Neutrophil-to-lymphocyte ratio may predict renal function decline in diabetes

Researchers have found that Neutrophil-to-lymphocyte ratio is a predictor of renal dysfunction in diabetes patients.The study has been published in Diabetes Metabolic Syndrome: Clinical Research & Reviews. 

Inflammation play an important role in the pathogenesis of diabetic kidney disease.Neutrophil-to-lymphocyte ratio has been evaluated as a biomarker of inflammation and has been widely evaluated as a biomarker in various medical and surgical prognoses.However its usefulness in diabetic kidney disease is not yet known.

The researchers conducted a prospective observational study that included outpatients, comprising of 184 men aged 73 ± 11 (mean ± standard deviation) years and 174 women aged 76 ± 10 years at baseline, from a rural hospital. They examined the relationship between baseline NLR calculated by analyzing the differential leukocyte counts in the complete blood count and the 2-year estimated glomerular filtration rate (eGFR) decline rate (i.e. 2-year eGFR-baseline eGFR) ∗100/baseline eGFR. Rapid eGFR decline rate was defined as a value < -25%.

The researchers found that NLR (β = 0.138, p = 0.007) as well as presence of antidyslipidemic medication, hemoglobinA1c, and urinary albumin excretion stage were significantly and independently associated with a rapid eGFR decline rate.The multiple linear regression analysis using rapid eGFR decline rates as objective variables were adjusted for confounding factors as explanatory variables. 

The multivariate-adjusted odds ratios (95% confidence interval) of the 2nd and 3rd tertiles of baseline NLR for rapid eGFR decline rate were 3.62 (0.70-18.7) and 8.03 (1.54-41.9), respectively. 

Multivariate-adjusted mean eGFR (95% confidence interval) values after 2 years categorized by tertile of baseline NLR were: 1st, 63.9 (61.8-66.1); 2nd, 60.8 (58.7-62.9); and 3rd, 58.9 (56.8-61.0).
The researchers concluded that these results suggest that baseline Neutrophil-to-lymphocyte ratio might be a useful biomarker for renal function decline in outpatients with type 2 diabetes. This biomarker may help evaluate renal function in diabetics.

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Transcendental meditation correlated with specific changes in the brain

A new study conducted at IMT School for Advanced Studies Lucca shows that the subjective feeling of well-being experienced by many people with the practice of meditation is correlated with specific changes in the brain.

The research, which appeared in Brain and Cognition, examined the effects of the technique known as Transcendental Meditation (TM), which consists in the silent repetition of a meaningless sound, a "mantra".

For the study, conducted at the Molecular Mind Laboratory (MoMiLab) of IMT School for Advanced Studies Lucca, the researchers enrolled 34 healthy young volunteers and divided them in two groups. The first one practiced Transcendental Meditation 40 minutes per day in two sessions of 20 minutes each, one in the morning and the other in the evening; the second group did not change its daily routine.

At the beginning of the study, the researchers also measured through psychometric questionnaires the anxiety and stress level of all the participants, as well as their ability to manage stressful situations. Each individual was also subjected to a functional magnetic resonance imaging test (fMRI), in order to measure brain activity at rest and changes in the functional connectivity among different cerebral areas. After three months, at the end of the study, the same tests were repeated.

The analysis of the data clearly showed that levels of anxiety and stress perceived by the subjects who followed the meditation program were significantly reduced in comparison with those of the volunteers who did not practice TM.

Magnetic resonance imaging also shows that the reduction of anxiety levels is associated with specific changes in the connectivity between different cerebral areas, such as precuneus, left parietal lobe and insula, which all have an important role in the modulation of emotions and inner states. In the control group, instead, none of these changes was observed".    Giulia Avvenuti, Ph.D. fellow at IMT School and first author of the study.

