Stress can throw off circadian rhythms and lead to weight gain – Medical News Today

Scientists at Weill Cornell Medicine in New York say that stress-induced circadian clock disruptions may influence weight gain.

A study published in June showed that mice with artificially increased stress levels and interrupted hormone releases experienced an increase in fat cell growth. Its results appear in Cell Reports.

The second study, published in August, found that fat cell precursors commit to becoming fat cells only within a few hours at night. This work appears in the Proceedings of the National Academies of Sciences (PNAS).

Mary Teruel, PhD, associate professor of biochemistry at Weill Cornell Medicine, was the senior author of both studies.

A lot of forces are working against a healthy metabolism when we are out of circadian rhythm, Dr. Teruel said in a press release. The more we understand, the more likely we will be able to do something about it.

In the Cell Reports study, Dr. Teruel and her team implanted pellets with glucocorticoids, a type of stress-related hormone, in mice. This was to mimic the effects of chronic stress or Cushings disease.

Cushings disease triggers elevated levels of cortisol, the bodys stress hormone.

The pellets released glucocorticoids under the skin of the mice at a steady rate over three weeks. The researchers also observed control mice with typical daily stress hormone fluctuations.

Although all the mice ate the same healthy diet, the mice with pellets ended up weighing over 9% more than the control mice.

The researchers observed whether the weight gain was from fat expansion and found that the brown and white fat of the pellet mice had more than doubled. Their insulin levels spiked as well.

To the teams surprise, the metabolic disturbances kept blood glucose levels low. Further, the disruptions prevented fat from accumulating in the blood or liver.

When the researchers removed the pellets, these changes reversed immediately.

Dr. Teruel explained to MNT: We saw this in our paper, basically, once we stopped flattening the corticoids, [the mice] started reversing [the fat mass gain] and the hyperinsulinemia went away so that increased insulin that seems to be causing the fat mass gains that went away when the restored rhythm.

She added that this study indicates that chronic stress can make weight gain more likely, even with a healthy, low fat diet.

If you stress the animals at the wrong time, it has a dramatic effect. The mice arent eating differently, but a big shift in metabolism causes weight gain, Dr. Teruel said in the release.

Dr. Teruels research team hopes that their findings lead to developing drugs that could help reset circadian rhythms to help people with obesity.

We dont know enough [yet], but one would think cortisol receptor antagonists or [] things that restore the cortisol rhythms would probably help a lot.

Dr. Mary Teruel

Experts understand that flaws in circadian clock genes can alter cell differentiation in fat, immune, skin, and muscle cells.

The PNAS study revealed that even though differentiation happens over a few days, differentiation commitment happens within only a few hours. The findings also show that daily bursts of cell differentiation seem to be limited to evening phases when people are normally resting.

The decision to become a fat cell happens rapidly over 4 hours. It is like a switch, Dr. Teruel said.

Medical News Today discussed this with Dr. Mir Ali, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California.

Dr. Ali explained how fat cells come to be: Fat cells form from [an] adipocyte progenitor cell or a type of cell that has not differentiated into its final form. The form it takes [to become] a fat cell depends on the hormonal and chemical stimulation it receives.

In the study, Dr. Teruel and her partners used fluorescent markers to observe daily fluctuations of fat cell production.

The researchers attached a red fluorescent protein to a protein that regulates circadian clock genes. They also attached a yellow fluorescent protein to peroxisome proliferator-activated receptor gamma (PPARG), a protein that controls fat cell production.

They discovered that during the rest period of the day, a certain circadian protein CCAAT enhancer binding protein alpha induces a rapid increase in the protein that regulates fat cell production.

The researchers also found that when PPARG levels hit a certain threshold, individual fat precursor cells irreversibly commit to differentiate within only a few hours, which is much faster than the rest phase and the overall multiday differentiation process.

Dr. Teruel and her team believe that working with this time window may open therapeutic strategies to use timed treatment relative to the [circadian] clock to promote tissue regeneration.

Dr. Ali said: These studies are interesting in that they show the timing and length of stimulation affect the formation and growth of fat cells. The implications of this are that if we can find a way to safely influence the cell to grow or not grow, it may affect obesity in humans.

However, he believed that more extensive research is needed to make the studies findings applicable to humans.

Dr. Teruel told MNT that she and her co-authors were just trying to work on basic mechanisms [] Right now, we need to show this is really a mechanism that happens []

The researchers do plan to replicate the studies with people. We are looking at protein ribbons and humans using saliva samples, Dr. Teruel shared with MNT. Were planning to do those kinds of experiments.

Their main objective, she said, is to figure out ways to restore circadian [rhythms].

Dr. Teruel mentioned that currently known strategies, such as meditation and regular sleep in the dark may help.

She expressed hope that there could be some pharmacological ways [to] fix this in the future as well.

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Stress can throw off circadian rhythms and lead to weight gain - Medical News Today

Is Oxygen the Answer to Long Covid? – WIRED

She was dead tired but couldnt sleep, couldnt think straight, and could barely walk. The muscle pain in her arms and legs was so bad that she spent days in bed. When she did get up, she used a wheelchair. And she couldnt focus on even the most trivial tasks, let alone work. But doctors couldnt agree on what was wrong with 41-year-old Maya Doari.

