Application Value of Enzymes Creates Good Market Development Prospects

Enzymes are protein molecules that act as specific catalysts for chemical reactions. Researchers have made significant contributions to the traditional and modern chemical industries by improving existing processes. Representative industrial applications of enzymes are concentrated in the fields of technology applications, feed industry, food processing and cosmetics. Enzymes are natural catalysts. They are produced by living organisms to increase the speed of the enormous and diverse learning reactions required for life. They involve all processes necessary for life, such as DNA replication and transcription, protein synthesis, metabolism, and signal transduction. And their ability to perform very specific chemical transformations makes them increasingly useful in industrial processes.

 

Enzymes are used in a variety of applications including technical applications, food manufacturing, animal nutrition, cosmetics, pharmaceuticals, and research and development tools. Currently, nearly 4,000 enzymes are known, of which about 200 original types of microorganisms are used commercially. However, only about 20 enzymes are produced on a real industrial scale. As the understanding of enzyme production biochemistry, fermentation processes and recovery methods increases, more and more industrial enzymes can be foreseen.

 

Enzymes have great potential in agriculture, biomass processing and biofuel production. In fact, some enzymes in agriculture have brought more effectiveness than traditional chemical processes, while at the same time being less harmful to the environment. Today, more and more enzymes are being used to increase agricultural productivity, improve biofuel quality, and achieve economical biomass conversion. The use of enzymes in arable agriculture and biofuels can alleviate the pursuit of agriculture and fossil energy. Therefore, new enzyme preparations are constantly being developed.

 

As a sustainable catalyst with a high reaction rate, enzymes are more concerned than chemical catalysts. Today, more and more chemical processes are replaced by enzymes due to clean and efficient catalytic performance. For example, in chiral synthesis, the enzyme exhibits extremely high stereospecificity, which is not observed in chemical catalysts, which simplifies the overall synthesis process.

 

The beauty and fascination of enzymes for research in industrial biotechnology are well-known. The total demand for enzymes in the global market is expected to increase rapidly in recent years. Carbohydrase will remain the main enzyme in the next few years. While strong growth in product categories will be led by multiple markets, including the food and beverage, animal feed and detergent industries. The application of medicinal enzymes will grow fastest as more per capita income in developing regions leads to more people getting health care.

 

 

 

 

 

Enzymes are protein molecules that act as specific catalysts for chemical reactions. Researchers have made significant contributions to the traditional and modern chemical industries by improving existing processes. Representative industrial applications of enzymes are concentrated in the fields of technology applications, feed industry, food processing and cosmetics. Enzymes are natural catalysts. They are produced by living organisms to increase the speed of the enormous and diverse learning reactions required for life. They involve all processes necessary for life, such as DNA replication and transcription, protein synthesis, metabolism, and signal transduction. And their ability to perform very specific chemical transformations makes them increasingly useful in industrial processes.

 

Enzymes are used in a variety of applications including technical applications, food manufacturing, animal nutrition, cosmetics, pharmaceuticals, and research and development tools. Currently, nearly 4,000 enzymes are known, of which about 200 original types of microorganisms are used commercially. However, only about 20 enzymes are produced on a real industrial scale. As the understanding of enzyme production biochemistry, fermentation processes and recovery methods increases, more and more industrial enzymes can be foreseen.

 

Enzymes have great potential in agriculture, biomass processing and biofuel production. In fact, some enzymes in agriculture have brought more effectiveness than traditional chemical processes, while at the same time being less harmful to the environment. Today, more and more enzymes are being used to increase agricultural productivity, improve biofuel quality, and achieve economical biomass conversion. The use of enzymes in arable agriculture and biofuels can alleviate the pursuit of agriculture and fossil energy. Therefore, new enzyme preparations are constantly being developed.

 

As a sustainable catalyst with a high reaction rate, enzymes are more concerned than chemical catalysts. Today, more and more chemical processes are replaced by enzymes due to clean and efficient catalytic performance. For example, in chiral synthesis, the enzyme exhibits extremely high stereospecificity, which is not observed in chemical catalysts, which simplifies the overall synthesis process.

 

The beauty and fascination of enzymes for research in industrial biotechnology are well-known. The total demand for enzymes in the global market is expected to increase rapidly in recent years. Carbohydrase will remain the main enzyme in the next few years. While strong growth in product categories will be led by multiple markets, including the food and beverage, animal feed and detergent industries. The application of medicinal enzymes will grow fastest as more per capita income in developing regions leads to more people getting health care.

The Ultimate Guide to Whole Genome Resequencing: Basic and Advanced Facts (VI)

  1. Types of experimental design

With the maturity and popularity of sequencers such as Illumina’s Nova-seq, X-Ten, the price of resequencing will continue to become more and more popular. Given that resequencing is already a common research tool, the scale of competition sequencing has slowly lost value, and most of us are not mathematics / statisticians, and it is difficult to develop new algorithms. In an era where test techniques and analysis methods are similar, to stand out, it is destined to strengthen relevant biological issues and understanding of various data analysis methods, and improve experimental design and data mining interpretation capabilities.

