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Abstract Background FMF (Familial Mediterranean Fever) is the most prevalent autoinflammatory disease. It arises due to mutations in the pyrin-encoding MEFV gene. Prolidase, an enzyme culpable of splitting the bonds of proline-containing dipeptides, is essential for matrix remodeling, collagen turnover, and cell proliferation. It has a crucial role in inflammation. Aim To compare serum levels of prolidase between FMF children during the attack-free periods and healthy children and to correlate it with different FMF disease criteria and inflammatory marker, also to investigate if it can serve as a marker for subclinical inflammation. Results Forty-one children diagnosed with FMF and 41 sex and age-matched apparently healthy children as a control group were included in this study, serum prolidase was measured by ELISA. The mean ± SD serum level of prolidase among FMF patients was 0.6 ± 0.2 mU/ml × 104, while among the control group, it was 1.3 ± 1.4 mU/ml × 104, a statistically significant difference existed between both groups, p value = 0.001. The level of serum prolidase was not correlated with FMF severity score, inflammatory markers, and other FMF disease criteria. Conclusion Serum prolidase level was lower among FMF patients during the attack-free period than in the healthy control group, it was not correlated with disease severity and was not predictive of the presence of subclinical inflammation. Further studies are needed to highlight the role of serum prolidase in FMF children.

Background: FMF (Familial Mediterranean Fever) is the most prevalent autoinflammatory disease. It arises due to mutations in the pyrin-encoding MEFV gene. Prolidase, an enzyme culpable of splitting the bonds of proline-containing dipeptides, is essential for matrix remodeling, collagen turnover, and cell proliferation. It has a crucial role in inflammation. Aim: To compare serum levels of prolidase between FMF children during the attack-free periods and healthy children and to correlate it with different FMF disease criteria and inflammatory marker, also to investigate if it can serve as a marker for subclinical inflammation. Results: Forty-one children diagnosed with FMF and 41 sex and age-matched apparently healthy children as a control group were included in this study, serum prolidase was measured by ELISA. The mean ± SD serum level of prolidase among FMF patients was 0.6 ± 0.2 mU/ml × 104, while among the control group, it was 1.3 ± 1.4 mU/ml × 104, a statistically significant difference existed between both groups, p value = 0.001. The level of serum prolidase was not correlated with FMF severity score, inflammatory markers, and other FMF disease criteria. Conclusion: Serum prolidase level was lower among FMF patients during the attack-free period than in the healthy control group, it was not correlated with disease severity and was not predictive of the presence of subclinical inflammation. Further studies are needed to highlight the role of serum prolidase in FMF children. [ABSTRACT FROM AUTHOR]

Simple Summary: Proline metabolism has been found to play an important role in neoplasms, but little is known about proline in gliomas or in the normal brain. This work investigates how the metabolism of proline in the brain and in gliomas of WHO grade 4 (GG4) may differ. A total of 20 pairs of samples were studied, consisting of both tumor and unaffected brain tissue, partially removed to make a surgical corridor. The levels of proline oxidase/proline dehydrogenase (POX/PRODH), Δ1-pyrroline-5-carboxylate reductases (PYCR1/2/3), prolidase (PEPD), and metalloproteinase-2 and -9 (MMP-2 and MMP-9) were measured. Proline concentration was evaluated. GG4 levels of POX/PRODH were found to be lower, while PYCR1, PEPD, and MMPs were significantly higher than in brain tissue. In GG4, proline concentration was 358% higher. The results confirm changes in proline metabolism in GG4, with a low-POX/PRODH/high-PYCR pattern like that in other neoplasms. High levels of PEPD and MMPs are in keeping with GG4 aggressiveness. Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline metabolism in the brain are somewhat historical. This study aims to investigate alterations of proline metabolism in gliomas of WHO grade 4 (GG4) in the context of the brain. A total of 20 pairs of samples were studied, consisting of excised tumor and unaffected brain tissue, obtained when partial brain resection was required to reach deep-seated lesions. Levels of proline oxidase/proline dehydrogenase (POX/PRODH), Δ1-pyrroline-5-carboxylate reductases (PYCR1/2/3), prolidase (PEPD), and metalloproteinases (MMP-2, MMP-9) were assessed, along with the concentration of proline and proline-related metabolites. In comparison to normal brain tissue, POX/PRODH expression in GG4 was found to be suppressed, while PYCR1 expression and activity of PEPD, MMP-2, and -9 were upregulated. The GG4 proline concentration was 358% higher. Hence, rewiring of the proline metabolism in GG4 was confirmed for the first time, with a low-POX/PRODH/high-PYCR profile. High PEPD and MMPs activity is in keeping with GG4-increased collagen turnover and local aggressiveness. Further studies on the mechanisms of the interplay between altered proline metabolism and the GG4 microenvironment are warranted. [ABSTRACT FROM AUTHOR]

ObjectivesSmoking causes inflammation, thickening, and narrowing of the airways. This inflammatory process is a reaction to free radicals and oxidants. Smoking affects collagen metabolism and tissue remodeling. Prolidase enzyme hydrolyzes iminodipeptides with hydroxyproline and C terminal proline. It plays a crucial role in the metabolism of collagen and the remodeling of the matrix. The present study aims to reveal the association of prolidase with inflammation caused by smoking and to compare serum prolidase levels with oxidative-antioxidative status in healthy individuals.MethodsA total of 76 participants (38 smokers and 38 nonsmokers) were involved in the present study. Serum cotinine levels were measured to show the exposure to nicotine in tobacco smoke by using the competitive inhibition enzyme immunoassay method. Serum prolidase, total oxidant status (TOS), and total antioxidant status (TAS) were determined by the enzyme-linked immunosorbent (ELISA) method, respectively. The correlation between smoking, serum prolidase levels, TOS, and TAS was investigated.ResultsTAS and serum prolidase levels of smokers were considerably lower than those in non-smokers (p

Plasma prolidase levels change as a determining factor for coronary artery disease and heart valve insufficiency. The aim of this study is to compare plasma prolidase levels in two groups with or without mitral regurgitation who underwent coronary artery bypass surgery (CABS). For this purpose, 45 patients who underwent CABS were included in the study; patients without mitral valve insufficiency who underwent CABS (25 patients) Group 1, patients with mitral valve insufficiency who underwent CABS (20 patients) Group 2. Venous blood was taken from all patients before and after CABS and their prolidase levels were measured. Preoperative and postoperative serum prolidase levels in group 1 were 1038.2 and 1289.43 U/L, respectively. In group 2, preoperative and postoperative serum prolidase levels were 1084.07 and 1337.74 U/L, respectively. A significant difference was found between preoperative and postoperative plasma prolidase levels of Group 1 and Group 2 included in the study (p<0.05). Plasma prolidase level was high in both groups. However, pre- and postoperative serum prolidase levels were found to be higher in patients with mitral valve insufficiency in Group 2. In conclusion, in this study, it was determined that the plasma prolidase level was higher in patients with mitral valve insufficiency who underwent CABS. [ABSTRACT FROM AUTHOR]

Cancer of the corpus uteri and cervix uteri, collectively ranks second among new cancer cases in women after breast cancer. Therefore, investigation of new anticancer agents and identifying new molecular targets presents a challenge to improve effectiveness of chemotherapy. In this study, antiproliferative activity of flavonoids derived from the buds of silver birch and downy birch was evaluated in endometrial cancer Ishikawa cells and cervical cancer HeLa cells. It was found that flavanol santin reduced viability of both cell lines better than other flavonoids, including apigenin and luteolin. Moreover, this activity was slightly higher than that induced by the chemotherapy drug, cisplatin. Santin promoted intrinsic and extrinsic apoptosis pathways in cancer cells, but it had low toxicity in normal fibroblasts. The mechanisms of impairing cancer cell viability included induction of oxidative proline catabolism, however in different ways in the cell lines used. In HeLa cells, increase of proline oxidation was due to activation of p53 leading to proline oxidase upregulation. In contrast, in Ishikawa cells, having basal proline oxidase level significantly higher than HeLa cells, santin treatment decreased its expression. Nevertheless, proline oxidation was induced in these cells since santin increased expression and activity of prolidase, an enzyme providing proline from protein degradation. In both cell lines, proline oxidation was associated with generation of reactive oxygen species leading to reduction in cell viability. Our findings reveal the involvement of proline oxidase in induction of apoptosis by santin and identify a role of prolidase in proline oxidase-dependent apoptosis.