The sac-like tissues surrounding her heart were inflamed, of that they were sure, so she was diagnosed with pericarditis. But when her left hand turned blueon and off for monthsher physicians told her dont try to understand, because they no longer could.

Neither could a vocal cord specialist, who mocked her when she tried to speak, hardly able to muster a soft whisper. And when she attempted physical therapy to relearn how to walk, she experienced seizures. I asked, Dont you think it could be connected to the Covid I had? They said no and sent me home, saying its psychological.

But her condition was real. And it may not be as unique as it sounds.

Three months earlier, Doaria homeopath who lives in a small village near Jerusalemhad come down with a 24-hour fever and strong bone pain. It was Covid. But after these initial symptoms passed, days later the real symptoms began. My doctors said my case was the worst long Covid they had ever seen.

Covid can have many lingering effects, and for now at least, long Covid is the catch-all phrase used to describe them. Over 200 symptoms have been gathered under this umbrella term, ranging from the commontiredness, fever, and brain fog, or difficulty thinkingto the more striking, like Doaris seizures and speech problems. The exact prevalence of long Covid is debated, but millions around the world have reported having lasting symptoms.

Yet today, a year after her long Covid symptoms arrived, Doari says they are 98 percent gone, a turnaround tied to new research that may have uncovered a promising long-Covid treatment.

Its called hyperbaric oxygen therapy, and in July Israeli researchers published a studywhich Doari participated inthat showed using this technique to deliver massive amounts of oxygen to the body appears to alleviate many of Covids cognitive and physical after-effects.

Hyperbaric oxygen therapy has been around for decades and typically entails getting into a hard-shell, pressurized tube where the air pressure is up to three times that of our atmosphere, and then breathing in concentrated oxygen. Originally intended to treat the bends, a dangerous condition that can result from deep-sea diving or high-altitude mountaineering, its now used to promote healing in cancer patients and burn victims and is even used by athletes eager for a performance boost or people looking to remove plastic surgery scars.

Breathing in concentrated oxygen under pressure raises the amount of it that dissolves in the blood, meaning that more oxygen gets delivered throughout the bodys tissues. This can then boost the power of the immune system and stimulate the release of stem cells and substances called growth factors, which help tissues heal.

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Is Oxygen the Answer to Long Covid? - WIRED

GlyNAC supplementation reverses aging hallmarks in aging humans – Baylor College of Medicine News

A randomized, double blind human clinical trial conducted by researchers at Baylor College of Medicine reveals that supplementation with GlyNAC a combination of glycine and N-acetylcysteine improves many age-associated defects in older humans and powerfully promotes healthy aging. This is relevant because until now, there have been no solutions toward improving many of these age-related declines in people. Published in the Journal of Gerontology: Medical Sciences, the study shows that older humans taking GlyNAC for 16-weeks improved many characteristic defects of aging. This includes oxidative stress, glutathione deficiency and multiple aging hallmarks affecting mitochondrial dysfunction, mitophagy, inflammation, insulin resistance, endothelial dysfunction, genomic damage, stem cell fatigue and cellular senescence. These were associated with improvements in muscle strength, gait speed, exercise capacity, waist circumference and blood pressure.

This is the first randomized clinical trial of GlyNAC supplementation in older humans, and it found that a wide variety of age-associated abnormalities improved in older adults supplemented with GlyNAC, while no improvements were seen in those receiving placebo, said corresponding author Dr. Rajagopal Sekhar, professor of medicine - endocrinology, diabetes and metabolism at Baylor.

The improvements in oxidative stress, glutathione levels and mitochondrial function in the muscle tissue of older humans taking GlyNAC were similar to the improvements in organs such as the heart, liver and kidneys of aged mice supplemented with GlyNAC as reported in the researchers recent publication. Taken together, the results of these studies show that GlyNAC supplementation can improve these defects in many different organs of the body. GlyNAC supplementation in aging mice increased their length of life mice by 24%, said Sekhar. Gait speed is reported to be associated with survival in older humans. Our randomized clinical trial found a significant improvement in gait speed in older humans supplemented with GlyNAC. This raises the interesting question of whether GlyNAC supplementation could have implications for survival in people. For the last 20 years, Sekhar has been studying natural aging in humans and animal models to understand why age-related declines occur and how to correct them. His work brings mitochondria, known as the batteries of the cell, as well as free radicals and glutathione to discussions about how they are connected. Sekhars work and discoveries could also help explain why we age and how to improve health while aging.

Mitochondria dysfunction, oxidative stress and aging

Mitochondria generate energy needed for supporting cellular functions. Therefore, normal mitochondrial function is critically important for a healthy life. Sekhar believes that improving the health of malfunctioning mitochondria in aging is the key to healthy aging. Energy supports life and mitochondria provide energy. I believe that mitochondrial health is vitally important to our well-being, and maintaining mitochondrial health as we age should be a high priority in our efforts to improve overall health, said Sekhar.

