Gelatinases and their tissue inhibitors are associated with oxidative stress: a potential set of markers connected with male infertility.

The expression and activity of matrix metalloproteinases (MMPs) may be regulated by oxidative stress in various pathophysiological processes; therefore, the aim of the present study was to analyse the associations between the expression of the gelatinases MMP-9 and MMP-2 and their tissue inhibitors TIMP-1, TIMP-2 and levels of total antioxidant capacity (TAC) and advanced oxidation protein products (AOPP) in seminal plasma prepared for artificial insemination. Levels of MMPs and TIMPs were evaluated using ELISA, whereas TAC and AOPP in the seminal plasma of 131 childless men and 38 fertile volunteers were determined spectrophotometrically. Seminal MMP-9 expression was higher in childless men than in fertile subjects, whereas there was no significant differences in MMP-2 expression between the analysed seminal groups. TIMP-1 and TIMP-2 expression was similar in all groups. However, TAC expression was significantly higher in infertile normozoospermic and oligozoospermic men and AOPP expression was higher in astheno-, oligo- and normozoospermic infertile patients than in fertile men. High AOPP, together with an increased MMP-9:TIMP-1 ratio alters the oxidative-antioxidative balance of the ejaculate, thereby reducing male fertility, and therefore these parameters may serve as additional diagnostic markers of semen quality and male reproductive potential.

Glycosylation changes in the salivary glycoproteins of alcohol-dependent patients: a pilot study.

AIM: Glycosylation of serum proteins is affected with prolonged heavy drinking, and carbohydrate deficient transferrin (CDT) is well established and highly specific biomarker of sustained alcohol consumption. However, total amount of sialic acid is not the only glycoepitope that may be altered as a result of the disease. This work is focused on glycan structures altered in salivary glycoproteins of alcoholics, indicating the most efficient carriers of such marker glycoepitopes. METHODS: Salivary glycoproteins of 31 alcohol-dependent patients and 21 healthy controls were studied by means of lectin ELISA and lectin blotting with the lectins specific for core and antennary fucose, α2,3-bound sialic acid as well as T and Tn antigens in O-glycans. RESULTS: In direct lectin ELISA, core fucosylation, α2,3 sialylation and expression of T-antigen were significantly lowered in the saliva of alcohol-dependent patients. In lectin blotting ten glycoprotein bands were analyzed. The profile of disease-related alterations was found to be complex, but all six lectins studied here were able to detect altered glycan structures. In some glycoproteins the tendency to correct the glycosylation profile was observed after 7 weeks of abstinence. CONCLUSION: Alterations in the glycosylation profiles in the salivary glycoproteins of alcohol-dependent people were found. Some of salivary glycoproteins, such as α-amylase, clusterin, haptoglobin, heavy and light chains of immunoglobulins, and transferrin, seem to be worthy of detailed glycosylation analysis in the detection of alcohol dependence. Further studies may allow one to estimate if such glycomarkers may also reflect the amount of alcohol intake or the duration of alcohol intake.

The Impact of Intermittent Hypoxic Training on Aerobic Capacity and Biometric-Structural Indicators among Obese Women-A Pilot Study.

