Level Of LL-37 Research Articles

Correlation between Vitamin D Levels and Antimicrobial Peptide LL-37 in Pediatric Patients Diagnosed with Sepsis

Abstract Objective Our objective was to examine potential differences in inflammatory markers, specifically antimicrobial peptide (AMP) LL-37 and interleukin-6 (IL-6), in the bloodstream of children with sepsis who had varying levels of vitamin D3. Methods A total of 59 pediatric patients diagnosed with sepsis from January 2021 to November 2021 were enrolled in this study. The pediatric patients with sepsis were categorized into three groups based on their levels of vitamin D3, and AMP LL-37, IL-6, and procalcitonin (PCT) were compared among the three groups. Discussion The LL-37 level in the group with vitamin D3 deficiency was notably lower than in the other two groups (p deficiency group vs. insufficiency group = 0.019, p deficiency group vs. normal group = 0.034), whereas the disparity between the group with vitamin D3 insufficiency and the group with normal vitamin D3 levels was not statistically significant. There was a positive correlation between the level of vitamin D3 and LL-37 in pediatric patients with sepsis (r = 0.324, p = 0.012). On the other hand, the level of IL-6 in pediatric patients with sepsis showed a positive correlation with both LL-37 (r = 0.474, p = 0.000) and PCT (r = 0.527, p = 0.000). Conclusion Pediatric patients with sepsis typically exhibit low levels of vitamin D3, which are positively correlated with the levels of serum LL-37. Furthermore, the presence of higher levels of serum LL-37 is positively correlated with higher levels of IL-6.

37. Plasma Level of the Antimicrobial Peptide LL37 (Cathelicidin) is Negatively Associated With Alcohol Use Disorder in US Veterans

37. Plasma Level of the Antimicrobial Peptide LL37 (Cathelicidin) is Negatively Associated With Alcohol Use Disorder in US Veterans

Cathelicidin (LL-37) causes expression of inflammatory factors in coronary artery endothelial cells of Kawasaki disease by activating TLR4-NF-κB-NLRP3 signaling.

Kawasaki disease (KD) is a type of vasculitis with an unidentified etiology. Cathelicidin (LL-37) may be involved in the development of the KD process; therefore, further research to investigate the molecular mechanism of LL-37 involvement in KD is warranted. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, NLRP3, and LL-37 in the sera of healthy subjects, children with KD, and children with pneumonia. Subsequently, human recombinant LL-37 or/and toll-like receptors 4 (TLR4)-specific inhibitor TAK-242 stimulated human coronary artery endothelial cells (HCAECs), CCK-8 was used to detect cell proliferation, flow cytometry to detect apoptosis, transmission electron microscopy to observe cytoskeletal changes, Transwell to measure cell migration ability, ELISA to detect inflammatory factor levels, Western blot analysis to analyze protein levels of toll-like receptors 4 (TLR4) and NF-κB p-65, and quantitative real-time polymerase chain reaction (qRT-PCR) to determine LL-37, NLRP3 mRNA levels. In this study, we found that the level of LL-37 was highly expressed in the serum of children with KD, and after LL-37 stimulation, apoptosis was significantly increased in HCAECs, and the expression levels of TLR4, NLRP3 and inflammatory factors in cells were significantly enhanced. Intervention with the TLR4-specific inhibitor TAK-242 significantly alleviated the LL-37 effects on cellular inflammation, TLR4, NLRP3 promotion effect. Our data suggest that LL-37 induces an inflammatory response in KD coronary endothelial cells via TLR4-NF-κB-NLRP3, providing a potential target for the treatment of KD.

Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on S. aureus infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of Hirudinaria manillensis (H. manillensis) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 μg/mL. The RK22 peptide rapidly killed S. aureus by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection.

