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ATHENA "desktop human" for drug and toxic agent screening gets a liver

ATHENA "desktop human" for drug and toxic agent screening gets a liver | Salus (Health) | Scoop.it

A five-year, US$19 million multi-institutional effort is working on developing a "desktop human" that could reduce the need for animal testing in the development of new drugs. The "homo minitus" is a drug and toxicity analysis system that would comprise four human organ constructs interconnected to mimic the response of human organs. The project has now reported success in the development of its first organ construct, a human liver construct that responds to exposure to a toxic chemical much like a real liver.

 

 


Via Ray and Terry's
Pasquale Valente's insight:

the ultimate goal of the project is to, "build a lung that breathes, a heart that pumps, a liver that metabolizes and a kidney that excretes."

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Salus (Health)
P4 (predictive, preventive, personalized, partecipatory) medicine
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Scientists create functioning "mini-lungs" to study cystic fibrosis

Scientists create functioning "mini-lungs" to study cystic fibrosis | Salus (Health) | Scoop.it
Researchers at the University of Cambridge have grown functional "mini-lungs" using stems cells derived from the skin cells of patients with a debilitating lung disease. Not only can the development help them in coming up with effective treatments for specific lung diseases like cystic fibrosis, but the process has the potential to be scaled up to screen thousands of new compounds to identify potential new drugs.

Creating miniature organoids has been the focus of many a research group, as it allows scientists to better understand the processes that take place inside an organ, figure out how specific diseases occur and develop or even work towards creating bioengineered lungs.

The research team from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute studied a lung disease called cystic fibrosis, which is caused by genetic mutation and shortens a patient's average lifespan. Patients have great difficulty breathing as the lungs are overwhelmed by thickened mucus.

To create working mini-lungs, the researchers took skin cells from patients with the most common form of cystic fibrosis and reprogrammed them to an induced pluripotent state (iPS), which allows the cells to grow into a different type of cell inside the body.

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HP1β Is a Biomarker for Breast Cancer Prognosis and PARP Inhibitor Therapy

HP1β Is a Biomarker for Breast Cancer Prognosis and PARP Inhibitor Therapy | Salus (Health) | Scoop.it
by Young-Ho Lee, Xiyong Liu, Fuming Qiu, Timothy R. O’Connor, Yun Yen, David K.

 

Abstract


Members of the heterochromatin protein 1 family (HP1α, β and γ) are mostly associated with heterochromatin and play important roles in gene regulation and DNA damage response. Altered expression of individual HP1 subtype has profound impacts on cell proliferation and tumorigenesis. We analyzed the expression profile of HP1 family by data mining using a published microarray data set coupled with retrospective immunohistochemistry analyses of archived breast cancer biospecimens. We found that the patient group overexpressing HP1βmRNA is associated with poorly differentiated breast tumors and with a significantly lower survival rate. Immunohistochemical staining against HP1α, HP1β and HP1γ shows that respective HP1 expression level is frequently altered in breast cancers. 57.4 - 60.1% of samples examined showed high HP1β expression and 39.9 - 42.6 % of examined tumors showed no or low expression of each HP1 subtype. Interestingly, comparative analysis on HP1 expression profile and breast cancer markers revealed a positive correlation between the respective expression level of all three HP1 subtypes and Ki-67, a cell proliferation and well-known breast cancer marker. To explore the effect of individual HP1 on PARP inhibitor therapy for breast cancer, MCF7 breast cancer cells and individually HP1-depleted MCF7 cells were treated with PARP inhibitor ABT-888 with or without carboplatin. Notably, HP1β-knockdown cells are hypersensitive to the PARP inhibitor ABT-888 alone and its combination with carboplatin. In summary, while increased HP1β expression is associated with the poor prognosis in breast cancer, compromised HP1β abundance may serve as a useful predictive marker for chemotherapy, including PARP inhibitors against breast cancer.


