Survey of Dipeptidyl Peptidase III Inhibitors: From Small Molecules of Microbial or Synthetic Origin to Aprotinin

Dipeptidyl peptidase III (DPP III) was originally thought to be a housekeeping enzyme that contributes to intracellular peptide catabolism. More specific roles for this cytosolic metallopeptidase, in the renin-angiotensin system and oxidative stress regulation, were confirmed, or recognized, only recently. To prove indicated (patho)physiological functions of DPP III in cancer progression, cataract formation and endogenous pain modulation, or to reveal new ones, selective and potent inhibitors are needed. This review encompasses natural and synthetic compounds with experimentally proven inhibitory activity toward mammalian DPP III. Except for the polypeptide aprotinin, all others are small molecules and include flavonoids, coumarin and benzimidazole derivatives. Presented are current strategies for the discovery or development of DPP III inhibitors, and mechanisms of inhibitory actions. The most potent inhibitors yet reported (propioxatin A and B, Tyr-Phe- and Phe-Phe-NHOH, and JMV-390) are active in low nanomolar range and contain hydroxamic acid moiety. High inhibitory potential possesses oligopeptides from the hemorphin group, valorphin and tynorphin, which are poor substrates of DPP III. The crystal structure of human DPP III-tynorphin complex enabled the design of the transition-state peptidomimetics inhibitors, effective in low micromolar concentrations. A new direction in the field is the development of fluorescent inhibitor for monitoring DPP III activity

Variations of Total Phenolic Content in Honey Samples Caused by Different Calibration Lines

In the review of total phenolic contents (TPCs) of acacia, lime, and chestnut honey samples from several literature sources, large differences were noticed, which cannot be attributed only to seasonal or geographical variations. The dependence of TPC on the process of construction of the calibration line is illustrated in the measurement of acacia, lime, and chestnut honey types from Croatia and neighbouring countries (Serbia, Italy, and Hungary). TPCs are determined for 39 uni-floral honey samples by four calibration lines and four TPC values are obtained for each honey sample. Obtained results are compared mutually, as well as with the literature results for honey samples of the same type. For each honey type, the average of all determined TPCs determined in this study is in the middle of literature values. The average TPC values for chestnut honey samples were found to be 1.5 and 3 times higher than those for lime and acacia, respectively. The effects of two factors regularly considered in the determination of calibration lines are analyzed: (1) the concentration range of the standard chemical and (2) whether the calibration line is drawn through the origin, or not. The final results strongly depend on these two factors that should be considered in future TPC estimations. This work is licensed under a Creative Commons Attribution 4.0 International License

The Comparative Analysis of the Impact of N-Acetyl-L-Cysteine and its Combination with Propolis on Quality-of-Life in Patients with Acute Bronchitis

Objectives: Evidence suggests that both N-Acetyl-L-cysteine (NAC) and NAC in combination with propolis (NAC-P) reduce symptoms of acute bronchitis and improve Health-Related Quality of Life (HRQoL). This study aimed to compare the impact of NAC and NAC-P therapy on acute bronchitis patients' quality of life. Design, setting, and subjects: A randomized, single-blind parallel-group study was achieved at Municipal Institute for Lung Diseases and Tuberculosis Medical Centre, Belgrade, Serbia. Patients with acute bronchitis were randomly assigned into two groups to receive NAC (200mg three times a day) or NAC-P (200mg+80mg three times a day) orally for a minimum of ten days. HRQoL of patients was measured twice (at two appointments) using the Leicester Cough Questionnaire (LCQ) and EQ-5D questionnaires. Results: The study included 42 patients in the NAC-P group and 43 in the NAC group. The correlation between the LCQ total score and Health State Values (HSV) was positive and statistically significant in the NAC-P and the NAC groups at the second appointment. The differences between values of EQ-5D scores were slightly higher (but not statistically significant) in the NAC-P group compared to the NAC group, indicating a more remarkable improvement of HRQoL using NAC-P. Conclusion: NAC-P and NAC may improve HRQoL in patients with acute bronchitis. EQ-5D scale values indicated that NAC-P might improve quality of life more than NAC. Our results may provide the basis for better decision-making by healthcare professionals when choosing the right therapy

UTJECAJ DUŽINE I TEMPERATURE SKLADIŠTENJA NA SVOJSTVA SJEMENA I KLIJANACA ENGLESKOG LJULJA (Lolium perenne L.)