However, the ability of mitochondria to work well declines as we age. How to improve the ability of these failing mitochondria to work is not well understood, and therefore no solutions have been available. Sekhars group discovered earlier that supplementing GlyNAC in aged mice corrected malfunctioning mitochondria. However, to definitively determine whether GlyNAC supplementation benefited people, a placebo-controlled randomized clinical trial was required.

Sekhar and his team conducted and completed such a randomized clinical trial which found that older people have widespread mitochondrial damage and other age-associated defects compared to young people. After 16-weeks of GlyNAC supplementation, mitochondrial function of older people improve toward levels found in young people. This was accompanied by improvements in multiple additional outcomes as reported in the publication. Analysis of the molecular data from the trial suggests that the GlyNAC supplementation is able to fill cells with younger and more efficient mitochondria. Collectively these exciting new discoveries hold great promise for improving our mitochondrial and general health as we age, Sekhar said.

A second vital benefit offered by supplementing GlyNAC is that it also helps protect the body from an important problem called oxidative stress. Oxidative stress is caused by high levels of toxic waste products known as reactive oxygen species or free-radicals. Oxidative stress can damage our cells, membranes, lipids, proteins and DNA, and is very common in aging. Glutathione is a natural antioxidant. Glutathione is made every day inside our cells and it works by protecting cells from harmful oxidative stress. However, in older people, glutathione levels are very low and the harmful oxidative stress is very high. GlyNAC supplementation corrects glutathione deficiency and lowers oxidative stress in older humans back to youthful levels, thereby solving both problems.

Sekhar believes that the restoration of mitochondrial health and correction of oxidative stress with GlyNAC supplementation are two powerful reasons which help explain why so many other age-related defects improve. It also accounts for the wide spectrum of health benefits.

Taking GlyNAC is not the same as taking glutathione: Introducing the Power of 3

It is really important to understand that this trial supplemented GlyNAC, and did not supplement glutathione, says Sekhar. This is because our body does not get its glutathione from food, but the body has to make its own glutathione every day. All our organs maintain different levels of glutathione in a delicate balance that favors health. Too little glutathione cannot fight the harmful oxidative stress, and too much glutathione could lead to harmful reductive stress, said Sekhar. This is why GlyNAC is a natural solution for correcting glutathione deficiency, because it provides the raw materials to help cells to make their own glutathione in just the right amount. We have seen that this repeatedly in all our prior studies supplementing GlyNAC, including this trial.

One of the intriguing questions from this trial is why so many improvements occur toward promoting health. We believe that this is due to the combined effort of three separate components glycine, cysteine (from NAC) and glutathione, and not just due to glutathione itself. Glycine and cysteine are both very important for cellular health on their own, and GlyNAC provides both. Glycine and cysteine are building blocks to form glutathione, which also has health benefits. We believe that the improvements in this trial and in our previous studies are the result of the combined effects of glycine and NAC and glutathione, and we refer to this combination as the Power of 3, said Sekhar.

GlyNAC improves several aging hallmarks in aging

The population of older adults is expected to exceed 2.1 billion by 2050, according to the World Health Organization. This predicted increase in the older human population will result in a rise of the need for healthcare and will intensify the stress on healthcare systems around the world. To understand what causes unhealthy aging, scientific research has identified nine aging hallmarks that represent specific defects that are believed to contribute to health decline while aging.

It is believed that correcting aging hallmarks could help people age in a healthier way, Sekhar said. However, we do not fully understand why these aging hallmarks occur in the first place, and therefore there have been no proven solutions via human randomized clinical trials to improve or correct aging hallmarks in aging humans.

The aging hallmarks that improved are mitochondrial dysfunction, altered intercellular communication, nutrient sensing, loss of proteostasis, genomic instability, cellular senescence and stem cell fatigue. The study participants were instructed not to change their usual diet or physical activity; therefore, nothing changed except for the GlyNAC supplementation. This tells us that benefits were due to GlyNAC supplementation. But we were really surprised to see so many aging hallmarks improve. This level of improvement offers clues as to how and why these aging hallmarks may be connected to one another, says Sekhar.

GlyNAC improves muscle strength in aging

GlyNAC supplementation improved muscle strength in the upper and lower extremity and a trend toward increased exercise capacity. These findings could have additional implications for improving the health of older humans, especially in terms of being able to be more physically active, said Sekhar.

This study was effort intensive and took many years to complete. I take this opportunity to thank all my co-investigators, nursing staff, and everyone who helped with this trial. I especially thank all the trial participants who volunteered to participate in this research, Sekhar said.

Sekhar led the study team consisting of Premranjan Kumar, Chun Liu, James Suliburk, Jean W. Hsu, Raja Muthupillai, Farook Jahoor, Charles G. Minard and George E. Taffet, all at Baylor College of Medicine. For this trial, Sekhar received funding support from the National Institutes of Health/National Institute of Aging, and philanthropic support from the McNair Medical Institute at the Robert and Janice McNair Foundation in Houston, TX.