QTL positioning (including GWAS, phenotype): in a broad sense, QTL positioning include classic linkage analysis and association analysis. The core difference between linkage analysis and association analysis in QTL positioning is that the characteristics of the studied group are different, but there is almost no statistical difference between the two analysis methods in statistics. In general, QTL mapping is a type of phenotypic identification method. We need to accurately measure the phenotype of all individuals, and then through the correlation analysis of phenotype and genotype (there are multiple models to choose from), locate the QTL related to the trait. As sequencing prices continue to fall, the core issue of QTL positioning is actually phenotyping. The accuracy of individual phenotype identification is affected by many factors, and its accuracy directly affects the effect of QTL localization. Because certain phenotypes must be performed under certain environmental conditions (for example, drought resistance must be observed under drought conditions), so individuals must be strictly controlled under similar environmental conditions for testing.

For human species, which can actively cooperate with experiments, phenotypic identification is often relatively easy. But for animal plants, accurate phenotypic identification means that this species has been domesticated. Only under the environment of artificial domestication and control of the living environment, accurate phenotype identification can become possible.

Population genetics (selection pressure analysis).

According to the research purpose and the characteristics of the experimental design, the editor mainly uses classic examples as examples to analyze the future experimental design and analysis methods.

The QTL positioning and selection pressure analysis are essentially different in experimental design (Savolainen et al. 2013) [animal and plant resequencing].

Somatic mutation.

High-depth sequencing to determine the mutation type, and then GWAS analysis, functional analysis of the contribution rate of each site. Combined with the transcriptome to express differential functional effects.

3.1 Resequencing GWAS mapping functional genes (QTL mapping (including GWAS, phenotype))

In 2017, Visscher and others reviewed the results of the whole-genome association analysis (GWAS) in the “10 Years of GWAS Discovery: Biology, Function, and Translation” in “The American Journal of HumanGenetics” in the title of The American Journal of HumanGenetics The development and application directions of the past ten years were prospected. The article points out that the results of GWAS have revealed hundreds of complex disease traits. In most studies on traits and diseases, mutation targets in the genome will appear very large. Therefore, future GWAS will be based on whole genome sequencing (Visscher et al. 2017).

Japanese researchers Yano et al. identified 26 loci (−log10 P ≥4.77) related to heading date by re-sequencing the whole genome of 176 Japanese japonica varieties and using a mixed linear model for GWAS correlation analysis The five regions of interest are located on chromosomes 1, 3, 6, 7, and 11, respectively. Among them, the peaks located on chromosomes 3 and 7 are consistent with the reported QTL mapping results of heading stage-related genes Hd6 and Hd2. The candidate region located on chromosome 1 is anchored between 36.30Mb and 36.65Mb (346Kb), including 91 loci associated with heading stage, these loci are distributed on 7 genes, of which the gene LOC_Os01g62780 and Arabidopsis. The HESO1 gene is homologous, and this gene exhibits delayed flowering in Arabidopsis. The analysis found that the valine at position 328 was mutated to isoleucine to form two haplotypes, and the varieties containing haplotype B headed Varieties that are later than haplotype A. The gene sequences of haplotype A and haplotype B were introduced into Nipponbare respectively. The flowering time of the haplotype B sequence was later than that of the haplotype A sequence and the control group, indicating that the new gene LOC_Os01g62780 and delay in rice Flowering related (Yano et al. 2016).

3.2 Population resequencing for adaptive evolution and functional gene positioning (population inheritance (selection pressure analysis))

To observe the traces of genes adapted to localization, the key factor is experimental design, especially the selection of groups. One of the key factors is whether there is migration between different groups, because localized adaptation is often associated with some degree of group isolation (whether it is artificial or natural isolation). The division of subgroups caused by geographical isolation is relatively easy to understand, for example, a high mountain blocks the possibility of migration between two subgroups.

So, how do subgroups arise from non-geographically isolated groups? In such a group, localized adaptation is the result of a balance of choice and migration. I have to mention one concept here: antagonistic pleiotropy, which seems to be more reasonable to be translated as “antagonism gene pleiotropy”. This concept actually says that in many cases, adaptation comes at a cost: that is, at the cost of loss of adaptability in other environments, a stronger local adaptability is obtained.

The significance of antagonistic pleiotropy is that the migration ability of the population is also reduced to a certain extent, thereby enhancing the localization adaptation. This also explains that the crops, livestock and poultry bred by human beings are somewhat more precious, and they are very dependent on the environment provided by human beings and have no adaptability under natural conditions. In fact, it is the cost of pursuing high yield in the process of human breeding selection. If it is not antagonistic pleiotropy, a dominant genotype is very strong in any environment, and it may slowly occupy other niche, resulting in the gradual fixation of this locus.

Most of the traits we focus on (especially the production traits of animals and plants) are related to adaptive selection. How to locate and screen these genes related to adaptive traits has been a hot spot in genomic research.

