(Press-News.org) CLEVELAND - As reported in Nature Communications, researchers from Cleveland Clinic's Lerner Research Institute have developed a novel, patient-derived model of ulcerative colitis, which will help advance studies into new treatments for the chronic inflammatory bowel disease.
The team used the model to identify a promising target that could be inhibited to slow disease progression.
Ulcerative colitis is characterized by abnormal reactions of the immune system that lead to inflammation and ulcers on the inner lining of the large intestines. It is a highly heterogeneous condition, both in terms of patients' symptoms and disease pathology.
Suppressing the overactive immune response with anti-inflammatory drugs is the current mainstay treatment for inflammatory bowel diseases, although these therapies have limited long-term efficacy in ulcerative colitis patients.
Research suggests that elements of both the immune system and the ulcerative colitis microenvironment (the surrounding, less diseased cellular components) interact to drive disease development and progression.
Considering that immune-suppressing drugs have demonstrated limited success in treating ulcerative colitis, researchers are interested to learn whether targeting elements of the microenvironment--including components of the intestinal lining (called the epithelium) and stem cell-like cells called stromal cells--may be a better or complementary treatment approach.
"Gaining a more comprehensive understanding of the complex interplay between immune and other cell types will be critical to developing new and more effective ulcerative colitis therapies and tailored, patient-specific treatment approaches," said Emina Huang, MD, staff in the Departments of Cancer Biology and Colorectal Surgery, and the study's lead author.
Dr. Huang, who is also a practicing colorectal surgeon, and her team developed their model using tissue samples from patients with ulcerative colitis who underwent surgery at Cleveland Clinic. They isolated a specific type of cell (called fibroblasts) that can be "reprogrammed" to develop into all-purpose, undifferentiated cells called induced pluripotent stem cells, which have emerged as a growing research priority.
The researchers then grew the stem cells in the lab into tiny, three-dimensional tissues that mimic actual organs (called organoids). They found that compared to healthy colon organoids, the diseased organoids reflected histological and functional features commonly observed in ulcerative colitis patients, including reduced mucus secretions, faulty barrier integrity of the intestinal lining and overexpression of select proteins (including one called CXCL8).
"Our in vitro model accurately mirrors what we observe in patients in the clinic and is much more dynamic than current models. For example, other organoid models only focus on the contributions of the epithelium, where ours reflects the contributions of other microenvironment components, too, like the stroma," said Dr. Huang.
After developing the model, the team was able to rapidly identify novel drug targets and candidates. They showed that inhibiting CXCL8 expression with a small molecule called repertaxin helped to slow disease progression.
"We look forward to further exploring repertaxin's potential benefit in other preclinical and eventual clinical studies," said Dr. Huang. "We are hopeful that others will also find this model useful in identifying other potential anti-ulcerative colitis drugs." She also noted that the approach used to develop this new ulcerative colitis model may also be used to model other complex diseases.
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Samaneh Sarvestani, PhD, a former research associate in Dr. Huang's lab, is first author on the study, which was supported in part by the National Institutes of Health and the American Society of Colorectal Surgeons. Dr. Huang is jointly appointment in the Digestive Disease and Surgery Institute at Cleveland Clinic.
Use of telehealth jumped sharply during the first months of the coronavirus pandemic shutdown, with the approach being used more often for behavioral health services than for medical care, according to a new RAND Corporation study.
Between mid-March and early May 2020, telehealth was used by more than 40% of patients with a chronic physical health condition and by more than 50% of those with a behavioral health condition, according to findings published in the Journal of General Internal Medicine.
Overall, almost half of the people who were undergoing treatment when the pandemic shutdown ...
In countries with a severe shortage of surgeons it is common for some operations to be carried out by medical staff with lower formal qualifications. Researchers at Karolinska Institutet, Sweden, have led an international study on the safety and efficacy of a common surgical procedure. The study, published in
JAMA Network Open, shows that inguinal hernia operations performed by associate clinicians at a hospital in Sierra Leone were just as safe and effective as those performed by doctors.
Many Sub-Saharan countries have a desperate shortage of surgeons, and to ensure that as many patients as possible can be treated, some operations are carried out by medical professionals who are not specialists in surgery. Such task sharing is supported by several bodies, including the World Health ...
Would you like to capture a chemical transformation inside a cell live? Or maybe revolutionize microchips' production by printing paths in a layer that has a thickness of just 100 nanometers? These and many other goals can now be achieved with the latest femtosecond laser created by a team of scientists led by Dr. Yuriy Stepanenko.
These days, there is a multitude of laser light sources. They each have their characteristics and different applications, such as observing stars, treating illnesses, and surface micro-machining. "Our goal is to develop new ones," says Yuriy Stepanenko, head of the team of Ultrafast Laser Techniques at the Institute of Physical Chemistry of the Polish Academy of Sciences. "We deal with sources that produce ultrashort pulses of light. Really very, ...
The study found a "systematic and quantifiable pattern" of political parties officers opting against fielding minority candidates where they perceive that their non-white appearance might prevent a win. This includes constituencies already held by the party, and those within reach, requiring just a small swing in the vote to change hands.
Dr Patrick English, from the University of Exeter, who carried out the research, said: "This combination of public opinion and party strategy is one of the most significant blockages to electing parliaments which fully reflect ...
A team of researchers from Colorado State University and the University of Cincinnati have discovered a new mode of snake locomotion that allows the brown tree snake to ascend much larger smooth cylinders than any previously known behavior.
This lasso locomotion, named because of a lasso-like body posture, may contribute to the success and impact of this highly invasive species. It allows these animals to access potential prey that might otherwise be unobtainable and may also explain how this species could climb power poles, leading to electrical outages.
Researchers said they hope the findings will help people protect endangered birds from the snakes.
The ...
Researchers reporting in Current Biology on January 11 have discovered that invasive brown tree snakes living on Guam can get around in a way that had never been seen before. The discovery of the snake's lasso-like locomotion for climbing their way up smooth vertical cylinders has important implications, both for understanding the snakes and for conservation practices aimed at protecting birds from them.
"Our most important finding is a new mode of snake locomotion," says co-senior author Julie Savidge of Colorado State University (CSU). "Only four major types have been recognized for nearly 100 ...
What The Study Did: Researchers examined pediatric COVID-19 hospitalization trends in 22 states for both severity among this population and spread of the virus.
Authors: Pinar Karaca-Mandic, Ph.D., of the University of Minnesota Carlson School of Management in Minneapolis, is the corresponding author.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamapediatrics.2020.5535)
Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including ...
What The Study Did: Medical records for patients admitted to an urban academic medical center were analyzed for race and ethnicity for evidence of racial bias in clinician documentation.
Authors: Jessica R. Balderston, M.D., of Virginia Commonwealth University Medical Center in Richmond, is the corresponding author.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamainternmed.2020.5792)
Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest ...
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"This study demonstrates a clear association between specific microbial species in the gut, certain foods, and risk of some common ...
Smartwatches and other battery-powered electronics would be even smarter if they could run AI algorithms. But efforts to build AI-capable chips for mobile devices have so far hit a wall - the so-called "memory wall" that separates data processing and memory chips that must work together to meet the massive and continually growing computational demands imposed by AI.
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Now, a team that includes Stanford computer scientist ...
