates phosphatidic acid, i.e., DGK can inhibit PKC activation under diabetic conditions. Indeed, it has been proven that DGK activation ameliorates diabetic nephropathy.
  • 1.0K
  • 27 Oct 2022
Topic Review
Hyperuricemia and Gout
Hyperuricemia is a risk factor for gout. It has been well observed that a large proportion of individuals with hyperuricemia have never had a gout flare(s), while some patients with gout can have a normuricemia. This raises a puzzle of the real role of serum uric acid (SUA) in the occurrence of gout flares. As the molecule of uric acid has its dual effects in vivo with antioxidant properties as well as being an inflammatory promoter, it has been placed in a delicate position in balancing metabolisms. Gout seems to be a multifactorial metabolic disease and its pathogenesis should not rely solely on hyperuricemia or monosodium urate (MSU) crystals. 
  • 1.0K
  • 22 Mar 2021
Topic Review
Insect ATP-Binding Cassette Transporters
ATP-binding cassette (ABC) transporters, a large class of transmembrane proteins, are widely found in organisms and play an important role in the transport of xenobiotics. Insect ABC transporters are involved in insecticide detoxification and Bacillus thuringiensis (Bt) toxin perforation. The complete ABC transporter is composed of two hydrophobic transmembrane domains (TMDs) and two nucleotide binding domains (NBDs).
  • 1.0K
  • 26 Nov 2021
Topic Review
Cancer, Retrogenes, and Evolution
The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumor at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon in some cases has been related to additional gene copies, including retrogenes. In addition, retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis.
  • 1.0K
  • 16 Apr 2021
Topic Review
Lipids
Lipids are hydrophobic or amphiphilic small molecules, including fatty acids and their derivatives, in particular esters, sterols, steroids and phospholipids.
  • 1.0K
  • 02 Aug 2023
Topic Review
Virus-Specific Immunity in TMEV-Induced Demyelination
The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) establishes persistent viral infections and induces chronic inflammatory demyelinating disease.
  • 1.0K
  • 31 May 2021
Topic Review
MicroRNAs
In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection.
  • 1.0K
  • 13 May 2022
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