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Sylwia Dzięgielewska-Gęsiak,1 Alicja Płóciniczak,2 Katarzyna Wilemska-Kucharzewska,1 Teresa Kokot,1 Małgorzata Muc-Wierzgoń,1 Ewa Wysocka21Department of Internal Medicine, Medical University of Silesia, 44-902 Bytom, Poland; 2Department of Laboratory Diagnostics, Poznan University of Medical Science, 60-569 Poznan, PolandObjective: Ageing is one of the major risks for atherosclerosis. The age-related changes of interactions between plasma lipids, oxidative stress, antioxidant defense, and glycation processes are still not established while we age. Thus, the aim of the study was to analyze such relationships in individuals at risk for atherosclerosis due to their age.Methods: Elderly and middle-aged persons with no acute disease or severe chronic disorder were assessed. Fasting plasma lipids (total cholesterol (T-C), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol, and triacylglycerols), thiobarbituric acid reacting substances (TBARS), plasma total antioxidant status (TAS), and glucose and glycated proteins (fructosamine (FA) and glycated hemoglobin (HbA1c)) were determined. An oral glucose tolerance test allowed exclusion of persons with type 2 diabetes.Results: Lipid profiles were significantly profitable, increased HDL-C especially (p

Malgorzata Muc-Wierzgon, Ewa Nowakowska-Zajdel, Katarzyna Klakla, Sylwia Dziegielewska-Gesiak, Edyta Fatyga, Teresa Kokot Department of Internal Medicine, Silesian Medical University, Katowice, PolandLapid et al recently published an interesting article in Clinical Interventions in Aging entitled: "Vitamin D and depression in geriatric primary care patients".1 Their conclusion that "lower vitamin D levels were associated with depression" was based on a study that analyzed the patients in primary care internal medicine "who had at least one total serum 25-hydroxyvitamin D [25(OH)D] level from 2004–2008. For those with multiple serum 25(OH)D measurements, authors used the index of first measurements".1View original paper by Lapid and colleagues.

Malgorzata Muc-Wierzgoń, Teresa Kokot, Ewa Nowakowska-Zajdel, Adam Błażelonis, Edyta Fatyga Department of Internal Medicine, Silesian Medical University, Bytom, PolandDear editorGil-Montoya et al has recently published an interesting article in Clinical Interventions in Aging entitled: “Oral health in the elderly patient and its impact on general well-being: a nonsystematic review”.1 Authors presented a non-systematic review of the published data regarding the oral health status of the elderly and its main repercussions, including its impact on general health and nutrition.View original paper by Gil-Montoya and colleagues.

The influence of low-energy defibrillation on changes in the ET-1 levels in the myocardium and on disruptions in coronary blood flow and microcirculation being their consequence still remains unclear. Myocardial microcirculatory dysfunction is considered as a significant cause underlying myocardial dysfunction in post-cardiac arrest syndrome. This study is aimed at evaluating time-dependent changes in ET-1 levels in serum and the heart of a healthy rabbit following the application of a low-energy two-phase shock impulse. The research was conducted in 35 healthy rabbits at the age of 36 - 42 weeks and with body mass from 3200 to 4150 grams. The animals were divided in a randomized way into four groups depending on the dose of the electrical energy planned for the application during the experiment. The life parameters of the animals were monitored with the application of BeneView T5 patient monitor. The concentration of endothelin-1 in the groups was measured before, 15 and 360 minutes after the application of the low-energy doublephase straight-lined electrical impulse. A transthoracic low-energy defibrillation shock impulse causes a long-term increase in the endothelin-1 levels in the heart muscle and blood serum in a healthy rabbit. The increase in ET-1 levels results from the effect of electrical energy, independently of consequences of the ischemia/reperfusion injury. The increase in the endothelin-1 levels may lead to capillary blood flow abnormalities in the heart, contributing to the development of its dysfunction in the course of postresuscitation disease. [ABSTRACT FROM AUTHOR]