"The fact that Transcendental Meditation has measurable effects on the 'dialogue' between brain structures involved in the modulation of affective states opens new perspectives for the understanding of brain-mind relationships" says Pietro Pietrini, IMT School's Director and coordinator of the study. "It also extends the results of recent research suggesting that drugs therapies and psychotherapy leverage on the same biological mechanism".

Transcendental Meditation has recently gained an increasing success worldwide as a relaxation practice also thanks to the David Lynch Foundation, which co-financed the study along with the Fondazione Cassa di Risparmio di Lucca. Founded in 2005 by the movie director David Lynch, who is himself a longtime practitioner and supporter of the social value of Transcendental Meditation, the David Lynch Foundation promotes TM practice as an approach to reduce stress in schools (as for the 'Quiet Time-Meditate Lucca' project at the Pertini High School) and workplaces, and to build resilience in victims of trauma.

"I am very happy of the results of this study that used the latest technology to show the beautiful benefits for the human beings of TM. Now I'm working to form my foundation also in Italy, with teachers who teach transcendental meditation in schools, work places and other groups, reaching as many people as possible" says David Lynch.

This new study, coherently with previous ones, shows that even a few months of practice of Transcendental Meditation have positive effects on psychological well-being and that these effects are correlated with measurable changes in the brain.

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Estrogen may facilitate the growth of liver metastases in non-sex-specific cancers

It is known that the tumour microenvironment plays an important role in the progression of cancer. But could estrogen present in this microenvironment facilitate the growth of liver metastases in women affected by colon, pancreatic and lung cancers? This is what a team of researchers from the Research Institute of the McGill University Health Centre (RI-MUHC) suggests, in a study that shows for the first time that the liver immune microenvironment reacts to metastatic cells differently in male and in female mice and that, indeed, the main female hormone estrogen can indirectly contribute to the growth of metastases. Their findings, recently published in Nature Communications, provide a rationale for further exploration of the role of sex hormones in female cancer patients and the potential benefits of anti-estrogen drugs such as tamoxifen in the treatment of hormone-independent cancers that metastasize to the liver. 

"What prompted us to begin this investigation was our finding that the immune microenvironments of liver metastases in male and female mice are regulated differently," says Dr. Pnina Brodt, senior scientist in the Cancer Research Program at the RI-MUHC and lead author of the study. "We were also aware of reports based on recent immunotherapy clinical trials that female patients do not respond to immunotherapy as well as male patients and that overall, patients with liver metastases respond more poorly to such treatments than patients without liver metastases." 

"We therefore wanted to identify factors unique to male and female responses to liver metastatic disease that could explain these findings and could eventually lead to improved immunotherapy outcomes for patients," adds Dr. Brodt. 

Dr. Brodt and her team looked at the interaction between metastatic cells entering the liver and the unique microenvironment of this organ, in mouse models of colon, pancreatic and lung carcinoma, malignant diseases that do not have a clear sex bias and are not depended on sex hormones for growth. 

By increasing and decreasing the levels of estrogen in their mouse models, the team discovered that estrogen plays a role in the expansion of liver metastases--a major cause of cancer-associated death. Specifically, they found that this hormone regulates the accumulation in the liver of bone marrow-derived innate immune cells such as the myeloid-derived suppressor cells (or MDSC) and immunosuppressive macrophages.

Cancer cell killers can become friends of the enemy
When metastatic cells enter the liver, innate immune cells are recruited, some from the bone marrow. These cells have the ability to kill cancer cells, but once in the tumour environment, they can also acquire immunosuppressive and tumour promoting functions. 

MDSCs, for instance, do not directly affect cancer cell growth, but can do so by changing the microenvironment around the tumour in the liver. 

"MDSCs can impede the activity of T lymphocytes, whose role is to kill the cancer cells. In this way, they act to promote--rather than curtail--the growth of metastases," explains Dr. Brodt, who is also Professor in the Departments of Surgery, Oncology and Medicine at McGill University. 

The team observed that estrogen induces an immune tolerant environment that helps the tumour cells grow, and that the removal of estrogen reduces the accumulation and activity of MDSCs that, in some way, become "friends" of the enemy. 