BACKGROUND: Obesity, a common lifestyle-related condition, is correlated with factors like inadequate physical activity. Its connection to diverse health issues presents a significant challenge to healthcare. This pilot study investigated the effects of hypoxic training on aerobic capacity and biometric-structural indicators in obese women. The secondary objective was to determine the feasibility, effectiveness, and safety of the planned research procedures and their potential for larger-scale implementation. MATERIAL AND METHODS: Forty-one non-trained women with first-degree obesity were randomly assigned to even normobaric hypoxic training (H + E), normoxic training (E), passive exposure to hypoxia (H), and a control group (C). Training sessions were conducted three times a week for four weeks (12 training sessions). Body composition parameters were assessed, metabolic thresholds were determined, and maximal oxygen consumption (VO2max) was measured before and after interventions. RESULTS: The results demonstrated that training in hypoxic conditions significantly affected somatic parameters, with the H + E group achieving the best outcomes in terms of weight reduction and improvements in body composition indicators (p < 0.001). Normoxic training also induced a positive impact on body weight and body composition, although the results were less significant compared to the H + E group (p < 0.001). Additionally, training in hypoxic conditions significantly improved the aerobic capacity among the participants (p < 0.001). The H + E group achieved the best results in enhancing respiratory endurance and oxygen consumption (p < 0.001). CONCLUSIONS: The results of this pilot study suggest, that hypoxic training can be effective for weight reduction and improving the aerobic capacity in obese women. Despite study limitations, these findings indicate that hypoxic training could be an innovative approach to address obesity and related conditions. Caution is advised in interpreting the results, considering both the strengths and limitations of the pilot study. Before proceeding to a larger-scale study, the main study should be expanded, including aspects such as dietary control, monitoring physical activity, and biochemical blood analysis.

Aberrant Mannosylated and Highly Fucosylated Glycoepitopes of Prostatic Acid Phosphatase as Potential Ligands for Dendritic-Cell Specific ICAM-Grabbing Nonintegrin (DC-SIGN) in Human Seminal Plasma-A Step towards Explaining Idiopathic Infertility.

Semen prostatic acid phosphatase (PAP) has been proposed as an endogenous ligand for dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), which plays a critical immuno-modulating role in maintaining homeostasis in the female reproductive tracts. In the current study, we assumed that semen PAP bears a set of fucosylated and mannosylated glycans, which may mediate the efficient binding of PAP to DC-SIGN. To investigate this hypothesis, we developed ELISA assays using Galanthus nivalis and Lotus tetragonolobus lectins capable of binding mannose-containing glycans or LewisX and LewisY motifs, respectively. In our assay with Galanthus nivalis, we detected that the relative reactivity of PAP mannose-presenting glycans in the normozoospermic idiopathic group was significantly higher than in the asthenozoospermic, oligozoospermic and oligoasthenozoospermic groups. Simultaneously, we observed slight differences in the relative reactivities of PAP glycans with Lotus tetragonolobus lectin among groups of patients with abnormal semen parameters. Subsequently, we examined whether DC-SIGN interacts with seminal plasma PAP glycans, and we detected a significantly higher relative reactivity in the normozoospermic group compared to the oligozoospermic group. Finally, we concluded that the significantly aberrant abundance of mannosylated functional groups of PAP among patients with semen disorders can suggest that PAP may thereby be engaged in modulating the immune response and promoting a tolerogenic response to male antigens in the female reproductive system.

Effects of Different Hydration Strategies in Young Men during Prolonged Exercise at Elevated Ambient Temperatures on Pro-Oxidative and Antioxidant Status Markers, Muscle Damage, and Inflammatory Status.

Physical exercise is associated with an increase in the speed of metabolic processes to supply energy to working muscles and endogenous heat production. Intense sweating caused by the work performed at high ambient temperatures is associated with a significant loss of water and electrolytes, leading to dehydration. This study aimed to examine the effectiveness of different hydration strategies in young men during prolonged exercise at elevated ambient temperatures on levels of pro-oxidative and antioxidant status, oxidative status markers (TAC/TOC), muscle cell damage (Mb, LDH), and inflammatory status (WBC, CRP, IL-1ß). The study was conducted on a group of 12 healthy men with average levels of aerobic capacity. The intervention consisted of using various hydration strategies: no hydration; water; and isotonic drinks. The examination was di-vided into two main stages. The first stage was a preliminary study that included medical exami-nations, measurements of somatic indices, and exercise tests. The exercise test was performed on a cycle ergometers. Their results were used to determine individual relative loads for the main part of the experiment. In the second stage, the main study was conducted, involving three series of weekly experimental tests using a cross-over design. The change in plasma volume (∆PV) measured im-mediately and one hour after the exercise test was significantly dependent on the hydration strategy (p = 0.003 and p = 0.002, respectively). The mean values of oxidative status did not differ signifi-cantly between the hydration strategy used and the sequence in which the test was performed. Using isotonic drinks, due to the more efficient restoration of the body's water and electrolyte balance compared to water or no hydration, most effectively protects muscle cells from the negative effects of exercise, leading to heat stress of exogenous and endogenous origin.

