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We are promoting the future of therapeutic approaches with biomedicine and health. We help support future life science products that help support health or wellness. We are also part of the pipeline process here with initiatives in drug discovery together with others in discovery biology, medicinal chemistry, pharmacology & toxicology, clinical testing, manufacturing.
It is our goal to explore and span the process of pharma discovery with synthetic biology and medicinal chemistry to cell regenerative therapies including stem cell treatment of chronic diseases.
We are for the assay of mRNA factors (e. g. transcriptional factors or TFs) using specialized cell culture systems and metabolic systems dynamic modeling. Bioinformatics tools for sequencing DNA are to discover likely TF binding sites, discovering up-regulated genes for biosynthetic pathway metabolism and gene-silencing protocols in genetic manipulation for organo-synthetic drug discovery, biopharmaceutical drug discovery and gene therapeutics.
With mRNA assays of TFs with genetic expression there is an area for drug discovery referred to, involving body weight/composition. It is proposed that tested proprietary natural extracts be used with in situ biopsy using implants/microsurgical techniques with muscle representing lean body mass (LBM), the central nervous system (CNS) hypothalamic centre for satiety and fat thermogenic tissue against a background baseline of TFs in cell tissue assays. This has predisposed us to further research implicating nutraceutical AAs like HIS (histidine) in animal livestock production in class domesticated and game animals and at various stages of their growth and development.
A cell systems approach with putative ligand-receptor binding structural-functional relationships, signalling and ion channel transduction will be used in mind-body axis studies (e. g. within the CNS and immunocompetent cell systems in the gut) in the fields of neurobiology & endocrinology and neurocrine function.
A Sprague-Dawley rat model, undergoing treatment on animals, for example, prolonged streneous exercise, followed by biopsy of neurocrine CNS centres (e. g. the pituitary), via conduct mRNA assays and expressed protein products, with further isolation and characterization using proteomics, conduct Southern and Western blotting studies, study cell signalling and nuclear protein activation and characterize further their gene products.
Approaches include future possibilities with mind-body psychoactives with putative roles of neurocrine factors in catecholamine and folate metabolism and possible roles in increased metabolic rate and health and longevity factors (the state-of-the-art in anti-aging research at this time involves approaches such as the discovery of human gene products SIRT 1-7 which control energy metabolism and cell survival which interact with nutritionals such as resveratrol in wine and with whom GlaxoSmithKline at the time of release of this story was pursuing research on efficacy trials II on more effective drug agents compared to resveratrol for diabetes II and inflammatory disease although other diseases such as aging with cancer and heart disease are also involved; research is being investigated at the Harvard Medical School and conjointly with UNSW Medical School), biopharmaceutical mood-altering functional, cognitive enhancing and kinesiologic therapeutics with possible developmental and geriatric applications, including links between exercise therapy and the onset of dementia and neurocrine deconditioning and anti-addiction therapies.
It is enticing to think that there are now direct linkages metabolically between aging/degenerative disease states and metabolism as with the gene products mentioned above and that, as we have espoused here, use of nutritionals can be a further avenue to discover or develop drugs that can enhance longevity and/or slow the aging and its disease processes.
Immunotherapeutics is a growing area of interest in health and agriculture. There are amongst the arsenel of techniques: immunomodulation (see below), immunosuppression (e. g. tissue transplantation) with drugs, immunocontrol such with protozoa in the gut rumen and immunoresponsive therapy such as Igs used against the insidious effects of the mutated SOD1 protein on other proteins and their accumulation in the neurological system (e. g. brain and spinal cord and peripheral nerves) and eventual paralysis and death in Amyotrophic Lateral Sclerosis (ALS).
The use of an expanded library of metabolosomic therapeutics such as postulating that the low molecular weight (LMW)-scale proteome that is systemic or ex situ, in vivo can be sequenced 'tagged' as has already been used to allow entry intracellularly of such proteins, is an approach that we are being made aware of. Proteomics could grow by leaps and bounds in the coming decade, along with the discovery of the 'magic bullets' of drug discovery.