Baylor College of Medicine holds a patent on GlyNAC, which has been licensed to Nestl Health Science. GlyNAC is marketed in the United States by Nestl Health Science under the name CelltrientTM Cellular Protect. Nestl Health Science did not provide financial or material support for this research work.

As he moves forward, Sekhar plans to expand on his work to understand more about the health benefits of GlyNAC supplementation on cells, tissues and organs of the body. He plans on seeking funding to conduct larger clinical trials in more typical older humans to increase our understanding of how GlyNAC could improve health in aging. Additionally, as reported in their previously published exploratory study, Sekhars group found that GlyNAC supplementation in older humans could improve memory and cognition. He has studied this further in aged mice and found that GlyNAC supplementation appears to correct multiple age-related declines directly in the brain, and was associated with improvements in memory and brain health a report on these emerging new and exciting findings is in development.

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GlyNAC supplementation reverses aging hallmarks in aging humans - Baylor College of Medicine News

Bluebird Bios first gene therapy for rare blood disease wins FDA approval – The Boston Globe

Zynteglo could change that by providing a healthy copy of the essential beta-globin gene to blood stem cells, allowing their bodies to make healthy blood cells and eliminate the need for regular transfusions. In clinical trials, about 90 percent of patients who got the one-time therapy no longer needed transfusions to treat their disease.

Dr. David A. Williams, chief of hematology/oncology at Boston Childrens Hospital, was impressed with the effectiveness of the therapy. This is clearly very clinically meaningful for the patients, he said.

Before Zynteglos approval, stem cell transplants were the only potentially curative options for people with beta thalassemia, but many people with the condition are unable to find a genetically-matched donor. Doctors who treat people with the condition were excited by the approval of Zynteglo.

This is really huge. The idea that now you have the option of a curative therapy for all patients is enormous, said Dr. Sujit Sheth, chief of the division of pediatric hematology/oncology at Weill Cornell Medicine.

Sheth noted that stem cell transplants carry the risk of immune rejection, which can be deadly. You have a far lower risk of complications from getting your own cells back than if youre getting it from someone else, he said.

Bluebird estimates that there are as many as 1,500 people with transfusion-dependent beta thalassemia in the United States. Thomas Klima, the firms chief commercial officer, told the Globe that as many as 850 of them may qualify for Zynteglo.

The firm expects about one-third of those patients to be pretty eager to get therapy, Klima added. Another third may need more information and time to think it over, and the final third may consider their current transfusion treatments fine.

Despite the relatively modest numbers of patients who may get the therapy, the approval is a major win for Bluebird, which has faced a series of troubles over the past few years that brought its stock falling about 98 percent from its peak in 2018. The firm said it would lay off 30 percent of its employees in April and warned investors it only had enough cash to last until the first half of 2023.

Over the last year we faced so many challenges, Klima said. But the group thats here now and the group thats getting ready to launch our gene therapies couldnt be more thrilled.

The therapy is made from a patients own blood stem cells collected during a hospital visit and shipped to the contract manufacturing firm Lonza, just south of Houston, TX. Once there, scientists will treat the cells with Bluebirds gene therapy, made from a lentivirus that shuttles the beta-globin gene into the cells.

After a quality check, cells are shipped back to the hospital. Before getting the altered cells infused, a patient must undergo chemotherapy to clear out space in their bone marrow for the new cells to engraft. Once they take hold, they will make new healthy red blood cells for years, potentially indefinitely.

Craig Butler, national executive director of the Cooleys Anemia Foundation a nonprofit patient organization for thalassemia is excited for people to have an alternative to time-consuming transfusions.

Its usually a full day process for someone, which means that theyre missing a day of work or a day of school, he said. The approval of Zynteglo means that they will no longer have to be bound to transfusions for the rest of their lives.

Wanda Sihanath, 26, was one of the first people to get the therapy in a clinical trial in 2014. She hasnt needed a transfusion in over eight years. It feels like really great not to be tethered to hospital and having to check in at least once a month, she said.

Sihanath, who lives in San Jose, was excited to hear that Zynteglo is approved. I am super stoked, she said, and is hopeful that the therapy will help untether people from regular hospital visits.

But the chemotherapy Sihanath got to prepare her body for the gene therapy may have affected her fertility, and she wishes she would have sought a little more counseling about getting the procedure at a young age. Doctors say that some young people may wish to hold off on getting the therapy.

The therapy will only be offered at a small number of centers across the United States, including at Boston Childrens Hospital.

Colleen Dansereau, the hospitals director of clinical operations of the gene therapy program, anticipates that the hospital will be ready to start the treatment procedure for a patient by September. But she anticipates it could take longer for Bluebird to get ready and for insurers to guarantee payment for the therapy.

Boston Childrens regularly provides transfusions for about 45 people with the condition, plus additional patients referred from other centers, Dansereau said.

The hospital may end up treating additional patients with beta thalassemia from other parts of the world where the disease is more prevalent, including the Middle East and Southeast Asia, Dansereau added. We anticipate that we could have an increase in our international services for this particular product.

