Although chronic inflammation is implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), the mechanisms responsible are unknown. We demonstrate that the overexpression of the collagen receptor, DDR1, correlates with reduced expression of spindle checkpoint genes, with three transcriptional signatures of aneuploidy and with a higher frequency of copy number alterations, pointing to a potential role for DDR1 in the acquisition of aneuploidy in DLBCL. In support of this, we found that collagen treatment of primary germinal centre B cells transduced with DDR1, not only partially recapitulated the aberrant transcriptional programme of DLBCL but also downregulated the expression of CENPE, a mitotic spindle that has a crucial role in preventing chromosome mis-segregation. CENPE expression was also downregulated following DDR1 activation in two B-cell lymphoma lines and was lost in most DDR1-expressing primary tumours. Crucially, the inhibition of CENPE and the overexpression of a constitutively activated DDR1 were able to induce aneuploidy in vitro. Our findings identify a novel mechanistic link between DDR1 signalling and chromosome instability in B cells and provide novel insights into factors driving aneuploidy in DLBCL.

• MeSH
• aneuploidie * MeSH
• B-lymfocyty metabolismus   MeSH
• chromozomální nestabilita * genetika   MeSH
• difúzní velkobuněčný B-lymfom * genetika   patologie   metabolismus   MeSH
• kolagen farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• receptor DDR1 * genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: The purpose of this study is to report novel and unusual USP6 fusion partners in aneurysmal bone cysts (ABCs). These findings may be useful in routine diagnostics as well as in studying the biology of USP6-related disorders. METHODS: A cohort of seven patients diagnosed with ABC examined between 2014 and 2023 at Motol University Hospital in Prague was included into this retrospective non-randomised study. All cases were analysed using histopathological evaluation, immunohistochemistry and Anchored multiplex RNA methods. Demographic characteristics and clinical data were also analysed. RESULTS: We identified two novel (ZFX and IP6K2), three unusual (MEF2A, EIF1 and COL1A2) and two common (CDH11) fusion partners with USP6 gene among all seven cases of ABC. CONCLUSIONS: Cases in our study were diagnosed as ABCs due to characteristic clinical and morphological presentation. However, not all cases are as self-evident, and molecular testing is necessary. The identification of these gene alterations can be useful in distinction between true ABC and ABC-like changes among many benign and malignant bone tumours.

• MeSH
• aneurysmatické kostní cysty * genetika   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• fúze genů MeSH
• kolagen typu I MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• retrospektivní studie MeSH
• thiolesterasa ubikvitinu * genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Full recovery from spinal cord injury requires axon regeneration to re-establish motor and sensory pathways. In mammals, the failure of sensory and motor axon regeneration has many causes intrinsic and extrinsic to neurons, amongst which is the lack of adhesion molecules needed to interact with the damaged spinal cord. This study addressed this limitation by expressing the integrin adhesion molecule α9, along with its activator kindlin-1, in sensory neurons via adeno-associated viral (AAV) vectors. This enabled sensory axons to regenerate through spinal cord injuries and extend to the brainstem, restoring sensory pathways, touch sensation and sensory behaviours. One of the integrin ligands in the injured spinal cord is tenascin-C, which serves as a substrate for α9β1 integrin, a key receptor in developmental axon guidance. However, the adult PNS and CNS neurons lack this receptor. Sensory neurons were transduced with α9 integrin (which pairs with endogenous β1 to form a α9β1 tenascin receptor) together with the integrin activator kindlin-1. Regeneration from sensory neurons transduced with α9integrin and kindlin-1 was examined after C4 and after T10 dorsal column lesions with C6,7 and L4,5 sensory ganglia injected with AAV1 vectors. In animals treated with α9 integrin and kindlin-1, sensory axons regenerated through tenascin-C-expressing connective tissue strands and bridges across the lesions and then re-entered the CNS tissue. Many axons regenerated rostrally to the level of the medulla. Axons grew through the dorsal grey matter rather than their normal pathway the dorsal columns. Growth was slow, axons taking 12 weeks to grow from T10 to the medulla, a distance of 4-5 cm. Functional recovery was confirmed through cFos activation in neurons rostral to the injury after nerve stimulation and VGLUT1/2 staining indicating new synapse formation above the lesion. Behavioural recovery was seen in both heat and mechanical sensation, as well as tape removal tests. This approach demonstrates the potential of integrin-based therapies for long distance sensory axon regeneration and functional recovery following thoracic and partial recovery after cervical spinal cord injury.