Putative agents with immunomodulatory effects being studied include actions of whey substrate studied in the lower gut, the well-studied fructans of fruits and vegetables with other sugars (e. g. raffinose, stacchyose, verbascose and galactose) and their role in neurocrine mind-body axis interactions with colon digestive health and putative systemic roles and ligno-material and lower gut health and oncogeneisis. On the subject of nutritionals, there is an issue in regulatory affairs with therapeutics that prevent and even reverse disease processes and the need to regulate them as drugs rather than as foods or nutraceuticals and the past continued trend of the cheaper route through bulk synthetic nutritionals and extractives, if available, rather than via vegetable or animal production.
Metabolic-related illnesses (e. g. nutritional imbalances/deficiencies), occupational-related diseases (e. g. exercise and diet with neurocrine factors and catabolic feedback with occurence, severity and duration of physical activity or exercise) and immunodeficiencies (preventative immunocompetency) are examples of disease processes we approach. Metabolic disorders are of particular interest and possible interventive modalities with nutritional (per os, enteric, parenteral), pharmacogenetic and organo-synthetic drugs: ketosis, acidosis, diabetes type II, putative roles for increased fat intake and disposition towards oncogeneisis including intake/uptake of fat and metabolic factors controlling fat depoting and metabolism and intake loss due to protein deficiency with amino acid imbalances and low protein levels, Kwashiorkor, burn victims or surgical convalescents and stress from hyper-caloric expenditure among a class of indentured labour may require appetite stimulants.
Obesity is a growing significant phenomenon in the world population and its morbidity risk factors. Approaches that have been successful are bariatric surgery, pharmacotherapeutic including receptor antagonists acting on the brain and fat digestive absorption blockers and have been met with some success and include more of the latest research on new drugs by the latest of reports. The recent reports on obesity drug research has still reinforced the current line in research for drugs (viz. receptor and enzyme binding relationships) and the study of structure-functional relationships in conventional drug research versus our more novel approach of use of physiological therapeutics and their drug-response relationships as a rationale as with nutritionals or from environmentally conditioned responsiveness.
Further exploring disease aetiology and pharmacogenesis is up to speculation as to the nature that the said above novel approaches might take as with metabolomic diseased states or modulation of the immunogeneic response including autoimmune diseases, inflammation-related disorders and cancers. We believe at Skye Blue that disease states can be protected against or even reversed and that biomolecular medical approaches might lead to better insight and discovery for avenues of cure of diseased states including genetic and developmental disorders, so-called rare, little-studied or orphan diseases. With the recent death of Britain's Margaret Thatcher (April, 2013) of stroke this decade reminds us of the need to "sink" disease research with growing demands or expectations for a cure. We propose here the need for discovering "elixirs" part of the special constructs in metabolomics as is beginning to be discovered [see: Biomolecular and Medical J. 2013 (c)] with nutrigenics as possible drug targets. This concept has far-reaching consequences in the treatment of diseases or keeping them under control with such allogenic substances.
There are parallels seen between fructan metabolism vis-a-vis Vit D metabolism with cholesterolemia and cardiovascular health, blood sugar levels, insulinemia and colon digestive tract health including oncogeneisis and leaves open the possibility of the role of endocrine factors in metabolism. The author at Skye Blue has conducted preliminary research on lanosterol functionality and synthetic reactivity and sequencing. A proposed schema for converting lanosterol back to its C-13 labelled derivative with roughly estimated yields was presented in an undegraduate seminar discussing methodologies which were adopted from the previous literature in principle and which were further adapted using organic chemical principles by the principal research worker (see below). Further research should study reactivity of steric derivatives of lanosterol to cholesterol and study of the differential reactivity of the ring system of the sterol molecule and the discovery to how drug candidates react to metabolic targets in intestines, bone, liver and kidney. Drugs can act in feedback inhibition (FBI) as 'enzyme agonists' as analogues to Vit D as theorized.