"The realization that cancer is a community of cells, not just the cancer cells, but also the cells that surround it has become an important part of how the scientific community now views cancer and how it should be treated," says Dr. Brodt.

Towards gender-specific cancer treatment?
In this era of personalized cancer management and with the worldwide effort to develop drugs that target the tumour microenvironment, awareness of the fact that male and female patients may respond differently to such treatments is very important. 

"This should now be taken into account to design better, more gender-specific treatment strategies, especially when we know that colorectal cancer incidence, for instance, is increasing in the younger population," says Dr. Brodt. 

There are several approved anti-estrogen drugs currently in routine clinical use. However, their use is restricted to patients with hormone-sensitive cancers such as breast cancer. 

Further investigation is warranted to determine if estrogen plays the same role in cancer patients, and if low toxicity anti-estrogen drugs such as tamoxifen could be used in conjunction with immunotherapy to neutralize the immunosuppressive environment in patients who have non-sex-specific cancers, are premenopausal and have higher levels of estrogen. 

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Immune cells rewire, repair brain while we sleep

Researchers have found that immune cells called microglia, which play an important role in reorganising the connections between nerve cells, fighting infections, and repairing damage, are also primarily active while we sleep.

Microglia serve as the brain’s first responders, patrolling the brain and spinal cord and springing into action to stamp out infections or gobble up debris from dead cell tissue.

“This research shows that the signals in our brain that modulate the sleep and awake state also act as a switch that turns the immune system off and on,” said study lead author Ania Majewska, Professor at University of Rochester in the US.

In previous studies, Majewska’s lab has shown how microglia interact with synapses, the juncture where the axons of one neuron connects and communicates with its neighbours.

The microglia help maintain the health and function of the synapses and prune connections between nerve cells when they are no longer necessary for brain function.

For the findings, researchers conducted the study on mice.

The current study points to the role of norepinephrine, a neurotransmitter that signals arousal and stress in the central nervous system.

This chemical is present in low levels in the brain while we sleep, but when production ramps up it arouses our nerve cells, causing us to wake up and become alert.

The study showed that norepinephrine also acts on a specific receptor, the beta2 adrenergic receptor, which is expressed at high levels in microglia.

When this chemical is present in the brain, the microglia slip into a sort of hibernation.

The study, which employed an advanced imaging technology that allows researchers to observe activity in the living brain, showed that when mice were exposed to high levels of norepinephrine, the microglia became inactive and were unable to respond to local injuries and pulled back from their role in rewiring brain networks.

“This work suggests that the enhanced remodeling of neural circuits and repair of lesions during sleep may be mediated in part by the ability of microglia to dynamically interact with the brain,” said the study's first author.

“Altogether, this research also shows that microglia are exquisitely sensitive to signals that modulate brain function and that microglial dynamics and functions are modulated by the behavioural state of the animal,” the first author said.

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Gut bacteria to play an important role in protecting against arsenic toxicity

 Microbes in the human gut play an important role in protecting against arsenic toxicity, new research suggests. Arsenic toxicity is a problem that affects an estimated 200 million people worldwide who are exposed to arsenic through contaminated food and drinking water. Long-term exposure to arsenic is associated with increased risk of cancer and cardiovascular diseases, among others.

A better understanding of how the microbiome protects against toxins like arsenic could benefit communities or villages with contaminated water sources through probiotic or other microbiome therapies, especially since it is not always practical or possible to replace a water source, said one of the researchers.

The study, conducted in mice, described the essentiality of gut microbiome for full protection against acute arsenic toxicity. "We found that depending on which microbiome the mice got, they were protected (against arsenic toxicity) to varying degrees," he said. 

Those results, suggest that the microbiome of some people may be more protective than others, he said.

The findings may answer the question of why some people who drink from a shared water source tainted with arsenic develop the disease later in life while others do not.

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