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Prostate Cancer and Prostatic Diseases Dec 2023Although skeletal muscle releases cytokines called myokines during exercise, the kinetics of the acute myokine response to exercise (exercise-induced circulatory myokine...
Acute effect of high-intensity interval aerobic exercise on serum myokine levels and resulting tumour-suppressive effect in trained patients with advanced prostate cancer.
PURPOSE
Although skeletal muscle releases cytokines called myokines during exercise, the kinetics of the acute myokine response to exercise (exercise-induced circulatory myokine level alteration) is unknown in patients with advanced prostate cancer. We measured myokine levels in serum obtained from patients with metastatic castrate-resistant prostate cancer (mCRPC) before and after exercise and assessed the growth-suppressive effect of the serum by applying it to a PCa cell line.
METHODS
Nine patients with mCRPC (age = 67.8 ± 10.1 years, time since mCRPC diagnosis 36.2 ± 22.5 months) undertook 34 min of a high-intensity interval exercise session on a cycle ergometer. Blood was collected immediately pre, post and 30 min post. Serum levels of secreted protein acidic and rich in cysteine (SPARC), oncostatin M (OSM), interleukin-6 (IL-6), interleukin-15 (IL-15), decorin, irisin, and IGF-1 were determined. Growth of the androgen-independent PCa cell line DU-145 exposed to serum collected at three points was measured.
RESULTS
There was a significant elevation of SPARC (19.9%, P = 0.048), OSM (11.5%, P = 0.001), IL-6 (10.2%, P = 0.02) and IL-15 (7.8%, P = 0.023) in serum collected immediately after exercise compared to baseline, returning to baseline after 30 min rest. A significant reduction in DU-145 Cell growth and the Cell Index area under the curve at 72 h incubation was observed with the presence of serum obtained immediately post-exercise (Cell Index at 72 h: 16.9%, P < 0.001; area under the curve: 15.2%, P < 0.001) and with the presence of serum obtained 30 min post-exercise compared to baseline (Cell Index at 72 h: 6.5%; area under the curve: 8.8%, P < 0.001).
CONCLUSION
This study provides preliminary evidence for an acute exercise-induced myokine response and tumour growth suppression in serum after a bout of high-intensity interval exercise in patients with advanced PCa.
Topics: Male; Humans; Middle Aged; Aged; Interleukin-6; Interleukin-15; Osteonectin; Prostatic Neoplasms, Castration-Resistant; Exercise
PubMed: 36446945
DOI: 10.1038/s41391-022-00624-4 -
Experimental Eye Research Oct 2023The harderian gland (HG) is a gland located at the base of the nictating membrane and fills the inferomedial aspect of the orbit in rodents. It is under the influence of...
The harderian gland (HG) is a gland located at the base of the nictating membrane and fills the inferomedial aspect of the orbit in rodents. It is under the influence of the hypothalamic-pituitary-gonadal axis and, because of its hormone receptors, it is a target tissue for prolactin (PRL) and sex steroid hormones (estrogen and progesterone). In humans and murine, the anterior surface of the eyes is protected by a tear film synthesized by glands associated with the eye. In order to understand the endocrine changes caused by hyperprolactinemia in the glands responsible for the formation of the tear film, we used an animal model with metoclopramide-induced hyperprolactinemia (HPRL). Given the evidences that HPRL can lead to a process of cell death and tissue fibrosis, the protein expression of small leucine-rich proteoglycans (SLRPs) was analyzed through immunohistochemistry in the HG of the non- and the pregnant female mice with hyperprolactinemia. The SRLPs are related to collagen fibrillogenesis and they participate in pro-apoptotic signals. Our data revealed that high prolactin levels and changes in steroid hormones (estrogen and progesterone) can lead to an alteration in the amount of collagen, and in the structure of type I and III collagen fibers through changes in the amounts of lumican and decorin, which are responsible for collagen fibrillogenesis. This fact can lead to the impaired functioning of the HG by excessive apoptosis in the HG of the non- and the pregnant female mice with HPRL and especially in the HG of pregnancy-associated hyperprolactinemia.
Topics: Pregnancy; Humans; Mice; Female; Animals; Proteoglycans; Extracellular Matrix Proteins; Hyperprolactinemia; Chondroitin Sulfate Proteoglycans; Decorin; Prolactin; Progesterone; Harderian Gland; Collagen; Extracellular Matrix; Estrogens
PubMed: 37580001
DOI: 10.1016/j.exer.2023.109612 -
International Urogynecology Journal Apr 2024The objective was to investigate the correlation between endogenous vaginal microecological alterations and female pelvic organ prolapse (POP).
INTRODUCTION AND HYPOTHESIS
The objective was to investigate the correlation between endogenous vaginal microecological alterations and female pelvic organ prolapse (POP).
