Reprogramming Fibroblasts in Vivo for Heart Repair – Lifespan.io News

Scientists from Duke University have found a way to make adult fibroblasts differentiate into cardiomyocytes, which might help develop better heart attack treatments [1].

Myocardial infarction, or heart attack, is a leading cause of death and disability. It happens when the blood flow to a part of the heart gets blocked, often by a blood clot, leading to cell death and necrosis [2]. When the blood flow is restored, the healing is similar to that of flesh wounds. Fibroblasts recruited to the area produce a lot of intracellular matrix elements, which results in the formation of stiff scar tissue. This decreases the hearts efficiency, negatively affecting future lifespan and healthspan.

This imperfect repair process reflects the changes we undergo after birth. Fibroblasts are multipotent cells that can differentiate into other cell types, such as adipocytes, chondrocytes, and cardiomyocytes, the heart muscle cells. This process is effective in fetuses and newborns, which is why cuts on a newborns skin often heal perfectly without leaving any scar tissue. However, after a fairly short time, fibroblasts become less inclined to differentiate, preferring to produce the extracellular matrix instead.

Scientists have been looking for ways to trick adult fibroblasts into behaving immaturely, differentiating into myocytes to heal myocardial infarction more effectively [3]. However, attempts at direct fibroblasts to myocytes reprogramming in vivo have been hampered by low reprogramming efficiency. Apparently, its hard to teach old fibroblasts new tricks.

In this new study, the researchers attempted to identify the changes in fibroblasts after birth and how these changes could be manipulated for therapeutic benefits. First, they isolated cardiac fibroblasts from neonatal and adult mice. All fibroblasts were identically passaged: that is, they had undergone roughly the same number of divisions, which made them of a similar cellular age. The fibroblasts were then transfected with a cocktail of four micro-RNAs (miRNAs) that had been shown by previous research to induce reprogramming of fibroblasts into cardiomyocytes, albeit with low efficacy.

Reprogramming worked well in neonatal, but not adult, fibroblasts. The researchers looked at transcription factors that were expressed differently in those two types of fibroblasts and then made several more attempts at reprogramming, each time adding a siRNA (short interfering RNA) to silence one of the candidate factors. Silencing Epas1, which was highly expressed in adult but not neonatal fibroblasts, seemed to work best, robustly increasing the number of reprogramming events in the culture. Conversely, overexpressing Epas1 in neonatal fibroblasts resulted in them losing their remarkable differentiation capacity.

To test their new insights, the researchers inflicted myocardial infarction on mice, and then delivered the reprogramming miRNA combo and the Epas1-blocking siRNA directly into the infarction border zone. Two months after the injury, no new cardiomyocytes appeared in mice that received sham treatment. In mice who received only the reprogramming cocktail, few reprogramming events occurred. However, in the mice that also received Epas1-blocking siRNA, about 20% of resident cardiomyocytes turned out to be former fibroblasts. The treatment also significantly improved cardiac function.

The authors hypothesized about the event that triggers the expression of Epas1 and moves myofibroblasts towards their adult differentiated phenotype. They suggest that this cue might be oxygen deprivation during birth, since low oxygen levels are known to induce Epas1 expression [4]. The researchers mention that low oxygen levels during birth might also be the stimulus behind cardiomyocyte cell cycle exit (adult cardiomyocytes are largely non-proliferative).

The researchers note that while they chose Epas1, which yielded good results, other transcription factors might be at play as well. Targeting several factors at once might lead to even better outcomes. For RNA delivery, the researchers used exosomes, a type of extracellular vesicles used by cells for communication. This method of delivery was popularized by recent COVID-19 vaccines that use it to deliver their RNA cargo.

Regaining the impressive regenerative abilities that we lose soon after birth might be the key to staving off numerous deadly diseases. This research underscores how pliable cell fate can be, and that we might be able to manipulate it to produce new differentiated cells in environments that normally do not allow this. Direct reprogramming of fibroblasts in vivo can also be used outside of the cardiac context, such as in producing new cartilage.

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[1] Sun, H., Pratt, R. E., Dzau, V. J., & Hodgkinson, C. P. (2023). Neonatal and adult cardiac fibroblasts exhibit inherent differences in cardiac regenerative capacity. Journal of Biological Chemistry, 104694.

[2] Ojha, N., & Dhamoon, A. S. (2021). Myocardial infarction. In StatPearls [Internet]. StatPearls Publishing.

[3] Chen, Y., Yang, Z., Zhao, Z. A., & Shen, Z. (2017). Direct reprogramming of fibroblasts into cardiomyocytes. Stem cell research & therapy, 8, 1-8.

[4] Peng, J., Zhang, L., Drysdale, L., & Fong, G. H. (2000). The transcription factor EPAS-1/hypoxia-inducible factor 2 plays an important role in vascular remodeling. Proceedings of the National Academy of Sciences, 97(15), 8386-8391.

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Melding Data Creates Wider Landscape of Brain Cancer – Cancer Health Treatment News

Brain cancer researchers have a new, panoramic visualization tool to help them navigate the complex disease. Built from several publicly available datasets of gene expression and DNA sequences, the new brain cancer landscape acts like a city-wide map of the disease, carefully assembled from neighborhood maps of different brain tumor subtypes.

As researchers, we can get so focused on comparing like with like that we lose sight of the proverbial forest for focusing too much on the leaves of a single tree, wrote Holland Lab computational biologist Sonali Arora, MS, in the paper describing the tool, published in Scientific Reports in March.

Her new map offers a detailed landscape of molecular alterations in brain tumors that will help cancer researchers move between different subtype neighborhoods, as well as between cancerous and healthy brain tissue. Its the first brain cancer computational visualization tool to combine different molecular datasets from both pediatric and adult brain tumors into one landscape, which will allow researchers to chase down key genes and biological pathways that shape development, tumor growth and treatment response, said Arora, who melded the datasets.

Now you can compare all kinds of things, like the expression of certain genes or pathways you can compare across all tumors types and normal brain, said Fred Hutch brain cancer researcher and Human Biology Division Director Eric Holland, MD, PhD. And thats something that hasnt been done before. Now you can compare and learn about gene expression in one tumor versus another, or one subset versus another.

The computational tool reveals biological processes that are ramped up or down in cancer compared to normal brain tissue. And because it draws on datasets from the U.S. and China, Arora was able to show that while tumors from both regions often share molecular alterations, there is a certain subset of glioma in patients from China that is not seen in the U.S.-based data.

And to enable scientists to explore her brain tumor map in 3D detail, Arora uploaded the landscape to the visualization tool Oncoscape, also developed in the Holland Lab.

Aroras landscape offers a way to visualize both normal and tumor samples and show tumor relationships not available in standard plotting methods, Fred Hutch colleague and cancer stem cell biologist Patrick Paddison, PhD, wrote in an email. Paddison and his team used the tool to help identify genes that are critical for brain tumor cells (but not healthy brain tissue), as well as their biomarkers.

Arora got the idea to build the landscape during the initial COVID-19 pandemic shutdown. She saw an opportunity to give brain cancer researchers a wider view of brain cancer by creating a map that combined data from multiple brain tumor subtypes housed in publicly available data repositories.

These datasets include a spectrum of molecular information, including tumors DNA sequences and the patterns of genes that are turned on and off in tumors. The Cancer Genome Atlas, or TCGA, a National Cancer Institutefunded program, includes samples from adult tumors that span 33 cancer types. Arora combined information from 702 TCGA patients with glioma and 270 patients with tissue samples in the Chinese Glioma Genome Atlas, or CGGA. To allow scientists to easily compare the differences and similarities between adult and childhood brain tumors, she added brain tumor data from the Children Brain Tumor Network, or CBTN. And to help scientists clarify how tumors differ from normal tissue, Arora included molecular information from 1,409 normal brain tissue samples in the Genotype Tissue Expression Project, or GTEx.