Influence of Vitamin D Deficiency on the Level of Salivary cathelicidin LL-37 in relation to Dental Caries Experience: A Case-Control Study

Background: Vitamin D improves innate immunity by enhancing the expression of antimicrobial peptides. The antimicrobial action of cathelicidin is widespread and effective against cariogenic bacteria. This research aimed to investigate the effect of vitamin D deficiency on the level of salivary cathelicidin concerning dental caries experience. Subjects and Methods: A case-control study was carried out, and the sample was composed of 80 females; the study group involved 40 females with a serum vitamin D concentration of less than 10 ng/ml. In addition to the control group involving 40 females who matched the case in number and age but serum vitamin D concentration of 30 ng/mol or more, their age range was 20-30 years. WHO 2013 index was used for the assessment of dental caries experience, and collection of unstimulated saliva was done to measure salivary cathelicidin. Results: Data from the current study showed that the mean values of the Decayed, Missing, and Filled Teeth index and its components (Decayed Teeth, Missing Teeth) were higher in the study group than those in the control one, with a significant difference for Decayed Teeth. Salivary cathelicidin was higher in the control group with a statistically significant difference. Conclusion: It was confirmed that serum vitamin D status and salivary cathelicidin levels are related. Vitamin D deficient patients who had higher Decayed, Missing, and Filled Teeth index values expressed a lower level of salivary cathelicidin than the control group.

Effects of acrylic dentures on oral mucosa and salivary antimicrobial peptide content in denture wearers

Relevance. Aging of the body leads to the development of an imbalance in the secretory immunity of the oral mucosa, with the loss of natural teeth leading to an even more rapid decline in the host’s oral defense reactions. However, studies on salivary antimicrobial peptides in denture users and their potential role in protecting against the development of inflammation are still scarce at this time.Purpose. To evaluate the effects of full removable acrylic dentures on the oral mucosa and analyze the content of antimicrobial peptides in the saliva of wearers of such dentures.Materials and methods. Sixty-seven (21 men and 46 women) elderly patients (61 to 74 years old) with complete tooth loss were examined and divided into 3 study groups. In the 1st control group the patients did not use any dentures. Patients in groups 2 and 3 were made full removable acrylic dentures for the upper and lower jaws, and in group 2 from the first day of the adaptation period was used domestic denture fixation cream ASEPTA PARODONTAL. Assessment of the denture bed on the hard palate was performed visually using the Schiller – Pisarev test. Microbiological examination for Candida albicans was performed by PCR-diagnostics. The content of antimicrobial peptides in saliva was assessed using ELISA kits by Hycult Biotech.Results. The use of the adhesive cream was found to improve the condition of the palatal mucosa by 25% on the 15th day and by 50% on the 30th day of the adaptation period. Candida albicans was detected in oral material in more than 55% of patients in all groups during their initial examination. In the group of patients using denture fixation cream, a significant decrease in Candida albicans carriage was noted, while an increase in Candida albicans detection of up to 70% was noted in those not using the cream. There was also an increase in the level of cathelicidin LL-37 in the saliva of patients without the use of the cream and with a marked increase in inflammation. One month after dentures in patients without cream use the content of alpha-defensins (HNP 1-3) was significantly lower than that of the group with cream and the control group.Conclusion. On the basis of the carried out clinical and laboratory study, the domestic ACEPTA adhesive cream should be recommended for optimization of the adaptation period to removable acrylic dentures as well as for their permanent use.

The Antimicrobial Peptide LL-37 as a Predictor Biomarker for Periodontitis with the Presence and Absence of Smoking: A Case-Control Study.