METHODS
Patients who underwent vaginal hysterectomy were retrospectively analyzed as the POP group (n = 30) and the non-POP group (n = 30). The vaginal microbial metabolites and enzyme levels were tested using the dry chemoenzymatic method. The mRNA and protein expression were tested using real-time quantitative PCR and immunohistochemistry. SPSS version 25.0 and GraphPad Prism 8.0 were performed for statistical analysis.
RESULTS
Compared with the non-POP group, the vaginal pH, HO positivity and leukocyte esterase positivity were higher in patients with POP (all p < 0.05). Further analysis showed that patients with pelvic organ prolapse quantification (POP-Q) stage IV had higher rates of vaginal pH, HO positivity and leukocyte esterase positivity than those with POP-Q stage III. Additionally, the mRNA expression of decorin (DCN), transforming growth factor beta 1 (TGF-β1), and matrix metalloproteinase-3 (MMP-3) in uterosacral ligament tissues were higher, whereas collagen I and III were lower. Similarly, the positive expression of MMP-3 in uterosacral ligament tissue was significantly upregulated in the POP group compared with the non-POP group (p = 0.035), whereas collagen I (p = 0.004) and collagen III (p = 0.019) in uterosacral ligament tissue were significantly downregulated in the POP group. Correlation analysis revealed that there was a significant correlation between vaginal microecology and collagen metabolism. In addition, MMP-3 correlated negatively with collagen I and collagen III (p = 0.002, r = -0.533; p = 0.002, r = -0.534 respectively), whereas collagen I correlated positively with collagen III (p = 0.001, r = 0.578).
CONCLUSIONS
Vaginal microecological dysbiosis affects the occurrence of female POP, which could be considered a novel therapeutic option.
Topics: Female; Humans; Pelvic Organ Prolapse; Vagina; Middle Aged; Retrospective Studies; Matrix Metalloproteinase 3; Decorin; Aged; Transforming Growth Factor beta1; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hysterectomy, Vaginal; Collagen Type I; Collagen Type III; RNA, Messenger; Ligaments; Microbiota; Adult
PubMed: 38488886
DOI: 10.1007/s00192-024-05759-7 -
Journal of Voice : Official Journal of... Sep 2023To explore the effects of short- and long-term cigarette smoke extract (CSE) stimulation on the expression of extracellular matrix (ECM) components and inflammatory...
OBJECTIVES
To explore the effects of short- and long-term cigarette smoke extract (CSE) stimulation on the expression of extracellular matrix (ECM) components and inflammatory cytokines in an in vitro model for studying Reinke's edema using human vocal fold fibroblasts (hVFF).
STUDY DESIGN
Experimental pilot study using intervention with CSE in vitro.
METHODS
Immortalized hVFF were pretreated with 5% CSE or control medium over a period of 2 or 8 weeks, followed by a final 3-day incubation time. We evaluated cell proliferation and examined gene and protein expression of control- and CSE-treated cells using quantitative polymerase chain reaction, Western Blot and enzyme linked immunosorbent assay.
RESULTS
Cell numbers of CSE-treated hVFF strongly decreased after 8 weeks and limited the overall duration of the experiment. We observed significant upregulations in gene expression and protein levels of inflammatory markers (cyclooxygenase COX1, COX2) and ECM components (decorin, matrix metalloproteinase 1, transglutaminase 2, gremlin 2) induced by CSE after 2 and 8 weeks. Interleukin 1 receptor 1, prostaglandin I2 synthase, collagen- and hyaluronan-related gene expression showed minor upregulations. The majority of the observed genes were similarly regulated at both time points. However, the CSE-induced mRNA level of COX1 was ablated after 8 weeks.
CONCLUSION
Long-term treatment did not yield results significantly different from the short-term protocol. Therefore, we propose that prolonged CSE exposure is not superior to short-term settings, which save both time and materials.
PubMed: 37696688
DOI: 10.1016/j.jvoice.2023.08.002 -
International Journal of Molecular... Jan 2024Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and...
Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced ( < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen ( < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis.
Topics: Humans; Biglycan; Decorin; Atherosclerosis; Plaque, Atherosclerotic; Extracellular Matrix Proteins; Aspirin; Collagen Type I; Thrombosis
PubMed: 38256024
DOI: 10.3390/ijms25020950 -
International Journal of Biological... Sep 2023Fish skin gelatin is an important functional product used in food, medicine and other industries. However, the structure and function of gelatins extracted with...
