Úvod: Dosud stále platí, že pozdní záchyt onemocnění karcinomem vaječníku je zásadní příčina jeho špatné prognózy. Zatím nebyl identifikován žádný dostatečně senzitivní a zároveň specifický marker ani kombinace markerů a zobrazovacích metod, které by jednoznačně umožňovaly záchyt časných, potenciálně dobře kurabilních stadií a dále prebiopticky diferencovaly skupinu ultrazvukově špatně odlišitelných benigní lézí od maligních tumorů. V designu retrospektivní studie byly zkoumány hladiny sérového vaskulárního endoteliálního faktoru D (VEGF-D). VEGF-D má vztah k nádorem indukované angiogenezi, lymfangiogenezi a remodelaci cév s efektem facilitace metastazování a zlepšené distribuce kyslíku a živin pro nádorovou tkáň. Na druhou stranu lymfatická síť slouží jako bariéra proti nádorové diseminaci a je to transportní systém pro imunitně činné elementy v potlačování nádorového bujení. Cílem studie bylo prověřit, zda existuje rozdíl v hladinách sérového VEGF-D ve skupině pacientek s maligními tumory, s benigními lézemi vaječníku a u zdravých kontrol bez patologického nálezu na adnexech. Metody: Retrospektivně bylo zhodnoceno 162 sér odebraných předoperačně a uchovaných procesem mrazení v biobance v letech 2022–2023. Testovaný soubor byl stratifikován na základě histopatologického výsledku vyšetření adnex na skupinu maligních tumorů (n = 54), skupinu benigních lézí (n = 47) a skupinu zdravých kontrol (n = 61). Ke statistickému vyhodnocení parametrů byly použity metody deskriptivní statistické analýzy. Pro porovnání sérových hladin VEGF-D byly použity neparametrické testy. Všechny analýzy byly uvažovány na hladině významnosti 5 %. Sérový VEGF-D byl analyzován metodou ELISA Quantikine® Human VEGF D R&D Systems a hodnoty byly odečteny spektrofotometricky na readeru TECAN. Výsledky: Výsledek srovnání deskriptivních statistických parametrů je ve vyšetřovaném souboru statisticky významný (p = 0,00067) pro rozdíl mezi hodnotami sérového VEGF-D v souboru benigních lézí a maligních tumorů. Dále existuje statisticky významný rozdíl mezi hodnotami pacientek s maligními tumory a mezi zdravými kontrolami (p = 0,0008). Mezi hodnotami u pacientek s benigními lézemi a u zdravých kontrol nebyl nalezen statisticky významný rozdíl (p = 0,4308). Ve srovnání s konvenčním markerem CA125 korelovala patologicky zvýšená hladina sérového CA125 s nízkou hodnotou sérového VEGF-D u pacientek s maligními tumory. Stejná shoda panovala ve srovnání s markerem HE4: vysoké sérové hladiny HE4 byly ve skupině pacientek s maligním tumorem doprovázeny nízkou hladinou VEGF-D, navíc v bodovém grafickém zobrazení se jasně stratifikovala skupina pacientek s maligními tumory od skupiny benigních lézí a zdravých kontrol. Závěr: S ohledem na získané výsledky má vyšetřování sérové hladiny VEGF-D potenciál diagnostického testu s přínosem ke stratifikaci obtížně prebiopticky diferencovatelných adnextumorů.
