Predator-released hydrocarbons repel oviposition by a mosquito - nature's insect repellents ?

                                                                   N-Heneicosane 

                                                                    N-Tricosane

Many animals use chemicals to communicate with each other. Pheromones (most of us are familiar with these class of semi-synthetic compounds-used mainly as insect repellents) which influence social and reproductive behaviors within a particular species, are probably the best known and studied. Kairomones are produced by an individual of one species and received by an individual of a different species, with the receiving species often benefiting at the expense of the donor.

Cohen and his Israeli colleagues focused on the interaction between two insect species found in temporary pools of the Mediterranean and the Middle East: larvae of the mosquito C. longiareolata and its predator, the backswimmer N. maculata. When the arriving female mosquitoes detect a chemical emitted by the backswimmer, they are less likely to lay eggs in that pool.

To reproduce conditions of temporary pools in the field, the researchers used aged tap water with fish food added as a source of nutrients. Individual backswimmers were then placed in vials containing samples of the temporary pools, and air samples were collected from the headspace within the vials. The researchers used gas chromatography-mass spectrometry to analyze the chemicals emitted by the backswimmers.

Cohen and his colleagues identified two chemicals, hydrocarbons called n-heneicosane and n-tricosane (see structures), which repelled egg-laying by mosquitoes at the concentrations of those compounds found in nature. Together, the two chemicals had an additive effect.

Since the mosquitoes can detect the backswimmer's kairomones from above the water's surface, predator-released kairomones can reduce the mosquito's immediate risk of predation, says Cohen. But they also increase the female mosquito's chance of dying from other causes before she finds a pool safe for her to lay her eggs in.

Researchers conclude that, these newly identified compounds, and others that remain to be discovered, might be effective in controlling populations of disease-carrying insects. It's far too soon to say, but there's the possibility of an advance in the battle against infectious disease.

http://www3.interscience.wiley.com/journal/123572945/abstract?CRETRY=1&SRETRY=0

Cashew Seed Extract an Effective Anti-Diabetic ?

Cashew seed extract (hydroethanolic extract) shows promise as an effective anti-diabetic, according to a new study from the University of Montreal (Canada) and the Université de Yaoundé (Cameroun). The investigation analyzed the reputed health benefits of cashew tree products on diabetes, notably whether cashew extracts could improve the body's response to its own insulin.

The researchers claims that hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (see structure), stimulated glucose transport into C2C12 myotubes in a concentration-dependent manner. Extracts of other parts (leaves, bark and apple) of cashew plant were inactive. Significant synergistic effect on glucose uptake with insulin was noticed at 100 g/mL CSE. CSE and AA caused activation of adenosine monophosphate-activated protein kinase in C2C12 myotubes after 6 h of incubation. No significant effect was noticed on Akt and insulin receptor phosphorylation. Both CSE and AA exerted significant uncoupling of succinate-stimulated respiration in rat liver mitochondria.

"Of all the extracts tested (out of leaves, bark, seeds and apples), only cashew seed extract significantly stimulated blood sugar absorption by muscle cells," says senior author Pierre S. Haddad, a pharmacology professor at the University of Montreal's Faculty of Medicine. "Extracts of other plant parts had no such effect, indicating that cashew seed extract likely contains active compounds, which can have potential anti-diabetic properties."

Researchers conclude that, activation of adenosine monophosphate-activated protein kinase by CSE and AA likely increases plasma membrane glucose transporters, resulting in elevated glucose uptake. In addition, the dysfunction of mitochondrial oxidative phosphorylation may enhance glycolysis and contribute to increased glucose uptake. These results collectively suggest that CSE may be a potential anti-diabetic nutraceutical.

Cashew tree products have long been reported to be effective anti-inflammatory agents, counter high blood sugar and prevent insulin resistance among diabetics. This study validates the traditional use of cashew tree products in diabetes and points to some of its natural components that can serve to create new oral therapies...

Ref  : http://www3.interscience.wiley.com/journal/123573729/abstract?CRETRY=1&SRETRY=0

Discovery of a Proneurogenic, Neuroprotective Chemical.....

Scientists from University of Texas Southwestern Medical Center, Dallas, lead by Dr.Steven McKnight,  have discovered a compound (see structure)  that restores the capacity to form newmemories in aging rats, likely by improving the survival of newborn neurons in the brain's memory hub. The research has turned up clues to a neuroprotective mechanism that could lead to a treatment for Alzheimer's disease.

