Category Archives: Bioorganic-medicinal

Researchers Reveal Genetic Basis for Toxic Algal Blooms

Algal bloom is a rapid increase or accumulation in the population of algae in freshwater or marine water systems, and is recognized by the discoloration in the water from their pigments.

A Harmful Algal Bloom (HAB) is an algal bloom that reasons terrible affects to other organisms through production of natural toxins, mechanical damage to different organisms, or by means of other manner.

In humans, the toxin can cause rashes, skin lesions, headaches and stomach pain.

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Despite decades of research, the trigger that causes algal blooms to begin poisoning their environment has long confounded scientists.

Now, researchers have found the genetic underpinning of domoic acid, a harmful neurotoxin. In a newresearchers describe three genes responsible for producing domoic acid in the phytoplankton Pseudo-nitzschia.

Monitoring how the clusters of genes behave could one day yield information on which environmental or biological triggers are responsible for activating them. That information could help fisheries and public health officials predict when harmful algal blooms will occur, allowing them to effectively prepare.

The “very small” cluster of genes responsible for the production of the toxin is a relatively rare phenomena compared to other similar organisms, indicating that they may serve some important biological function.

Researchers say “It’s not there to make us sick. There are different theories for why it’s there, including serving as a feeding deterrent,”

They speculate the toxin may deter organisms that would feed upon the algae.  Or it may be that the toxin allows algae to chemically bond to nutrients, such as iron, present in the water.

The discovery of these genes will allow us to explore many theories

Shaping the Future: Computational Exploration and Design of Functional Compounds

Researchers work on the development of forefront computational methods at the interface of chemistry, biology, physics and materials science. Highly accurate approaches derived from quantum mechanics have been the focus of their research, as have applications of their methods which include a broad range of systems – from (bio-) molecules over functional co-ordination compounds, to condensed phase systems. In-depth study and informed in silico design are carried out to obtain systems with desired properties and functionalities. Examples include complex processes such as solar light-driven catalysis for sustainable hydrogen production as a promising solution to the world’s energy problem.16

Theoretical and computational chemistry, biophysics, and materials science

Investigation of chiral systems

Chirality plays a vital role in many aspects of chemistry, biology, and physics. Vibrational Raman optical activity spectroscopy enables valuable information on the structure and dynamics of systems and has been widely used to study molecules in solution. Based on a newly developed approach, it became possible to present the first spectra for chiral metal complexes and a large metalloprotein, thus opening up an exciting field of research for coordination compounds as well as theoretical exploration of complex (bio-)molecules. The special case of Resonance Raman optical activity has also been further developed, which can provide important additional information due to resonance with electronically excited state(s).

Alongside static computational approaches, the group has presented a method for the first calculation of vibrational Raman optical activity spectra via forefront ab initio molecular dynamics, which includes effects such as anharmonicity and can treat systems at ambient environment.

Analysis of functional compounds

Having been involved in the study of various compounds ranging from (bio-)molecules over liquids to molecules on surfaces, recent group projects in collaboration with other groups have also, for example, concerned the investigation of electronic communication in dirhenium complexes, photoinduced proton-coupled electron transfer, and the development of refinement procedures for improved agreement of computational models and experimental data.

A Novel Drug for Liver Cancer

1Hepatocellular carcinoma (HCC) accounts for more than 90% of all liver cancers. Due to its restricted treatment options and poor diagnosis, there may be presently an unmet need for alternative, greater effective treatments. In a new study, researchers have developed a unique peptide drug known as FFW that might probably reduce tumor growth and gradual development of the cancer.

Previous research has examined SALL4, a protein related to tumor growth, as a prognosis marker and drug target for HCC, in addition to other cancers. However, it’s been previously categorized as an “undruggable target,” according to the researchers.

In prior studies, they observed that the SALL4 protein works with another protein, NuRD, to make an association typically imperative for the enhancement of cancers counting HCC.Drug molecules that act on protein interactions which incorporate SALL4-NuRD frequently require the target proteins to have a small “pocket” in their 3-d structure in which the drug molecule can reside and take effect.

 Rather than trying to find ‘pockets’ on SALL4, the research group designed a bio-molecule to block the interaction between SALL4 and NuRD. In lab experiments, blocking the interaction has brought about tumor cell death and decreased movement of tumor cells.