Aim: Chronic obstructive pulmonary disease (COPD) is a disease characterized by irreversible airway flow limitation and chronic airway inflammation. We aimed to investigate the clinical importance of serum prolidase enzyme, which is an indicator of collagen degradation, and Carbonic anhydrase (CA) III enzyme, which has an important function in acid-base regulation, in patients with COPD Methods : In this study, 56 stable COPD patients and 32 healthy subjects without smoking history and comorbidities were included. Serum CA III and prolidase enzyme levels were compared between the two groups. Results: The statistical difference was not found between the two groups in terms of prolidase enzyme levels (p=0.831). There was a statistically significant increase in CA III levels in the COPD group (p=0.001). There were moderate positively correlation between CAIII with partial pressure of carbon dioxide in blood (pCO2) and negatively correlation between CA III with partial pressure of oxygen in blood (pO2) in COPD patients (r:0.302, p lt;0.025; r:-0.314, p:0.02). Conclusions: We think that there is an important clinical relationship between CA III and COPD, and therefore, CA III may be a candidate biomarker in the follow-up of COPD.

To evaluate the serum level of prolidase, which is a marker of fibrogenic activity, in women with idiopathic primary ovarian insufficiency (POI). This is a prospective case-control study. Serum prolidase level was compared between the study group including 68 women with POI and control group including 65 normally menstruating women. Serum proline and hydroxyproline levels were also compared. Correlation analyses were performed between the prolidase level and POI related parameters including estradiol (E), follicle stimulating hormone (FSH), anti-mullerian hormone (AMH) levels, and presence of POI family history. Serum prolidase and proline level were significantly increased in women with the diagnosis of POI compared to the control group (1082.57 (147.53) vs 981.13 (223.26) U/L, 233.30 (83.16) vs 218.94 (82.59) µmol/L, respectively). Prolidase level found to have significant correlations with AMH, E, FSH levels, and presence of POI family history (r = −0.49, p = 0.001; r = −0.39, p = 0.001; r = 0.42, p = 0.001; r = 0.22, p = 0.01; respectively). In receiver operating characteristics analysis, prolidase was shown to be a discriminative factor for POI at 1031.14 U/L cut-off value with 75 % sensitivity and 65 % specificity. The area under curve was 0.71 [(95 % CI: 0.62–0.79), p = 0.001]. The current study revealed increased prolidase level in women with POI. Serum prolidase level was also negatively correlated with the serum AMH level. Considering the present findings, prolidase may be a candidate molecule in assessment of POI cases. [ABSTRACT FROM AUTHOR]

Background: Decreased collagen biosynthesis and increased collagenolysis can cause ectasia progression in the arterial walls. Prolidase is a key enzyme in collagen synthesis; a decrease in prolidase activity or level may decrease collagen biosynthesis, which may contribute to ectasia formation. Considering that, the variations in PEPD gene encoding prolidase enzyme were evaluated by analyzing next-generation sequencing (NGS) for the first time together with known risk factors in coronary artery ectasia (CAE) patients. Methods: Molecular analysis of the PEPD gene was performed on genomic DNA by NGS in 76 CAE patients and 76 controls. The serum levels of prolidase were measured by the sandwich-ELISA technique. Results: Serum prolidase levels were significantly lower in CAE group compared to control group, and it was significantly lower in males than females in both groups (p < 0.001). On the other hand, elevated prolidase levels were observed in CAE patients in the presence of diabetes (p < 0.001), hypertension (p < 0.05) and hyperlipidemia (p < 0.05). Logistic regression analysis demonstrated that the low prolidase level (p < 0.001), hypertension (p < 0.02) and hyperlipidemia (p < 0.012) were significantly associated with increased CAE risk. We identified four missense mutations in the PEPD gene, namely G296S, T266A, P365L and S134C (novel) that could be associated with CAE. The pathogenicity of these mutations was predicted to be "damaging" for G296S, S134C and P365L, but "benign" for T266A. We also identified a novel 5′UTR variation (Chr19:34012748 G>A) in one patient who had a low prolidase level. In addition, rs17570 and rs1061338 common variations of the PEPD gene were associated with low prolidase levels in CAE patients, while rs17569 variation was associated with high prolidase levels in both CAE and controls (p < 0.05). Conclusions: Our findings indicate that the low serum prolidase levels observed in CAE patients is significantly associated with PEPD gene variations. It was concluded that low serum prolidase level and associated PEPD mutations may be potential biomarkers for the diagnosis of CAE. [ABSTRACT FROM AUTHOR]

The potential of recombinant human prolidase (rhPEPD) to induce wound healing in an experimental model of IL-1β-induced inflammation in human fibroblasts was studied. It was found that rhPEPD significantly increased cell proliferation and viability, as well as the expression of the epidermal growth factor receptor (EGFR) and downstream signaling proteins, such as phosphorylated PI3K, AKT, and mTOR, in the studied model. Moreover, rhPEPD upregulated the expression of the β1 integrin receptor and its downstream signaling proteins, such as p-FAK, Grb2 and p-ERK 1/2. The inhibition of EGFR signaling by gefitinib abolished rhPEPD-dependent functions in an experimental model of inflammation. Subsequent studies showed that rhPEPD augmented collagen biosynthesis in IL-1β-treated fibroblasts as well as in a wound healing model (wound closure/scratch test). Although IL-1β treatment of fibroblasts increased cell migration, rhPEPD significantly enhanced this process. This effect was accompanied by an increase in the activity of MMP-2 and MMP-9, suggesting extracellular matrix (ECM) remodeling during the inflammatory process. The data suggest that rhPEPD may play an important role in EGFR-dependent cell growth in an experimental model of inflammation in human fibroblasts, and this knowledge may be useful for further approaches to the treatment of abnormalities of wound healing and other skin diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Caffeine, an alkaloid agent, has been globally used regularly in drinks, for the reduction in skin cancers and wrinkle formation. As a result of the previous, attempts have been carried out to use caffeine in cosmetology due to its antioxidant and UV ray protection effects. Our aim was to evaluate the effect of caffeine on collagen resynthesis via its effect on proline and prolidase biosynthesis on mice, orally and topically as mesoporous silica at three levels, and the influence on UV protection. In skin biopsies of orally and topically treated mice, the following was assessed using ELISA and Western blot techniques, the activity of prolidase, together with the concentrations of proline, beta integrin, insulin growth factor, protein kinases beta, and mitogen-activated protein kinase. Moreover, we loaded the caffeine on mesoporous silica and assessed the aforementioned parameters together with checkpoint kinase 1 and Rad3-related protein. Results Caffeine promoted collagen resynthesis in a dose-dependent manner. The mechanism of this process was found at the level of prolidase activity as caffeine significantly increased the enzyme activity. Caffeine also had a protective effect against UV exhibited by the over-expression of beta integrin, insulin growth factor together with the under-expression of protein kinases beta, mitogen-activated protein kinase, checkpoint kinase 1, and Rad3-related protein. Conclusions Our study revealed the superiority of SYL-C12 (mesoporous silica-loaded caffeine gel), compromising the high level of the three independent factors, in terms of the measured responses in mesoporous silica with caffeine. Moreover, caffeine promoted collagen resynthesis with significant protective effect against UV apoptotic damage.

