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Magical Peptides and Their Functions (III)

With the deepening of research on enzyme modulators and inhibitors, they play an increasingly important role in the health of organisms. Antibacterial peptides: also known as antibacterial functional peptides, it is usually associated with antibiotic peptides and antiviral peptides, including cyclic peptides, glycopeptidesand lipopeptides, such as gramicidin, bacitracin, polymyxin, lactic acid bacteria, Subtilisin and nisin, etc. Antimicrobial peptides have good thermal stability and strong antibacterial effect. In addition to microorganisms, animals and plants that can produce endogenous antibacterial peptides, effective antibacterial peptides can also be obtained by enzymatic hydrolysis of food proteins, such as antibacterial peptides obtained from lactoferrin. Lactoferrin is a glycoprotein that binds iron. As a prototype protein, it is considered to be a very important defense mechanism for the host against bacterial infections. Research biologists used pepsin to split lactoferrin and purified three antimicrobial peptides, which can act on E. coli, all in cationic form. These biological functional peptides are effective 30 minutes after contact with pathogenic bacteria and are good alternatives to antibiotics. Neuropeptides: After enzymatic hydrolysis of a variety of food proteins, neurological functional peptides will be produced, such as the opioid functional peptide derived from wheat gluten, which is the product of in vitro pepsin and thermolysin hydrolysis. Neurofunctional peptides include opioid functional peptides, endorphins, enkephalins and other regulatory peptides. Neurofunctional peptides play an important role in organisms. They can regulate emotions, breathing, pulse, body temperature, etc. Unlike ordinary analgesics, they have no side effects. Immune peptides. Immune functional peptides can stimulate the phagocytic ability of macrophages and inhibit the growth of tumor cells. We call this peptide an immune functional peptide. It is divided into endogenous immune functional peptides and exogenous immune functional peptides. Endogenous immune function peptides include interferons, interleukins and β-endorphins, which are the center of activating and regulating the body's immune response. Exogenous immune functional peptides mainly come from casein in biological milk and cow milk. Immune functional peptides have a variety of physiological functions. They can not only enhance the body’s immune ability and play an important immunomodulatory role in animals; but also stimulate the proliferation of lymphocytes in the body and enhance the phagocytic ability of macrophages to improve the body’s ability to external pathogenic substances. Flavoring peptides. Certain functional peptides can improve the palatability of food and improve the flavor of food. We call this peptide flavoring peptide. Contains the following: 1): Sour peptide: Sour peptide is usually related to sour taste and Umami taste. Umami has the taste of sodium glutamate, and it is usually composed of dipeptides or tripeptides containing sodium glutamate and sodium aspartate. The octapeptide isolated from papain-treated beef extract for the first time is called "delicious peptide" and is the best example of Umami's flavor. It is reported that the delicious peptide has a typical beef soup taste, which is mainly attributed to the synergistic effect of the N-terminal dipeptide Lys-Gly, the central acidic tripeptide Asp-Glu-Glu and the C-terminal tripeptide Ser-Leu-Ala. 2): Sweet peptides: The typical representatives of sweet peptides are dipeptide sweetener and alitame, which have the characteristics of good taste, high safety, and low calories. Among them, dipeptide sweeteners have been approved by more than 70 countries to be used in more than 500 kinds of foods and medicines, and can be used to enhance the sweetness of foods and adjust the flavor. In addition, lysine dipeptide has been proven to be an effective substitute for dipeptide sweeteners. It does not contain esters and is more stable during food processing and storage. 3): Bitter peptide: Bitterness is an important taste component of some foods such as beer, coffee, cheese and so on. Basic dipeptides such as ornithine-β-alanine exhibit a strong bitter taste, and glutamic acid oligomers are often used as bitter components in many foods. At present, research biologists have separated bitter peptides from fermented foods and enzymatic hydrolysis products of casein; 4): salty peptides: certain basic dipeptides, such as ornithyl taurine-hydrochloride, ornithyl Beta-alanine-hydrochloride exhibits a strong salty taste, sometimes accompanied by Umami flavor. However, studies have found that peptides are not salty in the absence of hydrogen chloride. It canbe developed as a substitute for high-sodium condiments.
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The First MET-14 Targeted Drug Might Be Launched within Months