The co-chaperone BAG3 plays critical roles in maintaining cellular proteostasis. It associates with 14-3-3 proteins during the trafficking of aggregation-prone proteins and facilitates their degradation through chaperone-assisted selective autophagy in cooperation with small heat shock proteins. Although reversible phosphorylation regulates BAG3 function, the involved phosphatases remain unknown. Here, we used affinity purification mass spectrometry to identify phosphatases that target BAG3. Of the hits, we evaluated the involvement of protein phosphatase-1 (PP1) using chemical inhibitors and activators in in vitro and cellular approaches. Our results demonstrate that PP1 can dephosphorylate BAG3-pS136 in cells and counteract 14-3-3γ association with BAG3 at this motif. Furthermore, protein phosphatase-5 (PP5) co-enriched with proteostasis-related proteins, and it has the capacity to dephosphorylate a BAG3 phosphorylation-site cluster regulating the interaction of BAG3 with small heat shock proteins and BAG3-mediated protein degradation. Our findings provide new insights into the regulation of BAG3 by phosphatases. This paves the way for future research focused on the precise control of BAG3 function through its regulatory proteins, potentially holding therapeutic promise for diseases characterized by disrupted proteostasis., (© 2024 Kokot et al.)

The actin-binding protein filamin c (FLNc) is a key mediator in the response of skeletal muscle cells to mechanical stress. In addition to its function as a structural scaffold, FLNc acts as a signaling adaptor which is phosphorylated at S2234 in its mechanosensitive domain 20 (d20) through AKT. Here, we discovered a strong dephosphorylation of FLNc-pS2234 in cultured skeletal myotubes under acute mechanical stress, despite high AKT activity. We found that all three protein phosphatase 1 (PP1) isoforms are part of the FLNc d18-21 interactome. Enzymatic assays demonstrate that PP1 efficiently dephosphorylates FLNc-pS2234 and in vitro and in cells upon PP1 activation using specific modulators. FLNc-pS2234 dephosphorylation promotes the interaction with FILIP1, a mediator for filamin degradation. Altogether, we present a model in which dephosphorylation of FLNc d20 by the dominant action of PP1c prevails over AKT activity to promote the binding of the filamin degradation-inducing factor FILIP1 during acute mechanical stress., (© 2024. The Author(s).)

Background: Women's nutrition should be different from that of men. Women have lower energy requirements than men. And the need for certain vitamins and minerals is higher in women, this applies to iron, calcium, magnesium, vitamin D and vitamin B9 (folic acid). This is related to hormonal changes including menstruation, pregnancy, breastfeeding and the onset of menopause. Through hormonal changes and the changing physiological state, women are at greater risk of anaemia, bone weakness and osteoporosis.The aim of the study was to assess changes in the dietary pattern among women from the Silesian Agglomeration in Poland between 2011 and 2022., Material and Method: The survey was conducted in 2011 (March-May 2011) and in 2022 (October-November 2022) among women living in the Silesian Agglomeration (Silesia region) in Poland aged 20-50. After consideration of the inclusion and exclusion criteria, 745 women were included in the final analysis, including 437 women screened in 2011 and 308 women screened in 2022.The research tool used in this publication was a survey questionnaire consisting of 2 parts. The first part of the questionnaire consisted of demographic data. The second part of the study focused on the dietary habits of the women surveyed and the frequency of consumption of individual foods (FFQ)., Results: More women in 2022 ate breakfast than in 2011 (77.6% vs. 63.8% p  < 0.001), were more likely to eat breakfast I at home (73.1% vs. 62.5%; p  < 0.001), were more likely to eat breakfast II (39.0% vs. 35.2%; p  = 0.001), were more likely to eat breakfast II at home (28.6% vs. 19.2%; p  = 0.002), and were more likely to eat lunch at work (16.6% vs. 3.4%; p  < 0.001). Women in 2022 were more likely to consume fast-food ( p  = 0.001), salty snacks (chips, crisps) ( p  < 0.001) and sweets ( p  < 0.001). Women in 2022 were more likely to consume whole-grain bread ( p  < 0.001), wholemeal pasta ( p  < 0.001), brown rice ( p  < 0.001), oatmeal ( p  < 0.001), buckwheat groats ( p  = 0.06), and bran ( p  < 0.001) than women in 2011. They were less likely to consume white bread ( p  < 0.0001), light pasta ( p  = 0.004), white rice ( p  = 0.008) and cornflakes ( p  < 0.001) in 2022.Women in 2022 were significantly more likely to consume vegetables ( p  < 0.001) than women in 2011., Conclusion: Eating habits in Silesia region women changed between 2011 and 2022. In 2022, women were more likely to choose cereal products considered health-promoting and rich in dietary fiber (including whole-grain bread, whole-grain pasta, oatmeal, bran) were more likely to consume vegetables, dry pulses and vegetarian dinners, and consumed less meat, cured meats, fish and dairy products. Consumption of fast-food, salty snacks (such as chips) and sweets increased., 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 © 2023 Białek-Dratwa, Kokot, Czech, Całyniuk, Kiciak, Staśkiewicz, Stanjek-Cichoracka, Słoma-Krześlak, Sobek, Kujawińska, Grot, Szczepańska and Muc-Wierzgoń.)

