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Category: biotech/medical – Page 2

How major nuclear protein complexes control specialized gene regulation in cancer and beyond

Precision and timing of gene expression is essential for normal biological functions and, when disrupted, can lead to many human diseases, including cancers. However, how molecular machines—protein complexes—that control gene expression locate to specific genes at specific times within the nuclei of our cells has remained a mystery.

Now, scientists at Dana-Farber Cancer Institute have discovered a new protein domain, SWIFT, found on a major chromatin remodeling complex family called mammalian SWI/SNF (mSWI/SNF or BAF) complexes, which helps these regulatory machines target particular genes to activate their expression.

The findings, published in Science, reveal how the SWIFT platform on mSWI/SNF complexes engage transcription factors (TF) to enable specialized cellular functions during both normal development and cancer. Particularly in human cancers, SWIFT-TF engagement sustains cancer-promoting gene expression and cell growth. Notably, breaking interactions with mutations halts cancer cell growth, flagging this new SWIFT-TF platform as a promising target for small molecule development.

First map of nerve circuitry in bone helps physicians identify key signals for bone repair

When a house catches on fire, we assume that a smoke alarm inside will serve one purpose and one purpose only: warn the occupants of danger. But imagine if the device could transform into something that could fight the fire as well.

In a new study in Science, a multi-institutional team led by researchers at Johns Hopkins Medicine has shown in mice that the body’s “pain alarms”―sensory neurons—actually have such a dual function. In the event of a bone fracture, these nerves not only report the trauma, but they also morph into “reconstruction commanders” that actively direct the cellular workforce to rebuild the skeleton.

Sensor lights up to reveal scopolamine, a common substance used for sexual assault

A team from the Universitat Politècnica de València (UPV) has led the development of a new sensor capable of quickly and easily detecting scopolamine, one of the substances most commonly used in crimes of chemical submission, especially in sexual assaults. The sensor detects the presence of this drug in less than five minutes with high sensitivity. The research is published in the journal Angewandte Chemie International Edition.

“Scopolamine is a substance that is difficult to detect using conventional methods, especially when found in drinks. For this reason, our group from the IDM Institute at the UPV set out to develop new, simple tools that can immediately alert us to its presence,” says Vicente Martí Centelles, a researcher at the Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM) at the UPV.

Lenacapavir treatment–emergent HIV-1 capsid resistance mutations are frequently associated with replication defects

Can HIV become resistant to lenacapavir?

An analysis of clinical isolates identifies mutations that shift the capsid protein’s lenacapavir binding pocket and endow resistance, but shows these mutations often come at a high fitness cost.

Read more in.

Treatment-emergent capsid mutations elicited by lenacapavir monotherapy showed variable drug resistance and viral fitness impacts.

Targeting B cells enhances STING agonism in liver cancer

The researchers used advanced laboratory and experimental models to uncover how B-cells contribute to immunotherapy resistance in liver cancer. Using liver cancer mouse models, they tested treatments that either blocked B-cells or targeted immune pathways.

They found that when tumors stopped responding to immunotherapy, B-cells moved into the tumor and formed clusters that looked like special immune structures called tertiary lymphoid tissues.

“Combining B-cell depletion with immunotherapy (anti-PD-1 ICB or the STING agonist BMS-986301) significantly improved survival and reduced metastasis,” said the author. “These exciting findings suggest that targeting B-cells or their signaling pathways could overcome acquired resistance and enhance the effectiveness of cancer immunotherapy, including in cases where the disease has spread.”

Scientists have identified a promising strategy to improve liver cancer immunotherapy: targeting B-cells. While immunotherapy has transformed cancer treatment by activating T-cells—a type of immune cell that fights cancerous cells—many patients still fail to respond. New research shows that B-cells—another type of immune cells that fight infections—may play a surprising role in limiting immunotherapy’s effectiveness.

The study was recently published in Nature Communications. The study’s principal investigator said that most current research efforts are focusing on activating T-cells against cancers. This study showed tumor-associated B-cells can create an environment that suppresses T-cell activity, allowing cancer cells to escape immune attacks.

“We observed a significant rise in B-cell activity in the tumor, suggesting they may play an important role in how cancer escapes treatment,” said the author. “By blocking these immunosuppressive B-cells, we may be able to remove this barrier and enhance the power of immunotherapy.”

Continue reading “Targeting B cells enhances STING agonism in liver cancer” | >

Patient Information: Prostatitis

📄 This JAMA Patient Page describes the types of prostatitis and its risk factors, diagnosis, and treatment.

Prostatitis involves infection, inflammation, or pain in the prostate gland and affects about 9% of men during their lifetime.

Patients with acute prostatitis typically have fever, chills, pelvic pain, sudden onset of frequent urination, and pain or burning during urination.

📄 Risk Factors, Diagnosis, and Treatment of CP/CPPS

Approximately 267 000 men in the US are diagnosed with CP/CPPS each year. Risk increases after age 50 years. Although other risk factors for CP/CPPS are unclear, men with CP/CPPS are more likely to have chronic pain syndromes such as fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome and higher rates of depression, anxiety, and panic disorder than unaffected men.

Anti-ANGPTL3 Antibody SHR-1918 for Homozygous Familial Hypercholesterolemia: A Nonrandomized Clinical Trial

Monthly subcutaneous SHR-1918, a fully human monoclonal antibody targeting ANGPTL3, was associated with reduced LDL-C in adults with homozygous familial hypercholesterolemia on stable lipid-lowering therapy.

Question Does SHR-1918, a fully human monoclonal antibody targeting angiopoietinlike 3 (ANGPTL3), lower the low-density lipoprotein cholesterol (LDL-C) level in adults with homozygous familial hypercholesterolemia (HoFH) taking stable lipid-lowering therapy?

Findings In this phase 2 nonrandomized clinical trial of 26 patients, SHR-1918 at 600 mg every 4 weeks was associated with a substantial reduction in LDL-C level exceeding half in adults with HoFH taking stable lipid-lowering therapy and was also associated with lower levels of other lipids, with evidence of a manageable safety profile.

Meaning The promising findings observed in this trial support the launch of a double-blind, placebo-controlled, phase 3 randomized clinical trial to verify the effect and safety of SHR-1918 for HoFH management.

Heart-brain connection via vagus nerve to keep the heart young

The secret to a healthier and “younger” heart lies in the vagus nerve. A recent study published in Science Translational Medicine has shown that preserving bilateral cardiac vagal innervation is an anti-aging factor. In particular, the right cardiac vagus nerve emerges as a true guardian of cardiomyocyte health, helping to preserve the longevity of the heart independently of heart rate.

‘When the integrity of the connection to the vagus nerve is lost, the heart ages more rapidly,’ explains the senior author.

‘Even partial restoration of the connection between the right vagus nerve and the heart is sufficient to counteract the mechanisms of remodelling and preserve effective cardiac contractility,’ adds another author.

‘We have developed an implantable bioabsorbable nerve conduit designed to promote and guide the spontaneous regeneration of the thoracic vagus nerve at the cardiac level,’ explains a co-author.

Treated adult male minipigs displayed improved global circumferential, longitudinal, and radial strains and reduced diastolic dyssynchrony. Histological analysis revealed partial repair with about 20% viable vagal fascicles, restoration of myocardial parasympathetic fibers, normalization of oxidative stress and aging markers, and prevention of interstitial fibrosis.

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