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Category: biotech/medical

A selective, brain-penetrant GalR1 antagonist restores cholinergic signaling in vitro and rescues cholinergic cognitive deficits in mice

In this study, we characterized PAC-832, a small-molecule GalR1 antagonist with sub-micromolar potency (IC50 = 0.28 μM), 30-fold selectivity over GalR2 and GalR3, and excellent brain penetration and drug-like properties. In functional cell-based assays, PAC-832 reversed galanin-mediated suppression of acetylcholine release. In a scopolamine challenge model, PAC-832 attenuated cognitive deficits in the Y-maze and NOR tasks, with effect sizes comparable to donepezil.

The scopolamine model is widely used in behavioral mouse research to evaluate compounds for procognitive activity. However, because scopolamine impairs cognition by blocking muscarinic receptors rather than by reducing acetylcholine release, our behavioral results do not directly assess whether PAC-832 acts by restoring cholinergic signaling in vivo, or whether it acts through an alternative downstream mechanism. Establishing the former will require direct measurement of acetylcholine release in the CNS (e.g. using microdialysis or biosensor-based approaches) and/or GalR1-dependent in vivo validation (e.g. using transgenic GalR1-knockout mice).

Nonetheless, our work addresses a longstanding pharmacological gap in the galanin field. Despite decades of work implicating galanin signaling in CNS function and disease, translational progress has been limited by a lack of subtype-selective, brain-penetrant small molecule galanin modulators. Recent therapeutic development within the galanin field has largely focused on GalR2 agonism, while GalR1-targeting approaches have remained dependent on peptide tools unable to pass the blood-brain barrier. PAC-832 is, to our knowledge, the first GalR1-selective small molecule antagonist with sufficient brain exposure to test the effects of GalR1 antagonism following peripheral administration.

A species of gut bacteria could ease anxiety and diarrhea-predominant IBS

Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating and changes in bowel movements, estimated to affect between 10% and 15% of people worldwide. Past studies suggest that in many cases this condition is accompanied by anxiety, an emotional state marked by worry, fear and/or overthinking about specific life events.

While IBS and anxiety are known to often occur together, the biological processes linking the two have not yet been fully elucidated. One possibility is that bacteria and other microorganisms living in the digestive tract, broadly referred to as gut microbiota, contribute to these biological processes.

Researchers at Wuhan University of Science and Technology and Huazhong University of Science and Technology carried out a study aimed at shedding more light on the biological mechanisms linking a type of IBS called diarrhea-predominant IBS (IBS-D), which is associated with frequent loose stools, with anxiety.

Single-cell dissection of plasma cell clonal evolution to smoldering multiple myeloma after CD19 CAR-T cell therapy in B-cell acute lymphoblastic leukemia

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of B-cell malignancies, achieving deep and durable remissions in patients with B-cell acute lymphoblastic leukemia (B-ALL).1 Despite remarkable therapeutic successes, rare but clinically significant secondary hematologic malignancies have been reported during CAR-T cell therapy, often driven by lineage switching or clonal selection.2 Moreover, CAR-T cell therapy drives profound remodeling of the immune microenvironment, and the sustained inflammatory signaling may promote clonal evolution and influence disease progression.3 High-resolution approaches, such as single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq), enable characterization of transcriptional programs, clonal identity, and temporal dynamics to dissect CAR-T cell therapy-induced clonal evolution and immune remodeling.4

Here, we report a case of B-ALL with B-cell receptor (BCR) heterogeneity at diagnosis that evolved into smoldering multiple myeloma (SMM) following CD19-targeted CAR-T therapy. The co-occurrence of B-ALL and SMM is exceptionally rare, as it requires malignant clones at distinct stages of B-cell development. This case provides a unique opportunity to dissect how CAR-T cell therapy drives B-lineage clonal evolution and reshapes the immune microenvironment. To this end, bone marrow mononuclear cells (BMMNC) were collected at multiple time points and subjected to longitudinal scRNA-seq and scBCR-seq to track dynamic changes in malignant and immune cell populations, thereby elucidating the mechanisms of clonal evolution and immune remodeling following CAR-T cell therapy. The patient gave informed consent and was enrolled in a clinical trial registered at clinicaltrials.gov (Identifier: NCT00123456).

A 13-second eye test may help predict recovery of consciousness after severe brain injury

A simple bedside eye test may help predict recovery of consciousness in patients with severe brain injuries, according to new research presented at the European Academy of Neurology (EAN) Congress 2026.

The study found that a previously overlooked phase of the pupil response to light, known as the late light-off response (LOR), predicted improvements in consciousness seven days later in patients with acute brain injury. In contrast, standard pupil measurements already widely used in intensive care units (ICUs), including the Neurological Pupil Index (NPi) and pupillary light reflex (PLR) latency, did not predict later gains in consciousness.

Scratching that bug bite might feel good at first but science explains why it’s a bad idea

You’ve likely heard it since childhood: Don’t scratch that bug bite or rash, you’ll make it worse. But why would something that feels so good be bad?