A research of seed storage period and storage temperature effects upon the seed quality and seedlings traits for the seeds of two perennial ryegrass cultivars (Bartwingo and Calibra) was conducted. Seeds were stored in hermetically sealed glass dishes at four different temperatures (room temperature about 21°C, 10°C, -20°C and -80°C) and for three different periods (9, 18 and 30 months). Upon completing the storage treatments the seed and seedling traits were tested by the rolled filter paper method. The research has revealed significant effects of storage temperature, storage period, cultivar and interactions upon all the investigated traits. The highest germination energy, germination and seedling plumule length were observed after the shortest (9-month) storage period, and the least after the longest (30-month) storage period. Seedling radicule was longest after 18-month storage period and shortest after 30 months. All the investigated traits had the highest values when seeds were stored at -80°C, and the least when the seeds were stored at room temperature. Cultivar Bartwingo has shown a greater germination energy and germination but Calibra has shown a greater seedling radicule and plumule length.Istraživanje utjecaja dužine i temperature skladištenja na svojstva sjemena i klijanaca engleskoga ljulja provedeno je sa sjemenom dva kultivara (Bartwingo i Calibra). Sjeme je pohranjeno u hermetički zatvorene staklene posude na sobnoj temperaturi te na 10, -20 i -80°C. Navedena svojstva mjerena su nakon 9, 18 i 30 mjeseci skladištenja metodom rolanoga filter papira. Dobiven je značajan utjecaj temperature, dužine skladištenja i kultivara te njihove interakcije za sva isptivana svojstva. Najveće vrijednosti za energiju klijanja i klijavost sjemena te dužinu stabljike dobivene su nakon 9 mjeseci skladištenja, a najmanje nakon 30 mjeseci. Korijen klijanaca bio je najduži nakon 18, a najkraćinakon 30 mjeseci skladištenja. Sva ispitivana svojstva imala su najveće vrijednostiskladištenjem na -80°C, a najmanje na sobnoj temperaturi. Kultivar Bartwingo imao je veću energiju klijanja i klijavost, a Calibra dužinu korijena i klijanaca

Aprotinin interacts with substrate-binding site of human dipeptidyl peptidase III

Human dipeptidyl peptidase III (hDPP III) is a zinc-exopeptidase of the family M49 involved in final steps of intracellular protein degradation and in cytoprotective pathway Keap1-Nrf2. Biochemical and structural properties of this enzyme have been extensively investigated, but the knowledge on its contacts with other proteins is scarce. Previously, polypeptide aprotinin was shown to be a competitive inhibitor of hDPP III hydrolytic activity. In the present study, aprotinin was first investigated as a potential substrate of hDPP III, but no degradation products were demonstrated by MALDI-TOF mass spectrometry. Subsequently, molecular details of the protein-protein interaction between aprotinin and hDPP III were studied by molecular modeling. Docking and long molecular dynamics (MD) simulations have shown that aprotinin interacts by its canonical binding epitope with the substrate binding cleft of hDPP III. Thereby, free N-terminus of aprotinin is distant from the active-site zinc. Enzyme-inhibitor complex is stabilized by intermolecular hydrogen bonding network, electrostatic and hydrophobic interactions which mostly involve constituent amino acid residues of the hDPP III substrate binding subsites S1, S1', S2, S2' and S3'. This is the first study that gives insight into aprotinin binding to an metallopeptidas

Svojstva klijanaca i biljaka engleskog ljulja nakon 5 godina skladištenja sjemena na različitim temperaturama

The aim of this research was to investigate the seed quality of perennial ryegrass after 5-year storage treatments at various temperatures. The seeds of two cultivars of perennial ryegrass (diploid Bartwingo and tetraploid Calibra) were used, and the storage treatment temperatures were: room temperature (about 21°C), 10°C, -20°C and -80°C. Seed quality traits (germination and seedlings’ root and shoot lengths) were determined before and after the storage treatments. Additionally, early development traits in mini-pots during the first two months of development (emergence, plantlet height, plantlet root length, fresh weight of roots and shoots) were tested. The research has shown significant effects of storage temperatures to all the investigated traits of seed quality and plantlets development. The highest average values for germination and seedling root and shoot lengths were obtained after the storage at -80°C, and the lowest after storage at room temperature. The highest average values for emergence, plantlet height and roots and shoots fresh weights were obtained after the storage at -20°C, while the root length was greatest after the storage at -80°C. Tetraploid cultivar Calibra had significantly greater average values than diploid Bartwingo for all the investigated traits except for germination and primary shoot length.Istraživanja su provedena s ciljem utvrđivanja kvalitete sjemena engleskoga ljulja skladištenoga 5 godina na različitim temperaturama. Korišteno je sjeme dvaju kultivara (diploid Bartwingo i tetraploid Calibra), koje je skladišteno na sobnoj te na temperaturama 10, -20 i -80°C. Prije i nakon skladištenja u klima komori utvrđena su svojstva sjemena i klijanaca (klijavost, dužine korijena i stabljike klijanaca). Također, nakon skladištenja, sjeme je posijano u kontejnere od stiropora. Određeno je nicanje, a nakon 2 mjeseca svojstva biljaka: visina, dužina korijena, svježa masa korijena i nadzemnoga dijela. Dobiven je značajan utjecaj temperature na sva ispitivana svojstva sjemena, klijanaca i biljaka. U prosjeku za kultivare najveće vrijednosti za klijavost sjemena, dužinu korijena i stabljike klijanaca dobivene su kod sjemena skladištenoga na -80°C, a najniže skladištenjem na sobnoj temperaturi. Najveće prosječne vrijednosti za nicanje, svježu masu korijena i nadzemnoga dijela biljaka dobivene su sjetvom sjemena skladištenoga na -20°C; visina biljaka bila je najmanja od sjemena skladištenoga na sobnoj temperaturi, a između ostalih vrijednosti nije bilo razlike. Dužina korijena bila je najveća sjetvom sjemena skladištenoga na -80°C. Nicanje, dužina korijena, svježa masa korijena i nadzemnoga dijela bile su najniže na sobnoj temperaturi. Tetraploidni kultivar Calibra imao je značajno veće prosječne vrijednosti za sva ispitivana svojstva, osim klijavosti sjemena i dužene stabljike klijanaca