This article aims to explain the altered oxidative status and thiol/disulfide homeostasis before and after surgery in children with congenital heart disease (CHD).

Although inflammation is the first step in wound healing, it contributes to the down-regulation of collagen biosynthesis delaying the process of tissue regeneration. The study was conducted to evaluate the effects of platelet-rich plasma (PRP) on interleukin-1β (IL-1β) – dependent inhibition of collagen synthesis, prolidase activity, and β1-integrin signaling in cultured human skin fibroblasts. PRP was obtained using the SmartPReP®2 Autologous Platelet Concentrate+ System. Collagen biosynthesis and prolidase activity were measured in confluent human skin fibroblast cultures with IL-1β, PRP, hyaluronic acid (HA), and mixtures of IL-1β with PRP or HA. Immunofluorescence bioimaging analysis was employed to evaluate the expression of β1 integrin receptor, cyclooxygenase-2 (COX-2), and nuclear factor- κB (NF-κB) protein. Incubation of fibroblasts with 2% PRP for 24 h contributed to about a 500% increase in collagen biosynthesis and a significant increase in the expression of β1-integrin receptor and prolidase activity, compared to the control cells. In the cells treated with IL-1β, collagen biosynthesis, β1-integrin receptor expression, and prolidase activity were decreased while COX-2 and NF-κB expressions were significantly increased. All these processes were recovered to control values by PRP or HA; however, PRP was found to act more effectively than HA. It was found that PRP counteracted IL-1β -dependent inhibition of collagen synthesis through the recovery of β1-integrin receptor expression and prolidase activity and down-regulation of COX-2 and NF-κB expressions in cultured fibroblasts. The data suggest that PRP evokes anti-inflammatory activity that is desirable in tissue regeneration. [ABSTRACT FROM AUTHOR]

[Display omitted] • Prolidase represents a valuable biological target. • Few ligands for prolidase have been identified so far. • Triggering prolidase has a great therapeutic potential. • Modified aminoacids are among the most promising ligands for prolidase. Prolidase (EC.3.4.13.9) is a Mn+2-dependent dipeptidase that is well known to play a crucial role in several physiological and pathological processes affecting humans. More in particular, this enzyme is involved in the cleavage of proline- and hydroxyproline-containing dipeptides (imidodipeptides), providing a fine regulation of the homeostasis of these two amino acids. Hyperactivity or deficiency of prolidase have been clearly associated to the development and progress of several acute and chronic syndromes (e.g. chronic liver fibrosis, viral and acute hepatitis, cancer, neurological disorders, inflammation, skin diseases, intellectual disability, respiratory infection). Thus, targeting prolidase and modulating its activity is an intriguing field of research with a great therapeutic potential for the next future and for the design of specific and selective drugs. Prolidase can be exploited in two essential ways: as an activator of proline containing prodrugs and by direct interaction. In this latter case, few specific ligands for the title enzyme have been described, but with no reports about their structure–activity relationship. The aim of this comprehensive review is to gather all available information on prolidase targeting so far reported in the literature, to rationalize the observed data and effect into a preliminary structure-relationship picture, to comment about the effectiveness of each reported ligands, and to address future research activities providing new potential and putative natural, semisynthetic, and purely synthetic molecules able to trigger prolidase as the main biological target. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies of various types of cancers have found proline metabolism to be a key player in tumor development, involved in basic metabolic pathways, regulating cell proliferation, survival, and signaling. Here, we systematically searched the literature to find data on proline metabolism in malignant glial tumors. Despite limited availability, existing studies have found several ways in which proline metabolism may affect the development of gliomas, involving the maintenance of redox balance, providing essential glutamate, and affecting major signaling pathways. Metabolomic profiling has revealed the importance of proline as a link to basic cell metabolic cycles and shown it to be correlated with overall survival. Emerging knowledge on the role of proline in general oncology encourages further studies on malignant gliomas. Background: Proline has attracted growing interest because of its diverse influence on tumor metabolism and the discovery of the regulatory mechanisms that appear to be involved. In contrast to general oncology, data on proline metabolism in central nervous system malignancies are limited. Materials and Methods: We performed a systematic literature review of the MEDLINE and EMBASE databases according to PRISMA guidelines, searching for articles concerning proline metabolism in malignant glial tumors. From 815 search results, we identified 14 studies pertaining to this topic. Results: The role of the proline cycle in maintaining redox balance in IDH-mutated gliomas has been convincingly demonstrated. Proline is involved in restoring levels of glutamate, the main glial excitatory neurotransmitter. Proline oxidase influences two major signaling pathways: p53 and NF- κB. In metabolomics studies, the metabolism of proline and its link to the urea cycle was found to be a prognostic factor for survival and a marker of malignancy. Data on the prolidase concentration in the serum of glioblastoma patients are contradictory. Conclusions: Despite a paucity of studies in the literature, the available data are interesting enough to encourage further research, especially in terms of extrapolating what we have learned of proline functions from other neoplasms to malignant gliomas. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to explore the significance of serum prolidase enzyme activity and oxidative stress in women with unexplained infertility (UEI). Methods: In this case‐control study (n = 160; 86 cases; 74 controls) prolidase enzyme activity and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and vitamin E were measured in plasma using enzyme‐linked immunosorbent assays. Results: Prolidase enzyme activity and TAS levels were particularly higher in the patient group (P = 0.013, P = 0.001, respectively). Decreased OSI levels were detected in the patient group (P = 0.001). There was a positive relationship of prolidase with vitamin E in both patient and control groups (r = 0.892, P = 0.001, and r = 0.659, P = 0.001, respectively). A positive, but weak, relationship was identified between prolidase activity and TOS levels and also between vitamin E and TOS levels in the UEI group (r = 0.265, P = 0.049, and r = 0.288, P = 0.014, respectively). No association was found between prolidase and TOS levels or between vitamin E and TOS levels in the control group (r = 0.0097, P = 0.527, and r = 0.085, P = 0.610, respectively). Conclusion: Our results showed an association between serum prolidase activity and oxidative stress in UEI patients. Further studies including greater groups are required to show the role of reactive oxygen species in UEI. This work demonstrated that increased serum prolidase activity and oxidative stress markers were associated with unexplained infertility. [ABSTRACT FROM AUTHOR]

