What Is: Obsessive-Compulsive Disorder

Scientific Frontline: Extended "At a Glance" Summary: Obsessive-Compulsive Disorder

The Core Concept: Obsessive-compulsive disorder is a complex, heterogeneous neurobiological condition driven by structural, genetic, and neurochemical dysregulation, defined by the presence of intrusive, ego-dystonic obsessions and repetitive, time-consuming compulsions.

Key Distinction/Mechanism: Unlike the ego-syntonic perfectionism of obsessive-compulsive personality disorder, primary obsessive-compulsive disorder operates via a "broken brake" mechanism where an overactive direct excitatory pathway and a failing indirect inhibitory pathway in the cortico-striato-thalamo-cortical circuitry prevent the suppression of unwanted thoughts and actions.

Origin/History: The diagnostic framework evolved significantly from the DSM-IV to the DSM-5, gaining its own discrete chapter. Key historical milestones include the late 1990s identification of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) by the US National Institute of Mental Health and the February 2009 FDA Humanitarian Device Exemption for Deep Brain Stimulation therapy.

Major Frameworks/Components:

• Clinical Diagnostics: Characterized by specific insight specifiers (good, poor, or absent) and the clinical necessity to differentiate the pathology from primary psychotic, personality, or tic disorders.
• Circuit Dysregulation: A structural imbalance within the cortico-striato-thalamo-cortical loops, specifically marked by an overactivation of the orbitofrontal and anterior cingulate loops.
• Neurochemical Landscape: Driven by localized cortical hyperexcitability resulting from imbalances of excitatory glutamate and inhibitory GABA, compounded by dopaminergic and serotonergic dysregulation within the forebrain.
• Genetic Susceptibility: Strongly linked to synaptic protein expression, including polymorphisms within the SLC1A1 gene affecting the EAAT3 transporter, and structural scaffolding proteins like SAPAP3 and SLITRK5.
• Immunological Intersections: The PANDAS hypothesis demonstrates that molecular mimicry following streptococcal infections can induce autoantibodies that target basal ganglia, generating acute neuroinflammation and psychiatric symptoms.
• Advanced Interventions: Treatment paradigms for treatment-refractory patients include glutamatergic modulating pharmacotherapies (riluzole, memantine, and N-acetylcysteine) and precise neuromodulation via Deep Brain Stimulation.

SARS-CoV-2 Nucleocapsid Protein and Long COVID

Dr. Melody Li with members of her lab.
Photo Credit: Timothy Archibald/UCLA Broad Stem Cell Research Center

Scientific Frontline: Extended "At a Glance" Summary: SARS-CoV-2 Nucleocapsid Protein

The Core Concept: The SARS-CoV-2 nucleocapsid protein is a viral structural component that packages the virus's genetic material and unexpectedly amplifies inflammatory signals in immune cells, contributing to profound tissue damage.

Key Distinction/Mechanism: While coronaviruses typically encode proteins to suppress early immune responses, the nucleocapsid protein acts as a "double-edged sword." It successfully dampens early antiviral defenses while simultaneously overactivating inflammatory pathways in macrophages, causing them to release tissue-damaging cytokines and chemokines.

Origin/History: Detailed in a recent study published in Science Advances by a UCLA research team led by virologist Melody Li, the research compared nucleocapsid proteins from SARS-CoV-1, MERS-CoV, and various SARS-CoV-2 variants, noting the Delta variant as the most inflammatory.

Major Frameworks/Components:

• Macrophages: Immune cells that detect viruses and coordinate early responses, which become hyperactivated by the nucleocapsid protein.
• Endothelial cells: The cells lining blood vessels that form vital protective barriers, such as the blood-brain barrier and the coronary artery lining.
• Vascular leakage: The breakdown of endothelial barriers caused by severe inflammatory signals, which was prominently observed in stem cell-derived heart models exposed to the Delta variant.
• Cytokines and chemokines: Chemical signals released by patrolling macrophages that drive the systemic hyperinflammatory response.

