Health
New research in The FASEB Journal identifies the mechanism by which tobacco smoke affects the expression of clock genes in the lung and resets levels of locomotor activity in the brain
As if cancer, heart disease and other diseases were not enough motivation to make quitting smoking your New Year's resolution, here's another wake-up call: New research published in the January 2014 issue of The FASEB Journal suggests that smoking disrupts the circadian clock function in both the lungs and the brain.
Translation: Smoking ruins productive sleep, leading to cognitive dysfunction, mood disorders, depression and anxiety.
“This study has found a common pathway whereby cigarette smoke impacts both pulmonary and neurophysiological function. Further, the results suggest the possible therapeutic value of targeting this pathway with compounds that could improve both lung and brain functions in smokers,” said Irfan Rahman, Ph.D., a researcher involved in the work from the Department of Environmental Medicine at the University of Rochester Medical Center in Rochester, N.Y. “We envisage that our findings will be the basis for future developments in the treatment of those patients who are suffering with tobacco smoke-mediated injuries and diseases.
Rahman and colleagues found that tobacco smoke affects clock gene expression rhythms in the lung by producing parallel inflammation and depressed levels of brain locomotor activity.
Short- and long- term smoking decreased a molecule known as SIRTUIN1 (SIRT1, an anti-aging molecule) and this reduction altered the level of the clock protein (BMAL1) in both lung and brain tissues in mice.
A similar reduction was seen in lung tissue from human smokers and patients with chronic obstructive pulmonary disease (COPD).
They made this discovery using two groups of mice which were placed in smoking chambers for short-term and long-term tobacco inhalation.
One of the groups was exposed to clean air only and the other was exposed to different numbers of cigarettes during the day. Researchers monitored their daily activity patterns and found that these mice were considerably less active following smoke exposure.
Scientists then used mice deficient in SIRT1 and found that tobacco smoke caused a dramatic decline in activity but this effect was attenuated in mice that over expressed this protein or were treated with a small pharmacological activator of the anti-aging protein.
Further results suggest that the clock protein, BMAL1, was regulated by SIRT1, and the decrease in SIRT1 damaged BMAL1, resulting in a disturbance in the sleep cycle/molecular clock in mice and human smokers. However, this defect was restored by a small molecule activator of SIRT1.
“If you only stick to one New Year's resolution this year, make it quitting smoking,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Only Santa Claus has a list longer than that of the ailments caused or worsened by smoking. If you like having a good night's sleep, then that's just another reason to never smoke.”
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Researchers at the University of Louisville have confirmed that using the heat profile from a person's blood, called a plasma thermogram, can serve as an indicator for the presence or absence of cervical cancer, including the stage of cancer.
The team, led by Nichola Garbett, Ph.D., published its findings online Jan. 8 in PLOS ONE.
"We have been able to demonstrate a more convenient, less intrusive test for detecting and staging cervical cancer," Garbett said. "Additionally, other research has shown that we are able to demonstrate if the current treatment is effective so that clinicians will be able to better tailor care for each patient."
To generate a plasma thermogram, a blood plasma sample is "melted" producing a unique signature indicating a person's health status.
This signature represents the major proteins in blood plasma, measured by Differential Scanning Calorimetry (DSC).
The team, which includes Brad Chaires, Ph.D., Ben Jenson, Ph.D., William Helm, M.D., Michael Merchant, Ph.D., and Jon Klein, M.D., Ph.D., from the University of Louisville School of Medicine, have demonstrated that the plasma thermogram profile varies when a person has or does not have the disease.
The team believes that molecules associated with the presence of disease, called biomarkers, can affect the thermogram of someone with cervical disease.
They used mass spectrometry to show that biomarkers associated with cervical cancer existed in the plasma.
"The key is not the actual melting temperature of the thermogram, but the shape of the heat profile," Garbett said. "We have been able to establish thermograms for a number of diseases. Comparing blood samples of patients who are being screened or treated against those thermograms should enable us to better monitor patients as they are undergoing treatment and follow-up. This will be a chance for us to adjust treatments so they are more effective."
Chaires noted that plasma thermograms have different patterns associated with different demographics, as well as for different diseases.
This results in a more thorough application of the test as a person's thermogram can be compared to specific demographic reference profiles or, even better, to the person's own profile.
Using a person's unique thermogram would provide the most accurate application of the test which could be used as part of a personalized medicine approach.
Further clinical study could result in the plasma thermogram as a compliment test to the traditional screening method for cervical cancer, the Pap smear and would be less intrusive and more convenient for the patient.
Additionally, because the plasma thermogram test could allow treatment effectiveness to be more easily monitored, treatment that was not working could be stopped sooner and replaced with more effective treatment.
In summary, the test could result in earlier detection, more effective therapeutic approaches and lowered health care costs for screening and treatment of cervical cancer.
The University of Louisville researchers see great promise for their technique being able to detect and monitor in a range of other cancers and diseases. The test is noninvasive and requires only a simple blood draw.
The plasma thermogram test has already been applied to identify multiple cancers, including melanoma, lung, cervical, ovarian, endometrial and uterine cancers and other diseases, including lupus, rheumatoid arthritis, Amyotrophic lateral sclerosis (Lou Gehrig's Disease) and Lyme disease.
The test has shown great promise as a prognostic indicator of disease, allowing physicians to monitor cancer patients more closely for remission, response-to-therapy and recurrence.
As a result of the promising research findings, Garbett, Chaires and Jenson have founded a start-up company, Louisville Bioscience, Inc. (LBIdx), which holds an exclusive license to the University of Louisville's Plasma Thermogram technology. They also are shareholders in the company.
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