Introduction: Tinnitus is defined as the perception of sound in the head or in the head in the absence of external sounds. The cause of tinnitus is still unknown. Objective: We aimed to compare the serum levels of total oxidant status, total antioxidant status, serum prolidase enzyme activity and the oxidative stress index in patients with tinnitus to those of normal subjects. Methods: Twenty five patients with tinnitus (mean age 34.3) and 25 healthy controls (mean age 37.2) were included in the study. Results: Total oxidant status levels in the patient group were significantly higher than in the control group (p = 0.037). The mean total oxidant status value was 2.54 ± 0.95 mmoL/L in the patient group, and 2.06 ± 0.98 mmoL/L in the control group. The mean oxidative stress index level was 0.22 ± 0.10 AU in the patient group, while it was 0.17 ± 0.08 AU in the control group. Oxidative stress index was significantly higher in the patient group (0.026). There was no significant difference between the groups in terms of total antioxidant status values (p = 0.838). The mean serum prolidase enzyme activity level was 202.74 ± 33.56 U/L in the patient group and 175.46 ± 42.68 U/L in the control group. Serum prolidase enzyme activity levels in the patient group were significantly higher than in the control group (0.040). Conclusion: We detected that the total oxidant status, oxidative stress index and serum prolidase enzyme activity levels were higher in patients with tinnitus when compared to the healthy controls. This finding suggests that oxidative stress index and serum prolidase enzyme activity may play a role in the etiopathogenesis of tinnitus. Resumo: Introdução: O zumbido é definido como a percepção de um som na cabeça na ausência de sons externos. A causa do zumbido ainda é desconhecida. Objetivo: Comparar os níveis séricos do estado oxidante total, estado antioxidante total, atividade da enzima prolidase sérica e o índice de estresse oxidativo em pacientes com zumbido e em indivíduos normais. Método: Foram incluídos no estudo 25 pacientes com zumbido (média de 34,3 anos) e 25 controles saudáveis (média de 37,2 anos). Resultados: Os níveis do estado oxidante total no grupo de pacientes foram significantemente maiores do que no grupo controle (p = 0,037). O valor médio do estado oxidante total foi de 2,54 ± 0,95 mmoL/L no grupo de pacientes e de 2,06 ± 0,98 mmoL/L no grupo controle. O nível médio de índice de estresse oxidativo foi de 0,22 ± 0,10 AU no grupo de pacientes, enquanto no grupo controle foi de 0,17 ± 0,08 AU. O índice de estresse oxidativo foi significantemente maior no grupo de pacientes (0,026). Não houve diferença significante entre os grupos em relação aos valores do estado antioxidante total (p = 0,838). O nível médio de atividade da enzima prolidase sérica foi de 202,74 ± 33,56 U/L no grupo de pacientes e de 175,46 ± 42,68 U/L no grupo controle. Os níveis de atividade da enzima prolidase sérica no grupo de pacientes foram significantemente maiores do que no grupo controle (0,040). Conclusão: Detectamos que os níveis de estado oxidante total, índice de estresse oxidativo e atividade da enzima prolidase sérica foram maiores nos pacientes com zumbido quando comparados aos controles saudáveis. Esse achado sugere que o índice de estresse oxidativo e a atividade da enzima prolidase sérica podem desempenhar um papel na etiopatogenia do zumbido.

Introduction. Familial Mediterranean Fever (FMF) is an autoinflammatory disease. Prolidase is a specific imidodipeptidase that plays a role in collagen degradation, and an important role in inflammation and wound healing. Hypoxia-inducible factor-1α (HIF-1) is an important protein in the regulation of immunological response, hemostasis, vascularization. The aim of the study was to compare serum prolidase and HIF-1α levels in patients with FMF in attack-free period and healthy control group.

The potential of recombinant human prolidase (rhPEPD) to induce wound healing in an experimental model of IL-1β-induced inflammation in human fibroblasts was studied. It was found that rhPEPD significantly increased cell proliferation and viability, as well as the expression of the epidermal growth factor receptor (EGFR) and downstream signaling proteins, such as phosphorylated PI3K, AKT, and mTOR, in the studied model. Moreover, rhPEPD upregulated the expression of the β1 integrin receptor and its downstream signaling proteins, such as p-FAK, Grb2 and p-ERK 1/2. The inhibition of EGFR signaling by gefitinib abolished rhPEPD-dependent functions in an experimental model of inflammation. Subsequent studies showed that rhPEPD augmented collagen biosynthesis in IL-1β-treated fibroblasts as well as in a wound healing model (wound closure/scratch test). Although IL-1β treatment of fibroblasts increased cell migration, rhPEPD significantly enhanced this process. This effect was accompanied by an increase in the activity of MMP-2 and MMP-9, suggesting extracellular matrix (ECM) remodeling during the inflammatory process. The data suggest that rhPEPD may play an important role in EGFR-dependent cell growth in an experimental model of inflammation in human fibroblasts, and this knowledge may be useful for further approaches to the treatment of abnormalities of wound healing and other skin diseases.

Recent studies on the regulatory role of amino acids in cell metabolism have focused on the functional significance of proline degradation. The process is catalysed by proline dehydrogenase/proline oxidase (PRODH/POX), a mitochondrial flavin-dependent enzyme converting proline into ∆1-pyrroline-5-carboxylate (P5C). During this process, electrons are transferred to electron transport chain producing ATP for survival or they directly reduce oxygen, producing reactive oxygen species (ROS) inducing apoptosis/autophagy. However, the mechanism for switching survival/apoptosis mode is unknown. Although PRODH/POX activity and energetic metabolism were suggested as an underlying mechanism for the survival/apoptosis switch, proline availability for this enzyme is also important. Proline availability is regulated by prolidase (proline supporting enzyme), collagen biosynthesis (proline utilizing process) and proline synthesis from glutamine, glutamate, α-ketoglutarate (α-KG) and ornithine. Proline availability is dependent on the rate of glycolysis, TCA and urea cycles, proline metabolism, collagen biosynthesis and its degradation. It is well established that proline synthesis enzymes, P5C synthetase and P5C reductase as well as collagen prolyl hydroxylases are up-regulated in most of cancer types and control rates of collagen biosynthesis. Up-regulation of collagen prolyl hydroxylase and its exhaustion of ascorbate and α-KG may compete with DNA and histone demethylases (that require the same cofactors) to influence metabolic epigenetics. This knowledge led us to hypothesize that up-regulation of prolidase and PRODH/POX with inhibition of collagen biosynthesis may represent potential pharmacotherapeutic approach to induce apoptosis or autophagic death in cancer cells. These aspects of proline metabolism are discussed in the review as an approach to understand complex regulatory mechanisms driving PRODH/POX-dependent apoptosis/survival. [ABSTRACT FROM AUTHOR]

Objective: The effects of erythropoietin (EPO) which has been frequently studied as an anti-epileptic agent, on peripheral tissues have not been investigated. This study investigated the effects on malondialdehyde (MDA), advanced protein oxidation products (AOPP), superoxide dismutase (SOD), prolidase and sialic acid (SA) levels in the heart, kidney and liver tissues of EPO pretreatment in pentylenetetrazole (PTZ)-induced seizures. Material and Method: Thirty three male adult rats were divided into three groups. A saline-injected control group, a 60 mg/kg PTZ-injected group to induce seizures and a 3000 IU/kg EPO-injected group 24 hours before seizures. After seizure severity and seizure latency were scored, the rats sacrificed, the tissues were immediately removed for biochemical analyses. Results: The PTZ-induced seizures increased MDA in kidney (p<0.01) and AOPP in liver (p<0.05) but didn’t alter these markers in heart tissue. In all three tissues, SOD didn’t change due to seizures. The SA levels increased in the heart (p<0.001), decreased in the kidney (p<0.001), and were unchanged in liver. Prolidase increased (p<0.05) only in kidney, and was unchanged in other tissues. EPO-pretreatment decreased seizure severity and increased seizure latency. It prevented the increase in MDA in the kidney (p<0.01) but increased AOPP (p<0.05) and decreased SOD (p<0.01) and further increased prolidase more than the seizures increased (p<0.01). EPO-pretreatment prevented the increase in AOPP in the liver (p<0.05) but was ineffective in PTZ-induced SA changes in the heart and kidney. Conclusion: We think that the increase in the heart SA level in seizures is an original finding and deserves investigation in the context of seizure-related cardiac arrhytmias. Also, despite the EPO’s anti-seizure effect, increased protein oxidaiton and prolidase, especially in the kidney, is an other important finding that needs further research. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate oxidative stress in patients with peripheral vertigo by measuring serum prolidase, malondialdehyde (MDA) and catalase levels. Methods: A total of 30 patients (age: 60 <) with peripheral vertigo and 30 healthy subjects were recruited. Blood samples were collected from both groups and serum prolidase levels were measured using enzyme-linked immunosorbent assay (ELISA). MDA and catalase levels were measured by the spectrophotometric method. Results: The most common cause of vertigo was BPPV (53.3%), followed by Ménière's disease (16.6%), vestibular neuritis (13.3%), lateral semicircular canal fistula (3.3%), and idiopathic vertigo (13.3%). Mean serum prolidase activity and MDA levels were significantly higher in the vertigo patients than in the control subjects (P < 0.05); however, there was no statistically significant difference in mean serum catalase levels between the groups (P > 0.05). Conclusion: We concluded that serum prolidase and MDA levels may be used as markers of oxidative stress in patients with peripheral vertigo. [ABSTRACT FROM AUTHOR]

