Our cells sends and receive millions of messages in the form of chemical signaling molecules. Cells communicate using these chemical signals. Regardless of nature of the signal, the target cell respond by the means of receptor, which binds the signal molecules(ligand) & initiates a response in target cell. Receptors are chemically protein or glycoprotein molecule which bind to signal molecules(ligand). Binding of ligand to its receptor causes conformational change in receptor that initiates a sequence of reaction leading to specific cellular responses. Based on location, Receptors are being classified as 1) Intracellular Receptors – Cytoplasmic Receptor & Nuclear Receptor 2) Cell Surface Receptors– G protein, Tyrosine Kinase Receptors & Janus Kinase Receptor

Estrogen and estrogen receptors (ERs) are critical regulators of breast epithelial cell proliferation, differentiation, and apoptosis. The Estrogen Receptors(ER) are believed to be a major contributing factor in the malignancy of breast cells. Targeting the ER signaling pathway has been a focal point in the development of breast cancer therapy. Approximately 70% of breast cancers are estrogen receptor-positive and this type of breast cancer is more common in postmenopausal women. Breast cancer, a genetically and clinically heterogeneous disease that originates from the mammary epithelial cells. It remains the leading cause of cancer deaths among females worldwide with about one in eight women (12 %) developing breast cancer in her lifetime. Woman’s risk for breast cancer is linked to her reproductive history and her lifetime hormonal exposure. The levels of estrogen in blood and tissue are associated with breast cancer carcinogenesis. Estrogen receptors belong to the Nuclear Receptor Superfamily. The two different forms of Estrogen Receptors(ER) – ERα  and  ERβ are coded by two distinct genes ESR1 and ESR2, located on chromosomes 6 and 14, respectively. ERα mediates unregulated cell proliferation in breast cells. However, ERβ opposes the actions of ERα by modulating the expression of ERα-regulated genes and reducing migration of cancer cells. Let’s know about Estrogen signalling pathway and what goes wrong in the pathway resulting in abnormal condition.

ESTROGEN SIGNALLING

Estrogen signaling includes two distinct pathways often referred to as genomic and non-genomic pathways. ERs are randomly distributed in the cell & are maintained in an inactive state by co-repressor proteins (NCORI, SMRT ). To activate ER- dependent transcription, ER-corepressor complexes need to be dissociated & replaced by co-activator complexes.

GENOMIC PATHWAY

DYSREGULATION OF GENOMIC PATHWAY

Co- activators contain LXXLL motif (L,leucine, X, any A.A) that interacts with ligand binding domain of ERα. These co-regulators are associated with various enzymes such as deacetylase, acetyltransferase, methyltransferase, ATPase, etc which regulate chromatin remodeling & directly or indirectly regulate target gene expression. Deregulation of coregulator expression is associated with tumor progression, metastasis, cancer cell migration & drug resistance. Binding of AIB1 & BCAS3(Breast carcinoma amplified sequence 3)  both ERα co-activators are known to induce Breast carcinogenesis.

NON-GENOMIC PATHWAY

Estrogens regulate activity of ERs by serving as ligand, Estrone(E1), Estradiol(E2) &Estriol(E3)- 3 forms of estrogen. E2 is important ligand of ERs. Depending on a cell type, small fraction of ERα is involved in non-genomic action by anchoring to PM. Non genomic signaling of estrogen involves, mobilization of secondary messengers & interaction with membrane receptors such as, IGF-1R(Growth factor-1-receptor), EGFR(Epidermal growth factor receptor), Stimulation of effector molecules such as Src & PI3K, Serine/theronine protein kinase(AKT), MAPK(Mitogen activated protein kinase)

B) Growth factors activate receptor tyrosine kinases, which activate MAPKs.  MAPKs can then phosphorylate and activate ERα either independent of E2 or synergize with E2 for optimal ERα activation.

C) Membrane associated ERα interacts and activates SRC kinase upon ligand binding. SRC kinase then phosphorylates and activates aromatase, which catalyzes conversion of androgens to estrogens within cells and amplify both genomic and nongenomic ERα-E2 signaling.

(D) Membrane anchored ERα can also activate various cytoplasmic kinases including PI3K-AKT-mTOR pathway through nongenomic actions, resulting in activation AKT pathway involved in cell proliferation and survival.

