Artificial Blood : Substitute of Red Blood Cells

Blood:-

It is a fluid connective tissue which mainly comprises of 4 components :- 1. Plasma , 2. R.B.C. , 3.W.B.C. ,4. Platelets.  As a connective tissue it has many function , out of which oxygen and carbon dioxide transportation is most important.

Artificial Blood :-

Many diseases like hiv ,terror attack ,blood loss injury and decline in natural blood donation,  etc . are main reasons that led development of infection safe blood substitute  { mainly RBC  substitute } .that is referred as Artificial blood .

It's aim is to provide alternative to blood transfusion.

There are 3 categories of artificial blood :- 1.HBOC  ( Hemoglobin Based Oxygen Carrier ) , 2.PFBOC  (Perfluorocarbon Based Oxygen Carrier ) , 3. Hematopoietic Stem Cells.  These categories are based upon chemicals that can carry and release oxygen.

1 .HBOC 

Hemoglobin forms 33% of RBC by mass . Unmodified Hemoglobin is not used because Of it's clinically unsuitable lifespan and it can damage our kidneys as free Hemoglobin take up nitric oxide causing vasoconstriction .

Ways of modification of Hemoglobin are :- genetically engineering version,  cross linking,  polymerization and encapsulation. 

Firstly, Hem Assist, diaspirin crosslink Hemoglobin  (DCLHb)  was developed but it failed due to morality due to savere vasoconstriction. Hemolink, it is Hemoglobin solution that has crosslink an o- rafrinose polymerised human Hemoglobin, but failed in 2003 due to its unsafe nature .Hemopure, crosslinked bovine (cow) Hemoglobin in salt solution for human use . There was also Oxyglobin for veterinary purpose. Polyheme, human Hemoglobin is polymerised then incorporated in electrolyte solution but rejected by fda in 2009 . After that ,many attempts were made but all were unsuccessful but still there is hope for future achievements.

2.PFBOC 

Perfluorocarbonchemicals are water insoluble thus they are mixed with nutrients and salt and form mixture that has 80 components . PFC particles are about 1/40 th in diameter of RBC thus they pass through capillaries. PFC solution is used in liquid breathing that act as intravascular oxygen carrier to temporarily augment oxygen delivery to tissue and carry more oxygen. 

PFBOC are solely man made and they should be removed within 480 hours as exhalation. 

First artificial blood was Perfluorocarbon Based product called as Fluosol-DA-20 developed by Green gross of Japan approved by FDA  in 1989 but withdrawn in 1994 due to  complexities in use and side deflects. 

Examples :- oxycyte, PHER-OXYGEN,  Perforin, NVX-108, etc 

3.Hematopoietic Stem Cells 

It is the possible mean of producing transferable blood. There was production of mature human blood cells using hematopoietic Stem Cells { these are removed from umbilical cord between mother and featus after birth using blood pharming } . The stem cell culture has same Hemoglobin content and morphology and life span as mature blood cells.  It was first used in U.S. Department of defence in 2010 

It is being used in humans from 2013 . 

In future,  we will further see  more new innovations in this concept for human welfare. 

Neurological Biomarker in Suicidal Thoughts : found in Brain scanning

Human is just like the computer whose CPU is brain .

Everything happening in our  body is just under neurological control. Researchers are going on various concept related to brain , out of which recent studies has find out The Potential Biomarker in Suicidal Thoughts by scanning our Brain.

It is diagnosed with PTSD  { Post Traumatic Stress Disorder } and MDD { Major Dipressive Disorder }
These both elevate suicidal risk like suicidal ideation,  attempts and death ,etc .
This situation is detected by noticing significantly elevated level of common receptor called mGluR5  { Metabotrophic Glumate Receptor 5 }  which is somehow linked with severity of PTSD  symptoms  like mood swings and anxiety, etc .
mGluR5 is very common receptor - docking port of other molecules found throughout the brain that is involved in emotional, thinking and memory  and other functions to regulate neurotransmitter that transmit message among neurons.

Using PET  { Positron Emission Topography}, researchers had found mGluR5 density in 5 frontal and limbic region of brain that is responsible for suicidal thinking. Then study has done on  29 participants with PTSD and 29 participants with MDD and other 29  healthy controls then concluded that mGluR5 availability in individuals with PTSD was significantly higher in all five brain regions, compared with healthy controls, as well as in three brain regions, compared with individuals with MDD. In particular, mGluR5 upregulation in all five brain regions was associated with self-reported suicidal ideation on the day of the brain scan in individuals with PTSD, but not in individuals with MDD. Moreover, higher mGluR5 availability was associated with mood disturbances in the PTSD group, whereas lower mGluR5 availability was associated with mood disturbances in the MDD group.

At last, the findings suggest that downregulating mGluR5 might decrease suicidal ideation and related symptoms in individuals with PTSD.

OBESITY : As Genetic Disorder

Obesity:- A disorder involving excessive body fat that increases the risk of health problems.

We all are aware about the cause of obesity that mainly include our living style , our environment,  our food habbit, etc .These activities only contribute 60 % in causing obesity but the rest of 40 % is due to genetic disorder. 

