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Researchers discover the mechanism of drug targets for COVID-19

 

In the latest issue of the journal Molecular Cell, a team of researchers from McGill University have uncovered the underlying mechanism through which drug targets control the progression of several inflammatory diseases, such as cancer, rheumatoid arthritis, and COVID1-9. These researchers have deciphered how cell receptors function within a patient’s body.

Whenever pathogens such as viruses attack human body, the body elicits defense mechanism. The complement system of cell receptors plays a pivotal role in eliciting a defensive response towards antagonistic pathogens. The pathogens that enter our body can either be bacteria or viruses. In the presence of a virulent attack, the complement system activates two membrane receptors, namely, C5aR1 and C5aR2. These were the findings of the international team of researchers.

Although the complement system should be activated in the presence of pathogens, there can be instances where the activation is excessive and uncontrolled. This is a dangerous situation as it can cause inflammation and even life-threatening complications in patients with COVID-19. Latest genetic technologies such as CRISPR are cutting-edge tools to unravel the exact functioning of C5Ar2 membrane receptor of cells, which were also observed through cryogenic electronic microscope. With this information, researchers identified therapeutic drug targets of COVID-19.

According to a noted medical professor, COVID-19 cases can be treated by blocking the activated expression of C5aR1 membrane receptor of cells. Moreover, Avdoralimab is a clinically tested drug that showed high efficacy in tackling severe pneumonia of COVID-19 patients. On the other hand, our current team of researchers were focused on targeting the expression of C5Ar2. For this purpose, they designed novel drug molecules that effectively clung to the receptor C5Ar2, blocking its activated expression and suppressing the related inflammation.

In molecular biology, it is a well-known fact that receptors surround human body cells. These receptors serve as drug targets, that is, the active ingredient of the drug exerts its pharmacological action on receptors, which also function as messengers. In other words, signals are transmitted and received by receptors of cells, which govern various physiological mechanisms in the human body. With the help of latest genetic technologies, our researchers could uncover important information pertaining to novel drug discovery and cell signaling processes.

 

 

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According to Cleveland Clinic, severe COVID-19 disease can be effectively controlled by steroid nasal sprays

 

Recently, a study conducted by Cleveland Clinic was published in the Journal of Allergy and Clinical Immunology. According to this study, severe COVID-19 infection was less likely to develop in subjects who used steroidal nasal sprays on a regular basis. These sprays were so effective that they reduced the chances of hospitalization and mortality by as much as 25%. Researchers at the Cleveland Clinic investigated 72,147 cases of COVID-19: all the patients were 18 years and above in terms of age. This is a very recent study that was conducted between April 1, 2020 and March 31, 2021.

The study cohort of patients included 12,608 hospitalized cases. Among them, as much as 2,935 cases were admitted to intensive care unit (ICU). Finally, the number of patients who died in hospital included 1,880. Interestingly, as much as 10, 187 patients were regularly using steroidal nasal sprays, which are nothing but corticosteroids administered through intranasal route. These patients used nasal sprays even before getting infected with COVID-19. Therefore, the chances of hospitalization declined by as much as 22% in these patients. Moreover, the need for ICU admission decreased by about 23% in these patients. Finally, the chances of dying in the hospital decreased by about 24%, as compared to patients who did not use steroidal nasal sprays.

These findings are quite encouraging to patients who regularly used intranasal corticosteroids. However, it does not mean that these corticosteroids are quite effective in treating and preventing COVID-19 disease. Yes, this seems contradictory but true. But several reports have endorsed the fact that in vitro use of intranasal corticosteroid would effective reduce the expression of ACE2, a protein receptor associated with SARS-CoV-2 virus. Thus, the virus would enter the cells and cause the spread of COVID-19. Nasal sprays contain corticosteroids, which belong to steroidal family of drugs. These nasal sprays are usually inhaled to control several nasal infections, such as stuffy nose, allergies, severe cold, etc.

