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Attenuates of NAD+ impair BMSC osteogenesis and fracture repair through OXPHOS

Controlling the adipo-osteogenic lineage commitment of bone marrow mesenchymal stem cell (BMSC) in favor of osteogenesis is considered a promising approach for bone regeneration and repair. Accumulating evidence indicates that oxidative phosphorylation (OXPHOS) is involved in regulating cell fate decisions. As an essential cofactor for OXPHOS, nicotinamide adenine dinucleotide (NAD) has been shown to correlate with the differentiation of stem cells. However, whether NAD manipulates BMSC lineage commitment through OXPHOS remains elusive. Therefore, it is critical to investigate the potential role of NAD on energy metabolism in mediating BMSC lineage commitment.

In this study, the mitochondrial respiration and intracellular NAD+ level were firstly compared between osteogenic and adipogenic cells. For validating the role of NAD in mitochondrial OXPHOS, the inhibitor of NAD+ salvage pathway FK866 and activator P7C3 were used to manipulate the NAD+ level during osteogenesis. Furthermore, a murine femur fracture model was established to evaluate the effect of FK866 on bone fracture repair.

We elucidated that osteogenic committed BMSCs exhibited increased OXPHOS activity and a decreased glycolysis accompanied by an elevated intracellular NAD+ level. In contrast, adipogenic committed BMSCs showed little change in OXPHOS but an upregulated activity in glycolysis and a decline in intracellular NAD+ level in vitro. Moreover, attenuates of NAD+ via salvage pathway in BMSCs diminished osteogenic commitment due to mitochondria dysfunction and reduced activity of OXPHOS. The cells were rescued by supplementing with nicotinamide mononucleotide. In addition, treatment with NAD+ inhibitor FK866 impaired bone fracture healing in vivo.

Patients with Advanced Gastric, Esophageal Cancers Maintain Quality of Life with Opdivo

Patients with advanced/metastatic non–human epidermal growth factor receptor 2 (HER2)-positive gastric/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC) and treated with Opdivo (nivolumab) and chemotherapy maintained their health-related quality of life (HRQoL) “with a reduced risk of definitive deterioration in disease-related and overall health status and without increased treatment-related symptom burden” when compared with patients treated with standalone chemotherapy, according to recent study findings.

Those findings, published in the Journal of Clinical Oncology, “can be helpful when counseling patients with advanced or metastatic GE/GEJC or EAC, providing reassurance that the benefits of adding (Opdivo) to chemotherapy extend not only to improved survival, but also to preservation of their quality of life and prolonged symptom control,” wrote Journal of Clinical Oncology associate editor, Dr. Andrew H. Ko, in a contextual commentary published alongside the study.

Analyzing patient-reported outcomes (PROs) from the phase 3 CheckMate 649 trial, researchers assessed 1,581 participants’ HRQoL via the EQ-5D and Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) scales, including the FACT-General (FACT-G) and Gastric Cancer subscale (GaCS), with the FACT-G GP5 item used to assess treatment-related symptom burden, and studied longitudinal changes in HRQoL measured with mixed models for repeated measures in the PRO analysis population of 1,360 randomly assigned patients, researchers detailed, noting that they also conducted time to symptom or definitive deterioration analyses.

Unlocking immortality: the science of reversing aging

When it comes to human longevity, you might envision nanobots helping our bodies operate more efficiently. But our bodies are biological machines in their own right, evolved to handle any situation in the real world from illness to cold to hunger. Our bodies heal themselves, and they can be programmed to do so if we understood that language better.

This video talks about DNA and genes, and the epigenetic mechanisms that read that information. The epigenetic clock is one way to measure the age of cells, and this can be reversed with current technologies. We discuss experiments by David Sinclair, which made blind mice see again, and experiments by Greg Fahy, which regenerated the immune system of humans and reset their cellular age by 2 years.

Asking our bodies to heal themselves could be one of the largest medical breakthroughs ever, instead of trying mainly chemical means of medication. And it has significant implications for whether or not we can achieve longevity escape velocity and continue to live more or less indefinitely. This promises to be a very interesting topic.

#aging #longevity #science.

The science of super longevity | Dr. Morgan Levine.
https://www.youtube.com/watch?v=B_CqKVU19ec.

Groundbreaking Research on Anti-Aging: Unlock the Secrets to Longevity | David Sinclair.

Spinal cord injury survivor: Drew’s resilience

After his traumatic spinal cord injury in 2010, Drew Clayborn was motivated by the question, “How do I get back to doing life?” Since then, Clayborn finished high school, graduated college and started a nonprofit dedicated to providing resources and guidance to individuals and families affected by spinal cord injury. Resilience, exemplified by Drew, is a key factor to flourishing after spinal cord injury, according to recent Michigan Medicine research.

To learn more about Drew’s story and resilience research, visit: https://healthblog.uofmhealth.org/brain-health/my-life-matte…ord-injury.

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#Resilience #PatientStories #UniversityOfMichiganHealth

The Untold Story of How The 2023 Nobel Prize in Chemistry Made Its Way Into Modern QLED Screens

The first people to make and use quantum dots were glassmakers. Working thousands of years ago, they realized that the same chemical mixture could turn glass into different colors, depending on how they heated it.

This year’s Nobel Prize in Chemistry honors three scientists who, along with their colleagues, students, and staff, figured out why the ancient glassmakers’ methods worked — and how to control them much more precisely. During the waning days of the Cold War, Alexei Ekimov and Louis Brus, working in separate labs on opposite sides of the Iron Curtain, both discovered the same thing: that tiny crystals (just millionths of a millimeter wide) act very differently than larger pieces of the exact same material. These tiny, weird crystals are called quantum dots, and just a few years after the Berlin Wall fell, Moungi Bawendi figured out how to mass-produce them.

That changed everything. Quantum dots are crystals so small that they follow different rules of physics than the materials we’re used to. Today, these tiny materials help surgeons map different types of cells in the body, paint vivid color images on QLED screens, and give LED lights a warmer glow.

Researchers reconstruct speech from brain activity, illuminating complex neural processes

Speech production is a complex neural phenomenon that has left researchers explaining it tongue-tied. Separating out the complex web of neural regions controlling precise muscle movement in the mouth, jaw and tongue with the regions processing the auditory feedback of hearing your own voice is a complex problem, and one that has to be overcome for the next generation of speech-producing protheses.

Now, a team of researchers from New York University have made key discoveries that help untangle that web, and are using it to build vocal reconstruction technology that recreates the voices of patients who have lost their ability to speak.

The team, co-led by Adeen Flinker, Associate Professor of Biomedical Engineering at NYU Tandon and Neurology at NYU Grossman School of Medicine, and Yao Wang, Professor of Biomedical Engineering and Electrical and Computer Engineering at NYU Tandon, as well as a member of NYU WIRELESS, created and used complex neural networks to recreate speech from brain recordings, and then used that recreation to analyze the processes that drive .

Divergent DNA: The Accidental Discovery That’s Shaking Genetics

Scientists testing a new method of sequencing single cells have unexpectedly changed our understanding of the rules of genetics.

The genome of a protist has revealed a seemingly unique divergence in the DNA

DNA, or deoxyribonucleic acid, is a molecule composed of two long strands of nucleotides that coil around each other to form a double helix. It is the hereditary material in humans and almost all other organisms that carries genetic instructions for development, functioning, growth, and reproduction. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).