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Krishan Maggon 's curator insight, March 14, 4:01 AM

Citation: Lee Y-H, Liu X, Qiu F, O’Connor TR, Yen Y, et al. (2015) HP1β Is a Biomarker for Breast Cancer Prognosis and PARP Inhibitor Therapy. PLoS ONE 10(3): e0121207. doi:10.1371/journal.pone.0121207

Rescooped by Pasquale Valente from Preventive Medicine
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Ingredient in Olive Oil Looks Promising in the Fight Against Cancer

Ingredient in Olive Oil Looks Promising in the Fight Against Cancer | Salus (Health) | Scoop.it
Molecular and Cellular Oncology.

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Memory B cells : Nature Reviews Immunology : Nature Publishing Group

Memory B cells : Nature Reviews Immunology : Nature Publishing Group | Salus (Health) | Scoop.it

Abstract

The immune system can remember a previously experienced pathogen and can evoke an enhanced response to reinfection that depends on memory lymphocyte populations. Recent advances in tracking antigen-experienced memory B cells have revealed the existence of distinct classes of cells that have considerable functional differences. Some of these differences seem to be determined by the stimulation history during memory cell formation. To induce rapid recall antibody responses, the contributions of other types of cells, such as memory T follicular helper cells, have also now begun to be appreciated. In this Review, we discuss these and other recent advances in our understanding of memory B cells, focusing on the underlying mechanisms that are required for rapid and effective recall antibody responses.


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Krishan Maggon 's curator insight, February 17, 4:26 AM
Memory B cellsTomohiro Kurosaki,Kohei Kometani& Wataru IseAffiliationsCorresponding authorNature Reviews Immunology (2015) doi:10.1038/nri3802Published online 13 February 2015
Gilbert Faure au nom de l'ASSIM's curator insight, February 17, 5:02 AM

where are they located? hidden??

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The role of CD95 and CD95 ligand in cancer - Nature.com

The role of CD95 and CD95 ligand in cancer - Nature.com | Salus (Health) | Scoop.it

Abstract

CD95 (Fas/APO-1) and its ligand, CD95L, have long been viewed as a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. In addition, these molecules are important in the immune elimination of virus-infected cells and cancer cells. CD95L was, therefore, considered to be useful for cancer therapy. However, major side effects have precluded its systemic use. During the last 10 years, it has been recognized that CD95 and CD95L have multiple cancer-relevant nonapoptotic and tumor-promoting activities. CD95 and CD95L were discovered to be critical survival factors for cancer cells, and were found to protect and promote cancer stem cells. We now discuss five different ways in which inhibiting or eliminating CD95L, rather than augmenting, may be beneficial for cancer therapy alone or in combination with standard chemotherapy or immune therapy.


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Krishan Maggon 's curator insight, February 8, 2:40 AM

Cell Death and Differentiation advance online publication 6 February 2015; doi: 10.1038/cdd.2015.3

The role of CD95 and CD95 ligand in cancer
OPEN

M E Peter1, A Hadji1,2, A E Murmann1, S Brockway1, W Putzbach1, A Pattanayak1and P Ceppi1

1Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Correspondence: ME Peter, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, 303 East Superior Street, Lurie-6-123, Chicago, IL 60611, USA. Tel: +1 312 503 1291; Fax: +1 312 503 0189; E-mail: m-peter@northwestern.edu

2Current address: Department of Pediatrics, Section of Hematology/Oncology/Stem Cell Transplantation, University of Chicago, Chicago, IL 60637, USA.

Received 8 December 2014; Revised 27 December 2014; Accepted 2 January 2015
Advance online publication 6 February 2015

GLG Pharma's curator insight, February 9, 7:58 AM

Another mediator in cancer cell death.

 

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Optogenetics captures synaptic transmission in live mammalian brain for the first time

Optogenetics captures synaptic transmission in live mammalian brain for the first time | Salus (Health) | Scoop.it

EPFL scientists Aurélie Pala and Carl Petersen have observed and measured synaptic transmission in a live animal for the first time, using optogenetics* to stimulate single neurons in the mouse barrel cortex (which processes sensory information from the mouse’s whiskers). They shined blue light on the neurons containing a gene-based light-sensitive protein, activating the neurons to fire. Then using microelectrodes, they measured resulting electrical signals in neighboring interneuron cells.