Intranasal corticosteroids are either sold over the counter or with the help of prescription. However, researchers still do not know the exact mechanism through which these nasal sprays control COVID-19 infection. The findings of this study were coupled with the fact that the expression of ACE2 was highest in the mucosal lining of the nose. Based on this, researchers developed the following hypothesis: the viral load and the expression of ACE2 receptor can be suppressed in the nose with the use of intranasal corticosteroids, making them quite effective against severe COVID-19 infection. However, future studies must be conducted to validate the hypothesis.

 

 

 

 

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A nasal vaccine effectively prevents the transmission of COVID-19

 

The pandemic of COVID-19 has caught the world on fire! Not in the literal sense of the term, but it’s just plain breathing of SARS-CoV-2 virus that leads to the development of this deadly disease in the human body. Currently, most people across the world are aware of vaccines that fight COVID-19. These vaccines are injected through intramuscular route and not through the nose, although the virus simply enters the body through the nose. Most notable companies manufacturing COVID-19 vaccines are Pfizer and Johnson & Johnson.

Scientists believe that nasal vaccine would be more effective in battling COVID-19. This is because the mucosal lining of the nose will develop immunity against the virus, preventing it from entering the body and attacking the lungs. Recently, iScience journal has reported about how biomedical researchers of the University of Houston have developed a subunit of an intranasal vaccine. This vaccine is quite effective in boosting the immunity of the nose against pathogens inhaled by breathing.

These researchers believe that nasal vaccines are non-invasive, boosting both systemic immunity and the immunity of the mucosal lining of the nose. A large population of subjects can be immunized by nasal vaccines. However, they also highlighted a major drawback of nasal vaccines. Antigens cannot be efficiently delivered by mucosal route of vaccination. Moreover, these vaccines need to include suitable adjuvants that boost the immune system effectively without causing any toxic reaction in the subject’s body.

To solve the drawbacks of nasal vaccines, these researchers worked together with nanoparticle experts at the pharmaceutical college affiliated with the University of Houston, Texas. The team of pharmacists successfully captured the agonist that stimulated interferon genes (STING), which were present within liposomes of cells. Thus, they produced the adjuvant and christened it as NanoSTING. The immune response of the human body was stimulated by the adjuvant. The size of a NanoSTING particle is very small at about 100 nm. Nevertheless, it possesses properties that are completely different from that of a normal adjuvant.

 

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SARS-CoV-2 infection can now be controlled by a combination of new drugs

 

Although developed countries have now relaxed the rules of lockdown, the pandemic of COVID-19 is now complicated with an even more severe infection of SARS-CoV-2. This infection would have impeded the bounce back to normal life had there been no effective drugs to control the situation. However, this significant threat is now averted by some breakthroughs in recent research studies. Scientists have developed a combination of drugs named Nafamostat and Pegasys to control the pandemic. They are easy to use, effective, and fulfill the criteria of availability.

Laboratory synthesis of combination drugs

The combination of drugs named Nafamostat and Pegasys were quite effective in suppressing the life-threatening infection of SARS-CoV-2. These drugs were tested at the Department of Clinical and Molecular Medicine, Norweigan University of Science and Technology. A special cell culture was prepared to perform this experiment. The results indicated that the combination of drugs were quite effective, indicating that it is fit for human consumption.

Currently, COVID-19 infection is being controlled by administering monotherapy of Nafamostat. The efficacy of this drug is being extensively tested in laboratories of Japan and other Asian countries. Erstwhile, Pegasys was used to treat patients with hepatitis C. A combination of these two drugs seemed to have a positive impact on patients suffering from SARS-CoV-2 infection.

There is a factor named TMPRSS2 in our cells. It causes the replication of SARS-CoV-2 virus in cells. The combination drugs of Nafamostat and Pegasys effectively attacks this factor in cells, according to a leading professor of molecular biology at the laboratory.  This observation has become a major good news for researchers who are determining how effective is Nafamostat drug against COVID-19 infection.