Brain Immune Cells Limit Alzheimer's Damage

Dr James Murray
Photo Credit: Courtesy of Swansea University

Scientific Frontline: Extended "At a Glance" Summary: Microglia and Neuronal Stability in Alzheimer's Disease

The Core Concept: Microglia, the primary immune cells of the brain, play a critical protective role in maintaining the stability of neuronal networks, challenging the traditional view that they act solely as drivers of neuroinflammation in Alzheimer's disease.

Key Distinction/Mechanism: While current experimental Alzheimer's treatments frequently attempt to reduce microglial numbers or activity by blocking the colony stimulating factor 1 receptor (CSF1R), this indiscriminate suppression increases abnormal, epilepsy-like electrical hyperexcitability in the brain and fails to improve memory.

Major Frameworks/Components:

• Microglia: The resident macrophage cells of the central nervous system that perform vital neuroprotective "housekeeping" tasks alongside their inflammatory responses.
• CSF1R Inhibition: The pharmacological targeting of the CSF1R receptor (using the drug GW2580) to deplete microglial populations.
• Network Hyperexcitability: The destabilization of brain electrical activity, leading to epilepsy-like events, which occurs when protective immune cells are removed.
• APP/PS1 Mouse Model: A well-established transgenic animal model used to study the pathological progression of Alzheimer's disease in vivo.

What Is: The Vagus Nerve

Scientific Frontline: Extended "At a Glance" Summary: The Vagus Nerve

The Core Concept: A massive, bidirectional neural superhighway (the tenth cranial nerve) that acts as the primary interface between the central nervous system and the peripheral viscera to dynamically maintain systemic homeostasis.

Key Distinction/Mechanism: Rather than functioning merely as a top-down efferent command cable, the vagus nerve features a stark 80/20 afferent-to-efferent fiber ratio, operating primarily as a vast sensory array that continuously reports deep interoceptive data to the brain before modulating immune, cardiac, and enteric states via precise biochemical cascades.

Origin/History: Derived from the Latin word for "wanderer," key historical milestones include Friedrich Arnold’s 1832 description of the auricular reflex arc, Otto Loewi’s 1921 discovery of vagal chemical neurotransmission via acetylcholine, and Claudio Franceschi’s 2000 framework of "inflammaging" resulting from age-related vagal decline.

Infectious Disease Pathology: In-Depth Description

Infectious disease pathology is the specialized medical and scientific discipline dedicated to studying the macroscopic, microscopic, and molecular alterations in host tissues caused by infectious agents. Its primary goal is to elucidate the mechanisms of pathogenesis—analyzing how viruses, bacteria, fungi, prions, and parasites invade a host, evade the immune system, and induce structural and functional tissue damage—to inform definitive diagnosis, targeted therapies, and public health interventions.

What Is: Enteric Nervous System: The Second Brain

Scientific Frontline: Extended "At a Glance" Summary: The Enteric Nervous System (ENS)

The Core Concept: The Enteric Nervous System (ENS) is a highly sophisticated, autonomous network of approximately 500 million neurons and supportive glial cells embedded within the human gastrointestinal tract. Often referred to as the body's "second brain," it operates independently of the central nervous system to govern digestion, mucosal immunity, and systemic physiological homeostasis.

Key Distinction/Mechanism: Unlike traditional peripheral nerves that passively relay brain commands, the ENS acts as an autonomous sensory-motor computing matrix. It detects local physical and chemical stimuli via Intrinsic Primary Afferent Neurons (IPANs), processes this data through complex interneuron circuits, and executes precise muscular and secretory reflexes using over 30 distinct neurotransmitters, including massive quantities of locally synthesized serotonin.