Prolidase (peptidase D), encoded by the PEPD gene, is a ubiquitously expressed cytosolic metalloproteinase, the only enzyme capable of cleaving imidodipeptides containing C-terminal proline or hydroxyproline. Prolidase catalyzes the rate-limiting step during collagen recycling and is essential in protein metabolism, collagen turnover, and matrix remodeling. Prolidase, therefore plays a crucial role in several physiological processes such as wound healing, inflammation, angiogenesis, cell proliferation, and carcinogenesis. Accordingly, mutations leading to loss of prolidase catalytic activity result in prolidase deficiency a rare autosomal recessive metabolic disorder characterized by defective wound healing. In addition, alterations in prolidase enzyme activity have been documented in numerous pathological conditions, making prolidase a useful biochemical marker to measure disease severity. Furthermore, recent studies underscore the importance of a non-enzymatic role of prolidase in cell regulation and infectious disease. This review aims to provide comprehensive information on prolidase, from its discovery to its role in health and disease, while addressing the current knowledge gaps.

To compare prolidase enzyme activity (PEA) in serum and polyp specimens of patients with nasal polyps obtained before and after the oral steroid therapy. Thirty three patients with nasal polyps (39 ± 13 years) received 1 mg/kg of oral steroids. Serum samples were collected from each patient, but nasal polyp specimens could be obtained only from 23 patients (38 ± 13 years) before and after the oral steroid therapy. PEA was measured by ELISA method. Serum PEA values were 210 (176–242) U/L and 184 (147–217) U/L before and after the oral steroid therapy, respectively (p = 0.015). Polyp tissue PEA was 1337 (738–2130) U/g and 871 (590–1663) U/g before and after the oral steroid therapy, respectively (p = 0.429). In patients with nasal polyps, significantly lower serum PEA after the oral steroid therapy may be a consequence of the role of prolidase enzyme in inflammatory processes which are important for the development of nasal polyps. More comprehensive studies with larger sample sizes are needed to elucidate the role of PEA in the pathogenesis of nasal polyps. [ABSTRACT FROM AUTHOR]

Prolidase (EC.3.4.13.9) is a dipeptidase known nowadays to play a pivotal role in several physiological and pathological processes. More in particular, this enzyme is involved in the cleavage of proline- and hydroxyproline-containing dipeptides (imidodipeptides), thus finely regulating the homeostasis of free proline and hydroxyproline. Abnormally high or low levels of prolidase have been found in numerous acute and chronic syndromes affecting humans (chronic liver fibrosis, viral and acute hepatitis, cancer, neurological disorders, inflammation, skin diseases, intellectual disability, respiratory infection, and others) for which the content of proline is well recognized as a clinical marker. As a consequence, the accurate analytical determination of prolidase activity is of greatly significant importance in clinical diagnosis and therapy. Apart from the Chinard's assay, some other more sensitive and well validated methodologies have been published. These include colorimetric and spectrophotometric determinations of free proline produced by enzymatic reactions, capillary electrophoresis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, electrochemoluminescence, thin layer chromatography, and HPLC. The aim of this comprehensive review is to make a detailed survey of the in so far reported analytical techniques, highlighting their general features, as well as their advantages and possible drawbacks, providing in the meantime suggestions to stimulate further research in this intriguing field. [Display omitted] • A survey of methods for the determination of prolidase activity is outlined. • Many of the methods are based on the Chinard's ninhydrin colorimetric reaction. • Sensitive and powerful methodologies have been developed during the last two decades. • Capillary electrophoresis and MALDI-TOF are nowadays the most sensitive ones. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2) is an oncogenic receptor tyrosine kinase amplified in approximately 20% of breast cancer (BC). HER2-targeted therapies are the linchpin of treating HER2-positive BC. However, drug resistance is common, and the main resistance mechanism is unknown. We tested the hypothesis that drug resistance results mainly from inadequate or lack of inhibition of HER2 and its family member epidermal growth factor receptor (EGFR). We used clinically relevant cell and tumor models to assess the impact of targeted degradation of HER2 and EGFR on trastuzumab resistance. Trastuzumab is the most common clinically used HER2 inhibitor. Targeted degradation of HER2 and EGFR was achieved using recombinant human protein PEPDG278D, which binds to the extracellular domains of the receptors. siRNA knockdown was used to assess the relative importance of EGFR and HER2 in trastuzumab resistance. Both HER2 and EGFR are overexpressed in all trastuzumab-resistant HER2-positive BC cell and tumor models and that all trastuzumab-resistant models are highly vulnerable to targeted degradation of HER2 and EGFR. Degradation of HER2 and EGFR induced by PEPDG278D causes extensive inhibition of oncogenic signaling in trastuzumab-resistant HER2-positive BC cells. This is accompanied by strong growth inhibition of cultured cells, orthotopic patient-derived xenografts, and metastatic lesions in the brain and lung of trastuzumab-resistant HER2-positive BC. siRNA knockdown indicates that eliminating both HER2 and EGFR is necessary to maximize therapeutic outcome. This study unravels the therapeutic vulnerability of trastuzumab-resistant HER2-positive BC and shows that an agent that targets the degradation of both HER2 and EGFR is highly effective in overcoming drug resistance in this disease. The findings provide new insights and innovations for advancing treatment of drug-resistant HER2-positive breast cancer that remains an unmet problem. [ABSTRACT FROM AUTHOR]

The research included the isolation of prolidase from human amniotic fluid using different biochemical techniques, One proteinous peak had been isolated by gel filtration using sephadex )G-50) and from sephadex (G-100) that produced by ammonium sulphate precipitation (60%) after dialysis. The approximately molecular weight of the enzyme using gel filtration chromatography (G-100) was (52269.7) Dalton and specific activity of 13516.6 unit/mg protein with 75 fold of purification. The results showed that the optimum conditions of purified enzyme from amniotic fluid were at (50 µg/ml) of protein as a source of the enzyme using (60 mM/L) Tris-HCl buffer solution at pH (8.0) act for (32) minutes at (39°C). Using Line Weaver-Burk plot, the values of maximum velocity (Vmax) and Michaelis constant (Km) were found to be (3448.2 U/L) and (10 mM/L) respectively using Gly-Pro as a substrate. Finally, also, involved the study of the effect pharmacological chemicals compounds on the enzyme activity, the results showed that the drug chemical compounds for type ceramide, metoclopramide, pseudoephedrine, diphenhydramine-HCl, chloramphnicol, paracetamol and allopurinol give the inhibition type competitive, with increased in Km value to 66.6, 71.42, 52.63, 55.55, 83.33, 90.9 and100.0 mM/L respectively for inhibitors above, while the others pharmacological compounds for theophlline anhydrous, caffeine anhydrous, metronidazole and chlorpheniramine maleate, give the inhibition type of non-competitive with decreased in Vmax values to 2173.9, 2439.0, 2000.0 and 2325.58 U/L respectively, but dexathamazone was an activator to the prolidase approximately 27.18 U/L.

