CAXXÖN LABS

Cancer Nutrition From Brain Neural Cells

This molecule plays a high impact role between tumor and brain

The connection and development trend between human brain cells and tumor cells was always a highly attractive subject to neurologists. Brain cells consume a large amount of energy from our blood, so do the tumor cells. According to the newest evidence found in CAXXÖN Labs, it was suspected that a portion of energy taken or absorbed by tumor cells was released from brain. The key actor in this route map was played by glucose cycle. Before the more results unleashed, let's take a sneak peek in how glucose move in cells. "Once it is in the periplasm, glucose is internalized to the cytoplasm and phosphorylated by the phosphoenolpyruvate: sugar phosphotransferase system (PTS) [2]. Either when glucose is present in the medium at a very low concentration or when the PTS system is inactivated, other transport proteins such as the high-afnity ABC transporter Mgl system and the galactose:H+ symporter GalP contribute to its import. Under these conditions, the internalized glucose is phosphorylated by the enzyme glucokinase in an ATPdependent reaction."

Growth-dependent recombinant product formation kinetics can be reproduced through engineering of glucose transport and is prone to phenotypic heterogeneity

Apo Open Form of Glucose/Galactose Binding Protein, RCSB PDB

Solution structure of the C1-subdomain, RCSB PDB

Blood-Brain Barrier

The blood-brain barrier (BBB) is one of the most essential protection mechanisms in the central nervous system (CNS). It selectively allows individual molecules such as small lipid-soluble molecules to pass through the capillary endothelial membrane while limiting the passage of pathogens or toxins.The blood-brain barrier (BBB) is one of the most essential protection mechanisms in the central nervous system (CNS). It selectively allows individual molecules such as small lipid-soluble molecules to pass through the capillary endothelial membrane while limiting the passage of pathogens or toxins.

Reference:

Journal of Controlled Release

Volume 270, 28 January 2018, Pages 290-303

Brain infiltration by cancer cells

The role of micro-RNAs

A number of recent studies has identiﬁed micro-RNAs (miRNAs) as key regulators of cancer cells survival and metastatic spread. Indeed, approximately 30% of human genes are likely to be regulated by miRNAs and miRNAs have been shown to regulate a variety of biological processes, including cell proliferation, cell differentiation and cell death. In this section miRNA involved in metastases, though with different molecular mechanisms are described.

miRNAs are an endogenous, highly conserved class of non-coding 20-24 nucleotides small RNAs that regulate gene expression at post-transcriptional level by binding to 3’-UTR of target mRNAs, thus leading to inhibition of mRNA translation and degradation. Several reports have elucidated the role of certain miRNAs as a class of oncogenes or tumor suppressors, depending upon their targeted genes.In addition, several studies have reported that miRNAs genomic locations are frequently associated to genomic regions involved in cancer. It has been calculated that about 50% of known miRNAs are located inside or close to fragile sites in minimal regions of loss of heterozygocity, regions of ampliﬁcations and common breakpoints associated with cancer.

Crossing the BBB

The key step during BM formation is the migration of cancer cells through BBB. Anatomically, the BBB is formed by brain microvascular endothelial cells (BMVECs), that form tight junctions without pores, and perivascular elements including pericytes, astrocytes, oligogendrocytes and the basement membrane. This complex structure represents a physical barrier for cells and molecules, selected on the basis of their molecular weight and charge. In addition, this barrier regulates the diffusion processes and the brain parenchyma homoeostasis by highly selective transport mechanisms mediating ﬂux of solutes and molecules and by a metabolic barrier consisting of highly speciﬁc enzymes.

Tumor cells recognize and bind to components of the vascular membrane, thereby initiating extra-vasation and promoting the formation of the tumoral niche that will host the new neoplastic formation. The brain vascular endothelium is therefore very important in counteracting cell extra-vasation but, nevertheless, cancer cells adopt different strategies to overcome this obstacle. Although the exact molecular mechanisms that trigger BM are still poorly understood, increasing evidence are shedding new light on the processes underlying the ability of cancer cells to cross the BBB.