Major Frameworks/Components: 

• The Myenteric Plexus (Auerbach's Plexus): Located deep between the circular and longitudinal muscular layers of the gut, this network primarily orchestrates smooth muscle contraction and the rhythmic phenomena of the peristaltic reflex.
• The Submucosal Plexus (Meissner's Plexus): Situated in the submucosa near the gut lumen, this network regulates localized gastrointestinal secretion, mucosal blood flow, and the selective absorption of water and nutrients.
• Enteric Glial Cells (EGCs): Dynamic, non-neuronal support cells that heavily outnumber neurons. They are indispensable for maintaining the intestinal epithelial barrier, supporting the stem cell niche via WNT ligands, and actively coordinating mucosal immune responses.
• The Gut-Brain Axis (GBA): A bidirectional communication superhighway between the ENS and the central nervous system, primarily utilizing the vagus nerve—which functionally acts as a massive sensory conduit, sending 90% of its data upward to the brain.
• Braak's Hypothesis: A paradigm-shifting neurological framework suggesting that idiopathic Parkinson's disease physically originates in the ENS via misfolded alpha-synuclein proteins, which propagate in a prion-like manner retrogradely up the vagus nerve to the brain.

Tomato-Soy Juice Lowers Systemic Inflammation

These high-lycopene tomatoes used to make the juice were developed by study co-author David Francis, an Ohio State expert in tomato breeding and genetics.
Photo Credit: The Ohio State University

Scientific Frontline: Extended "At a Glance" Summary: Tomato-Soy Juice and Systemic Inflammation

The Core Concept: A specialized functional food intervention combining high-lycopene tomato juice and soy isoflavone extract has been shown to significantly lower pro-inflammatory proteins in healthy adults with obesity.

Key Distinction/Mechanism: Unlike generic tomato juice, this specially bred and formulated beverage leverages a concentrated combination of plant-based phytochemicals (lycopene and soy isoflavones) to actively reduce blood levels of specific cytokines, including Interleukin-5 (IL-5), Interleukin-12p70 (IL-12p70), and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Origin/History: The high-lycopene tomatoes were originally developed by Ohio State University researchers for prostate cancer studies. A recent four-week clinical trial published in Molecular Nutrition & Food Research established the combined juice's broader anti-inflammatory efficacy in humans.

Major Frameworks/Components:

• Lycopene: A carotenoid phytochemical responsible for the red color in tomatoes, noted for its strong antioxidant properties.
• Soy Isoflavones: Plant-derived flavonoids that mimic the action of the hormone estrogen, utilized for their anti-inflammatory capabilities.
• Cytokines: Pro-inflammatory proteins produced by the immune system that serve as trackable markers of systemic inflammation.
• Metabolomics: The analysis of molecular products (metabolites) in urine to confirm and track biological changes driven by the nutritional intervention.

Researchers identify a key protein in the inflammatory response to infections

From left to right, researchers Carlos Sebastián, Jorge Lloberas, Carlos Batlle and Antonio Celada.
Photo Credit: Courtesy of University of Barcelona

Scientific Frontline: Extended "At a Glance" Summary: The Role of Protein Polμ in the Inflammatory Response

The Core Concept: Polμ (Polymerase mu) is a crucial protein that facilitates DNA repair in macrophages during an immune response, ensuring the survival of these essential cells. By protecting innate immune cells from the genetic damage caused by their own pathogen-destroying mechanisms, Polμ enables effective tissue repair and limits chronic inflammation.

Key Distinction/Mechanism: When macrophages engulf pathogens, they release high volumes of reactive oxygen species (ROS) to neutralize the external threat. While effective against infectious agents, ROS inadvertently induce severe DNA damage within the macrophages themselves. Polμ functions as the primary repair mechanism for this specific genetic damage, allowing the macrophages to survive the hostile environment they create and subsequently trigger the necessary tissue repair processes.

Major Frameworks/Components:

• Macrophages: Innate immune system cells that act as the body's first line of defense, responsible for both eliminating pathogens and initiating post-inflammatory tissue repair.
• Reactive Oxygen Species (ROS): Highly reactive chemical molecules deployed by macrophages to destroy infectious agents, which simultaneously pose a collateral threat to the cell's own DNA integrity.
• DNA Polymerase mu (Polμ): The specific polymerase protein that mitigates ROS-induced DNA damage, sustaining macrophage viability throughout the full cycle of the inflammatory response.

