September 25, 2022

Selective Display of a Chemoattractant Agonist on Cancer Cells Activates the Formyl Peptide Receptor 1 on Immune Cells

Current immunotherapeutics often work by directing components of the immune system to recognize biomarkers on the surface of cancer cells to generate an immune response.
However, Bio Med Frontiers variable changes in biomarker distribution and expression can result in uneven patient response. The development of a more universal tumor-homing strategy has the potential to improve selectivity and extend therapy to cancers with decreased expression or absence of specific biomarkers.
Here, we designed a bifunctional agent that exploits the inherent acidic microenvironment of most solid tumors to selectively graft the surface of cancer cells with a formyl peptide receptor ligand (FPRL).
Our approach is based on the pH(Low) Insertion Peptide (pHLIP), a unique peptide that selectively targets tumors in vivo by anchoring onto cancer cells in a pH-dependent manner.
We establish that selectively remodeling cancer cells with a pHLIP-based FPRL activates formyl peptide receptors on recruited immune cells, potentially initiating an immune response towards tumors.

N-terminal pro brain natriuretic peptide reference values in community-dwelling older adults.

Available upper reference levels (URLs) in older adults for N-terminal pro brain natriuretic peptide (NT-proBNP), an established biomarker for heart failure, are mainly based on small samples. We aimed to identify NT-proBNP URL in a population-based reference sample of individuals aged ≥65 years.
 We analysed established NT-proBNP predictors using quantile regression among 2459 participants of two-independent population-based cohorts located in Germany, Our Supplier the Activity and Function in the Elderly Study (ActiFE, n = 1450) and the Study of Health in Pomerania (SHIP-TREND-0, n = 1009). Based on predictors a reference population of 441 subjects (ActiFE, n = 227; SHIP-TREND-0, n = 214) without history of diabetes, cardiovascular, or pulmonary diseases and with systolic blood pressure (BP) <140 mmHg, diastolic BP ≥60 and ≤90 mmHg, haemoglobin in men ≥14 and ≤18 g/dL and in women ≥12 and ≤16 g/dL, GFR ≥60 mL/min/1.73 m2 , CRP <5 mg/L, BMI ≥18 and ≤33 kg/m2 , and hs-cTnI <40 ng/L were built with NT-proBNP median levels and 97.5% quantiles reported stratified by sex and age.
In a secondary analysis the URL among 97 SHIP-TREND-0 participants with a left ventricular ejection fraction (LVEF) ≥50 and no diastolic dysfunction were estimated.
The median age in the identified reference sample was 70 years, with 41.9% and 40.2% male participants in ActiFE and SHIP-TREND-0, respectively.
We observed an age-dependent increment of NT-proBNP levels with higher values in women compared to men. Notably, NT-proBNP levels were >125 ng/L in 165 participants (37.4%), with NT-proBNP URL (97.5% quantiles) equal to 663, 824, 592, and 697 ng/L in men, and 343, 463, 2641, 1276 ng/L in women for ages 65-69, 70-74, 75-79, and 80+ years, respectively. In the secondary analysis with a LVEF ≥50 and no diastolic dysfunction (35 men and 62 women) NT-proBNP levels >125 ng/L were still observed in 38 (39.2%) participants.
This reference sample of apparently healthy asymptomatic older adults showed an age-related increment of NT-proBNP levels with URL markedly higher than the European Society of Cardiology recommended cut-off of 125 ng/L for the diagnosis of heart failure in ambulatory settings.
Identifying URL in those ≥80 years remains complex.
Our results attempt to provide a frame for the further investigation of age-specific NT-proBNP cut-offs in older adults.
Considering the demographic changes, further evaluation of NT-proBNP URL in larger samples of older adults followed by the validation of age-specific cut-off values for the identification of heart failure in those 65 years or older are urgently needed.

A novel antimicrobial peptide derived from human BPIFA1 protein protects against Candida albicans infection.

  • Bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1) is an innate immunity defense protein. Our previous studies proved its antibacterial and antiviral effects, but its role in fungi remains unknown. The study aimed to identify antifungal peptides (AFP) derived from BPIFA1, and three antimicrobial peptides (AMP1-3) were designed.
  • The antifungal effects were proved by growth inhibition assay. AMP3 activity was confirmed by germ tube growth experiment and XTT assay. Its effects on cell wall and membrane of Candida albicans were assessed by tannic acid and Annexin V-FITC/PI double staining, respectively.
  • Additionally, scanning electron microscope (SEM) and transmission electron microscopy (TEM) were used for morphological and ultrastructural observation.
  • The expression of ALS1, EAP1, and SUN41 was tested by qPCR. Ultimately, three AMPs could fight against C. albicans in vitro, and AMP3 was highly effective. It functioned by destroying the integrity of cell wall and normal structure of cell membrane.
  • It also inhibited biofilm formation of C. albicans. In addition, AMP3 down-regulated the expression of ALS1, EAP1, and SUN41, those are known to be involved in virulence of C. albicans. Altogether, the study reported successful development of a novel AFP, which could be used as a new strategy for antifungal therapy.

Novel Antioxidant Peptides from Crassostrea Hongkongensis Improve Photo-Oxidation in UV-Induced HaCaT Cells.

Enzymatic hydrolysates from Oysters (OAH) display multiple biological activities. Previously, a 3~5 KDa oyster ultrafiltration component (OUP) showed a high property of preventing skin oxidation. Subsequently, we identified specific peptides with such activity.
OUP was fractionated stepwise by Sephadex-G25 and RP-HPLC, and active fractions were screened using UV-irradiated HaCaT cells.
The most active fractions (OP5-3) were analyzed by LC-MS/MS and a total of 17 peptides were identified. Results from mass spectrometry showed that OP5-3 consisted of peptides with a molecular weight range of 841.51-1786.92 Da.
Six of these peptides were synthesized for validating the activity of resisting skin oxidation in the same cell model.
All six peptides showed varying degrees of antioxidant activity, while pretreatment of HaCaT cells with AIVAEVNEAAK alleviated UV cytotoxicity, inhibited metalloproteinase 1 (MMP-1) expression, and showed the highest activity to resist UV-induced skin photo-oxidation among these peptides.
In addition, results from molecular docking analysis of MMP-1 with AIVAEVNEAAK showed that AIVAEVNEAAK suppresses its enzymatic activity by directly interacting with MMP-1 and thus exhibit anti-photoaging activity.

Combining Prognostic Nutritional Index and Brain Natriuretic Peptide as a Predicting Tool for Heart Transplantation.

Our study aimed to evaluate the potential of the prognostic nutritional index (PNI) and Brain natriuretic peptide (BNP) in predicting the prognosis of heart transplantation (HTx).
We retrospectively investigated 489 patients undergoing HTx between 2015 and 2020 in our center. The relationship between preoperative index and prognosis was analyzed respectively, the optimal cut-off values for preoperative PNI and BNP level were evaluated with receiver operating curve analysis.
Uni-variate analysis and multivariate analysis were used to compare baseline data (sex, age, diagnosis, etc.) of groups divided by the level of PNI and BNP.
Propensity score matching (PSM) was applied to eliminate bias.
We calculated the C-index from the prediction efficiency of PNI and BNP. During the period, 489 recipients undergoing HTx in our center were included according to the inclusion criteria; 383 (78.3%) males and 106 (21.7%) females were included in this study, with a median age of 47.57 years old. The ROC curve showed that the optimal cut-off values of each indicator were verified as 49.345 for PNI, and 4397.500 for BNP.

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The multivariate analyses indicated that PNI (p = 0.047), BNP (p = 0.024), age (p = 0.0023), and waiting time (p = 0.012) were risk factors for all-cause death after HTx. Propensity score matching generated 116 pairs based on PNI level and 126 pairs based on BNP level, and the results showed that OS (overall survival) was significantly correlated with PNI (n = 232, p = 0.0113) and BNP (n = 252, p = 0.0146). Our study implied that higher PNI and lower BNP level had direct correlation with better survival after HTx. Combining PNI and BNP together would be a potential clinical preoperative instrument to predict the survival of patients after HTx, especially in short-term survival.

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