Friday, 4 May 2018

The Estrogenic Receptor: A Molecular Medicine

The recognizable proof of the estrogen receptor (ER) in the research center gave a mechanism to portray the objective site specificity of estrogen activity in uterus, vagina, pituitary organ, and breast cancer. In particular, a test was built up to anticipate the result of antihormonal treatment in breast cancer, and an objective was distinguished to grow new medications for the treatment and counteractive action of breast cancer. The advancement of tamoxifen for the treatment of all phases of ER-positive breast cancers has brought about the enhanced survival of breast cancer patients. Nonetheless, the identification of specific ER modulation, i.e., estrogen-like activity in bones and reducing the circulating cholesterol  has brought about the advancement of multifunctional pharmaceuticals with the objective of anticipating breast and uterine cancer as well as osteoporosis and coronary illness.
The connection amongst hormones and breast cancer development and advancement has been perceived for over a century. It is accounted for that expulsion of the ovaries from premenopausal women with breast cancer created a sensational decrease in tumor size and enhanced the patient's anticipation. The measure of the tumor expanded and diminished amid the menstrual cycle, in premenopausal ladies with cutting edge breast cancer. Unfortunately, oophorectomy did not profit all patients. Just 1/3 of the patients reacted to ovarian removal and reactions which lasted, for 1-2 years. From that point onward, oophorectomy was replaced by ovarian irradiation for premenopausal patients, though adrenalectomy and hypophysectomy turned into the treatment alternatives for postmenopausal patients. Notwithstanding, the disclosure of estrogenic hormones delivered in the ovary prompted the scan for a restorative antagonist to lessen breast cancer in individuals inclined to the infection by their affectability to estrogenic hormones.
The predominant theory to clarify estrogenic activity was that estrogens apply their activities by taking an interest in enzymatic procedures of digestion. However, progresses in radioisotope chemistry for tritium, encouraged the distinguishing proof of a receptor protein that intervenes the different activities of estrogen without metabolic adjustment of the hormone itself. These revelations gave the vital knowledge to comprehend the complexities of steroid endocrinology and opened the way to molecular targeting in the treatment and prevention of breast cancer.

Thursday, 26 April 2018

Bioconjugated Nanogels

Nanogels are otherwise called as nanocarriers for the encapsulation and delivery of biomolecules. Designing nanogels as delivery systems for biomolecules with a capacity to respond to the external physical and chemical signals like pH and temperature. Moreover, it has enhanced permeability and retention (EPR) effect, due to their extremely small size. There are many advances that have been developed in designing nanogels for various purposes. Some of them are as follows:

  • Nanogels for intracellular delivery of genetic materialNowadays, gene therapy designed for delivery of antisense oligodeoxynucleotides (ODNs), plasmid DNA (pDNA), siRNAs and micro RNAs (miRNAs) used in targeted inhibition of specific mRNA sequences has developed as one of the most favourable method to treat and diagnose diseases like cancer, neurodegenerative disorders and viral infections. However, the major tests in designing an intracellular gene delivery system exist in crossing the cell membranes without being premature degraded by endogenous enzymes and providing a controlled release of the genetic material into the cell nucleus without inducing cytotoxicity and an immune response following degradation.
  • Nanogels for specific targeted protein delivery - The major problem in using proteins and peptides as therapeutic agents are the protein stabilization in delivery reservoirs at physiological pH values and temperatures and the proper design of protein carriers for the sustained and targeted delivery. One of the approaches in overcoming these limitations is to entrap proteins into hydrogel nanoparticles (nanogel), which can reduce denaturation of proteins by forming a colloidal stable complex with proteins at the nanometer scale (<50 nm).
  • Bioconjugated hydrogel nanoparticle as vaccine delivery or adjuvant systemsRecently, multi-responsive polymeric nanogels have developed a new vaccine delivery system which is capable of initiating innate immune response or enhancing antigen delivery. Therefore, in the case of genetic material and protein encapsulation, nanogels intrinsic properties allow protecting vaccine antigens from degradation in vivo and, by bioconjugation with antibodies or specific ligands, could increase active targeting specificity. Among them, polysaccharide-based nanogels such as cationic cholesterol-bearing pullulan (cCHP) appear to be very appealing as vaccine delivery systems due to their great biocompatibility and the abundance in unprocessed sources.