"This neuroprotective compound, called P7C3, holds special promise because of its medication-friendly properties. It can be taken orally, crosses the blood-brain barrier with long-lasting effects, and is safely tolerated by mice during many stages of development." claims Dr.Steven McKnight

In hopes of finding compounds that might protect such vulnerable neurons during this process, Pieper, McKnight and colleagues tested more than 1000 small molecules in living mice. One of the compounds, designated P7C3 (see structure), corrected deficits in the brains of adult mice engineered to lack a gene required for the survival of newborn neurons in the hippocampus. Giving P7C3 to the mice reduced programmed death of newborn cells,  normalizing stunted growth of branch-like neuronal extensions and thickening an abnormally thin layer of cells by 40 percent. Among clues to the mechanism by which P7C3 works, the researchers discovered that it protects the integrity of machinery for maintaining a cell's energy level.

To find out if P7C3 could similarly stem aging-associated neuronal death and cognitive decline, the researchers gave the compound to aged rats. Rodents treated with P7C3 for two months significantly outperformed their placebo-treated peers on a water maze task, a standard assay of hippocampus-dependent learning. This was traced to a three fold higher-than-normal level of newborn neurons in the dentate gyrus of the treated animals. Rats were used instead of mice for this phase of the study because the genetically engineered mice could not swim.

Prolonged treatment of aged rats with P7C3 also enhanced the birth of new neurons. "Aged rats normally show a decline in neurogenesis associated with an inability to form new memories and learn tasks," Pieper explained..

In their study, rats treated with P7C3 each day showed evidence of an increase in the formation of newborn neurons and significant improvements in their ability to swim to the location of a missing platform, s standardized test of larning and memory in rats.

The key to the treatment's success is the protection of newborn neurons, the researchers report. In fact, they explained, the normal process by which newborn neurons are incorporated into the brain as mature cells is a long and perilous one. Notably, they say that two other drugs (Dimebon and Serono compounds) -- both of which bear structural similarities to P7C3 -also encourage the growth of new neurons. It's tempting to think that all three compounds work in the same way the researchers pinpointed a derivative of P7C3, called A20, which is even more protective than the parent compound. They also produced evidence suggesting that two other neuroprotective compounds eyed as possible Alzheimer's cures may work through the same mechanism as P7C3. The A20 derivative proved 300 times more potent than one of these compounds currently in clinical trials for Alzheimer's disease. This suggested that even more potent neuroprotective agents could potentially be discovered using the same methods. Following up on these leads, the researchers are now searching for the molecular target of P7C3 -  key to discovering the underlying neuroprotective mechanism.

Ref : http://www.cell.com/retrieve/pii/S0092867410006720

Plant extract may be effective against inflammatory bowel disease

In continuation of my update on Broccoli and other Brassica family...
Plant extract may be effective against inflammatory bowel disease

How Dietary Supplement (Broccoli, Cabbage) May Block Cancer Cells....

In continuation of  how dietary supplement may block cancer cells... In my earlier blogs,  I have mentioned that, natural compound formed during the autolytic breakdown of glucobrassicin present in food plants of the Brassica genus, including broccoli, cabbage, Brussels sprouts, cauliflower and kale) are responsible for the anticancer activity associated with broccoli and other Brassica genus.

Now researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James) have discovered how a substance  (see below structure) that is produced when eating broccoli and Brussels sprouts can block the proliferation of cancer cells.

Compelling evidence indicates that the substance, indole-3-carbinol [(above structure, I3C) : Glucobrassicin (right structure) is a type of glucosinolate that can be found in almost all cruciferous plants, such as cabbages  and broccoli, degradation by the enzyme myrosinase is expected to produce an isothiocyanate, indol-3-ylmethylisothiocyanate- which is unstable and hydrlyses to give, I3C, as most dominant degradation product], may have anticancer effects and other health benefits, the researchers say. These findings show how I3C affects cancer cells and normal cells.

The laboratory and animal study discovered a connection between I3C and a molecule called Cdc25A, which is essential for cell division and proliferation. The research showed that I3C causes the destruction of that molecule and thereby blocks the growth of breast cancer cells.

"Cdc25A is present at abnormally high levels in about half of breast cancer cases, and it is associated with a poor prognosis," says study leader Xianghong Zou, assistant professor of pathology at the Ohio State University Medical Center.

For this study, Zou and his colleagues exposed three breast cancer cell lines to I3C. These experiments revealed that the substance caused the destruction of Cdc25A. They also pinpointed a specific location on that molecule that made it susceptible to I3C, showing that if that location is altered (because of a gene mutation), I3C no longer causes the molecule's destruction.

Last, the investigators tested the effectiveness of I3C in breast tumors in a mouse model. When the substance was given orally to the mice, it reduced tumor size by up to 65 percent. They also showed that I3C had no affect on breast-cell tumors in which the Cdc25A molecule had a mutation in that key location.