A major hurdle of this type of research is with animals that starts with lanosterol (animals and fungi) which convert this to cholesterol via the cytochrome P-450 superfamily of enzymes in 19 steps and to 7-dehydrocholesterol and upon irradiation to cholecalciferol or Vit D3 and to related hormones like calcidiol in the liver and kidney. Enzyme affinity and avidity to drug analogues is a question open to experimentation with structure-mechanisms to be studied with the enzymes involved in proteomics, structural folding studies, x-ray crystallography and structure-proofing to make the lanosterol side-chain derivatives bind constructively by residue replacement. Orientation and proximity (e. g. hydrogen-bonding between the aldehyde group of the prosthetic side-chain and amino acid residues of the enzymes) of atomic residues is apropos here.
The previous undergraduate senior independent project (SIP) conducted with Kalamazoo College, Kalamazoo MI USA by the principal is a thesis (unrefereed with references for documentation), in concept, a valid schema of chemical reactions using synthetic methods to help solve a synthetic biological problem. (There are other methods, for e. g., using a combination of chemical inferences with the study of the series of upregulated biosynthetic steps in the pathway.)
Cholesterolemia control with dietary phytosterols, exercise, oat fibre or bran and branched fibre and reduction in saturated fat are factors that present leads for further drug discovery or research and more aggressive controls of hypercholesterolemia.
It should be noted that colon tract health is also dependent on bulk fibre intake (and, perhaps, other endproducts from the diet) and gut-motor function in relation to risk for lower bowel cancer.
The latest news which has again renewed the debate of inflammation (see below) and research uncovering mechanisms to diseases such as inflammation implicated with cancer and Alzheimer's is a drug that treats both skin T-cell lymphoma and Alzheimer's called by the trade name Targetrin (R) (bexarotene) that activates the surface protein and which produces ApoE which breaks down beta amyloid plaque (unlike Alzheimer's e4 allele) and improves cognitive function in mice to be tested further in human trials. Bexarotene acts by presumably activating ApoE allele variants (viz. e2 and e3 allele of which at least one is carried in 16% and 95% of the Caucasoid population, while in 27% of the population at least 1 e4 allele occurs which results in considerable debilitation in terms of onset and progression of Alzheimer's). The inflammation response by last reports is highly implicated in the onset itself of Alzheimer's. A hypothesis we are putting forth at Skye Blue of bexarotene's recent find as to a mechanism is via cell signaling pathways with cell surface receptor binding and intracellular nuclear factors [also termed transcription factors, TFs (see above)] signaling as one would be led to think involved with inflammation and that inflammation's genetic products have been directly implicated with cancer (viz. apoptosis, proliferation, angiogenesis, invasion, metastasis). The immune response, inflammation and cancer share common paths of cellular communication in terms of cell signalling implying common factors in their aetiology with the inflammation response. Genetic counselling or diagnosis and gene therapy might be called for as an interventive in at least 27% of the Caucasoid population, for example as was indicated unless, of course, other interventives are found for the disease response and its symptoms and causes.
SKYENEWS: Research leading to technological breakthroughs: research on new anti-psychotic/psychotropic drugs that improve mental cognition (i. e. focusing, reasoning, memory, energy level) in schizophrenia/bipolar and developmental disabilities and social affect/mood and withdrawal; the research studying the interactions between nutrients in feed and the genetics of animal body mass and composition and further drug research for growth in animal production; the role of adult stem cell and cancer research with phagocytotic/cytotoxic immune cells against tumour cell activity; new conjectures on energy metabolism and expenditure or excercise; neurocrine factors and the endocrine system and cell survival or eventually related to studies on longevity with identified genes, have begun.
SKYENEWS: The 'mind-body' axis is being explored at Skye Blue and including the range of parameters and centres of function involved with mental faculties of the brain and their effects, for example on immunologic, neuro/exocrine and <vital organ> function with support for health & wellness in general and with longevity and the question of applications of pharmacopieacal agents. Occupational-related, other life-style and environmental factors can also of course contribute to long-term wellness and the health status of the body.