A low dosage of combination drugs is needed against SARS-CoV-2 infection

The combination of Nafamostat and Pegasys drug is needed to low doses to tackle the serious infection of SARS-CoV-2. Not only has the clinical outcome of patients been positive, the side-effects of this combination therapy been minimum. These clinical advantages have been highlighted by a leading researcher at the laboratory. Although the combination of drugs is not cheap, it is indeed quite inexpensive. Thus, these life-saving drugs can be rendered to patients infected with SARS-CoV-2 all across the world. The only limitation is the fact that Pegasys drug is quite costly.

Scientists all across the world are working hard in the fight against COVID-19 pandemic, which has caused 4.55 million deaths all across the world. Moreover, there are many remote areas in this world where the cause of death is not known accurately, leading to a growing number of deaths unreported. Although an international team of researchers worked at the laboratory, the cohort of patients was only from Norway.

 

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The International Knowledge Civilization and Nanotechnology Conference (IKNC)

Harrisco is organizing the International Knowledge Civilization and Nanotechnology Conference on 19-21st August, 2021 in Seoul, South Korea. This interdisciplinary conference is inviting papers on public health, arts and humanities, religion, etc. The conference is specially focused on vaccines developed for the pandemic of COVID-19.

All overseas researchers can attend the event through online webinar. The conference papers will be reviewed by a strict panel of professors who have published papers in high impact international SCI journals. High quality selected papers will be published completed in a special issue of following SCI journals: The Journal of Dharma (Arts and Humanities), Iranian journal of public health (biomedical papers), and Ethiopian Journal of Health Development (Biomedical papers).

The last date for submission of Abstracts is 31st July, 2021. The last date for abstract acceptance is 3rd August, 2021. The due date for early registration is 6th August, 2021. All abstracts and papers will be checked for plagiarism by CopyKiller software. Complete papers can be submitted by 25th September, 2021. The conference is held in partnership with BIT Congress, an academic conference company in Beijing, China.

The 3rd IKNC conference invites interdisciplinary researchers and experts from both industry and academia. These people will present their work at a global platform and disseminate their knowledge pertaining to innovations. Novice researchers should use this platform for networking with the peer review team of eminent scientists who will also hold talks and presentations at the event.

How to submit the papers? This is the most frequently asked question by interested researchers. We have given all information on conference website www.iknc.org. The official language for abstract is English and researchers have to submit contact details of corresponding authors. The affiliation of authors should also be presented in the abstract. The wordcount limit for all abstracts is 150 words. In case of engineering papers, it should never exceed 250 words. All accepted abstracts need to receive Harrisco editing certificate by 5th August, 2021.

Authors whose abstracts have been accepted are requested to submit their full papers for the conference. A selected list of high quality papers will be published in full in the conference proceeding. All submissions have to be made in the Word template. Authors have to follow the guidelines of the journals that have collaborated with Harrisco for the conference. The guidelines will be provided to the authors with the letter of acceptance.

The online submission system will be accepting full papers till 25th September, 2021. The review process is rigid as the collaborated journals are high impact journals indexed by SCI, SSCI, A&HCI. After adhering to stringent review process, the selected high quality papers will be published after the author pay the additional publication fees.

It is mandatory to send all accepted papers to Harrisco for editing, and the company would be providing Harrisco editing certificate to these papers. Please refer to the company website en.harrisco.net. Both oral and video presentations would be for 20 minutes each. The authors would be given 5 minutes for Question and Answer session.

 

 

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In clinical drug trials of heart disease, women and older patients are under-represented


Doctors have to refer to randomized clinical trials to determine the best ways of treating patients. Furthermore, doctors refer to this information to also determine the most suitable drug that can be prescribed to these patients. Heart illness is the most common disease that afflicts the common man.

In recent years, it has been proven that the number of women having heart ailments would be greater than the number of men having the same ailment. Compared to younger people, older people have a greater tendency of developing heart condition. Does the data presented in clinical trials actually exhibit reality?