Ref :  American Association for Cancer Research : Cancer Prevention Research, Xianghong Zou et al.,

Antihypertensive Drugs May Protect Against Alzheimer's Disease....

Researchers at Mount Sinai School of Medicine have found that the drug carvedilol (see structure), currently prescribed for the treatment of hypertension, may lessen the degenerative impact of Alzheimer's Disease and promote healthy memory functions.  

"These studies are certainly very exciting, and suggest for the first time that certain antihypertensive drugs already available to the public may independently influence memory functions while reducing degenerative pathological features of the Alzheimer’s disease brain," said study author Giulio Maria Pasinetti, MD, PhD, Saunders Family Professor of Neurology and Director of the Center of Excellence for Novel Approaches to Neurotherapeutics at Mount Sinai School of Medicine....

Dr. Pasinetti’s team found for the first time that carvedilol, a blood pressure lowering agent, is capable of exerting activities that significantly reduce Alzheimer’s disease-type brain and memory degeneration. This benefit was achieved without blood pressure lowering activity in mice genetically modified to develop Alzheimer’s disease brain degeneration and memory impairment.

They also found that carvedilol treatment was capable of promoting memory function, based on assessments of learning new tasks and information and recall of past information, which is already chemically stored in the brain. In the study, one group of mice received carvedilol treatment and the other group did not. The scientists conducted behavioral and learning tests with each group of mice, and determined that it took the mice in the carvedilol significantly less time to remember tasks than the other group.

Ongoing clinical research is in progress to test the benefits of carvedilol, which may prove to be an effective agent in the treatment of symptoms of Alzheimer’s disease,   hope they will come out with positive results...

Ref : http://www.j-alz.com/issues/21/vol21-2.html

Ingredient in red wine may prevent some blinding diseases

In continuation of my update on Resveratrol.......
Ingredient in red wine may prevent some blinding diseases

Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides..

When I  was working with one of the leading agrochemicals company, I was using 4-chlorobenzotriflouride as starting material for my two projects (trifluralin and a pyrazole derivative with diflouromethyl substituted phnyl).  I know how difficult is to introduce the triflouromethyl group (use of anhydrous HF to convert CCl3 to CF3) and that is why we got the starting material imported. 

Now, MIT chemists have designed a new way to attach a trifluoromethyl group to certain compounds, which they believe could allow pharmaceutical companies to create and test new drugs much faster and potentially reduce the cost of drug discovery. 

MIT Chemistry Professor Stephen Buchwald, who led the research team, says achieving the synthesis has been a long-standing challenge for chemists. "Some people said it couldn't be done, so that's a good reason to try," says Buchwald, the Camille Dreyfus Professor of Chemistry at MIT.

With the new reaction, the CF₃ group can be added at a much later stage of the overall drug synthesis. The reaction can also be used with a broad range of starting materials, giving drug developers much more flexibility in designing new compounds.  Though many groups are trying, the major challenge has been finding a suitable catalyst  to transfer the CF₃ entity from another source to the carbon ring. 

CF₃^- (trifluoromethyl negative ion) tends to be unstable when detached from other molecules, so the catalyst must act quickly to transfer the CF₃ group before it decomposes. The MIT team chose to use a catalyst built from palladium i.e., BrettPhos (see structure). MIT team is not the first to try palladium catalysis for this reaction, but the key to their success was the use of a ligand (a molecule that binds to the metal to stabilize it and hasten the reaction) called BrettPhos 2-(Dicyclohexylphosphino)-3,6-dimethoxy-2'-4'-6'-tri-i-propyl-1,1'-biphenyl,  which they had previously developed for other purposes. 

During the reaction, a CF₃ group is transferred from a silicon carrier to the palladium, displacing a chlorine atom. Subsequently, the aryl-CF₃ unit is released and the catalytic cycle begins anew. The researchers tried the synthesis with a variety of aryl compounds and achieved yields ranging from 70 to 94 percent of the trifluoromethylated products. 

Researchers conclude that, in its current state the process is too expensive for manufacturing use. For drug discovery, however, it may lower overall costs because it streamlines the entire synthesis process.

"For discovery chemistry, the price of the metal is much less important," says Kinzel....

Ref :  http://www.sciencemag.org/cgi/content/abstract/328/5986/1679

Blueberry consumption is beneficial for hepatic diseases....

We know that blueberry has many chemicals such as anthocyanins, proanthocyanidins, resveratrol, flavonols and tannins and how blueberry inhibit mechanisms of cancer cell development and inflammation in vitro. Similar to red grape, some blueberry species contain in their skins significant levels of resveratrol a phytochemical. 