She then used a technique called uniform manifold approximation and projection for dimension reduction, or UMAP, to simplify the large, complex data and make it easier to detect key relationships between molecular changes and tumors. Arora also used a computational technique called batch effect correction, which to her knowledge has not been used at this scale before. This strategy helps scientists clear away variation in data that arises because samples are processed under different conditions and see true biological variation.

In Aroras UMAP, brain tumors that share gene expression patterns cluster together in the same subtypes. And like a city map, her landscape shows which subtype neighborhoods are near neighbors, and which are across town. Arora was able to see how biological processes differed between normal tissue and cancer, and between different cancer types, including tumors from adult and pediatric patients.

There are clearly some pathways that are upregulated, Arora noted.

Relationships between tumor types, as well as tumors and key genes and biological processes, quickly jumped out, she said. For the most part, tissue from gliomas taken from patients in the U.S. and China clustered into the same neighborhoods, save for two clusters of glioma subtypes seen in the CGGA but not the TCGA data. Its already known that the same cancer type may manifest differently in different regions around the world, and the new brain tumor landscape could help scientists figure out how and why this occurs for glioma as well, the researchers said.

The UMAP showed that in comparison with normal brain tissue, glioma tumors from adults had higher levels of key cancer-promoting biological processes, including those that promote cell growth and DNA repair. Some pediatric tumors had also ramped up these processes. The UMAP also reveals pathways ramped down in tumors, including some neurotransmitter pathways.

Researchers can use the UMAP to dig deeper into these pathways, and explore individual genes involved at different steps in each biological process, Arora said.

You can visualize the expression of each of those genes over the brain tumor map, she said. By using the UMAP, she was able to see that while a specific process in this case, a type of DNA repair might be elevated in cancer cells, the expression level of individual genes involved in that process might vary, with some remaining the same as in normal brain tissue.

To help researcher examine the relationship between DNA changes and brain tumors, Arora built a smaller UMAP using the samples from TCGA and the CBTN that included DNA sequence information. This gave a window into the range of DNA mutations that can drive cancer, from changes in single DNA letters, to the replication or loss of larger chunks of DNA. Sometimes these changes can cause two genes to be fused together, forming a new Frankengene that may drive cancer by acting differently than either of its parent genes. Aroras UMAP showed that certain gene fusions were more common in specific brain cancer subtypes.

Now youre able to compare a group of tumors amongst each other, Holland said. Thats unusual, he noted: Its far more common for scientists to study and report on one tumor type. These cross-subtype comparisons could help brain cancer researchers discover treatment targets shared by multiple brain tumor types, or those unique to specific subtypes.

Paddison used the UMAP to uncover vulnerabilities or genes and biological processes that cancer cells need but healthy cells dont in different subsets of both adult and childhood brain tumors.

Precision oncology is the tailoring of a cancer patients treatment plan to their tumors unique blend of vulnerabilities. While cancer researchers have made great strides, there remains a lot to discover about the treatment targets lurking within tumors, and how to determine which therapies will provide the greatest benefit to which patients.

Aroras UMAP, combined with Oncoscapes data visualization capabilities, will help further those discoveries, Holland said.

It will make it easier for brain cancer researchers like Paddison to uncover what drives brain tumors, whether its from DNA mutations or large-scale changes in gene expression patterns. Identifying key genes or pathways in the UMAP could help researchers better choose candidate therapies for clinical trials, Holland said.

This type of approach could be used to more precisely place patient tumors in continuum of adult or pediatric brain tumors to better predict outcomes and survival, Paddison said.

Using tumor landscapes, incorporating patient clinical as well as tumor molecular landscapes, to refine diagnosis and treatment is Hollands hope as well.

You could imagine a world where a given tumor is sequenced, and then placed on the landscape. Then your nearest neighbors on the landscape could tell you what your diagnosis actually is, but also what your expected outcome would be, Holland said.

Aroras multi-dataset brain cancer UMAP is to my knowledge, the first pseudo pan-cancer approach to a really interactive way of learning about, and predicting, new tumor behaviors, he said.

This work was supported by the National Institutes of Health, the Jacobs Foundation and the National Science Foundation.

This article was originally published April 10, 2023, by Fred Hutch News Service. It is republished with permission.

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Melding Data Creates Wider Landscape of Brain Cancer - Cancer Health Treatment News

2023-04-24 | OTCPK:BRTXD | Press Release | BioRestorative … – Stockhouse

--Clinical data from safety run-in scheduled to be released in second half of 2023.

MELVILLE, N.Y., April 24, 2023 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (BioRestorative”, BRTX” or the Company”) (NASDAQ:BRTX), a clinical stage company focused on stem cell-based therapies, today announced that it has completed enrollment for the safety run-in component of its Phase 2 clinical study of BRTX-100 targeting patients suffering from chronic lumbar disc disease (cLDD).

BRTX-100 is the Company’s lead clinical candidate, a novel cell-based therapeutic engineered to target areas of the body that have little blood flow. BRTX-100 is currently being evaluated in connection with a Phase 2 clinical trial to treat cLDD. The trial is prospective, randomized, double-blinded and controlled. The trial will evaluate the safety and preliminary efficacy of a single dose of BRTX-100. A total of up to 99 eligible patients will be randomized at up to 15 clinical sites in the United States to receive either the investigational drug (BRTX-100) or control in a 2:1 fashion.

Lance Alstodt, Chief Executive Officer of BioRestorative Therapies, stated The completion of patient recruitment and enrollment for the safety run-in component of our Phase 2 study of BRTX-100 is a very significant milestone for our company. Positive safety data would enable us to initiate unrestricted enrollment across all of our clinical sites and, of course, establish a strong safety profile for BRTX-100. In addition, we would be able to leverage the BRTX-100 platform across other indications within the body on an investigational basis with potentially a shorter timeline from a regulatory pathway perspective.”

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Disc/Spine Program (brtxDISC): Our lead cell therapy candidate, BRTX-100, is a product formulated from autologous (or a person’s own) cultured mesenchymal stem cells collected from the patient’s bone marrow. We intend that the product will be used for the non-surgical treatment of painful lumbosacral disc disorders or as a complementary therapeutic to a surgical procedure. The BRTX-100 production process utilizes proprietary technology and involves collecting a patient’s bone marrow, isolating and culturing stem cells from the bone marrow and cryopreserving the cells. In an outpatient procedure, BRTX-100 is to be injected by a physician into the patient’s damaged disc. The treatment is intended for patients whose pain has not been alleviated by non-invasive procedures and who potentially face the prospect of surgery. We have commenced a Phase 2 clinical trial using BRTX-100 to treat chronic lower back pain arising from degenerative disc disease.

Metabolic Program (ThermoStem®): We are developing a cell-based therapy candidate to target obesity and metabolic disorders using brown adipose (fat) derived stem cells to generate brown adipose tissue (BAT”). BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in animals may be responsible for additional caloric burning as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:

Email: ir@biorestorative.com

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2023-04-24 | OTCPK:BRTXD | Press Release | BioRestorative ... - Stockhouse

IVG: Tech that can turn skin cells into babies – NewsBytes

IVG: Tech that can turn skin cells into babies

Apr 24, 2023, 04:46 pm 3 min read

It's amazing what science can do these days. In vitro gametogenesis (IVG) is a remarkable reproductive technology that can create babies from skin cells! It has the potential to change the lives of many who face infertility challenges or can't conceive naturally, including same-sex couples and postmenopausal women. Let's delve into understanding the science behind this game-changing technology for the future of parenthood.

