Here are 10 Powerful anti-inflammatory foods
10 Superfoods To Crush Inflammation!
Inflammation
Robots help put brakes on inflammatory diseases.
Atlas of necroptotic pathway expression in human intestinal crypts. CREDIT WEHI
A groundbreaking study conducted by WEHI has unveiled revolutionary techniques for detecting necroptosis, a crucial factor in various inflammatory diseases such as psoriasis, arthritis, and inflammatory bowel disease. These findings signify a significant leap forward in the accurate diagnosis of necroptosis and present practical methods that can be replicated in hospitals worldwide. This offers a promising avenue for the development of new treatment approaches for inflammatory diseases and has the potential to significantly improve the lives of millions of individuals globally.
At a glance
- Necroptosis is a form of cell death, one of the body’s natural processes for removing unwanted or dangerous cells. In some people, this process can go awry and trigger disease.
- Researchers have developed automated techniques to pinpoint when and where necroptosis happens in patients.
- The findings could lead to better diagnosis and personalised treatments for numerous inflammatory diseases.
Catching the cell death ‘culprit’
Necroptosis, a type of cell death associated with inflammation, has long been suspected as the ‘culprit’ driving many debilitating diseases associated with gut, skin, and lung conditions. However, identifying which cells undergo necroptosis in real-life situations has been difficult.
WEHI’s Dr Andre Samson, co-leader of the study, said the findings had cracked a challenging and hotly debated area of science.
“It is so exciting to finally be able to catch necroptosis in the act,” Dr Samson said.
The new methods precisely located necroptosis in patients with ulcerative colitis or Crohn’s disease, providing critical insights into how this cell death process contributes to various inflammatory diseases.
The findings further revealed that necroptosis responds not just to inflammation, but also to bacterial changes or immune issues.
“Among other results, we also found that when proteins like Caspase-8 cluster together in cells, it’s a sign of necroptosis,” Dr Samson said.
“This is a major leap forward in our journey to eventually delivering new medicines that can treat a long list of inflammatory diseases by stopping necroptosis.
“It helps us understand when and where necroptosis happens, both in healthy and disease situations.”
Lifesaving atlas for the future
The research opens new windows to understanding the intricate mechanisms of cell death and its connection to inflammatory diseases.
The team behind the study referred to their work as an “atlas of necroptosis” because it provides a precise map of which cells in the body are capable of undergoing necroptosis.
“We can now confidently visualise where and when necroptotic cell death can happen in the body,” said Prof Murphy.
In the spirit of collaboration, Prof Murphy emphasised that a key goal of the study was to discover a solution that could be easily replicated in both the laboratory and clinical settings.
“Most importantly, researchers and clinicians around the world will now be able to use these new methods, especially as liquid handling robots for immunostaining are common in hospitals and pathology departments worldwide,” he said.
“The next phase is to use these robotic methods to advance our understanding of which diseases could benefit from medicines that block necroptosis.”
The successful development of these automated methods to detect necroptosis in patients is just the beginning. The research team plans to extend their techniques to investigate other gut diseases, such as coeliac disease, and a broader range of inflammatory conditions of the skin, lung and kidney.
Unpicking the Origins of Rheumatoid Arthritis
Rheumatoid arthritis (RA) is an autoimmune disease that causes joint inflammation and destruction.1 There is currently no cure – and although there are many treatments, their effectiveness varies from person to person, suggesting an undefined pathogenic diversity.1 Deep characterisation of myeloid cell subsets by single-cell RNA sequencing across healthy and inflamed tissues in RA has identified new pathogenic cell states and subsets – with data from five large-scale studies. However, subset overlap across studies and compartments – such as in blood versus synovial tissue – has not yet been systematically investigated.
Presenting at the 2024 EULAR congress in Vienna, Sebastien Viatte explained, “We wanted to map monocyte subsets and states across studies and compartments to identify blood monocyte precursors of inflammatory synovial macrophage subsets observed in people with RA.”
With this in mind, the group set out to discover whether quiescent human blood monocyte states are pre-committed to an inflammatory synovial transcriptional program. First, peripheral blood mononuclear cells (PBMC) from healthy volunteers and RA patients with clinically well-controlled disease (quiescent PBMC) were enriched for monocytes by negative selection and subjected to single-cell RNA sequencing. The researcher then used published myeloid cell subsets to map onto their template based on the similarity of their expression scores. Hierarchical methods were applied to merge similar clusters and create a consensus map, and random forests were used to merge over-clustered data and identify novel myeloid cell states – and generate a final taxonomy of monocyte states in healthy human blood. Finally, to provide experimental validation at the protein level, PBMC from 19 RA patients with uncontrolled inflammation were deeply immunophenotyped, and inflammatory cell states with increased abundance in RA were identified.