Now research team led by Ming-Liang Cheng, MD, from Department of Infectious Diseases, Guiyang Medical College, Guiyang,  have found that blueberries could reduce liver indices, serum levels of hyaluronic acid and alanine aminotransferase, and increase levels of superoxide dismutase and decrease levels of malondialdehyde in liver homogenates compared with the model group.  Meanwhile, the stage of hepatic fibrosis was significantly weakened. Blueberries increased the activity of glutathione-S-transferase in liver homogenates and the expression of Nrf2 and Nqo1 compared with the normal group, but there was no significant difference compared with the model group. 

The authors suggest that blueberry consumption is beneficial for hepatic diseases (including fibrosis)....

I read an article in the same lines, where in the  researchers from Miyazaki prefecture of southern Japan and University of Miyazaki, screened nearly 300 different agricultural products for potential compounds that suppress HCV replication and uncovered a strong candidate in the leaves of rabbit-eye blueberry (native to the southeastern US). They purified the compound and identified it as proanthocyandin (a polyphenol similar to the beneficial chemicals found in grapes and wine). While proanthocyandin can be harmful, Kataoka and colleagues noted its effective concentration against HCV was 100 times less than the toxic threshold. The researchers are  hoping to explore the detailed mechanisms of how this chemical stops HCV replication....

Ref :  http://www.biologynews.net/archives/2009/08/07/the_hepatitis_healing_power_of_blueberry_leaves.html

Liquid Crystals - A New Way to Better Data Storage ?

In continuation of my update on liquid crystals (after a long gap)....

As cell phones and computers continue to shrink, many companies are seeking better ways to store hundreds of gigabytes of data in small, low-power devices. A special type of liquid crystal (similar to those used in computer displays and televisions) offers a solution  and lasers can encode data throughout a liquid crystal known as holographic storage, the technique makes it possible to pack much more information in a tiny space.   

But attempts to use liquid crystals for data storage have had limited success. In order to reliably record and rewrite data, researchers must figure out a way to uniformly control the orientation of liquid crystal molecules as the most liquid crystal technologies currently rely on physical or chemical manipulation, such as rubbing in one direction, to align molecules in a preferred direction. 

In an important advance, scientists at the Tokyo Institute of Technology have created a stable, rewritable memory device that exploits a liquid crystal property called the "anchoring transition". Researchers  demonstrated memory and rewritable bistable devices based on an anchoring transition of a nematic liquid crystal on a perfluoropolymer surface. Spontaneous orientation changes between planar and homeotropic occur on cooling and heating with a large temperature hysteresis. Orientation switching also occurs by applying an electric field with a response time of several milliseconds depending on the field strength claims the researchers.

Using either a laser beam or an electric field, the researchers can align rod-like liquid crystal molecules in a polymer. Their tests show that the liquid crystal created by the team can store data, be erased and used again...

"This is the first rewritable memory device utilizing anchoring transition," said Hideo Takezoe, who led the research. And because the device is bi-stable -- the liquid crystals retain their orientation in one of two directions -- it needs no power to keep images, adds Takezoe.

 Ref : http://jap.aip.org/japiau/v107/i12/p123108_s1?isAuthorized=no

Resveratrol in Red Wine Neutralizes Toxicity of Proteins Related to Alzheimer's

We know that, Resveratrol (found in the skin of red grapes and is a constituent of red wine, see structure)  (trans-resveratrol) is a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi.  And also it has been reported to possess diverse activities such as, anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects in mouse and rat models of testings. In the only positive human trial, extremely high doses (3–5 g) of resveratrol in a proprietary formulation have been necessary to significantly lower blood sugar.Claims of anti-aging effects of the same compounds is to be still established.

Now researchers led by Rensselaer Professor Peter M. Tessier, have come up with an interesting finding i.e., resveratrol - has the ability to neutralize the toxic effects of proteins linked to Alzheimer's disease. 

As per the claims by the researchers, resveratrol picks out the clumps of peptides that are bad and leaves alone the ones that are benign, it helps us to think about the structural differences between the peptide isoforms (different packing arrangements of a particular peptide) Deformations of a particular peptide  the Aβ1-42 peptide,   have been linked to Alzheimer's disease. 

Improperly folded peptides have been shown to collect in accumulations called "plaques (often found near areas of cell death in diseased brain)" within the brain.

Researchers conclude that, though it is not clear that resveratrol is able to cross the blood-brain barrier. However, the molecule has garnered interest in recent years for its potential impact on cancer and aging...

Ref : http://www.jbc.org/content/early/2010/05/28/jbc.M110.133108....