To be continued in Part VIII…

Pathogens and Food Poisoning

Researchers analyzed information from a database of people. They tracked food poisoning cases in some US laboratories, covering millions of people. The researchers found some food-borne pathogens, including bacteria, virus and parasites. Here are some details.

  1. Campylobacter

One of the most common foodborne disease bacterium is Campylobacter, which is often found in raw poultry. Campylobacter is a zoonotic disease. Wild animals, domestic animals and pets are important hosts of Campylobacter, and many countries have detected a high rate of infection in the intestines of pigs, cattle, sheep, chickens, ducks and pigeons. Infected animals usually have no obvious symptoms, but can discharge bacteria to the outside for a long time, causing human infections. In developed countries, eating raw or undercooked poultry meat is the most common cause of Campylobacter infection. The resulting cases in the United States, New Zealand and other places account for 10% -50% of the total. Due to the limited sanitary conditions in developing countries, water-borne transmission is the most common, and Campylobacter can be isolated from river, stream, mountain spring, and well water. Drinking unsterilized milk is also an important cause of infection. In addition, direct contact with infected animals and pets is often the cause of infection for slaughterhouse workers and children.

  1. Salmonella

The second most common bacterium is Salmonella, with 16 infections per 100,000 people; followed by Shigella and Escherichia coli (STEC), 4 infections per 100,000 people. Some Salmonella species are specifically pathogenic to humans, some are only pathogenic to animals, and others are both human and animals. Salmonellosis is a general term for different forms of humans, domestic animals and wild animals caused by various types of salmonella. The feces of people infected with Salmonella or carriers can contaminate food and cause food poisoning. According to statistics, among the various types of bacterial food poisoning in various countries of the world, food poisoning caused by Salmonella often ranks first.

  1. E. coli

E. coli is a normal resident bacterium in the intestines of animals, and a small part of them cause disease under certain conditions. The serotypes of E. coli can cause gastrointestinal infections in humans or animals, mainly caused by specific fimbria antigens, pathogenic toxins and other infections. In addition to gastrointestinal infections, it can also cause urinary tract infections, arthritis, and meninges Inflammation and septic infection.

  1. Staphylococcus

Staphylococcus food poisoning is mainly caused by leftover food and leftovers. It should be noted that only ingesting live bacteria with food without staphylococcal enterotoxin will not cause food poisoning, and only ingesting a poisonous dose of the enterotoxin will cause disease. Staphylococcus food poisoning has a short incubation period, generally 2-5 hours, rarely exceeding 6 hours. Sudden onset, staphylococcal food poisoning symptoms include nausea, vomiting, upper and middle abdominal pain and diarrhea, vomiting is the most significant. However, it usually recovers quickly within a few hours to 1-2 days.

  1. Botox

Botulinum toxin poisoned by botulinum is a neurological food poisoning. It is often caused by eating cured meat contaminated with botulinum, poorly prepared canned food, and edible bean paste, stinky tofu and stale fish, pork. Among the various types of food poisoning that have been reported, reports of botulism are relatively rare, but the poisoning consequences are extremely serious. The incubation period is 12-48 hours or longer, no fever, and gastrointestinal symptoms are rare. The symptoms of botulism food poisoning mainly include headache, dizziness, drooping eyelids, diplopia, dilated pupils, aphonia, dysphagia, difficulty in breathing, even respiratory paralysis and even death, the mortality rate is more than 50%.

  1. Halophiles

Halophilic bacteria are a kind of marine bacteria, so it is called halophilic bacteria, also known as vibrio parahaemolyticus. It widely lives in marine products, fish and crabs in seawater. Therefore, the source of pollution causing halophilic food poisoning is often seafood, the most common being shrimp, crab or various marine fish. The incubation period varies from 1 hour to 4 days, most of which is around 10 hours, and generally recovers faster.

The researchers concluded that “more control measures are needed” to prevent foodborne diseases, including “new or revised performance standards for meat and poultry, and strengthening training and guidance for industry and inspection personnel” etc.

The Research of Proteolytic Targeting Chimeras (I)

In recent years, cell therapy, immunotherapy and gene editing technology have developed rapidly. In the research and development of new drugs, the research of traditional small-molecule drugs is facing unprecedented challenges. The research of small molecule inhibitors urgently needs to find a new breakthrough from the mechanism of action. Traditional small molecule inhibitors work by occupying the active site or binding pocket of the target protein, thereby inhibiting the activity of the target protein and directly blocking the specific function of the target protein. Due to the limitation of the mechanism of action, small molecule inhibitors mainly have the following problems: higher drug concentrations are required to fully occupy the binding site of the target protein, and it can also lead to side effects such as off-target effects; many potential drug targets do not have clear active sites, such as backbone proteins, transcription factors, and non-enzymatic proteins. It is difficult to find corresponding high-affinity small molecule inhibitors.