Zynteglo is the third gene therapy approved by the FDA. The Roche gene therapy Luxturna, which treats a genetic eye disease, was approved in 2017 with a price tag of $850,000. The Novartis gene therapy Zolgensma, which treats spinal muscular atrophy, was approved in 2019 with a cost of $2.1 million. The FDA could approve a fourth gene therapy, also made by Bluebird, in September.

Ryan Cross can be reached at ryan.cross@globe.com. Follow him on Twitter @RLCscienceboss.

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Bluebird Bios first gene therapy for rare blood disease wins FDA approval - The Boston Globe

Molecular Map Reveals Insights Into the Genetic Drivers of CLL – The ASCO Post

By The ASCO Post Staff Posted: 8/16/2022 2:43:00 PM Last Updated: 8/16/2022 3:15:33 PM

A newly constructed map of the landscape of genetic changes in chronic lymphocytic leukemia (CLL) may provide a better understanding of this complex malignancy that could lead to more accurate prognoses for patients, improved diagnostics, and novel treatments. These research findings were published by Knisbacher et al in Nature Genetics, and the study was conducted by an international collaboration of investigators, including teams from the Mass General Cancer Center, the Dana-Farber Cancer Institute, and the Broad Institute of MIT and Harvard.

CLL exists as either a slowly or rapidly growing cancer and has been linked to certain genetic mutations, but it has yet to be fully characterized. Previous analyses have provided only fragments of a CLL map, each focusing on particular types of patients or limited data. To provide a more thorough understanding of the biological underpinnings of CLL and its molecular subtypes, scientists set out to construct a map from the largest CLL data set to date. To build the CLL map, the team analyzed variations in genetic sequences, gene-expression patterns, and chemical modifications to DNAor genomic, transcriptomic, and epigenomic datafrom 1,148 patients.

Such a CLL map could eventually be leveraged in the clinic, wherein the genomic features of new patients can be compared with the treatments and outcomes of patients with similar genetic profiles, said co-senior and co-corresponding author Catherine Wu, MD, Chief of the Division of Stem Cell Transplantation and Cellular Therapies at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. This profiling could potentially help more accurately tailor prognosis and treatment of a new patient based on their particular molecular features, getting closer to precision medicine.

Key Findings

The scientists identified 202 genes109 of which were novelthat when mutated, could potentially drive CLL, and they refined the characterization of subtypes of CLL with distinct genomic characteristics and prognoses. Beyond genetic sequences, the expression patterns of certain genes further subcategorized CLL and provided valuable prognostic information.

Our study has revealed that the genetic and biologic landscape of CLL is more complex than previously appreciated, said co-senior and co-corresponding author Gad Getz, PhD, Director of Bioinformatics at the Mass General Cancer Center and Director of the Cancer Genome Computational Analysis group at the Broad Institute. Patients clinical outcomes were associated with a combination of genomic, transcriptomic, and epigenomic featuresintegrating these data could predict a patients likelihood of experiencing remission vs developing more advanced cancer.

We are releasing a CLL map portal that is based on the CLL map and will be an interactive website for translational researchers to use as a resource for further investigationsuch as learning more about the different drivers and subtypes of CLL, said Dr. Getz.

Disclosure: This work was supported by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. For full disclosures of the study authors, visit nature.com.

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Molecular Map Reveals Insights Into the Genetic Drivers of CLL - The ASCO Post

MESO NUMISMATICS, INC. Management’s Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) – Marketscreener.com

Forward-Looking Statements

Certain statements, other than purely historical information, including estimates, projections, statements relating to our business plans, objectives, and expected operating results, and the assumptions upon which those statements are based, are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward-looking statements generally are identified by the words "believes," "project," "expects," "anticipates," "estimates," "intends," "strategy," "plan," "may," "will," "would," "will be," "will continue," "will likely result," and similar expressions. We intend such forward-looking statements to be covered by the safe-harbor provisions for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995, and are including this statement for purposes of complying with those safe-harbor provisions. Forward-looking statements are based on current expectations and assumptions that are subject to risks and uncertainties which may cause actual results to differ materially from the forward-looking statements. Our ability to predict results or the actual effect of future plans or strategies is inherently uncertain. Factors which could have a material adverse effect on our operations and future prospects on a consolidated basis include, but are not limited to: changes in economic conditions, legislative/regulatory changes, availability of capital, interest rates, competition, cybersecurity, and generally accepted accounting principles. These risks and uncertainties should also be considered in evaluating forward-looking statements and undue reliance should not be placed on such statements. We undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Further, information concerning our business, including additional factors that could materially affect our financial results, is included herein and in our other filings with the SEC.

Since the acquisition of Global Stem Cell Group in August last year, our focus has been mainly dedicated to its operations serving the markets in the regenerative medicine industry. We still have numismatics operation, but the overall plan for the company is too move from the sale of coins, paper currency, bullion and medals into what we believe is a more lucrative opportunity for our company.

We work with doctors and their staff to provide products, solutions, equipment, services, and training to help them be successful in the application of Stem Cell Therapies. Our team combines solutions from extensive clinical research with the manufacturing and commercialization of viable cell therapy and immune support related products that we believe will change the course of traditional medicine around the world forever. Our strategy allows us the ability to create immediate revenue streams through product sales, distribution, and clinical applications, driven by our extensive education platform. Our revenue comes directly from the training and the seminars, from the resale of these kits, products, and equipment, services, and from the reoccurring application of our process using the kits and solutions we provide.