• MeSH
• axony MeSH
• Dependovirus genetika   MeSH
• genetické vektory MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nervové receptory * metabolismus   fyziologie   patologie   MeSH
• obnova funkce fyziologie   MeSH
• poranění míchy * patologie   patofyziologie   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• proteiny nervové tkáně metabolismus   genetika   MeSH
• regenerace nervu * fyziologie   MeSH
• tenascin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

PURPOSE: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis. METHODS: Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined. RESULTS: Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications. CONCLUSION: We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.

• MeSH
• biologické markery krev   MeSH
• hodnocení rizik metody   MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• kolagen typu I krev   MeSH
• konsensus MeSH
• lidé MeSH
• osteoporotické fraktury prevence a kontrola   etiologie   MeSH
• osteoporóza * diagnóza   patofyziologie   farmakoterapie   krev   terapie   MeSH
• peptidové fragmenty krev   MeSH
• peptidy krev   MeSH
• prokolagen krev   MeSH
• remodelace kosti * fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• přehledy MeSH

Pulmonary artery banding is a surgical procedure performed when there is a shunt between the left and right ventricle. Its aim is to constrict the lumen of the pulmonary artery by using a band to reduce blood flow to the lungs. In this study, we report the results of investigating the mechanical properties of a composite composed of poly(L-lactide-co-ε-caprolactone) layers and a collagen matrix (PLCL-COLL). PLCL layers were obtained by electrospinning, impregnated with collagen solution, and finally cross-linked to increase the stiffness of the material. Bands of PLCL-COLL were implanted into a rat peritoneum and explanted after 1, 3, and 6 months in vivo. The mechanical properties of the material before and after implantation were determined using uniaxial tensile tests. The same was done with samples of strips prepared from GORE-TEX material. By comparing the results of tensile tests before implantation and after explantation, it was found that PLCL-COLL degrades in the rat's body and that it exhibits a mechanical response showing of elastic modulus values that correspond well to arterial biomechanics (elastic modulus measured in the initial linear region of the deformation was found to be: 4.14 MPa ± 1.11 MPa, 2.34 MPa ± 1.02 MPa, 1.11 MPa ± 0.77 MPa, and 0.88 MPa ± 0.60 MPa before implantation, and 1, 3, and 6 months after implantation respectively). Similar to the elastic modulus, the strength of the PLCL-COLL composite decreased during in vivo exposure (1.32 ± 0.32 MPa, 0.60 ± 0.26 MPa, 0.44 ± 0.11 MPa, and 0.46 ± 0.28 MPa before implantation, and 1, 3, and 6 months after implantation respectively). In our experiments, PLCL-COLL material was always more compliant than GORE-TEX (elastic modulus 34.7 MPa ± 2.06 MPa before implantation, and 9.35 MPa ± 6.80 MPa after implantation). The results suggest that PLCL-COLL could be a suitable candidate for the development of artery banding tapes, and also for further use in cardiovascular surgery.

• MeSH
• arteria pulmonalis * chirurgie   MeSH
• biokompatibilní materiály chemie   MeSH
• biomechanika MeSH
• kolagen * chemie   metabolismus   MeSH
• krysa rodu rattus MeSH
• mechanické jevy * MeSH
• peritoneum * chirurgie   MeSH
• pevnost v tahu MeSH
• polyestery * chemie   metabolismus   MeSH
• testování materiálů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The circular economy of animal by-products rich in collagen focuses on converting collagen into peptides with a defined molecular weight. Collagen hydrolysates prepared by biotechnological methods from chicken gizzards, deer tendons, and Cyprinus carpio skeletons can be an alternative source of collagen for cosmetic products that traditionally use bovine or porcine collagen hydrolysates. Collagen hydrolysates were characterized by antioxidant activity, surface tension, solution contact angle, and other parameters (dry weight, ash content, and solution clarity). Furthermore, the vibrational characterization of functional groups and their molecular weight was performed using the GPC-RID method. Subsequently, emulsion and gel cosmetic matrices were prepared with 0.5% and 1.5% collagen hydrolysates. Microbiological stability, organoleptic properties, and viscosity were investigated. Verification of the biophysical parameters of the topical formulations was performed in vivo on a group of volunteers by measuring skin hydration and pH and determining trans-epidermal water loss. Fish collagen hydrolysate was the most suitable for cosmetic applications in the parameters investigated. Moreover, it also effectively reduces wrinkles in the periorbital region when used in a gel matrix.