They also used an advanced imaging technique (two-photon microscopy) that allowed them to look deep into the brain of the live mouse and identify the type of each interneuron they were studying.

The data showed that the neuronal transmissions from the light-sensitive neurons differed depending on the type of interneuron on the receiving end. Only a few studies have directly investigated synaptic transmission between specific neocortical neurons in vivo, presumably due to the technical difficulties in obtaining intracellular recordings from connected pairs of neurons in vivo, the authors say in their (open-access) paper in Neuron.


The research overcomes a limitation of in vitro (lab) studies, where associated biomolecules are different from those in a live animal, and where cutting neural tissue for lab work also introduces artifacts, the researchers suggest. “This is a proof-of-concept study,” says Pala, who received her PhD for this work. “Nonetheless, we think that we can use optogenetics to put together a larger picture of connectivity between other types of neurons in other areas of the brain.”


The scientists are now aiming to explore other neuronal connections in the mouse barrel cortex. They also want to try this technique on awake mice, to see how switching neuronal activity on and off with a light can affect higher brain functions.


* Optogenetics works by inserting the gene of an light-sensitive protein into live neurons, from a single cell to an entire family of them. The genetically modified neurons then produce the light-sensitive protein, which sits on their outside, the membrane. There, it acts as an electrical channel – something like a gate. When light is shone on the neuron, the channel opens up and allows electrical ions to flow into the cell; a bit like a battery being charged by a solar cell. The addition of electrical ions changes the voltage balance of the neuron, and if the optogenetic stimulus is sufficiently strong it generates an explosive electrical signal in the neuron



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Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris. - PubMed - NCBI

Abstract

Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although the sustained virologic response rate in the treatment of genotype 1 using new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has been improved by more than 70%, several severe side effects such as skin rash/ageusia and advanced anemia have become a problem. Under these circumstances, a new type of anti-HCV oral drug with few side effects is needed. Our recently developed HCV drug assay systems, including the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line-derived ORL8 and ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding renilla luciferase to replicate efficiently. Using these systems as anti-HCV candidates, we have identified numerous existing medicines that can be used against HCV with few side effects, such as statins and teprenon. To obtain additional anti-HCV candidates, we evaluated a number of oral health supplements, and found that the capsule but not the liquid form of Cordyceps militaris (CM) (Ascomycotinanorth, North Chinese caterpillar fungus), which is used as a Chinese herbal medicine, exhibited moderate anti-HCV activity. In combination with interferon-α or ribavirin, CM exhibited an additive inhibitory effect. Among the main components of CM, cordycepin, but not ergosterol, contributed to the anti-HCV activity of CM. In consideration of all these results, we suggest that CM would be useful as an oral anti-HCV agent in combination with interferon-α and/or ribavirin.

Pasquale Valente's insight:

 "cordyceps militaris would be useful as an oral anti-HCV agent in combination with interferon-α and/or ribavirin"

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Pasquale Valente's curator insight, December 30, 2014 2:16 AM

"cordyceps militaris would be useful as an oral anti-HCV agent in combination with interferon-α and/or ribavirin."

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Neuroscience: How to Become Immune to Stress

Neuroscience: How to Become Immune to Stress | Salus (Health) | Scoop.it

Most people intuitively understand that exercise can improve your mood, but it was only last week that scientists figured out how it works. Their findings are of enormous importance to everybody who experiences stress at work.

According to a recent article in the New York Times, exercising causes your muscles to release a set of chemicals that block other chemicals the body releases in response to frequent stress.

In other words, constant stress brings you down, but consistent exercise lifts you up.


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Majority of weight loss occurs 'via breathing'

Majority of weight loss occurs 'via breathing' | Salus (Health) | Scoop.it
The results suggest that the lungs are the main excretory organ for weight loss, with the H20 produced by oxidation departing the body in urine, feces, breath and other bodily fluids.