Global Stem Cells Group is a leader in the Stem Cell and Regenerative Medicine fields, covering clinical research, patient applications, along with physician training through our state-of-the-art global network of companies. The Company's mission is to enable physicians to make the benefits of stem cell medicine a reality for patients around the world. They have been educating doctors on the science and application of cell-based therapeutics for the past 10 years. Our professional trademarked association "ISCCA" INTERNATIONAL SOCIETY FOR STEM CELL APPLICATION is a global network of medical professionals that leverages these multinational relationships to build best practices and further our mission.

The Company envisions the ability to improve "health-span" through the discovery and developments of new cellular therapy products, and cutting-edge technology.

Global Stem Cells Group, as almost everyone else in the world, was severely affected by the covid 19 pandemic. As we look to recover in 2022, we are integrating every aspect of the regenerative medicine industry. During 2022, we plan to add manufacturing and commercialization of viable cell therapy and immune support related products that we believe will change the course of traditional medicine around the world forever.

We believe this strategy will allow us the ability to increase our current revenues and create immediate revenue streams through product sales, distribution, and clinical applications, driven by our extensive education platform here are our main projects and revenue generators for 2022 and beyond.

Results of Operations for the Three Months Ended June 30, 2022 and 2021.

Revenue increased by 1,831% in the amount of $288,752 for the three months ended June 30, 2022, compared to the same period in 2021. The key reason for the increase in revenue was a result of the acquisition of Global Stem Cells Group, Inc. on August 18, 2021. Revenue from viable cell therapy and immune support related products along with physician training was $297,521 and a decrease in sale of coins, metals and paper money of $8,769 for the three months ended June 30, 2022, compared to the same period in 2021.

Listed below are the revenues, cost of revenues and gross profits by Company for the three months ended June 30, 2022:

We expect to increase our revenues in future quarters from our operations associated with Global Stem Cells with less expected revenues in future quarters associated with our numismatic operations.

Operating expenses increased by 99% in the amount of $255,634 for the three months ended June 30, 2022, compared to the same period in 2021. Listed below are the major changes to operating expenses:

Advertising and marketing fees increased by $80,817 for the three months ended June 30, 2022, compared to the same period in 2021, primarily due to the acquisition of Global Stem Cells Group, Inc. on August 18, 2021.

Depreciation and amortization increased by $35,125 for the three months ended June 30, 2022, compared to the same period in 2021, primarily due to completion of Cancun lab in May 2022.

General and administrative expense increase by $125,359 for the three months ended June 30, 2022, compared to the same period in 2021, primarily due to the acquisition of Global Stem Cells Group, Inc. on August 18, 2021.

Other expense increased by $456,085 for the three months ended June 30, 2022, compared to the same period in 2021, primarily as a result of the increase in interest on promissory notes. During the six months ended June 30, 2021, we received $11,400,000 in proceeds received from the issuance of promissory notes. We expect other expense to increase in future quarters as a result of the interest on the new debt.

We recorded a net loss of $1,493,065 for the three months ended June 30, 2022, as compared with a net loss of $926,077 for the same in 2021.

Results of Operations for the Six Months Ended June 30, 2022 and 2021.

Revenue increased by 2,941% in the amount of $594,387 for the six months ended June 30, 2022, compared to the same period in 2021. The key reason for the increase in revenue was a result of the acquisition of Global Stem Cells Group, Inc. on August 18, 2021. Revenue from viable cell therapy and immune support related products along with physician training was $596,270 and a decrease in sale of coins, metals and paper money of $1,883 for the six months ended June 30, 2022, compared to the same period in 2021.

Listed below are the revenues, cost of revenues and gross profits by Company for the six months ended June 30, 2022:

We expect to increase our revenues in future quarters from our operations associated with Global Stem Cells with less expected revenues in future quarters associated with our numismatic operations.

Operating expenses increased by 190% in the amount of $761,900 for the six months ended June 30, 2022, compared to the same period in 2021. Listed below are the major changes to operating expenses:

Advertising and marketing fees increased by $135,194 for the six months ended June 30, 2022, compared to the same period in 2021, primarily due to the acquisition of Global Stem Cells Group, Inc. on August 18, 2021.

Professional fees increased by $262,824 for the six months ended June 30, 2022, compared to the same period in 2021, primarily due to audit and accounting expenses.

Depreciation and amortization increased by $61,902 for the six months ended June 30, 2022, compared to the same period in 2021, primarily due to completion of Cancun lab in May 2022.

General and administrative expense increase by $216,667 for the six months ended June 30, 2022, compared to the same period in 2021, primarily due to the acquisition of Global Stem Cells Group, Inc. on August 18, 2021.

Other expense increased by $1,271,308 for the six months ended June 30, 2022, compared to the same period in 2021, primarily as a result of the increase in interest on promissory notes. During the six months ended June 30, 2021, we received $11,400,000 in proceeds received from the issuance of promissory notes. We expect other expense to increase in future quarters as a result of the interest on the new debt.

