Medical Bulletin 07/November/2025

Diabetic kidney disease (DKD) is a major cause of chronic kidney failure, with early detection remaining a clinical challenge. Conventional markers like creatinine and albumin often fail to signal problems until significant damage has occurred. Metabolomics, which enables the simultaneous measurement of hundreds of tiny molecules (metabolites) in the blood, offers a more sensitive window into the subtle chemical shifts that precede symptoms—potentially unlocking new pathways for diagnosis, monitoring, and individualized treatment of DKD.

The team recruited 52 subjects from Osmania General Hospital, Hyderabad, including 15 healthy controls, 23 individuals with type 2 diabetes, and 14 with both diabetes and kidney disease. Using advanced liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), the researchers measured nearly 300 metabolites from blood samples collected between June 2021 and July 2022. Dietary and lifestyle factors were carefully recorded, and blood chemistry was rigorously analyzed.

Analysis revealed 26 metabolites that differentiated diabetics from healthy participants. While several were well-known—such as glucose, cholesterol, and 1,5-anhydroglucitol—several others, including valerobetaine, ribothymidine, and fructosyl-pyroglutamate, were novel in the context of diabetes and kidney disease. These metabolites may provide new clues about pathways involved in DKD, highlighting the broad metabolic disruptions triggered by diabetes beyond sugar imbalance alone.

Lead researcher Prof. Pramod Wangikar emphasized that though the pilot sample is small, the results demonstrate metabolomics’ potential for early DKD detection and patient stratification, which could lead to personalized treatments and improved outcomes. Larger, multi-center studies are planned to refine and validate these promising biomarkers for clinical use in India and beyond.

REFERENCE: Sneha Rana, Vivek Mishra, Prajval Nakrani, Lakshman Kumar Ega, Manisha Sahay, Rakesh Kumar Sahay, Pramod P. Wangikar; Whole Blood Metabolome Profiling for Stratification of Type 2 Diabetes Patients and Identification of Biomarkers for Diabetic Kidney Disease in Asian Indian Adults; Journal of Proteome Research; doi: 10.1021/acs.jproteome.5c00188

Scientists successfully reverse anxiety by restoring brain’s chemical balance

Scientists at the Institute for Neurosciences, led by Juan Lerma, have uncovered a specific neural mechanism in the amygdala that drives anxiety, depression, and social withdrawal, with striking implications for future treatments. Published recently in iScience, the study demonstrates that correcting an imbalance in excitability within a precise subset of neurons can reverse these pathological behaviors in mice, illuminating a targeted pathway for addressing mood disorders.

The amygdala, central to emotion processing, contains multiple neuronal populations contributing to complex behaviors. Lerma’s team focused on the basolateral amygdala, where genetically modified mice overexpressing the Grik4 gene exhibit increased GluK4 glutamate receptor levels, heightening neuronal excitability. These mice displayed pronounced anxiety and social deficits analogous to human psychiatric conditions like autism and schizophrenia.

Using advanced genetic engineering and viral vector delivery, the researchers selectively normalized Grik4 expression in basolateral amygdala pyramidal neurons. This recalibration restored normal communication with inhibitory “regular firing neurons” located in the centrolateral amygdala. Electrophysiological recordings confirmed the reestablishment of synaptic balance, while behavioral assays—including tests for anxiety, depression, and social interaction—showed significant reversal of deficits. For example, affected mice regained interest in open spaces and social novelty.

Importantly, applying this approach to wild-type mice exhibiting natural anxiety further validated the findings, indicating the mechanism’s broader applicability beyond engineered models. While anxiety and social withdrawal symptoms improved, cognitive impairments such as object recognition memory remained, suggesting other brain areas like the hippocampus are involved in these functions.

Lead author Álvaro García emphasized that restoring excitability balance in specific amygdala circuits could revolutionize treatment strategies by offering more localized, efficient interventions for mood and social behavior disorders. This work lays the groundwork for future therapies targeting neural circuit dysfunctions underlying affective illnesses, potentially transforming clinical approaches to anxiety and depression.

REFERENCE: Alvaro García, M. Isabel Aller, Ana V. Paternain, Juan Lerma. Central role of regular firing neurons of centrolateral amygdala in affective behaviors. iScience, 2025; 28 (6): 112649 DOI: 10.1016/j.isci.2025.112649

Nanotechnology boosts cancer drug potency 20,000-fold, eliminating side effects

Scientists at Northwestern University have achieved a groundbreaking advance by redesigning a classic chemotherapy drug, 5-fluorouracil (5-Fu), into a novel nanoparticle formulation that dramatically enhances its potency and safety. Published in ACS Nano on October 29, 2025, this research exemplifies the emerging field of structural nanomedicine, which engineers drug architecture at the nanoscale to improve delivery and therapeutic efficacy.

5-Fu is traditionally limited by poor solubility and low cellular uptake, resulting in suboptimal cancer cell targeting and significant toxicity to healthy cells. To overcome these challenges, Professor Chad A. Mirkin’s team synthesized spherical nucleic acid (SNA) nanostructures by integrating chemotherapy molecules directly into the DNA strands coating tiny spherical nanoparticles. These SNAs exploit natural scavenger receptors, particularly abundant on myeloid leukemia cells, to enable highly selective and efficient drug internalization.

The researchers employed sophisticated chemical synthesis to attach 5-Fu molecules to oligonucleotides, which were then assembled onto phospholipid core liposomes forming the SNA architecture. The new formulation was rigorously tested in animal models of acute myeloid leukemia (AML), a rapidly progressing and difficult-to-treat blood cancer.

Remarkably, SNA-5-Fu entered leukemia cells 12.5 times more efficiently than conventional 5-Fu, exhibited up to 20,000-fold greater cytotoxicity, and slowed cancer advancement by a factor of 59. Importantly, this potent therapeutic effect occurred with no detectable damage to healthy tissues or overt side effects, a significant improvement over standard chemotherapy’s harsh profile.

Professor Mirkin described the breakthrough as a potential paradigm shift that transforms weak, toxic chemotherapy agents into precision nanomedicines with improved outcomes. With multiple SNA drugs already in clinical trials, this pioneering approach may soon extend beyond cancer to tackle infections, neurodegenerative diseases, and autoimmune disorders—ushering in a safer, more effective era of drug design and delivery.

REFERENCE: Taokun Luo, Young Jun Kim, Zhenyu Han, Jeongmin Hwang, Sneha Kumari, Vinzenz Mayer, Alex Cushing, Roger A. Romero, Chad A. Mirkin. Chemotherapeutic Spherical Nucleic Acids. ACS Nano, 2025; DOI: 10.1021/acsnano.5c16609