NORMAL REGULATED PATHWAY

DEREGULATED PATHWAY

When E2 binds to activated ERα receptor , Depalmitoylation at cysteine477 (detachment of fatty acid molecule from the membrane) The dissociated molecule then interacts with signaling molecule PI3K. PI3K converts PIP2 into PIP3, which interacts with PH domain of AKT Transfer AKT to cell membrane along with PDK1, resulting in conformational change in AKT & exposed T308 & S473 undergoes phosphorylation. Further, PIP3-dependent phosphorylation by m-TOR, resulting in full activation of AKT/Protein Kinase B. Promotes cell Proliferation, survival & apoptosis.

When E2 binds to activated membrane ERα, Palmitoylation at cysteine477 localize ERα to PM. Responsible for ligand-induced activation of PI3K-AKT-mTOR pathway, resulting in Breast cancer cell.

Bacteria are known to regulate their cooperative activities & physiological processes through a mechanism called “Quorum Sensing” (QS), in which bacteria communicate within themselves or within different species by releasing, sensing & responding to small diffusible signal molecules eg; Acylated homoserine lactones (AHLs) named as Autoinducer. QS allows microorganisms to control the behaviour of the entire bacterial population by secreting these signalling molecules. When the concentration of signal molecules reaches a certain threshold with bacterial population density, the expression of certain specific genes gets activated to regulate the bacteria population to undergo adaptation. These adaptations may activate a variety of cellular processes including virulence, drug resistance mechanism, tolerate antibiotics, biofilm formation in order to harm the host. QS exists in various bacteria, whether in Gram negative or Gram positive , but signal molecules they use to transmit information varies as different like human languages.

Antibiotics are used widely around the world besides antibiotic resistance is spreading faster than ever before. It takes 10-15 years to develop a new antibiotic but by this period bacteria become resistant to that drug, which is a serious problem to be considered. Most antibiotics currently used are designed to directly kill pathogenic bacteria. This “life or death” has caused them selection pressure promoting the evolution of microbial resistance and has become serious threats to human health. The large-scale use of antibiotics in the clinical treatment had led to multi-resistance mechanisms by microorganisms against the target of antibiotics.

Microbial Resistance mechanisms

1. Passivation of antibiotics through the chemical modification

Microorganism produces certain chemicals that inactivate the mechanism of the drug. By secretion of a modified enzyme changes the chemical structure of antibiotic drugs leading to inactivation or loss of activity of antibiotics. The enzymatic mechanism includes antibiotic degradation and derivatization of antibiotic chemical groups which leads to inactivating the drugs or destroying the molecules themselves so that no longer antibiotics can interact with microorganisms. eg; Bacterial enzyme, Beta-lactamase destroys the active component(the beta-lactam ring) of penicillins.

2. Efflux pump systemic

Here microorganisms use antibiotic pumps to expel antibiotics. Antibiotics usually enter the cell through the cell membrane in order to effectively attack specific targets. Microorganisms assemble efflux pump protein on their cell membrane to expel antibiotic drugs from cells. Bacterial efflux pumps are composed of the outer membrane channel protein, the fusion protein, and cytoplasmic efflux protein. Any foreign particle including protein, antibiotics is selectively or non-selectively eliminated from bacteria. Excretion rate is usually faster than drug penetration rate, thereby controlling drug level in the cell to non-sensitive level. They even have a variety of microbial efflux pump system such as lipophilic, hydrophilic efflux system that targets drugs of different chemical properties.

3. Modification of drug trageting genes

Microbes have evolved different strategies, which include modifying the target site, thereby reducing the affinity for antibiotic molecules to bind to the target site.

4. Biofilm Formation

Biofilm is an effective drug barrier, which significantly reduces antibiotic permeability. Bacteria are connected to each other through proteins & DNA, especially extracellular polysaccharides forming insurmountable barriers, which can reduce the permeability of antibiotic drugs & improve the survival rate of bacteria in the biofilm. Biofilms provide protection to microorganisms for altered PH, osmolarity, nutrients, mechanical or shear forces & also blocks access to antibiotics and the host’s immune cells.

This special environment in the biofilm makes bacteria in the membrane produce heterogeneity & produce antibiotics against other bacteria. Heterogeneity of bacteria has led to different levels of drug resistance against bacterial cells, where new research is emphasized more in this area.