In most cases, the data does not actually represent the true picture. A new study was recently published in the journal Circulation: Cardiovascular Quality and Outcomes. Professor Quoc Dinh Nguyen works at Université de Montreal’s Faculty of Medicine.

He supervised a team of researchers who tested new heart drugs on mostly men (71 per cent); however, the majority of people afflicted with heart disease were mostly women. Moreover, the average age of male patients with heart disease was 63; however, the average age of patients who suffered the two most common heart diseases was in the range of 68–69 years.

In the past 20 years, the gender and age gap between subjects participating in drug trials has hardly diminished; however, the population seems to be aging rapidly. Professor Quoc Dinh Nguyen is a geriatrician who works at the Centre Hospitalier de l’Université de Montréal (University of Montreal Hospital Center).

In most drug clinical trials, both women and older patients are under-represented; therefore, both these groups of patients would receive comparatively lesser care. Unlike a young patient, an older patient does not really respond much to several treatments and medications.

Many-a-times, it is very difficult for patients to receive an exact dosage or intervention; moreover, each medication has a set of severe side-effects. However, we do not know the specific course of medication until and unless a large number of older patients are included in clinical trials. Most studies also do not include women in their clinical trials.

In the present scenario, the findings are obtained from a clinical trials conducted predominantly on male and younger subjects. These results do not really patient outcome of women and older subjects generally. Nguyen examined the issue closely while working as a geriatric resident.

They discussed with colleagues to realize that heart disease is a grey area to receive effective treatment. Resident physicians of other departments (anaesthesiology, psychiatry, emergency medicine, and cardiology) also collaborated in their efforts of improving the results.

A brief history

Nearly 20 years ago, researchers were concerned about how under-represented were several sections of the society, especially women. The results of clinical trials were quite often problematic in nature. With a team of researchers headed by Nguyen, we set off to find out if these practices had improved significantly.

The 25 most frequently cited clinical trials were examined closely every year. The examination period was of twenty years, ranging from 1996 to 2015. The data was published in the U.S National Health and Nutrition Examination Survey 2015-2016; this data compared how prevalent was cardiovascular disease in America . The data was classified in terms of following parameters: age and gender.

The research team examined data of following medical conditions: coronary artery disease, hypertension, heart failure, atrial fibrillation. This team also examined several risk factors contributing to cardiovascular diseases. This research team closely examined the correlation between diabetes and heart disease. Previous studies have reported that diabetic patients were more likely to suffer from coronary heart disease.

Bad results

Currently, a greater number of women and older patients are included in clinical trials; therefore, there has been a slight improvement in the representational bias of clinical trials. Eric Peters works as an anesthesiologist at the CHU Saint-Justine children’s hospital; he is the second author of this study.

Depending on our calculations, it would take another 90 years to understand whether clinical trial studies could present data correctly without bias. We need to correctly understand the factors contributing to coronary heart disease. The factors leading to aging population must also be considered in this situation.

After analyzing 500 clinical trials, we arrived at the following conclusion: only 29 percent of participants were women in this clinical trial. Moreover, the average age of participants was just 63 years. According to Nquyen, the reality is quite different in the hospital emergency rooms and departments; these departments are of internal medicine, cardiology, and geriatric medicine.

Women and older patients were hardly represented in clinical trials that were focused on determining the factors associated with CAD and heart failure. Women represent more than 54.6 percent of CAD patients. In clinical trials, more than 27.4 percent of participants for CAD were women.

Is heart disease really a man thing?

It is a general perception that men are afflicted with heart disease; however, most medical research studies have reported about results that are completely obsolete. Heart disease is the leading cause of women’s death in Canada. Fewer men die of heart disease in Canada. In general, heart disease would affect women at a later stage in life.

Nearly after 10 years, women would die of coronary artery disease and heart failure. There has been steady decline in the death caused by heart disease in women; moreover, death caused due to heart disease would be greater in men. One of the most common hypothesis is the fact that men receive timely medical treatment unlike women.