SKYENEWS: A growing interest is that in gene therapy and pharmacology and the treatment in concept of what is termed as the metabolosome ('-ome' = cell metabolism and its perspectives in cell growth, proliferation and development and function) and how drugs interact by modulation and prophylaxis and with the future of gene therapy, pre- and post-partum. The metabolosome and genetic mutations and how drugs can play a role in developmental conditions such as cerebral palsy, dementia, bipolar and schizophrenic mental disorders and other developmental diseases is open for further investigation.There are also so-called 'metabolic diseases' such as those instigated by occupation, health and nutrition and a new field that studies nutritional genomics or the genetic variance and response to nutrition (see: Bio-pharmacor Drug Discovery an SBO company on the BiotechnologyIreland.com website for more).
SKYENEWS: New phytobotanical think-tank launched at Skye Blue and the future prospects for markets of phytobotanical nutritionals and organo-sourced production and marketing for more sustainability, decreased lability, and better logistical delivery. Skye Blue's involvement with phytobotanicals that are, for example, psychotropics, viz. activating to brain function including insight, reasoning and memory, such as the tea botanical from two plants from the Peruvian jungle called a concoction: ayahuasca (a-ya-wat-ka) has already been studied by medical science to activate the neocortex, amygdala and insula (insular cortex) which are involved with personality and insight, impulses and emotions and early memories. At this time, therapeutic uses of this phytobotanical are for treatment of drug addiction including the addiction itself over several months therapy. It is striking that there are complex structure-function relationships between the human brain and substances of plant origin. This may beg the question of how close homologies vs variants exist with structure-function of neuroreceptors that are targets for such drugs. Classes of receptors and their ligands will be discovered it is predicted including their homologues. The search for variants and better acting drugs, for example, using the psychotropic ayahuasca will involve mutating cultures of nerve cells and doing receptor-ligand binding studies and studying what structural-functional relationship exist between both and how to articulate and improve drug structure and its function. (See: http://hum-molgen.org/companies/profile.php3/3811-organobotanie.)
SKYENEWS: A new publication outlines the demand for foods in the future with complex carbohydrates reviewing new and proposed research in fortifying these plant crops (e.g. cereals, fruits and vegetables, orphaned crops as the sweet potato, bananas and cassava) and their health-conferring benefits regards inflammatory response and occupational-related diseases such as atherosclerosis, diabetes and cancers. We are publishing this new paper on the links between chronic inflammation, immunonogeneic response and disease states, such as diabetes, atherosclerosis and cancer, and their links to both nutritionals, Vit D and fructans, in the lower gut, a clue to the linkage between the two factors and other diseases also linked to the prolonged chronic elicitation or aggravation of the inflammation response. We invite editorial oversight on the investigation of the inflammation process including published/unpublished research findings on this exciting and growing field in health research.
SKYENEWS: Obesity usually results from cumulative weight gain from eating foods rich in starches and fats and processed foods such as sugars. It has been noted that weight gain occurs over ~48 hrs. after ingestion of the sugars that travel to muscle for gluconeogenesis and to fat cells and eventually are stored in the fat depots (e. g. thighs and abdomen). Like diabetes drugs that facilitate entry into the liver and supposedly block breakdown of storage glycogen from the liver there should be drugs that slow entry of glucose and gluconeogenic substrates from amino acids, to a lesser degree, and so with fatty acids, to breakdown the insidious 48 hrs. cycle of ingestion, circulation, uptake, reversal and eventual storage and their facilitated transport across the kidneys with the diabetic drugs available on the market. This would be true for those with a marked genetic predisposition to weight excessive gain from overeating certain foods that are more "fattening" as dieticians have put it and who do not exercise after or in between meals to shed off excess calories.