ANTIOKSIDATIVNI ODGOVOR U LISTU JAGODA (Fragaria x ananassa Duch) NA TRETMANE BIOSTIMULATORIMA UZ REDUCIRANU GNOJIDBU DUŠIKOM I KALIJEM

Strawberry cultivar Elsanta was grown in peat based substrate in a green house. Full dose and 50% reduced nitrogen and potassium fertilization were applied during fruit bearing period in spring, along with biostimulators Viva®, Megafol® and their combination. The specific activities of guaiacol peroxidase (GPXs; EC 1.11.1.7), catalase (CATs; EC 1.11.1.6), ascorbate peroxidase (APXs; EC 1.11.1.11) and glutathione reductase (GRs; EC 1.6.4.2) in strawberry leaf were stimulated by biostimulators and reduced fertilization. The strongest link seen here was between the enzymes of ascorbate-glutathione cycle (APXs and GRs), which were positively related to trifoliate leaf fresh mass (TLFM). The highest TLFM was observed in Megafol® treated plants.Sorta jagoda Elsanta uzgajana je u tresetnom supstratu u plasteniku. Puna doza i 50% smanjena doza dušika i kalija primjenjene su tijekom proljetnoga plodonošenja, uz primjenu biostimulatora Viva®, Megafol® i njihove kombinacije. Specifične aktivnosti gvajakol peroksidaze (GPXs; EC 1.11.1.7), katalaze (CATs; EC 1.11.1.6), askorbat peroksidaze (APXs; EC 1.11.1.11) i glutation reduktaze (GRs; EC 1.6.4.2) u listu jagode bile su značajno više poslije tretiranja biostimulatorima i reduciranom gnojidbom. Najjača povezanost uočena u ovom istraživanju, bila je između enzima askorbat-glutation ciklusa (APXs i GRs), koji su bili u pozitivnoj korelaciji s masom svježega lista (TLFM). Najveća masa svježega lista (TLFM) uočena je na biljkama tretiranim Megafolom®

ANTIOKSIDATIVNI ODGOVOR U LISTU JAGODA (Fragaria x ananassa Duch) NA TRETMANE BIOSTIMULATORIMA UZ REDUCIRANU GNOJIDBU DUŠIKOM I KALIJEM

Strawberry cultivar Elsanta was grown in peat based substrate in a green house. Full dose and 50% reduced nitrogen and potassium fertilization were applied during fruit bearing period in spring, along with biostimulators Viva®, Megafol® and their combination. The specific activities of guaiacol peroxidase (GPXs; EC 1.11.1.7), catalase (CATs; EC 1.11.1.6), ascorbate peroxidase (APXs; EC 1.11.1.11) and glutathione reductase (GRs; EC 1.6.4.2) in strawberry leaf were stimulated by biostimulators and reduced fertilization. The strongest link seen here was between the enzymes of ascorbate-glutathione cycle (APXs and GRs), which were positively related to trifoliate leaf fresh mass (TLFM). The highest TLFM was observed in Megafol® treated plants.Sorta jagoda Elsanta uzgajana je u tresetnom supstratu u plasteniku. Puna doza i 50% smanjena doza dušika i kalija primjenjene su tijekom proljetnoga plodonošenja, uz primjenu biostimulatora Viva®, Megafol® i njihove kombinacije. Specifične aktivnosti gvajakol peroksidaze (GPXs; EC 1.11.1.7), katalaze (CATs; EC 1.11.1.6), askorbat peroksidaze (APXs; EC 1.11.1.11) i glutation reduktaze (GRs; EC 1.6.4.2) u listu jagode bile su značajno više poslije tretiranja biostimulatorima i reduciranom gnojidbom. Najjača povezanost uočena u ovom istraživanju, bila je između enzima askorbat-glutation ciklusa (APXs i GRs), koji su bili u pozitivnoj korelaciji s masom svježega lista (TLFM). Najveća masa svježega lista (TLFM) uočena je na biljkama tretiranim Megafolom®