This bio-molecule, peptide FWW, is a small chain of amino acids which can interfere with these interactions and efficiently block the large protein-protein interaction surface, without needing a “pocket” to take effect. Moreover, the researchers observed that FWW should reduce the growth of Sorafenib-resistant HCC, while utilized in combination with Sorafenib.2

Focusing on the SALL4-NuRD interaction need to have vital implications for the treatment of HCC, this can translate to a broader range of cancers with accelerated SALL4. In the latest work, the research team has additionally demonstrated a powerful approach to appropriately target oncogenes formerly considered undruggable.

 “Moving forward, researchers hope to analyze how the targeting of these protein interactions may pan out in different cancer types.”

Alcoholism and Addiction

A drug that decreases alcohol’s effects on the brain

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Alcohol use disorders may have devastating effects on a person’s health, relationships, and finances. But for some, the feeling they get when taking a drink temporarily outweighs those other issues. Researchers have built up a novel medication that declines alcohol’s effects at the brain’s “reward system,” causing rats to self-administer the beverage less frequently.

Once devoured, the liquor goes into the brain and associated with the neurotransmitters and their receptors incorporating some worried in reward-system pathways. When activated, these pathways can cause emotions of pleasure, relaxation, and craving. Even though alcohol-treatment pills that interfere with the reward system exist, these pills aren’t very powerful and may have extreme aspect results. For effective treatment, researchers concentrated their efforts on a protein receptor known as GPR88 which is found dominatingly in reward-associated regions of the brain. Previous studies on genetically modified mice which lack GPR88 protein showed that these animals seek and consume alcohol more than normal mice. This led the researchers to surprise if a drug that stimulates GPR88 ought to reduce alcohol cravings. They had formerly developed a synthetic small molecule that activates GPR88 in vitro; however, this molecule couldn’t effectively pass the blood-brain barrier.

The researchers tweaked the structure of the compound to make it more likely to go into the brain. They arrived at a molecule called RTI-13951-33 that become effective, selective for GPR88 and will pass the blood-brain barrier. Whilst given RTI-13951-33, non-engineered rats drank less alcohol than earlier than they received the drug. In comparison, the rats gave themselves sugar water on the equal frequency with or without the drug. The researchers are now analyzing the molecule in both wild-type mice and those that lack the GPR88 receptor to show that the drug is specific for that receptor.

Paper Machine for Molecular Diagnostics

Paper Machine is a device that fuses sample preparation and Loop-mediated Isothermal Amplification (LAMP) with endpoint area using a handheld UV source. The model integrates paper microfluidics (to enable fluid dealing with) and a multi-layer structure that allows a focal outlined paper strip to slide all through a fluidic path, and to allow the introduction of a test, wash buffers, and recognition reagents with insignificant pipetting. This gadget makes a dynamic seal that neutralizes evaporation amid incubation at 65 °C for an hour. This break is sufficient to allow a LAMP reaction for the Escherichia coli malB quality to proceed with an intelligent affectability of single target duplicate.

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Using a dsDNA analogue of the target region inside the malB gene of E. coli, the LAMP reaction is running inside the cellulose fiber lattice of a paper plate with a coherent affectability of a single duplicate of the target sequence. Target can be moved to the response plate by applying greater example volumes. This may permit less correct metering of sample. Further, the usage of greater example volumes may improve identification at low focuses by growing the probability of getting the target in the sample volume.

The present work is engaged around replacing this detection scheme with one that conveys a colorimetric signal visible with the unaided eye in the light. The use of fluid amplification reagents in this place will neutralize application in resource-limited conditions. Now, the work is fixated on lyophilizing these reagents on-board to address this issue. This “paper machine,” as presented, is minimal effort through its use of paper microfluidics and an isothermal upgrade reaction with endpoint discovery.

A New Drug Puts Cancer Cells Permanently to ‘SLEEP’

Scientist discovered anti-cancer drug without the usual side effects of conventional cancer treatments.2
Research up to now has proven progress in delaying cancer relapse in addition to treating some forms of cancer.

The technique of preventing the growth of tumours occurs without damaging any cell’s DNA, which takes place in traditional treatments including chemotherapy and radiotherapy.

The future of cancer therapy might be is to have directed and focused treatments so as to work on specific patient groups. A new kind of approach to cancer therapy that is preventing cancer cells from growing, however, leaving the normal cells especially unaffected and that’s by harnessing the body’s normal defences against unrestricted growth.