Axolotl (Ambystoma mexicanum): The Metazoa Explorer

 Axolotl (Ambystoma mexicanum)
Photo Credit: LoKiLeCh
(CC BY-SA 3.0)

Taxonomic Definition

The axolotl (Ambystoma mexicanum) is a paedomorphic amphibian belonging to the family Ambystomatidae within the order Urodela (Caudata). Historically distributed throughout the high-altitude lakes of the Valley of Mexico, its natural geographic range is currently restricted to the highly modified canal system and wetland remnants of Lake Xochimilco in southern Mexico City.

UCLA scientists identify zombie immune cells as a driver of fatty liver disease, inflammation and aging

Microscopy image showing senescent macrophages in red and cholesterol-laden lipid droplets – a key driver of senescence – in green.
Image Credit: Lizeth Estrada, Covarrubias Lab

Scientific Frontline: Extended "At a Glance" Summary: Senescent Macrophages in Fatty Liver Disease and Aging

The Core Concept: Cellular senescence is a biological stress response where cells cease dividing but do not die, instead lingering in tissue and emitting a toxic cocktail of inflammatory signals. In the liver, immune cells known as macrophages can enter this "zombie" state, continuously accumulating and driving the chronic inflammation associated with both aging and fatty liver disease.

Key Distinction/Mechanism: Unlike healthy macrophages that function to engulf cellular debris and pathogens, senescent macrophages are dysfunctional and perpetually inflamed. This pathological state is triggered not just by age, but by excess dietary cholesterol, and is identifiable by a unique molecular signature combining two specific proteins: p21 and \(TREM2^+\).

Major Frameworks/Components:

• Cellular Senescence: The biological mechanism where stressed cells permanently arrest their cell cycle and adopt a senescence-associated secretory phenotype (SASP), releasing pro-inflammatory factors.
• Pathological Cholesterol Metabolism: The process by which chronic exposure to high levels of LDL cholesterol overwhelms macrophage metabolic capacity, forcing them into senescence.
• The Geroscience Hypothesis: The theoretical framework proposing that targeting fundamental mechanisms of biological aging—such as the accumulation of senescent cells—can concurrently treat or prevent multiple age-related diseases.

Study shows mechanisms of aortic aneurysm progression and potential drug therapies

Graphical abstract of the study showing that Tet2-driven clonal hematopoiesis promotes aortic aneurysm progression through macrophage-to-osteoclast-like differentiation.
Image Credit: Nagoya University / Jun Yonekawa and Yoshimitsu Yura

Scientific Frontline: Extended "At a Glance" Summary: Mechanisms of Aortic Aneurysm Progression

The Core Concept: Aortic aneurysms are abnormal and potentially fatal enlargements of the aorta that are significantly accelerated by clonal hematopoiesis, an age-related condition wherein blood-forming stem cells acquire genetic mutations.

Key Distinction/Mechanism: Driven by Tet2 gene mutations, affected macrophages abnormally differentiate into osteoclast-like cells via the RANK/RANKL signaling axis. This cellular transformation degrades the extracellular matrix and thins elastin fibers within the aortic wall, directly fueling the rapid expansion of the aneurysm.

Major Frameworks/Components:

• Clonal Hematopoiesis: The age-related accumulation of genetic mutations in hematopoietic stem cells.
• Tet2 Gene Mutation: A specific genetic alteration that initiates the abnormal transformation of macrophages.
• Macrophage-to-Osteoclast-like Differentiation: The pathological adaptation of immune cells that results in elevated expression of osteoclast markers (such as TRAP and MMP-9) and subsequent vascular tissue degradation.
• RANK/RANKL Signaling Axis: The primary molecular pathway driving this detrimental cellular differentiation, sharing a fundamental pathogenesis with osteoporosis.

How bacteria suppress immune defenses in stubborn wound infections

Experiments found that wounds infected with E. faecalis (seen here) had dampened immunity, allowing E. faecalis to persist and enabling co-infecting bacteria like E. coli to thrive. A mouse model allowed researchers to study how lactic‑acid‑driven immune suppression promotes persistent, polymicrobial infections.
Image Credit: Janice Haney Carr / Centers for Disease Control and Prevention

Scientific Frontline: Extended "At a Glance" Summary: Bacterial Immune Suppression in Chronic Wounds

The Core Concept: Enterococcus faecalis (E. faecalis) is a highly resilient bacterium that suppresses the body’s initial immune defenses in wounds by releasing large amounts of lactic acid. This localized acidification deactivates key immune cells, allowing E. faecalis and other co-infecting microbes to establish persistent, hard-to-treat infections.

