LL-37 news and clinical trials

Researchers reviewed evidence linking the LL-37 peptide and MRGPRX2 receptor signaling to mast cell activity in rosacea. The study noted that while animal models support this pathway, direct selective functional testing in human rosacea patients is currently lacking.

Researchers identified cathelicidin (CAMP) as an age-dependent regulator of bone repair in mice. CAMP promotes fracture healing in young animals by supporting osteogenesis, but it constrains healing in aged animals.

Researchers found that chicken cathelicidin-3 (cCATH-3) protected 80% of mice from APEC infection compared to 20% survival for cCATH-1. This protection occurred through CCL3-mediated macrophage chemotaxis and enhanced bacteriocidal activity.

Researchers found that adding an N-terminal biphenyl motif from LL-37 to a short cathelicidin derivative improves activity against gram-negative bacteria by >16-fold. The biphenyl pharmacophore increases membrane permeabilization in the 14-mer peptide without affecting its stability.

Researchers used a genetic approach to show that Streptococcus pyogenes protease SpeB does not significantly impact the killing of the bacteria by the peptide LL-37. Even though SpeB cleaves LL-37, the bacterial CovRS system maintains its sensitivity to the resulting LL-37 fragments.

This review summarizes how the human cathelicidin LL-37 regulates apoptosis by exerting either proapoptotic or antiapoptotic effects. These outcomes depend on factors like cell type and peptide concentration, which researchers must understand to develop the peptide for cancer therapy.

A review article discussed translational hurdles for LL-37 as an oral antimicrobial treatment, citing rapid salivary clearance, high production costs, and proteolytic degradation. The authors proposed a roadmap focusing on peptide engineering, nanocarriers, and endogenous peptide induction.

Researchers demonstrated that LL-37 inhibits angiogenesis, migration, and invasion in gastric cancer cell lines and mouse models. The peptide achieves this by inactivating the NF-κB/IL-6 signaling axis, which reduces the expression of IL-6 and VEGFA.

Researchers developed d-GK17, a D-enantiomeric derivative of LL-37 designed to resist proteolysis. Preclinical validation showed it possesses potent antimicrobial and antibiofilm effects while remaining stable in serum and wound environments.

Researchers developed a detergent-free method for producing recombinant LL-37 by fusing it to calmodulin. This approach improves solubility by covering the aggregation-prone surfaces of LL-37 and allows for efficient purification via enterokinase cleavage.

Researchers mapped how human LL-37 and its fragments bind Cu(II) and Zn(II) ions. The study found that metal coordination enhances the antimicrobial and antibiofilm activities of these peptides, suggesting their fragments could serve as new antibiofilm agents.

A study published in Bioinformation found that salivary cathelicidin LL-37 levels increased progressively from healthy controls to oral squamous cell carcinoma cases in 80 participants. The findings suggest salivary LL-37 is a reliable, non-invasive biomarker for early cancer detection.

An observational study of 58 individuals with obstructive sleep apnea found that plasma LL-37 levels were significantly higher in patients with an AHI < 15 (75.3 ± 29.3 ng/L) than in those with an AHI ≥ 15 (47.1 ± 18.3 ng/L). The findings suggest LL-37 may be a biomarker for sleep quality.

Researchers engineered a fusion protein by linking LL-37 to the ferritin light chain to improve its stability and target inflammatory lesions via scavenger receptor A. In a murine sepsis model, this protein showed superior antibacterial and anti-inflammatory efficacy compared to free LL-37.

Researchers synthesized LL-37 analogs with Dap building blocks and oxa-acid spacers, finding that specific modifications increased proteolytic stability against PR3 up to 5.7-fold. The modified peptides shifted functional profiles from microbicidal activity to suppressed neutrophil degranulation.

A study of 214 suspected autoimmune neutropenia cases found that incorporating pro-LL-37 levels and absolute neutrophil counts may improve diagnostic accuracy. Patients positive for antibodies in three tested assays showed significantly higher pro-LL-37 levels and lower neutrophil counts.

Researchers found that combining LL-37 with adipose-derived stem cells accelerates diabetic wound repair in mice by upregulating NRROS in stem cells. This process activates TGF-β/SMAD and Hippo/TEAD1 signaling pathways to improve fibroblast activity.

Researchers reported that melanoma-derived exosomes containing hsa-miR-221-5p suppress keratinocyte LL-37 expression to promote tumor progression. The study suggests that preserving or increasing LL-37 signaling could counteract melanoma growth and immunosuppression.

Researchers published a study showing that poly-D,L-lactic acid (PDLLA) reduced inflammation in a rosacea-like mouse model. PDLLA treatment promoted an IL-10-linked signaling program that suppressed mTORC1 activity and alleviated clinical lesion areas.

Researchers determined that RNA acts as a concentration-dependent regulator that affects peptide assembly and function. While RNA preserves the cytotoxic activity of the virulence factor PSMα3, it attenuates LL-37 cytotoxicity toward host cells while maintaining its antibacterial function.

Scientists investigated the antimicrobial mechanism of cathelicidin-DM from the Asian common toad. The study found the peptide binds to membranes and shows interfacial activity, though it paradoxically perturbs zwitterionic vesicles while sparing negatively charged ones.

Researchers published a study showing that the cathelicidin precursor proPMAP-37 acts as an immunomodulator by binding to lipopolysaccharide (LPS) and inhibiting M1 macrophage polarization. This study supports the potential of proPMAP-37 as an anti-inflammatory agent for agricultural use.

Researchers developed a hydrogel scaffold incorporating the antimicrobial peptide LL-37 for gingival soft tissue regeneration. In rat models, the scaffold increased neovascular density, improved collagen organization, and demonstrated anti-inflammatory effects.

International immunopharmacology withdrew a study regarding Oroxylin A and LL-37 because it was an accidental duplication of an article published elsewhere.

Researchers identified and characterized four cathelicidin paralogs in tiger frog lungs. The peptide AS34 showed potent broad-spectrum antimicrobial activity and anti-inflammatory properties, while all four peptides suppressed nitric oxide production in macrophages.

Researchers demonstrated that LL-37 selectively inhibits osteosarcoma cell viability and tumor growth by targeting the PTEN/AKT/mTOR-SREBP2/SQLE axis to suppress cholesterol synthesis. In a 143B cell xenograft model, LL-37 treatment inhibited tumor growth with efficacy comparable to cisplatin.

Researchers investigated vitamin D levels in diabetic patients with periodontitis and found that serum 25(OH)D 3 insufficiency correlated with increased periodontal inflammation. However, total amounts of gingival LL-37 were not directly correlated with serum vitamin D levels.

The authors published a corrigendum regarding their previously reported study on Oroxylin A and its role in suppressing LL-37 generated rosacea-like skin inflammation.

A review in the International Journal of Molecular Sciences explains that while Aβ and LL-37 are protective under physiological conditions, their interaction during chronic infection or dysregulation promotes neuroinflammation and contributes to Alzheimer's and other neurodegenerative diseases.

Investigators evaluating 500 samples from the AZACS study found that elevated LL-37 IgG levels are associated with prior myocardial infarction and show a negative correlation with blood pressure.

Recep Tayyip Erdogan University registered an observational trial to evaluate levels of 25(OH)D3 and the antimicrobial peptide LL-37 in the peri-implant sulcus fluid of 72 participants. The study aims to correlate these levels with clinical markers and inflammatory cytokines.