Protein phosphorylation on serine and threonine residues is a widely distributed post-translational modification on proteins that acts to regulate their function. Phosphoprotein phosphatases (PPPs) contribute significantly to a plethora of cellular functions through the accurate dephosphorylation of phosphorylated residues. Most PPPs accomplish their purpose through the formation of complex holoenzymes composed of a catalytic subunit with various regulatory subunits. PPP holoenzymes then bind and dephosphorylate substrates in a highly specific manner. Despite the high prevalence of PPPs and their important role for cellular function, their mechanisms of action in the cell are still not well understood. Nevertheless, substantial experimental advancements in (phospho-)proteomics, structural and computational biology have contributed significantly to a better understanding of PPP biology in recent years. This Review focuses on recent approaches and provides an overview of substantial new insights into the complex mechanism of PPP holoenzyme regulation and substrate selectivity., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

A detailed understanding of the sequence preference surrounding phosphorylation sites is essential for deciphering the function of the human phosphoproteome . Whereas the mechanisms for substrate site recognition by kinases are relatively well understood, the selection mechanisms for the corresponding phosphatases pose several obstacles. However, multiple pieces of evidence point towards a role of the amino acid sequence in the direct vicinity of the phosphorylation site for recognition by phosphatase enzymes. Peptide library-based studies for enzymes attaching posttranslational modifications (PTMs) are relatively straight forward to carry out. However, studying enzymes removing PTMs pose a challenge in that libraries with a PTM attached are needed as a starting point. Here, we present our methodology using large synthetic phosphopeptide libraries to study the preferred sequence context of protein phosphatases. The approach, termed "phosphopeptide library dephosphorylation followed by mass spectrometry" (PLDMS), allows for the exact control of phosphorylation site incorporation and the synthetic route is capable of covering several thousand peptides in a single tube reaction. Furthermore, it enables the user to analyze MS data tailored to the needs of a specific library and thereby increase data quality. We therefore expect a wide applicability of this technique for a range of enzymes catalyzing the removal of PTMs., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

B cell antigen receptor (BCR) signaling is initiated by protein kinases and limited by counteracting phosphatases that currently are less well studied in their regulation of BCR signaling. Here, we used the B cell line Ramos to identify and quantify human B cell signaling components. Specifically, a protein tyrosine phosphatase profiling revealed a high expression of the protein tyrosine phosphatase 1B (PTP1B) in Ramos and human naïve B cells. The loss of PTP1B leads to increased B cell activation. Through substrate trapping in combination with quantitative mass spectrometry, we identified 22 putative substrates or interactors of PTP1B. We validated Igα, CD22, PLCγ1/2, CBL, BCAP, and APLP2 as specific substrates of PTP1B in Ramos B cells. The tyrosine kinase BTK and the two adaptor proteins GRB2 and VAV1 were identified as direct binding partners and potential substrates of PTP1B. We showed that PTP1B dephosphorylates the inhibitory receptor protein CD22 at phosphotyrosine 807. We conclude that PTP1B negatively modulates BCR signaling by dephosphorylating distinct phosphotyrosines in B cell-specific receptor proteins and various downstream signaling components., (© 2021 Schwarz et al.)

The phosphatases PP1 and PP2A are responsible for the majority of dephosphorylation reactions on phosphoserine (pSer) and phosphothreonine (pThr), and are involved in virtually all cellular processes and numerous diseases. The catalytic subunits exist in cells in form of holoenzymes, which impart substrate specificity. The contribution of the catalytic subunits to the recognition of substrates is unclear. By developing a phosphopeptide library approach and a phosphoproteomic assay, we demonstrate that the specificity of PP1 and PP2A holoenzymes towards pThr and of PP1 for basic motifs adjacent to the phosphorylation site are due to intrinsic properties of the catalytic subunits. Thus, we dissect this amino acid specificity of the catalytic subunits from the contribution of regulatory proteins. Furthermore, our approach enables discovering a role for PP1 as regulator of the GRB-associated-binding protein 2 (GAB2)/14-3-3 complex. Beyond this, we expect that this approach is broadly applicable to detect enzyme-substrate recognition preferences.