Background: Oxidative damage is of great importance for patients with breast cancer. Thus, studies were performed to identify the relationship between breast cancer and oxidative stress biomarkers.

Prolidase is a metal-dependent peptidase specialized in the cleavage of dipeptides containing proline or hydroxyproline on their C-termini. Prolidase homologues are found in all kingdoms of life. The importance of prolidase in human health is underlined by a rare hereditary syndrome referred to as Prolidase Deficiency. A growing number of studies highlight the importance of prolidase in various other human conditions, including cancer. Some recent studies link prolidase's activity-independent regulatory role to tumorigenesis. Furthermore, the enzyme or engineered variants have some applications in biotechnology. In this short review, we aim to highlight different aspects of the protein the importance of which is increasingly recognized over the last years. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the association of prolidase activity in streptozotocin (STZ) induced diabetic rat model with hippocampus-dependent spatial memory functions in chronic hyperglycemic conditions. Towards this, a single dose of STZ (30 mg/kg, i.p.) was administered to 4-month-old female Sprague Dawley rats and hyperglycemia was confirmed in all the STZ treated rats. To assess the spatial memory, at the time intervals of 9 days, 30 days and 90 days post STZ administration, the animals were subjected to Barnes maze task. Prolidase activity and glucose concentration in the serum were measured at these time points. With prolonged duration of hyperglycemia, severe impairment in spatial memory functions was seen in STZ induced diabetic rats which was correlatable with reduction in prolidase levels (P <0.05), thus suggesting that alterations in synaptic integrity due to prolidase mediated extracellular matrix remodeling as the possible mechanism of memory defects observed during chronic diabetes. [ABSTRACT FROM AUTHOR]

Objective: Uncontrolled inflammation and oxidative stress are responsible for the pathogenesis of familial Mediterranean fever (FMF) and its complications. Increased serum prolidase enzyme activity (SPEA) has been shown to correlate with inflammation and oxidative stress. This study aimed to evaluate the relationship between SPEA and FMF disease. Materials and Methods: A total of 124 participants were included in this cross-sectional study. Patients were divided into two groups depending on the presence or absence of FMF attacks. Group 1 consisted 69 patients who were attack free. Group 2 consisted of 11 patients who suffered FMF attacks. A total of 44 healthy volunteers were included in the study (Group 3). Clinical features and laboratory data were recorded. SPEA was analyzed by using spectrophotometry. Results: SPEA of Group 2 was found to be statistically significantly higher than that of Groups 1 and 3 (p=0.004 and p=0.006, respectively). SPEA was positively correlated with the presence of attack (rs =0.265, p=0.003), erythrocyte sedimentation rate (rs =0.269, p=0.003), and C-reactive protein (rs =0.199, p=0.027). The relationship between FMF attack and SPEA was evaluated by receiver operating characteristics analysis. Sensitivity and specificity were 91% and 67%, respectively, with an SPEA cut-off point of 817 U/L (AUC=0.769 [95% CI 0.626-0.912, p=0.003]). Conclusion: The FMF attack and the associated acute phase response may have an effect on increased SPEA. In FMF patients, an increased SPEA may play a role in both pathogenesis and progression of complications caused by the inflammatory process. [ABSTRACT FROM AUTHOR]

In many types of cancer, reactive oxygen and nitrogen products have been detected at high levels. Arylesterase, and paraoxonase1 are esterase enzymes that have strong antioxidant characteristics. The prolidase enzyme is a rate -limiting metalloenzyme which also plays a role in collagen turnover, and is dependent on its NO-activity. In this study, we aimed to investigate the possible relationship between serum paraoxonase1, arilesterase and prolidase enzyme activity in patients with squamous cell carcinoma of the oral cavity and to investigate the etiology and mechanism of oral cavity cancer. The study included 24 patients with oral cavity cancer, and 22 healthy age - and sex-matched individuals. Arylesterase, paraoxonase1 and prolidase activities were measured using spectrophotometry. Paraoxonase1 activity was 11.6±2.32 nmol/l in the patient group and 29.46±6.18 nmol/l in the controls. Arylesterase activity was 32.2±14.57 nmol/l in the patient group and 80.71±7.23 nmol/l in the controls. Prolidase activity was 39.51±3.02 nmol/l in the patient group and 19.53±1.13 nmol/l in the controls. The mean paraoxonase1 and arylesterase levels in the patient group were statistically lower than the control group and the mean prolidase levels were high (p = 0.0001). In our study, arylesterase and paraoxonase1 enzyme activity was low in patients with oral cav ity cancer. The prolidase activity was higher in the same group. As a result, paraoxonase1, arylesterase and prolidase enzyme activities play an important role in the etiopathogenesis of oral cavity cancers. In addition, more research should be done on bot h clinical and molecular levels of oral cavity cancer. [ABSTRACT FROM AUTHOR]

Objectives: Smoking causes inflammation, thickening, and narrowing of the airways. This inflammatory process is a reaction to free radicals and oxidants. Smoking affects collagen metabolism and tissue remodeling. Prolidase enzyme hydrolyzes iminodipeptides with hydroxyproline and C terminal proline. It plays a crucial role in the metabolism of collagen and the remodeling of the matrix. The present study aims to reveal the association of prolidase with inflammation caused by smoking and to compare serum prolidase levels with oxidative-antioxidative status in healthy individuals., Methods: A total of 76 participants (38 smokers and 38 nonsmokers) were involved in the present study. Serum cotinine levels were measured to show the exposure to nicotine in tobacco smoke by using the competitive inhibition enzyme immunoassay method. Serum prolidase, total oxidant status (TOS), and total antioxidant status (TAS) were determined by the enzyme-linked immunosorbent (ELISA) method, respectively. The correlation between smoking, serum prolidase levels, TOS, and TAS was investigated., Results: TAS and serum prolidase levels of smokers were considerably lower than those in non-smokers ( p  < 0.001, p  = 0.012 respectively). However, no differences were observed in TOS between the two groups. There was no statistically significant correlation between serum prolidase levels, TAS, and TOS. Moreover, no relationship was observed between respiratory function parameters and serum prolidase levels., Conclusion: To the best of our knowledge, the present study is the first study to demonstrate the role of prolidase in smoking-related inflammation. The results achieved in the present study suggest that smoking creates an imbalance in the oxidant-antioxidant activity. Smoking decreases prolidase levels, leading to decreased collagen turnover. Chronic pulmonary disease might be related to this decrease in collagen turnover., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yıldırım and Kulaksızoglu.)

OBJECTIVE: Although the underlying mechanism is not yet fully understood, Cardiac Syndrome X (CSX) is defined as microvascular dysfunction. Prolidase plays a role in collagen synthesis. Increased serum prolidase activity (SPA) has been shown to correlate with collagen turnover. Augmented collagen turn-over may be associated with vascular fibrosis and microvascular dysfunction. In this study, we assessed whether there was a correlation between CXS and prolidase activity. METHODS: This case-control study included 45 consecutive CSX patients (mean age 50.7±6.5 years, 27 women) and 40 healthy controls (mean age 51.2±6.5 years, 25 women). Prolidase activity was determined with the Human Xaa-Pro Dipeptidase/Prolidase enzyme-linked immunosorbent assay kit (Cusabio Biotech Co. Ltd, China). RESULTS: Mean prolidase activity was 898.8±639.1 mU/mL in the CSX group and 434.1±289.8 mU/mL in the control group (p<0.001). In ROC analysis, it was found that the SPA value above 350 mU/mL sympathizes with the diagnosis of CSX. CONCLUSION: Increased SPA in CXS patients may play an essential role in the pathophysiology of CSX, leading to augmented oxidative stress and vascular fibrosis, endothelial dysfunction, and increased microvascular resistance. [ABSTRACT FROM AUTHOR]