However, recent studies suggest that genetics contribute in  obesity with the discovery of more than 50 genes that are strongly associated with obesity. While changes in the environment have significantly increased obesity rates over the last 20 years, the presence or absence of genetic factors protect us from or predispose us to obesity. “Genes may co-determine who becomes obese, but our environment determines how many become obese That’s why obesity prevention efforts must focus on changing our environment to make healthy choices easier choices, for all.

There are 2 ways of genetic mutation i.e. 1.single gene mutation and 2.multipe gene mutation 

■Single gene mutation {Monogenic Mutation }:-

It is the deletion or addition or any other changes that occur on single gene which further affect the coding of protein and led to malfunctioning which causes obesity. It is severe form of obesity that is mostly seen before 2 years of age . This mutation is included in leptin Receptor, proliferate opiomelanocortin and there are 2 gene on chromosome 18 close to melanocortin 4 Receptor gene which causes Monogenetic obesity. 

It includes syndrome like Prader willing and Barde Biede .


■Multiple gene mutation :-
It is due polymorphism in gene due to which multiple genes predipose to gain weight by controlling metabolism under dietary conditions. 

FTO { Fat Mass and Obesity Associated Gene}:-

It is gene that is present on chromosome 16 that is found in 43 % of the world's population that predipose to gain weight . This gene is dependent on our family inheritance. In this case , if both the parents are obese then the upcoming 80%  generation is obese and 10 % would be normal and 10 % less than normal weighted .

Effect of this gene are :- 1. Increases hunger level ,

2. Increases caloric intake, 3. Reduce satiety, 4. Reduce control over eating, 5. Increases tendency to be sedentary , 6. Increases tendency to store body fat .

• Obesogenic and leptogenic genes response to weight loss and it's management. 

• There are 41 sites in human genome that cause obesity under favourable conditions. 

• Scientists had found additional locci and quantitative trait locci for BMI .

• There are 30 genes on chromosome 12 that is responsible for BMI of our body .

• SNPS increases disease risk that mean obesity is accompanied mental retardation and reproductive anomalies.

Thrifty Gene Hypothesis Postulates :- 

It states that due to dietary scarcity during human evolution which had made population prone to obesity as during this period our body adapted to store fat as source of energy. 

• DNA methylation is a form of epigenetic modification that controls whether genes are turned on or off.

There are total 79 syndromes responsible for  obesity . Out Of the 79 syndromes, 43 have never been assigned a name, the review found. And scientists have fully figured out the underlying genetics of just 19 of the syndromes. For others, scientists have reported a partial understanding of the underlying genetics, according to the review. However, the researchers identified 22 syndromes for which scientists knew nothing about the gene or the chromosome associated with them.

Finally we can found that risk of obesity cannot be determined by only genotype  but also by gene - gene interaction. Rather than genetic reason,  overall cause of obesity is genetic environment interaction which interplay between genetic makeup and life experiences

CAR-T Cell Therapy : A Cellular Immunotherapy In Cancer

Cellular Immunotherapy:- 

It is the innovative way in treatment of the cancer in which our body's own immune system participate to fight against cancer . In this our body cells them self detect and destroy  cancer cells.

CAR-T Cell Therapy :-

CAR-T cells { Chimeric Antigen Receptor T- Lymphocyte }  therapy is basically renowned in cellular Immunotherapy as  a game changer in the treatment of cancer. This therapy is based on biotechnology i.e. recombinant technology.  In this therapy important step is tumor immuno suppression and then reactivate the immune system.

Process In CAR-T Therapy :-

1.T lymphocytes are  extracted from WBC present in  blood of the person .

2. Then T lymphocytes undergo genetic engineering in which changes are made in surface of Receptor of       T lymphocytes  . It can be made by combination of 2 functions  in an  synthetic Receptor , this is done by moeitis or pieces of proteins and form recombinant proteins, this is known as " Chimeric Receptor "

 ● First of all , CAR ectodomain is derived from          recombinant single change variable fragment as  ScFv of monoclonal antibody . Thus, this domain      provide target recognition. 
 ● secondly, Intracellular domain is derived from      costimulatory receptor or other immune Receptor.      Thus, this domain activate T lymphocytes .
● Both the domains are grafted on either side of         spacer and transmembrane domain .
Thus , we finally obtain synthetic CAR transgene .

3. Then , this CAR-T cells get multiplicated and this is to be done once during lifetime  as our immune   system start generating new CAR-T cells itself .

Working of CAR-T cells :-

This Receptor specifically target on surface tumor antigens independent of MHC Antigen.  Activated CAR-T cells release cytotoxic compound like  Perforin and Grazyme B. And also activate , proliferate inflammatory cytokines help in curing tumor cells .

This therapy is useful in treatment of ALL { Acute lymphoblastic leukemia and after too many hardships it works on malignant gliomas i.e. solid tumor.

Before this xenograft mouse model have been employed in preclinical studies to assess tumor killing ability of CAR-T cells in vivo .

There will be many more development in curing cancer in future.