Protein phosphatase-1 (PP1) drives a large amount of phosphoSer/Thr protein dephosphorylations in eukaryotes to counteract multiple kinases in signaling pathways. The phosphatase requires divalent metal cations for catalytic activity and contains iron naturally. Iron has been suggested to have an influence on PP1 activity through Fe 2+ and Fe 3+ oxidation states. However, much biochemical and all structural data have been obtained with recombinant PP1 containing Mn 2+ ions. Purifying iron-containing PP1 from Escherichia coli has thus far not been possible. Here, we present the preparation, characterization, and structure of iron-bound PP1α in inactive and active states. We establish a key role for the electronic/redox properties of iron in PP1 activity and shed light on the difference in substrate specificity between iron- and manganese-containing PP1., (© 2018 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Aim: This study assessed the nutritional status and physical activity levels of 150 female students aged 10-18 from three top Polish ballet schools, where the most promising dancers go on to pursue professional ballet careers., Methods: We analysed the girls' body composition, physical activity level (PAL) and PAL coefficient. The ballet students also completed a questionnaire., Results: The results revealed large deficiencies in the body weight and body fat of the young ballerinas. The mean body mass index (BMI) for the group was 16.8 kg/m 2 . Polish centile charts showed that 18% of the girls had BMIs below the norm and 54% had a lower than average body fat content, with a mean of 15.6%. The body fat content was lowest (13.8%) in the 13- to 15-year age group. On average, girls aged 10-12 had 15.7% body fat, while girls aged 16-18 had 18.4%. The mean values for the anthropometric measurements were higher in older girls. The majority (72%) of the respondents reported high physical activity levels, defined as more than 15 hours of exercise per week., Conclusion: Special attention should be paid to low BMIs and body fat in young ballet school dancers aged 10-15 years., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Toll-like receptors (TLRs) are involved in transduction of molecular signals in immune process such as induction and regulation of immunity, production of cytokines, and recognition of specific molecular patterns on the surface of microorganisms, but also in cancer development-which was partially proven in previous studies. There is a lack of detailed research on differentiating levels of TLR expression in colorectal cancer at different stages of its advancement, so in our study we want to determine whether there is such a difference of TLRs and TLR-connected protein expression. In this study, 83 samples of colorectal adenocarcinoma (varying clinical degrees) and 40 slices of healthy colon tissue have been analyzed. The delivered material was subjected to homogenization and extraction of total RNA. The isolated RNA was subsequently purified and valued quantitatively and qualitatively. Quantification was performed using a spectrophotometer GeneQuant II. The RNA concentration in the tested samples was determined spectrophotometrically. A qualitative assessment was performed by performing electrophoresis on a 1% agarose gel stained with ethidium bromide. The expression profile of the genes encoding the TLRs was determined using oligonucleotide microarray HG-U133A. To determine the mRNA (messenger RNA), differentiate cancerous tissue from normal colon using PL-Grid Infrastructure. The results were analyzed statistically, taking a significance level P < 0.05. In the study were found three proteins, DUSP2, IFNγ, EIF4A1, associated with TLR system, that differentiate early stages of colorectal cancer of healthy tissue, moreover eleven, inter alia: vascular endothelial growth factor (VEGF), which differentiate high stage of cancer of healthy tissues. The results emphasize the role of pathways associated with TLR activation in the pathogenesis of colorectal cancer. In summary, molecular studies on the development of colorectal cancer will enable the introduction of minimally invasive genetic diagnosis of early forms of cancer. In addition, identification of new signaling pathways can provide the basis for developing new therapeutic methods.

Nitric oxide (NO) has emerged as a potent effector molecule for a post-resuscitation disease as a result of the low-energy defibrillation. In this article, the authors anlysed the changes of endogenous nitric oxide levels in serum of 35 healthy rabbits after the transthoracic application of low-energy two-phase shock impulse. The animals were randomised into four groups according to the electrical energy dose to be applied during the experiment. Life parameters of the animals were monitored using the BeneViev T5 patient monitor. The nitric oxide concentration in the groups was measured before, 15 and 360 minutes after applying the low-energy two-phase linear electrical impulse. From 15 to 360 minutes the decrease in nitric oxide concentration was observed. The effect was dependent on single impulse and accumulated energy volumes. The highest decrease of NO concentration was observed in 15 minutes following the application of two electrical impulses of accumulated energy of 8 J/kg/bm. After 360 minutes following the application, a significant increase in nitric oxide levels was recorded. The changes in the nitric oxide levels in the blood serum 15 minutes after the defibrillation may initiate the vasomotor disorders as a result of the low-energy influence of the shock impulse.