SKYENEWS: The 'metabolosome' will prove to be a formidable model to prove and use in T2D (type II diabetes) where obesity or weight gain in fat tissue leading to insulin resistance and a lack of glucogenic regulation in the blood can be impacted by new factors in LBM (lean body mass or muscle tissue), a storage depot for protein and gluconeogenic substrates and their possible relation to endocronological systemic control in the circulatory system to attenuate fluxes in glucose levels in the blood pre-prandially and post-prandially (before and after a meal is ingested). New endocronological drugs and physiotherapeutic interventions (e.g. core and resistance exercises) can be used to increase LBM to better help regulate gluconeogenesis and blood glucose levels. The liver is a reservoir of glucogenic substrates in the form of glycogen and is released typically pre-prandially and has to be controlled in the T2D condition with an inhibitor as with the drug metformin.
SKYENEWS: Energy-burning constituents in foods (e. g. s.: coffee, green tea, dragon fruit, etc.) are to be further studied for their role in energy metabolism not only in weight loss but in further perspectives of longevity and health and wellness (see above).
SKYENEWS: At Skye Blue we have shown interest in psychotropy and psychotropic, anti-psychotic drugs used in treating both bipolar disorders and schizophrenia. Certain older psychotropics improve thinking process, presumably by improving recall functions, focus, associative and cognitive functions. Adducively, these drugs help thinking process and is consistent with the observation that it lowers anxiety levels or works as an anti-anxiety medication and improves the 'ushering' of sleep and regularizes sleeping patterns in disturbed sleep which accompanies mental health disorders (e. g. apo-methoprezine). Also, certain anti-psychotics helps with symptoms such as lack of energy and social withdrawal or depression (e. g. Abilify, Zeldox). Psychotropy may be equilibrated with drugs based on a 'titre' in brain-damage or mental retardation or it is speculated with underperforming 'normal' individuals and geriatric patients including the aged, those suffering from dementia and Alzheimers. Much more research on newer psychotropics (e. g. Abilify, Zeldox, Invega) are needed including their potential side-effects (e. g. physical affect, tardive dyskinesia). It has been oberved in 'normal' individuals undergoing psychotropy in a psychosocial rehabilative setting with such residents that thinking and daily work habits and outcome is more 'orthogonal', i. e. they work more congruently with others and their work output is increased and of better, and in other cases, of remarkably better quality.
SKYENEWS: It was recently highlighted in discussions at SkyeBlue.org that the <titre> that psychiatrists assess in their patients suffering and recovering from bipolar and schizophrenic disorders would presumably due to, rooted in the chemical imbalance, first of all, viz. too little serotonin in the former requiring serotonin uptake inhibitors and too much dopamine requiring antagonists to dopamine, as has been observed firsthand, a lack of logical or rationality in thought processing, experiences of lack of lucidity of thought, lack of cognition in terms of inputs of perception and thinking or processing. There is a need to obviously find better drugs that aide in cognitive/enhancement programs with pharmacists available to geriatrics and other mental health rehabilative settings.
SKYENEWS: There is now a trend in pharmacy for use of cognitive/enhancement programs with drugs for various mental health-related conditions such as addictions, ADHD, autism, developmental disabilities, mental health issues such as bipolar disorders and schizophrenia and dementias. At this time our speculations are only theoretical and speculative at best and will require further investigation and research study.
SKYENEWS: The recent find with newer drug anti-psychotic interactions in the brain between, for e. g., Invega and Abilify, is that canceling the other removes the 'in toto' response or activating effect on cognition (e. g. on awareness, alertness, problem solving, recall, associative thinking, etc.) and thus overall higher level performance parameters attainable by the candidate on the newer drug regimens. Thus, the practice with psychiatric drugs by adding or cancelling the other in terms of common drug interactions as perscribed to patients exists, is concluded.