To make up for the limitation that small molecule inhibitors are mainly used to regulate the activity of target proteins, researchers have begun to study how to directly regulate the expression level of proteins in the body, and have achieved many results; such as RNA interference, antisense oligonucleotides and gene editing, etc.  However, due to drug-producing, transmembrane, and clinical application reasons, such technologies need to be further improved. Proteolysis targeting chimeras (PROTACs) breaks through the mode of action of traditional small molecule inhibitors and can directly induce the degradation of substrate proteins through the ubiquitin-proteasome protein degradation pathway in vivo, which has attracted widespread attention from researchers.

Proteolysis targeting chimeras (PROTACs) are a class of compounds which can induce the poly-ubiquitination of the target proteins and promote their degradation. As a bifunctional molecule, RPOTAC has a wide range of space for application and development. PROTAC is a new direction in the field of drug discovery, and the strategy of regulating protein content in vivo by degrading target proteins greatly expands the range of potential drug targets.

Proteolytic targeting chimeras are small bifunctional molecules, one end binding to the target protein link by a chain to the other end binding to E3 ubiquitin ligase. After PROTAC enters the cell, its target protein (protein of interest (POI)) ligand specifically binds to the target protein, and the other end of the E3 ligase (E3 ligand) binds to the E3 ligase (E3 ligase). Thereby, a POI-PROTAC-E3 ligase ternary complex is formed. E3 ligase mediates the ubiquitin-binding enzyme E2 to ubiquitinate the target protein. After the ternary complex is dissociated, the target protein labeled with ubiquitin is delivered to the protease degradation in the body (proteasome), thereby selectively reducing the level of the target protein. This process does not require the target protein ligand to occupy the binding site for a long time. It only needs the short-term formation of a ternary complex to complete the ubiquitination of the target protein. The ubiquitinated protein can be recognized and degraded by the proteasome, and PROTAC can function multiple times in the cell.

Figure 1. PROTAC recruitment of an E3 ligase for target protein degradation via the ubiquitin-proteasome pathway.

Due to the lack of small molecular ligands for E3 ubiquitin ligase, the first generation of PROTAC was based on peptide motifs as ligands for E3 ubiquitin ligase. Although these molecules provide proof of concept for PROTAC, the sequences lack cellular permeability, thus limiting its use as a chemical probe. Studies have confirmed that the target proteins that can be successfully degraded by peptide PROTAC include androgen receptor (AR), methionine aminopeptidase 2 (MetAP2), and protein kinases (AKT, PI3K). These studies confirm that regulating protein half-life by targeting E3 ligase is a potential strategy for potential drug development. However, these peptides, PROTAC, have poor transmembrane absorptivity, low activity in degrading proteins, and degradation activity is still at the micromolar level.

The second generation of PROTAC is a small molecule PROTAC. The use of small molecules as part of the E3 ubiquitin ligase has enabled rapid development of small molecule-based PROTAC technology. Small molecule-based PROTAC offers many advantages over peptide-based PROTAC. Most importantly, PROTAC based on small molecules is more promising for drug development because small molecules are more easily absorbed by the body. At present, more than 600 E3 ligases have been found in the human body, but currently the only E3 ligases involved in the reported PROTAC are mouse double minute 2 homologue (MDM2), cellular inhibitor of apoptosis protein 1 (cIAP1), cereblon (CRBN), von Hippel-Lindau (VHL)etc., mainly due to the lack of small molecule ligands with high affinity and specific E3 ligase.

Recruiting E3 ubiquitin ligase MDM2

In 2008, Vassilev et al. used Nutlin-3a as a ligand for the E3 ubiquitin ligase MDM2. The PROTAC is a linker between Nutlin-3a and a non-steroidal androgen receptor (AR) ligand via a polyethylene glycol chain.

Figure 2. Recruiting MDM2’s small-molecule PROTAC

Recruiting E3 ubiquitin ligase cIAP1

cIAP1 is an intrinsic inhibitor of apoptosis. Itoh et al. used cIAP1 inhibitor aprotinin b (bestatin) as the E3 ligase recognition group, and designed and synthesized a small molecule PROTAC that targets the degradation of intracellular retinoic acid binding protein Ⅱ (CABP-Ⅱ). This molecule can induce 75% CABP-Ⅱ degradation in cancer cells at 10 μmol·L-1. Studies have shown that such small molecules PROTAC have the following limitations: 1) Because bestatin is an aminopeptidase inhibitor, it often accompanies off-target effects and causes adverse reactions. 2) Due to the lower activity of degraded proteins, higher concentrations are required to exert pharmacological effects. 3) IAP ligands often induce IAP ubiquitination and are then degraded. For these reasons, further development of bestatin as an E3 ubiquitin ligase ligand has been limited.

Figure 3. Recruiting cIAP1’s small-molecule PROTAC

Recruiting E3 ubiquitin ligase CRBN

In recent years, thalidomide and its derivatives lenalidomide and po-malidomide have attracted great interest from researchers as potent immunomodulators. A recent study found that thalidomide combined with E3 ligase CRBN can lead to the degradation of IKZF1 and IKZF3, indicating that thalidomide and its derivatives can be introduced into the design of PROTAC as an E3 ligase recognition moiety.