New use of old drugs (Metformin & AICAR ) in treating hepatitis C...

In continuation of my update on Metformin...

Researchers from  University of Leeds have found drugs such as antidiabetic  drug  Metformin  (right  structure)  and                AICAR, (5-Amino-4-imidazole carboxamide ribonucleotide) below right structure) used to combat obesity, can prevent the hepatitis C virus from replicating in the body.

Drugs such as Metformin and AICAR work by stimulating an enzyme called AMP kinase (AMPK) which regulates energy within our cells,  the very enzyme that hepatitis C virus represses to enable it to replicate. As per the claim by the researchers, the hepatitis C virus switches off AMPK so that the cell continues production of lipids and membranes, both of which are vital to its survival. 

AMPK's usual function is to conserve the energy balance in cells (it does by temporarily shutting down the production of lipids (fats) and membranes) when it senses an increase in energy requirements. Researchers  claim that, when a cell becomes infected by a virus,  AMPK gets activated and  shuts down certain functions of the cell temporarily until the cell's energy is rebalanced. 

Building on this finding, the research team were able to examine how cells would react when treated with common drugs that stimulate AMPK. They found that in infected cells, the drugs were able to halt virus replication, enabling cells to clear the infection...

"We're very excited about these findings," says Professor Mark Harris from the University's Faculty of Biological Sciences. "These drugs are already on the market, and whilst substantial clinical trials still need to take place before they can be used to treat hepatitis C infection, we think it could be an enormous step forward in the battle against the virus."  ....

Ref : http://www.leeds.ac.uk/news/article/825/new_use_for_old_drugs_in_treating_hepatitis_c?research

Crizotinib Shows Dramatic Results for Shrinking Tumors (lung cancer)....

Patients with a specific kind of lung cancer may benefit from a Phase III clinical trial offered by the Moores UCSD Cancer Center. The new drug, crizotinib (structure), under development by Pfizer, showed dramatic results in reducing lung cancer tumors in some patients during Phase I and II clinical trials.

"The results of the first two trials have been very encouraging," said Lyudmila Bazhenova, MD, assistant clinical professor at UC San Diego School of Medicine and a member of the Moores UCSD Cancer Center...

According to a preliminary study,  57% of patients had their tumors reduced and at eight weeks of the treatment, 87% showed disease stabilization.

The Phase III clinical trial will compare crizotinib with standard-of-care chemotherapy in the treatment of ALK-positive recurrent NSCLC. Through a randomized selection process, patients will either be treated with chemotherapy or crizotinib. If the patients who are given the chemotherapy do not respond to treatment, they will be given crizotinib at the end of the trial....

Ref : http://ucsdnews.ucsd.edu/newsrel/health/06-22ShrinkingTumors.asp

FDA approves Jevtana to treat men with prostate cancer

In continuation of my update on Cabazitaxel......

FDA approves Jevtana to treat men with prostate cancer

Synergistic activity of Sorafenib and Sulforaphane abolishes pancreatic cancer...

In continuation of my update on "Sorafenib", I find this info interesting to share with...

A team led by Professor Dr. Ingrid Herr, Head of the Department of Molecular Oncosurgery, a group of the Department of Surgery at Heidelberg University Hospital, have come up with an interesting finding, i.e.,  Sorafenib  (used for advanced liver and kidney cancer) also appears to be effective against cancer stem cells in pancreatic cancer. It inhibits resistant tumor stem cells and is also especially effective in combination with sulforaphane, an organic compound found in broccoli. 

In their tests on cancer cells and mice, the researchers showed that sorafenib inhibited typical properties of cancer stem cells from pancreas tumors and greatly reduced tumor growth. However, this effect lasted only for a short time and after four weeks, new colonies of cancer stem cells formed that no longer reacted to further treatment with sorafenib. The resistance is probably related to a certain metabolic pathway, the NF-kB pathway, that is activated by sorafenib, claims the researchers. 

Naturally occurring substance(s) e.g., sulforaphane (vegetables from the cruciferous family such as broccoli and cauliflower possess a high content of sulforaphane, an anti-cancer compound)  that block precisely this undesired NF-KB pathway and thus make the dangerous cells vulnerable.  The experiments show that sulforaphane prevents the activation of the NF-kB pathway by sorafenib and hence the combination treatment reinforces the effect of sorafenib without causing additional side effects. Researchers conclude that the invasive potential of cancer cells was prevented  and  metastasis was completely blocked in cell culture experiments. 

"We assume that nutrition may be a suited approach to break therapy resistance of cancer stem cells and thus make tumor treatment more effective," Professor Herr suggested....

Ref : http://cancerres.aacrjournals.org/content/70/12/5004