Limitation of using nanogels as targeted delivery systems is represented by their low target site specificity. Therefore, by conjugation of nanogels or nanogel compounds with biomolecules such as ligands, proteins or other molecules having molecular recognition specificity, the specificity for targeted delivery will improve. Attachment of biomolecules allows a rapid internalization of nanogels into the cells through endocytosis.

Thursday, 12 April 2018

Stem Cells for Neurological disorders

Due to the loss of neurons and glial cells, neurological disorders like Parkinson’s disease, stroke and multiple sclerosis are caused. Nowadays, stem cells are cultured to develop neurons and glia to minimise the neurological disorders.  Moreover, efforts have been taken to reduce the death of neurons and glial cells produced by stem cells, within the central nervous system.

On account of a few disorders, increases can probably be induced just with transplanted cells produced from undifferentiated cells in vitro, while in different conditions the stimulation of endogenous CNS stem cells might be valuable. In the case of Huntington’s disease, it is caused by the demise of projection neurons in the striatum. Stem cell treatment means to re-establish or save brain function by replacing and ensuring striatal neurons. In creature models of HD, cell substitution utilizing fetal striatal neurons advances functional recovery and some proof from clinical trials shows this can also happen in patients. By contrast, stem cell based methodologies are still in their earliest stages, and the reproduction of striatal neural hardware has not been appeared in animals.

Before we apply stem-cell treatments to patients, we should have the capacity to control the expansion and separation of stem cells into particular cell phenotypes and to prevent tumor formation. Besides, the viability of stem cells and their systems of activity ought to be exhibited in animal models with pathology and symptomatology resembling the human sickness. It might be hard to interpret information got in creatures to people as a result of animal varieties contrasts in the level of neuronal plasticity and an inadequate learning of illness mechanisms. We should see how to impact the neurotic tissue condition, including inflammatory and resistant responses, to permit productive repair. Finally, we should recollect that however energizing the neurobiological components may be, the clinical convenience of stem cells will be controlled by their capacity to provide patients with neurological disorders with protected, durable and considerable upgrades in quality of life.

Friday, 6 April 2018

The Druggable Genome

The subsets of approximately 30,000 genes in the human genome that can bind to drug like molecules by expressing proteins are called as “The Druggable Genome”.  This concept is raised because of the limitation of molecular targets for which commercially viable compounds can be developed. This means that “The Druggable Genome” which has the ability to produce proteins to bind with drugs.
Commercially viable drug means an orally bioavailable compound. Physico-chemical properties are necessary to improve the oral bioavailability of drug which can be formalized by the Lipinski “rule of five” analysis. Most successful drug achieves their activity by searching for a binding site on protein with a small endogenous molecule. It is necessary that a drug must bind to its target molecule with a reasonable potency, to be more effective.
Survey has been taken to find the molecular targets for a drug to bind on its binding site. Analysis of International Drug Database and the Pharmaprojects Database recognise 399 non-redundant molecular targets. In that, several proteins are targeted by experimental drugs and some are eliminated because of its inactivity according to the rule of five analysis. Most of the drugs identified in this survey are competitive. Those targets fall into the six gene families:
·         G-protein Coupled Receptors (GPCRs)
·         Serine/Threonine and Tyrosine protein kinases
·         Zinc metallo-peptidases
·         Serine proteases
·         Nuclear hormone receptors
·         Phosphodiesterases
New methods such as protein drugs, antibody therapies, DNA vaccines and non-oral drug delivery systems, could expand the range of potential targets those which can’t be identified by rule of five analyses. The limited number of molecular targets for the drug suggest that the druggable genome to be produced in a cost-effective manner. This will be the major innovation for the pharmaceutical industry, not just in the case of science, but also in the case of business.

Friday, 30 March 2018

Database of Interacting Proteins (DIP)

The Database of Interacting Proteins is a database that archives tentatively decided protein – protein interactions. It gives established researchers an incorporated arrangement of apparatuses for extracting data about protein collaboration systems. The DIP inventories roughly 11 000 novel interactions among 5900 proteins are from in excess of 80 life forms; most of them are from yeast, Helicobacter pyloriand human. Instruments have been created that enable clients to examine, imagine and coordinate their own trial information with the data about protein– protein associations accessible in the DIP database.
The structure of the DIP has been designed to capture the essential information about protein–protein interactions available from experimental data. The database is implemented as a relational database composed of four tables. Protein Table lists proteins participating in an interaction within DIP. It provides, besides the DIP accession number, cross-references to the three major sequence databases (SWISS-PROT, GenBank, and PIR) as well as additional information about the proteins such as keyword, localization and cellular function.
DIP change envelops combination of the database with various effectively existing, settled natural databases, for example, SWISS-PROT, TRANSPATH, KEGG, and YPD to enable clients to effortlessly get to accumulate the greater part of the data about a solitary protein. To this we expect to build the quantity of cross-references revealed for each DIP section.