Key Distinction/Mechanism: Unlike bacteria that simply resist antibiotics, E. faecalis actively sabotages the host immune system through a targeted, two-step mechanism. The secreted lactic acid enters macrophages via the MCT-1 lactate transporter and simultaneously binds to the GPR81 lactate-sensing surface receptor. Engaging both pathways effectively shuts down the macrophage's downstream inflammatory response by preventing the activation of NF-κB, a critical intracellular immune alarm signal.

Major Frameworks/Components:

• Microenvironmental Acidification: The use of bacterial lactic acid to actively lower wound pH and alter the local tissue environment.
• Macrophage Deactivation: The direct targeting and suppression of the primary immune cells responsible for initiating the clearance of pathogens.
• Receptor-Mediated Silencing: The specific engagement of MCT-1 and GPR81 pathways to block intracellular immune signaling.
• NF-κB Inhibition: The molecular silencing of the host's fundamental "danger" alarm network.
• Polymicrobial Facilitation: The cascade effect wherein the dampened localized immunity creates an opportunistic environment for secondary pathogens, such as Escherichia coli, to rapidly colonize and proliferate.

What Is: Cellular Senescence

In the center, a single senescent "zombie" cell appears aged, enlarged, and distressed. It is actively emitting a glowing, noxious-looking mist or aura (representing the toxic SASP inflammatory factors). Surrounding it are healthy, vibrant, translucent cells
Image Credit: Scientific Frontline

Scientific Frontline: Extended "At a Glance" Summary: Cellular Senescence

The Core Concept: Cellular senescence is a biological paradigm in which a unique subpopulation of cells permanently and irreversibly stops dividing but evades apoptosis (programmed cell death). Instead of dying off, these arrested "zombie cells" remain metabolically hyperactive and linger within mammalian tissues.

Key Distinction/Mechanism: Senescence is distinct from quiescence, which is a temporary, reversible resting state in the G0 phase of the cell cycle. Senescence strictly locks cells in a permanent arrest during the G1 or G2 phases. Rather than clearing out, these cells secrete a complex, toxic cascade of inflammatory factors known as the Senescence-Associated Secretory Phenotype (SASP), which actively drives systemic tissue degradation and remodels the local cellular microenvironment.

Origin/History: The phenomenon was first documented in 1961 by researchers Leonard Hayflick and Paul Moorhead. They discovered that cultured primary human fibroblasts possess a strictly finite replicative lifespan, establishing a biological boundary now universally canonized as the Hayflick limit.

What Is: Macrophage

A realistic scientific visualization of a macrophage, a crucial immune cell, actively engulfing bacteria with its extended pseudopods.
The image provides a detailed look at the cell's internal structure during this defense process.

Scientific Frontline: Extended "At a Glance" Summary: Macrophage

The Core Concept: A macrophage is a highly versatile and essential metazoan immune cell primarily known for its ability to engulf particulate matter (phagocytosis), while also acting as a central orchestrator of tissue homeostasis, morphogenesis, metabolic regulation, and the bridge between innate and adaptive immunity.

Key Distinction/Mechanism: Unlike the historical dogma that all macrophages continuously derive from circulating blood monocytes, modern immunology distinguishes self-renewing tissue-resident macrophages (derived from embryonic progenitors) from short-lived, monocyte-derived macrophages recruited only during acute inflammation. Mechanistically, macrophages operate via an active, receptor-mediated "zipper" mechanism, utilizing specialized surface receptors to recognize targets, trigger actin-driven engulfment, and process the engulfed material within a hostile, highly acidic phagolysosome.