In a transendothelial migration model, highly metastatic melanoma cells migration has ben found to be mediated by interaction of the α4β1 integrin with its ligand vascular cell adhesion molecule-1 (VCAM-1) on the surface of activated endothelial cells. VCAM-1 is expressed by endothelial cells only upon activation by inﬂammatory stimuli like TNF-α or interferon-γ, suggesting that highly metastatic melanoma cells preferentially leave the blood vessels at sites of inﬂammation.

In a very similar experimental model, the matrix metallo-proteinase 1 (MMP1) was found to play a critical role in BBB penetration; in parallel experiments cyclooxygenase-2 (COX2)-mediated prostaglandin synthesis promotes proliferation of tumor initiating cells by activating tumor-associated astrocytes followed by secretion of the chemokine CCL7.

The process of transendothelial migration of melanoma cells has been further investigated by other in vitro studies showing that the ability of these cells to cross the BBB is related to melanotransferrin expression levels on the cell surface, to the ﬁbrinolytic system and to serine proteases released by melanoma cells.

Reference:

J Cancer Metastasis Treat 2016;2:90-100.

10.4103/2394-4722.172661

Regneration Project mRNA

Messenger Ribonucleic acid Therapeutics (mRNA-T)

RNA interference (RNAi) is being widely used in functional gene research and is an important tool for drug discovery. However, canonical double-stranded short interfering RNAs are unstable and induce undesirable adverse effects, and thus there is no currently RNAi-based therapy in the clinic. Scientists have developed a novel class of RNAi agents, and evaluated their effectiveness in vitro and in mouse models. The novel class of RNA were synthesized on solid phase as single-stranded RNAs that, following synthesis, self-anneal into a unique helical structure containing a central stem and two loops. They are resistant to degradation and suppress their target genes. Agents directed against TGF ameliorate outcomes and induce no off-target effects in three animal models of lung disease. The results of this study support the pathological relevance of TGF in lung diseases, and suggest the potential usefulness of these novel RNA agents for therapeutic application.

Refernce

The original uploader was Sverdrup at English Wikipedia., Public domain, via Wikimedia Commons

CAXXÖN Labs Stand by Taiwan

CEO/ Reinforcement COVID/ APAC group

5.15.2021

The situation of COVID-19 is getting critical in Taiwan APAC. Researchers, developers, and projects in CAXXON group are working to explore cures for some of the complex diseases. Our scientists are the cornerstone of what we do. No medicine or vaccine would be possible without their restless innovation, imagination, and dogged pursuit of cures. Now our partners in southeast Taiwan, and APAC regions are facing difficult situations, fighting for deadly COVID-19.

We are humble, we are agile, we are strong, we are devoted, we stand by all our partners in Taiwan.

Regeneration Project aPhrodite

Wounded Skin Regeneration (WSR)

A wound is a break or opening in the skin. Your skin protects your body from germs. When the skin is broken, even during surgery, germs can enter and cause infection. Wounds often occur because of an accident or injury.

Wounds heal in stages. The smaller the wound, the quicker it will heal. The larger or deeper the wound, the longer it takes to heal. When you get a cut, scrape, or puncture, the wound will bleed. Not all wounds bleed. For example, burns, some puncture wounds, and pressure sores do not bleed. Once the scab forms, your body's immune system starts to protect the wound from infection.

Tissue growth and rebuilding occur next.

-Over the next 3 weeks or so, the body repairs broken blood vessels and new tissue grows.

-Red blood cells help create collagen, which are tough, white fibers that form the foundation for new tissue.

-The wound starts to fill in with new tissue, called granulation tissue.

-New skin begins to form over this tissue.

-As the wound heals, the edges pull inward and the wound gets smaller.

Regeneration Project aRchimedes

Bone Gla-protein Regenration (BGR)

Osteocalcin (Or bone gla-protein)is secreted solely by osteoblasts and thought to play a role in the body's metabolic regulation. In its carboxylated form it binds calcium directly and thus concentrates in bone.

In its uncarboxylated form, osteocalcin acts as a hormone in the body, signalling in the pancreas, fat, muscle, testes, and brain.