To be continued in Part II…

What is chemokines and more

 

Chemokines: A class of small cytokines or signaling proteins secreted by cells. Because they have the ability to induce directed chemotaxis of nearby reactive cells, they are named chemotactic cytokines.

 

Brief introduction

When the human body defends and removes foreign bodies such as invading pathogens, it has a function of directing chemotactic immune cells, and some substances can cause this function called chemokines or chemokines,

Also called chemokine, chemokine or chemical hormone. Chemokines are a family of small-molecule cytokine proteins. These small proteins are named for their ability to direct cellular chemotaxis. Some of these proteins have other names in the history of chemokines, including the SIS cytokine family, the SIG cytokine family, the SYC cytokine family, and the platelet factor-4 family.

 

Common structural features of chemokine proteins include small molecular weight (approximately 8-10 kDa) and four conserved cysteine residues to ensure their tertiary structure.

Some chemokines are considered to be pro-inflammatory cytokines and can induce cells of the immune system to enter the site of infection during the immune response. Some chemokines are believed to maintain the body’s self-regulation and control cell migration during normal tissue maintenance or development. Chemokines are present in all vertebrates, some viruses and some bacteria, but have not been found in other invertebrates.

Chemokines are divided into four main subfamilies: CXC, CC, CX3C, and XC. All these proteins exert their biological effects by interacting with transmembrane receptors (called chemokine receptors) linked to the G protein. These proteins bind to chemokine receptors. Chemokine receptors are G protein-coupled transmembrane receptors are selectively expressed on the surface of target cells.

 

Structure

All chemokines are small, with molecular weights between 8 and 10 kDa. About 20-50% of them are identical; that is, they have the same gene sequence and amino acid sequence homology. They also possess conservative amino acids, which are important for forming their three-dimensional or tertiary structure. For example, in most cases, four cysteines interact to form a Greek key shape, which is a chemokine feature. Intramolecular disulfide bonds usually connect the first to third cysteine residues, and the second to fourth cysteine residues, which are numbered when they appear in the protein sequence of the chemokine. A typical chemokine protein is produced in the form of a peptide precursor, and during its secretion from the cell, a signal peptide of approximately 20 amino acids is cleaved from the active (mature) part of the molecule. In chemokines, the first two cysteines are near the n-terminus of the mature protein, the third cysteine is in the molecular center, and the fourth is near the C-terminus. After the first two cysteines, there is a loop of about 10 amino acids, called the N loop.

 

Features

The main role of chemokines is to induce directional migration of cells. Cells attracted by chemokines migrate to the source of chemokines along the signal of increased concentration of chemokines. Some chemokines control the chemotaxis of immune cells during immune surveillance, such as inducing lymphocytes to lymph nodes. The chemokines in these lymph nodes monitor the invasion of pathogens by interacting with antigen presenting cells in these tissues. These are called steady-state chemokines and are produced and secreted without stimulating the source cells.Some chemokines play a role in development; they can stimulate new blood vessel formation (angiogenesis); guide cells into tissues and provide specific signals for cell maturation. The key role of other chemokines in inflammatory response can be released by a variety of cells in response to bacterial and viral infections; it can also be released due to non-infectious stimuli such as silica inhalation and urinary tract stones. Chemokine release is usually caused by stimulation of inflammatory cytokines such as interleukin-1 (IL-1). The main role of inflammatory chemokines is to act as a chemotactic agent for leukocytes, attracting monocytes, neutrophils and other effector cells from the blood to the site of infection or tissue damage. Certain inflammatory chemokines can activate cells to initiate an immune response or promote wound healing. They are released by many different cell types and guide the cells of the natural and adaptive immune systems.

 

The main function of chemokines is to manage the migration (homing) of leukocytes to their respective locations during inflammation and homeostasis.

Basal homing effect: Basal steady-state chemokine produced in thymus and lymphoid tissue. The chemokines CCL19 and CCL21 (expressed in lymph nodes and lymphatic endothelial cells) and their receptor CCR7 (expressed in cells destined to home to these organs) are the most stable functions of their homes in homing Good illustration. The use of these ligands allows antigen-presenting cells (APCs) to transfer to lymph nodes during an adaptive immune response. Other homeostatic chemokine receptors include: CCR9, CCR10, and CXCR5, which are important for tissue-specific leukocyte homing as part of the cell address. CCR9 supports leukocyte migration into the intestine, CCR10 supports skin migration, and CXCR5 supports b cell migration to lymph node follicles. CXCL12 (SDF-1) produced in bone marrow promotes the proliferation of B progenitor cells in the bone marrow microenvironment.