The development of the drug is at a pre-clinical stage. The research indicates that by targeting certain proteins recognized to play the primary function in the development of cancer, doctors can essentially prevent the disease.

These proteins are known as KAT6A and KAT6B and they’re proteins that affect certain genes most commonly observed in cancers. The disease-causing protein that has been targeted has actually not been able to be targeted before with a small-molecule potential drug. Researchers developed a small molecule that inhibits these proteins.

The way that those epigenetic drugs work especially this drug is that it freezes the cell, however, does not kill it off. In case you are at a late stage disease and have lots of tumours in your body, we obviously need to get rid of that first before seeking to prevent the cells from growing. This drug could be definitely beneficial after the usage of initial therapy that gets rid of the original tumour mass and we might use that new type of epigenetic drug to prevent any tumours from developing back, that’s a truly beneficial concept and idea.

Would EEL swim through the bloodstream to deliver a drug…??

1The robotic eel – Animating inanimate matter

Researchers found initial steps towards creating a microscopic “eel” that would swim through the bloodstream to deliver a drug to cells or genes.
Why an eel??
In comparison with most sea creatures, the eel has a notably easy system for swimming.

The technique to construct drug-delivery eel is as follows:

Step 1: Neuron Creation

Neurons oscillate among two states—excitatory and inhibitory. In the excitatory mode, they cause other neurons to fire. When they’re inhibitory, they hold other neurons from firing. As it occurs, there’s a category of chemical reactions that oscillates between two states, similar to those of a neuron.

BZ reaction is going back and forth between states of activity and inactivity. Researchers changed it into analogous to the exhibitory/inhibitory behaviour of nerve cells. This led to appearance to BZ reactions to create his synthetic neurons.

Step 2: Neural Network Building

The neurons looked like an ice dice tray with two columns, every divided into person ice dice cubicles. Researchers filled each of the ice dice chambers with a liquid solution containing the chemical substances necessary for the BZ reaction. BZ reaction became energetic (excitatory), it released a molecule that activates the second one field’s BZ reaction.

Next, the BZ reaction turned inactive (inhibitory). It then released a molecule that traveled to the ice cube field at once throughout from it, effectively suppressing, or placing on maintaining, the BZ response in that container.2A pattern emerged. One after the other, the BZ reactions in a column has been activated. After all the BZ reactions in the first column were completed, the reactions in the second column came out of the gap then begun up.

Remarkably, the BZ reactions had been interconnected and communicated with one another in the same order as the eel’s spinal neurons, going off one by one, one column after the other.

Step 3: Put the neural network into a gel

They selected a chemical-responsive form-changing gel into which they will implant his ice cube tray apparatus. They’re hoping the material will behave in the identical manner an eel’s frame does in response to the firings of its neurons.

New drugs for the Management of Obesity

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An alternative to Comprehensive life-style management

Comprehensive life-style management like weight loss plan, physical workout, and behaviour modification are the best approaches to deal with obesity. An alternative to that is drug-based therapy. Even though now not preferred or prescribed till life-style changes fall short in reaching that goal, pharmacotherapy offers a possibility for the obese population to obtain weight loss and to reduce the incidence of related health dangers like cardiovascular disorder, diabetes, cancer, and stroke.

Only a limited number of drugs are currently available that have either serious side effect profiles or modest efficacy for the long-term treatment of obesity. Most of the anti-obesity drugs function by altering the patient’s appetite or by reducing fat absorption. Currently, orlistat is the only drug approved by the FDA for long-term use. Under these circumstances, a novel histamine 3 receptor (H3R) agonist was identified recently by a drug discovery research organization lead to new candidate drugs for the management of obesity.

A systematic exploration of β-lactams and pyrrolidinone derivatives by making use of an efficient chemistry ought to result in exciting findings. Most of the molecules have been prepared in a single flask chemical transformation frequently termed as one-pot protocols. Four components were reacted in methanol at room temperature, and the Ugi response was monitored by using thin layer chromatography (TLC). Once the primary reaction was complete, reagents for the second transformation were added followed by means of monitoring of the reaction by TLC. The products have been isolated through filtration, and complex chromatographic techniques were not required. This kind of chemical transformation reduces the quantity of chemical waste and therefore is beneficial for developing sustainable chemical processes.

