International Journal of Translational Science

Editorial

Pranela Rameshwar — 2024-04-20

This second issue of the International Journal of Translational Science (River Publisher) have six papers with the theme of translational science. One of the journal’s goals is to submit early clinical trials to alert other scientists and stakeholders of the data. The issue publishes an article demonstrating long-term benefit of facial regeneration. The described process showed the outcome of stromal vascular fraction and extracellular matrix. The study did not address long-term effect. However, since this clinical study used autolo- gous cells, there is implied safety in the approach. The issue includes a study that supports alternative treatments and approach for mental illness. This study fits with the journal’s goal to be inclusive in clinical approaches as well as to bring international studies to the global audience. Lakey et al. showed the potential for a novel peptide to drop blood glucose levels in immune deficient mice. Although this is an early outcome, the experimental evidence suggests that the peptide could show clinical benefit as the group proceeds with additional studies. The study by Levit et al. outlines a novel effect by Porphyromonas gingivalis infection on cardiovascular risk. The group presents potential biomarkers to predict early risk; hence relevance to preven- tive care that is likely to mitigate cardiovascular risk. This issue also include a basic science study on a clinical issue, namely preeclampsia (PE). These patients are treated with aspirin to prevent PE. This authors demonstrated aspirin reseting the function of placenta stem cells. The group further showed that the reset stem cells could mitigate inflammation, indicating that aspirin could be involved in counteracting the mother’s inflammatory response via placenta stem cells. The question is how fast research and experimental trials could get to the clinic. This was addressed in an opinion article by William Faloon. The author used available data to discuss FDA delays in approving drugs. This is a must-read article that carefully discuss drug approval delays that appear to continue to date.

Long Term Rejuvenation of Facial Skin by Transplantation of Autologous Stromal Vascular Fraction and Pre-conditioned Matrix: A Clinical Study

N. Cuylits. Phu — 2024-04-20

Background: For skin rejuvenation, today no procedure describes a specific treatment of the extracellular matrix (ECM) combined with stromal vascular fraction (SVF) from adipose tissue. A new product AmeaCell^® , allows SVF extraction and ECM preconditioning in hypoxic conditions. Hypoxia significantly increased the adhesion of adipose derived stem cells and enhace their proliferation and differentiation.

Objective: This clinical study aimed to evaluate safety and efficiency of this new procedure, over one year.

Material and methods: The study was performed on 23 patients. After a liposuction and fat proceed, SVF and the matrix were extracted and preconditioned following Ameacell^® procedure, then injected into wrinkles. Results were scored for WSRS and GAIS scales at 6, 12 months after surgery.

Results: No serious adverse reactions occurred. Regarding efficiency, whatever the baseline, the Ameacell^® procedure triggered an improvement of WSRS score in most patients after one year follow-up: 75% of patients when WSRS score at baseline 2; 83% of patients when WSRS score at baseline 3. This is in accordance with the GAIS scored by both investigators and patients.

Conclusion: This one-year follow-up clinical study using Ameacell^®procedure, exhibited an improvement of facial skin appearance.

Plant Medicine, Psychedelics and the Inner-Sciences of Mental Wellness: Implications for Healthy Longevity and Rejuvenation

Jeffrey L. McNairy — 2024-04-20

Rythmia Life Advancement Center is the first and currently only medically licensed Ayahuasca center in the world. Rythmia is helping to bridge the gap between the Western medical model of health care with the indigenous healing modalities of Latin America. The “Rythmia Way” program uses a variety of modalities, in addition to Ayahuasca, to help individuals find meaning in their lives and overcome depression, anxiety, trauma and PTSD. The quickly growing field of psychedelic medicine is in need of a format to facilitate the use of these substances in the most effective manner. The rapid rate of healing can pose challenges for traditional providers, which is why Rythmia is at the forefront of this field and is collecting hundreds of thousands of data points to effectively tailor and manage a safe plant medicine experience. Self-reported patient data, combined with observational program participation is collected and evaluated to enable individuals to achieve the most effective outcomes regarding their goals and intentions.

Mental health issues are becoming the number one health concern in the post-pandemic world. Depression and anxiety are preventing millions from living a productive life. Mental health issues are the leading cause of suicide globally. The information collected at Rythmia Life Advancement Center in Costa Rica shows a programmatic strategy that is effective at reducing depression, anxiety, and symptoms related to trauma, based on self-reported participant exit surveys. The traditional routes for individuals suffering from these mental health conditions (psychotropic medication, therapy, hospitalization, etc.), are not producing the outcome results necessary for society to thrive. Rythmia L.A.C. is providing a blueprint for the healthcare industry to follow which addresses these problems in a quick and efficient manner.