Glycosylation: Rising Potential for Prostate Cancer Evaluation.

Prostate cancer is the second most commonly diagnosed cancer among men. Alterations in protein glycosylation are confirmed to be a reliable hallmark of cancer. Prostate-specific antigen is the biomarker that is used most frequently for prostate cancer detection, although its lack of sensitivity and specificity results in many unnecessary biopsies. A wide range of glycosylation alterations in prostate cancer cells, including increased sialylation and fucosylation, can modify protein function and play a crucial role in many important biological processes in cancer, including cell signalling, adhesion, migration, and cellular metabolism. In this review, we summarize studies evaluating the prostate cancer associated glycosylation related alterations in sialylation, mainly α2,3-sialylation, core fucosylation, branched N-glycans, LacdiNAc group and presence of truncated O-glycans (sTn, sT antigen). Finally, we discuss the great potential to make use of glycans as diagnostic and prognostic biomarkers for prostate cancer.

Influence of Nordic Walking Training on Vitamin D Level in the Blood and Quality of Life among Women Aged 65-74.

INTRODUCTION: Demographic forecasts indicate the progressive aging process of societies in all countries worldwide. The extension of life span may be accompanied by deterioration of its quality resulting from a decrease in physical activity, mental or even social performance, and a deficit in certain chemical compounds responsible for proper functioning of the body. AIM: The aim of the study was to evaluate the influence of a 12-week Nordic walking (NW) training intervention on the level of vitamin D in the blood and quality of life among women aged 65-74 years. MATERIALS AND METHODS: The study comprised 37 women aged 65-74 (x = 68.08, SD = 4.2). The subjects were randomly assigned to 2 groups: experimental group (NW), which consisted of 20 women who underwent an intervention in the form of Nordic walking training for 12 weeks, and the control group (C), including 17 women who underwent observation. In the experimental group, training sessions were held 3 times a week for 1 h. At that time, the C group was not subject to any intervention. The SF-36 questionnaire was used to measure quality of life. Vitamin D was assessed based on the results of biochemical blood tests. The analysed parameters were assessed twice-before and after the completed intervention or observation. RESULTS: Comparison of the results regarding trials 1 and 2 allowed to note statistically significant improvement in quality of life for all health components and factors in the NW group. Analysis of vitamin D levels demonstrated a statistically significant increase in the NW group. In group C, no significant changes in the analysed parameters were observed. CONCLUSIONS: Regularly undertaking Nordic walking training significantly influences the improvement of self-evaluation regarding the components of physical and mental health, as well as the concentration of vitamin D in women aged 65-74 years.

High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.

An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization. However, the exact role of PSA glycosylation in male fertility is not clear. To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner. In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides. The method was successfully applied on a cohort consisting of seminal plasma from infertile and fertile men (N = 102). Forty-four glycopeptides were quantified in all samples, showing mainly complex-type glycans with high levels of fucosylation and sialylation. In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures. Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men. Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.

The Potential Role of Seminal Plasma in the Fertilization Outcomes.

For human infertility both male and female factors may be equally important. Searching for molecular biomarkers of male infertility, neglected for decades, and the attempts to explain regulatory mechanisms of fertilization become thus extremely important. Apart from examination of the structure and function of male gametes, also the possible importance of seminal plasma components should be considered. In this article we discuss data that indicate for the substantial significance of active seminal plasma components for conception and achievement of healthy pregnancy. Seminal plasma impact on the storage and cryopreservation of human and animal sperm and regulatory role of glycodelin on human sperm capacitation as well as hypothesized course of female immune response to allogenic sperm and conceptus has been discussed. The possible involvement of carbohydrates in molecular mechanism of fetoembryonic defense has been also mentioned.

