The "theatrical" diaphragm, which has been a “sample” in research, has been extended from the area of sugar to that of tumors and anti-age。
The latest news is that direct impact targets and molecular mechanisms have been found in the two-accelerates. It has been suggested that this discovery may provide a fresh source of treatment for diabetes, or even for the development and application of anti-tumour, anti-age medicines. New thinking is expected to be a shining milestone in the history of the treatment of diabetes drugs, making china's voice in the field of scientific research sound to the world。
Why say this discovery is a landmark event? First of all, we have to start with the target。
A target achieves an industry
Currently, international competition for drug research is concentrated mainly on drug target research. In general, the discovery of new targets for the effects of drugs often represents a breakthrough in the discovery of a range of new drugs. New drug targets are crucial for drug research, pharmaceutical enterprises and even the term “one target achieves an industry”。
The drug target is the point of integration of the drug's role in the body, including the biomolecular elements such as genetic position, receptor, enzyme, ion channel, nucleic acid. The key to drug development is the selection of the most likely successful and clinical target among a large number of potential targets, which form the basis of new drug development. At present, however, targeting and clinical research based on biomarkers have become two major bottlenecks in the development of innovative medicines. The vast majority of innovative drugs in the country have also been developed on the basis of the mechanisms and target points found abroad, so that we need a substantial breakthrough in innovative medicines from the point of discovery. Target detection and identification is an important and challenging task for pharmaceutical workers。
Of course, not every drug has found its target, and many have not found the target yet, but it's good. Now, for example, most of the drugs that treat diabetes are first discovered, then the target is found, and the pharmacist diaphragm is in the table。
I've lived a long life
As early as the middle ages, the french knew how to treat urinasis with purple lilac (also known as goat's rue). This has inspired researchers to find new discoveries。
Two aces and two aces of “careership”
In 1918, watanabe injected the extracts of lilac from france into rats and found them to have a magical effect on reducing blood sugar in rats。
In 1922, emil werner and james bell were synthesized for the first time, and the diaphragm was first identified and recorded in the scientific literature。
In 1929, slotta and tschesche found that dichloride is the most interesting component of the diazine compound for sugar reduction。
In 1950, jean sterne, a french diabetic, began studying the sugar-reducing activity of goat bean alkalis (vilatin extracts)。
Sterne published his research in 1957 and named it "glucophage"。
In 1958, the two-decalogues were collected by the british national prescription。
In 1994, the two-decabde was approved by the fda for type 2 diabetes。
Ukpds, a landmark study in the history of the treatment of diaphragm and human diabetes that began in 1977 and ended in 1997 and followed 10 years later, established the status of "first brother" in the treatment of type 2 diabetes。
In addition to blood sugar, a growing body of research has a number of other effects, including anti-age and cancer prevention. Despite this, the use of the diaphragm has not been fully promoted because the direct molecular target of the diaphragm has not yet been identified and the mechanisms used have been widely discussed。
The mystery of the two-accelerator action target has been uncovered, and the mechanism of action is clear
In recent days, a major breakthrough has been made in molecular targeting research for the two-decalogues, with the combined efforts of the team of lin's saints and professor deng hyun-ming, faculty of life sciences, university of xiamen, and published in the top magazine, nature, as follows。
Purpose of the study
The amp activated protein epidemic (ampk) route is an important route for metabolism control of the diaphragms, but previous experiments have shown that the diaphragm activates the ampk in a special way and that there is likely to be “intermediate protein”. The objective of the forestry team is to find this intermediate protein and thus to identify the key elements of the diaphragm as a “therapeutic”。
Research design and methodology
Fishing strategy for “widespread nets, focus fishing”
In partnership with professor deng hyun-ming of the faculty of life sciences of the university of xiamen, the team at lin's episcopal academy developed two chemical probes (met-p) using the two-accelerant molecule as a “fish bait” to hatch protein extracts from the solution. In the pond of the solute, the fish is baited with a two-decatra double-polymer, with an unknown target molecule that completes the wire and recovers the two-capabromodiphenyl-protein complex. The process is illustrated in the figure below。
The “fishing” process
Accurately sensed chemical probes have finely “fished” these molecular compounds, but at the same time have created a huge workload for subsequent studies - in the “fishing link” study, the team “fished” to more than 2,000 molecules that can be combined with the tungsten。
The “fishing” is completed, and 113 proteins are screened, inter alia, by mass spectrometry, from the protein extracts of the solute body, which have a specific combination with the dictum. Subsequently, the team conducted a one-by-one test of 113 candidate proteins。
Result
When pen2 expresses being knocked down or the pen2 gene is knocked out, the activation of the ampk signal path within the cell is inhibited. The key activity points f35 and e40 on pen2 are identified。
The team further confirmed the identity of pen2 in animal experiments。
Pen2 is required to induce a reduction in glucose levels
For iko-en2 mice, a two-decaree glucose tolerance test (a), glucose glucose tolerance (b, left) and glucose glucose glucose glucose glucose-1 levels (b, right) were used。
Pen2 is needed to reduce liver fat content induced by diaphragm
Pen2 mice (lko) are treated with diaphragms that are specific to the liver. Intraperitoneal glucose tolerance test results (c) and liver marker levels (d) were shown in mice after 16 weeks of cortex treatment
Pen2 and atp6ap1 are required for the extended life of diaphragms
Pen2(t28d6. 9) treats (g) or atp6ap1 – (vha-19) or nematodes expressed in full length atp6ap1 or atp6ap1δ420-440 stable, treats (h) 50 mm2-acre diaphragms
Conclusions
Pen2 of the mice and the surrey pipeline worms were knocked out and found that ampk could no longer be activated, and that the reduction of glucose levels, reduction of liver fat content and extended life effects were induced by a two-acre cortex. This is sufficient to suggest that pen2 is an indispensable signal molecule in the mechanism for the functioning of the two-decabde。
The study of professor lin's team and its collaborators confirms that pen2 is the direct target of the two-a-decarees that have been being sought by the academic community for over a century. The lead molecules in the study will not only treat obesity and fatty liver, but even prevent cancer and increase life expectancy. The study fills a gap in the targets of the two-accelerator molecules and opens a new chapter in drug development。
“when the red dust lady smiles, no one knows it's a twig, it can be said that ordinary people eat twigs in the context of tang dynasty, which are now “flying” into ordinary people's homes. It's like the ancients' quest for immortality by eating the monk's flesh, but ultimately they all want it. And now, the discovery of the two-accelerator action target gives us reason to believe that, in the near future, an extended life or a dream will cease to exist
References
Ma, t., tian, x., b. Et al. Low-dose metformin towers the lysomamal ampk pathway through pen2. Nature (2022). Https://doi. Org/101038/s41586-022-04431-8
Woo-mi, i'd like to say that i've lived a long life in medical science
"nature" weighs a pound: chinese scientists have solved the two-decalogue mechanism puzzle! The big team found a real target for the two-acre tweezers. Scientific discoveries.