Via ClickTell Consulting
Pasquale Valente's insight:

"eat less move more"

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ClickTell Consulting's curator insight, December 19, 2014 8:40 AM

The results suggest that the lungs are the main excretory organ for weight loss, with the H20 produced by oxidation departing the body in urine, feces, breath and other bodily fluids.


Although the findings of the paper may alter how weight loss is understood, strategies for losing weight should remain unchanged. Eating less and moving more is a surefire way to combat the overindulgences of the festive season.

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Zinc blood test could lead to early diagnosis of breast cancer

Zinc blood test could lead to early diagnosis of breast cancer | Salus (Health) | Scoop.it
Thanks to techniques normally used to analyze trace metal isotopes for studying climate change and planetary formation, early diagnosis of breast cancer could one day be possible via a simple bloo...

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'Huge breakthrough' in understanding how the immune system recognises cancer

'Huge breakthrough' in understanding how the immune system recognises cancer | Salus (Health) | Scoop.it
US researchers have revealed the identity of molecules on the surface of cancer cells which allow the body's immune system to identify and destroy them.

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New device yields close-up look at cancer metastasis | KurzweilAI

New device yields close-up look at cancer metastasis | KurzweilAI | Salus (Health) | Scoop.it
Engineers at Johns Hopkins Institute for NanoBioTechnology (INBT) have invented a lab device to give cancer researchers an unprecedented microscopic look at metastasis (spread of tumor cells, causing more than 90 percent of cancer-related deaths), with the goal of eventually stopping the spread, described in their paper in the journal Cancer Report.

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Is Cancer Growth Nocturnal?

Is Cancer Growth Nocturnal? | Salus (Health) | Scoop.it
Scientists hope that their findings provide evidence that administering certain treatments in time with the body's day-night cycle could boost their efficiency.

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Graham Player Ph.D.'s curator insight, October 7, 2014 11:36 AM

This study reveals there may be an advantage in considering the time of day when administering certain cancer treatments.

Professor Yosef Yarden of the Weizmann Institute of Science, one of the study's researchers, points out that "cancer treatments are often administered in the daytime, just when the patient's body is suppressing the spread of the cancer on its own."

You can read the full report published in the journal Nature Communications here - http://www.nature.com/ncomms/2014/141003/ncomms6073/full/ncomms6073.html

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Study of thousands of brains reveals tau as driver of Alzheimer's disease

Study of thousands of brains reveals tau as driver of Alzheimer's disease | Salus (Health) | Scoop.it
By examining more than 3,600 postmortem brains, researchers at Mayo Clinic's campuses in Jacksonville, Florida, and Rochester, Minnesota, have found that the progression of dysfunctional tau protein drives the cognitive decline and memory loss seen in Alzheimer's disease. Amyloid, the other toxic protein ...

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IBM Healthcare Industry: 2020 Vision - YouTube

http://www.ibm.com/healthcare As the global healthcare industry begins to redefine value and success for a more sustainable and value-based healthcare system...
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Promising peptide for traumatic brain injury, heart attack and stroke | KurzweilAI

Promising peptide for traumatic brain injury, heart attack and stroke | KurzweilAI | Salus (Health) | Scoop.it
Strokes, heart attacks, and traumatic brain injuries are separate diseases with certain shared pathologies that achieve a common end: cell death and human injury due to hypoxia, or lack of oxygen.

In these diseases, a lack of blood supply to affected tissues begins a signaling pathway that ultimately halts the production of energy-releasing ATP molecules — a death sentence for most cells.

By employing derivatives of humanin, a naturally occurring peptide encoded in the genome of cellular mitochondria, researchers at Ben Gurion University of the Negev are working to interrupt this process,

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Software analyzes human genome in as little as 90 minutes

Software analyzes human genome in as little as 90 minutes | Salus (Health) | Scoop.it
Whereas it took 13 years and cost US$3 billion to sequence a human genome for the first time, senior author Peter White notes that now "even the smallest research groups can complete genomic sequencing in a matter of days." The chokepoint lies in the next step: calibrating and analyzing the billions of generated data points for genetic variants that could lead to diseases.