Inflammation homing: inflammatory chemokines produce high concentrations during infection or injury and determine the migration of inflammatory leukocytes to the damaged area. Typical inflammatory chemokines include: CCL2, CCL3 and CCL5, CXCL1, CXCL2 and CXCL8. A typical example is CXCL-8, which is a neutrophil chemoattractant. Compared with steady-state chemokine receptors, there is a clear confusion between binding receptors and inflammatory chemokines. This often complicates research on receptor-specific therapies

 

Types

Structural classification

Chemokines can be divided into four subfamilies of CXC, CC, C, and CX3C according to the arrangement of their amino-terminal (N-terminal) cysteine:

CC chemokine subfamily: CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL10, CCL11, CCL12, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22 , CCL23, CCL24, CCL25, CCL26, CCL27, CCL28

CXC chemokine subfamily: CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16, CXCL17

C chemokine subfamily: XCL1, XCL2

CX3C chemokine subfamily: CX3CL1

 

Functional classification

Chemokines are divided into two categories according to their functions:

Balance chemokine in the body: produced in certain tissues, responsible for the migration of basic leukocytes. Including: CCL14, CCL19, CCL20, CCL21, CCL25, CCL27, CXCL12 and CXCL13. (This classification is not strict, for example: CCL20 can also be used as a pro-inflammatory chemokine)

Pro-inflammatory chemokines: formed under pathological conditions (under pro-inflammatory stimuli, such as IL-1, TNF-α, LPS, or viruses), and actively participate in the inflammatory response, attracting immune cells to the site of inflammation. For example: CXCL-8, CCL2, CCL3, CCL4, CCL5, CCL11, CXCL10.

 

About us

Starting from a small supplier of proteins and enzymes for academic institutes and biotech companies, Creative BioMart has always been focusing on developing high quality protein products and efficient protein manufacturing techniques. Over the past decade, our products and services are proven to have served our customers well and we have become one of the most trustworthy brands in the market. Here are some our products: CCNA1CCNCCCNG1CCRL2, etc.

 

The history and preparation method of metal powder

Metal powder refers to a group of metal particles with a size of less than 1 mm. Including single metal powder, alloy powder and certain refractory compound powder with metallic properties, it is the main raw material of powder metallurgy.

The elemental metal is generally silver-white. When the metal is under certain conditions, it is a black powder. Most metal powders are black.

Historical traceability

The preparation and application of metal powder have a long history. In ancient times, gold, silver, copper, bronze and some oxide powders were used as paints for coloring and decoration of pottery, jewelry and other utensils. In the early 20th century, American Coolidge (W.D. Coolidge) used hydrogen reduction tungsten oxide to produce tungsten powder to produce tungsten wire, which was the beginning of modern metal powder production. Since then, a variety of powders such as copper, cobalt, nickel, iron, and tungsten carbide have been prepared by chemical reduction, which has promoted the development of early powder metallurgy products (oily porous bearings, porous filters, cemented carbide, etc.); The carbonyl method is used to prepare iron powder and nickel powder. In the 1930s, the iron powder was first produced by the vortex grinding method, and then the iron powder was produced by the solid carbon reduction method at a low cost. In the early 1930s, the molten metal atomization method also appeared. This method was originally used to produce low melting point metals such as tin, lead, aluminum and other powders. In the early 1940s, it developed into iron powder produced by high-pressure air atomization. In the 1950s, high pressure water atomization was used to produce alloy steel and various alloy powders. In the 1960s, various atomization methods were developed to produce high-alloy powders, which promoted the development of high-performance powder metallurgy products. Since the 1970s, a variety of gas-phase and liquid-phase physicochemical reaction methods have emerged to produce coated powders and ultrafine powders with important uses.

Powder properties

Metal powder is a loose substance, its performance comprehensively reflects the nature of the metal itself and the characteristics of individual particles and the characteristics of the particle group. Generally, the properties of metal powders are divided into chemical properties, physical properties and technological properties. Chemical properties refer to metal content and impurity content. Physical properties include the average particle size and particle size distribution of the powder, the specific surface and true density of the powder, the shape, surface morphology and internal microstructure of the particles. Process performance is a comprehensive performance, including powder fluidity, bulk density, tap density, compressibility, formability and sintered size changes. In addition, for some special applications, the powder is required to have other chemical and physical properties, such as catalytic performance, electrochemical activity, corrosion resistance, electromagnetic performance, internal friction coefficient, etc. The performance of metal powder depends to a large extent on the production method of powder and its preparation process. The basic properties of the powder can be determined by specific standard testing methods. There are many methods for measuring the particle size and distribution of powder. Generally, sieve analysis method (> 44μm), sedimentation analysis method (0.5 100μm), gas permeation method, microscope method, etc. Ultrafine powder (<0.5μm) was measured by electron microscope and X-ray small angle scattering method. Metal powders are conventionally divided into five grades: coarse powder, medium powder, fine powder, fine powder and superfine powder.

Preparation method

Generally, it is divided into mechanical method and physical chemical method according to the principle of transformation. It can be directly refined from solid, liquid and gaseous metals, and can also be converted from metal compounds in different states through reduction, pyrolysis, electrolysis Made. Carbides, nitrides, borides, and silicides of refractory metals can generally be prepared directly by compounding or reducing-combining methods. Due to different preparation methods, the shape, structure and particle size of the same powder often vary greatly (Figure 2). The preparation method of the powder is listed as follows. Among them, the most widely used are reduction method, atomization method and electrolysis method.

