Progressive bronchiectasis and CMC in a patient with STAT1 GOF — a rare case of primary immunodeficiency

Bronchiestasis is a common complication developing in patients with primary immunodeficiency disorders. AD GOF STAT1 defi-ciency is characterized by CMC, repeated infections, and autoimmunity. It is the most frequently diagnosed entity in a group of PIDs with CMC. Here, we present the first Polish case of a female patient with early-onset bronchiestasis accompanied by CMC and a severe course of infections who was genetically diagnosed with AD GOF1 STAT1 mutation at the age of 15

Stężenie interleukiny-6, receptora dla interleukiny-6 i glikoproteiny 130 oraz cytokin zależnych od limfocytów Th17 u pacjentek z cukrzycą ciążową

Introduction: Interleukin-6 (IL-6) is a pleiotropic cytokine which signals through a cell surface receptor complex consisting of a cognatereceptor subunit (IL-6R) and glycoprotein 130 (gp130), which is considered an antagonist to the IL-6R/IL-6 pathway. The aim of the present study was to assess IL-6/IL-6R/gp130 system and Th17 associated cytokines in different time points during and after pregnancy in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT).Material and methods: Serum levels of IL-6, sIL6R, sgp130, IL-17 and IL-23 were measured in 91 women divided into three groups: GDMin the 24th–28th week of gestation (visit 1), NGT at the 1st visit and GDM in the 29th-32nd week, and NGT at both visits.Results: The patients with GDM recognised at the 1st visit had significantly higher IL-6 (p = 0.02) and sgp130 (p = 0.03) concentrations than had the women with NGT, whereas the women with GDM diagnosed at the 2nd visit had elevated sIL-6R concentrations (p = 0.03). The patients with low sIL-6R but high sgp130 concentration had significantly higher glucose levels (p = 0.04) and lower IL-6 values (p = 0.04) than had the patients with low sIL-6R and sgp130 concentrations. IL-17 and IL-23 were detected in approximately one-third of the population studied. A trend towards higher IL-17 levels was observed in the subjects with GDM, but the differences were not significant.Conclusions: Our results suggest that an increased serum sgp130 concentration in the patients with GDM might represent a compensatory mechanism, controlling intracellular IL-6 signalling and preventing the activation of the IL-6/IL-6R pathway.Wstęp: Interleukina-6 (IL-6) jest plejotropową cytokiną, która przekazuje sygnał do wnętrza komórki za pośrednictwem receptora błonowego złożonego z właściwej podjednostki receptorowej (Il-6R) i glikoproteiny 130 (gp130), uważanej za antagonistę kompleksu IL-6R//IL-6. Celem pracy była analiza szlaku IL-6/IL-6R/gp130 i cytokin zależnych od limfocytów Th17 w II i III trymestrze ciąży oraz po porodzie u pacjentek z cukrzycą ciążową i prawidłową tolerancją glukozy.Materiał i metody: Dokonano pomiaru stężenia IL-6, IL6R, gp130, IL-17 i IL-23 w surowicy 91 kobiet podzielonych na 3 podgrupy: pacjentki z cukrzycą ciążową zdiagnozowaną w 24.–28. tygodniu ciąży (wizyta 1), pacjentki z prawidłową tolerancją glukozy w trakcie 1 wizyty i cukrzycą ciążową rozpoznaną w 29.–32. tygodniu ciąży oraz pacjentki z prawidłową tolerancją glukozy w trakcie obu wizyt.Wyniki: U pacjentek z cukrzycą ciążową rozpoznaną w trakcie 1 wizyty wykazano istotnie wyższe stężenia IL-6 (p = 0,02) i gp130(p = 0,03) w porównaniu z kobietami z prawidłową tolerancją glukozy, podczas gdy pacjentki z cukrzycą ciążową rozpoznaną w trakcie 2 wizyty charakteryzowały się wyższym stężeniem IL-6R (p = 0,03). U pacjentek z niskim stężeniem IL-6R i wysokim stężeniem gp130 obserwowano znamiennie wyższe wartości glikemii (p = 0,04) i niższe stężenia IL-6 (p = 0,04) w porównaniu z kobietami z niskimi stężeniami IL-6R i sgp130. Obecność krążących IL-17 i IL-23 stwierdzono u około 1/3 spośród badanych kobiet. Wykazano również tendencję do wyższych stężeń IL-17 u pacjentek z cukrzycą ciążową, różnice nie były jednak istotne statystycznie.Wnioski: Wyniki sugerują, że podwyższone stężenie gp130, obserwowane u kobiet z cukrzycą ciążową, może stanowić mechanizm kompensacyjny, zapobiegający nadmiernej aktywacji szlaku IL-6/IL-6R