Why are women excluded from clinical trial?

In general, most women were excluded from clinical trials because it was advisable to give them medication during pregnancy; however, this principle should not have been applicable to drugs used for treating heart condition. This is because most patients with heart conditions are usually more than 60 years of age.

To select a woman to participate in clinical trial, we also need to consider the age of the woman. To ensure the adequate participation of women in clinical trials, older patients should be recruited. This is because women are afflicted with cardiovascular disease at a comparatively later stage of treatment, unlike men.

In general, it is difficult to conduct clinical trial of older patients. This is because most older subjects would find it difficult to move around; moreover, it is usually tougher for them to undergo a battery of clinical tests. Older the patients, higher would be their difficulty in moving around. In general, older patients do require several medications as they are afflicted with several ailments.

 

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Verapamil: an effective therapy for type 1 diabetes

To promote the functioning of beta cells and insulin in patients with type 1 diabetes, researchers have developed a novel strategy that minimizes the requirements of insulin and the incidence of hypoglycemia. These researchers have worked at the Comprehensive Diabetes Center at the University of Alabama in Birmingham, USA.

The journal Nature Medicine published these findings recently. Verapamil is the most commonly used drug for controlling blood pressure; it was approved for oral administration in the year 1981. Following the administration of verapamil, type 1 diabetes patients were able to produce greater amounts of insulin. Thus, their daily requirement of insulin was reduced substantially and their blood sugar levels were also in control.

The drug verapamil is not just safe and effective for type 1 diabetes but also a promising therapy that provides new hope to people living with this life-threatening condition. These were positive results confirmed in a human clinical trial that was randomized and double-blinded in nature; the clinical trial was controlled by placebo.

Verapamil has shown promising results in improving the function of beta cells in pancreas; the functioning of beta cells is related to the control of insulin production. Optimum levels of insulin ensure a good quality of life in patients. Under such a scenario, type 1 diabetes patients have new hope. It is otherwise difficult to control such a life-threatening condition that offers no hope.

Although this drug does not sound like a complete cure for type 1 diabetes, it is however a promising therapy for altering a life-threatening condition: type 1 diabetes. Such patients need to boost the production of insulin in their body in order to have better disease control.

A clinical trial was conducted on animal models in the year 2014. In this clinical trial, it was reported that the condition of type 1 diabetes could be completely reversed by administering verapamil. Then, they conducted a human clinical trial to determine the effects of this drug.

For more than three decades, the drug verapamil has been approved by the FDA for the treatment of high blood pressure. Current research findings are path-breaking in the sense that the drug is quite safe and effective in the treatment of type 1 diabetes patients. In patients with type 1 diabetes, the body’s immune system attacks beta cells of the pancreas.

These beta cells are responsible for the production of insulin. Insulin is the hormone that controls blood sugar levels in the patient. The production of insulin decreases substantially when the beta cells of pancreas are destroyed in the human body.

Consequently, blood sugar levels would rise in the human body and the patient would become extremely dependent on external sources for insulin. The function of beta cells can be preserved effectively when a patient is administered verapamil.

This drug induces the body to produce more insulin. In various clinical trials, it has been proved that the participants’ dependency on external insulin decreases substantially. Several individuals with type 1 diabetes can effectively regulate their blood sugar levels with this strategy.

In the human clinical trial, the drug verapamil was administered to 24 patients. These patients were in the age group of 18 to 45 years. Over the course of one year, verapamil was administered to 11 patients while a placebo drug was administered to 13 patients.

Only patients with type 1 diabetes were included in this clinical trial. They received insulin therapy to manage their condition throughout the duration of this clinical trial. The total daily dose of insulin was monitored in both the groups, that is, the group that received verapamil and the group that received placebo.

