Anticancer compounds for B cell cancer therapy targeting cellular stress response — ScienceDaily

0 Comments

Researchers at The Wistar Institute and collaborators from the University of Notre Dame are developing anticancer compounds targeting a pathway of the endoplasmic reticulum (ER) stress response implicated in the development of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and lymphoma. The study was published online today in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research.

The ER is an important organelle in our cells that oversees the quality control of protein folding under normal conditions and responds to the accumulation of misfolded proteins found under stressful conditions by activating specific mechanisms and signaling pathways such as the IRE-1/XBP-1 pathway that triggers a cascade of events that brings cells back to normal physiological conditions.

The laboratory of Chih-Chi Andrew Hu, Ph.D., professor in the Immunology, Microenvironment & Metastasis Program at Wistar, and collaborators show that targeting the ER stress signaling response is an effective strategy against various B cell cancers that rely upon ER stress signaling response to survive under stressful conditions.

The Wistar Institute and Notre Dame teams are working together to advance a new class of compounds to inhibit IRE-1 protein and block the function of the IRE-1/XBP-1 pathway, which promotes survival of malignant B cells such as MM and CLL cells. The IRE-1 inhibitors being developed by Hu and collaborators have shown promising activity in several preclinical cancer models, compared to other commercially available IRE-1 inhibitors having variable and inconsistent ability to selectively target ER stress signaling in vitro and in vivo.

“We carefully compared many published inhibitors of the IRE-1/XBP-1 pathway with our own inhibitors, showing that our compounds are the most reliable small molecule inhibitors for targeting this pathway in malignant B cells and that many of the other published inhibitors we tested have subpar activity or adverse off-target effects,”

StanChart Tech Boss Heeds Bank’s Post-Wuhan Stress Lessons: Q&A

0 Comments

(Bloomberg) — From sourcing 2,000 laptops for computer-less staff to boosting remote working capacity 20-fold, Michael Gorriz spent the year at the center of a global bank’s scramble to cope with an office-emptying pandemic.

Standard Chartered Plc’s chief information officer had a ringside seat for the start of the crisis. While his bank is headquartered in London, the German-born Gorriz works from Singapore — a five-hour flight to Wuhan, the Chinese epicenter of the coronavirus outbreak. StanChart’s branch in Wuhan was locked down, giving an early inkling of what life under Covid-19 might be like.



a man wearing a suit and tie: Michael Gorriz


© via Bloomberg
Michael Gorriz

Michael Gorriz

Loading...

Load Error

Courtesy of Standard Chartered

The pandemic drove thousands of older customers online for the first time, stress-testing technology for a company that’s bet heavily on digital banking. The Wuhan outbreak also gave Gorriz a unique perspective on enabling working from home at a time when the crisis still seemed remote in global banks’ western bases.

“My management team and I speculated this might not be the end, so we just kept on pushing,” said Gorriz, who spearheaded a drive to increase the number of remote login channels for employees from 5,000 at the start of the year to more than 100,000 six weeks after the first Chinese lockdown.

With the worst of the pandemic seemingly over in StanChart’s Asian markets, Gorriz, who has been in his role in 2015, is turning his attention to the lessons he learned as the chief technologist.

His comments have been edited and condensed.

How has banking changed?

The pandemic was a good proving point for digital capabilities, both our internal operations and also in our customer interactions. In institutional banking, where there was still a high willingness to see customers physically, obviously all the customers were concerned and scared about

Is COVID Stress Making You Numb? Stop Blaming Yourself!

0 Comments

After months of combating Covid stress, you might wonder why one more thing – the election, wildfires, civil unrest or boredom setting in – causes you to go numb. You have no feelings and all the common excesses like streaming videos, eating sweets, or pouring an extra glass of wine seem so appealing.

A new approach to dealing with the toxic emotions caused by the pandemic and unrest of 2020 is to see the problem as a stress wire. A wire triggered that numbness! What’s so appealing about this approach, which is emotional brain training, is that we can visualize, target, and switch off the root cause of that numbness in our brain: the stress-reactive neural circuit. 

Laurel Mellin, PhD

Switch off the reactive wire and feel better faster.

