Stem Cells Treating Rheumatoid Arthritis

 

As someone who's family has dealt with having a loved one deal with rheumatoid arthritis, I have seen them run through a wide array of treatment options. They tried everything from chemotherapeutic injections to dietary changes and natural remedies, however the only treatment that has worked so far is stem cell treatment. According to an article published by Frontiers in Immunology journal, Mesenchymal stem cell (MSC) treatment uses embryonic mesodermal stem cells for their regenerative properties to promote healing in the recipient. The MSCs secrete a regenerative bioactive factor that acts as a signal to surrounding cells. These factors stimulate site-specific and tissue-specific stem cells of the patient rather than growing into tissue producing cells. Thus, initiating growth of local cells native to the patients own body.

            MSC’s are found naturally in a few main areas of the body which include bone marrow, the umbilical cord, adipose tissue and synovial membranes (the layer surrounding joints which can be affected by rheumatoid arthritis and osteoarthritis). Each of these areas where MSCs are found have distinct advantages and disadvantages in treatment applications. Bone marrow derived MSCs (BM-MSCs) was the first site used for extraction in research studies due to its safety and effectiveness. BM-MSCs are marked by their high differentiation potential which is associated with a high repair potential. However, the disadvantages of BM-MSC’s include the risk of harvesting, condition of the donor, and risk of infection. In the case of the use of these stem cells to treat rheumatoid arthritis, the goal is to reduce the synovial inflammation which leads to synovial hypertrophy, ultimately resulting in bone and cartilage erosion. All these processes leave the patient with severe joint pain and a lack of mobility. In a non-arthritic joint T-lymphocytes and B cells monitor and control inflammation and swelling. When treated with BM-MSCs, however, studies have shown promising progress in the effectiveness of inflammation reduction. Additionally, studies have found that MSCs might be even more effective in treating the swelling of synovial fluid by promoting stimulation of regulating immune cells. Ultimately having a positive outlook on treatment options for subsiding swelling in joints and preventing further degradation of bone and cartilage tissues.

Hwang JJ, Rim YA, Nam Y, Ju JH. Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis and Osteoarthritis. Front Immunol. 2021 Mar 8;12:631291. doi: 10.3389/fimmu.2021.631291. PMID: 33763076; PMCID: PMC7982594.

Animal Preclinical Models Show Evidence behind "Chemo-Brain"

    Chemo-Brain is the colloquial term for a side effect of chemotherapy treatment that is only commonly talked about amongst cancer survivors. It is the impairment of memory, attention, and cognitive processing that occurs once someone has been exposed to a chemotherapeutic agent. Chemo-Brain is a condition that can be related to by most all cancer survivors yet there is not much research that has been conducted on it. Many survivors have been told that they are not actually experiencing it while others have had to quit jobs or change lifestyles in order to accommodate for it. Any ongoing and recent research about Chemo-Brain needs to be given attention so that cancer survivors and chemotherapy patients with these symptoms can feel validated. One of the strongest pieces of evidence behind Chemo-Brain is a research article published in 2021 called "Animal models of chemotherapy-induced cognitive decline in preclinical drug development". Researchers John et al were able to find evidence in animal models regarding a correlation between chemotherapy exposure and cognitive decline. They found that there were altered neurotransmitter levels, microtubule disintegration, neuroinflammation, reduced neurogenesis, and mitochondrial dysfunction that were found in each of the animals that were exposed to chemotherapeutic agents regardless of which agent was used. This is all to say that the brains of the animals became inflamed, were not able to form new connections between neurons as efficiently and were overall reduced the function of the brain. This all occurred because the chemotherapeutic drugs used caused higher amounts of cytokines in the brain. These cytokines can cause inflammation, so the brain cells became too compacted together and were therefore not able to function at full capacity (John et al., 2021). This research must be brought into human trials to see if this occurs in human patients undergoing chemotherapy.

References

John, J., Kinra, M., Mudgal, J., Viswanatha, G. L., & Nandakumar, K. (2021). Animal models of chemotherapy-induced cognitive decline in preclinical drug development. Psychopharmacology, 238(11), 3025–3053.