We recorded a net loss of $3,170,029 for the six months ended June 30, 2022, as compared with a net loss of $1,398,384 for the same in 2021.

Liquidity and Capital Resources

Since inception, the Company has financed its operations through private placements and convertible notes. The following is a summary of the cash and cash equivalents as of June 30, 2022 and December 31, 2021.

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Illinois Innovation Network honors innovators from across state – University of Illinois

The Illinois Innovation Network (IIN) announced recipients of its second-annual innovation awards Wednesday at the Illinois State Fairs Tech Prairie STEAM Expo, recognizing individuals from the IINs 15 hubs who have made key advances in research, technology commercialization and education.

The awards were presented to faculty, staff or scientists from IIN hubs in four of the IINs key subject areas: computing and data, environment and water, food and agriculture, and health and wellness. The IIN also presented awards for an open category of innovation and to a student innovator from IIN hubs.

It is our honor to celebrate these innovators and their discoveries, said Jay Walsh, vice president for economic development and innovation for the University of Illinois System, which coordinates the IIN. They all are shining examples of the fantastic research and discovery happening across our state.

Innovators were honored for developments in using numerous data streams to provide in-depth forecasting systems for agricultural ecosystems, the discovery and utilization of microbial biomes to produce new materials from organic waste, creating a new method to manufacture biodegradable plastic from agricultural biomass and food waste, and a new program that gives children the opportunity to gain real-life space exploration experience.

These innovators are an example of one of the things I love most about our state: we have brilliant people coming up with solutions to some of the worlds most difficult challenges, said Bruce Sommer, director of economic development and innovation at the University of Illinois Springfield, whose office facilitated the awards program. I am encouraged by the diversity of our recipients and the incredible work that they are doing.

IIN Innovation Award recipients Computing & Data Category Kaiyu Guan, Blue Waters associate professor in ecohydrology and remote sensing, University of Illinois Urbana-Champaign Dr. Guan developed the technology to observe and measure land and water resources for every farm on the planet, which powers his startup company Habiterre. Habiterre integrates data streams from satellites, airplanes, automobiles and ground sensor networks to create a comprehensive view of farmland. Those data streams are processed with the companys fusion algorithms, which eliminate gaps in the data and remove the effects of clouds, and have been verified with actual ground truth information, creating a quantitative analysis of individual fields at a 30-meter (100-foot) resolution and at a daily frequency, recording the past 20+ years. Then they apply scientific models and proprietary algorithms to evaluate crop growth conditions, water use, biochemical status, and management practices. Starting with a well-established scientific model for simulating entire agriculture ecosystems, Habiterre added proprietary improvements that incorporate hundreds of variables above and below ground, then it constrained the model with actual observations, create a reliable, realistic and holistic view of each farm. This effort has created the most advanced model for crop growth, carbon cycles, and nutrient dynamics. Using AI and advanced mathematical tools to combine the data and model, we have created the first real forecasting capabilities for agro-ecosystems. Habiterre can directly see how different components of carbon, water, and nutrients change during the growth season and how they are impacted by farming practices. Additionally, the company can create simulations that make it possible to predict the outcomes of various changes, from switching crop varieties and management practices, to assessing the impacts of climate change. With the aid of supercomputers and cloud computing, they can process millions of farm-level simulations simultaneously, allowing us to achieve field-level accuracy over large geographic areas.

Environment & Water Category Scott Hamilton-Brehm, associate professor in biological sciences, Southern Illinois University Carbondale Dr. Hamilton-Brehm is an innovator in the discovery and utilization of geothermal and subsurface microbial biomes to perform green remediation and recovery of organic waste to produce new materials and to produce value-added materials and food. Hamilton-Brehm holds two patents, led the student team that received funding as one of the finalists in the Carbon Removal XPRIZE competition, and was part of the team selected for funding through the NASA Deep Space Food Challenge. Dr. Hamilton-Brehm also led the efforts by SIU to produce for the State of Illinois over 100,000 vials of Viral Transport Medium (VTM) during the early days of the COVID-19 pandemic. The Carbon Removal XPRIZE award focused on the innovative use of Oxidative Hydrothermal Dissolution (OHD) to convert captured carbon, in the form of almost any plant-based waste biomass, into a water-soluble liquid. The resulting liquid can then be pumped into natural or man-made geologic recesses where microbes will eat the waste, thereby sequestering the carbon contained within the waste. The advantage of this approach over air-based carbon capture is dramatically revealed when one recognizes that one pound of raw plant matter contains about the same amount of carbon as one million liters of air. Hamilton-Brehm and his team were selected as one of the top 60 teams worldwide for the XPRIZE. More recently, Hamilton-Brehm and his team played a crucial role in obtaining funding from NASA through the Deep Space Food Challenge program to develop their next-generation food production system called Bites, which will utilize plastic and biomass waste as the carbon source for food generation.