Introduction: Until now, it is still true that late detection of ovarian cancer is a major cause of its poor prognosis. So far, no sufficiently sensitive and specific marker or combination of markers and imaging methods has been identified that would unambiguously allow the detection of early potentially highly-curable stages and furthermore prebioptically differentiate a group of poorly distinguishable benign lesions from malignant tumours on ultrasound. In a retrospective study design, serum levels of vascular endothelial growth factor D (VEGF-D) were investigated. VEGF-D is related to tumour-induced angiogenesis, lymphangiogenesis, and vascular remodelling with the effect of facilitating metastasis and improved oxygen and nutrient distribution into tumour tissue. On the other hand, the lymphatic network serves as a barrier against tumour dissemination and is a transport system for immune-active elements in suppressing tumorigenesis. The aim of this study was to investigate that there is a difference in serum VEGF-D levels in a group of patients with malignant tumours, benign ovarian lesions, and healthy controls without pathological findings in the adnexa. Methods: 162 sera collected preoperatively and preserved by a freezing process in a biobank in 2022–2023 were retrospectively evaluated. The test set was stratified on the basis of histopathological results of the adnexal examination into the malignant tumour group (N = 54), benign lesion group (N = 47), and healthy control group (N = 61). Descriptive statistical analysis methods were used for the statistical evaluation of the parameters. Nonparametric tests were used to compare serum VEGF-D levels. All analyses were considered at a significance level of 5%. Serum VEGF-D was analysed by ELISA Quantikine® Human VEGF D R&D Systems and values were read spectrophotometrically on a TECAN reader. Results: The result of the comparison of descriptive statistical parameters was statistically significant (P = 0.00067) for the difference between serum VEGF-D levels in the set of benign lesions and malignant tumours. Furthermore, there was a statistically significant difference between the values of patients with malignant tumours and healthy controls (P = 0.0008). No statistically significant difference was found between the values of patients with benign lesions and healthy controls (P = 0.4308). Compared to the conventional marker CA125, pathologically elevated serum CA125 levels correlated with low serum VEGF-D levels in patients with malignant tumours. The same concordance was observed in comparison with the HE4 marker: high serum HE4 levels were accompanied by low VEGF-D levels in the group of patients with malignant tumours; moreover, the dot plot clearly stratified the group of patients with malignant tumours from the group of benign lesions and healthy controls. Conclusion: In view of the results obtained, the investigation of serum VEGF-D levels has the potential of a diagnostic test with a contribution to the stratification of the difficult of prebioptically differentiating adnexal tumours.
Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.
Bone nonunion delays fracture end repair and is associated with inflammation. Although bone nonunion can be effectively repaired in clinical practice, many cases of failure. Studies have confirmed that BMP-2 and nHA/PA66 repaired bone defects successfully. There are few studies on the effects of the combined application of BMP-2 and NHA/PA66 on bone nonunion osteogenesis and inflammation. We aimed to investigate the expression level of inflammation-related genes in patients with bone nonunion and the effect of BMP-2-infected mesenchymal stem cells combined with nHA/PA66 on the level of inflammation in femur nonunion rats. We searched for a gene expression profile related to bone nonunion inflammation (GSE93138) in the GEO public database. Bone marrow mesenchymal stem cells (MSCs) of SD rats were cultured and passed through. We infected the third generation of MSCs with lentivirus carrying BMP-2 and induced the infected MSCs to bone orientation. We detected the expression level of BMP-2 by RT-PCR and the cell viability and alkaline phosphatase (ALP) activity by CCK8 and then analyzed the cell adhesion ability. Finally, the levels of related inflammatory factors, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and Erythrocyte Sedimentation Rate (ESR), were detected in nonunion rats. Our findings: The patients with nonunion had up-regulated expression of 26 differentially inflammatory genes. These genes are mainly enriched in innate immune response, extracellular region, calcium ion binding, Pantothenate and CoA biosynthesis pathways. The expression level of BMP-2 in the Lenti-BMP-2 group was higher (vs. empty lentivirus vector group: t=5.699; vs. uninfected group t=3.996). The cell activity of the MSCs + BMP-2 + nHA/PA66 group increased gradually. After being combined with nHA/PA66, MSCs transfected with BMP-2 spread all over the surface of nHA/PA66 and grew into the material pores. MSCs + BMP-2 + nHA/PA66 cells showed positive ALP staining, and the OD value of ALP was the highest. The levels of CRP, IL-6, TNF-alpha, and ESR in the MSCs + BMP-2 + nHA/PA66 group were lower than those in the MSCs and MSCs + nHA/PA66 group but higher than those in MSCs + BMP-2 group. The above comparisons were all P<0.05. The findings demonstrated that the expression level of inflammation-related genes increased in the patients with bone nonunion. The infection of MSCs by BMP-2 could promote the directed differentiation of MSCs into osteoblasts in the bone marrow of rats, enhance the cell adhesion ability and ALP activity, and reduce inflammation in rats with bone nonunion.
- MeSH
- dospělí MeSH
- femur metabolismus patologie MeSH
- fraktury femuru metabolismus genetika MeSH
- kostní morfogenetický protein 2 * metabolismus genetika MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezenchymální kmenové buňky * metabolismus MeSH
- nezhojené fraktury * genetika metabolismus MeSH
- osteogeneze MeSH
- potkani Sprague-Dawley * MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- zánět * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- krysa rodu rattus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: This study evaluated maxillary growth and dental arch relationships at 5 and 10 years of age in patients with unilateral cleft lip and palate (UCLP) who underwent early cleft lip and palate surgery. METHODS: 28 patients with UCLP who underwent cleft lip surgery in neonatal age and cleft palate surgery at average age of 7 months without orthodontic treatment (intervention group) were measured for intercanine and intermolar distances and for dental arch length. These measurements were compared with those of 30 healthy participants in a control group. Dental arch relationships in the intervention group were evaluated by 5-YO index at 5 years and the GOSLON Yardstick score at 10 years of patients' age. RESULTS: Patients in the intervention group had significantly shorter mean intercanine distance and arch length than control patients at both 5 and 10 years of age (p<.001 for all). There were no significant differences in intermolar distance at both 5 (p = .945) and 10 years (p = .105) of patients' age. The average 5YO index increased from 2.46 to an average GOSLON 10-year score of 2.89 in intervention group. CONCLUSION: Intercanine distance and dental arch length of patients with UCLP are significantly reduced at 5 and 10 years after early cleft lip and palate surgeries compared to the healthy population. Dental arch relationships at 5 and 10 years of patients with UCLP show comparable outcomes to those reported by other cleft centers. CLINICAL SIGNIFICANCE: This study evaluates maxillary growth in UCLP patients 5 and 10 years of age who underwent early primary lip and palate surgery.
- MeSH
- dítě MeSH
- lidé MeSH
- maxila * chirurgie růst a vývoj MeSH
- maxilofaciální vývoj MeSH
- předškolní dítě MeSH
- průřezové studie MeSH
- rozštěp patra * chirurgie MeSH
- rozštěp rtu * chirurgie MeSH
- studie případů a kontrol MeSH
- zubní oblouk * růst a vývoj patologie chirurgie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Caspase-12 is a molecule whose functions are still not well understood. Although its expression has been found in various tissues, specific roles have been described in only a few cases. These include the effect of caspase-12 on murine bone cell differentiation during craniofacial development. This work focused on the development of the limbs taking place through endochondral ossification, which precedes the formation of the cartilaginous growth plate. Caspase-12 was described here for the first time in growth plate chondrocytes during physiological development. Using pharmacological inhibition, caspase-12 was found to affect chondrogenesis. Limb-derived micromass cultures showed a significantly increased area of chondrogenic nodules after caspase-12 inhibition and there were changes in gene expression, the most significant of which was the reduction of Mmp9. These data point to potential new functions of caspase-12 in chondrogenesis.
- MeSH
- buněčná diferenciace MeSH
- chondrocyty * MeSH
- chondrogeneze * fyziologie MeSH
- inhibitory kaspas farmakologie MeSH
- kaspasa 12 * metabolismus genetika MeSH
- kultivované buňky MeSH
- matrixová metaloproteinasa 9 metabolismus genetika MeSH
- myši MeSH
- růstová ploténka růst a vývoj MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Mammalian neurons lose the ability to regenerate their central nervous system axons as they mature during embryonic or early postnatal development. Neuronal maturation requires a transformation from a situation in which neuronal components grow and assemble to one in which these components are fixed and involved in the machinery for effective information transmission and computation. To regenerate after injury, neurons need to overcome this fixed state to reactivate their growth programme. A variety of intracellular processes involved in initiating or sustaining neuronal maturation, including the regulation of gene expression, cytoskeletal restructuring and shifts in intracellular trafficking, have been shown to prevent axon regeneration. Understanding these processes will contribute to the identification of targets to promote repair after injury or disease.
- MeSH
- axony * fyziologie MeSH
- lidé MeSH
- neurogeneze * fyziologie MeSH
- neurony fyziologie MeSH
- regenerace nervu * fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: The Hueter-Volkmann law (HVL) of the response of growth plate to compression load is a basic concept in orthopaedics. However, little is known about the origin of HVL and its history. MATERIALS AND METHODS: A literature search was performed in original publications and historical sources. RESULTS: An analysis of all Volkmann ́s and Hueter ́s texts has shown that none of their publications was based on experiments, but on the data in the literature and their own clinical observations. They did not deal at all with the effect of pressure on the growth plate and mentioned this structure only marginally. The authors coined the opinion that increased pressure retards and decreased pressure accelerates bone growth. Julius Wolff criticized the HVL and concentrated all his arguments in the book "The law of bone remodeling". According to him, increased pressure leads to bone formation, decreased pressure to its resorption. The Wolff-Volkmann dispute was addressed in the German literature by a number of authors. Walther Müller in his monograph "The normal and pathological physiology of the bone" criticized Wolff for his concept of interstitial bone growth. In Müller ́s view, HVL applies to the growing bone and Wolff confuses growth with hypertrophy of the mature bone. CONCLUSION: The circumstances of the emergence of HVL are inaccurately and incompletely described in the current literature, as they are mostly taken from secondary sources. HVL, as it is presented today, is not the original formulation, but the result of a long historical evolution.
- MeSH
- dějiny 19. století MeSH
- dějiny 20. století MeSH
- lidé MeSH
- ortopedie * dějiny MeSH
- remodelace kosti fyziologie MeSH
- růstová ploténka * fyziologie MeSH
- vývoj kostí fyziologie MeSH
- Check Tag
- dějiny 19. století MeSH
- dějiny 20. století MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- přehledy MeSH
INTRODUCTION: Fibroblast growth factor 20 (Fgf20), a member of the Fgf9 subfamily, was identified as an important regulator of bone differentiation and homeostasis processes. However, the role of Fgf20 in bone physiology has not been approached yet. Here we present a comprehensive bone phenotype analysis of mice with functional ablation of Fgf20. METHODS: The study conducts an extensive analysis of Fgf20 knockout mice compared to controls, incorporating microCT scanning, volumetric analysis, Fgf9 subfamily expression and stimulation experiment and histological evaluation. RESULTS: The bone phenotype could be detected especially in the area of the lumbar and caudal part of the spine and in fingers. Regarding the spine, Fgf20-/- mice exhibited adhesions of the transverse process of the sixth lumbar vertebra to the pelvis as well as malformations in the distal part of their tails. Preaxial polydactyly and polysyndactyly in varying degrees of severity were also detected. High resolution microCT analysis of distal femurs and the fourth lumbar vertebra showed significant differences in structure and mineralization in both cortical and trabecular bone. These findings were histologically validated and may be associated with the expression of Fgf20 in chondrocytes and their progenitors. Moreover, histological sections demonstrated increased bone tissue formation, disruption of Fgf20-/- femur cartilage, and cellular-level alterations, particularly in osteoclasts. We also observed molar dysmorphology, including root taurodontism, and described variations in mineralization and dentin thickness. DISCUSSION: Our analysis provides evidence that Fgf20, together with other members of the Fgf9 subfamily, plays a crucial regulatory role in skeletal development and bone homeostasis.
- MeSH
- fenotyp MeSH
- fibroblastové růstové faktory * metabolismus genetika MeSH
- fyziologická kalcifikace MeSH
- kosti a kostní tkáň metabolismus patologie diagnostické zobrazování abnormality MeSH
- myši inbrední C57BL MeSH
- myši knockoutované * MeSH
- myši MeSH
- osteogeneze MeSH
- rentgenová mikrotomografie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Patologická kalcifikace v kůži a v podkoží je poměrně heterogenním tématem. Z etiopatogenetického hlediska jsou patologické kalcifikace rozdělovány na dystrofické, metastatické, idiopatické a iatrogenní. Zvlášť je vyčleňována kalcifylaxe. Ektopická osifikace v dermatologii je jevem vzácným, vznikajícím buď jako izolovaný nález, či jako součást řady nádorů, pro které je osifikace typickým znakem. Práce shrnuje problematiku patologické kalcifikace a ektopické osifikace v dermatologii a dermatopatologii. Článek předkládá definici, stručný popis etiopatogeneze a výčet nejčastějších onemocnění spojených s jednotlivými typy patologického ukládání vápníku v kůži, podkoží a měkkých tkáních. Text dále shrnuje problematiku osteoma cutis z hlediska klinického obrazu a histopatologie. V závěru je uveden stručný přehled diagnostických a terapeutických možností.
Pathological calcification in the skin and subcutaneous tissue is relatively heterogenous issue. From the etiopathogenetic point of view, the pathological calcifications are divided into dystrophic, metastatic, idiopathic, and iatrogenic type. Calciphylaxis is distinguished as a distinctive type. Ectopic ossification in dermatology is a rare phenomenon, which arises as an isolated finding or as a part of the range of tumours, in which the ossification is a typical feature. The article summarizes the topic of the pathological calcification and the ectopic ossification in dermatology and dermatopathology. The paper presents the definition, the brief description of the etiopathogenesis and the list of the most common diseases connected to the particular types of the pathological calcium deposition in the skin, the subcutaneous tissue and the soft tissue. The review also summarizes the problematics of the osteoma cutis from the view of the clinical picture and the histopathology. Finally, the short summary of the diagnostic and therapeutic alternatives is discussed.
- Klíčová slova
- osteoma cutis,
- MeSH
- kalcinóza * diagnóza etiologie klasifikace patologie terapie MeSH
- kůže patologie MeSH
- lidé MeSH
- osteogeneze * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- výukové testy MeSH