This study was conducted for the period from 15/12/2019 to 30/01/2020 in the laboratories of Samarra General Hospital and outpatient clinics, as 40 samples were collected (20) a sample infected with rheumatoid arthritis diagnosed by doctors and (20) healthy samples as a control group. Their ages ranged between (35-80) years. As 6 ml of venous blood was withdrawn and (4) ml was placed in plastic tubes and free from anticoagulant for the purpose of Determination concentrations (Prolidase, MDA, Ceroplasmin) and (2) ml to Erythrocyte Sedimentation rate ESR, and the results were statistically analyzed by testing the variance at a significant level P≤ 0.05. The results showed a significant increase in the effectiveness of prolidase enzyme in patients with rheumatoid arthritis compared to the control group at a significant level P≤ 0.05 and an increase in the concentration of Ceroplasmin, ESR and malondialdehyde in the patients group compared to the control group P≤ 0.05 [ABSTRACT FROM AUTHOR]

This review is focused on recent data on the role of proline (Pro) in collagen biosynthesis and cellular metabolism. It seems obvious that one of the main substrates for collagen biosynthesis Pro is required to form collagen molecule. The question raised in this review is whether the Pro for collagen biosynthesis is synthesized "de novo", comes directly from degraded proteins or it is converted from other amino acids. Recent data provided evidence that extracellular Pro (added to culture medium) had significant, but relatively little impact on collagen biosynthesis in fibroblasts (the main collagen synthesized cells) cultured in the presence of glutamine (Gln). However, extracellular Pro drastically increased collagen biosynthesis in the cells cultured in Gln-free medium. It suggests that Pro availability determines the rate of collagen biosynthesis and demand for Pro in fibroblasts is predominantly met by conversion from Gln. The potential mechanism of this process as well as possible implication of this knowledge in pharmacotherapy of connective tissue diseases is discussed in this review. [ABSTRACT FROM AUTHOR]

Background/Aims: Proline availability for proline dehydrogenase/proline oxidase (PRODH/POX) may represent switching mechanism between PRODH/POX-dependent apoptosis and autophagy. The aim of the study was to evaluate the impact of overexpression of prolidase (proline releasing enzyme) on apoptosis/autophagy in breast cancer MCF-7 cells. Methods: The model of MCF-7 cells with prolidase overexpression (MCF-7PL) was obtained. In order to targeting proline for PRODH/POX-dependent pathways substrate for prolidase, glycyl-proline (GP) was provided and proline utilization for collagen biosynthesis was blocked using 2-methoxyestradiol (MOE). Cell viability was determined using Nucleo-Counter NC-3000. The activity of prolidase was determined by colorimetric assay. DNA, collagen and total protein biosynthesis were determined by radiometric method. Expression of proteins was assessed by Western blot and immunofluorescence bioimaging. Concentration of proline was analyzed by liquid chromatography with mass spectrometry. Results: Prolidase overexpression in MCF-7PL cells contributed to 10-fold increase in the enzyme activity, 3-fold increase in cytoplasmic proline level and decrease in cell viability and DNA biosynthesis compared to wild type MCF- 7 cells. In MCF-7PL cells MOE and GP significantly decreased the number of living cells. MOE inhibited DNA biosynthesis in both cell lines while GP evoked inhibitory effect on the process only in MCF-7PL cells. In both cell lines, MOE or MOE+GP inhibited DNA and collagen biosynthesis. Although GP in MCF-7 cells stimulated collagen biosynthesis, it inhibited the process in MCF-7PL cells. The effects of studied compounds in MCF-7PL cells were accompanied by increase in the expression of Atg7, LC3A/B, Beclin-1, HIF-1α and decrease in the expression of PRODH/POX, active caspases-3 and -9. Conclusion: The data suggest that overexpression of prolidase in MCF-7 cells contributes to increase in intracellular proline concentration and PRODH/POX-dependent autophagic cell death. [ABSTRACT FROM AUTHOR]

Background: Behçet's disease is an autoimmune, chronic, inflammatory, multisystemic disease. Although oral aphthae, genital ulcers, skin lesions and uveitis are commonly seen in the disease, vasculitis is the main pathological finding. There is no laboratory finding specific to Behçet's disease. The levels of various routine parameters such as erythrocyte sedimentation rate and C-reactive protein have been shown to be high in Behçet's disease, however, the change in these parameters is not always consistent with clinical activity. The aim of this study was to investigate the relationship between Behçet's disease and ischemiamodified albumin, methylglyoxal and serum prolidase activity. Materials and Methods: 35 Behçet patients and 35 controls were included in to the study. Serum ischemia-modified albumin levels and prolidase activity were measured spectrophotometrically (Perkin Elmer Lambda 25 UV/Vis, US) and serum methylglyoxal levels were measured by Thermo Ultimate 3000 Ultra-High Performance Liquid Chromatography. Results: In the Behcet group, serum ischemia-modified albumin (p <0.001), prolidase, methylglyoxal (p <0.001), neutrophil lymphocyte ratio (p = 0.011), platelet lymphocyte ratio (0.015), erythrocyte sedimentation rate (p = 0.047), erythrocyte distribution width (p=0.021), neutrophil (p=0.007) levels were found to be significantly higher than the control group, whereas mean corpuscular hemoglobin concentration value was found to be significantly lower than the control group (p = 0010). Conclusions: Serum ischemia modified albumin, methylglioxal levels and prolidase activity were statistically significantly different in the Behçet group compared to the control group. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) is composed of a mixture of various growth factors, macro and micronutrients, any change in ECM may leads to abnormal hormonal secretion and may cause disorders. Prolidase, a manganese dependent cytosolic matrix metalloproteinase plays an important role in the cell growth and recycling of proline for collagen biosynthesis. As it can remodel the tissue matrix, it may play some role in the development of ovarian follicle and also in pathophysiology of poly cystic ovary syndrome. aim aimed to compare the activity of prolidase and hormonal profile in women with PCOS and their controls. Eighty women includes: 40 patients with polycystic ovary syndrome, 40 control group aged 18–40. Serum enzyme activity of prolidase in all study population was evaluated spectrophotometrically. PCOS group have significantly higher LH/ FSH ratio and testosterone than their control group. Significantly higher levels of serum prolidase were observed in PCOS group in comparison to their control group. Furthermore, it has been found that prolidase levels increase with the number of antral follicle count in ovaries. Significant difference between prolidase levels in PCOS and control shows that it may be used as a diagnostic marker. In addition, there is a positive correlation found between prolidase levels and number of anrtal follicle count hence may be used as a prognostic marker to monitor disorder status. [ABSTRACT FROM AUTHOR]