Food & Agriculture Category Lahiru Jayakody, assistant professor in microbiology, Southern Illinois University Carbondale Dr. Jayakody is a young innovator in synthetic microbiology and green chemistry and holds or has applications for seven patents. His patents on engineering robust microbial cell factories apply to developing multiple technologies, including valorization of unconventional feedstock such as industrial-wastewater streams and waste plastic. He developed a novel thermo-bio-catalytic hybrid process to valorize untapped waste carbon in the agricultural biomass, i.e., high-toxic aldehydes and aromatics, industrial food waste, and waste plastic. His innovative approach merged engineered microbial-based biofunneling and biofunctionalization of organic substrates with Dr. Ken Anderson's (2021 IIN Innovation Award) Oxidative Hydrothermal Dissolution technology (OHD), to produce advanced platform chemicals to replace incumbent petrochemicals and microbial-based food ingredients for next-generation food production. Jayakody partnered with one of the world's leading green tea manufacturers, Ito En Japan, to develop and commercialize technology to manufacture novel biodegradable plastic from waste tea, coffee, and postconsumer polyethylene terephthalate (PET) bottles. The generated chemicals will be used to make advanced PET alternatives and smart food packaging materials. He also leads the team "Bites," which has invented a next-generation food production system using this technology. His innovative synthetic microbial-based process converts waste plastic into edible, 3D printed, customized, nutritious food for astronauts. His team was one of 18 winners of the Phase I NASA Deep Space Food Challenge and the only Illinois-based team.

Health & Wellness Category Mohammad Islam, research assistant professor in chemistry, University of Illinois Chicago Dr. Islam has recently engineered a cell-based method of preventing infection from the SARS-CoV-2 virus. Spike protein (S) of SARS-CoV-2 uses human receptor containing angiotensin-converting enzyme 2 (ACE2) cells to initiate viral entry into the body. By preventing the receptor binding domain (RBD) of S protein from binding with ACE2 cells, SARS-CoV-2 can be prevented from infecting the human body. Dr. Islam developed an ACE2 decoy receptor that binds with the RBD of SARS-CoV-2 spike protein with low nanomolar affinity and 10-fold affinity enhancement over the wildtype. Dr. Islam used computational mutagenesis and molecular dynamics simulations to design the soluble decoy ACE2, which is known as ACE2-FFWF. This research was published in the Journal of Chemical Information and Modelling, (J. Chem. Inf. Model. 61, 46564669) where Dr. Islam acted as the principal investigator and the corresponding author of the paper. Dr. Islams research develops and advances a new class of soluble sACE2 that can act as potential therapeutics against variants of concern, namely omicron, alpha, beta, delta, delta plus, and gamma.

Open Category Keith Jacobs, statewide 4-H STEM specialist, University of Illinois Extension Keith Jacobs is uniquely contributing to the recruitment, diversification and mentoring of the next generation workforce in computing and STEM. Jacobs designed a new program called 4-H in Space that gives middle and high school youth the opportunity to gain real-life experience in space exploration by building, programming, and launching real satellites into orbit. The students gain deep experience in subjects like coding, mechanical engineering and astronomy, all of which help hone their STEM skills. Jacobs expects to reach some 2,000 young people in this first year of the program, with a goal of reaching 10,000 young people by 2025. Additionally, Jacobs developed partnerships with the Laboratory for Advanced Space Systems in Illinois (LASSI), and the International Space Station national Laboratories (ISSNL) to create unique hands-on learning opportunities for youth in the program. A select group of youth the Illinois Mission Command team traveled to the Kennedy Space Center in Florida in July 2022, where they designed an experiment to be launched and tested on the International Space Station. In collaboration with the LASSI group in the University of Illinois Urbana-Champaigns Aerospace Engineering Department, Mission Control youth will code and launch a cube satellite in 2023. Youth will then monitor and analyze data received from the programmed sensors in space. The youth in Mission Control reflect the racial and ethnic diversity of Illinois, and reflect Jacobs commitment to inspiring under-represented youth to pursue STEM careers. Jacobs innovative program design is already being scaled to other states through the network of land-grant universities. To date, he has trained and mentored 4-H staff in three other states. In 2023, his curriculum 4-H in Space will be made available, with the potential reach the 7 million youth in 4-H across the country.

Student Category Pierre Paul, We Hear You, Distillery Labs Paul and his team have developed We Hear You, an AI-based sign language translator as well as a personalized automatic door opener fob for persons with disabilities that are accommodated under the Americans with Disabilities Act. Currently, the ADA guidelines only provide guidance based on the minimum standards and requirements that have to be met. We Hear You's mission is to improve the quality of life for persons with disabilities, and they are actively seeking to create solutions that proactively resolve the challenges that they continue to face even when there are accessible pathways throughout their daily journeys. Pierre and his team have validated the problem they're solving in providing innovative solutions that solve accessibility issues. They have won a number of competitions including the Social Innovation Challenge, and the Big Idea Competition while at Bradley University. Additionally, they have been incubated at Bravelaunch, gBETA Distillery Labs, and most recently at UIUCs iVenture Accelerator.

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Illinois Innovation Network honors innovators from across state - University of Illinois