IVG would allow nearly anyone to become a biological parent

This technology can help same-sex couples have children who are biologically related to both parents. It can enable single individuals to procreate without another person's genetic contribution. IVG can also allow groups of more than two individuals to procreate together, resulting in children who are genetically related to all the individuals involved. A game-changer for potential parents, IVG could transform the idea of family.

IVG is not the same as IVF

IVG should not be confused with in vitro fertilization (IVF), which has been helping couples with fertility for decades. While IVF is a well-established process, IVG is a new reproductive technology that is still in the research and development phase.

What's the science behind this assisted reproductive technology?

IVG can produce sperm and egg cells in a lab from almost any adult cell. This is done by using skin and blood cells to reverse engineer a special type of cell called induced pluripotent stem cells (iPSC). iPSCs are adult cells that have been genetically modified to an embryonic state. That means they can be used to produce eggs and sperm for reproduction.

Scientists have made significant strides in the development of IVG

In 2016, Japanese researchers successfully created viable eggs from the skin cells of mice and implanted them into female mice, resulting in healthy baby mice. The mice were healthy and able to have offspring of their own from the grown egg cells. In 2018, another researcher based in Japan was able to grow an early-stage egg from human stem cells derived from blood.

IVG may help preserve endangered species

IVG also has the potential to help protect endangered animal species by creating viable egg and sperm cells from stored tissue samples. This is important for animals with low reproduction rates, as it allows their genetic material to be saved without the need for live animals. It could also be helpful in bringing back extinct species whose tissue samples are preserved by scientists.

The ethical concerns of IVG

The ethics related to IVG are complicated, as it raises concerns about embryo farming and the commodification of reproduction. IVG also has the potential to enable direct gene editing, which could have unknown consequences. And there's a risk of unauthorized use of biological material, like hair or skin cells, to generate embryos, which raises crucial questions about privacy and consent.

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IVG: Tech that can turn skin cells into babies - NewsBytes

Healing the unhealable: New approach helps bones mend themselves – Science Daily

Young babies and newborn mice can naturally heal damage to the bones that form the top of the skull, but this ability is lost in adults. In a new study published in Proceedings of the National Academy of Sciences, University of Pittsburgh researchers developed a novel approach that promoted bone regeneration in mice without implantation of bone tissue or biomaterials.

The technique uses a device similar to an orthodontic wire used to realign teeth to carefully stretch the skull along its sutures, activating skeletal stem cells that reside in these wiggly seams. In adult mice, the technique repaired damage to the skull that otherwise would not have healed on its own.

"Our approach is inspired by babies because they have an amazing ability to regenerate bone defects in the calvarial bones that make up the top of the skull," said senior author Giuseppe Intini, D.D.S., Ph.D., associate professor of periodontics and preventive dentistry at the Pitt School of Dental Medicine, member of the McGowan Institute for Regenerative Medicine and an investigator at UPMC Hillman Cancer Center. "By harnessing the body's own healing capacity with autotherapies, we can stimulate bone to heal itself. We hope to build on this research in the future to develop novel therapies for people."

Trauma, congenital defects and surgery to treat cancer or other diseases are common causes of damage to the skull. After people reach the age of about 2 years, such injuries don't heal on their own.

"In babies, the calvarial bones are not completely fused, so the sutures where stem cells reside are still open," said Intini. "We wondered whether the unfused sutures had something to do with the bone regenerative capacity observed in babies and hypothesized that we could reverse engineer this in adults by mechanically opening the sutures to activate the stem cell niche and boost stem cell numbers."

In mice -- which have very similar skull development to humans -- the researchers used a so-called bone distraction device to carefully apply a controlled pulling force to the calvarial bones, strong enough to slightly widen the sutures but not enough to cause a fracture. Using single-cell RNA sequencing and live-imaging microscopy, they found that the number of stem cells in the expanded sutures of these animals quadrupled.

As a result, mice treated with the device regenerated bone to heal a large defect in the skull.

"If you can effectively activate the stem cell niche, you can increase the number of stem cells and sustain regeneration of bone defects," said Intini. "Remarkably, we showed that the defect can heal even if it's away from the suture."

Although the approach was effective in healing skeletally mature 2-month-old mice, the age that roughly translates to young adulthood in humans, it did not work in 10-month-old, or middle-aged, rodents.

"In older mice, the quantity of stem cells in calvarial sutures is very low, so expanding this niche is not as effective in boosting healing capacity," Intini explained. "Overcoming this challenge is a focus of research to come."

Current treatments for damage to the skull are usually bone grafts or implantation of biomaterials that act as scaffolds for bone regeneration, but these approaches are not always effective and come with risks, said Intini.

The researchers are investigating how their findings could be used to inform novel therapies in people, not just to heal skull injuries but also fractures in long bones such as the femur. Bone distraction devices are already used to treat certain conditions such as a birth defect called craniosynostosis, in which the calvarial bones fuse too early, so expanding this technique to promote bone regeneration could be a future focus of clinical trials.

Intini and his team are also investigating non-mechanical approaches to activate skeletal stem cells such as medications.

Other authors who contributed to the study were Zahra A. Aldawood, D.M.Sc, of the Harvard School of Dental Medicine and Imam Abdulrahman Bin Faisal University; Luigi Mancinelli, Ph.D., Xuehui Geng, M.D., M.S., Taiana C. Leite, D.D.S., M.S., and Roberta Di Carlo, Ph.D., all of Pitt; Shu-Chi A. Yeh, Ph.D., and Charles P. Lin, Ph.D., both of Massachusetts General Hospital; Jonas Gustafson, of Seattle Children's Research Institute; Katarzyna Wilk, M.S., Joseph Yozgatian, D.D.S., M.M.Sc., Ph.D., Sasan Garakani, D.D.S., and Seyed Hossein Bassir, D.D.S., D.M.Sc., of the Harvard School of Dental Medicine; and Michael L. Cunningham, M.D., Ph.D., of the Seattle Children's Research Institute and the University of Washington.

This research was supported by the National Institutes of Health's National Institute of Dental and Craniofacial Research (grants #R00DE021069 and #R01DE026155).

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Healing the unhealable: New approach helps bones mend themselves - Science Daily

STEMTECH CORP Management’s Discussion and Analysis of Financial Condition and Results of Operations. (form 10-K) – Marketscreener.com

The following discussion should be read in conjunction with our financialstatements, including the notes thereto, appearing elsewhere in this annualreport. The following discussion contains forward-looking statements thatreflect our plans, estimates and beliefs. Stemtech's actual results could differmaterially from those discussed in the forward-looking statements. Factors thatcould cause or contribute to such differences include but are not limited tothose discussed below and elsewhere in this annual report. Stemtech's auditedfinancial statements are stated in United States Dollars and are prepared inaccordance with United States Generally Accepted Accounting Principles.

Stemtech Corporation was incorporated under the laws of the State of Nevada,U.S. on September 4, 2009. Our registration statement on Form S-1 was filed withthe SEC was declared effective on May 15, 2013. On August 19, 2021, the Companyentered into a Merger Agreement with Stemtech Corporation by which the Companyacquired one hundred percent of the shares of STEMTECH CORPORATION in exchangefor the issuance of 37,060,000 shares of the Company, approximately 85% of theissued and outstanding shares of the Company.