In the pancreas, osteocalcin acts on beta cells, causing beta cells in the pancreas to release more insulin.

In fat cells, osteocalcin triggers the release of the hormone adiponectin, which increases sensitivity to insulin.

In muscle, osteocalcin acts on myocytes to promote energy availability and utilization and in this manner favors exercise capacity.

In the testes, osteocalcin acts on Leydig cells, stimulating testosterone biosynthesis and therefore affects male fertility.

In the brain, osteocalcin plays an important role in development and functioning.

An acute stress response, colloquially known as the fight-or-flight response, stimulates osteocalcin release from bone within minutes in mice, rats, and humans. Injections of high levels of osteocalcin alone can trigger an ASR in the presence of adrenal insufficiency.

Normal Range:

The levels of osteocalcin in your serum (the liquid part of the blood) are usually reported in ng/mL (nanograms per milliliter).

The normal range is around 8 – 32 ng/mL. Levels can vary slightly between labs, due to differences in equipment, chemicals, and methods used.

Some labs give a different range for men, pre- and post-menopausal women.

Low Osteocalcin

Causes:

Low osteocalcin levels usually indicate lower bone turnover.

Causes shown below are commonly associated with low osteocalcin levels. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret your value, taking into account your medical history, symptoms, and other test results.

Regeneration Project aThena

CAXXÖN LABS have created several patented technology boosting up the leap of bio-regeneration.

Aging Skin Regeneration (AGR)

The characteristic features of aging skin include wrinkles, dryness of the skin, reduced skin thickness, loss of elasticity, dermal and epidermal atrophy, reduced rate of epidermal cell proliferation and cellular senescence. External factors that mainly contribute to skin aging include sunlight, UV radiation, chemicals, pollutants, and smoking. Besides external stimuli, endogenous processes that trigger aging process include excessive free radical production, nuclear/mitochondrial gene mutation, cellular senescence, shortening of telomere, reduced cell proliferation, and impaired immune functioning. In recent years, many scientific studies have revealed that advanced glycation end products (AGEs) are also among the crucial contributory factors of skin aging.

Accumulation of AGEs in the skin has been observed both in diabetes and during chronological aging. Proteins with slow turnover rate, such as collagen I and IV, as well as long-lived proteins, such as fibronectin, are primary targets of glycation reaction in the skin. Moreover, excessive deposition of AGEs in sun-exposed skin areas suggests that solar radiation, especially UV radiation, may play an important role in the formation of AGEs. Apart from sunlight, other external factors that are responsible for increased formation and deposition of AGEs in the skin include smoking and diet. The amount of AGEs in the food mainly depends on the method of preparation. For example, fried foods contain higher amount of AGEs as compared to boiled foods. About 10-30% of ingested AGEs are absorbed in the body and may participate in skin aging. Mechanistically, AGEs can react with proteins, lipids, and nucleic acids and alter their normal physiological functioning. Upon binding to their receptors, AGEs can also trigger a cascade of signaling pathways, leading to reduced cell proliferation, increase cellular senescence and apoptosis, decreased extracellular matrix synthesis, increased formation of free radicals and pro-inflammatory mediators, etc. All these processes can potentially contribute to skin aging.

Strategies to Control AGEs Since autofluorescence is an intrinsic property of AGEs, measurement of skin fluorescence is an effective method of detecting AGE deposition in the skin. Studies have found that skin fluorescence positively correlates with many age-related disorders, such as cardiovascular diseases, renal disorder, macular degeneration, and overall mortality. Given the immense involvement of AGEs in age-related disorders, including skin aging, effective strategies/interventions are needed to prevent, or at least control, their accumulation in the body. In this regard, most efficient strategies include removal of already formed AGEs from the body by degrading glycated proteins; inhibiting the formation of AGEs; and antagonizing AGE-mediated signaling cascade.

Harvard Dutta, Sanchari Sinha. 2018. Glycation and Skin Aging. News-Medical, viewed 03 January 2021, https://www.news-medical.net/health/Glycation-and-Skin-Aging.aspx.