Saturday, 24 March 2018

Antibiotic Resistance Transfer Mechanism

Bacteria have developed resistance towards most of the drugs nowadays. Those bacteria are called as multi-drug resistant bacteria which include methicillin-resistant Staphylococcus aureus (MRSA); vancomycin resistant Enterococcus (VRE), ESBL (extended spectrum beta-lactamase) producing Enterobacteriaceae. European Molecular Biology Laboratory has introduced a major antibiotic resistance transfer mechanism on molecular basis to fight against these multi-drug resistant bacteria. They also established molecules and a proof-of-principle for blocking this transfer.
The major reason for resistance spreading in bacteria is transposon also called as jumping DNA. Transposons are genetic elements that can change its location in the genome. When it is transferred into the genome, it carries antibiotic resistance genes with them. Therefore, Barabas group at EMBL focus on transposons and their molecular structure.
EMBL researchers discovered a transposon insertion machine to insert transposase protein into the DNA in an inactive state. After binding it into the DNA, it prevents the cleavage and destruction of transposon due to its inactivity. The transposon shape itself focus the DNA to unwind and separate it to transfer the antibiotic resistance into the host genome. So, to avoid the antibiotic resistance transfer, we must maintain the inactivity of transposase protein. By blocking its architecture, we can able to maintain its inactivity. Another method is a DNA mimic that binds to the transposon’s open site, so that the DNA replacement cannot be done to transfer the antibiotic resistance. By this method, we can target the specific bacteria and not all the bacteria in our body.
More and More innovations are yet to be discovered and shared. But there is a place where we can share everything that happens in the field of Molecular biology and medicine. And that place is nothing but our conference titling “6th Annual Congress on Biology and Medicine of Molecules” occurring on September 17-18, 2018 in Abu Dhabi, UAE.
For more details, please go through:
Journal Reference:
  1. Anna Rubio-Cosials, Eike C. Schulz, Lotte Lambertsen, Georgy Smyshlyaev, Carlos Rojas-Cordova, Kristoffer Forslund, Ezgi Karaca, Aleksandra Bebel, Peer Bork, Orsolya Barabas. Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance. Cell, 2018; DOI: 10.1016/j.cell.2018.02.032

Friday, 16 March 2018

Future of Molecular Biology and Medicine

Molecular techniques have changed our insight into cell and tissue work in both health and illness. As of now we have, some of new and capable medications based on a comprehension of correspondence between cells by messenger molecules like cytokines. Besides, there is extraordinary helpful framework of molecules which manage cell grip, motility, multiplication, survival, and demise. Reasonable control of cell and tissue work, for restorative finishes might be substantially nearer than you might expect.
Proximity was adequate to start flagging events or drive their impact on translation. Engineered little molecule instigated dimerization of the T cell receptor gave the main proof that proximity could be utilized to comprehend signal transduction. A recognizing highlight of little particle induced proximity frameworks is the capacity to start a procedure halfway and perceive the following request of occasions with exact control. The fast reversibility of induced proximity has empowered exact examination of cell and epigenetic memory and empowered the development of engineered administrative circuits. Joining of CRISPR-Cas advances into CIP systems has expanded the extent of these strategies to examine quality direction on minutes, at any locus, in any hereditary setting. Besides, CIPs have been utilized to dissect the components overseeing apparently surely knew forms, going from transport of proteins between the Golgi and endoplasmic reticulum to synaptic vesicle transmission. Late advances in proximity-induced apoptosis, hindrance of conglomeration, and specific corruption of endogenous proteins will probably yield new classes of medications very soon rather than later.
Join us at the conference Biology Medicine 2018 going to be held at September 17-18, 2018 in Abu Dhabi, UAE and get more details about the future of molecular biology and medicine.

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The Estrogenic Receptor: A Molecular Medicine

The recognizable proof of the estrogen receptor (ER) in the research center gave a mechanism to portray the objective site specifici...