Stemtech has pioneered and patented a whole new category of dietary supplements.Stemtech's advanced Stem Cell Nutrition formulations are one-of-a-kind naturalproducts designed to help support the three most important aspects of stem cellphysiology: 1) Releasing more stem cells; 2) their circulation in the blood; and3) Migration into tissues, where they can perform their daily function ofrenewal and rejuvenation for optimal health. We actually harness the incrediblepower of adult stem cells. How does this work? Adult stem cells are releasedfrom your bone marrow into the bloodstream, they then Circulate in thebloodstream and flow to the tissues most in need. As they arrive, the adult stemcells migrate into the tissues, reproduce and become new, healthy cells of thosetissues. This process takes place every single day, even without tissue damage,as part of the natural renewal system of the body. It is important to understandthat Stemtech's products do not contain stem cells. They are composed of naturalbotanicals and other ingredients that have been clinically documented to supportthe performance of your own adult stem cells. Stemtech also offers ourall-natural OraStem toothpaste, which is a tooth whitener, breath freshener,anti-microbial, stem cell attracting and promotes good gum health. In December2022, our new Cellect One Rapid Renew Stem Cell Peptide Night Cream. CellectOne is a Stemtech proprietary formula containing an FDA patented ingredient, RedOak Bark, which enables deep penetration to promote good skin health.

While sales of products obviously create the cash flow, our real business modelis not just "sales", but lateral penetration. We do this through our IBPs -"Independent Business Partner" Sales Forces, and we invest much energy ingrowing our IBPs. Post public listing and funding, Stemtech is projecting theaddition of 30,000 new independent business partner reps over the next 12 to 24months, adding to the existing IBPs. With an enhanced compensation plan, IBPswill be even more incentivized to build their network, attracting additionalindustry leaders. IBPs are a testimonial to our product and business model,lowering our customer acquisition costs.

We are now reinstituting contests, travel incentives, cruises, other trips,Business Academies for Training, regional conferences, our Annual Conventionwith new product launches. Our IBPs offer highly flexible yet steady incomewhich is most adapted to todays "Laptop & Cellphone Lifestyle", with structuredand organized weekly Corporate training calls, a personalized website, backoffice tracking, oversight and management Tools, Reports, Training Materials andSocial Sharing. Stemtech also launched the Stemtech AdvanceOffice Mobile App,based on the Verb Technology platform in September 2022, improvingcommunication, sharing of information, training videos and other content forrecruiting, on-boarding, customer retention and measuring key performanceindicators for the IBP business.

Stemtech launched a new marketing program in January 2022, with sales continuingto come in from returning consumers who believe in the quality products. UntilSeptember 2021, the Company had operated on an extremely tight budget, withinadequate working capital and difficulties fulfilling orders. Since the cashinfusions noted in "Financing" infra, the company now has the resources tocontact and re-engage the over 200,000 former distributors. With this new cashinfusion, the Company has engaged experienced marketing and social mediaprofessionals to initiate new marketing strategies which are expected to bringincreased activity. Moreover, we are now better positioned to absorb significantnew clientele as the company has directed significant cash towards ourinventory, and we now have enough inventory on hand to fulfill over $3 milliondollars' worth of new orders, an inventory level we have not had since goinginto bankruptcy in 2017. Management conservatively believes that given the cashon hand and working expenditures as describe above, we can reinvigorate sales tobe more consistent with the company's previous revenue historically, as we wererecognized 4 times in the Inc 5000 Magazine's list of fastest growing companies.

Below this IBP level, we have our "DTC" (Direct To Consumer) network marketingDistribution model. This integrative model allows us an immediate globalpresence and ability to operate in multiple countries on any continent. We areuniquely positioned in this post pandemic economy beset by supply chain issues,as this method requires no up-front or required buy-in of inventory, withmonthly shipments available for known recurring sales. This platform has us nowoperating at the intersection of the ecommerce economy, social economy and gigeconomy.

The Company has been making great strides the past year, having filed our"Orastem" trademark registration in Mexico as noted in our press release ofAugust 23, 2022. In addition, Stemtech filed our new 'stemceuticals' trademarkregistration. We also have been fortunate to have Dr. Bankole Johnson join ourLife Sciences Advisory Board in September, as well as the introduction of awhole new line of stem cell skin care products. Life Factor Research bringstheir expertise in research, development and product formulations enabling theCompany to now organically develop whole new lines of Stemceuticals. This newarrangement enables Stemtech to offer more new, cutting-edge products to anever-growing market interested in improved health and quality of life.

Below this IBP level, we have our "DTC" (Direct To Consumer) network marketingDistribution model. This integrative model allows us an immediate globalpresence and ability to operate in multiple countries on any continent. We areuniquely positioned in this post pandemic economy beset by supply chain issues,as this method requires no up-front or required buy-in of inventory, withmonthly shipments available for known recurring sales. This platform has us nowoperating at the intersection of the ecommerce economy, social economy and gigeconomy.

Implications of Being an Emerging Growth Company

Emerging Growth Company - We are an emerging growth company as defined inSection 2(a)(19) of the Securities Act of 1933, as amended, or the SecuritiesAct. We will continue to be an emerging growth company until: (i) the last dayof our fiscal year during which we had total annual gross revenues of at least$1.07 billion; (ii) the last day of our fiscal year following the fifthanniversary of the date of the first sale of our common stock pursuant to aneffective registration statement under the Securities Act; (iii) the date onwhich we have, during the previous 3-year period, issued more than $1.0 billionin non-convertible debt; or (iv) the date on which we are deemed to be a largeaccelerated filer, as defined in Section 12b-2 of the Securities Exchange Act of1934, as amended, or the Exchange Act, which means the market value of ourcommon stock that is held by non-affiliates exceeds $700 million as of the priorJune 30.

As an emerging growth company, we are exempt from:

We have elected to use the extended transition period for complying with new orrevised accounting standards under Section 102(b)(1) of the Jumpstart OurBusiness Startups Act.

We are also a smaller reporting company as defined in Rule 12b-2 of the ExchangeAct. As a smaller reporting company, we are not required to provide selectedfinancial data pursuant to Item 301 of Regulation S-K, nor are we required tocomply with the auditor attestation requirements of Section 404(b) of theSarbanes-Oxley Act of 2002. We are also permitted to provide certain modifiedexecutive compensation disclosure under Item 402 of Regulation S-K.

The accompanying consolidated financial statements have been prepared inaccordance with accounting principles generally accepted in the United States ofAmerica ("U.S. GAAP"). Such consolidated financial statements and accompanyingnotes are the representations of the Company's management, which is responsiblefor their integrity and objectivity. All intercompany accounts and transactionshave been eliminated in consolidation.

Our consolidated financial statements have been prepared assuming that we willcontinue as a going concern and, accordingly, do not include adjustmentsrelating to the recoverability and realization of assets and classification ofliabilities that might be necessary should we be unable to continue inoperation. We expect we will require additional capital to meet our long-termoperating requirements. We expect to raise additional capital through, amongother things, the sale of equity or debt securities.

Year Ended December 31, 2022 Compared to the Year Ended December 31, 2021.

During the years ended December 31, 2022 and 2021, net sales were $4,559,399 and$4,321,245, respectively. The increase of $238,154 is primarily due to slightincreases in the overall sales of the subsidiaries due to the increase in IBPsin 2022.

During the years ended December 31, 2022 and 2021, our total operating expenseswere $8,418,761 and $6,508,356, respectively. The increase of $1,910,405 isprimarily attributable to an increase in stock compensation granted to vendorsand officers in 2022.

During the years ended December 31, 2022 and 2021, total non-operating expenseswere $3,513,830 and $3,900,838, respectively, resulting in an increase of$387,008. The difference is primarily due to the gain on extinguishment of debtof $3,799,356 in 2022, the decrease in interest expense of $4,232,358, partiallyoffset by the changes in fair value of derivative liabilities from a gain of$4,553,372 at December 31, 2021 to a loss of $3,223,271 at December 31, 2022 inconnection with the note payable issued in September 2021.

Our net loss for the years ended December 31, 2022 and 2021, was $8,632,828 and$7,111,109, respectively. The increase in net loss was caused by the factorsdescribed above.