Moreover, we also monitored the amount of insulin produced in these groups. Factors such as the percentage of change in insulin and HbA1C levels were also monitored. There were patients who experienced hypoglycemic events; all such events of each patient were recorded in our human clinical trial.

A continuous glucose monitoring system was used to determine the healthy blood glucose levels of each patient. Patients with type 1 diabetes do have therapeutic options for hope. In fact, such patients should be able to deal with the illness in a promising way following the successful administration of verapamil.

Insulin dependency was substantially reduced in patients with type 1 diabetes following the administration of verapamil. The quality of life was significantly improved in these patients. The risk of comorbidities would be improved when the overall blood sugar levels was controlled in patients. Thus, a patient with type 1 diabetes would not develop several other comorbidities, such as kidney disease, blindness, and heart attack.

 

 

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Researchers develop a remote-controlled cancer immunotherapy system

 

An innovative ultrasound system has been developed to destroy genetically controlled processes in live T cells of the immune system. This team of researchers can destroy cancer cells. By developing non-invasive immunotherapeutic strategies, cancer cells can be manipulated and destroyed.

A novel strategy was used to improve the practical applications of mechanogenetics, which is a scientific discipline that improves the expression of genetics and activity of cells. T cells were mechanically destroyed by ultrasound. To genetically control cells, mechanical signals were used.

This experimental study establishes how mechanogenetics system is remote controlled and T cells are manipulated by chimeric antigen receptor (CAR). Cancer cells can be targeted and killed with this innovative approach. Researchers have modified CAR-T cells with mechano-sensors, genetically transducing modules.

This innovative approach was termed as therapy of CAR-T cells, which provided a paradigm shift for the treatment of cancer. Life-threatening complications develop when CAR-T cells are non-specifically targeted. The precision and the accuracy of CAR-T cell specific immunotherapy was improved in an unprecedented manner.

This innovative immunotherapy was used to target solid tumors. At the same time, off-tumor activities were minimized. Microbubbles were combined with streptavidin and they were attached to cell surface. Mechanical vibration and the stimulation of Piezo1 ion specific channels was performed by microbubbles when they were exposed to waves of ultrasound.

This led to the entry of calcium ions into the cell, triggering the following downstream pathways: the activation of calcineurin, the dephoshorylation of NFAT and the translocation into the nucleus. With recognition and destruction of targeted cancer cells, chimeric antigen receptor (CAR) was used to initiate the expression of genes.

 

 

 

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Cancer stem cells can now be destroyed by targeting metabolism

Cancer is a fatal illness with poor prognosis and survival rate, especially when it has progressed to a metastatic state. Scientists have not yet been able to decipher why patients become resistant to chemotherapeutic drugs and therapies. To address this objective, researchers worked diligently at  the Rogel Cancer Center—it is affiliated to the University of Michigan.

They made an important breakthrough in the year 2003. The lead supervisor was Dr S. Wicha, MD for the team of researchers. They found that there are cancer stem cells that act like a fuel within a tumor. Although this group of cells is immensely small, they are the ones that trigger the growth and metastasis of cancer.

The simple strategy was then to simply kill the group of cancer stem cells, and the long lost battle against cancer could be defeated easily. But, is this so easy to sound hopeful for cancer patients? Not really, cancer is such a condition that can relapse and attack patients even after they have been cured temporarily.

Currently, there has been an important discovery: cancer stem cells do not really exist in ONLY a single state but they are exhibited in different states; they are immensely plastic in nature. This implies that different forms can be easily adopted by cancer stem cells.

They could be in a dormant state for some point of time and then easily bounce back into uncontrolled growth, leading to formation of tumor. Multiplication and spreading, the two characteristic features of cancer stem cells, have been attributed to its most important property: plasticity.

Presently, patients are treated with targeted therapies for combating cancer. Although these therapies are effective, they have been successful in destroying tumor cells only for a certain period of time. There are many cases in which patients develop resistance to these targeted therapies.