Reduction method

Using a reducing agent to seize the oxygen in the metal oxide powder, the metal is reduced to a powder. Gas reducing agents include hydrogen, ammonia, coal gas, and converted natural gas. Solid reducing agents include carbon and metals such as sodium, calcium, and magnesium. Hydrogen or ammonia reduction, commonly used to produce tungsten, molybdenum, iron, copper, nickel, cobalt and other metal powders. Carbon reduction is commonly used to produce iron powder. With strong metal reducing agents sodium, magnesium, calcium, etc., tantalum, niobium, titanium, zirconium, vanadium, beryllium, thorium, uranium and other metal powders can be produced (see metal thermal reduction) Nickel, copper, cobalt and their alloys or coated powders can be prepared by reducing metal salt aqueous solutions with high-pressure hydrogen (see hydrometallurgy). The powder particles produced by the reduction method are mostly irregular shapes of sponge structure. The particle size of the powder mainly depends on factors such as reduction temperature, time and the particle size of the raw material. The reduction method can produce most metal powders and is a widely used method.

Atomization

The molten metal is atomized into fine droplets and solidified into powder in the cooling medium (Figure 3). Figure 4 The widely used two-stream (melt flow and high-speed fluid medium) atomization method is to use high-pressure air, nitrogen, argon, etc. (gas atomization) and high-pressure water (water atomization) as the jet medium to crush the metal liquid stream. There are also centrifugal atomization methods that use rotary disk crushing and the melt itself (consumable electrodes and crucibles) to rotate, as well as other atomization methods such as hydrogen-dissolved vacuum atomization and ultrasonic atomization. Due to the small droplets and good heat exchange conditions, the condensation speed of the droplets can generally reach 100 ~ 10000K / s, which is several orders of magnitude higher than when casting ingots. Therefore, the composition of the alloy is uniform and the structure is fine. The alloy material made of it has no macrosegregation and excellent performance. Aerosolized powders are generally nearly spherical, and water atomization can produce irregular shapes. The characteristics of the powder such as particle size, shape and crystalline structure mainly depend on the properties of the melt (viscosity, surface tension, superheat) and atomization process parameters (such as melt flow diameter, nozzle structure, pressure of the spray medium, flow rate, etc.). Almost all metals that can be melted can be produced by the atomization method, especially suitable for the production of alloy powders. This method has high production efficiency and is easy to expand industrial scale. It is not only used for mass production of industrial iron, copper, aluminum powder and various alloy powders, but also used to produce high purity (O2 <100ppm) high temperature alloy, high speed steel, stainless steel and titanium alloy powder. In addition, the rapid cooling powder (condensation speed> 100,000K / s) produced by the quenching technology has been paid more and more attention. It can be used to produce high-performance microcrystalline materials (see fast-cooling microcrystalline alloys).

Electrolytic method

Direct current is applied to the metal salt aqueous solution, and metal ions are discharged on the cathode to form a deposit layer that is easily broken into powder. Metal ions generally originate from the dissolution of the same metal anode, and migrate from the anode to the cathode under the action of current. The factors affecting the particle size of the powder are mainly the composition of the electrolyte and the electrolysis conditions (see electrolysis of aqueous solution). Generally, the electrolytic powder is mostly in the form of dendrites with high purity, but this method consumes a large amount of electricity and has a high cost. The application of electrolytic method is also very extensive, commonly used to produce copper, nickel, iron, silver, tin, lead, chromium, manganese and other metal powders; alloy powder can also be prepared under certain conditions. For rare refractory metals such as tantalum, niobium, titanium, zirconium, beryllium, thorium, and uranium, composite molten salts are often used as electrolytes (see molten salt electrolysis) to prepare powders.

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NK Cells Shed Important New Light to Cancer Vaccine Development

There exist numerous sufferings resulted from miscellaneous diseases on the long march of human history. Threatened by these horrible illnesses, few people could fight back and survive until the emergence of vaccines.

 

Vaccine refers to a biological product intended to prevent diseases induced by bacteria, viruses, tumor cells, etc., which enable the body to produce specific immunity and make the recipient obtain immunity through vaccination. Through years of development of modern medicine, nowadays ordinary people have access to the vaccination various diseases from the moment of the birth, such as chickenpox, hepatitis B, tuberculosis, etc.

 

These diseases, which used to have a high mortality rate, have become no longer dreadful owing to the appearance of the vaccine. However, what dreaded at present are no longer these diseases, but a more incurable disease “cancer”, which poses a giant challenge in the cancer vaccine development.