Rainbow trout proteins as potential source of biologically active peptides

Bioaktywne peptydy pochodzące z białek żywności mogą pełnić funkcje regulatorów układu sercowo-naczyniowego, nerwowego czy pokarmowego. Do najlepiej znanych bioaktywnych peptydów należą fragmenty białek o właściwościach przeciwnadciśnieniowych, z których większość to inhibitory enzymu konwertującego angiotensynę I (inhibitory ACE). Celem badań było określenie profilu potencjalnej aktywności biologicznej wybranych białek pstrąga tęczowego (Oncorhynchus mykiss) przy użyciu narzędzi bioinformatycznych dostępnych w bazie BIOPEP. Materiał i metody. Sekwencje aminokwasowe 7 białek pochodzących z tkanki mięśniowej pstrąga pobrano z bazy danych UniProt. Dla każdej z wybranych sekwencji wyznaczono częstotliwość występowania biologicznie aktywnych fragmentów (parametr A) oraz potencjalną aktywność biologiczną (parametr B) białek. Następnie przeprowadzono symulowaną proteolizę in silico z wykorzystaniem 6 enzymów proteolitycznych. Wyniki. Największą liczbę sekwencji biopeptydów (1999) zidentyfikowano w kolagenie pstrąga, w tym najwięcej fragmentów o aktywności inhibitora ACE. Białko to charakteryzowało się największą wartością parametrów A (0,7316) i B (0,1651) dla peptydów o aktywności inhibitora ACE ze wszystkich przebadanych sekwencji. Ficyna i papaina uwalniały największą liczbę bioaktywnych fragmentów z badanych białek pstrąga tęczowego. Wnioski. Na podstawie otrzymanych wyników można stwierdzić, że kolagen jest najbogatszym źródłem peptydów bioaktywnych z przebadanych sekwencji aminokwasowych białek pstrąga tęczowego. Ficyna i papaina mogą być wykorzystane do produkcji hydrolizatów lub peptydów o potencjalnej aktywności biologicznej z tkanki mięśniowej pstrąga.Bioactive peptides derived from food proteins are considered as regulators of the cardiovascular, nervous, and digestive systems. Peptides with antihypertensive activity are the best recognized bioactive peptides, of which angiotensin I-converting enzyme inhibitors (ACE inhibitors) are the most known. The aim of presented study was to determine the profile of the potential biological activity of a selected rainbow trout (Oncorhynchus mykiss) protein using bioinformatics tools from the Bioactive Proteins and Peptides database – BIOPEP. Material and methods. Amino acid sequences of 7 proteins originated from trout meat tissue were taken from the UniProt database. The frequency of occurrence of bioactive fragments in protein sequence (parameter A) and potential biological activity of protein (parameter B) were determined for all selected proteins using a procedure built into the BIOPEP database. Then, in silico proteolysis was performed using 6 proteolytic enzymes, which acted separately. Results. It was found that the largest number of bioactive peptides sequences (1,999) was hidden in trout collagen, including the largest number of ACE inhibitors. Collagen was characterized by the highest value of the parameter A (0.7316) and B (0.1651) for fragments with ACE inhibitory activity. Ficin and papain released the largest number of bioactive fragments from the trout proteins tested. Conclusions. Based on these results, it can be concluded that collagen is the richest source of bioactive peptides when compared with the trout proteins studied. Ficin and papain can be used to produce hydrolysates or peptides with potential biological activity from trout meat tissue

Multi-Bioactivity of Protein Digests and Peptides from Oat (Avena sativa L.) Kernels in the Prevention of the Cardiometabolic Syndrome

The aim of this study was to characterize the digests and peptides derived from oat kernel proteins in terms of their major enzyme inhibitory activities related to the prevention of cardiometabolic syndrome. It also entailed the characteristics of antioxidant bioactivity of the analyzed material. The study was carried out using coupled in silico and in vitro methods. The additional goal was to investigate whether identified peptides can pervade Caco-2 cells. Based on the results of bioinformatic analysis, it was found that the selected oat proteins may be a potential source of 107 peptides with DPP-IV and/or ACE inhibitory and/or antioxidant activity. The duodenal digest of oat kernels revealed multiple activities. It inhibited the activities of the following enzymes: DPP-IV (IC50 = 0.51 vs. 10.82 mg/mL of the intact protein), α-glucosidase (IC50 = 1.55 vs. 25.20 mg/mL), and ACE (IC50 = 0.82 vs. 34.52 mg/mL). The DPPH• scavenging activity was 35.7% vs. 7.93% that of the intact protein. After in silico digestion of oat proteins, 24 peptides were selected for identification using LC-Q-TOF-MS/MS. Among them, 13 sequences were successfully identified. One of them, i.e., VW peptide, exhibited triple activities, i.e., DPP-IV and ACE inhibitory and DPPH• scavenging activity. The multifunctional peptides: PW, TF, VF, and VW, were identified in the basolateral samples after transport experiments. Both in silico and in vitro analyses demonstrated that oat kernel proteins were the abundant sources of bioactive digests and peptides to be used in a diet for patients suffering from cardiometabolic syndrome