Liquidity and Capital Resources

In spite of increasing revenues, we are not yet profitable, and we cannotprovide any assurance of when we will be profitable. We incurred a net loss of$8,632,828 and $7,111,109 for the years ended December 31, 2022 and 2021,respectively. During the year ended December 31, 2022, we met our short-termliquidity requirements from our existing cash reserves and proceeds from theissuance of notes payable of $611,266, net proceeds from financing arrangementsof $214,249 and stock issued for cash of $100,002.

As of December 31, 2022, our current assets were $612,370 compared to $1,600,039in current assets at December 31, 2021. As of December 31, 2022, our currentliabilities were $7,415,791 compared to $9,387,038 at December 31, 2021. Currentliabilities at December 31, 2022 were comprised of $3,396,543 of accountspayable and accrued expenses, $2,717,633 of derivative liabilities, $482,885 inconvertible notes, $446,246 of nonconvertible notes payable, $214,249 offactoring liability, $119,065 in current operating lease liabilities and $39,170in deferred revenues.

Stockholders' deficit decreased from $4,005,446 as of December 31, 2021 to$3,171,918 at December 31, 2022. This change was primarily caused by theissuance of common stock for the conversion of debt of $828,000 during the yearended December 31, 2022.

Cash Flows from Operating Activities

We have not generated positive cash flows from operating activities. For theyear ended December 31, 2022, net cash flows used in operating activities were$1,216,948 which is primarily due the change in working capital accounts. Thenet loss of $8,632,828 and $3,799,356 gain on extinguishment of debt was offsetby $3,223,271 loss from the change in fair value of derivative liabilities,$3,996,187 stock based compensation, and $2,428,539 amortization of debtdiscount. Adjustments for changes in operating assets and liabilities were dueto a decrease in inventories of $278,352, an increase in deferred revenues of$39,170, a decrease in prepaid expenses and other current assets of $37,645 andan increase in long term deposits of $15,627 offset by an decrease in accountspayable and accrued expenses of $683,058 and an increase in accounts receivableof $24,047. For the year ended December 31, 2021, net cash flows used inoperating activities were $1,914,093.

Cash Flows from Financing Activities

We have financed our operations primarily from either the issuance of our sharesof common stock or notes payable. For the year ended December 31, 2022, wegenerated $338,734 cash from financing activities which consists of $611,266from the issuance of convertible promissory notes, $214,249 proceeds fromfactoring arrangement and $100,002 proceeds from issuance of stocks for cash,partially offset by payments on notes payable of $586,783. For the year endedDecember 31, 2021, net cash flows provided by financing activities were$2,628,739.

Plan of Operation and Funding

We expect that working capital requirements will continue to be funded through acombination of our existing funds and further issuances of equity securities anddebt instruments.

Existing working capital, further advances and debt instruments, and anticipatedcash flow are expected to be adequate to fund our operations over the next threemonths. We have no lines of credit or other bank financing arrangements.Generally, we have financed operations to date through the proceeds of theprivate placement of equity and debt instruments. In connection with ourbusiness plan, management anticipates additional increases in operating expensesand capital expenditures relating to: (i) acquisition of inventory; (ii)developmental expenses associated with a start-up business; and (iii) marketingexpenses. We intend to finance these expenses with further issuances ofsecurities and director loans. Thereafter, we expect we will need to raiseadditional capital and generate revenues to meet long-term operatingrequirements. Additional issuances of equity or convertible debt securities willresult in dilution to our current shareholders. Additional financing may not beavailable upon acceptable terms, or at all. If adequate funds are not availableor are not available on acceptable terms, we may not be able to take advantageof prospective new business endeavors or opportunities, which couldsignificantly and materially restrict our business operations. We will have toraise additional funds in the next twelve months in order to sustain and expandour operations. We currently do not have a specific plan of how we will obtainsuch funding; however, we anticipate that additional funding will be in the formof equity financing from the sale of our common stock. We have and will continueto seek to obtain short-term loans from our directors, although no futurearrangement for additional loans has been made. We do not have any agreementswith our directors concerning these loans. We do not have any arrangements inplace for any future equity financing.

Off-Balance Sheet Arrangements

As of the date of this report, we do not have any off-balance sheet arrangementsthat have or are reasonably likely to have a current or future effect on ourfinancial condition, changes in financial condition, revenues or expenses,results of operations, liquidity, capital expenditures or capital resources thatare material to investors.

The Company is authorized to issue up to 200,000,000 shares of common stock, parvalue $0.001 par value. Each outstanding share of common stock entitles theholder to one vote per share on all matters submitted to a stockholder vote. Allshares of common stock are non-assessable and non-cumulative, with nopre-emptive rights.

On September 3, 2021, the Company executed a Convertible Promissory Note,Securities Purchase Agreement and ancillary agreements with Leonite. Per theterms of the Agreements with Leonite, the Company was tendered $410,000, whichis open with right of redemption for one year. Prior to the maturity date of thenote, the Company at its option, has the right to redeem in cash in part or inwhole, the amounts outstanding. Should Leonite wish to convert this debt intoequity, the conversion price shall be sixty-five percent of the lowest intradayprice during the previous 21 days. Pursuant to the Agreements, the Company hasearmarked the net proceeds for immediate cash infusion for normative workingcapital purposes and capital expenditures. Leonite. has agreed that neither itnor any of its affiliates shall engage in any short-selling or hedging of ourcommon stock during any time.

On September 3, 2021, the Company finalized a Promissory Convertible Note,Securities Purchase Agreement and ancillary agreements with MCUS. Per the termsof the Agreements with MCUS., the Company was tendered $500,000, which theCompany utilizes for normative working capital purposes and capitalexpenditures. The note is open with right of redemption for nine months. MCUShas agreed that neither it nor any of its affiliates shall engage in anyshort-selling or hedging of our common stock during any time during the term ofthe Agreements. Pursuant to the Agreements, the Company is required to registerall shares which Leonite may acquire. The foregoing is a summary description ofcertain terms of the Agreements. For a full description of all terms, pleaserefer to the original Agreements which were filed as an 8K with the SEC onSeptember 10, 2021.

On September 17, 2021, the Company finalized a $1,400,000 investment into ourCompany with Sharing Services Global Corporation, a publicly traded company("SHRG") via a Convertible Promissory Note, a Share Purchase Agreement andWarrant Agreement. Per the terms of the Agreements, the Company was tendered thefull $1,400,0000, which is open with right of redemption at 10% interest perannum until September 9, 2024.

Edgar Online, source Glimpses

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STEMTECH CORP Management's Discussion and Analysis of Financial Condition and Results of Operations. (form 10-K) - Marketscreener.com

The UCB banking market to grace digital transformation curve at a … – Digital Journal

PRESS RELEASE

Published April 19, 2023

NEW YORK : UCB is collected from the umbilical cord of a newborn baby and also retrieved from the placenta after delivery. It is enriched with adult stem cells and these stem cells play a vital role in regulating all biological activities and in developing tissues in the human body.

The UCB banking marketreached USD 13,515.8 million in 2014 at a CAGR of 6.1%, to reach USD 19,335.6 million by 2020.

Globally, UCB banking market is growing rapidly due to increasing prevalence of chronic diseases coupled with the regenerative medicines. In addition, various government associations and initiatives are also supporting the growth of the market. North America has the largest market share, followed by Europe and Asia-Pacific, in the global UCB banking market. The global UCB banking market was valued at 10,900 million in 2010 and reached USD 12,774.8 million in 2013.

Umbilical cord blood banking is a process of collecting and storing umbilical cord blood for future medical use. Umbilical cord blood is a rich source of hematopoietic stem cells that can be used to treat various diseases such as leukemia, lymphoma, and other blood disorders. The umbilical cord blood banking market is growing at a rapid pace due to increasing awareness among parents about the potential benefits of storing their childs cord blood. This report aims to provide an overview of the umbilical cord blood banking market, its current trends, and future prospects.