It is essential for microbes to adapt & cope with these stressful situations. Thus a bacteria have devised complex mechanisms. Multiple drug resistance mechanisms expressed by these microorganisms had made it difficult to overcome and solve the problem of microbial resistance. In the struggle b/w microorganisms & antibiotics, more & more microorganisms have evolved multiple resistance mechanisms & have become “super bacteria”. Currently inhibiting bacterial QS has become a new promising antibacterial strategy.

Coumarin’s showed a Anti-Quorum Sensing Activity

Coumarins are a class of natural compounds based on benzopyrones. Coumarins are identified as secondary metabolites in about 150 different plant species. 7,8-dihydroxy-4-methylcoumarin was identified as the most effective anti-QS compound which had the ability to inhibit cell-to-cell communication in bacterial communities. At the same time when we look at its structural features, particularly the hydroxy group positions, well-responded to all anti-QS active coumarins. It was significantly noted as an increase in the antibacterial effect upon the hydroxylation of coumarins at positions 6,7, or 8. It showed that hydroxylation at position 7 increased anti-QS activity, while hydroxylation of coumarin at positions 6 & 7 decreased this activity in comparison to conventional coumarin. It also showed that Coumarin when combined with other Plant-Derived small molecules showed an effective response. 7.8-dihydroxy-4-methylcoumarin with 4-hexyl-1.3-benzendiol and gamma-octalactone demonstrated a synergetic anti-QS effect. Coumarins are characterized by a special mechanism through inhibition of the metabolism of cyclic 3,5-diguanylate (c-di-GMP), an intracellular intermediate involved in the regulation of bacterial exopolysaccharide synthesis, biofilm formation, adhesion, and virulence. Besides Coumarins are proposed for medical uses due to their proven biological activity such as Anti-inflammatory, Anti-ulcerogenic, Anticoagulant & are also Antioxidants.

Ref;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143945/ ; https://www.mdpi.com/2076-2607/8/3/425/htm

Inflammatory Bowel Disease (IBD), is a chronic and life-threatening inflammatory disorder of the gastrointestinal tract that arises due to host-microbial interactions in a genetically susceptible individual. It can affect people of all ages, including children & geriatric populations, and can affect all aspects of life. However, IBD is increasing in the emerging population, mainly in the industrialized countries of Asia, Africa, and South America. IBD is a group of autoimmune diseases that are characterized by inflammation of both the small & large intestine in which elements of the digestive system are attacked by the body’s own immune system. IBD includes Crohn’s disease & Ulcerative Colitis.

Crohn’s Disease; Is an IBD that causes inflammation anywhere along the lining of the digestive tract, from mouth to anus in a discontinuous pattern. Crohn’s exhibits histologically a thickened submucosa, transmural inflammation, fissuring ulceration & granulomas.

Ulcerative colitis; Involves the rectum & can affect part of the colon or the entire colon in a continuous pattern. Here the inflammation is limited to the mucosa & submucosa with cryptitis & crypt abscesses.

Causes; The exact cause of IBD remains unknown, one possible cause is an immune system malfunction, abnormal immune response causes the immune system to attack the cells in the digestive tract.

• Nucleotide-binding oligomerization domain 2 (NOD2) is the first gene found to be associated with increase in the susceptibility to Crohn’s disease, which is frequently mutated in patients with Crohn’s disease, occuring in around one-third of the patients.
• Environmental factors to plays a important role in pathogenesis of IBD. Studies have shown that increased consumption of milk protein, animal protein, medium chain fatty acids, fast foods containing many fat & sugar rich components exacerbate the development of Crohn’s disease.
• Smoking is another example of disease- specific modifier that seems to worsen Crohn’s disease. Smoking has been shown to affect cellular & humoral immune response & to promote colonic mucus production.
• Other factors that influence the development of IBD, includes not limited to psychological stress, appendectomy is another independent risk factor for developing Crohn’s disease.

IBD appears as a result of abnormal host immune responses to the intestinal microbiota. The gastrointestinal tract of the human body is colonized by a vast range of microorganisms that numerically exceed host cells by around 10 times. The gut contains 1000-5000 different species from Firmicutes, Bacteroidetes, Proteobacteria & Actinobacteria. These microorganisms contain around 100-fold as many genes present in the human genome.