All told, this work generated an exhaustive reference atlas comprising 11 monocyte states across anatomical compartments relevant to RA. For example, it was possible to show that different clusters, in fact, represent the same inflammatory synovial macrophage subset and are transcriptionally similar to an IL1B+ monocyte subset present in quiescent peripheral blood.
The findings also revealed that four quiescent monocyte states in the peripheral blood of both RA patients and healthy individuals expand in the blood of patients with uncontrolled RA. These likely represent blood precursors of pathogenic tissue macrophages.
This work is important because it not only defines a new monocyte cell taxonomy relevant for RA – with 11 continuous cell states that dynamically transition into each other across anatomical compartments – but also identifies potential blood precursors of pathogenic tissue macrophages.
Food’s Protective Power Against Inflammation
Inflammation can be good, signalling your body’s attempt to fight off infection or heal an injury. But when inflammatory cells soldier forth when you’re not sick or injured, chronic inflammation can ensue, contributing to obesity, cardiovascular disease, diabetes, and even autoimmune disease and cancer. The good—no, great—news is that the foods you eat can dramatically affect inflammation in your body, helping not only to prevent it but to fight it if it’s already started. Join Dr. Katsumoto as she discusses how foods can be anti-inflammatory—and how the ones you choose can also help the planet.
RA and lupus – targets were discovered on RNA to short-circuit inflammation.
A new study details the high-throughput process for rapid screening and identification of mysterious long non-coding RNA.
UC Santa Cruz researchers have discovered that LOUP is a multifunctional gene in immune cells called monocytes. LOUP can work inside the nucleus to control its neighbour SPI1. They also discovered that LOUP RNA can leave the nucleus and produce a small peptide in the cytoplasm leading to an increase in the protein SPI1 and causing downregulation of NF-kB, the master controller of inflammation. CREDIT Carpenter Lab, UC Santa Cruz
UC Santa Cruz researchers have discovered a peptide in human RNA that regulates inflammation and may provide a new path for treating diseases such as arthritis and lupus. The team used a screening process based on the powerful gene-editing tool CRISPR to illuminate one of the biggest mysteries about our RNA–the molecule responsible for carrying out genetic information in our DNA.
This peptide originates within a long non-coding RNA (lncRNA) called LOUP. According to the researchers, the human genome encodes over 20,000 lncRNAs, making it the largest group of genes produced from the genome. But despite this abundance, scientists know little about why lncRNAs exist or what they do. This is why lncRNA is sometimes called the “dark matter of the genome.”
The study, published May 23 in the Proceedings of the National Academy of Sciences (PNAS), is one of the few in the existing literature to chip away at the mysteries of lncRNA. It also presents a new strategy for conducting high-throughput screening to rapidly identify functional lncRNAs in immune cells. The pooled-screen approach allows researchers to target thousands of genes in a single experiment, which is a much more efficient way to study uncharacterized portions of the genome than traditional experiments focusing on one gene at a time.
The research was led by immunologist Susan Carpenter, a professor and Sinsheimer Chair of UC Santa Cruz’s Molecular, Cell, and Developmental Biology Department. She studies the molecular mechanisms involved in protection against infection. Specifically, she focuses on the processes that lead to inflammation to determine lncRNAs’ role in these pathways.
“Inflammation is a central feature of just about every disease,” she said. “In this study, my lab focused on determining which lncRNA genes regulate inflammation.”
This meant studying lncRNAs in a type of white blood cell known as a monocyte. They used a modification of the CRISPR/Cas9 technology, called CRISPR inhibition (CRISPRi), to repress gene transcription and find out which of a monocyte’s lncRNA plays a role in whether it differentiates into a macrophage—another type of white blood cell that’s critical to a well-functioning immune response.
In addition, the researchers used CRISPRi to screen macrophage lncRNA for involvement in inflammation. Unexpectedly, they located a multifunctional region that can work as an RNA and contain an undiscovered peptide that regulates inflammation.
Ms Carpenter said that understanding that this specific peptide regulates inflammation gives drugmakers a target to block the molecular interaction behind that response to suppress it. “In an ideal world, you would design a small molecule to disrupt that specific interaction instead of targeting a protein that might be expressed throughout the body,” she explained. “We’re still far from targeting these pathways with that level of precision, but that’s definitely the goal. There’s a lot of interest in RNA therapeutics right now.”