Rythmia Life Advancement Center is a licensed medical facility from the Costa Rican Ministry of Health, founded by Gerard Powell, and located in the Blue Zone Province of Guanacaste, Costa Rica. Mr. Powell was a self-made multimillionaire who had developed a severe drug and alcohol problem and lived a self-destructive lifestyle up until the age of 50. After 2 failed suicide attempts, an unsuccessful 60-day inpatient stay at a drug rehab, and 5 years of therapy riddled with relapse and depression, Mr. Powell discovered Ayahuasca as a treatment modality that showed benefit to mitigate his mental health issues. The lifechanging impact of Ayahuasca on Mr. Powell’s life was transformational and took place over a very short period of time. Mr. Powell was so enthusiastic about his profound level of healing that he wanted to share what he experienced with the world. In July of 2014, he enlisted the help of his therapist, Dr. Jeff McNairy, to participate in the Ayahuasca experience, and to help establish the first and only medically licensed Ayahuasca center in the world. Upon receiving Dr. McNairy’s personal breakthroughs with the plant medicine, he made the decision to shift his career from health care management of drug and alcohol rehabilitation and his therapy practice in Los Angeles, California, to help create the first of its kind wellness center based around Ayahuasca. Since Rythmia’s opening in January 2016, over 15,000 guests have participated in the program with a 97% success rate, determined by exit survey data gathered upon discharge.

Ayahuasca is an indigenous plant-based medicinal drink, originating from the Amazon basin of South America. Shamans from this region of Latin America have been using this remedy for over three thousand years. Indigenous tribes consume Ayahuasca as a method to heal physical and “spiritual” ailments. The drink is made up of two plants: one is a vine known as Banisteriopsis caapi which contains three important alkaloids (harmine, harmaline, and tetrahydroharmine) which are Monoamine Oxidase-Inhibitors (MAO-I’s). The second plant is a N,N-Dimethyltryptamine (DMT) rich leaf-based plant named Psychotria viridis, which is found regionally where the shamanic tribes originate. When these two plants are reduced, mixed together, and consumed orally, they produce a psychedelic response in humans that creates a serotonin response said to enhance personal connection with self, nature, and others. The peak reaction point of the Ayahuasca is approximately 2 hours, with a half-life of DMT being anywhere from 2.5 to 4 hours. The contraindication risk for Ayahuasca is primarily with SSRI medications, which interact with MAO-I’s to potentially produce a serotonin syndrome in the brain. Participants must have at least 30 days free and clear from SSRI’s before drinking Ayhuasca, as well as be free of illicit drugs, alcohol, and other psychtropic medications. A certain amount of preparation is required prior to the consumption of Ayahuasca, in order to ensure a safe and effective experience.

Rythmia has established an admission protocol in which users must undergo multiple screenings before entering the program. The aim is to prevent any complications following ayahuasca ingestion. This is why there is a policy of 30 days without the use of any substance that affects certain neurochemical receptors and neurotransmitters. Additionally, applicants should not have any cardiac conditions, and on a psychological level, the absence of psychiatric illnesses such as bipolar disorder, schizophrenia, or prior episodes of psychosis is required. As a result of participation in the program, users have reported the resolution of psychiatric conditions such as depression, anxiety, post-traumatic stress, as well as a reduced need for pharmaceutical support upon returning home. Finding a greater connection with loved ones and overall life satisfaction is also reported by participants from post-program follow-up.

The “Rythmia Way” is a program based on specific directives from the CEO and Owner of Rythmia (Gerard Powell) that allow participants to maximize their experience with Ayahuasca. The program is comprised of various classes, Ayahuasca sessions, and workshops that teach three major intentions guests use to obtain their goals: 1. Show Me Who I’ve Become, 2. Merge Me Back With My Soul At All Costs, and 3. Heal My Heart. These intentions, when followed, will empower the individual to learn about their ego, no longer live in a dissociated state, and heal past traumas that are blocking them from being vulnerable in healthy ways and succeeding in life. Rythmia is a data driven program that looks at process and outcome data to fine tune and create a way of obtaining the highest success rates. The combination of informational classes and integration workshops helps provide guidance and understanding to the plant medicine experience.

As global jurisdictions begin to legally allow Ayahuasca as a legitimate health modality to be used under strict supervision and control, Rythmia Life Advancement Center is positioned to expand and create further opportunities for individuals to obtain significant and long-lasting healing. DMT is currently a Schedule 1 substance that is banned in most of the world. Certain exemptions are beginning to be made for research, communities of high risk and minimal resources, and as an alternative method for healing that is being re-evaluated since the UN Convention on Psychotropic Substances of 1971. As education and grass-roots organizations make headway in the areas of legalization, standards of care will need to be instituted to ensure safety, efficacy, and lasting duration of the process. Rythmia has set the standard of care in this field and will continue to lead the world as governments and health care agencies understand the benefits of these organic and ancient plants that have been combined thousands of years ago for the good of humanity as well as the earth. This commentary described an early clinical treatment that would require controlled clinical trial to transition as standard of care.

Advances in Stem Cell and Regenerative Therapies in Autoimmune and Metabolic Diseases: Implications for Healthy Longevity

Jonathan R. T. Lakey — 2024-04-20

Type 1 diabetes (T1D) is an important autoimmune disease characterized by the destruction of insulin-secreting β-cells in pancreatic islets of Langerhans resulting in hyperglycemia. More than 1.3 people in United States are suffering from T1D, and current treatments have failed to offer a lasting cure. T1D management requires lifelong daily injections of exogenous insulin to control blood sugar levels and secondary complications of this progressive disease, unless receiving pancreas or islet transplant with its associated risks from immunosuppression.