A major issue is finding a valid biomarker able to diagnose periodontal disease with the presence and absence of risk factors. Indeed, the association between smoking and periodontal diseases and its impact on the manifestation of antimicrobial peptides has been delineated in clinical and epidemiological investigations. The antimicrobial peptide cathelicidin (LL-37) is pivotal in preserving periodontal health. This investigation examines and contrasts the levels of cathelicidin in the saliva of smokers and nonsmokers of periodontitis. The study also seeks to establish this biomarker's diagnostic ability to differentiate between periodontal health and disease. The study involved the collection of unstimulated saliva samples from 160 participants, comprising 80 patients diagnosed with periodontitis (40 of whom were smokers and 40 were nonsmokers) and 80 periodontitis-free individuals (40 smokers and 40 nonsmokers). The clinical periodontal parameters were assessed, including recording the probing pocket depth, the level of clinical attachment, and the percentage of bleeding on probing. Subsequently, enzyme-linked immunosorbent assays were conducted to quantify the protein levels of LL-37 in the saliva samples obtained from the subjects mentioned above. The highest level of salivary LL-37 was found in the nonsmoker periodontitis (NSP) patients, followed by the group of smoker periodontitis (SP) and then nonsmoker healthy (NSH) group, while the lowest level was found in the healthy smoker (HS) group. At the same time, the LL-37 seems to be a very good biomarker in differentiating periodontal health from disease with the presence and absence of smoking. Periodontitis results in a significant elevation of salivary LL-37 levels in smoker and nonsmoker patients compared to healthy individuals. These levels are positively correlated with the periodontal parameter and can serve as a valuable diagnostic tool to predict periodontitis, whereas smoking significantly reduces these levels.

Expression and significance of serum vitamin D and LL-37 levels in infants with bacterial pneumonia.

To investigate the significance of vitamin D and human antimicrobial peptide LL-37 in the occurrence and development of bacterial pneumonia in infants. From January 2021 to January 2022, 80 infants with bacterial pneumonia were selected, including 33 cases of gram-positive bacterial infection (GP) and 47 cases of gram-negative bacterial infection (GN). During the same period, 40 infants who underwent health examination in The Affiliated Hospital of Hangzhou Normal University served as the healthy control group. On the day of admission, peripheral blood was collected from pneumonia patients, and during physical examination of controls; and serum LL-37 levels were measured by enzyme-linked immunosorbent assay (ELISA) and serum 25-hydroxyvitamin D [25(OH)D] levels were measured by electrochemiluminescence. The differences in serum LL-37 and 25(OH)D levels and their correlation with disease severity were compared. Pearson correlation was used to analyze the correlation between serum 25(OH)D and LL-37 levels in infants with bacterial pneumonia. The levels of 25(OH)D and 25(OH)D deficiency were significantly lower in patients than in controls (all P < 0.05), and the levels of serum LL-37 were significantly higher in pneumonia patients than in controls (P < 0.05). There was no significant difference in serum 25(OH)D and LL-37 levels between cases with GP and GN (all P > 0.05). The serum 25(OH)D level was lower in the severe pneumonia group than in the mild pneumonia group and controls, and the 25(OH)D deficiency rate was higher; the difference was statistically significant (all P < 0.05). The LL-37 level in the severe pneumonia group was lower than that in the mild pneumonia group but higher than that in the control group, and the difference was statistically significant (P < 0.05). The 25(OH)D level was positively correlated with the LL-37 level (r = 0.8, P < 0.05), and the 25(OH)D level was negatively correlated with procalcitonin (PCT) and length of hospital stay (rs = -0.3, -0.3, P < 0.05); the LL-37 level was negatively correlated with PCT and length of hospital stay (rs = -0.4, -0.2, P < 0.05) in infants with bacterial pneumonia. A low level of vitamin D is present in infants with bacterial pneumonia, and its status affects the severity and outcome of pneumonia. The level of LL-37 is increased in infants with bacterial pneumonia, but it shows a downward trend with progression of the disease.