Request For Free Sample Report of Umbilical Cord Blood Banking Market @https://www.persistencemarketresearch.com/samples/3043

Some of the major players operating in the UCB Banking Market:

However, strict license and accreditation procedures and high cord blood Banking Market fee in private banks hampers the growth of global UCB Banking Market. As a result, the global UCB Banking Market is expected to grow a CAGR of 6.1% during 2014-2020.

North America has the largest market for UCB Banking Market. Increasing prevalence of chronic diseases is key driver of UCB Banking Market in the region. In addition, various government associations have also led to the importance of cord blood donation and services for its future use in North America.

Similarly, the European UCB Banking Market is mainly driven by the increasing prevalence of diseases. In addition, increased awareness about therapeutic applications of cord blood and rising number of live births are also contributing in the growth of the UCB market in the region.

In Asia-Pacific, UCB Banking Market is growing due to rising aging population and increasing prevalence of chronic diseases. In addition, several government associations and increasing number of live births are also increasing the demand of cord blood Banking Market services in the region.

Get Premium Research Report @https://www.persistencemarketresearch.com/checkout/3043

Market Drivers

Globally, UCB Banking Market is growing rapidly due to increasing prevalence of chronic diseases coupled with the regenerative medicines. In addition, various government associations and initiatives are also supporting the growth of the market. North America has the largest market share, followed by Europe and Asia-Pacific, in the global UCB Banking Market. The global UCB Banking Market was valued at 10,900 million in 2010 and reached USD 12,774.8 million in 2013.

Globally, increasing prevalence of chronic diseases coupled with the emerging field of regenerative medicines is driving the UCB Banking Market. In addition, various government associations and initiatives are also supporting in the growth of the UCB Banking Market.

Market Restraints

Strict license and accreditation procedures impede the growth of UCB Banking Market. In addition, high Banking Market cost in private UCB banks is also hampering the growth of UCB Banking Market. Allogeneic hematopoietic stem cell transplantation and cord tissue storage are some of the major trends in UCB Banking Market.

Access full report @ https://www.persistencemarketresearch.com/market-research/umbilical-cord-blood-Banking Market-market.asp

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Persistence Market Research is a U.S.-based full-service market intelligence firm specializing in syndicated research, custom research, and consulting services. Persistence Market Research boasts market research expertise across the Healthcare, Chemicals and Materials, Technology and Media, Energy and Mining, Food and Beverages, Semiconductor and Electronics, Consumer Goods, and Shipping and Transportation industries. The company draws from its multi-disciplinary capabilities and high-pedigree team of analysts to share data that precisely corresponds to clients business needs.

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The UCB banking market to grace digital transformation curve at a ... - Digital Journal

How umbilical cords from babies are saving cancer patients’ lives – Daily Mail

Cancer patient Nilush Aponso knows he is only alive today thanks to a decision by two anonymous mothers to donate the umbilical cords of their newborn babies.

The blood the cords contained provided life-saving cells to cure his cancer.

Nilush, 42, from Barwell, Leicester, who owns a doggy day centre, had an aggressive type of blood cancer, acute myeloid leukaemia.

Initially, chemotherapy had seemed to clear the disease but three months after his treatment finished, the cancer returned.

He was told that the only treatment option left was a stem cell transplant donated cells that would make their way to his bone marrow, where they could grow and make healthy new blood cells.

Nilush, 42, from Barwell, Leicester, had an aggressive form of blood cancer. He said he encourages the customers at his doggy daycare to donate

Xin Tong with her husband Justas Budraitis and their baby daughter Luna Budraitis (pictured) from Manchester. The couple donated baby Luna's cord blood

'I'd spent eight months in and out of hospital, having three lots of chemotherapy and trying different types of drugs, more than I can remember,' says Nilush. 'But none of them worked and doctors told me my only option left was a transplant.'

Stem cells can be taken from a donor's blood or bone marrow, but the patient's tissue type needs to be matched.

'My younger brother was tested to see if he was a match, but sadly he wasn't,' says Nilush. 'And as I'm Sri Lankan, I was told the chance of finding a match was much lower than usual because there is a shortage of people from minority ethnic backgrounds on the bone marrow register.'

Those from a minority ethnic background have only a 37 per cent chance of finding a bone marrow match from an unrelated donor, whereas someone from a white Caucasian background has a 72 per cent chance because there are many more from this population signed up to the register.

A recruitment drive among the Sri Lankan community in London couldn't find a match for Nilush, so the only chance for him was a transplant of stem cells from cord blood, i.e. that which remains in the placenta and umbilical cord following the birth of a baby.

Stem cells from cord blood don't have to be as highly matched in terms of the donor tissue type as adult stem cells.

This blood is rich in blood stem cells similar to those found in bone marrow, and because these cells have the ability to transform themselves into different types of cells, they can be used to treat a range of blood cancers, genetic disorders and immune deficiencies.

The charity Anthony Nolan, which runs the oldest bone marrow register in the UK, is now campaigning to encourage more parents to donate their baby's cord blood.

Since starting its cord blood storage programme in 2008, 324 of its donations have been used for life-saving transplants: the charity aims to bank 800 cords a year, from as diverse a population as possible.

The major benefit of cord blood stem cell transplants is they're less likely to be rejected by the host than an adult donor's cells.

'The stem cells from cord blood are more nave as they haven't been exposed to the environment or pathogens that could cause disease to a patient,' explains Dr Roger Horton, lead cord specialist at Anthony Nolan.

'They don't react in a way that could negatively impact the patient's health as much long term, which is always a possibility with cells from adult donors. So we are able to have a higher degree of mismatch and the transplant can still be a success.'

If no suitable donor is found, the charity will scour international registers for a match, as happened with Nilush.

He knows the stem cells used in his transplant came either from the cord blood of a baby born in the U.S. or from one born in Australia, as both matched.

'I'm all over the place a Sri Lankan, living in England, with an immune system from an American or an Australian,' Nilush laughs.

As well as increasing the number of transplants possible, cord blood stem cells extend the age range of patients to those of retirement age.

'With adult donor cells, high doses of chemotherapy are needed to thoroughly clean out the patient's own immune system and the side effects of this can be too harsh for older patients or those with other complications,' explains Dr Horton.

'But when using cord blood, you can use much less intense chemo, so it's broadened the window for transplant to people who have recently retired or older.'

Cord blood transplants have also increased the survival rates of some blood cancers, particularly in young patients with high-risk blood cancers. The exact figures are due to be published later this year.

The drawback of using these cells is an umbilical cord only holds 70ml to 300ml of blood.

'It's a finite amount, so we can't go back for a top-up if a patient needs more, which of course we can do if an adult donor is a match,' Dr Horton adds. (And with some diseases 'only adult donor cells will work as it can be given in greater amounts'.)

The actual transplant is relatively simple, Dr Horton says.

'The bag of cord blood, which has been stored at minus 196c, is defrosted in a waterbath at the patient's bedside and is infused via a central line into the chest, in a process lasting less than 20 minutes,' he says.

'It then takes between seven and 28 days to repopulate the bone marrow and create a functioning immune system.'

After having the cord blood transplant in November 2013, Nilush had to stay in hospital for two months. Since then, he has remained cancer free.

Yet when he was diagnosed in June 2012, after losing weight and having no energy, he was told his cancer was so aggressive that he had to start treatment immediately. He wasn't even given the time to go home first.

'I just had to start the chemotherapy straight away,' he recalls.

Anthony Nolan collects cord blood from babies born at five hospitals: St Mary's Oxford Road and St Mary's Wythenshawe, both in Manchester; Leicester Royal Infirmary; Leicester General Hospital and King's College Hospital in London.

