LL-37 顕微鏡の下: 奇跡の科学か危険信号か?
Cut to the chase. Evidence. Pull up a chair. Let’s get this straight. Buddy, he’s your buddy. Hey everybody, time to talk about a peptide we haven’t covered before. And this is called LL37. It’s quite unique and not really like the other peptides we’ve covered. It’s considered a human cathalicin antimicrobial peptide and it’s made up of 37 amino acids and it’s a key component of the innate immune system. In the past we’ve covered the innate verse adaptive immune system. But let’s quickly review it once again. Although these two facets of immunity are distinct, they’re also complimentary. The innate immune system is our first line of defense. the natural barriers our body has against foreign germs and invaders. The protective fortresses in a way our skin, the hairs in our nose, mucous membranes and cell types like neutrfils and macrofasages that recognize certain pathogenic patterns to neutralize them. And while the innate immune system is more non-specific, the adaptive immune system is just that, adaptive. Slower to respond and more specific for antigenic invaders, consisting of belymphosytes and Tlymphosytes to target patterns it’s seen before and form memories of novel threats so it can help eliminate them in the future. This obviously isn’t a complete overview, but more of a simple layout of immune architecture. Catholicins are a family of antimicrobial peptides that play a central role in the innate immune system. In humans, the only cathitin is LL37 which came about from cleavage of what’s called the 18 kilodont human cathicin antimicrobial protein and thus it’s thought to align with amunom modulation antimicrobial effects thought to act as part of this firstline innate immune system. And it appears that interest in LL37 isn’t just a modern-day occurrence, but something that’s been building over the past 15 years or so. But one thing that makes conceptualizing this antimicrobial precursor protein complex is the fact that it’s widely expressed from epithelial cells to the respiratory tract, gastrointestinal environment, reproductive system to immunity. Now, LL37 initially became of interest because it was discovered to prevent biofilm formation of certain bacteria. Bacteria biofilms are kind of like a microscopic shell used to propel their invasion and prevent their dissolution. And so, an ability of a compound to destroy them demonstrates an immune capability. And although we don’t know exactly how LL37 does this, it’s quite interesting regardless. Moreover, within the immune system, LL37 seems to recruit immune cells to enhance defenses to microbial invasion seen to modulate activity of neutrfils, macrofasages, dendritic cells, and it may even help neutralize lipopolysaccharides, which are a key invading pathogen expressed by bacteria. And LL37 is also known to be quite angioenic, promoting formation of new blood vascule and its related involvement with features of wound healing. In a similar vein, it’s thought to be interwoven with features of cancer as well in a bit of a controversial manner, which adds another layer of complexity to understanding this antimicrobial peptide. This is likely quite a complex topic to dissect in general because LL37 is the widely expressed only human cathicum peptide. But on top of that, receptors in different cells may respond to LL37 activity in a different manner. And to emphasize the peptides dichotomy, I’ll attach a line from a recently published review which states, “L37 has been found to have contrasting effects on different types of cancers. For certain cancers, such as breast, lung, and ovary cancer, LL37 is tumorogenic and facilitates the cancer formation process. While in other cancers like colon, and gastric cancers, LL37 has been proven to be anti-cancer.” quite intricate, cool, and concerning at the same time. But let’s segue into why you actually care, which is because there’s a sect of the biohacking community interesting in supplementing with exogenous LL37 use. But before we dive in, I’m going to quickly ask for your support. If you do enjoy evidence-based researchbacked peptide content, the best way to help me out, believe it or not, is to give a like and subscribe. Most of my channel’s viewers aren’t subscribed. And to keep this heavily researched, reference cited content going, I’d appreciate your continued support. So, thanks a lot. Let’s move on and summarize preclinical research and animal models and the actual human trials that have occurred. We’ve already mentioned from the biohackers POV the sum of research from a pre-clinical standpoint and involvement within the innate immune system subsequent modulatory effects a controversial impact on cancer and likely angioenic blood flow augmenting properties in animal models particularly murine or mouse models of sepsis LL37 administrations demonstrated protective effects by improving survival and modulating effects of inflammation. In other words, helping the animals survive severe infections by stopping certain immune