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Anti-inflammatory drug JAK inhibitors (JAKi) reduces pain in rheumatoid arthritis (RA) but the mechanism is not clear.

To figure out if JAKi directly acted on human sensory neurons, the authors found they expressed JAK1 and STAT3.

The show that RA synovial fluid addition to human induced pluripotent stem cell (iPSC)-derived sensory neurons led to phosphorylation of STAT3 (pSTAT3), which was completely blocked by the JAKi tofacitinib.

The researchers also discovered that RA synovial fluid was enriched for the STAT3 signalling cytokines IL-6, IL-11, LIF, IFN-alpha and IFN-beta, and their requisite receptors present in peripheral nerves post-mortem.

They observed upregulation of pain-relevant genes with STAT3-binding sites, an effect which was blocked by tofacitinib in cytokine treated iPSCs. LIF also induced neuronal sensitisation, highlighting this molecule as a putative pain mediator.

Tofacitinib reduced the firing rate of sensory neurons stimulated with RA synovial fluid indicating role for JAKi in controlling analgesic properties. https://sciencemission.com/RA-synovial-fluid-induces-JAK-dep…tivation-o


Research led by Gui de Chauliac Hospital in Montpellier, France, and the University of Bologna in Italy reports that oveporexton improves wakefulness and reduces cataplexy episodes in patients with narcolepsy type 1. Findings suggest a potential therapeutic alternative to existing narcolepsy treatments without hepatotoxic effects associated with other treatment types.

Narcolepsy type 1 is a marked by and episodes of muscle weakness known as cataplexy. Orexin, a neuropeptide crucial for regulating wakefulness and preventing rapid-eye-movement (REM) sleep transitions, is deficient in patients with narcolepsy type 1. Current treatments primarily address symptoms without targeting the underlying orexin system itself.

Previous efforts have successfully targeted orexin receptor 2 (OX2R) to restore wakefulness and reduce cataplexy in patients with OX2R-targeting drugs. Liver-related side effects have so far limited clinical use, and the need for safe OX2R-targeting agents remains.

Currently, half of patients with non-Hodgkin’s lymphoma and acute lymphoblastic leukemia—two types of cancer that affect blood cells—do not respond adequately to treatment with CAR-T cells. The therapy involves harvesting the patient’s own defense cells (T lymphocytes), modifying them in the laboratory to make them capable of destroying tumor cells, and reinjecting them into the body. These refractory cases usually relapse after conventional immunotherapy.

To overcome this problem, Brazilian researchers have developed a more powerful version of CAR-T cells. The details of the research were published in the journal Cancer Research.

CAR-T cell immunotherapy is revolutionary and has saved many people’s lives in recent years. However, there are still a significant proportion of patients who don’t respond to this treatment.

Scientists have long been fascinated with the physiological changes that birds undergo before and during migration. Some birds eat so much fat before their journeys that they double in body weight. In some species, their hearts are enlarged to pump more blood, or their digestive tracts grow and then shrink. But researchers have only recently started to explore at a fundamental level how migratory birds get the energy required to keep themselves aloft for days on end without eating.

Last year, two independent groups published research that explored migratory bird physiology in the lab and field to probe what happens at the subcellular level that allows birds to cover vast distances. They both found answers in biology’s most fundamental engine: mitochondria.

Their studies show how small changes in the number, shape, efficiency and interconnectedness of mitochondria can have huge physiological consequences that contribute to birds’ long-duration, continent-spanning flights.

Can AI speed up aspects of the scientific process? Microsoft appears to think so.

At the company’s Build 2025 conference on Monday, Microsoft announced Microsoft Discovery, a platform that taps agentic AI to “transform the [scientific] discovery process,” according to a press release provided to TechCrunch. Microsoft Discovery is “extensible,” Microsoft says, and can handle certain science-related workloads “end-to-end.”

“Microsoft Discovery is an enterprise agentic platform that helps accelerate research and discovery by transforming the entire discovery process with agentic AI — from scientific knowledge reasoning to hypothesis formulation, candidate generation, and simulation and analysis,” explains Microsoft in its release. “The platform enables scientists and researchers to collaborate with a team of specialized AI agents to help drive scientific outcomes with speed, scale, and accuracy using the latest innovations in AI and supercomputing.”

Using global land use and carbon storage data from the past 175 years, researchers at The University of Texas at Austin and Cognizant AI Labs have trained an artificial intelligence system to develop optimal environmental policy solutions that can advance global sustainability initiatives of the United Nations.

The AI tool effectively balances various complex trade-offs to recommend ways of maximizing carbon storage, minimizing economic disruptions and helping improve the environment and people’s everyday lives, according to a paper published today in the journal Environmental Data Science.

The project is among the first applications of the UN-backed Project Resilience, a team of scientists and experts working to tackle global decision-augmentation problems—including ambitious sustainable development goals this decade—through part of a broader effort called AI for Good.

University of New Mexico researchers studying the health risks posed by gadolinium, a toxic rare earth metal used in MRI scans, have found that oxalic acid, a molecule found in many foods, can generate nanoparticles of the metal in human tissues.