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Category: biotech/medical – Page 402

While studying the effects of glutamine deprivation, Boa Kim & team noticed dramatic clustering of glutaminase throughout endothelial cells

The team now report on a mechanism underlying kidney tumor cell growth involving the cancer-driving protein HIF2α that blocks clustering/activation of glutaminase—revealing a new therapeutic target in renal clear cell carcinoma:

The figure shows glutamine deprivation induces GLS1 clustering within mitochondria in HUVEC (top) and HELA (bottom) with mitochondrial protein (green) and GLS (red).

1Department of Medicine, Cardiovascular Institute, and Institute of Diabetes Obesity and Metabolism, and.

2The Abramson Family Cancer Research Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3McAllister Heart Institute, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.

Cutaneous Melanoma: A Review

The incidence and prevalence of cutaneous melanoma in the US and worldwide have increased over the last 5 decades.

Cutaneous melanoma presents as a new, changing, or irregularly pigmented skin lesion. Risk factors for cutaneous melanoma include UV radiation exposure, skin type, presence of benign and atypical nevi, and personal or family history of melanoma.

This Review summarizes current evidence regarding the epidemiology, pathophysiology, diagnosis, and treatment of cutaneous melanoma.

Improvements in melanoma mortality over the last decade are attributed to the advent of multiple effective therapies,6 including immune checkpoint blockade with anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibodies (ipilimumab), anti–programmed cell death protein 1 (PD-1) antibodies (nivolumab, pembrolizumab), and anti–lymphocyte activation gene 3 protein (LAG-3) antibodies (relatlimab), as well as oral combination targeted therapy with B-Raf protein (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors (eg, encorafenib + binimetinib, vemurafenib + cobimetinib, dabrafenib + trametinib).

This review summarizes current evidence regarding epidemiology and risk factors, clinical presentation, diagnosis, and management of cutaneous melanoma (Box).

Dysfunctions of Circulating Adaptive Immune Cells in End-Stage Liver Disease

End-stage liver disease (ESLD) from acute liver failure to compensated advanced chronic liver disease and decompensated cirrhosis at different stages (chronic decompensation, acute decompensation with or without acute-on-chronic liver failure) has high disease severity and poor patient outcome. Infection is a common complication in patients with ESLD and it is associated with a high mortality rate. Multiple mechanisms are involved in this marked susceptibility to infections, noticeably the inadequate immune response known as immune paresis, as part of cirrhosis-associated immune dysfunction (CAID). Specifically in the adaptive immune arm, lymphocyte impairments—including inadequate activation, reduced ability to secrete effector molecules and enhanced immune suppressive phenotypes—result in compromised systemic immune responses and increased risk of infections.

Boosting One Mitochondrial Protein Increases Lifespan And Slows Aging in Mice

Tiny biological batteries known as mitochondria keep the body’s cells running smoothly, and their gradual decline is linked to a wide range of age-related diseases. Now scientists think they have found a way to keep mitochondria powered for longer.

A protein called COX7RP is key to this discovery from researchers at the Saitama Medical University and Chiba University in Japan. The protein is thought to help mitochondria form supercomplexes, structures that improve energy efficiency.

In the new study, male mice engineered to produce extra COX7RP showed a host of differences compared with controls, including a 6.6 percent increase in average lifespan and indicators of an extended healthspan – being able to live healthier for longer.

Molecular Switch for Repairing Central Nervous System disorders

A molecular switch has the ability to turn on a substance in animals that repairs neurological damage in disorders such as multiple sclerosis (MS), Mayo Clinic researchers discovered. The early research in animal models could advance an already approved Food and Drug Administration therapy and also could lead to new strategies for treating diseases of the central nervous system.

Research by Isobel Scarisbrick, Ph.D., published in the Journal of Neuroscience finds that by genetically switching off a receptor activated by blood proteins, named Protease Activated Receptor 1 (PAR1), the body switches on regeneration of myelin, a fatty substance that coats and protects nerves.

“Myelin regeneration holds tremendous potential to improve function. We showed when we block the PAR1 receptor, neurological healing is much better and happens more quickly. In many cases, the nervous system does have a good capacity for innate repair,” says Dr. Scarisbrick, principal investigator and senior author. “This sets the stage for development of new clinically relevant myelin regeneration strategies.”