Macrophage immune cells need constant reminders to retain memories of prior infections

Image Credit: © 2026 Gorin et al.
Originally published in Journal of Experimental Medicine

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Macrophages do not possess inherent long-term memory but instead rely on constant stimulation from residual interferon-gamma molecules sequestered on their surface to maintain a primed state against repeat infections.
• Methodology: Researchers exposed human macrophages to interferon-gamma, identifying that the resulting "enhancer" DNA domains were not permanent but were actively maintained by lingering cytokine signals; blocking these signals reversed the memory state.
• Key Data: Temporary exposure generated thousands of new genetic enhancers that persisted for days, yet these memory markers were rapidly erased when the residual surface-bound interferon-gamma was pharmacologically inhibited.
• Significance: The study fundamentally shifts the understanding of innate immune memory from a stable cellular reprogramming event to a reversible, environment-dependent condition driven by tissue "staining" with cytokines.
• Future Application: New treatments could target and erase maladaptive macrophage memories to resolve autoimmune disorders such as lupus, rheumatoid arthritis, and type 1 diabetes without permanently compromising the immune system.
• Branch of Science: Immunology and Molecular Genetics
• Additional Detail: Lead author Dr. Aleksandr Gorin describes the phenomenon as tissues being "stained" by cytokines, which creates a sustained signaling loop that keeps local macrophages on high alert.

Plastic particles increase inflammation and cross barriers

Lukas Kenner, visiting professor, Department of Molecular Biology.
Photo Credit: Medizinische Universität Wien

Scientific Frontline: "At a Glance" Summary

• Core Discovery: Micro- and nanoplastics (MNPs) exacerbate chronic inflammatory bowel diseases (IBD) and penetrate biological barriers to accumulate in vital organs beyond the gastrointestinal tract.
• Methodology: Researchers utilized a mouse model of ulcerative colitis, orally administering polystyrene particles—a common plastic found in food packaging—to analyze molecular and histological interactions with the intestinal mucosa and immune system.
• Mechanism of Action: MNP exposure triggers pro-inflammatory activation of macrophages and induces gut dysbiosis, characterized by a decrease in beneficial bacterial species and an increase in potentially harmful, pro-inflammatory microbes.
• Data Point: Nanoplastic particles smaller than 0.0003 millimeters (0.3 micrometers) demonstrated the highest mobility, successfully traversing the intestinal barrier to deposit in the liver, kidneys, and bloodstream.
• Contextual Findings: The uptake of MNPs into the intestinal mucosa is significantly intensified during active inflammatory states, suggesting a feedback loop where existing inflammation facilitates further plastic accumulation.
• Primary Implication: MNPs are an underestimated environmental factor in the pathogenesis of chronic inflammatory diseases, highlighting an urgent need to evaluate the systemic health risks posed by the migration of the smallest particles into major organ systems.

Canine Ocular Melanosis

Pathophysiology, genomic architecture, clinical progression, and therapeutic management of canine ocular melanosis
Image Credit: Scientific Frontline

In the discipline of veterinary ophthalmology, few conditions present as complex a challenge as Canine Ocular Melanosis (OM). Predominantly affecting the Cairn Terrier, yet not exclusive to this breed. This hereditary disorder is characterized by a relentless, progressive infiltration of pigmented cells within the ocular tissues, leading to severe morbidity through the development of intractable secondary glaucoma. Historically and colloquially referred to as "pigmentary glaucoma," this terminology has largely been abandoned in the academic literature in favor of "ocular melanosis" to more accurately reflect the underlying pathological process: a primary proliferation and migration of melanocytes, rather than a passive dispersion of pigment granules as seen in human pigmentary glaucoma. The disease represents a significant welfare concern due to the chronic pain associated with ocular hypertension and the eventual, often bilateral, loss of vision. Furthermore, its entrenched status within the Cairn Terrier gene pool, driven by an autosomal dominant mode of inheritance and a late age of onset, poses a profound dilemma for breeders and geneticists alike.  