Separately, the NHS collects cord blood from University College London Hospital, St George's Hospital in London and Luton & Dunstable University Hospital.

'Immediately after the baby is born, and the placenta is delivered, one of our collectors takes away the placenta and umbilical cord,' says Dr Horton.

Once collected, the blood is processed and tested to ensure it is free of viruses and bacteria, and is used either for research or is frozen and banked to be used for patients in the UK or around the world. It's the same process for cord blood collected by the NHS.

Anthony Nolan works with the NHS in sharing the register and together they store about 35,000 cord blood donations in Nottingham and Bristol. Unlike blood donations, cord blood can be stored indefinitely.

Despite the amount already stored, more donations are needed, particularly to help patients from African, African-Caribbean, Asian, Chinese, Jewish, Eastern European and Mediterranean communities.

Xin Tong, 34, and Justas Budraitis, 29, donated their daughter's cord blood.

Xin was a blood donor in China and is pleased that her daughter Luna has followed suit, saying: 'She was born a life-saver'

The couple, from China and Lithuania respectively, met when they were studying at Manchester University. Now married and still living in the city, their daughter Luna was born on October 26, 2022, weighing 8lb 9oz.

'We wanted to welcome her into the world by doing something with significance,' says Xin, an e-commerce account manager.

We saw the posters up in the hospital about donating when we went for antenatal checks and decided to sign up,' Xin explains. 'It was a simple process and we were told that when we went to hospital for the birth I should tell the midwife, who would inform Anthony Nolan.

'I ended up going into hospital early as Luna had stopped growing and needed to be induced, but I was still able to donate the umbilical cord.'

Xin was a blood donor in China and is pleased that her daughter has followed suit.

'She was born a life saver she's really special,' says Justas, who is an IT consultant.

Understandably, Nilush and his wife Helen, 55, are also vocal about the importance of cord donation.

'I tell all my customers about its benefits and since then two of them have donated successfully,' Nilush says, proudly.

'I wish everyone would look into it. I don't know when the parents donated or who they are, but their decision to donate their babies' umbilical cords is why I am here today. And I want other people to have the same chance.'

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How umbilical cords from babies are saving cancer patients' lives - Daily Mail

Alzheimer’s study shows improved memory and mood with … – Drug Target Review

Using rodent models, the researchers emphasized the potential of newly generated neurons in adulthood to serve as therapy for addressing the functional deficits and pathology associated with Alzheimers disease.

In adult human brains, the hippocampus generates new neurons (adult-born neurons, or ABNs) throughout life, helping to maintain memories and regulate emotions. Scientists call this process adult hippocampus neurogenesis (AHN). In people with Alzheimers disease, this process is impaired, leading to reduced production of ABNs with poorer qualities. Given that Alzheimers patients often develop both cognitive symptoms (such as memory loss) and non-cognitive symptoms (such as anxiety and depression) for which AHN plays a critical role, one way to help Alzheimers patients achieve symptom relief could be to restore AHN.

Published in the journal Cell Stem Cell, scientists from University in Chapel Hill School of Medicine, US, demonstrated that stimulating a brain region called Supramammilary nucleus (SuM) located in the hypothalamus effectively enhanced adult-born neurons in the otherwise impaired Alzheimers brains of mice. After patterned stimulation of SuM, Alzheimers brains developed more ABNs with improved qualities. Importantly, activation of these SuM-modified ABNs restored both cognitive and affective deficits in Alzheimers mouse models.

It has been a longstanding question whether AHN can be sufficiently enhanced in impaired Alzheimers brains to improve brain function, said senior author Dr Juan Song. An important point to consider when addressing these questions is the low-level hippocampal neurogenesis, which becomes even lower in Alzheimers patients.

By manipulating a small number of ABNs in the Alzheimers brain, we demonstrate that ABNs can be enhanced even in the presence of Alzheimers pathology, and these enhanced ABNs are important for the restoration of behaviours and hippocampal function.

To enhance ABNs in Alzheimers brains, Song and colleagues adopted an elegant two-step ABN-enhancing strategy by first stimulating SuM using a patterned optogenetic paradigm with the goal of promoting the generation and developmental properties of ABNs, followed by stimulating the activity of SuM-enhanced ABNs using chemogenetics.

Optogenetics involves the use of light to alter the activity of brain cells expressing light-sensitive opsin genes. Chemogenetics involves the use of inert molecules to alter the activity of brain cells expressing designers receptors.

Interestingly, SuM stimulation alone or activation of ABNs without SuM stimulation failed to restore behavioural deficits in Alzheimers mice. Song said. These results suggest that multi-level enhancement of ABNs namely increasing their number, improving their developmental properties, and enhancing their activity is required to achieve their therapeutic benefits in Alzheimers brains.

When Song and colleagues further analysed the protein changes in the hippocampus of Alzheimers mice in response to activation of SuM-enhanced ABNs, the researchers found that several well-known protein pathways were activated inside cells. These pathways include the ones important for synaptic plasticity of neuronal cells that allow enhanced communication among them, as well as the ones important for phagocytosis of non-neuronal microglia that allow efficient plaque clearance.

It is striking that multi-level enhancement of ABNs through combined SuM and ABN stimulations allows such a small number of ABNs make profound functional contribution in diseased Alzheimers brains, Song said. We are eager to find out the mechanisms underlying these beneficial effects mediated by activation of SuM-enhanced ABNs on Alzheimers pathology and hippocampal function. Future efforts will be needed to develop drugs that mimic these beneficial effects mediated by activation of SuM-enhanced ABNs. Ultimately, the hope is to develop first-in-class, highly targeted therapies to treat Alzheimers and related dementia.

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Alzheimer's study shows improved memory and mood with ... - Drug Target Review

Biden Weaponized Health Care on Abortion, Transgender, COVID-19 – Daily Signal

FIRST ON THE DAILY SIGNALA coalition of conservative leaders and former federal government political appointees has compiled a game plan for the next conservative president to restore the Department of Health and Human Services to a focus on health care rather than forcing a leftist agenda down Americans throats.

From the COVID-19 pandemic to abortion funding and transgender mandates, HHS has twisted federal law and the pursuit of public health to marginalize people of faith and promote bureaucrats and leftist activism, warns a report edited by Roger Severino, former director of the HHS Office of Civil Rights under President Donald Trump. He argues that the next conservative president must reverse these abuses and return HHS to its proper role: the promotion of public health.

Few areas of life are more important, and more subject to abuse, than public health, Severino, vice president of Domestic Policy at The Heritage Foundation, told The Daily Signal in a statement Monday. Unfortunately, our public health agencies have replaced science and medicine with politics and ideology, and Americans now face shorter life spans as a result. Reform can only happen if entrenched special interests, from lawless bureaucratic leaders and Big Pharma, are reined in and rooted out. (The Daily Signal is The Heritage Foundations news outlet.)

Severino organized and edited a major report in the book Mandate for Leadership, compiled by the 2025 Presidential Transition Project, noting that after the COVID-19 pandemic was over, U.S. life expectancy continued to drop precipitously. A copy of the report on HHS was provided exclusively toThe Daily Signalfor this article.

The Heritage Foundation helped launch the 2025 Presidential Transition Project (also known as Project 2025) to equip a potential conservative president to govern effectively from Day One.

HHS has an outsized impact on the federal government, from its role in declaring public health emergencies to its management of Medicare and Medicaid to its $1.6 trillion annual budget. Under Presidents Joe Biden and Barack Obama, HHS has also used its power over health policy to promote abortion and transgender ideology.