The immunological dysregulation in IBD is characterized by epithelial damage (abnormal mucus production, defective repair), expansion of inflammation-driven by intestinal flora & a large number of cells infiltrating into the lamina propria includes T cells, B cells, macrophages, neutrophils results in failure of immune regulation. The intestinal immune system is divided into innate immunity & adaptive immunity. Innate immunity includes the barrier function of the intestinal mucosa, antibacterial proteins, the acid PH value of the stomach to limit microbial growth. Whereas Adaptive immunity is pathogen-specific & is usually initiated under the circumstances in which the innate immune responses cannot circumvent the stimulation of a pathogen. After exposure to a pathogen, it usually takes several days to finally activate adaptive immune responses, including T & B cells. The initiation of immune response to intestinal flora is tightly regulated & this regulation determines the occurrence of immune tolerance or a defensive inflammatory response. Disturbance of the balance of these responses can cause IBD.

What if we had a supplement that could sense the disturbance to the microbiome & restore balance to treat this chronic disease?

Francisco Quintana, an immunologist & neurologist at MIT’s Broad Institute & Harvard Medical school, and his colleagues have genetically engineered yeast that can respond to inflammation & successfully relieve IBD symptoms in mice. Previous studies have found that people with IBD have an unbalanced gut microbiome with lower overall diversity & more bacterial species that drive inflammation. Scientists believe that these yeast probiotics could help to restore this balance, neutralize & reduce the inflammatory molecule. Patients with IBD carry an abundance of microbial species that produces excessive ATP, which promotes inflammation. Meanwhile, host immune cells that drive inflammation also secrete ATP, further exacerbating the situation.

The researchers engineered Saccharomyces cerevisiae, the same yeast species that facilitate bread and beer-making, to detect ATP with the human receptors. They used CRISPR-Cas 9, a type of gene-editing technology, to introduce a gene that is activated by inflammation in the gut. They linked the activation of this receptor to secret the enzyme apyrase, which degrades ATP. The result is, probiotic that senses a pro-inflammatory molecule, extracellular ATP(eATP), generates a proportional self-regulated response to neutralize it. The engineered yeast produces different amounts of enzyme, depending on how many inflammatory signals are produced. In the mouse model of IBD, the probiotic performed better than standard therapies for IBD. This approach could work to mitigate inflammation not only in gut but also in other parts of the body. The therapy also helped to restore the balance of gut flora in the mice and this therapy can even help with other inflammatory conditions, including diseases like Parkinson’s disease that are anchored or initiated in the gut.

This approach is the next step of personalized medicine, going one step beyond that to adjust therapy only to those specific areas of the patient that are diseased. With this knowledge, we have the ability to develop novel personalized treatments for IBD patients.

Ref; https://www.the-scientist.com/sponsored-article/engineered-yeast-robots-destroy-inflammatory-molecules-in-an-ibd-mouse-model-69092

The Coronavirus disease 19 (COVID-19) is a highly transmittable & pathogenic viral infection caused by Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) which caused global pandemic that led to dramatic loss of human lives. Coronavirus can be classified into 4 genera namely; Alpha coronavirus, Beta coronavirus, Gamma coronavirus, and Delta coronavirus. When we look at its morphology it is large, enveloped, single stranded positive sense RNA virus with 5′ cap structure and 3′ Poly A tail structure & genome ranges from 27 to 32kb. It encodes 4 structural proteins on its surface, namely Nucleocapsid(N) protein, Membrane(M) protein, Spike(S) protein and Envelop(E) protein & several non-structural proteins. The genome is packed inside a helical capsid formed by nucleocapsid protein (N). The membrane protein(M) & envelope protein (E) are involved in virus assembly, whereas spike protein(S) mediates virus entry into host cells. The genetic material of the virus, RNA is made up of molecules, each part of this code contain instructions for how to make one specific protein that allows the virus to function. A virus has one goal, to make more of itself because it’s so simple it can’t do by its own, so it uses us. Every time virus infects a person it uses their cells to make copies of itself, while replicating this code again & again it eventually makes a mistake, sometimes it deletes or adds a letter, that mistake is called mutation and it slightly changes instructions for making the virus & that slightly altered virus is a variant.