Fish skin gelatin is an important functional product used in food, medicine and other industries. However, the structure and function of gelatins extracted with different methods differ significantly, thus limiting its production and application. This study used dry-salting, wet-salting, pepsin, acid and heat methods to extract gelatins from the skins of tilapia, grass carp and sea perch. Then, their structural characteristics (micro- and ultra-structure, amyloid-like fibril, etc.) and functional properties (viscosity, emulsifying performance, antioxidant abilities, etc.) were analyzed, and interaction between gelatin components were also explored. According to the results, the gelatins extracted with dry-salting and wet-salting methods had better reticular structure, larger fiber length/height, and higher viscosity properties, emulsifying and antioxidant capacity. The gelatin extracted by applying heat has the highest gel strength, and the gelatin extracted using pepsin had better thermal stability, water absorption capacity, and fat absorption capacity. Further analysis of component interaction showed that 11 types of collagens detected in the gelatins might promote the conversion of collagen to gelatin through self-assembly ability. The co-assembly of different types of collagens enhanced the properties of gelatin. Decorin had a positive effect on gelatin network structure, but Metallopeptidase inhibited the formation of network structure. Different methods can produce personalized gelatin products according to specific needs. The mining of component interaction would reveal the mechanism of gelatin formation and promote the development of gelatin synthetic biology.
Topics: Animals; Gelatin; Antioxidants; Pepsin A; Chemical Phenomena; Collagen
PubMed: 37479198
DOI: 10.1016/j.ijbiomac.2023.125813 -
Marine Drugs Jul 2023Fish skin gelatin is an important functional product in the food, cosmetics, and biomedicine industries, and establishing a green and effective fish skin gelatin...
Fish skin gelatin is an important functional product in the food, cosmetics, and biomedicine industries, and establishing a green and effective fish skin gelatin extraction method is an effective way to obtain high-quality gelatin and improve its production efficiency. In this study, a trypsin method was used to extract the skin gelatin of sea perch, tilapia, and grass carp, and the microstructures of skin gelatin of these three fish species were analyzed, with such functional characteristics as thermal stability, gel strength, and emulsifying properties measured. The study results show that the skin gelatin of sea perch and tilapia obtained through the trypsin method has a relatively big molecular mass, a dense network structure, and a stable trihelix conformation. In addition, the skin gelatin of these three fish species has a relatively high β-turn content in the secondary structure, good gel strength, and water absorption properties. The compositions of the collagen-associated proteins in the skin gelatins of these three fish species extracted with the trypsin method are significantly different from each other, with positive effects of decorin and biglycan on the stability of the network structure of gelatin and a certain damaging effect of metalloendopeptidase on the network structure of gelatin. The skin gelatin of tilapia has high thermal stability and good emulsifying performance. Therefore, this gelatin type has bright application prospects in such fields as food processing, cosmetics, and drug development. In contrast, the skin gelatin of grass carp has poor functional properties. Therefore, there are significant differences among the structures and functions of skin gelatin extracted from different kinds of fish through the trypsin method. This finding has provided a useful reference for the production of customized fish gelatin according to demand.
Topics: Animals; Perches; Gelatin; Tilapia; Carps; Trypsin
PubMed: 37623704
DOI: 10.3390/md21080423 -
Pregnancy Hypertension Dec 2023Identifying preeclamptic women with an increased risk of severe maternal complications can aid in timely interventions to optimize pregnancy outcomes. Newer biomarkers...
Identifying preeclamptic women with an increased risk of severe maternal complications can aid in timely interventions to optimize pregnancy outcomes. Newer biomarkers such as Decorin and markers of endo glycocalyx disruption were assessed in earlier studies for its role in predicting preeclampsia, but their role in identifying those with adverse maternal outcomes is limited. This study aimed to evaluate the association of these biomarkers with adverse maternal outcomes in women with severe pre-eclampsia. Markers of glycocalyx disruption may be further explored for their role along with clinical features and other biomarkers in identifying women at higher risk of maternal complications.
Topics: Pregnancy; Humans; Female; Pre-Eclampsia; Decorin; Glycocalyx; Pregnancy Outcome; Biomarkers
PubMed: 37844412
DOI: 10.1016/j.preghy.2023.10.010 -
BMC Cancer Nov 2023There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving... (Observational Study)
Observational Study
BACKGROUND
There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP).
METHODS
Proximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts.
RESULTS
In total nine proteins; chemokine (C-C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman's Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19-9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain.
CONCLUSIONS
This is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as "chemo brain". It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition.
TRIAL REGISTRATION
Clinical Trial Registration: NCT03724994.
Topics: Humans; Albumins; Ampulla of Vater; Blood Proteins; CD28 Antigens; Duodenal Neoplasms; Matrix Metalloproteinase 7; Pancreatic Neoplasms; Prospective Studies; Quality of Life
PubMed: 37936126
DOI: 10.1186/s12885-023-11562-2 -
Revista Espanola de Cardiologia... May 2024The CHADS-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value....
INTRODUCTION AND OBJECTIVES
The CHADS-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment.
METHODS
Deep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification.
RESULTS
The LAAT group had higher CHADS-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHADS-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices.
CONCLUSIONS
Protein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.
PubMed: 38729344
DOI: 10.1016/j.rec.2024.04.008