• MeSH
• antioxidancia chemie   farmakologie   MeSH
• aplikace lokální MeSH
• kapři metabolismus   MeSH
• kolagen * chemie   MeSH
• kosmetické přípravky * chemie   MeSH
• kur domácí MeSH
• kůže metabolismus   účinky léků   MeSH
• lidé MeSH
• proteinové hydrolyzáty * chemie   farmakologie   MeSH
• stárnutí kůže účinky léků   MeSH
• viskozita MeSH
• vysoká zvěř MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Preeclampsia is a major pregnancy complication that results in significant maternal and infant mortality and morbidity, yet difficulties remain in the diagnosis of preeclampsia based on clinical parameters alone. The objective was to assess the performance of a hand-held point-of-care (POC) immunoassay in a clinical environment for glycosylated fibronectin (GlyFn) for the prediction of preeclampsia within 4 weeks of sampling. METHODS: Multinational European prospective observational pilot study of predominantly high-risk patients in the second half of pregnancy to assess a point-of-care immunoassay for GlyFn in predicting preeclampsia within 4 weeks of sampling. GlyFn was measured using a second generation hand held POC immunoassay. Results were considered normal for GlyFn concentrations of < 350 μg/mL, positive for GlyFn concentrations of 351-600 μg/mL, and high-positive for GlyFn concentrations > 600 μg/mL. RESULTS: Preeclampsia developed in 16 (19%) of 84 subjects and was associated with a shorter gestational age at delivery 35.3 weeks vs. 37.3 weeks for non-preeclamptics, n = 82; p = 0.001), a higher risk of fetal growth restriction (FGR; 31.2% vs. 10.3% for non-preeclamptics, p = 0.046), and an increased risk of preterm birth < 37 weeks gestation (83.3% vs. 33.3% for non-preeclamptics, (n = 78; p = 0.003). GlyFn positive or high positive was seen in 13/16 (81%) and in 35/68 (51.5%), yielding a sensitivity of 81%, a specificity of 49%, a positive predictive value of 27%, and a negative predictive value of 92%. GlyFn positive or high positive was also associated with preterm birth < 37 weeks in singleton pregnancy non-preeclamptic patients. Preterm birth occurred in 4.8% of those with normal GlyFn, in 26.7% with positive GlyFn, and in 50% of those with high GlyFn in singleton gestations without preeclampsia (p = 0.008). CONCLUSION: The ability to use this test in a POC format provides a method for practitioners to quickly determine risk for preeclampsia in their pregnant patients and offers an affordable alternative, as a single analyte to other diagnostic or screening tests that require laboratory-based testing or ultrasound equipment. Independent of preeclampsia, an elevated GlyFn was also correlated with preterm delivery and requires further study.

• MeSH
• biologické markery analýza   MeSH
• dospělí MeSH
• fibronektiny * analýza   MeSH
• gestační stáří MeSH
• glykované proteiny MeSH
• imunoanalýza metody   MeSH
• lidé MeSH
• pilotní projekty MeSH
• point of care testing MeSH
• prediktivní hodnota testů MeSH
• preeklampsie * diagnóza   MeSH
• prospektivní studie MeSH
• těhotenství MeSH
• vyšetření u lůžka MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Background: Low back pain (LBP) is one of the common musckloskeletal diseases and usual treated by epidural steroid injection (ESI). ESIs improve patients' quality of life, reduce lumbar radicular pain, and postpone spinal surgery. The mechanism of improvement is yet unscertain, perhaps involve type α collagen (COL2α) for bone maintenance, hence, we sought to investigate the role of injected steroids in bone healing focusing on the role of COL2α.Methods: All patients in this research were diagnosed by specialists based on their histories and clinical features and associated diseaeses or compiling therapy. Serum samples collected from LBP patients and control group for comparisons.Results: The present study found a significant (<0.0001) increase in the concentration of COL2α in patients with LBP after injection with ESI treatment compared with patients before injection and healthy individuals.Conclusion: ESI helps LBP sufferers by boosting COL2α, which repairs damaged tissues.

