The preclinical drug works by inhibiting the kinase Cdk5 which is found in mature neurons. Cdk5 has long been linked to neuropsychiatric and neurodegenerative disorders, but prior inhibitors have largely failed to cross the blood-brain barrier and enter the brain.
A new preclinical drug reported by James Bibb, Ph.D., and colleagues has the potential to combat depression, brain injury, and cognitive disorders. The drug, which is notable for being brain-permeable, works by inhibiting the kinase enzyme Cdk5.
Cdk5 is an important signaling regulator in brain neurons. Over three decades of research, it has been linked to neuropsychiatric and degenerative disorders such as Alzheimer’s.
Circa 2020 Immortality of the heart and heart regeneration.
Cardiovascular diseases represent the major cause of morbidity and mortality worldwide. Multiple studies have been conducted so far in order to develop treatments able to prevent the progression of these pathologies. Despite progress made in the last decade, current therapies are still hampered by poor translation into actual clinical applications. The major drawback of such strategies is represented by the limited regenerative capacity of the cardiac tissue. Indeed, after an ischaemic insult, the formation of fibrotic scar takes place, interfering with mechanical and electrical functions of the heart. Hence, the ability of the heart to recover after ischaemic injury depends on several molecular and cellular pathways, and the imbalance between them results into adverse remodeling, culminating in heart failure. In this complex scenario, a new chapter of regenerative medicine has been opened over the past 20 years with the discovery of induced pluripotent stem cells (iPSCs). These cells share the same characteristic of embryonic stem cells (ESCs), but are generated from patient-specific somatic cells, overcoming the ethical limitations related to ESC use and providing an autologous source of human cells. Similarly to ESCs, iPSCs are able to efficiently differentiate into cardiomyocytes (CMs), and thus hold a real regenerative potential for future clinical applications. However, cell-based therapies are subjected to poor grafting and may cause adverse effects in the failing heart. Thus, over the last years, bioengineering technologies focused their attention on the improvement of both survival and functionality of iPSC-derived CMs. The combination of these two fields of study has burst the development of cell-based three-dimensional (3D) structures and organoids which mimic, more realistically, the in vivo cell behavior. Toward the same path, the possibility to directly induce conversion of fibroblasts into CMs has recently emerged as a promising area for in situ cardiac regeneration. In this review we provide an up-to-date overview of the latest advancements in the application of pluripotent stem cells and tissue-engineering for therapeutically relevant cardiac regenerative approaches, aiming to highlight outcomes, limitations and future perspectives for their clinical translation.
Cardiovascular diseases represent the major cause of morbidity and mortality worldwide, accounting for 31% of all deaths (Organization WH 2016). Myocardial infarction (MI) is associated with necrosis of the cardiac tissue due to the occlusion of the coronary arteries, a condition that irrevocably diminishes oxygen and nutrient delivery to the heart (Thygesen et al., 2007). While effective therapies, including surgical approaches, are currently used to treat numerous cardiac disorders, such as valvular or artery diseases, available therapeutic treatments for the damaged myocardium are still very limited and poorly effective. Furthermore, after an ischaemic insult, the formation of fibrotic scar takes place, interfering with mechanical and electrical functions of the cardiac tissue (Talman and Ruskoaho, 2016).
Mitochondrial uncoupling by agents such as BAM15 may mitigate age-related decline in muscle mass and function by molecular and cellular bioenergetic adaptations that confer protection against sarcopenic obesity.
Background Sarcopenic obesity is a highly prevalent disease with poor survival and ineffective medical interventions. Mitochondrial dysfunction is purported to be central in the pathogenesis of sarcopenic obesity by impairing both organelle biogenesis and quality control. We have previously identified that a mitochondrial-targeted furazano[3,4-b]pyrazine named BAM15 is orally available and selectively lowers respiratory coupling efficiency and protects against diet-induced obesity in mice. Here, we tested the hypothesis that mitochondrial uncoupling simultaneously attenuates loss of muscle function and weight gain in a mouse model of sarcopenic obesity.
A team of researchers at the National Institute of Health Doutor Ricardo Jorge in Portugal, working with a colleague at Lusófona University, also in Portugal, has found that the monkeypox virus has been evolving at a faster rate than expected. In their paper published in the journal Nature Medicine, the researchers describe their genetic study of the virus collected from 15 samples.
Monkeypox is a double-stranded DNA virus from the same genus as smallpox, and it mostly infects people in Africa. Scientist have known of its existence since the 1950s. Despite its name, the virus is more commonly found in rodents than monkeys. Prior research has shown that there are two main varieties of monkeypox: West African and Congo Basin—the former is far less deadly and is the clade that has infected several thousand people outside Africa. Prior research has also shown that viruses like monkeypox typically only mutate once or twice in a given year.