 

Vaccine is an auto-immune preparation for preventing infectious diseases, made of pathogenic microorganisms and/or their metabolites through artificial attenuation, inactivation or genetic modification, which retains the ability of the pathogen to stimulate the animal’s immune system. Then, the immune system can follow the original memory produced at the vaccination to produce certain protective substances when attacked by the corresponding pathogen. Similarly, tumor vaccines kill tumors by recognizing tumor specific antigen or tumor-associated antigen tumor associated antigen to activate antigen-presenting cells and induce antigen-specific immune responses. The novel cancer vaccine development aims to find a new target to replace tumor cells, which can trigger immune responses and memories without causing cancer.

 

So as to develop a qualified cancer vaccine that may bring new hope for abundant patients, countless researchers and industrial companies have engaged in this field. A recent study published in Proceedings of the National Academy of Sciences reported that natural killer cells (NK cells) probably are the key to developing potential cancer vaccines. As a type of white blood cell belonging to the innate immune system, NK cells can patrol the body to find harmful cells, such as cancer cells or viral infections, but they cannot effectively memory these harmful cells.

 

Scientists have long known that T cells and B cells can empower the body’s immune system long-term memory. In this study, researchers tried to determine how NK cells trigger immune memory in the absence of T cells or B cells, likely opening a whole new field of immunological research. NK cells use specific receptors to decide whether a cell faces a threat, and Ly49 may be involved. A specific protein is used to vaccinate mice that have been depleted of T cells or B cells, the receptor of which can recognize foreign threats. When inoculated mice are exposed to melanoma cells that express the same protein, the self-protective mechanisms can prevent mice from cancer.

 

When the researchers repeated the experiment in mice lacking the Ly49 protein, they found no protective mechanism against cancer in mice. Now researchers can successfully immunize mice that lack both T and B cells to help protect them against cancer, perhaps because of the Ly49 receptor.

 

Although there is no final conclusion on NK cells’ function to develop cancer vaccines, the results suggest that vaccination of mice without T and B cells may be effective against cancer, which may inspire some researchers or industrial companies to adjust their research projects on vaccine development services for a long-anticipated success.

Research Progress of Drugs for Rheumatoid Arthritis (RA)

  1. The pathological mechanism of rheumatoid arthritis

 

Rheumatoid arthritis (RA) is a chronic autoimmune disease, whose main clinical manifestations are synovitis, cartilage injury and symmetrical joint injury. RA often occurs in small joints such as hands and feet, which can also affect other systems outside the joint, even lead to joint deformity and loss of function. The prevalence of rheumatoid arthritis is 5% – 10%, which is regionally differentiated. Women are more likely to suffer from rheumatoid arthritis than men, and the functional disability of RA patients will reduce their work ability and participation, increase their medical costs, and further aggravate the social burden.

 

The joint injury and the more serious symptoms of RA are caused by the immune complexes formed by the combination of anti-citrullinated autoprotein antibody produced by RA patients and citrullinated autoprotein antigen in vivo, and then, together with rheumatoid factor (RF), a large number of complements are activated, which mediates abnormal immune response. The exact cause of the disease has not been fully elucidated, but it has been proved to be related to genes (epigenetic modification, protein post translational modification), environment and infection.

 

  1. Research Progress of drugs for rheumatoid arthritis

There emerge innovative treatments targeting RA, especially in the past 30 years. Although there is not a way to cure RA patients, yet early diagnosis, early intervention, and instant treatment can help control the disease more effectively and improve the life quality of patients.

 

At present, associate drugs include small molecule therapeutic drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), (disease modifying antirheumatic drugs (DMARDs), and biomacromolecule therapeutic drugs, such as tumor necrosis factor alpha inhibitors, B-cell inhibitors, cytokine receptor inhibitors, target nuclear factors Biological preparations of receptor activator ligand kappa B (RANKL) and target granulocyte macrophage colony stimulating factor, etc.

 

In the progress of drug development, antibody design & engineering approachessectors of biotechnology are playing a role. Successful cases like rituximab and belimumab are monoclonal antibody drugs, and biological agents targeting granulocyte macrophage colony stimulating factor (GM-CSF).

 

Many life science companies are working on the monoclonal antibody (mAb) discovery & modification technologies to make progress in developing effective treatment of RA. Creative Biolabs, as a leading figure in this field, is providing the comprehensive phage display & antibody library services that are capable of delivering monoclonal antibodies from many host species, human, monkey, rodents, chicken, camel, and shark, etc. To meet with majority of the research conditions and requirements, the immune antibody libraries can reach a diversity of 108-10. As proficient as it can be, Creative Biolabs offers phage display library construction solutions touching upon the entire antibody discover pipeline from screening to stability improvement, as well as high-standard products, such as Premade Phage Display Antibody Libraries, Immunized Human Antibody Libraries, all of which are supported by the professional technical staff.

 

 

With the elucidation of the pathological mechanism of RA, the treatment of RA has been improved from the initial small molecule chemosynthetic drugs to the macromolecular biological agents, and the inhibition of disease inflammatory factors to the direct targeting of disease pathogenic channels. Although there are no drugs that can completely cure, yet it is hopeful that with the increasingly clear pathological mechanism of RA, new treatment targets may also become the direction of treatment in the future.