• MeSH
• biologické markery analýza   MeSH
• bolesti zad * farmakoterapie   MeSH
• glukokortikoidy aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• injekce epidurální * metody   MeSH
• klinická studie jako téma metody   MeSH
• kolagen typ II * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• management bolesti metody   MeSH
• radikulopatie etiologie   farmakoterapie   MeSH
• regenerace kostí účinky léků   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Right ventricular dysfunction (RVD) is common in patients with heart failure with reduced ejection fraction, and it is associated with poor prognosis. However, no biomarker reflecting RVD is available for routine clinical use. METHODS: Proteomic analysis of myocardium from the left ventricle and right ventricle (RV) of patients with heart failure with reduced ejection fraction with (n=10) and without RVD (n=10) who underwent heart transplantation was performed. Concentrations of 2 ECM (extracellular matrix) proteins with the highest myocardial upregulation in RVD, FMOD (fibromodulin) and FBLN5 (fibulin-5), were assayed in the blood and tested in a separate cohort of patients with heart failure with reduced ejection fraction (n=232) to test for the association of the 2 proteins with RV function and long-term outcomes. RESULTS: Multivariable linear regression revealed that plasma concentrations of both FMOD and FBLN5 were significantly associated with RV function regardless of the RV function assessment method. No association of FMOD or FBLN5 with left ventricular dysfunction, cardiac index, body mass index, diabetes status, or kidney function was found. Plasma levels of FMOD and FBLN5 were significantly associated with patient outcomes (P=0.005; P=0.004). Area under the curve analysis showed that the addition of FBLN5 or FMOD to RV function assessment had a significantly higher area under the curve after 4 years of follow-up (0.653 and 0.631, respectively) compared with RV function alone (0.570; P<0.05 for both). Similarly, the combination of MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score, FBLN5, and FMOD had a significantly larger area under the curve (0.669) than the combination of MAGGIC score+RVD grade (0.572; P=0.02). The Kaplan-Meier analysis demonstrated that patients with the elevation of both FMOD and FBLN5 (ie, FMOD >64 ng/mL and FMOD >27 ng/mL) had a worse prognosis than those with the elevation of either FBLN5 or FMOD (P=0.03) demonstrating the additive prognostic value of both proteins. CONCLUSIONS: Our study proposes that circulating levels of FMOD and FBLN5 may serve as new biomarkers of RVD in patients with heart failure with reduced ejection fraction.

• MeSH
• biologické markery * krev   MeSH
• extracelulární matrix - proteiny krev   metabolismus   MeSH
• fibromodulin * MeSH
• funkce levé komory srdeční fyziologie   MeSH
• funkce pravé komory srdeční fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• proteiny vázající vápník krev   metabolismus   MeSH
• proteomika * metody   MeSH
• senioři MeSH
• srdeční komory patofyziologie   metabolismus   MeSH
• srdeční selhání * patofyziologie   metabolismus   krev   MeSH
• tepový objem * fyziologie   MeSH
• transplantace srdce MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: The aging process is intricately linked to alterations in cellular and tissue structures, with the respiratory system being particularly susceptible to age-related changes. Therefore, this study aimed to profile the activity of proteases using activity-based probes in lung tissues of old and young rats, focusing on the expression levels of different, in particular cathepsins G and X and matrix Metalloproteinases (MMPs). Additionally, the impact on extracellular matrix (ECM) components, particularly fibronectin, in relation to age-related histological and ultrastructural changes in lung tissues was investigated. MATERIALS AND METHODS: Lung tissues from old and young rats were subjected to activity-based probe profiling to assess the activity of different proteases. Expression levels of cathepsins G and X were quantified, and zymography was performed to evaluate matrix metalloproteinases activity. Furthermore, ECM components, specifically fibronectin, were examined for signs of degradation in the old lung tissues compared to the young ones. Moreover, histological, immunohistochemical and ultrastructural assessments of old and young lung tissue were also conducted. RESULTS: Our results showed that the expression levels of cathepsins G and X were notably higher in old rat lung tissues in contrast to those in young rat lung tissues. Zymography analysis revealed elevated MMP activity in the old lung tissues compared to the young ones. Particularly, significant degradation of fibronectin, an essential ECM component, was observed in the old lung tissues. Numerous histological and ultrastructural alterations were observed in old lung tissues compared to young lung tissues. DISCUSSION AND CONCLUSION: The findings indicate an age-related upregulation of cathepsins G and X along with heightened MMP activity in old rat lung tissues, potentially contributing to the degradation of fibronectin within the ECM. These alterations highlight potential mechanisms underlying age-associated changes in lung tissue integrity and provide insights into protease-mediated ECM remodeling in the context of aging lungs.

• MeSH
• extracelulární matrix metabolismus   ultrastruktura   MeSH
• fibronektiny * metabolismus   MeSH
• kathepsin G metabolismus   MeSH
• krysa rodu rattus MeSH
• lyzozomy ultrastruktura   metabolismus   MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• plíce * ultrastruktura   metabolismus   MeSH
• proteasy metabolismus   MeSH
• stárnutí * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH