Application of Gene Chip Technology in Disease Resistance Detection

The detection of disease resistance by gene chip technology can be realized in two aspects: 1. In the tumor, the resistance to the drug is analyzed by detecting the expression change of the tumor resistance gene; 2. In the infectious disease, the pathogen is Drug resistance can be detected in two ways: expression profiling detects drug-induced expression changes to analyze drug resistance; oligonucleotide microarrays detect subtypes or mutation sites of genomic sequences to analyze drug resistance. I. Expression of multidrug resistance genes The detection of resistance to cytotoxic drugs in cancer therapy is an important cause of treatment failure and an important factor limiting chemotherapy. The mechanism is complex and is determined by the overall characteristics of the tumor, such as the proportion of viable cells, the availability of blood, special cellular mechanisms, and multidrug resistance phenotypes. Multidrug resistance refers to when tumor cells are exposed to a certain chemistry. Treatment drugs can cause cross-resistance to drugs and other structurally unrelated drugs, which can be caused by different mechanisms, such as overexpression of genes such as MDR1, MRP, LRP, topoisomerase II and glutathione metabolism. In addition, other gene expression changes that promote DNA repair and inhibit apoptosis may also lead to multidrug resistance. Detection of changes in multidrug resistance gene expression can not only study the different drug resistance mechanisms of malignant tumors, but also can be used for clinical diagnosis to guide the development of treatment options. Several multidrug resistance assays have been established. At the RNA level, there are: Northern blot, Slot blot, RT-PCR, Rnase protection assay and in situ hybridization. The detection methods at the protein level are immunohistochemistry, Western. Blot and flow cytometry. These methods can only study one gene at a time, and the efficiency is low, and it is difficult to quantitatively detect the increase in the expression of drug resistance genes. The gene expression profiling chip can detect thousands of gene expression at the same time, which can greatly accelerate the research in this aspect. When designing the chip, the known tumor-related genes and marker genes can be spotted on the chip, and at the same time, on the chip. It also contains all currently reported resistance genes. This allows you to get information on all aspects of the tumor at the same time. In addition, gene chips can also help discover new drug resistance genes. Second, the detection of pathogen resistance The bacteria can be called multi-drug resistant bacteria (MDR) for three or more different types of antibiotics. The global situation of MDR infection is very serious, and it poses a great threat to infants, immunodeficiency and the elderly. According to data from the Centers for Disease Control and Prevention (CDC) in 1992, there are 13,300 hospitalized patients because of the antibiotics used. Resistance, bacterial infections are not controlled and die. MDR infection has become a difficult point in research and a research hotspot. MDR is mostly a conditional pathogen, and Gram-negative bacilli (GNR) account for a large proportion, such as Klebsiella pneumoniae, Escherichia coli, bacillus sphaeroides, Serratia marcescens, Phytophthora, Shigella in Enterobacteriaceae. Genus, Salmonella, etc., as well as Pseudomonas aeruginosa, Acinetobacter, Influenza, etc. There are methicillin-resistant Staphylococcus (MRS) in Gram-positive bacteria, especially MRSA and MRSE; vancomycin-resistant Enterococcus (VRE) has been reported in the intensive care unit (ICU) in recent years. Significantly increased; penicillin-resistant Streptococcus pneumoniae (PRSP), often cause pneumonia, meningitis, bacteremia and otitis media, human tuberculosis. In addition, there are gonococcal, meningococcal, and Vibrio cholerae. Drug resistance, also known as drug resistance, generally refers to a state in which the drug reactivity of a pathogen is reduced. This is due to the long-term application of antibacterial drugs, the pathogens produce a reaction that reduces the effect of the drug by producing an enzyme that inactivates the drug, and changes the original metabolic process, so that the dose of action is constantly increasing. There are many mechanisms for the resistance of bacteria to antibiotics. The most important ones are the production of inactivated enzymes, such as β-lactamase, aminoglycoside inactivating enzymes, etc., followed by target changes such as penicillin-binding proteins (PBPs). Changes, etc.; other changes in membrane permeability, affecting the entry of drugs; bacterial pumping system increased, enhanced, to discharge drugs that have entered the bacteria; and active transport of membranes decreased, establish new metabolic pathways, increase antagonistic drugs Etc. Two or more mechanisms can often be initiated simultaneously. The occurrence and development of drug-resistant bacteria and MDR are the widespread use of antimicrobial agents, especially the absence of indications. Find drug-resistant genes of drug-resistant bacteria, and design new antibiotics according to these drug-resistant genes, or divide the drug-resistant bacteria into different subtypes, and use corresponding antibiotics for different subtypes to achieve the purpose of improving the therapeutic effect. Foreign countries use gene chip technology to detect changes in drug-resistant bacteria genes, that is, to detect drug-resistant genes. For example, Michael Wilson used this method to detect changes in fatty acid synthase II, fbpC, efpA, fadE23, fadE24 and ahpC genes in tuberculosis bacilli. It provides targets for the action of new drugs and directs the inhibition of the synthesis of these target agents and drugs. In infectious diseases, the detection of drug resistance of pathogens can be carried out in two ways: 1. The expression profile chip detects drug-induced changes in gene expression to analyze drug resistance; 2. The oligonucleotide chip detects subtypes of genomic sequences. Or mutation sites to analyze their resistance. Gene chip can not only detect multiple drug resistance genes of drug-resistant bacteria at the same time, but also detect multiple drug resistance genes of multiple drug-resistant bacteria at the same time. It has a guiding role in the clinical application of drugs and the synthesis of new drugs.

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