Progressive Bronchiectasis and CMC in a Patient with STAT1 GOF—A Rare Case of Primary Immunodeficiency

Bronchiestasis is a common complication developing in patients with primary immunodeficiency disorders. AD GOF STAT1 defi-ciency is characterized by CMC, repeated infections, and autoimmunity. It is the most frequently diagnosed entity in a group of PIDs with CMC. Here, we present the first Polish case of a female patient with early-onset bronchiestasis accompanied by CMC and a severe course of infections who was genetically diagnosed with AD GOF1 STAT1 mutation at the age of 15

Increased Maternal and Cord Blood Betatrophin in Gestational Diabetes.

The aim of the study was to compare maternal and cord blood levels of betatrophin--a new peptide potentially controlling beta cell growth--as well as in its mRNA expression in subcutaneous adipose tissue, visceral adipose tissue and placental tissue obtained from pregnant women with normal glucose tolerance (NGT) and gestational diabetes (GDM).Serum betatrophin and irisin concentrations were measured by ELISA in 93 patients with GDM and 97 women with NGT between 24 and 28 week of gestation. Additionally, maternal and cord blood betatrophin and irisin, as well as their genes (C19orf80 and Fndc5) expression were evaluated in 20 patients with GDM and 20 women with NGT at term.In both groups, serum betatrophin concentrations were significantly higher in the patients with GDM than in the controls (1.91 [1.40-2.60] ng/ml vs 1.63 [1.21-2.22] ng/ml, p=0.03 and 3.45 [2.77-6.53] ng/ml vs 2.78 [2.16-3.65] ng/ml, p=0.03, respectively). Cord blood betatrophin levels were also higher in the GDM than in the NGT group (20.43 [12.97-28.80] ng/ml vs 15.06 [10.11-21.36] ng/ml, p=0.03). In both groups betatrophin concentrations in arterial cord blood were significantly higher than in maternal serum (p=0.0001). Serum irisin levels were significantly lower in the patients with GDM (1679 [1308-2171] ng/ml) than in the healthy women between 24 and 28 week of pregnancy (1880 [1519-2312] ng/ml, p=0.03). Both C19orf80 and Fndc5 mRNA expression in fat and placental tissue did not differ significantly between the groups studied.Our results suggest that an increase in maternal and cord blood betatrophin might be a compensatory mechanism for enhanced insulin demand in GDM

Serum irisin concentration in patients with normal glucose tolerance (NGT) and gestational diabetes (GDM) from Group 2; data were analyzed by Mann-Whitney U test and shown as medians with interquartile ranges.

<p>Serum irisin concentration in patients with normal glucose tolerance (NGT) and gestational diabetes (GDM) from Group 2; data were analyzed by Mann-Whitney U test and shown as medians with interquartile ranges.</p

Clinical characteristics of Group 1 during pregnancy.

<p>Data are shown as medians (interquartile range), NGT, normal glucose tolerance, GDM, gestational diabetes mellitus, differences between NGT and GDM groups were analyzed by Mann-Whitney U test.</p><p>Clinical characteristics of Group 1 during pregnancy.</p

Clinical characteristics of Group 2.

<p>Data are shown as medians (interquartile range), NGT, normal glucose tolerance, GDM, gestational diabetes mellitus, differences between NGT and GDM groups were analyzed by Mann-Whitney U test.</p><p>Clinical characteristics of Group 2.</p

Serum betatrophin concentration in patients with normal glucose tolerance (NGT) and gestational diabetes (GDM) from Group 2; data were analyzed by Mann-Whitney U test and shown as medians with interquartile ranges.

<p>Serum betatrophin concentration in patients with normal glucose tolerance (NGT) and gestational diabetes (GDM) from Group 2; data were analyzed by Mann-Whitney U test and shown as medians with interquartile ranges.</p