ACCESS TO THE HUMAN CELLS

Virus has envelope containing spike protein on its surface. This spike protein on virus unlocks/ gains access to interior of human cell through ACE2( angiotensin converting enzyme2). Virus uses ACE2 as receptor to unlock the human cells. It has not been entry point for just coronavirus, but also for multiple virus. ACE2 receptor exists abundance on the surface of lung cells.

There is another second protein called TMPRSS2 which allows virus to reproduce & eventually leads it to transmission within the cell. It was found that cells from nasal cavity, eye, lung, gut, heart and kidney have these proteins. Now the virus overcomes the cell metabolism to its own advantage and uses cells to multiply & make its own replicas, so within 2 days you have millions of viruses in your body. Now your body starts recognizing this invasion, body then fights by producing antibodies which recognizes foreign virus, attacks them and kills them. This is the normal process that takes place in the body when any foreign bodies attacks.

Now within 4-5 days, when antibodies are sufficient in number, viruses are large in number there is fight between these two(antibodies & viruses). Our immune system now produces certain chemicals into bloodstream know as CYTOKINES these are chemicals that causes the body to have higher temperature, bodyache, like incase if you have throat infection, you experience sore throat this is because, cells in the throat have maximum of viruses & there is a fight going on inside and hence because of the irritation you get cough.

Incubation period for virus means, from the entry of the virus to its first symptom, on an average of 5 days. 1st symptom maybe fever, bodyache, headache, even diarrhea and has to be kept in the mind as first day of infection producing symptom. If fever goes higher or sore throat persist for 3 continuous days and on 4 -5 day if your fever comes down and you have no symptoms, check for another 5 days & if you have no symptoms, then you are a Corona Warrior. 80% of the people have only minor symptoms which settles in 3-4 days. Remaining 10-20% people takes dangerous turn. Fever which had settled within 4-5days, it comes back or if it was there now you have a higher degree of fever & if you had a cough, now you experience deep hacking cough. The 3 symptoms indicating that your disease is taking to a dangerous turn are;

• Higher fever than before or if you have no fever, you will have new fever with higher temperature
• Chest congestion or difficulty in inspiration & expiration process.
• Deep hacking cough, which makes you difficult even when you are sleeping.

CYTOKINE STORM

When a foreign invaders enters our body, our immune system produces antibodies to destroy them. But sometimes our immune system gets hyperactivated & instead of killing foreign invaders, it gets excited itself & start killing its own cells, leading to cytokine storm.

Cytokines are the small proteins produced by the immune system, which act as signaling molecules that convey the message between different immune system cells. Your immune cells uses cytokines to communicate. Cytokine proteins are important in order to have unified immune response against foreign invaders. These signaling molecules are produced by many different immune cells, such as Mast cells, macrophages, B-cells, T- cells. There are few types of cytokines namely

Interferons – These protein inhibit virus from replicating. If a cell gets invaded by a virus, this signals other cells to put a shields so that virus doesn’t spread.

Interleukins- These protein regulate immune and inflammatory responses. They are mainly produced by white blood cells & their job is to send signals to WBCs to report for duty.

Chemokines- These call the cells to the site of infection. The ability to call in other cells using chemical message is a process referred to as chemotaxis.

Now if we get infected with virus or bacteria, the cytokine concentration increases and due to hyperactivated response of immune system, it releases more cytokines to signal neighboring immune cells & this leads to fail in identifying/differentiating between invader and our own cells.

CYTOKINE STORM EFFECTS

When virus attacks lung cell, they cause damage to cell. The damaged cells releases chemicals including histamine, prostaglandins etc .These chemicals sends signals to WBCs to recover from damage & to releases cytokine. When cytokines comes in the close proximity to the lung cells, there will be a huge rush of cytokines, signaling more & more WBCs to come in, now this area results in swelling. As more & more cytokines are moving in the close proximity to damaged lung cell, the wall of blood vessels becomes thinner and thinner, this causes leak of fluid from blood vessels into neighbouring lung tissue & as fluid is moving to lung tissue, now water content from blood vessels are moving out leaving with only a cellular components in blood vessel and due to this reason, blood cells in the blood vessels start sticking instead of free flow, leading to blood clot and when there is a clot formation, the required amount of blood, oxygen won’t reach to your different organs & hence Cytokine storm leads to Multiple Organ Dsyfunction. That’s the reason why most of the covid patient faced comorbidity death like liver failure, kidney failure, heart failure which is the part of cytokine storm.