SKYENEWS: The most recent news to come out of Skye Blue in regards to our hypothetical modeling of sheep immunogeneic cell lines is as follows: 1) a humeral haemocytotic germinal cell line primed with hormonal cell blockers to growing cancer cells would be an e. g. of an anti-CD47 signaling agent or hormone encouraging an effective macrophagic phagocytotic outcome, 2) a systemic CNS-sourced neurhormonal activation of complement cytotoxicity and phagocytosis of cancer cells (an e. g. in the literature is with acetylcholine and other anti-tumour cytotoxic T-cell immune response mechanisms).
SKYENEWS: Cognitive enhancers are coming now into the fore and are also within theories of 'plasticity' of brain structure and function. At Skye Blue we have always speculated as to whether cognitive enhancers (e. g. processing, problem solving, storage, and retrieval functions) earlier on have further down the line could have a neuroprotective effect, a new frontier of research in neuroscience, against Alzheimers or other dementias. Although we speculate that dementias are a type of developmental disorder of the brain to protect against onset and any progression. The brain progresses in stages as it is hypothesized so we at Skye Blue have put forward these new concepts, viz.: cognitive enhancement, neuroplasticity, neurodevelopmental disorders and neuroprotective interventions. The recent studies of Reelin proteins in the brain that can reverse the overt signs of abberant cellular anatomical plaque and amyloid-beta fibril entanglements can 'reverse' this clinical phenotype of Alzheimers via the Reelin cell signaling pathways and recovery of cognate cognitive deficits. (Cf. further to: http://www.ub.edu/web/ub/en/menu_eines/noticies/2014/03/010.html).
Novel functional foods are being currently investigated actively. They include whey substrates, fructans and other water-soluble carbohydrates (WSCs) and polyphenols or lignans. One example would be currently undertaken with whey protein-derived products and immunosupression of murine lymphocyte function and the inflammation response with irritated bowel syndrome and it should be further speculated as to possible systemic effects in such phenomenon as atherosclerosis with vascular disease and Alzheimer's plaque formation within the central nervous system (CNS).
Immunomodulation with Hepatitis C Virus (HCV) NS4 protein and peptides in suppressing the cellular immune function of Th1 by inhibiting IL-12 production, induce anti-inflammatory cytokine IL-10 production and inhibit T cell response to bystander antigens with diseases such as diabetes type I, multiple sclerosis and rheumatoid arthritis amongst other synthetic and natural immodulatory molecules are in the development stages along with synthetic non-native immunomodulatory mimics of known and unknown tumour antigen peptides in breast cancer.
There is an issue being tabled currently and should be of interest to food and drug regulatory bodies (as all issues with drugging and drug discovery and development here) regards manipulating the antioxidant content of genetically-modified organismal (GMO) or marker-assisted selected (MAS) fruits & vegetables with natural nutritional anti-oxidants (also available as commercially available natural extracts) to address cancer and anti-aging chronic processes as fruits and vegetables and their complex carbohydrates have been suggested at 10-12 the average size of servings/day for diabetes type II, cardiovascular disease and health and various cancers.
The larger issue of tabling GMO foods & drugs, albeit, nutritionals, as controlled substances taken per os (in addition to parenteral and intravenous nutritionals) has in the past been with less 'unpalatable' enzyme technology, bacterial fermentation culture with their rec-plasmids DNA elements (see N. W. Dunn and Lactobacillus) and with a few GMO Bt varieties for grains, cotton and vegetables for food & bioenergy. Population, of which ranks China, India, the U.S.A., Brazil and a few other Asian and African countries, in the top 10, is the major factor driving GMO use with pressures on production and/or their other benefits (e. g. health & nutrition). Other new biotechnologies that are emergent: aquaculture (e. g. algal, fish and seaweed), not to be overlooked, viz., with respect to microbiotia (bacterial, protozoal and fungal), crops, forestry and cattle, with acceleration of growth and increasing size (e. g. in salmon 6.7x as efficient in terms of feed inputs required than other livestock), improving nutritional content (e. g. Vit. A in yellow rice), drought-resistance and disease-resistance (e. g. in sugarcane to viruses and Brucellosis in cattle). One now commonly used biotechnology is reproductive breeding technology including in vitro fertilization (IVF) and multiple ovulation embryo transfer (MOET) from superior sires with surrogate cows, which results in reduction of generation time and improves herd quality.
Proteomics (the study of the protein complement and its interactions) and drug discovery has recently involved using the proteome (ie. the complement of protein in vivo or ex vivo) as a 'finger print' for drug targets. It is proposed here that the proteome is a rich source of information for metabolites and products of its processes, for e. g. as inhibitors to inflammation to be elucidated within aetiology of disease (e. g. diabetes, atherosclerosis, multiple sclerosis, Alzheimer's and cancers) and metabolites that support processes of the wild-type (as opposed to the mutant) allele. Another, is the nutritional proteome which, as has been stated, is rich in metabolites implicated in growth, reproduction and health. We would like further speculation and for new finds to be made to shed light on this new area for drug discovery. Along this type of research would also be the assay of mRNAs or transcript factors (TFs), also termed as referred to above, with the proteome 'array' with in vivo and ex vivo samplings upon exposure to nutrients and nutrient factors.
Therapeutic modalities of interest are ionotropic modalities including psychotropic drug therapy, metabotropic modalities including reversing muscle and bone wasting with aging due in part to a lack of responsiveness of essential amino acid phosphorylation upon assimilation and anabolic signalling with current approaches of optimizing protein:energy ratios and resistance exercise and less effective and inconvenient drug use to maintain bone resilience and strength as measures in use and developmental pharmacogeneic with putative biopharmaceuticals as they interact with developmental timelines and illness including psychiatric bipolar and schizophrenic disorders [there are other known theories such as (see Blalock) autistic aminoexcitatory toxicity and brain architecture of the limbic, cerebellar and pre-frontal cortex systems of the brain and glutathione overexpression], immunogeneic approaches at this time include feed antigeneic stimulation, feeding antibodies (MAbs) through food or directly, immunomodulation by various approaches and cytotoxic/phagocytotic biopharmacogeneic activation of the cellular immune system.
Other interventive therapeutic modalities also currently in use include: surgical, electrophysiological, physiotherapeutic, radiochemical, chemotherapeutic and gene therapeutic (e. g. with selectively targeted allogenic genetically modified specialized organ cell transplantation). There are now combined modalities relating both to advantage with treatments such as genetic analysis therapy that can predict predisposition and even onset with immunogeneic therapy (viz. suppression) with diabetes type I.
SKYENEWS: In our continued search and development with the use of synthetic biology for the advancement of Vit D activated-forms of the drugs and their pharmacogenic effects to T2Diabetes, atherosclerosis and heart disease or health (in general) and cancers, including lower bowel cancer, we propose a precursor derivative (a steroidal 'lipoic' aldehyde) synthesized (see: Flores, 1980, SIProject, Hum-Molgen.De) through the body's natural metabolic synthetic pathways to Vit D's activated forms to act as 'agonists' against the feedback inhibition (FBI) to the drug with <increases in effectivity in therapeutic indices>. There are, as we speak, alternative approaches which may be less effective using Vit D at its receptors for various tissue types and/or gene selectivity with Vit D receptor modulators (VDRMs) that act with ligands (it is interesting to note here that recent use of non-seco-steroidal VDR ligands, unlike activated forms of steroid-like Vit D, have been developed for this) resulting in their increased effect.
SKYENEWS: It has been recently speculated at SkyeBlue as to the lower gut's status as an endocrine / immuno centre protecting against onset of cancers waiting to be mined for biopharma, for e. g. bioactive peptides. We believe in exploring possibilities as evidence weighs heavily towards further speculation: VitD, fructan, and now certain milk food proteins, e. g. bovine casein and lactoferrin, have been demonstrated to protect against cancer of the lower bowel or colon (large intestines). Do they 'just so happen' to act together, we speculate, or is this an organ and system or probable 'centre', as we call it, reflecting the fact that the organ system is involved in protecting or preventing against colon and other cancers -with yet to be discovered requisite endocrine / immuno functions, protecting against and acting after its onset.