In this new effort, the researchers collected samples from 15 patients and subjected them to genetic analysis to learn more about how quickly the virus is evolving. They found the virus has mutated at a rate six to 12 times as high as was expected. The researchers suggest the sudden accelerated rate of mutation in the virus may be a sign that the virus has developed a new way to infect people—currently, it is believed to move from person to person through close contact with open lesions, through body fluids or by airborne droplets.
Researchers have discovered that the human liver never ages beyond just three years old, no matter how old an individual is.
The liver is an amazing organ. Not only is it capable of regenerating itself to repair damage from toxins, like alcohol, but the liver apparently never ages, either.
According to new research, the liver is almost always just under three years old. The concept of liver age has been a medical conundrum for decades. Studying animal livers has yet to offer any kind of answer, so scientists with TU Dresden looked at human livers to try to discern more about our body’s filter.
An international team of scientists at TU Dresden analyzed the livers of multiple individuals between the age of 20 and 84. Every individual’s liver cells showed that they were roughly the same age. “No matter if you are 20 or 84, your liver stays on average just under three years old,” Dr. Olaf Bergmann, lead researcher on the study, explained in a release.
Korea Brain Research Institute (KBRI, President Pann Ghill Suh) announced on Mar. 4 that its research team led by principal researcher Yoichi Kosodo has developed a technology to mass produce cerebral cortex neurons utilizing Induced pluripotent Stem Cells (iPS). The research outcome will be published in the March issue of Scientific Reports.
Scientists expect that it will be possible to treat brain diseases by restoring damaged area in the brain by mass producing neurons utilizing stem cells even though cerebral neurons die if one suffers from degenerative brain diseases such as dementia and Parkinson’s Disease.
In fact, a research team of Kyoto University in Japan conducted clinical test of transplanting neurons made of iPS into the brain of a patient with Parkinson’s disease. In Parkinson’s disease, neurons that generate the neurotransmitter dopamine die, resulting in symptoms such as muscle stiffness and tremor in hands and feet. Through the clinical test, the patient was treated with new neurons.
A few years ago, Jürgen Knoblich and his team at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) have pioneered brain organoid technology. They developed a method for cultivating three-dimensional brain-like structures, so called cerebral organoids, in a dish. This discovery has tremendous potential as it could revolutionize drug discovery and disease research. Their lab grown organ-models mimic early human brain development in a surprisingly precise way, allowing for targeted analysis of human neuropsychiatric disorders, that are otherwise not possible. Using this cutting-edge methodology, research teams around the world have already revealed new secrets of human brain formation and its defects that can lead to microcephaly, epilepsy or autism.
In a new study published in Nature Biotechnology, scientists from Cambridge and Vienna present a new method that combines the organoid method with bioengineering. The researchers use special polymer fibers made of a material called PLGA) to generate a floating scaffold that was then covered with human cells. By using this ground-breaking combination of engineering and stem cell culture, the scientists are able to form more elongated organoids that more closely resemble the shape of an actual human embryo. By doing so, the organoids become more consistent and reproducible.
“This study is one of the first attempts to combine organoids with bioengineering. Our new method takes advantage of and combines the unique strengths of each approach, namely the intrinsic self-organization of organoids and the reproducibility afforded by bioengineering. We make use of small microfilaments to guide the shape of the organoids without driving tissue identity, ” explains Madeline Lancaster, group leader at MRC Laboratory of Molecular Biology in Cambridge and first author of the paper.
Leading bipartisan moonshots for health, national security & functional government — senator joe lieberman, bipartisan commission on biodefense, no labels, and the centre for responsible leadership.
Senator Joe Lieberman, is senior counsel at the law firm of Kasowitz Benson Torres (https://www.kasowitz.com/people/joseph-i-lieberman) where he currently advises clients on a wide range of issues, including homeland and national security, defense, health, energy, environmental policy, intellectual property matters, as well as international expansion initiatives and business plans.
Prior to joining Kasowitz, Senator Lieberman, the Democratic Vice-Presidential nominee in 2000, served 24 years in the United States Senate where he helped shape legislation in virtually every major area of public policy, including national and homeland security, foreign policy, fiscal policy, environmental protection, human rights, health care, trade, energy, cyber security and taxes, as well as serving in many leadership roles including as chairman of the Committee on Homeland Security and Government Affairs.
Prior to being elected to the Senate, Senator Lieberman served as the Attorney General of the State of Connecticut for six years. He also served 10 years in the Connecticut State Senate, including three terms as majority leader.
In addition to practicing law, Senator Lieberman is honorary national founding chair of No Labels (https://www.nolabels.org/), an American political organization composed of Republicans, Democrats and Independents whose mission is to “usher in a new era of focused problem solving in American politics.”