DIAGNOSIS OF STORM

When our own cells have turned against us. We need to prevent release of cytokines in the body, we need to suppress our immune system. There are certain factors/ indications which has to be checked to prevent cytokine storm.

• Ferritin protein; Increases high before the cytokine storm.
• C- Reactive Protein(CRP) ; Increases high, not only here but in any sort of infection in the body.
• Interleukin 6 ; Increases high, in the case of viral infection.

WHY FIRST LUNG CELLS ?

Virus is recognized by human body by our immune system, spike protein on the surface of virus is recognized by antibodies. Some cells in our body have similar appearance & structure to that of virus spike protein, these are specifically seen more in the blood vessels of lungs .

In the lungs, antibodies which are supposed to only attack foreign viruses, recognizes these similar cells & attacks them, causing normal cells to damage. when the cells get damaged, the normal smoothness of blood vessels interior is lost, cells lining the wall of blood vessels become rough hence blood cells start sticking there, resulting in formation of clot & blocks the passage of blood vessel and no more blood can pass. So if this happens in lungs, the normal exchange of oxygen that happens b/w air and your blood in the alveoli of your lung is not going to happen, no blood flow, no oxygenation and when no oxygenation your saturation of oxygen in your blood keeps going down, you start feeling breathlessness & have a problem in breathing depending upon the severity of damage to the lungs. This is all not because of virus persisting in your lung but because body’s reaction to the viruses, autoantibodies attacking our own cells.

ROLE OF STEROIDS

On 5th or 6th day if patient has come up with high fever, bad cough & breathlessness, saturation below 94% this is where steroids has to be given to prevent cytokine storm and another important thing is, steroid alone doesn’t stop the clotting of blood within the lung blood vessel, so we have to combine it with anticoagulant. The 2 medication which has to the taken at this stage, steroids with anticoagulant. In the case of steroids, timing is very important & taking steroids all alone without the consultation is again a dangerous thing. Taking steroids at the early stage of disease ( first 5 days of the disease), results in multiplication phase of the virus to be prolonged, leading your disease to be prolonged.

Steroids are used to treat inflammatory conditions which may be seen in serious COVID-19 cases. WHO recommends corticosteroids (i.e dexamethasone, hydrocortisone or prednisone) to give orally or intravenously for the treatment of patients with severe COVID-19. Treatment showed to reduce the length of time on ventilation for the patients with critically ill. Steroids has to be taken once a day for atleast 7-10 days & anticoagulants has to be continued for 3 weeks, not 10 days like steroid because tendency of blood clotting has 3 weeks, so that it can cover. Dosage of the steroid shouldn’t be more than 2mg/kg. Though steroids are effective to reduce infection associated with inflammation but they suppress our immunity. When you are on the course of steroids & anticoagulants dramatically you become better, fever is gone, cough is better, but again on 5th day on the course of steroids, you start having a fever again and this time it is not virus, but as normal immunity is being suppressed, a normal bacteria in your lungs attacks your body and causes Pneumonia which should be covered with antibiotics. Steroids do benefit in huge way in life saving way, but it encourage infection by bacteria within our lungs and this is the only stage, when antibiotics has to be taken. Taking antibiotics at the 1st symptom is actually encouraging bacterial resistance, resulting in bacteria becoming resistant against drug, because no antibiotics ( like Azithromycin or Doxycycline) do anything in eliminating the virus, they doesn’t work against virus But are useful in protecting patient from bacterial pneumonia which happens at the 5 day after starting steroids. Steroids are diabetogenic- those who are pre-diabetic they become frank diabetic, when they are on steroids which is the another drawback of steroids.

Than taking our disease to more complications and to the dangerous turn, let’s prevent it and it is important to take right medication at the right time and to follow the simple protocols, such as wearing a mask, social distancing, washing hands. The novel coronavirus spreads so rapidly that it has changed rhythm of the globe. SARS-Cov-2 virus entered our country in March 2020 and somehow we managed to come out of first wave. It again strike our nation in its mutant form & thus Covid 19 second wave emerged. Now again epidemiologists and various scientists have predicted 3rd wave. So let us together prevent it.