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The IL-20 subfamily of cytokines [mdash] from host defence to tissue homeostasis : Nature Reviews Immunology : Nature Publishing Group

The IL-20 subfamily of cytokines [mdash] from host defence to tissue homeostasis : Nature Reviews Immunology : Nature Publishing Group | Salus (Health) | Scoop.it
Abstract

The interleukin-20 (IL-20) subfamily of cytokines comprises IL-19, IL-20, IL-22, IL-24 and IL-26. These cytokines are all members of the larger IL-10 family, but have been grouped together to form the IL-20 subfamily based on their usage of common receptor subunits and similarities in their target-cell profiles and biological functions. Members of the IL-20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. In this Review, we describe the cellular sources and targets of the IL-20 subfamily cytokines, and we detail how their expression is regulated. Much of our understanding of the unique biology of this group of cytokines is still based on IL-22, which is the most studied member of the IL-20 subfamily. Nevertheless, we attempt a broader discussion of the emerging functions of IL-20 subfamily cytokines in host defence, inflammatory diseases, cancer and metabolism.


Via Krishan Maggon , Gilbert Faure au nom de l'ASSIM
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Krishan Maggon 's curator insight, December 14, 2014 2:22 AM

NATURE REVIEWS IMMUNOLOGY | REVIEW

 The IL-20 subfamily of cytokines — from host defence to tissue homeostasisSascha Rutz,Xiaoting Wang& Wenjun OuyangAffiliationsCorresponding authorNature Reviews Immunology 14, 783–795 (2014) doi:10.1038/nri3766Published online 25 November 2014
Gilbert Faure au nom de l'ASSIM's curator insight, December 14, 2014 4:14 AM

nice review

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Miniature Portable Dialysis Machine on Fast Track for FDA Approval - Industry Tap

Miniature Portable Dialysis Machine on Fast Track for FDA Approval - Industry Tap | Salus (Health) | Scoop.it
Portable Dialysis Machines A Reality

Dialysis machines are needed by patients with renal (kidney) failure to clean their blood of wastes produced by the body. In 2008, Dr. Victor Gura, an internationally known kidney specialist at Cedars-Sinai Medical Center, proposed the first miniature portable dialysis machine..
An Alternative to Conventional Dialysis

The US Food & Drug Administration’s (FDA) fasttrack program, Innovation Pathway, streamlines the approval process for breakthrough technologies. In 2012, the “Wearable Artificial Kidney” (WAK), promoted by the Wearable Artificial Kidney Foundation, Inc., was awarded fast-track status, along with two other renal projects.

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James Mwangi's curator insight, December 28, 2014 7:20 PM

Current WAK devices will allow dialysis patients to return to a more normal routine while having their vital signs, fluids and electrolyte balance continuously monitored.

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FDA approves blood test that predicts risk of coronary heart disease

FDA approves blood test that predicts risk of coronary heart disease | Salus (Health) | Scoop.it

Coronary heart disease (CHD) kills more than 385,000 people in the United States each year, and more than half of those who die suddenly have no previous symptoms.


A new blood test that could reduce CHD-related illness and mortality by predicting the risk of future heart disease has been cleared by the US Food and Drug Administration (FDA). The PLAC Test for Lp-PLA2 screens for cardiovascular inflammation which can lead to a build up of rupture-prone plaque and result in a heart attack or stroke.




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How Exercise Changes Our DNA

How Exercise Changes Our DNA | Salus (Health) | Scoop.it
Exercise, a new study finds, changes the shape and functioning of our genes, an important step on the way to improved health and fitness.

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Liz PT ATC CSCS's curator insight, December 21, 2014 10:40 PM

Epigenetics, baby. It can improve your quality of life.