cells from dying in a way that makes inflammation worse. Keeping inflammation under control, helping white blood cells catch and neutralize bacteria. Now, I’d like to spend the rest of our time talking about human clinical evaluation because it does exist and it’s certainly fascinating, at least if you’re a nerd like me. And honestly, if you made it this far, you are too. Like it or not, the most robust of human data comes from an analysis of patients with hard to heal venus leg ulcers. And this was called the heal LL37 trial, which was preceded by a smaller trial showing potential benefit. And it was a well-conducted phase 2B study that came out of different sites in Sweden and in Poland. It consisted of just under 150 participants. And it looked at topical LL37 use at different dosages versus placebo versus standard compression therapy over 13 weeks with twice weekly application and a 4-month follow-up period. And compared to placebo, the LL37 groups were without significant improvement. analysis after the research was conducted which is called post hoc analysis showed perhaps favorable outcomes with LL37 in those with larger wounds but generally speaking post hoc analysis is less reliable and when looking at the primary end points there didn’t seem to show any consistent benefit however it was generally well tolerated with more concerning outcomes like infection thought to be unrelated to LL37 there was another trial in diabetic foot ulcers that came out of Indonesia, which in a low sample size population showed a proposed enhanced rate of healing in treatment groups in those with mild infection. However, there didn’t appear to be decreased markers of inflammation or bacterial colonization within those groups. There’s also a less relevant and arguably less reliable case study that looked at a 63-year-old woman with invasive melanoma treated with injectable LL37. But 45 days into the trial, she developed many vicular and bulbous lesions over her trunk and extremities filled with inflammatory infiltrate, prompting its discontinuation, ultimately highlighting a possible severe adverse dermatologic outcome to injectable use of the peptide. Now, I’ll conclude by emphasizing some data showing some possible promise in the context of a viral illness that over the past 5 years has taken the world by storm. Due to monetization and concerns that an in-depth discussion would get my video lost in the algorithm in not a good way. I won’t discuss every facet, but I will say there’s a possibility LL37 via oral intake could possibly increase clearance of this virus, but results are unclear due to small sample sizes and lack of reproducibility. But an interesting sect of data I’ll link in the references below. Ultimately, LL37’s interesting given its prevalence in human immunohysiology. However, its unclear role in cancer, limited human clinical data, adverse dermatologic skin related concerns, and low yield results at this point added to my list of those painted with red flags to keep an eye on. I’m curious to hear what you think. So, leave a comment below and a like if you feel so inclined. But, I hope you enjoyed this video. Thank you for watching. If you are looking for additional ways to support the channel, I’ll link the Patreon in the description below, as well as the links to a BPC57 20page educational guide and our growing peptide codeex online catalog of different peptides that give brief overviews of the research impressions and links to my videos on the topic. But most importantly, thank you for watching. I hope you have a great day. Take care. Pull up a chair. Let’s get this straight. Peptide buddy. He’s your peptide buddy.
Let’s review the unique peptide LL-37 – thought to be involved with immunity, blood flow,, wound healing and cancer. Thanks for watching!
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📚 References
The immune system. First of two parts – https://pubmed.ncbi.nlm.nih.gov/10882768/
LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases – https://pubmed.ncbi.nlm.nih.gov/38540740/
Cathelicidin LL-37: a multitask antimicrobial peptide – https://pubmed.ncbi.nlm.nih.gov/20049649/
Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial – https://pubmed.ncbi.nlm.nih.gov/34687253/
Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy – https://pmc.ncbi.nlm.nih.gov/articles/PMC9445486/
Therapeutic Potential of Cathelicidin Peptide LL-37, an Antimicrobial Agent, in a Murine Sepsis Model – https://pubmed.ncbi.nlm.nih.gov/32825174/
Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial – https://pubmed.ncbi.nlm.nih.gov/37480520/
Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: A detailed examination of the clinicopathologic features – https://pubmed.ncbi.nlm.nih.gov/29665030/
Efficacy and safety of Oral LL-37 against the Omicron BA.5.1.3 variant of SARS-COV-2: A randomized trial – https://pubmed.ncbi.nlm.nih.gov/37605995/
#LL37 #Peptides #Biohacking #Immunity #biohacking #health
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