Using Adderall Responsibly

    It is not uncommon for people in today's fast-paced world to seek ways to improve their focus, concentration, and overall cognitive performance with Adderall. Prescription drugs containing amphetamine and dextroamphetamine are marketed as Adderall, and they influence the brain's neurotransmitters by stimulating the central nervous system. This drug is mainly prescribed to treat ADHD, which helps patients with these conditions become more focused and control their impulsivity. Due to its Schedule II status as a controlled substance, Adderall carries a risk of abuse and dependence. Once a proper diagnosis has been established, it must be used under the close supervision of a healthcare provider. For people with ADHD, when taken as directed, it can have a significant positive impact and help them live more focused and productive lives. The misuse of Adderall is among the major issues surrounding the drug. To enhance their cognitive abilities or maintain alertness and wakefulness for prolonged periods of time, some individuals use the medication over-the-counter. Misuse of prescription stimulants can result in serious health problems like heart attacks, seizures, elevated blood pressure, and even lethal overdoses. It also discusses the possibility of psychological dependence, since some people may grow very dependent on the drug in order to stay focused or get high. Even when used as directed, Adderall can have negative effects, just like any other drug. These adverse effects may include: nervousness or anxiety; insomnia; elevated blood pressure and heart rate; decreased appetite; digestive problems; and the possibility of mood swings. It is imperative that patients follow the recommended dosage and usage guidelines to reduce the likelihood of Adderall misuse. Through raising awareness of the potential risks of abuse, public awareness campaigns and educational initiatives can encourage the responsible use of Adderall. Adderall is a helpful medication for those who genuinely need it to treat conditions like narcolepsy and ADHD. When used as prescribed, it can lead to significant improvements in focus and overall quality of life. Abuse of Adderall, however, can become addictive and carries a significant risk to one's health. Remember that appropriate usage, precise diagnosis, and consistent contact with medical professionals are crucial for safely optimizing this medication's benefits while lowering its risks. Understanding the truth about Adderall is ultimately the first step to safeguarding your health and well-being if you are considering using the medication.

NIDA. 2018, June 6. Prescription Stimulants DrugFacts. Retrieved from https://nida.nih.gov/publications/drugfacts/prescription-stimulants on 2023, October 18

Mindful-based Interventions within the Workplace

The topic that I was interested in was looking at stress and some ways to manage it. Especially within the workplace, but I believe that a technique like this should be applied to a lot of different places where stress levels are high like schools. Mindfulness-based interventions (MBI) is a time of thoughtfulness that comes from the Buddhist idea of mindfulness. This entails for the person to aware of their thoughts, feelings, bodily sensations and surrounding environment. Never really attaching yourself to any ideas and just being in tune with your surroundings. It's related to being accepting, compassionate, and nonjudgmental. This is done by controlling your breathing, walking, or sitting, and really focusing on filtering out your thoughts. The tradition of mindfulness is becoming something that is not just a Buddhist tradition, but a popular technique that is being used in the educational setting and healthcare. In this research, they looked at the cumulation of all the publications about MBIs and their effects on stress disorders like depression, anxiety, insomnia, eating disorders, addiction, ADHD, and PTSD. They also looked at chronic diseases that affect physical health like pain, hypertension and cardiovascular disease, diabetes, cancer and asthma.

The implication of MBIs is heavily discussed in ethics and the research points out the use of this in business and military settings which may be a cause for concern due to the morals that are encouraged through this technique. However, in a general context, MBI was shown to have a great benefit in helping common mental, physical and social health conditions. I believe that a system like MBI should be implemented in high stress jobs and settings in order to create better workplace environment and happier contributors to society. Happier people means better work efficacy which means more work being done. 