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Non-cardiovascular effects associated with statins. - Bmj

Statins form the pharmacologic cornerstone of the primary and secondary prevention of atherosclerotic cardiovascular disease. In addition to beneficial cardiovascular effects, statins seem to have multiple non-cardiovascular effects. Although early concerns about statin induced hepatotoxicity and cancer have subsided owing to reassuring evidence, two of the most common concerns that clinicians have are myopathy and diabetes. Randomized controlled trials suggest that statins are associated with a modest increase in the risk of myositis but not the risk of myalgia. Severe myopathy (rhabdomyolysis) is rare and often linked to a statin regimen that is no longer recommended (simvastatin 80 mg). Randomized controlled trials and meta-analyses suggest an increase in the risk of diabetes with statins, particularly with higher intensity regimens in people with two or more components of the metabolic syndrome. Other non-cardiovascular effects covered in this review are contrast induced nephropathy, cognition, cataracts, erectile dysfunction, and venous thromboembolism. Currently, systematic reviews and clinical practice guidelines indicate that the cardiovascular benefits of statins generally outweigh non-cardiovascular harms in patients above a certain threshold of cardiovascular risk. Literature is also accumulating on the potential non-cardiovascular benefits of statins, which could lead to novel applications of this class of drug in the future.


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Warning Signs—Two studies identify pre-cancerous state in the blood

Warning Signs—Two studies identify pre-cancerous state in the blood | Salus (Health) | Scoop.it

Researchers from the Broad Institute of MIT and Harvard, Harvard Medical School and Harvard-affiliated hospitals have uncovered an easily detectable, “pre-malignant” state in the blood that significantly increases the likelihood that a person will go on to develop blood cancers such as leukemia, lymphoma or myelodysplastic syndrome.


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Trinity scientists make breakthrough in understanding Parkinson's disease - Science Codex

Trinity scientists make breakthrough in understanding Parkinson's disease - Science Codex | Salus (Health) | Scoop.it
The scientists showed that the Parkin protein functions to repair or destroy damaged nerve cells, depending on the degree to which they are damaged People living with Parkinson's disease often have a mutated form of the Parkin gene, which may explain...

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Krishan Maggon 's curator insight, November 15, 2014 1:50 AM

 The problems in Parkinson's disease may be the failure to clear away sick nerve cells with faulty cellular battery packs, to make way for healthy replacements. Instead, sickly and dysfunctional nerve cells may accumulate, which effectively prevents the recruitment of fresh replacements.

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Study on effect of astragali radix polysaccharides in improving learning and memory functions in aged rats and its mechanism

Zhongguo Zhong Yao Za Zhi. 2014 Jun;39(11):2071-5. English Abstract; Research Support, Non-U.S. Gov't
Pasquale Valente's insight:
Abstract

To observe the effect of Astragali Radix polysaccharides (APS) on the learning and memory functions of aged rats, in order to explore its mechanism for improving the learning and memory functions. Natural aging female SD rats were selected in the animal model and randomly divided into the control group, the APS low-dose group (50 mg x kg(-1)), the APS high-dose group (150 mg x kg(-1)) and the piracetam-treated group (560 mg x kg(-1)). They were orally administered with the corresponding drugs for consecutively 60 days. Besides, a young control group was set. The learning and memory functions of the rats were tested by the open-field test and the Morris water maze task. The Western-blot method was used to observe the levels of relevant neural plasticity protein N-methyl-D-aspartate receptor (NMDA receptor) in hippocampus, calcium/calmodulin dependent protein kinase II (CaMK II), protein kinase (PKA), the phosphorylation level of CAMP response element binding protein (CREB) and the protein expression of brain derived neurotrophic factor(BDNF). In this study, the authors found that the learning and memory functions and the hippocampus neural plasticity protein expression of the aged rat group were much lower than that of the young control group (P < 0.01). Compared with the aged rat group, the APS group showed the significant improvement in the impaired learning and memory functions of aged rats and the up-regulation in the hippocampus neural plasticity protein expression. The results showed that APS may improve the learning and memory functions of aged rats by increasing the expressions of relevant neural plasticity proteins.

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