Source: Laurel Mellin, PhD

That wire is a “real entity,” a neural circuit. How refreshing. We can use scientific strategies to deal with that wire as when we switch off that wire, our symptom switches off, too. We get relief, and due to the nature of neuroplasticity, every time we switch if off, the brain changes. The wire becomes weaker, so we are less likely to trigger that “numbness circuit.” We have more control over our psychological responses. On the first day of this series, you imagined that you had a resiliency pathway in your brain that takes you from stress to joy. Now, on this second day of the series on The Stress Vaccine, imagine why it is so important for you to use that pathway.  

That resiliency pathway effectively switches off the root cause of your issue, the reactive wire. We all have some of these wires and a new way to take care of our emotional health is to visualize these wires, then process our emotions through our resiliency pathways and

New clues about the link between stress and depression — ScienceDaily

0 Comments

Researchers at Karolinska Institutet in Sweden have identified a protein in the brain that is important both for the function of the mood-regulating substance serotonin and for the release of stress hormones, at least in mice. The findings, which are published in the journal Molecular Psychiatry, may have implications for the development of new drugs for depression and anxiety.

After experiencing trauma or severe stress, some people develop an abnormal stress response or chronic stress. This increases the risk of developing other diseases such as depression and anxiety, but it remains unknown what mechanisms are behind it or how the stress response is regulated.

The research group at Karolinska Institutet has previously shown that a protein called p11 plays an important role in the function of serotonin, a neurotransmitter in the brain that regulates mood. Depressed patients and suicide victims have lower levels of the p11 protein in their brain, and laboratory mice with reduced p11 levels show depression- and anxiety-like behaviour. The p11 levels in mice can also be raised by some antidepressants.

The new study shows that p11 affects the initial release of the stress hormone cortisol in mice by modulating the activity of specific neurons in the brain area hypothalamus. Through a completely different signalling pathway originating in the brainstem, p11 also affects the release of two other stress hormones, adrenaline and noradrenaline. In addition, the tests showed that mice with p11 deficiency react more strongly to stress, with a higher heart rate and more signs of anxiety, compared to mice with normal p11 levels.

“We know that an abnormal stress response can precipitate or worsen a depression and cause anxiety disorder and cardiovascular disease,” says first author Vasco Sousa, researcher at the Department of Clinical Neuroscience, Karolinska Institutet. “Therefore, it is important to find out

Participants in an eight-week mindfulness-based stress reduction course reported significant improvement in levels of pain, depression and disability — ScienceDaily

0 Comments

A mindfulness-based stress reduction (MBSR) course was found to benefit patients with chronic pain and depression, leading to significant improvement in participant perceptions of pain, mood and functional capacity, according to a study in the Journal of the American Osteopathic Association. Most of the study respondents (89%) reported the program helped them find ways to better cope with their pain while 11% remained neutral.

Chronic pain is a common and serious medical condition affecting an estimated 100 million people in the United States, which correlates with annual costs of approximately $635 billion. The small-scale study was conducted in a semi-rural population in Oregon where issues of affordability, addiction and access to care are common. Participants received intensive instruction in mindfulness meditation and mindful hatha yoga during an eight-week period.

“Many people have lost hope because, in most cases, chronic pain will never fully resolve,” says Cynthia Marske, DO, an osteopathic physician and director of graduate medical education at the Community Health Clinics of Benton and Linn County. “However, mindful yoga and meditation can help improve the structure and function of the body, which supports the process of healing.”

Healing and curing are inherently different, explains Dr. Marske.

“Curing means eliminating disease, while healing refers to becoming more whole,” Dr. Marske says. “With chronic pain, healing involves learning to live with a level of pain this is manageable. For this, yoga and meditation can be very beneficial.”

The study found mindful meditation and yoga led to significant improvements in patients’ perceptions of pain, depression and disability. Following the course, Patient Health Questionnaire (PHQ-9) scores, a standard measure of depression, dropped by 3.7 points on a 27-point scale. According to Dr. Marske, some patients experience a similar drop from the use of an antidepressant.

“Chronic pain often goes hand-in-hand with depression,”