What is the cause of drug resistance in cancer patients? Most scientists believe that drug resistance is triggered once again by cancer stem cells. Because cancer stem cells have high plasticity, they change their form completed when subjected to targeted therapies.

The resultant effect is that cancer stem cells are completely unrecognizable to these therapies following change of form. The patient thus develops resistance to therapies and the patients’ condition deteriorates consistently.

The conclusion: multiple stem cell therapies must be developed to effectively combat every form of cancer stem cell. This is a humungous task to achieve according to scientists at the Rogel Cancer Center. Cell metabolism is the key feature that controls the plasticity of cancer stem cells.

How do we eliminate the plasticity of cancer stem cells? Well, all we need to do is to target the metabolism of cancer stem cells. In other words, cancer stem cells can be effectively attacked by destroying cell metabolism.Mitochondria are cell organelles that supply energy to cells, irrespective of its kind. This includes cancer stem cells.

Mitochondria are organelles that perform cellular respiration, depending completely on the supply of oxygen. Cells derive energy from mitochondria, which converts sugar or glucose molecules into energy with the help of cellular oxygen.

Cancer stem cells are very unique due to its plasticity. When they are in the dormant state, they derive energy from glucose molecule. When they grow in a proliferative state, cancer stem cells depend completely on oxygen. Given the mechanism of deriving energy for sustenance and proliferation, researchers attacked both forms of cell metabolism observed in cancer stem cells.

They used a drug that is conventionally used for treating arthritis. This drug can effectively block the functioning of mitochondria in cancer stem cells. The levels of cellular glucose were further manipulated to obstruct the pathway of energy. They performed this experiment on cancer-stricken mice.

To their surprise, they had effectively knocked off all the cancer stem cells from the mice. This is an important breakthrough in cancer research, and the findings of this study have attracted a lot of attention. The complete experiment has been published in Cell Metabolism, a peer-reviewed SCI journal.

The general public may wonder why this study is so path-breaking and innovative in nature. Well, the conventional cancer therapy makes use of highly toxic chemicals to destroy cells in a tumor. Here, researchers adopted a completely different pathway to control the explosion of cancer stem cells: they destroyed the cell metabolism associated with the proliferation of tumor cells.

According to the lead researcher Dr. Wicha, further studies must be conducted to understand how metabolism controls the efficacy of human immune system. This could open a new chapter in cancer research: scientists could then focus their efforts on developing novel combinatorial techniques for cancer treatment.

These techniques must aim at effectively combining existing immunotherapies with anti-stem cell therapies. The concept is refreshing and offering new hope; however, extensive clinical trials must be conducted to validate results.

 

 

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Bioengineering proteins for personalized medicine

One of the latest developments in biotechnology is genetic engineering of cellular biology without the use of actual cell. This technique is termed as cell-free protein synthesis (CFPS). Chemicals, biomaterials, and medicines can be synthesized easily with this sustainable method. Cell-free systems have one major shortcoming: they cannot manufacture glycosylated proteins, that is, proteins attached to carbohydrates.

There are several biological processes involving the process of glycosylation. For the prevention and treatment of diseases, it is important to understand the reaction mechanism of glycosylation. Our main purpose is to control this process and synthesize glycosylated proteins through cell-free systems.

A team of researchers have collaborated to devise a novel approach and overcome this shortcoming. The team of researchers includes following people: Dr. Matthew DeLisa, Professor of Chemical and Biomolecular Engineering at Cornell University and Dr. Michael Jewett, associate professor of chemical and biological engineering at NorthWestern University.

They have devised a novel system by capitalizing on the recent advancements of CFPS technology. They have been successful in developing the missing glycosylated component through a simple reaction, which is carried out in “one-pot” system. After glycosylating the desired protein, it can be freeze-dried for later use. To use the protein for further synthesis, it can be reactivated by adding only water. The frozen protein would get thawed and retain back its natural properties at room temperature.