On February, FDA granted priority approval for the oral MET targeted drug camatinib (INC280). If all goes well, the first targeted drug for the treatment of non-small cell lung cancer with MET exon 14 skip mutation will be available in months. The Geometry mono-1 study showed that carmartinib monotherapy for advanced non-small cell lung cancer with skip mutations in MET exon 14 has an objective response rate of 67.9% in newly treated patients, and an objective response rate of 40.6% in patients who have previously received chemotherapy. The most common adverse reactions were peripheral edema, nausea and vomiting, most of which were mild. Camatinib is effective in treating MET mutations Jumping mutations in exon 14 of MET account for 3-4% of newly diagnosed advanced non-small cell lung cancer, and no corresponding targeted drugs have been approved for marketing. The Geometry mono-1 study showed that camatinib as a single agent (dose 400mg orally twice a day) was used to treat MET exon 14 skipping mutations, and EGFR\ALK are wild-type advanced non-small cell lung cancer, the objective remission rate of 67.9% in newly treated patients, and the median progression-free survival was 9.13 months. The objective response rate of patients who had previously received chemotherapy was also as high as 40.6%, and the median progression-free survival was 5.42 months. The most common (incidence rate>25%) treatment-related adverse reactions of camatinib monotherapy include peripheral edema, nausea, and vomiting, most of which are mild. 33.1% of patients had grade 3/4 serious adverse reactions, 10.3% of patients discontinued the drug due to suspected adverse reactions related to carmartinib treatment, and grade 3/4 serious adverse reactions related to carmartinib treatment included peripheral edema. Nausea, vomiting, fatigue and decreased appetite. Camatinib can also combat EGFR-targeted drug resistance
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Pertuzumab and codrituzumab Dual-target Neoadjuvant PEONY Study of HER2-positive Breast Cancer

SABCS is the world's largest and most influential breast cancer conference. Since 1977, it has developed into a five-day seminar with more than 7,000 scientific researchers and doctor representatives from more than 90 countries around the world. At this year's SABCS, the Phase III PEONY study of Pertuzumab + codrituzumab dual-targeted neoadjuvant treatment of HER2-positive breast cancer in the Asian population led by Professor Shao Zhimin will show the results of the first analysis. In 2012, Lancet Oncol published a NeoSphere Phase II study to evaluate the efficacy and safety of neoadjuvant therapy for codrituzumab + pertuzumab combined with docetaxel in patients with locally advanced, inflammatory or early HER2-positive breast cancer Sex. NeoSphere study results showed that patients who received pertuzumab and codrituzumab plus docetaxel had significantly higher pathological complete remission rate than patients who received codrituzumab plus docetaxel, bpCR (45.8 % vs29%, P = 0.0141), tpCR (39.3% vs 21.5%). There was no significant difference in tolerance. Then the 5-year data analysis of the NeoSphere study was published in 2016 by Lancet Oncol, and the results show that the triple target of Qupa can bring the benefits of PFS (86% vs 81%). Regardless of PFS or DFS, combined dual-targeted neoadjuvant therapy is superior to other groups. This is because Pertuzumab and codrituzumab exhibit complementary mechanisms of action in the anticancer activity of HER2-positive breast cancer patients. The combined application of the two blocks the formation of homo- and heterodimers by acting on different extracellular domains of the HER-2 protein, thereby blocking its downstream signaling and inhibiting tumor cell proliferation; at the same time, the ADCC effects of the two superimpose, It has a synergistic effect and activates immune NK cells to completely eliminate tumor cells. Due to differences in race, region, lifestyle, etc., the Asian population is different from the Western population. Can the NeoSphere research results be applicable to Asian populations? Under the leadership of Professor Shao Zhimin Shao, PEONY research was conducted jointly with many centers from mainland China and Taiwan, South Korea and Thailand. PEONY (NCT02586025) is a randomized, multicenter, double-blind, placebo-controlled phase III trial of Asian populations (Mainland China, Taiwan, South Korea, Thailand). The main comparison is Pertuzumab in neoadjuvant Differences in efficacy, safety, and tolerability between the anti-codrituzumab + docetaxel regimen and the placebo + codrituzumab + docetaxel regimen. This study enrolled early (T2–3, N0–1) / locally advanced (T2–3, N2 or N3; T4, any N) breast cancer patients who had confirmed HER2-positive, randomized in a 2: 1 ratio before surgery Enter Pertuzumab + codrituzumab + Docetaxel regimen group or Placebo + codrituzumab + Docetaxel regimen group, both regimens are 4 courses, one every 3 weeks Course of treatment. After the operation, the patient received 3 courses of FEC chemotherapy and continued to use 13 courses of Pertuzumab + codrituzumab or Placebo + codrituzumab until 1 year. The primary endpoint of this study was the total tpCR ([ypT0 / is, ypN0]). When the patient completed the operation, the tpCR results were evaluated by the external review committee (IRC). PEONY reached the main endpoint of the study. The results showed that the tpCR of the triple target group of tropa was significantly increased to 180% of the single target group of trastap (39.3% vs 21.8%, P = 0.0014), and the safety results were consistent with the previously known Par Safety data of codrituzumab.
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