A lot of things can cause itchiness, sometimes serious diseases. Whatever the cause, doctors have long warned that scratching too much can damage the skin. Now researchers better understand why even a mildly annoying itch could put you on an itch-and-scratch cycle if you give in.

How did they find out? In part by putting tiny “cones of shame” onto mice to uncover what happens on a cellular level when an itch gets scratched—or left alone.

Hospital AI tool predicts low blood sugar in patients up to 24 hours in advance

Cedars-Sinai Health Sciences University investigators developed an AI-based model that can identify hospitalized patients at risk of low blood sugar up to 24 hours before the condition occurs. The long short-term memory (LSTM) model, described in npj Digital Medicine, could help clinicians intervene earlier and prevent complications, including, in severe cases, seizures, coma and long-term heart arrhythmias.

The model addresses a longstanding challenge in hospital care. Low blood sugar, also called hypoglycemia, is a common and potentially life-threatening complication among hospitalized patients, including those receiving diabetes treatment, those who are fasting before procedures or those in critical care. However, there are no widely used tools for predicting which hospitalized patients may develop hypoglycemia.

“Today, most hospital care for hypoglycemia is reactive, and we respond after a patient’s blood sugar drops,” said Roma Gianchandani, MD, senior author of the study and vice chair of quality and innovation in the Department of Medicine and program director for diabetes.

Don’t forget about thrombosis in acute promyelocytic leukemia

Firstly, why examine the role of thromboembolic disease in APL when serious bleeding is essentially universal? Thromboembolic episodes are more common than may be appreciated in this setting. The 16% incidence of thromboembolic events observed by Rodriguez-Viega and co-workers is higher than the 12% found in patients with acute myeloid leukemia.5 Furthermore, the major cause of treatment failure in APL is early death and the development of clotting is associated with early death. Early death in APL occurs most frequently during the first 24–48 hours after presentation. Understandably, very few, if any, of such patients are enrolled on clinical trials. Enrollment on a trial would facilitate further insights into thromboembolic events and may pave the way for prevention and therapeutic intervention.

Secondly, why are patients with APL predisposed to develop thrombosis? After all, the disease is infamous for its life-threatening and potentially catastrophic bleeding. This prominent characteristic was recognized by Dr. Leif Hillstad, who is credited with the first description of APL as a distinct clinical entity in 1957.6 Acute promyelocytic leukemia cells are associated with the release of plasminogen activator inhibitor-1, tissue factor, and TNFα. These proteins, together with a decrease in thrombomodulin which functions as an anticoagulant by binding to thrombin, favor the balance towards thromboembolic events7 (Figure 1). Alternatively, with the generation of annexin II, plasminogen activators, and podoplanin, a transmembrane protein which interacts with cell lectin superfamily 2 (CLEC-2) on platelets to induce platelet aggregation and adhesion to lymphatic vessels,8 bleeding is much more commonly present. Furthermore, direct proteolysis of fibrinogen and von Willebrand factor contributes to bleeding. This compilation of processes explains why some patients with APL have bleeding while others have thromboembolic episodes and some have both depending on the balance of procoagulant and anticoagulant proteins. However, bleeding, usually clinically manifested by large ecchymoses on the trunk and extremities, is the major hallmark of the disease.

Finally, how can thromboembolic events in APL be prevented? The most important thing is to maintain a high level of suspicion. The report by Rodriguez-Veiga and co-workers reminds us to be vigilant for the possibility of thromboembolic events in patients with APL. The risk of thrombosis was 1.4% among low-risk patients (presenting WBC 40×109/L), 4.9% for intermediate-risk patients (WBC 10×109/L and platelet count 10×109/L). In contemporary practice, low-and intermediate-risk groups are combined since outcomes among these patients proved to be similar.

Advances in materials science are helping unlock secrets of nanomaterials

New instruments on the horizon promise the most precise tools yet to study and experiment on the smallest and most complex materials ever manufactured. In a paper published in the journal Nature Materials, University of Cincinnati assistant professor Hanxun Jin highlighted advances in ultrasensitive technology to measure and manipulate some of the tiniest nanomaterials used in manufacturing, aerospace, medicine and more.

And when Jin says tiny, he means really tiny. Semiconductor nanocrystals called quantum dots that are used in TV screens are so small they’re considered zero-dimensional. That makes the field of nanomaterials characterization a particularly exciting one, Jin said.

New oral heart failure drug appears to be safe and well tolerated in 58-patient early clinical trial

An early clinical study shows that a new oral drug is safe and well tolerated in patients with chronic heart failure. The study, led by researchers at Karolinska Institutet, has been published in The Lancet.

Heart failure with reduced pumping capacity means that the heart struggles to pump blood effectively around the body. Despite current treatments, many patients’ conditions worsen over time, and existing drugs that strengthen the heart’s contractions can cause serious side effects, such as heart rhythm disturbances and effects on blood pressure.

In the study, researchers investigated a new drug, AC01, which targets the body’s ghrelin receptor. Ghrelin is a hormone that influences metabolism and growth hormone release, and its receptor is also found in heart muscle. AC01 is intended to strengthen the heart’s pumping ability through a different biological mechanism from traditional heart-stimulating drugs, thereby reducing the risk of side effects.

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