Антимікробні пептиди (HNPs 1-3 та LL-37) як біомаркери активності запального процесу в дітей, хворих на H. pylori-асоційовану виразку дванадцятипалої кишки

Various gastrointestinal and extragastrointestinal diseases are associated with H. pylori in children and adolescents, but the strongest recommendations for testing and treatment are made only in children and adolescents with duodenal ulcer (DU). The inability of natural immune mechanisms to recognize and eliminate H. pylori leads to the development of acute inflammation. The most promising developments so far are studies of the antibacterial effect of endogenous antimicrobial peptides (AP), among which defensines 1-3 (human neutrophil peptides, HNPs 1-3) and cathelicidins (LL-37) are the most important for the human body. Purpose - to investigate the concentration of HNPs 1-3 and LL-37 in the blood of children with DU in order to determine the activity of the inflammatory process of the mucous membrane. Materials and methods. 65 children aged 7-18 years, suffering from DU and 25 healthy children of the corresponding age (comparison group) were examined. The level of HNPs 1-3 and LL-37 was determined in blood plasma by enzyme-linked immunosorbent assay according to the manufacturers instructions. Results. Patients were divided by age, sex, location and size of the ulcer, presence of the H. pylori bacterium. A toxigenic strain of H. pylori was detected in 80.9% of examined children, and the level of HNPs 1-3 in blood plasma was 3 times higher and the level of LL-37 was 2.5 times higher in children with H. pylori-associated DU than in healthy children (p=0.01). Concentrations of HNPs 1-3 and LL-37 in blood plasma were higher in patients with an active inflammatory process in the mucous membrane and were positively correlated with the degree of inflammation activity (r=0.67, p=0.05 and r=0.69, p=0.01). After eradication therapy, AP levels decrease, while the degree of decrease directly depends on the activity of the inflammatory process. Conclusions. Probably higher concentrations of HNPs 1-3 and LL-37 were found in the blood plasma of children with H. pylori-associated DU. Considering the direct correlations between the levels of HNPs 1-3 and LL-37 and the degree of activity of the inflammatory process, these indicators can be used as biomarkers of the adverse course of H. pylori-associated DU. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Cathelicidin LL-37 level in presence and absence of vitamin D in cultured macrophages isolated from elderly women

Introduction: Vitamin D deficiency and frequent infections are the two common worldwide phenomenon among elderly. Recent studies have demonstrated that vitamin D regulates the expression of specific endogenous antimicrobial peptides like cathelicidin LL-37 of macrophages and neutrophils, which is active against a broad spectrum of infectious agents. Therefore, the objective of the present study was to determine the level of cathelicidin LL-37 in macrophages of elderly women (classified according to serum 25(OH)D level) after exposure to Vibrio cholera infection and to find out the effect of 1,25(OH)2D added in vitro. Methods: This study was conducted among 40 randomly selected rural elderly women aged between 60 to 70 years of age. Their vitamin D status was assessed by the estimation of serum 25(OH)D and classified into three groups viz. sufficient (14 members), insufficient (13 members), and deficient (13 members). Later, their peripheral blood mononuclear cells (PBMC) were isolated and cultured from fresh blood. 1,25(OH)2D supplementation was given selectively at a dose of 10 ×10-8 M for 72 hours in the culture media; then exposed to infection and screened according to the objectives of this study. Results: Macrophages in all groups, except vitamin D deficient group, responded significantly in terms of LL-37 release during exposure to Vibrio cholera infection. Considering in vitro 1,25(OH)2D, supplementation responded significantly (p&lt;0.05) in all three groups. Conclusion: Vitamin D can be used as a prophylaxis to enhance cathelicidin LL-37 release for all three groups as in the present study.

Prognostic Impacts of LL-37 in Relation to Lipid Profiles of Patients with Myocardial Infarction: A Prospective Cohort Study.