Ref;https://youtu.be/CJzo6JIqhCw

Humans have always created waste over a years. Solid waste, garbage, trash has been dropped into streets, sewage, landfills, waterways all over. Advances have been made globally to confront complex problems of waste generation, collection, and disposal. Currently, about 2.01 billion metric tons of municipal solid wastes are produced annually worldwide. The world bank estimates, overall waste generation will increase to around 3.40 billion metric tons by 2025. Out of total municipal waste collected on average, 94% is dumped on land and 5% is composted.

Nowadays, Plastics have become a worldwide recognized problem. These synthetic durable, non-reactive, cheap, conventional plastics play a vital role in our day-to-day life. They have taken constant place in our lives, by providing series of incredible benefits, besides they bring huge remarkable impact on soil, on our environment and health, Humans have generated around 380 million tons plastics every year, from which only 9% has been recycled and remaining ends up in landfill sites or oceans and recycled plastics causes more problems to the environment than original plastics due to the mixing of additives, colors, stabilizers, etc. Hence, there is an urgent need of reducing mankind’s dependencies on these nonrenewable resources. To overcome these crises, Biodegradable plastics take the best option to protect the environment against petroleum-based plastics.

There are many biodegradable plastics with different degrees of biodegradability such as starch-based, soy-based, cellulose-based, lignin-based, but among them, Polyhydroxybutyrate( PHBs), bacterial based bioplastics are the best and 100% biodegradable ones. PHB is a biologically produced biodegradable substance synthesized as inclusion bodies in numerous bacteria like Bacillus, Azotobacter chroococcum, Ralstonia eutrophus, Bacillus megaterium etc. PHBs are the energy reserve in the form of water-insoluble dense granules present in the cytoplasm of bacteria, they use them to store energy when they lack enough nutrients to reproduce. When microbes are under stress conditions or imbalanced condition of nutrients or in presence of excess carbon sources, they result in the production of granules inside their cells, resembling a very good property to those of synthetic plastics besides fully biodegradable. On degradation, they produce carbon dioxide, methane, mineral salts, water, and biomass to the environment and this PHB is well-posed for commercial adoption use due to better biodegradable properties in many types of environment.

Through these kinds of an alternative approach for the production of renewable, biodegradable plastics, could make a huge difference in the treatment of waste management, PHB is widely used for various biomedical applications, food packaging, plant pots, packing of beauty products, pharmaceutical industries, etc. Further chemical modifications with PHB could result in properties of the polymer to great extent. Thus by increasing the production of PHB, could bring a positive environmental effect. In next coming years, statistics of plastic waste usage could drastically reduce to make a better, toxic-free, green environment.

Turritopsis nutricula (The immortal jelly fish)

There is organism in great wide world of ours ,Turritopsis nutricula defining itself as an immortal organism in animal kingdom.

Distribution : Originating from the Caribbean sea ,this unique creature has spread all over the world and now it has been found in both temperate and tropical regions,though it prefers warmer water.

SIZE : It is around 4-5 millimeter tall and wide.

This Immortal jelly fish has ability to reactivate its genetic instructions from earlier in its life cycle.Thus by escaping death it achieves potential immortality. In case of sure death,it revert back to young version of itself.

Now, let us try to understand its life cycle

Usually corals, sea anemones & jelly fish belongs to group of animals called cnidarians. Turritopsis nutricula belongs to hydrozoans. Some jelly fish change forms at different phases of their life cycle,while others remain in one form for their entire life.There are two basic body shapes which exit in the life cycle of jelly fish.

1. Polyp form ( which remains attached to surface)
2. Medusa form (which is a free floating,adult form)

Now let us the discuss the way that they are biologically immortal. Normally ,in hydrozoans life cycle ,Medusae ( matured jellyfish) spawn( fertilize) sperm and eggs. Any fertilized eggs becomes small larvae called PLANULA. when these planula settles somewhere below the sea,a new hydroid colony grows once again which are called as POLYPS ,these eventually grow in colonies and releases more medusae and these medusae develop into matured jellyfish and this is how the cycle is with both sexually and asexually reproduction.