This team of researchers successfully published their paper titled “Single-pot Glycoprotein Biosynthesis Using a Cell-Free Transcription-Translation System Enriched with Glycosylation Machinery.” This paper was published in the latest July issue of Nature magazine. DeLisa and Jewett are the two senior lead authors of this study.

According to DeLisa, they have been successful in devising the world’s first glycosylated protein through cell-free technology. This protein could be very useful in various therapeutic areas, including the development of vaccines. This is because the protein can be freeze-dried and used in various locations, indicating the portability of these protein molecules. This is a path-breaking, powerful invention that can unshackle the existing models of manufacturing proteins.

With this technology, protein-based medicine can be easily developed and transported to remote areas. Thus, the lives of several people would be saved like never before. The cost of life-saving drugs and vaccines would decrease with this novel method of synthesis.

Local small-batch production of life-saving drugs can now be carried out in remote locations with low resources. Life-saving drugs have been costly till date; however, this technology aims to bring down the cost of these life-saving drugs. Therefore, poorer patients in remote areas can now have access to better healthcare.

DeLisa is a senior scientist who has spearheaded several research studies in biomedical eningeering. He has always focused on investigating the molecular mechanisms associated with the biogenesis of underlying proteins in a living cell.

It is important to note that the living cell is a complex environment wherein the main barrier is the cell wall. His lab has done extensive research on several living cells, such as Escherichia coli (E.coli). According to DeLisa, it is difficult to make important breakthroughs in cell synthesis as cell walls act as barriers in the transportation of materials, including proteins. The cell wall screens all the molecules before permitting them into the cell.

Jewett works at a sophisticated biomedical laboratory in NorthWestern University. A lot research studies have been conducted into advancing the technique of cell-free synthesis, that is, efforts were made to replicate the natural biomachinery outside the cell.

A collaboration between DeLisa and Jewett was nothing but fruitful in addressing their common goal: synthesis of glycosylated proteins through cell-free systems. According to Jewett, there is always a tug of war in engineering the cells of bacteria. The cell only wants to grow and survive. As a scientist, we are trying to maneuver its capability and reaction mechanisms.

To develop this novel method of synthesis, cell extracts were prepared by the team using a high quality strain of E. coli. This strain of E. coli was specifically optimized to grow in laboratory conditions.

This strain of E.Coli was termed CLM24. Key components of glycosylation were used to enrich this strain of E.Coli with high selectivity. A simple reaction scheme was used to synthesize the resultant extracts. The team has christened this synthesis process as “cell-free glycoprotein synthesis (CFGpS)”

What is the unique selling point of this method? Well, the cell-free extracts obtained by this method have the complete molecular machinery required for the synthesis and glycosylation of proteins.

Therefore, a molecular biologist has to simply include all DNA instructions required for the synthesis of a glycosylated protein in the desired form. Thus, CFGpS has completely broken the shackles of the existing cell-based method. Thanks to CFGpS method, we can now synthesize complex glycoproteins within a single day.

The further advantage of CFGpS method is the fact that it is highly modular in design; therefore, several varieties of glycoproteins can be easily prepared using a variety of diverse cell extracts. In this experiment, researchers used a lab-grown strain of E.coli for preparing cell extracts. It is important to note that E.coli is a simple cell, which cannot carry out glycosylation on it is own.

Nevertheless, we were able to develop CFGpS platform by using this simple strain of E.coli. This implies that a completely blank slate of E.coli cells could be engineered biologically to develop into a glycosylated system of desired capacity. With this method, the structure of carbohydrates can not only be controlled but also be manipulated to suit our needs.

We can synthesize highly complex glycoproteins. This was not possible till date with the existing cell-based systems. The field of personalized medicine is growing by leaps and bounds in developed countries, including the USA. This is a very attracted protocol for on-demand drug synthesis.

A simple test tube could now be used instead of a large bioreactor for drug synthesis. The whole concept of personalized medicine has received a paradigm shift with this novel method. Based on the physiology of a patient, we can now develop a unique protein molecule for drug delivery.