Background. In vivo studies show that LL-37 inhibits the progression of atherosclerosis and predicts a lower risk of recurrent ischemia in patients with acute myocardial infarction (AMI), which could be mediated by the modulation of lipid metabolism. The current study aimed to investigate the effects of various lipid contents on the prognostic impacts of LL-37 in patients with AMI. Methods. A total of 1567 consecutive AMI patients were prospectively recruited from March 2017 to January 2020. Patients were firstly stratified into two groups by the median level of LL-37 and then stratified by levels of various lipid contents and proprotein convertase subtilisin/kexin type 9 (PCSK9). Cox regression with multiple adjustments was performed to analyze associations between LL-37, lipid profiles, PCSK9, and various outcomes. The primary outcome was major adverse cardiovascular event (MACE), a composite of all-cause death, recurrent MI, and ischemic stroke. Results. During a median follow-up of 786 (726–1107) days, a total of 252 MACEs occurred. A high level of LL-37 was associated with lower risk of MACE in patients with elevated lipoprotein(a) (≥300 mg/L, hazard ratio (HR): 0.49, 95% confidence interval (CI): 0.29–0.86, p = 0.012) or PCSK9 levels above the median (≥47.4 ng/mL, HR: 0.57, 95% CI: 0.39–0.82, p < 0.001), which was not observed for those without elevated lp(a) (<300 mg/L, HR: 0.96, 95% CI: 0.70–1.31, p = 0.781, p interaction = 0.035) or PCSK9 (<47.4 ng/mL, HR: 1.02, 95% CI: 0.68–1.54, p = 0.905, p interaction = 0.032). Conclusions. For patients with AMI, a high level of LL-37 was associated with lower ischemic risk among patients with elevated lp(a) and PCSK9.

The level of antimicrobial peptides in different clinical forms of urinary tract infections in children

The aim. To study the content of antimicrobial peptides in the serum of children with urinary tract infections depending on the clinical form of the disease and to establish their pathogenetic role in the development of various clinical forms of pathology. Materials and methods. The study groups consisted of 84 children (mean age – 10.0 ± 1.3 years). The main group was divided into subgroups: the first subgroup – 17 children with acute pyelonephritis, the second subgroup – 21 patients with chronic pyelonephritis, the third subgroup – 16 patients with acute cystitis, the fourth subgroup – 10 patients with unspecified urinary tract infections. The control group consisted of 20 relatively healthy children. The study of the content of cathelicidin, hepcidin and lactoferrin was performed by enzyme-linked immunosorbent assay. Results. The development of urinary tract infection was accompanied by a statistically significant increase in the content of cathelicidin (P &lt; 0.05). The highest level of serum cathelicidin was registered in children of the first (P &lt;0.05) and third subgroups (P &lt; 0.05). In the other two subgroups, the level of LL-37 had only a trend towards increasing (P &gt; 0.05). The level of hepcidin in the main study group was statistically lower than in the control group (P &lt; 0.05). The development of chronic pyelonephritis and acute cystitis occurred amid a statistically significant decrease in hepcidin levels by 2.5 and 1.7 times (P &lt; 0.01 and P &lt; 0.05, respectively). The level of lactoferrin in the general group was within the control group figures (P &gt; 0.05), however, there was a statistically significant decrease in serum lactoferrin in a subgroup of children with unspecified urinary tract infections (P &lt; 0.05). We determined a relationship between hepcidin and lactoferrin levels in the investigated groups and found a clear direct relationship in a subgroup of children diagnosed with chronic pyelonephritis (r = 0.58, P &lt; 0.01). Conclusions. Each nosological form of urinary tract infection has its own configuration of antimicrobial peptides. The analysis of the relationship between hepcidin and lactoferrin, the antimicrobial peptides that limit the access of the pathogens to serum iron, indicates the synchronization of the body’s defense mechanisms aimed at eliminating the pathogen.

Cord blood antimicrobial peptide LL37 levels in preterm neonates and association with preterm complications

