Molecular Science

          Cancer cells rapidly metabolise glucose solely into lactic acid during the Warburg effect, creating ATP without oxidative phosphorylation. As a result, NADPH and ATP levels, which are required for the anabolic process, fall. Normally, cells create NADPH via the Krebs cycle with the input of acetyl-CoA. However, because glucose is converted to pyruvate and then to lactic acid, no acetyl-CoA is produced via the link reaction. The FAO pathway provides acetyl-CoA and NADPH to cancer cells. As a result, the FAO pathway becomes critical for cancer cell survival. Cancer treatment/remedy might be developed by targeting the FAO pathway or cancer metabolism.         Despite the availability of plenty of oxygen, there is a remarkable increase in glycolysis and a reduction in oxidative phosphorylation of glucose in tumour cells. The "Warburg Effect" refers to this peculiar aerobic glycolysis. It is a characteristic of a rapidly develo...

Enhancers are gene regulatory sequences present at both upstream and downstream of the transcription unit. They are cis-acting elements (50-1000bp) regulating both spatial and temporal control of gene expression e.g. activating in specific cells. Enhancers as non-coding sequences can also be a transcription unit i.e. generating non-coding enhancer RNA (eRNA) regulating the transcription of the gene. eRNA is divided into Class 1, Class 2 and Class 3 (involved in binding with TFs, and controlling gene expression). Due to chromatin folding, these enhancers are spatially close to the promoter while being far linearly. The enhancer is bound by activator proteins which shows specific binding with transcription mediator complex and chromatin regulators thus recruiting RNA Polymerase2. Enhancer units in the genome could be discovered by DNase sensitivity assay, H3K4 methylation pattern (monomethylation - activation, trimethylation - repression), H3K27 acetylation, ChIP analysis of coactivator ...

The occurrence of microbial infection has expanded significantly over the past few decades. Persistent use of antimicrobial medications in treating contaminations has driven the development of resistance among the different microbial strains. Multidrug resistance (MDR) is characterized as insensitivity or resistance of a microorganism to the directed antimicrobial medicines (Singh, 2013, Tanwar et al., 2014). As shown by the world health organization, most of the microorganisms which include Escherichia coli against antibiotics as cephalosporin and fluoroquinolones, Klebsiella pneumoniae against cephalosporin and carbapenems, Staphylococcus aureus against methicillin, Streptococcus pneumonia against penicillin, Nontyphoidal Salmonella against fluoroquinolones, Shigella species against fluoroquinolones, Neisseria gonorrhoeae against cephalosporin, and Mycobacterium tuberculosis against rifampicin, isoniazid, and fluoroquinolone have developed the drug resistance, which prompts them inca...

Adult cells from the body (maybe from skin, liver, stomach, blood, etc.) are taken and reprogrammed into pluripotent nature in which they can give rise to any particular cell lineage. These cells can be of major use in cancer therapies, research, development, etc. These IPSC cells behave just like embryonic stem cells in terms of gene expression, differentiation, and growth factor secretion. The cells are not differentiated and can be maintained in these stages with the introduction of transcription factors such as OCT3/4, SOX2, KLF4, and c-myc.  Junying Yu et al prepared Induced Pluripotent Stem Cell lines by isolating trans-acting factors from mammalian oocytes and transferring them to somatic cells for reprogramming into an undifferentiated state. It was seen that four transcription factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to maintain induced Pluripotent Stem (iPS) cells in culture conditions. These cells are further used to differentiate cells into all three germ l...

The below-listed papers have been reviewed and their summary is illustrated to construct the essence of histone deacetylases in cancer progression.   HDAC inhibitor as novel anticancer therapeutics.  Many of the drugs inhibiting HDACs are in clinical phase-2 and phase-3 trials while one drug for T-Cell lymphoma has been proven by the FDA. It affects DNA histone interaction at the N-terminal of core histone-protein and histone-histone interaction. Its interactive non-histone protein partners are tubulin, Hsp90, beta-catenin, etc. Its high expression leads to cancer, as it suppresses p53 which is a tumor suppressor and due to translocation, HDAC is fused with other proteins (repressor or activator) which recruit it to the gene promoter site. HDAC is divided into four classes (Class 1, Class 2(a, b), Class 3, and Class 4) and 2 families (based on homology) which are the Rdp3/Hda1 family and Sirtuin family (NAD+ Dependent Sir2). Family members show sequence similarity in the ...

Topoisomerases are nuclear enzymes involved in DNA replication, transcription, chromosomal segregation, and recombination. There are two types of topoisomerases found in all cells: type I enzymes that cut single-stranded DNA and type II enzymes that cut and pass double-stranded DNA. Topo2 is involved in endoreduplication as well as mitotic chromosomal segregation following replication. Inhibiting topo2 in cells may cause a cascade of events ranging from endoreduplication and polyploidy to cell death. Etoposide is employed as an anticancer drug by targeting the topo2-DNA complex, however, its induction of the DNA strand break-stable complex may result in chromosomal translocation and, ultimately, a particular kind of leukaemia. There are two types of topoisomerase 2 inhibitors. Class 1 chemicals, such as etoposide and doxorubicin, are known as classical poisons because they stabilise the DNA-Topo 2 complex by producing lesions with broken DNA strands and protein covalently bound to them...

Introduction The cellular import and export pump aid in the maintenance of calcium signaling homeostasis by altering cytosolic Ca+2 concentration, which may be reversed by pumps. Calcium is imported into the cell by voltage-dependent calcium channels (VDCC), SOCC, NSCC, NCX (exchange), and NCKX (co-transport) from the extracellular side. It may also be exported out of the ER and SR via RyR controlled by IP3R to regulate the cytosolic concentration of calcium (100nM-1mM). SERCA pumps restore calcium ions into the ER and SR after voltage-gated Ca+2 channels export calcium ions out of the cell. CaN activation (PP2B), followed by NFAT dephosphorylation. Cyclosporin and voclosporin are two medicines that target CaN. Calcium Sensors and Adaptors Calmodulin (CaM) - Ubiquitous adaptor protein and specifically bind to Ca+2. ❖ Contain EF Hand domain (helix-loop-helix motif) bind to Ca. ❖ Ca bind to 7 O2 atoms (chelate Ca+2) of aa in a bipyramidal pentagonal shape. ❖ Binding with Ca induces dimer...