Rebalancing the Gut: How AI Solved a 25-Year Crohn’s Disease Mystery

Electron micrographs show how macrophages expressing girdin neutralize pathogens by fusing phagosomes (P) with the cell’s lysosomes (L) to form phagolysosomes (PL), compartments where pathogens and cellular debris are broken down (left). This process is crucial for maintaining cellular homeostasis. In the absence of girdin, this fusion fails, allowing pathogens to evade degradation and escape neutralization (right).
Image Credit: UC San Diego Health Sciences

The human gut contains two types of macrophages, or specialized white blood cells, that have very different but equally important roles in maintaining balance in the digestive system. Inflammatory macrophages fight microbial infections, while non-inflammatory macrophages repair damaged tissue. In Crohn’s disease — a form of inflammatory bowel disease (IBD) — an imbalance between these two types of macrophages can result in chronic gut inflammation, damaging the intestinal wall and causing pain and other symptoms. 

Researchers at University of California San Diego School of Medicine have developed a new approach that integrates artificial intelligence (AI) with advanced molecular biology techniques to decode what determines whether a macrophage will become inflammatory or non-inflammatory. 

The study also resolves a longstanding mystery surrounding the role of a gene called NOD2 in this decision-making process. NOD2 was discovered in 2001 and is the first gene linked to a heightened risk for Crohn’s disease.

Immune system meets cancer: Checkpoint identified to fight solid tumor

Immunofluorescence image of the expression of PHGDH (red) and CD3 T cells (green) in cryosectioned AE17 mesothelioma.
Image Credit: Zhengnan Cai

Checkpoint PHDGH in tumor-associated macrophages influences immune response and tumor growth

A study by a scientific team from the University of Vienna and the MedUni Vienna, recently published in the top-class journal Cellular & Molecular Immunology, has a promising result from tumor research: The enzyme phosphoglycerate dehydrogenase (PHDGH) acts as a metabolic checkpoint in the function of tumor-associated macrophages (TAMs) and thus on tumor growth. Targeting PHGDH to modulate the cancer-fighting immune system could be a new starting point in cancer treatment and improve the effectiveness of clinical immunotherapies.

Our immune system constantly fights emerging cancer cells that arise from mutations. This process is controlled, among other things, by different types of macrophages. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the tumor microenvironment. They come from tissue-resident immune cells circulating in the blood that penetrate the tumor and differentiate there in response to various messenger substances (cytokines) and growth factors. In most solid tumors, TAMs are paradoxically considered to be tumor-promoting ("protumorigenic") overall: they promote tumor growth and metastasis by suppressing the immune response, promoting the vascular supply to the tumor and also increasing resistance to drug therapies – i.e. they generally correlate with a poor prognosis for the affected patients. Previous attempts to influence TAMs proved unsatisfactory because many patients had only a limited response to these therapeutic approaches. This underlines the urgency of finding new active ingredients and strategies.

Mice study suggests metabolic diseases may be driven by gut microbiome, loss of ovarian hormones

Mice that received fecal implants from donors that had their ovaries removed gained more fat mass and had greater expression of liver genes associated with inflammation, Type 2 diabetes, fatty liver disease and atherosclerosis. The findings may shed light on the greater incidence of metabolic dysfunction in postmenopausal women. The team members included, from left: molecular and integrative physiology professor Erik R. Nelson; Kelly Swanson, the director of the Division of Nutritional Sciences and the Kraft Heinz Endowed Professor in Human Nutrition; and animal sciences professor Brett R. Loman.
  Photo Credit: Fred Zwicky

The gut microbiome interacts with the loss of female sex hormones to exacerbate metabolic disease, including weight gain, fat in the liver and the expression of genes linked with inflammation, researchers found in a new rodent study.

The findings, published in the journal Gut Microbes, may shed light on why women are at significantly greater risk of metabolic diseases such as obesity and Type 2 diabetes after menopause, when ovarian production of female sex hormones diminishes.

“Collectively, the findings demonstrate that removal of the ovaries and female hormones led to increased permeability and inflammation of the gut and metabolic organs, and the high-fat diet exacerbated these conditions,” said Kelly S. Swanson, the director of the Division of Nutritional Sciences and the Kraft Heinz Endowed Professor in Human Nutrition at the University of Illinois Urbana-Champaign who is a corresponding author of the paper.  “The results indicated that the gut microbiome responds to changes in female hormones and worsens metabolic dysfunction.”