BackgroundCathelicidin/LL-37 plays a significant role in the human immune defense reaction. Preterm human immature organs being exposed to inflammation-induced injury was the critical denominator leading to the common preterm associated complications. Previous study showed LL37 concentration in preterm neonates was lower in tracheal aspirates and breast milk as compared to term infants. An adults study showed decreased LL-37 levels was a risk factor for patients in developing severe chronic obstructive pulmonary disease (COPD). However, little is known about the regulation of human cord blood LL37 in preterm neonates and the association with preterm complications. This study was designed to investigate the concentration of LL37 in cord blood of preterm infants and correlation with preterm complications.MethodsSingleton infants born in June 2017 to August 2021 in the study hospital were enrolled. Maternal and neonatal clinical characteristics were collected. LL37 levels, pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in cord blood and LL37 levels in serum 48–72 hours after birth were measured by enzyme-linked immunosorbent assay. The serum level of LL37 in preterm and term neonates were compared, the perinatal factors possibly affecting the LL37 levels were investigated and the relationship between LL37 level and preterm outcomes were analyzed.ResultsCord blood LL37 levels in preterm infants were lower than that in term neonates. Cord blood LL37 level was positively correlated with gestational age in preterm. Prenatal steroid administration in preterm neonates decreased cord blood LL37 level. LL37 level was obviously lower in patients with bronchopulmonary dysplasia (BPD). Multiple line regression analysis showed higher LL37 level in cord blood was an independent protective factor for BPD. The concentration of pro-inflammatory factor IL-6 was negatively correlated with LL37.ConclusionCord blood LL37 levels increased during gestation and decreased after perinatal steroid usage. Very preterm infants who displayed higher cord blood LL37 level had reduced risk of developing BPD. Regulation of pro-inflammatory cytokine IL-6 may be associated with the protective effect of LL37 on BPD.

The Correlation of Antibacterial Peptides Concentration in Umbilical Cord Blood and Early Onset Sepsis in Preterm Infants.

Umbilical cord blood from singleton preterm infants was collected during delivery, and the concentration of LL37 was measured. C-reactive protein (CRP), white blood cell count (WBC), platelets (PLT), and mean platelet volume (MPV) were determined within 3 days after birth. The differences in LL37, CRP, WBC, PLT, and MPV levels between the two groups were compared. Pearson correlation method was used to analyze the correlation between these factors. The early individual value of each detected index for early onset sepsis was analyzed by ROC curve. The level of LL37 in umbilical cord blood of sepsis group was significantly higher than those in the control group (383.85 ± 46.71 vs. 252.37 ± 83.30 ng/ml). Meanwhile, the levels of CRP, WBC, and MPV in the sepsis group were significantly higher than those in the control group (CRP:5.73 ± 4.19 vs. 2.50 ± 2.77 mg/L; WBC: 13.47 ± 12.35 vs. 6.83 ± 3.55 × 109/L; MPV: 11.20 ± 1.11 vs. 8.90 ± 0.68 fL), the level of PLT was significantly lower than those in the control group (PLT: 161.00 ± 38.51 vs. 241.50 ± 49.85 × 109/L) (P < 0.05). Pearson correlation analysis showed that the expression of LL37 was negatively correlated with PLT level (r = −0.9347, P < 0.0001), and positively correlated with MPV level (r = 0.9463, P < 0.0001). ROC curve analysis showed that the area under curve of LL37 for diagnosis of early onset sepsis was 0.875, the prediction probability was 0.7, the sensitivity was 90.0% and the specificity was 80.0%.

High Human Antimicrobial Peptide LL-37 Level Predicts Lower Major Adverse Cardiovascular Events after an Acute ST-Segment Elevation Myocardial Infarction.

Aims: We previously associated acute ST-elevation myocardial infarction (STEMI) with decreased plasma LL-37 levels. Therefore, this study investigated whether plasma LL-37 levels could predict ischemic cardiovascular events in patients after STEMI. Methods: We prospectively collected peripheral plasma samples and clinical and laboratory data from consecutive patients who presented with STEMI and underwent primary percutaneous coronary intervention at Fuwai Hospital between April and November 2017. Enzyme-linked immunosorbent assay measured plasma LL-37 levels, and we followed the patients for 3 years. Major adverse cardiovascular events (MACEs) were a composite of all-cause mortality, reinfarction, unscheduled revascularization, or ischemic stroke. Results: The study included 302 patients divided into high (≥ median) and low LL-37 level (＜median) groups. The cumulative incidence of MACE (29.1% vs. 12.6%, p=0.0003), all-cause death (12.6% vs. 3.3%, p=0.003), reinfarction (7.1% vs. 2.0%, p=0.04), and unscheduled revascularization (13.0% vs. 5.4%, p=0.04) were higher in the low than those in the high LL-37 level group. Multivariable Cox regression analysis showed that higher LL-37 level independently predicted lower risks of MACE (hazard ratio [HR] 0.390; 95% confidence interval [CI] 0.227–0.669; p＜0.001), all-cause death (HR 0.324; 95%CI 0.119–0.879; p=0.027), and unscheduled revascularization (HR 0.391; 95%CI 0.171–0.907; p=0.027). Conclusions: High basal plasma level of human LL-37 may predict lower 3-year risks of ischemic cardiovascular events in patients after STEMI.