Head and Neck Cancer

Head and neck cancer is the seventh most common cancer worldwide. In 2024, approximately 58 450 individuals were diagnosed with oral cavity and pharynx cancer and 12 650 were diagnosed larynx cancer in the US.

Although many malignancies originate in the head and neck region, the term head and neck cancer typically applies to tumors arising in the lining or mucosa of the upper aerodigestive tract. Approximately 90% of head and neck cancers are caused by squamous cell carcinoma.

This Review summarizes the epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment of head and neck squamous cell carcinomas (HNSCC) of the upper aerodigestive tract.

This review examines the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of head and neck squamous cell carcinomas of the upper aerodigestive tract.

Clinical Usefulness of Left Ventricular Global Longitudinal Strain as a Predictor of Prognosis in Patients With Acute Ischemic Stroke (GLS‐STROKE Study)

LV‐GLS 18% predicts mortality, recurrent stroke, and poor mRS-based functional outcome after acute ischemic stroke. @Minkwan_Kim84

LV‐GLS Globally, stroke is the second‐leading cause of death and the third most common cause of combined death and disability.1 Over the past decade, stroke‐related death has been steadily declining; however, health care expenditures associated with stroke have continued to increase.1, 2 Recurrence of ischemic stroke adversely affects patient prognosis and increases the mortality rate.3 Previous studies have identified several clinical factors contributing to the occurrence and recurrence of ischemic stroke, including stroke subtype, age, hypertension, atrial fibrillation (AF), heart failure (HF), and diabetes.2, 4

HF is also a risk factor for stroke and is associated with stroke recurrence and death.5, 6 Left ventricular (LV) global longitudinal strain (LV‐GLS), a measure of myocardial deformation along the long axis of the left ventricle, is assessed using the speckle‐tracking method. It is a sensitive measure of myocardial fiber shortening and has become a reliable parameter for evaluating subtle systolic dysfunction.7 In patients with acute HF, LV‐GLS is frequently reduced regardless of the LV ejection fraction (LVEF), the traditional measure of LV systolic function. LV‐GLS has also been shown to be a superior prognostic marker for death than LVEF.8 Furthermore, in severe mitral regurgitation and severe aortic stenosis, LV‐GLS has proven useful as a predictor of postoperative outcomes and a tool for identifying patients who may benefit from early surgical intervention.9, 10 Recent research has demonstrated that LV‐GLS can effectively predict incident strokes in patients who are stroke naïve.11 However, to date, no study has evaluated the prognostic implications of LV‐GLS in patients with acute ischemic stroke (AIS) about subsequent cardiovascular outcomes. In this study, we aimed to investigate the prognostic utility of LV‐GLS, a novel marker of subclinical LV dysfunction, in patients with AIS.

Sub-millimeter-sized robots can sense, ‘think’ and act on their own

Robots small enough to travel autonomously through the human body to repair damaged sites may seem the stuff of science fiction dreams. But this vision of surgery on a microscale is a step closer to reality, with news that researchers from the University of Pennsylvania and the University of Michigan have built a robot smaller than a millimeter that has an onboard computer and sensors.

Scientists have been trying for decades to develop microscopic robots, not only for medical applications but also for environmental monitoring and manufacturing. However, they have faced formidable challenges. Existing microbots typically require large, external control systems, such as powerful magnets and lasers, and cannot make autonomous decisions in unfamiliar environments.

The hidden physics of knot formation in fluids

Knots are everywhere—from tangled headphones to DNA strands packed inside viruses—but how an isolated filament can knot itself without collisions or external agitation has remained a longstanding puzzle in soft-matter physics.

Now, a team of researchers at Rice University, Georgetown University and the University of Trento in Italy has uncovered a surprising physical mechanism that explains how a single filament, even one too short or too stiff to easily wrap around itself, can form a knot while sinking through a fluid under strong gravitational forces.

The discovery, published in Physical Review Letters, provides new insight into the physics of polymer dynamics, with implications ranging from understanding how DNA behaves under confinement to designing next-generation soft materials and nanostructures.

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