The similarity of Lyme borreliosis to other diseases and its complex pathogenesis present diagnostic and therapeutic difficulties. The changes that occur at the cellular and molecular levels after a Borrelia sp. infection still remain poorly understood. Therefore, the present study focused on the expression of TLR and TLR-signaling genes in human dermal fibroblasts in the differentiation of an infection with Borrelia burgdorferi sensu lato spirochetes. Normal human dermal fibroblasts were cultured with the spirochetes of Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii. Total RNA was extracted from the cells using TRIzol reagent. The analysis of the expression profiles of TLRs and TLR-related genes was performed using commercially available oligonucleotide microarrays of HG-U133A. The GeneSpring 12.0 platform and significance analysis of microarrays were used for the statistical analysis of microarray data. The analyses using the oligonucleotide microarray and QRT-PCR techniques permitted to identify the genes encoding TLR4 and TLR6 as specific for infection with B. afzelii and B. burgdorferi sensu stricto. In turn, TLR3 was only characteristic for an infection with B. burgdorferi sensu stricto. There were no changes in the TLR gene expression after infection with B. garinii. Our findings confirm that Borrelia has a major effect on fibroblast gene expression. Further characterization of changes in gene expression may lead to valuable insights into the role of the toll-like receptor in the pathogenesis of Lyme disease and may provide guidelines for the development of diagnostic markers for an infection with a particular Borrelia genospecies. Moreover, this will help to identify better treatment strategies for Lyme disease.

The aim of this study was to identify the best prognostic parameters for quickly assessing fluid volume status in the context of nutritional status and water balance in older persons and to facilitate decision-making of the general practitioner (GP). This pilot study was conducted with 142 volunteers aged 60 years or older who were Polish students of the University of the Third Age. Inclusion and exclusion criteria for the study were defined. Assessment tools included: the Mini Nutritional Assessment questionnaire (MNA®) and the anthropometric measurements. Weight and body composition analysis were determined by Bioelectrical Impedance Analysis (BIA) using the Tanita MC-780 multi frequency segmental Body Composition Analyzer. According to the MNA scale, 89.2% of the sample was wellnourished and 10.8% were at risk of malnutrition. A total of 47.1% participants had normal body mass index, 20.6% were overweight, and 32.3% were obese. The BIA showed that females had more fat mass (FM) compared to males (35.84% vs 23.90%), while men had more free fat mass (FFM) and total body water (TBW; 61.16% vs 45.22% and 53.31% vs 45.22%respectively). There were no statistically significant differences in FM, FFM, and TBW by age. The ratio of Extracellular to Total Body Water (ECW/TBW) was higher in women than in men (46.76% vs 43.66%). Of all measures, only ECW/TBW increased significantly with age and sex, especially after 65 years. We propose that ECW/TBW may be used as the first, simple, and fast indicator of water volume status in the context of nutritional status and water balance in older subjects. Systematic control of the ECW/TBW by GP or nurse may increase senior independence, resulting in longer self-maintenance at home and reduced hospital admissions.

Increasing numbers of reports about the role of adamalysins (ADAM) in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin-like growth factors (IGF1, IGF2), vascular growth factor (VEGF), tumor necrosis factor α (TNFα) and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients.

Advances in genomics, molecular pathology and metabolism have generated many candidate biomarkers of colorectal cancer with potential clinical value. Epidemiological and biological studies suggest a role for adiposity, dyslipidaemia, hyperinsulinemia, altered glucose homeostasis, and elevated expression of insulin-like growth factor (IGF) axis members in the risk and prognosis of cancer. This review discusses some recent past and current approaches being taken by researches in obesity and metabolic disorders. The authors describe three main systems as the most studied metabolic candidates of carcinogenesis: dyslipidemias, adipokines and insulin/IGF axis. However, each of these components is unsuccessful in defining the diseases risk and progression, while their co-occurrence increases cancer incidence and mortality in both men and women.