The Association of Early Childhood Caries with Salivary Antimicrobial Peptide LL37 and Mutans Streptococci.

This study aims to determine the relation of salivary LL37 level and mutans streptococci levels in early childhood caries (ECC). A case-control study was performed in children ≤71 months old. Unstimulated whole saliva was collected and the level of salivary LL37 was measured using an enzyme-linked immunosorbent assay kit. The mutans streptococci oral bacteria were isolated from saliva and identified using a modified SB-20 culture medium (SB-20M). Data were analyzed using descriptive statistics, bivariate, and Spearman's rank correlation analysis. The was a variability of salivary LL37 level among the children and the level was significantly associated with age and races. The median (IQR) value of salivary LL37 in caries-free (CF) children was significantly higher 393.50 (580.55) ng/mL compared to 172.50 (234.65) ng/mL in the ECC group. The ECC children exhibited a significantly higher count of S. mutans and S. sobrinus compared to the CF children. An inverse weak correlation between salivary LL37 and dmft was also observed. The low salivary LL37 level and higher S. mutans and S. sobrinus count in ECC supported the protective role of salivary LL37 against dental caries. Further studies are required to explore the definite relation between salivary LL37 levels and dental caries.

Antimicrobial Peptide LL-37 Drives Rosacea-Like Skin Inflammation in an NLRP3-Dependent Manner

Rosacea is a chronic inflammatory skin disease characterized by immune response-dependent erythema and pustules. Although the precise etiology of rosacea remains elusive, its pathogenesis is reportedly associated with an increased level of antimicrobial peptide LL-37. However, molecular mechanisms underlying the progression of rosacea via LL-37 remain poorly understood. Here, we examined the potential role of LL-37 in rosacea-like skin inflammatory phenotypes at a molecular level. Our invitro data demonstrated that LL-37 promotes NLRP3-mediated inflammasome activation in lipopolysaccharide-primed macrophages, indicated by the processing of caspase-1 and IL-1β. LL-37 was internalized into the cytoplasm of macrophages through P2X7 receptor-mediated endocytosis. Intracellular LL-37 triggered the assembly and activation of NLRP3-ASC inflammasome complex by facilitating lysosomal destabilization. Consistent with these invitro results, intradermal LL-37 administration induced invivo caspase-1 activation and ASC speck formation in the skin of Nlrp3-expressing, but not in Nlrp3-deficient, mice. Intradermal injection of LL-37 elicited profound recruitment of inflammatory Gr1+ cells and subsequent skin inflammation. However, LL-37-induced rosacea-like skin inflammation was significantly abrogated in Nlrp3-deficient mice. Furthermore, an NLRP3-specific inhibitor, MCC950, markedly reduced LL-37-triggered rosacea-like phenotypes. Taken together, our findings clearly indicate that NLRP3 inflammasome activation plays a crucial role in LL-37-induced skin inflammation and rosacea pathogenesis.