The organic screening of these compounds found out that they’re notably particular to H3R and did no longer interfere with associated isoforms including H1R, H2R, and H4R. A careful research of structural capabilities was finished to understand the pharmacophore this is required to design molecules with improved efficacy and safety.

In the next stage of our research, we evaluated the efficacy of the most activ2e molecule in mice. It was also interesting to observe that our molecule stimulates a hypophagic response in mice reflecting the reduction in food consumption. The computational analysis of physicochemical and pharmacokinetic properties of the recognized actives recommends that these molecules may possess proper bioavailability and permeability, which might be essential parameters for developing a candidate drug.

Moreover, researchers checked the viable covalent interaction of these molecules with different proteins by performing luciferase assay. Further research to optimize and develop candidate drugs from the recognized actives is currently underway.

New Gene associated with Parkinson’s disease

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Dopamine is a major neurotransmitter in the brain. A dopamine deficiency is associated with Parkinson’s disease, while overactive dopaminergic systems are associated with schizophrenia and other mental diseases. Recent research associated with the new gene related to the Parkinson’s disease. From this research, it is easy to design new therapies to slow neurodegeneration in the brains of patients with Parkinson’s disease and other related disorders.

NFE2L1 is a protein that controls the expression of genes involved in the differentiation and survival of dopamine neurons. NFE2L1 levels are reduced in dopamine neurons in the brains of Parkinson’s disease patients.   A large-scale of the genomic study f2ound that a minor allele of NFE2L1 can lower Parkinson’s risk. These observations imply that neuron death in Parkinson’s disease may result in part from a loss of the Neuroprotective action of NFE2L1. It hypothesizes that an increase of NFE2L1 can alleviate neuron death in rodent models of Parkinson’s disease. The results of the study will shed light on the ability of NFE2L1 to reduce neurotoxicity throughout the brain. By increasing NFE2L1 levels in the brain, it will be developing the Parkinson’s diseases therapies.

 It creates the new clinical application for those compounds which increase NFE2L1 levels in the brain, either by stimulating the protein’s expression or blocking the Protein’s destruction by the proteasome. NFE2L1 can relieve neuron demise related with alpha-synuclein amassing and aggregate formation- the trademark pathology of Parkinson’s – in pre-clinical models of Parkinson malady. Alpha-synuclein (also known as α-synuclein) is a protein whose function is crucial for the healthy brain. It is of remarkable interest to Parkinson’s researchers due to the fact it is a primary constituent of Lewy bodies, protein clumps which can be the pathological hallmark of Parkinson’s disease.

Most popular vitamin and mineral supplements provide no health benefit, study finds

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The most generally devoured vitamin and mineral supplements give no reliable medical advantage or mischief, recommends another examination drove by analysts.

Specialist found that multivitamins, vitamin D, calcium and vitamin C – the most widely recognized supplements – demonstrated no favorable position or included hazard in the counteractive action of cardiovascular infection, heart assault, stroke or sudden passing. For the most part, vitamin and mineral supplements are taken to add to supplements that are found in nourishment.

Scientists were shocked to discover so couple of constructive outcomes of the most well-known supplements that individuals devour .Researchers audit found that on the off chance that you need to utilize multivitamins, vitamin D, calcium or vitamin C, it does no mischief – however there is no evident favorable position either.”

The investigation discovered folic corrosive alone and B-vitamins with folic corrosive may decrease cardiovascular ailment and stroke. In the mean time, niacin and cancer prevention agents demonstrated a little impact that may imply an expanded danger of death from any reason.

“These discoveries recommend that individuals ought to be aware of the supplements they’re taking and guarantee they’re appropriate to the particular vitamin or mineral inadequacies they have been informed with respect to by their social insurance supplier.

Analysts looked into supplement information that incorporated A, B1, B2, B3 (niacin), B6, B9 (folic corrosive), C, D and E; and carotene; calcium; press; zinc; magnesium and selenium. The term ‘multivitamin‘ in this survey was utilized to portray supplements that incorporate most vitamins and minerals, as opposed to a chosen few.

“Without huge positive information – separated from folic corrosive’s potential decrease in the danger of stroke and coronary illness – it’s most gainful to depend on a solid eating regimen to get your fill of vitamins and minerals. Up until this point, no exploration on supplements has demonstrated us anything superior to anything sound servings of less handled plant sustenances including vegetables, foods grown from the ground.”