However, Turritopsis are different.when they become threatened by physical activities or starvation , in such conditions they transform back to juvenile polyp stage by shinking their tentacles and body they sink to ocean floor to start a new cycle . over a time when a condition is favorable, new genetically identical clones of original jellyfish are released from polyp into sea and later polyp gets transformed into medusae and later medusae gets mature and develop into mature jellyfish and again if they are threatened ,the process can be repeated over and over. The way T.nutricula is able to live forever is through the process called as TRANSDIFFERENTIATION,it is process in which change of cell or tissue from one differentiated state to another OR it is the process of differentiation of a tissue-specific stem cell into another type of cell,for example,a bone marrow stem cell differentiating into a neuron.During this process it help them to survive by reducing metabolic requirements which help them to turn to polyp besides it can encyst. As a cyst T.nutricula can stay dormant for extended periods of time until environmental conditions are favorable to restart its life cycle. In most of jellyfish,once their adulthood is reached, asexual reproduction is no longer possible. But T.nutricula has two forms. Sexual reproduction and asexual reproduction, if there are enough sexually mature jellyfish, will be able to reproduce sexually and if, population density is low it can just revert back and can produce asexually,which is known as biologically immortal.

BENIFITS OF T.nutricula

THIS natural process( Transdifferentiation)has inspired many researchers to find stem cells to renew damaged or dead tissues in humans,so that many diseases like cancer and many more can be treated. This organism has found itself as great important. If a cell or organism undergoes aging , there are two biological processes. 1. Negative regulation of cell division. 2.Positive regulation of apoptosis may occur. Furthermore aging and neurodegenerative diseases are directly associated with these two biological processes while cancer ,aging does not happen hence these two processes are inversely associated. Thus T. nutricula has been a great tool in cancer ,aging and neurodegenerative related disorder.

Another interesting thing is these soft bodies rely on thousands of venom containing stinging cells on their tentacles called Cnidocytes, for their protection and prey capture. this venom ejected via a nematocyst , is a whip like a hollow tube which lies coiled under high osmotic pressure. when mechanical or chemical stimuli activate ( physical touch) ,an external trigger happens ,the lid of the cell breaks and opens,due to this sea water rushes in due to change in osmotic pressure ,this forces a microscopic barbed harpoon (nematocysts) to shoot out ,to penerate and inject into victim.

Humans might benefit from these stings of jellyfish, scientists are working on manipulating Cnidocytes to deliver medicine with nematocytes rarely 3% of size of typical syringe needle so it would help in the medical field. Besides it has harmful effects too ,the venom released by nematocysts causes contraction in heart muscles and even rapid death in case of rapid dose. Thus in such cases we should remove nematocyts by applying salt water followed by hot water and in these cases avoid applying cold water or fresh water.

One day in future humans may live for hundreds or even thousands of years and this may well be achieved because of research on immortal jellyfish . You could have ability to transform back into younger version of yourself enabling you to live forever.

REf:http://ed.ted.comhttps://youtu.be/yQduHyiWe9o ref:https://www.google.com/url?sa=t&source=web&rct=j&url=http://tnutricula-bethelu-corylundeen.weebly.com/unique-life-cycle.html&ved=2ahUKEwijt5-zoe_qAhWf4HMBHSrYCVYQFjAVegQIBRAB&usg=AOvVaw1m9nsa3uJn8oMawITwd_8h&cshid=1596183811583

What is Gene Editing?

Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism.

Rather than directions going one way from DNA to RNA to proteins,latest study shows that RNA itself modulates how DNA is transcribed using Gene Editing

Genome editing is technology that give the ability to change organisms DNA or can be altered at particular locations in genome.CRISPR-CAS9 is a recent genome editing which has been developed.It is short clustered regularly interspaced short palindromic repeats & is associated with protein 9.

CRISPR -CAS9 System consist of two components

1. DNA cutting protein called CAS9.
2. RNA molecule known as GUIDE RNA (sg RNA) bound together,they form a complex,that can identify & cut specific sections of DNA

How Does CRISPR -CAS9 Works?

CRISPR -CAS9 work similarly,A small piece of RNA with short ‘Guide’sequence that attaches to target sequence of DNA in genome.RNA also binds to CAS9 enzyme .As in bacteria,the modified RNA is used to recognize the DNA sequence,CAS9 enzyme cuts the DNA at targeted location .Instead CAS9 other enzymes like(cpf 1) can also be used.Once DNA is cut,uses the cells own DNA repair machinery to add or delete pieces of genetic material or to alter DNA by replacing an existing segment with customized DNA sequence.

Now let us have a clear idea by having a view on this below video.

Recently,CRISPR gene editing in US for the first trial in cancer patient suggets that technique is Safe.