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a) Overview Paper: Chronic Inflammation, Immunogeneicity and Disease: the promise of new drug discovery, has appeared in the Biomolecular and Medical Journal (Est. 2008).
We are publishing this new paper on the links between chronic inflammation, immunonogeneic response and disease states, such as diabetes, atherosclerosis and cancer, and their links to both nutritionals, Vit D and fructans, in the lower gut, a clue to the linkage between the two factors and other diseases also linked to the prolonged chronic elicitation or aggravation of the inflammation response. We invite further editorial oversight on the investigation of the inflammation process including published/unpublished research findings on this exciting and growing field in health research. There are new monoclonal antibodies administered by subcutaneous injection that can be used against products of genes that help activate inflammation or possibly act to enhance the production of gene products that help modulate the inflammation cascade, with nutritionals. Vaccines would of course not be a functional route, unlike the in vitro, ex vivo therapeutic modality of producing monoclonal antibodies. The immune response as outlined and small molecules in the inflammatory response could interact in future drug trials and thus affect immunogeneicity in a negative way in fighting disease. Systemic inflammatory response syndrome (SIRS) could be used as a model for the study of whether drug trials will have this issue of interactions with the immune system and affect disease fighting ability of the body. The cytokine storm as described elsewhere is an uncontrolled feedback cascade eliciting T cell response and macrophages to the site of infection; however, over response can lead to complications and even death. (Thank you for our respondent, cf.: WordPress.com blogspot, mentioned above who gave feedback on the cytokine storm.)
b) "Inflammation and Alzheimer's: how hot is the link for Pharma discovery?" The evidence: inflammatory molecules/ mechanisms are present and elevated in the brain, inflammation may be a necessary component of pathogenesis, inflammation may be sufficient for neurodegeneration, clinical trials (indirect and direct) with medications against inflammation suggest slowed progression and delayed onset of the disease. Are there cell signalling mechanisms yet to be discovered that control directly Alzheimer's via the inflammatory response? And what does this mean for new drug discovery? These will be explored.
c) "Inflammation, Vit D and Cancer: what are the links?" Vit D is an example of how nutrients have demonstrated cell programming and interactions with genetic expression (epigenetics). Vit D also has been demonstrated demographically to be related to the incidence of cancers. And, of course, inflammation is involved with cancer and its onset and controlling it also limits the incidence of the latter. This paper will explore the possible role of inflammation and its control using Vit D and related drug candidates for protecting against Cancers.
d) "Inflammation and Multiple Sclerosis (MS): finding new evidence and drug discovery." Zn2+-dependent Matrix Metallo-Proteins (Zn2+-MMPs) are implicated in multiple sclerosis and the autoimmuno-inflammatory response. Coloured fruits and vegetables for alleviation of MS through diet were thought to provide for anti-oxidative relief and thus inflammation but now its complex carbohydrates with low glycaemic load (GL) has been associated with lower CRP and adiponectin involved with inflammation and related obesity. There is now a need to study further the role of low and high GL on the inflammatory response particular of MS, the specificity of MS's MMPs as factors in disease including inflammation and the treatment with drugs to specifically and efficiently inhibit MMPs. Also, mechanisms of water-soluble carbohydrates (WSCs) and non-structural carbohydrates (NSCs) and their systemic role in minimizing biomarkered targets using small organic molecular drug agents, new relationships between nutritionals and genetics of diseased processes yet to be found.
e) Liver disease (inflammation). f) Heart disease. g) Parkinsonianism. h) Bone inflammation. i) Skin inflammation.
f) In Biomolecular and Medicine Journal we published an Editorial exploring possible avenues for drug discovery suggested by milk food proteins recently studied to have a direct relationship with chronic inflammation in addition to other functional foods or nutraceuticals such as VitD and fructans. Go to link: http://dannflores9.wordpress.com/ and read more.
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Last update of this entry: April 03, 2018