The age of developing diabetes and FTO polymorphisms (rs9939609, rs1421085, and rs9930506).

INTRODUCTION: Type 2 diabetes (T2DM) is a common complex metabolic disorder that has a strong genetic predisposition. Fat mass and obesity-associated protein (FTO) is one of the genes of interest to us. Hypomethylation of a CpG site in the FTO gene was significantly associated with the risk of T2DM. The aim of the study was to find the answer to the question of whether the polymorphism changes of the FTO gene in the pathogenesis of type 2 diabetes are comparable in young, middle aged, and elderly people. MATERIAL AND METHODS: The study involved 282 consecutive patients with type 2 diabetes, who attended a primary healthcare clinic in Southern Poland. The study subjects were divided into three groups according to the age at which type 2 diabetes mellitus was diagnosed (> 40 years old, 40-60 years old, and > 60 years old). The genotyping of rs9939609, rs1421085, and rs9930506 FTO polymorphisms was conducted using TaqManPre-designed SNP Genotyping Assay. RESULTS: No statistically significant difference was shown between the examined FTO polymorphism (rs9939609, rs1421085, and rs9930506) distribution between the subjects diagnosed with diabetes < 40 years , 40-60 years, and > 60 years old. CONCLUSIONS: There were no statistically significant relationships between the different analysed anthropometric and other parameters and distribution of examined FTO polymorphisms (rs9939609 , rs1421085, and rs9930506). The age of diabetes was not affect by the tested FTO polymorphisms (rs9939609 , rs1421085, and rs9930506).

Preliminary MALDI-TOF-MS analysis of seminal plasma N-glycome of infertile men.

Glycosylation pattern within reproductive tract is now suggested to be involved in providing female immune tolerance for allograft sperm and developing embryo, but the information whether impaired glycosylation may influence male fertility potential is still limited. We have analyzed seminal plasma N-glycome in pooled samples derived from fertile and infertile men by means of MALDI-TOF/TOF tandem mass spectrometry. Among infertile subjects, normozoospermic, oligozoospermic, asthenozoospermic and oligoasthenozoospermic samples were obtained. Eighty-six oligosaccharides were identified in all the analyzed samples. Differences in the content of unique glycans: high mannose and hybrid type, lacking terminal sialic acid and highly fucosylated were found when samples derived from infertile subjects with different semen patterns were compared to the fertile control. The content of highly branched glycans was 3-fold elevated in normozoospermic infertile men, while the expression of highly fucosylated oligosaccharides was increased in asthenozoospermic, oligozoospermic and oligoasthenozoospermic samples. Sialylation of oligosaccharides was decreased in oligozoospermic, oligoasthenozoospermic and especially asthenozoospermic samples, but increased in infertile normozoospermic subjects. Altered glycosylation observed in seminal plasma may reflect similar changes in sperm surface glycoproteins, and may disturb sperm interaction with female immune system. We suggest that at least some cases of unexplained male infertility may be associated with impaired glycosylation.

The analysis of sialylation, N-glycan branching, and expression of O-glycans in seminal plasma of infertile men.

Carbohydrates are known to mediate some events involved in successful fertilization. Although some studies on the glycosylation of seminal plasma proteins are available, the total glycan profile was rarely analyzed as a feature influencing fertilization potential. In this work we aimed to compare some glycosylation traits in seminal plasma glycoproteins of fertile and infertile men. The following findings emerge from our studies: (1) in human seminal plasma the presence and alterations of O-linked glycans were observed; (2) the expression of SNA-reactive sialic acid significantly differs between asthenozoospermia and both normozoospermic (fertile and infertile) groups; (3) the expression of PHA-L-reactive highly branched N-glycans was significantly lower in oligozoospermic patients than in both normozoospermic groups. Indication of the appropriate lectins that would enable the possibly precise determination of the glycan profile seems to be a good supplement to mass spectrum analysis. Extension of the lectin panel is useful for the further research.