Aim: Ibuprofen is an older agent, but its intravenous form is a very new drug. The aim of this study was to investigate whether intravenous form of ibuprofen has protective effect against renal ischemia reperfusion injury at two different doses such as 10-30 mg/kg. Material and Methods: Thirty-two Wistar Albino type female rats were divided into 4 groups as sham, control, IBU-10, IBU-30. In the control group, 60 minutes renal ischemia and 60 minutes reperfusion were performed. In the ibuprofen groups, at the 45th minute of ischemia, ibuprofen was administered in different doses at 10 mg/kg and 30 mg/kg through intraperitoneally. After 60 minutes of ischemia, the clamps were opened. Renal tissue and blood samples were collected from the rats at the end of the reperfusion period. Serum TAS, TOS and prolidase enzyme levels were analyzed in plasma samples. Both histopathological and biochemical evaluations were performed with kidney tissue. Results: In the groups given intravenous ibuprofen, less cellular damage was always detected. Cellular damage indicators were significantly lower in the treated rats than in the control group. Serum and tissue prolidase values were different between groups (p<0.001, p<0.001). Serum TAS and TOS levels were also different between groups (p=0.001, p=0.003). Serum OSI levels were also different between groups (p=0.017). Conclusion: The biochemical and pathological results obtained in our study suggest that intravenous ibuprofen, has a protective effect against kidney damage. We believe that our study will shed light on future clinical prospective studies. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate whether Serum Prolidase Activity (SPA) levels and plasma levels of glycogen phosphorylase BB (GPBB) isoform could be used as apotential diagnostic biomarker in Acute Ischemic Stroke (AIS) patients or not. Materials and methods: SPA levels showed no significant evaluation in 40 patients and glycogen phosphorylase BBwere prospectively evaluated in 40 patients aged between 40to70 ywho were admitted within 24 h of the onset of AIS. The control group included 40 healthy volunteers of similar age without any disease. Results:There is a significant elevation in the level of GPBB in ischemic strokegroup and compared with control group. For Control, the observations of GPBB had an Min = 1.27.For Stroke, the observations of GPBB had an Min = 1.3837 There was a significant positive correlation between stoke and Glycogen phosphorylase (rpb = 0.7473, p< .001). The correlation coefficient between Stroke and Glycogen phosphorylase was 0.7473 indicating a large effect size. This indicates that moving from the Not having to having Stroke is associated with an increase in Glycogen phosphorylase. Therefore, Stroke tends to be associated with higher values of Glycogen phosphorylase There was small effect size correlation between Stroke and Prolidase (rpb = -0.1396, p0.2177). As the computed p-value is greater than the significance level alpha=0.05. Prolidase is not associated with stoke. Conclusions: 1. This study shows there is significant elevation in enzyme level of glycogen phosphorylase BB (GPBB) in ischemic strokegroup and compared with control group. 2. This study shows There was small effect size correlation between Stroke and Prolidase, Prolidase is not associated with stroke. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the predictive power of plasma prolidase activity and oxidative-stress parameters for distinguishing in patients with various causes of non-traumatic abdominal pain who presented to the emergency department.Methods: This study enrolled 100 consecutive adult patients and 100 age- and sex-matched healthy controls. The patients were divided into surgically treated patients (STP); medically treated patients (MTP) and nonspecific abdominal pain (NSAP) patients. As predictors of early oxidative changes, the plasma prolidase activity, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were assessed using a novel automated method.Results: No significant difference was observed between the patients and the controls with respect to age or sex (p = 0.837 and 0.188, respectively). The plasma TOS, OSI value, and prolidase activity were significantly higher in the patients with abdominal pain than in the controls (p < 0.001, p = 0.001, and p < 0.001, respectively); however, there was no significant difference in the TAS (p = 0.211). The mean plasma TOS, OSI value, and prolidase activity differed significantly among the three groups (p < 0.001, p = 0.001, and p < 0.001, respectively). The STP had the highest TOS and prolidase activity. However, there was no significant difference in the mean plasma TAS in either group of patients (p = 0.419).Conclusion: The plasma prolidase activity and TOS level, as biomarkers of oxidative stress, enable discrimination of patients with NSAP from those with surgical abdominal pain that requires emergent surgical treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are diseases of elderly men and are related to increased oxidative stress (OS). Although prolidase has a role in collagen metabolism, it is also used to evaluate OS in many diseases. However, there is a lack of data about serum prolidase activity (SPA) in prostate cancer. The aim of this study was to evaluate and compare SPA levels in males with BPH and PCa. Methods Evaluation was made of a total of 81 men who underwent transrectal ultrasound guided prostate biopsy for a definitive diagnosis due to high PSA levels. Patients were separated into 2 groups as BPH and PCa patients. Pre-biopsy malondialdehyde (MDA), superoxide dismutase (SOD), PSA levels and serum prolidase activities (SPA) were compared between the groups and the correlations of SPA with the other parameters were also investigated in both groups. Results BPH was diagnosed in 51 patients and PCa in 30. The mean age of patients was similar in both groups as 63.25 ± 5.81 years in the BPH group 65.30 ± 7.35 years in the PCa group(p:0.081). The median MDA and SOD levels were insignificantly increased in the PCa patients. SPA values were similar in BPH and PCa patients. SPA did not correlate with age, PSA, MDA or SOD levels in either group. Conclusions Our study results revealed that serum prolidase activity is similar in BPH and PCa cases and is not correlated with MDA, SOD or PSA levels.

Background/Aim: The purpose of this study was to investigate gingival crevicular fluid (GCF) alkaline phosphatase (ALP) and prolidase levels in subjects with different periodontal status. Material and Methods: Fifteen periodontitis, fifteen gingivitis and fifteen healthy subject were included. GCF samples were collected from participants. Probing depth, clinical attachment level, gingival index was recorded. ALP and prolidase levels were determined in GCF by spectrophotometrically. Results: Higher values of ALP were found in periodontitis compared with gingivitis and healthy control (p0.05). Additionally, no significant correlation was detected between ALP and prolidase (r= -0.309, p>0.05). Conclusion: Our preliminary data suggest that low prolidase level in periodontitis was not associated with ALP and clinical parameters, which represent periodontal destruction and inflammation.

Tomasz Guszczyn,1 Arkadiusz Surażyński,2 Ilona Zaręba,2 Edyta Rysiak,2 Janusz Popko,1 Jerzy Pałka2 1Department of Pediatric Orthopedics and Traumatology, 2Department of Medicinal Chemistry, Medical University of Białystok, Białystok, Poland Abstract: The study was conducted to evaluate the effects of platelet-rich plasma (PRP), supernatant of PRP (SPRP) obtained by centrifugation, and supernatant of activated PRP (SActi-PRP) obtained by Ca2+ solution-treated PRP on collagen biosynthesis, prolidase activity, and β1-integrin signaling in cultured human skin fibroblasts. Incubation of fibroblasts with 5% PRP for 24 h contributed to ~5-fold increase in collagen biosynthesis compared to the control. In the cells treated with 5% of SPRP or SActi-PRP, collagen biosynthesis showed a 3-fold increase of the control. PRP, SPRP, and SActi-PRP stimulated prolidase activity similar to collagen biosynthesis. Collagen biosynthesis and prolidase activity are regulated by β1-integrin receptor signaling. Incubation of fibroblasts with PRP for 24 h contributed to a dose-dependent increase in the expression of β1-integrin receptor, while SActi-PRP increased the process to a much lower extent. SPRP had no effect on the β1-integrin receptor expression. All the studied fractions of blood increased the expression of FAK as well as the expression of phosphorylated MAP-kinases. However, PRP was found to be the most effective stimulator of expression of these particular kinases. These studies suggest that a complex of factors, including growth factors, adhesion molecules, and prolidase contained in PRP, all evoke growth and collagen-promoting activities in human dermal fibroblasts. Keywords: fibroblasts, FAK, MAPK

Dermatophyte infections are superficial fungal infections. Tinea pedis is a dermatophyte infection of the feet and interdigital spaces. An evaluation was made of the chitotriosidase (ChT) concentrations, prolidase activity and the possible association between these biomarkers in tinea pedis. Study subjects were comprised of 42 patients with tinea pedis and 40 healthy subjects. Serum ChT concentrations and prolidase activity were determined in study population. Higher ChT concentrations were found in patients than controls (p < 0.001). We did not find any difference between groups in terms of prolidase activity (p = 0.162). We also did not found any correlation between ChT and prolidase activity. ChT seems to have roles during the inflammatory conditions in patients with tinea pedis. Whereas prolidase activity is not associated with the tinea pedis. [Med-Science 2018; 7(1.000): 191-193]