Peptide therapy aims to alter the response of cells by inducing or reducing cellular responses appropriate to the type of peptides used. The aim of this study was to investigate the protective effect on autoimmunity of Mito Organelle (MO) Peptides on the function and survival of peptides on pancreatic β-cells in non-obese diabetes (NOD) mice model. MO peptide product (Biopep Inc) is a mixture of organ-specific cellular extracts that were extracted from organ specific cells, homogenized, filtered, and sterilized.

MO Peptides administered twice-weekly (IM) over 17-week period in NOD mice model were able to prevent the progression of autoimmune-mediated β–cell destruction and the onset of hyperglycemia (blood glucose >300 mg dL) as compared to the saline treated control mice.

These studies will help understand the mechanisms of immunological protection in T1D and may serve as a model for other autoimmune disorders with peptides.

What Could Explain Delay for Age-Reversal Clinical Trials?

William Faloon — 2024-04-20

This is a commentary article using data reported by the United States Drug Approval (FDA) system for clinical trials. The text surmised reasons for this delay. The data show continued delay to impact drugs reaching patients. Instead of increasing drug approval, the statistics showed a trend of increased numbers of drug on hold. The reason for these delays need to be evaluated, and perhaps to apply new technologies to evaluate the data.

Restore Veto Property in Low Dose Aspirin/ASA Treated Preeclampsia Placenta Mesenchymal Stem Cells: Insights Into ASA-mediated Clinical Response*

Kimone A. Powell — 2024-04-20

Preeclampsia (PE) is a pregnancy complication characterized by elevated blood pressure, proteinuria, and other laboratory abnormalities. PE affects 2–8% of pregnancies globally and can lead to preterm birth and other complications for the mother and fetus. Successful pregnancy depends on the ability of the mother’s immune system to tolerate the allogeneic fetus. However, in PE, this immune tolerance is exacerbated by inflammation. Transforming growth factor β (TGF-β) is important to retain an immune balance in healthy pregnancy. In PE, TGF-β level is reduced, with an imbalance of the T-cell subset pool to favor inflammation. Omics studies by our group reported an increase in TGF-β signaling when PE-derived placenta mesenchymal stem cells (P-MSCs) were treated with low dose aspirin (ASA). This correlated with increased cycling quiescence and epigenetic changes, resembling healthy P-MSCs. This study tested the hypothesis that ASA could restore the veto property of P-MSCs to mitigate inflammation. ASA (10 mM) treated P-MSCs from PE and healthy placentas increased TGFβ1 and its receptor. The ASA treated MSCs, when added as third-party cells to a one-way mixed lymphocyte reaction, suppressed T-cell proliferation. Prediction studies with omics data indicated that ASA-mediated TGFβ signaling could explain ASA-induced blunting of cell apoptosis. Together, the findings support ASA-mediated expression of TGFβ1 and its receptor on P-MSCs from PE to restore the ability to be licensed as immune suppressor to mitigate PE inflammation. The findings provide new insight into the benefit of ASA treatment for PE.

Porphyromonas gingivalis Infection is Associated with Increased Vascular Inflammation in Patients with and Without Coronary Artery Disease

Courtney Levit — 2024-04-20

Vascular inflammation is a critical measure of risk for major adverse cardiac events in patients with and without known coronary artery disease. It is recognized that patients with poor oral hygiene tend to have an increased prevalence of coronary artery disease and myocardial infarction. Porphyromonas gingivalis (PG) is the keystone pathogen leading to periodontal disease. Despite evidence suggesting a link between active PG infection and coronary artery disease, there is limited data investigating whether PG can contribute to increased markers of vascular inflammation in patients with coronary artery disease. In this study, we studied 112 consecutive patients who presented at a community preventive cardiology clinic who consented to be assessed for the presence of PG. Subjects were enrolled in a mouth along assessment with measures of vascular inflammation, which was part of their routine clinical care. The average age of patients was 70.4 ± 8.5 years with 48.6% of the patients positive for PG and 20.5% with a history of coronary artery disease (CAD). The distribution of PG positivity was 48.3% and 34.8% in patients without and with a history of CAD, respectively. Patients with CAD have significantly greater levels of high sensitivity C-reactive protein (hsCRP_ (1.3 ± 0.3 vs. 3.2 ± 1.1 mg/dL, p = 0.04) and MPO (245.1 ± 19.4 vs. 371.4 ± 39.1 pmol/L, p = 0.003). Patients without a history of CAD, only Myeloperoxidase (MPO) was significantly increased. Statin use was significantly greater in those patients with a history of CAD. Interestingly, statin use tended to be greater in PG+ patients (71% vs. 62%) regardless of CAD status. The data from this early study demonstrate a link between active PG infection and increase in markers of vascular inflammation, especially in patients with established CAD. The findings suggest PG as a marker of cardiovascular risk, especially in patients with residual inflammatory risk.