Severinos team lays out five overarching goals for a conservative president intent on reshaping HHS: (1) protecting life from conception, protecting the rights of conscience of health care workers, and defending biological reality against gender identity ideology; (2) empowering patients to make their own health care choices, enabling providers to offer more options, and unleashing markets to drive down costs and improve quality; (3) promoting stable and flourishing married families instead of LGBT activism and single motherhood; (4) correcting the errors of the COVID-19 pandemic and preparing for the next health emergency; and (5) closing the revolving door between government and Big Pharma, where regulators leave government and work for companies they have regulated and pharmaceutical executives move from industry into regulatory agencies.

Severinos team breaks down the massive bureaucracy of HHS and presents specific recommendations for each branch of the behemoth agency. This article focuses on a few of the specific issues that motivate the major changes he recommends.

Many of the reports critiques and recommendations for a future HHS trace back to the departments abuses during the COVID-19 pandemic. It notes that while the HHS secretary declared a public health emergency, the threshold for what constitutes a public health emergencyhow many cases, hospitalizations, deaths, etc.was never defined.

Severinos team recommends that Congress restrict HHSs ability to declare indefinite public health emergencies, in part by establishing a set time frame for any emergency.

The report also recommends that the HHS secretary investigate, expose, and remediate any instances in which HHS violated peoples rights by colluding with Big Tech companies to silence dissent on COVID-19.

Severinos team says the Centers for Disease Control and Prevention should be broken up into two separate organizations: one dedicated to gathering scientific data and one responsible for making public health recommendationsan inescapably political function. The report notes that the CDC previously held back public health information on COVID-19 partially due to fear that the information might be misinterpreted.

CDC should report on the risks and effectiveness of all infectious disease-mitigation measures dispassionately and leave the should and must policy calls to politically accountable parties, the report suggests. Congress should ensure that CDCs legal authorities are clearly defined and limited to prevent an arbitrary and vacillating exercise of power, as the U.S. experienced during the pandemic.

Severinos report recommends that the Food and Drug Administration, not the CDC, should regulate vaccines, and calls for reforms to prevent the National Institutes of Healths inappropriate industry ties that create serious conflicts of interest.

The report notes that the National Institute of Allergy and Infectious DiseasesAnthony Faucis division of the NIHowns half of the patent for the Moderna COVID-19 vaccine, among thousands of other pharma patents. According to NIH documents, NIH Director Francis Collins, Fauci, and Faucis deputy director, Clifford Lane, all received royalty payments from pharmaceutical companies between 2009 and 2014.

The report faults NIH for funding gain-of-function viral research that may have been responsible for COVID-19.

Severinos team recommends HHS change many policies to protect unborn life and maternal health and to honor the religious convictions of Americans who object to the use of aborted baby body parts in medical research.

The CDC should fund studies into the risks and complications of abortion and require states to report abortion complications and babies born alive despite an attempted abortion, the team writes. It should prohibit research on aborted baby body parts, since such research can be easily replaced with research on adult stem cells. And it should avoid promoting abortion as health care.

The report condemns the CDCs current abortion and maternal mortality reporting systems as woefully inadequate, since states provide those statistics on a voluntary basis. Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mothers state of residence, and by what method.

Severinos team urges the FDA to reconsider its approval of chemical abortion drugs, an approval that currently faces a court challenge. The report notes that the complication rater for chemical abortion is four times higher than that of surgical abortion and that the chemical abortion drug mifepristone has been associated with 26 deaths of pregnant mothers, over 1,000 hospitalizations, and thousands more adverse events. It also calls the approval of this drug politicized and illegal from the start.

The report also calls for the FDA to loosen its restrictions on foreign-made vaccines that were not derived through or tested on aborted baby cells, reinstituting a Trump-era waiver for Japanese-made vaccines.

It urges the Centers for Medicare and Medicaid Services to block Planned Parenthood from receiving Medicaid funds and to redirect funds to health centers that provide real health care for women.

Severinos team urges HHS to audit the Centers for Medicare and Medicaid Services for compliance to the Hyde Amendment, which prevents federal funding of abortions, and to perform a full review of HHS efforts to promote abortion in the wake of the Supreme Courts overturning Roe v. Wade.

The report also urges various HHS departments to rescind ideologically motivated fearmongering guidance that the Biden administration released in the wake of the courts ruling, such as warnings about state governments targeting women for getting abortions.

Radical actors inside and outside government are promoting harmful identity politics that replaces biological sex with subjective notions of gender identity,' Severinos team warns. The report urges a potential conservative president to reverse this trend.

Bidens HHS has interpreted Section 1557 of the Affordable Care Act (also known as Obamacare), which prohibits discrimination on the basis of sex in health care, to forbid discrimination on the basis of gender identity and sexual orientation as well. Severinos team urges a future HHS secretary to explicitly revoke this guidance, as HHS did under Trump.

The report says that the Centers for Medicare and Medicaid Services should reissue and expand upon its 2016 decision that it cannot recommend gender reassignment surgery for Medicare beneficiaries, citing the growing body of evidence that such interventions are dangerous. (Many doctors recently testified in favor of a Florida rule blocking Medicaid coverage for experimental transgender interventions.)

The report also urges HHS to withdraw guidance allowing taxpayer funds to pay for cross-sex transitions.

It faults the NIH for having been at the forefront in pushing junk gender science, and encourages the agency to fund studies into the short-term and long-term negative effects of [cross-sex] interventions, including affirmation, puberty blockers, cross-sex hormones and surgeries, and the likelihood of desistence [abandoning the desire to change ones sex] if young people are given counseling that does not include medical or social interventions.

Severinos team notes that under liberal administrations, the office of HHS that he led, the Office for Civil Rights, has amassed a poor record of devoting resources to conscience and religious freedom enforcement and is often complicit in approving or looking the other way at the administrations own attacks on religious liberty.

The report encourages a prospective conservative president to direct the Office for Civil Rights to return to the Trump-era policies that initiated robust enforcement of these conscience laws. It urges HHS to reestablish waivers for state and child welfare agencies, especially for faith-based adoption and foster care agencies, which had previously been excluded from federal programs because they were unwilling to place children with same-sex couples.

Severinos team warns that Medicare and Medicaid operate runaway entitlements that stifle medical innovation, encourage fraud, and impede cost containment, in addition to which their fiscal future is in peril.

The report urges the Centers for Medicare and Medicaid Services to increase Medicare beneficiaries control over their own care; reduce regulatory burdens on doctors; ensure sustainability and value for both beneficiaries and taxpayers; and reduce fraud, waste, and abuse. It favors Medicare Advantage and urges Medicare to pay the same amount for outpatient procedures that it does for inpatient hospital services. It also encourages Medicare to reform payments along the lines of intensity and value of service, as opposed to a fee-for-service model.

Severinos team warns that Medicaid has a higher percentage of improper payments than any other federal program, and encourages the program to stop covering nonmedical services like air conditioning and housing. The report says the Centers for Medicare and Medicaid Services should give states more flexibility to strengthen program integrity and to incentivize personal responsibility through work requirements and private insurance.

Severinos team encourages HHS to decommission the CDC and NIH Foundations, nonprofit entities whose boards are populated with pharmaceutical company executives.

Private donations to these foundationsa majority of them from pharmaceutical companiesshouldnot be permitted to influence government decisions about research funding or public health policy, the report urges.

We must shut and lock the revolving door between government and Big Pharma, it adds. Regulators should have a long cooling off period on their contracts (15 years would not be too long) that prevents them from working for companies they have regulated. Similarly, pharmaceutical company executives should be restricted from moving from industry into positions within regulatory agencies.

Severinos team recommends more changes to HHS, including a prioritization of fatherhood in the many social programs HHS controls, and the elimination of the Head Start preschool program and the NIH Office of Equity, Diversity, and Inclusion.

Correction: This article has been corrected to reflect the authorship of the Project 2025 HHS report.

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