Sources:

   Rachael A. Heckenberg a, a, b, AbstractObjectiveMindfulness-based interventions (MBI) have been related with improved job satisfaction, Kivimäki, M., Niedhammer, I., Eddy, P., Eller, N. H., Bakker, A. B., Grossman, P., Irving, J. A., Lundberg, U., Adam, E. K., Thayer, J. F., Brown, K. W., Jadad, A. R., Kabat-Zinn, J., Malarkey, W. B., Gex-Fabry, M., … O’Leary, K. (2018, September 22). Do workplace-based mindfulness meditation programs improve physiological indices of stress? A systematic review and meta-analysis. Journal of Psychosomatic Research. https://www.sciencedirect.com/science/article/abs/pii/S0022399918305749?via%3Dihub

    Zhang, D., Lee, E. K. P., Mak, E. C. W., Ho, C. Y., & Wong, S. Y. S. (2021). Mindfulness-based interventions: an overall review. British medical bulletin, 138(1), 41–57. https://doi.org/10.1093/bmb/ldab005

Narcolepsy

One interesting physiological issue is narcolepsy, a rare and intriguing neurological disorder characterized by excessive daytime sleepiness, sudden and uncontrollable episodes of falling asleep (known as cataplexy), and disruptions in the sleep-wake cycle. Narcolepsy is thought to result from a deficiency in the neurotransmitter hypocretin (or orexin), which plays a crucial role in regulating wakefulness and sleep. This condition can significantly impact a person's daily life, making it challenging to stay awake and alert during the day, leading to accidents and difficulties with work or social activities. 

Narcolepsy is estimated to affect about 1 in 2,000 people, and its exact cause remains a subject of ongoing research. The most common form of narcolepsy, Type 1 narcolepsy, is often associated with the loss of hypocretin-producing cells in the brain. Various studies have contributed to our understanding of this condition, such as "Narcolepsy and Low CSF Hypocretin (Orexin) Concentration in Monozygotic Twins" published in the New England Journal of Medicine in 2000. Further research is essential to develop more effective treatments and management strategies for narcolepsy, ultimately improving the quality of life for individuals living with this condition. 

Source: Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., ... & Yanagisawa, M. (1999). Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell, 98(4), 437-451. URL: https://www.ncbi.nlm.nih.gov/pubmed/10481909

Worms with ADHD??

    

    The title of this post likely left you confused, you're probably wondering first of all, how can a worm be on the spectrum and second of all why does it matter? I was wondering these same things in my first meeting with Dr. Streifel when she was explaining her potential research projects I could be a part of. Through my research experience, I learned how much the microscopic worms known as C. elegans can inform us about the human brain's dopamine pathways and how a trace metal in our water may be triggering inattentive ADHD.

    Dr. Sydney Brenner proposed C. elegans as an ideal model to learn about a myriad of different human diseases. These hermaphroditic worms that live for less than 3 weeks mirror over "40% of human disease related genes" (Airton et al., 2022). Despite the fact that C. elegans have a mere 302 neurons as compared to the 86 billion neurons present in the human brain, C. elegans have a fully intact dopaminergic system and are fully capable of having ADHD. Despite a few key differences, the worms have most of the same receptors, synaptic components, and neurotransmitters. (Schmeisser and Parker, 2018). A tell tale sign of ADHD is low level dopamine, with a major culprit being dysregulation of the dopamine transporter (DAT). The dopamine transporter is an essential target for medication and a hot topic of research (Madras, 2005). In my research we can visualize the dopamine transporters using worms with a green fluorescence protein. 

    Now that you are convinced that a 1nm nematode can have ADHD and is also an excellent animal model for experimentation, you are ready to hear the premise of my research. Trace metals such as manganese, iron, calcium, copper, and cobalt are essential for the function of our body, but too much and there can be deadly neurotoxic effects on your brain. The metal we are studying, manganese, can cause a deadly disease known as Manganism which results in Parkinson like symptoms. It has also been known to cause ADHD like symptoms in children exposed to high levels of the metal (Farias, 2010). In 2020 there was an epidemiological study conducted on children across Denmark that found that manganese levels greater than 100ug/L caused a 51% increase in the inattentive subtype of ADHD in females, and a 20% increase in males (Shullehner, 2019). With the "safe" limit of manganese in US drinking water being 300 ug/L, I am eager to determine if low level exposure to manganese causes an increase in the incidence of ADHD in my C. elegans ("Manganese in Drinking Water," 2023). 