Diagnostic Predictors of Active Tuberculosis Infection in Diabetic Patients with Latent Tuberculosis: A Review on Cathelicidin and 1,25-dihydroxyvitamin D3

Background: Diabetes Mellitus has been identified as one of factors causing increased risks of latent TB infection. The roles of cathelicidin LL-37, 1.25(OH)2D3 as well as their correlation with specific IFN-γ in latent TB has not been extensively identified. Aims and Objectives: Our study was aimed to identify proportion of latent TB infection in patients with DM and to identify the role of cathelicidin, 1.25(OH)2D3, vitamin D and other clinical factors as predictors for active TB infection in diabetic patients with latent TB. Methods: Our study was conducted in 2 stages. The first-stage study was a cross-sectional study to identify the proportion of latent TB infection in patients with DM without any history of TB, which was continued with a case-control study to identify the roles of predictive biomarkers (cathelicidin LL-37, 25(OH)D3, 1.25(OH)2D3 and IFN-γ) as well as clinical predictive factors for active TB infection in diabetic patients with latent TB. Results: Out of 242 diabetic patients without any history of TB who underwent screening test for latent TB, there were 78 (33.2%) subjects with a diagnosis of latent TB and 1 subject was diagnosed with active TB. There was significant association on the level of cathelicidin LL-37 in DM patient with latent TB, active TB and without TB infection (23.49 ng/mL vs. 49.6 ng/mL vs. 10.46 ng/mL, P 9.5% and cathelicidin LL-37 levels of > 30 ng/mL were predictors for latent TB into active TB in DM patients. Conclusion: Cathelicidin LL-37 can serve as a biomarker of latent TB progressiveness in patients with DM.

Characterization of Pro- and Anti-Inflammatory Tissue Factors in Rosacea: A Pilot study

Rosacea is a chronic inflammatory skin disease mainly affecting the facial skin. Our aim was to determine the appearance of pro- and anti- inflammatory cytokines in rosacea-affected facial tissue. Materials and Methods: Rosacea tissue were obtained from eight patients (aged 35 to 50 years). The control group (CG) included four facial skin samples (49 to 70 years). Routine staining and immunohistochemistry for IL-1, IL-10, LL-37, HBD-2, and HBD-4 proceeded. Results: Inflammation was observed in all the rosacea samples. A statistically significant difference was seen between epithelial HBD-2 positive cells in comparison to the control. There was a strong positive correlation between HBD-4 in the epithelium and HBD-4 in the connective tissue, IL-10 in the epithelium and IL-1 in the connective tissue, and IL-1 in the epithelium and IL-10 in the connective tissue. Conclusion: Increased levels of IL-10 and decreased levels of IL-1 show the balance between anti- and pro-inflammatory tissue responses. A significant amount of HBD-2 in the epithelium proves its important role in the local immune response of rosacea-affected tissue. The last effect seems to be intensified by the elevated level of LL-37 in the epithelium.

Clinical and immunological aspects of early reproductive losses in patients with adenomyosis

Aim. To evaluate the clinical and immunological features of the early gestational period in patients with adenomyosis.Materials and methods. The study included 110 patients with first spontaneous pregnancy in 6–9 weeks. 75 pregnant women with a history of grade 1 adenomyosis were divided into two groups: group 1 comprised 43 patients with a threatened miscarriage, group 2 included 32 patients without a threat of pregnancy termination. Group 3 (control) included 35 pregnant women without a burdened history with a physiological pregnancy course. The cytokine profile of peripheral blood and cervical mucus was studied, as well as the level of LL-37 (cathelicidin) antimicrobial peptide.Results. A pro-inflammatory shift of the cytokine balance as well as increased pro-angiogenic activity, determined by the VEGF-R2 / VEGF-A ratio, were observed in pregnant women with grade 1 adenomyosis during a physiologically ongoing pregnancy in the 1st trimester. A threatened miscarriage in the presence of adenomyosis is accompanied by statistically significant changes in the cytokine profile, a decrease in pro-angiogenic activity and an increased level of LL-37 in cervical mucus.Conclusion. Pregnancy with adenomyosis of the 1st degree, in the absence of other risk factors, is complicated by a threatened miscarriage in more than half of cases. The revealed clinical and immunological aspects of early reproductive losses require further in-depth study, since these signs may indicate the presence of chronic endometritis in patients with adenomyosis not determined by non-invasive research methods.