References

Farias, A. (2010). Manganese in children with attention-deficit/hyperactivity disorder: Relationship with methylphenidate exposure. Journal of child and adolescent psychopharmacology. https://pubmed.ncbi.nlm.nih.gov/20415606/#:~:text=Earlier%20studies%20associated%20elevated%20levels,by%20high%20levels%20of%20Mn.

Madras, B. (2005). The dopamine transporter and attention-deficit/hyperactivity disorder. Biological psychiatry. https://pubmed.ncbi.nlm.nih.gov/15950014

Manganese in drinking water fact sheet & frequently asked questions. Iowa National Department of Resources. (2023). https://www.iowadnr.gov/Portals/idnr/uploads/water/wso/docs/ManganeseFactSheetandFAQ.pdf

Martins, A. C., Gubert, P., Li, J., Ke, T., Nicolai, M. M., Moura, A. V., Bornhorst, J., Bowman, A. B., & Aschner, M. (2022, September 29). caenorhabditis elegans as a model to study manganese-induced neurotoxicity. Biomolecules. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599542/#B23-biomolecules-12-01396

Schmeisser, K., & Parker, A. J. (2018). Worms on the Spectrum - C. elegans models in autism research. Experimental Neurology, 299, 199–206. https://doi.org/10.1016/j.expneurol.2017.04.007

Schullehner, J., Thygesen, M., Kristiansen, S. M., Hansen, B., Pedersen, C. B., & Dalsgaard, S. (2019). Exposure to manganese in drinking water during childhood and association with attention-deficit hyperactivity disorder: A nationwide cohort study. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.3369767

Are Neuroenhancements Ethical?

    As we go further and further into the future, many ideas that were previously only explored in science fiction are becoming more of a reality. One of these ideas is neuroenhancement or utilizing certain techniques to enhance people to make them better through the use of technology. Even when disregarding the potential ethical dilemmas that come with the actual implementation of this sort of technology into a person, whether that be through surgery or through some sort of drug, there are other ethical dilemmas that are apparent when looking at the outcomes that will result from this sort of technology. One study focused on determining the general consensus of the use of neuroenhancements, whether they be neuronal implants that enhance brain function or a performance-enhancing drug. The mean scores indicated that many people agreed with their use in a military setting, given that it was well tested before use, as well as the fact that people should be able to freely decide if they want to take part in programs designed with neuroenhancements in mind. However, they also expressed some agreement with statements regarding allowing people to keep neuroprostheses after active duty ends, which may be helpful in some cases but could pose a threat depending on how the particular implant functions.  

    Initial concerns about ethics arise when determining the role that neuroenhancements play in the rest of the affected person’s life. As stated previously, it is clear that the patient's autonomy be prioritized throughout the whole process, making sure that they are well educated on the risks and outcomes of procedures, and that the procedures themselves are non-mandatory. Other concerns, particularly those relating to non-malfeasance, are harder to exactly quantify. Since these supposed implants would make potential candidates better soldiers, the doctors who are performing these surgeries would in some ways be indirectly harming those who it would be used against. These ethical dilemmas don’t just stop at the military level, however, as there is potential that these enhancements could cause lasting harm to the patient if not properly managed. Additionally, another study specifically mentions how the autonomy of children could be implicated if their parents decide to allow them to undergo enhancement that significantly changes their life. Even though there are many positive benefits that could come with the proper use of neuroenhancements, there are many ethical pitfalls that make them less appealing than initially thought. 

Sources:

Chatterjee A. The ethics of neuroenhancement. Handb Clin Neurol. 2013;118:323-34. doi: 10.1016/B978-0-444-53501-6.00027-5. PMID: 24182389.

Sattler, S., Jacobs, E., Singh, I., Whetham, D., Bárd, I., Moreno, J., Galeazzi, G., & Allansdottir, A. (2022). Neuroenhancements in the Military: A Mixed-Method Pilot Study on Attitudes of Staff Officers to Ethics and Rules. Neuroethics, 15(1). https://doi-org.dml.regis.edu/10.1007/s12152-022-09490-2