The glycoprotein clusterin (CLU) is involved in cell proliferation and DNA damage repair and is highly expressed in tumor cells. Here, we aimed to investigate the effects of CLU dysregulation on two human astrocytic cell lines: CCF-STTG1 astrocytoma cells and SV-40 immortalized normal human astrocytes. We observed that suppression of CLU expression by RNA interference inhibited cell proliferation, triggered the DNA damage response, and resulted in cellular senescence in both cell types tested. To further investigate the underlying mechanism behind these changes, we measured reactive oxygen species, assessed mitochondrial function, and determined selected markers of the senescence-associated secretory phenotype. Our results suggest that CLU deficiency triggers oxidative stress-mediated cellular senescence associated with pronounced alterations in mitochondrial membrane potential, mitochondrial mass, and expression levels of OXPHOS complex I, II, III and IV, indicating mitochondrial dysfunction. This report shows the important role of CLU in cell cycle maintenance in astrocytes. Based on these data, targeting CLU may serve as a potential therapeutic approach valuable for treating gliomas.

• MeSH
• Astrocytes * metabolism   pathology   MeSH
• Clusterin * metabolism   genetics   MeSH
• Humans MeSH
• Membrane Potential, Mitochondrial * physiology   MeSH
• Mitochondria * metabolism   MeSH
• Cell Line, Tumor MeSH
• Oxidative Stress physiology   MeSH
• Oxidative Phosphorylation MeSH
• DNA Damage MeSH
• Cell Proliferation * MeSH
• Reactive Oxygen Species metabolism   MeSH
• Cellular Senescence * physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.

• MeSH
• Antigens, Neoplasm MeSH
• Adult MeSH
• Carbonic Anhydrase IX metabolism   genetics   MeSH
• Carcinoma, Renal Cell * pathology   metabolism   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA, Mitochondrial genetics   metabolism   MeSH
• Mitochondria * metabolism   pathology   genetics   MeSH
• Mutation MeSH
• Von Hippel-Lindau Tumor Suppressor Protein genetics   metabolism   MeSH
• Kidney Neoplasms * pathology   metabolism   genetics   MeSH
• Electron Transport Complex II * metabolism   genetics   MeSH
• Aged MeSH
• Succinate Dehydrogenase genetics   metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: This study aims to explore the lasting effects of stress experienced by pregnant women during World War II (WWII) on body and head measurements of their adult daughters. METHODS: The research sample consists of 336 female university students born in Poland between 1925 and 1951. The data include body measurements and socioeconomic information (parental occupation and number of siblings) acquired from questionnaires collected between the 1950s and 1970s. Student's t-test, Mann-Whitney test and Analysis of Variance were used to analyze differences in body measurements between groups of women born before and during the war, as well as the possible influences of socioeconomic variables. RESULTS: The mean measurements of body height, symphysion height, and waist circumference were lower in women conceived and born during the war compared to those born in the pre-war period. In contrast, the mean measurements of biacromial (shoulder) width, trunk length, and three head dimensions were higher in women conceived and born during the war. Additionally, the number of siblings appeared to be a significant factor that may have influenced the body measurements of women in both groups. For instance, a higher number of living siblings, particularly sisters, was associated with reduced body dimensions, such as body height and waist circumference, while a greater number of deceased siblings was linked to an increase in certain body dimensions. CONCLUSION: The results suggest that war-related prenatal conditions may have influenced the postnatal growth and development of women conceived and born during the war. Notably, the direction of these changes varied, which indicates that the growth response to the war-related conditions was a complex adaptation, reflecting both positive and negative changes in different body parts, rather than a uniform pattern of growth suppression.

• MeSH
• World War II * MeSH
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Stress, Psychological MeSH
• Socioeconomic Factors MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Poland MeSH

A ubiquitous property of bacteria is their ability to move toward more suitable environments, which can also facilitate host-associated activities like colonization and offer the cell several benefits such as bacteria moving towards a favorable gradient or away from a harmful gradient is known as chemotaxis. Bacteria achieve this by rotating flagella in clockwise and anticlockwise directions resulting in "run" and "tumble." This ability of bacteria to sense and respond to any type of change in the environmental factors like pH, osmolarity, redox potential, and temperature is a standard signal transduction system that depends on coupling proteins, which is the bacterial chemotaxis system. There are two architectures for the coupling proteins in the chemotaxis system: CheW and CheV. Typically, a signal transduction system for chemotaxis to form a core signaling complex couples CheA activity to chemoreceptor control: two CheW coupling protein molecules span a histidine kinase CheA dimer and two chemoreceptors (also known as methyl-accepting chemotaxis protein, MCP) trimers of dimers which further transfer the signal to the flagellar motor through CheY. The current review summarizes and highlights the molecular mechanism involved in bacterial chemotaxis, its physiological benefits such as locating suitable nutrients and niches for bacterial growth, and various assay techniques used for the detection of chemotactic motility.

• MeSH
• Bacteria * metabolism   genetics   MeSH
• Bacterial Proteins metabolism   genetics   MeSH
• Chemotaxis * physiology   MeSH
• Flagella physiology   MeSH
• Bacterial Physiological Phenomena * MeSH
• Methyl-Accepting Chemotaxis Proteins metabolism   MeSH
• Signal Transduction MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

A new group of potent histone deacetylase inhibitors (HDACis) capable of inhibiting cell growth and affecting cell-cycle progression in Tohoku Hospital Pediatrics-1 (THP-1) monocytic leukaemia cells was synthesized. The inhibitors belong to a series of hydroxamic acid derivatives. We designed and synthesized a series of 22 N-hydroxycinnamamide derivatives, out of which 20 are new compounds. These compounds contain various substituted anilides as the surface recognition moiety (SRM), a p-hydroxycinnamate linker, and hydroxamic acids as the zinc-binding group (ZBG). The whole series of synthesized hydroxamic acids inhibited THP-1 cell proliferation. Compounds 7d and 7p, which belong to the category of derivatives with the most potent antiproliferative properties, exert a similar effect on cell-cycle progression as vorinostat and induce apoptosis in THP-1 cells. Furthermore, compounds 7d and 7p were demonstrated to inhibit HDAC class I and II in THP-1 cells with comparable potency to vorinostat and increase acetylation of histones H2a, H2b, H3, and H4. Molecular modelling was used to predict the probable binding mode of the studied HDACis in class I and II histone deacetylases in terms of Zn2+ ion chelation by the hydroxamate group.

• MeSH
• Apoptosis * drug effects   MeSH
• Cell Cycle drug effects   MeSH
• Histone Deacetylases metabolism   MeSH
• Histone Deacetylase Inhibitors * pharmacology   chemical synthesis   chemistry   MeSH
• Hydroxamic Acids * pharmacology   chemical synthesis   chemistry   MeSH
• Coumaric Acids * pharmacology   chemistry   chemical synthesis   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents * pharmacology   chemical synthesis   chemistry   MeSH
• Drug Screening Assays, Antitumor MeSH
• Molecular Docking Simulation MeSH
• THP-1 Cells MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Non-tuberculous mycobacteria (NTM) are pathogens that are widely distributed in the environment and cause increasing rates of human infections. High levels of antimicrobial resistance shown by these bacteria complicate infection management and limit treatment options. The complex structure of cell walls and features such as biofilm formation are responsible for intrinsic resistance in NTMs. Antimicrobial resistance can be explained by four basic mechanisms: (i) limitation of drug uptake, meaning antibiotic entry is limited due to the presence of a hydrophobic and low permeability cell wall and a small number of porin channels, (ii) enzymatic modification of antibiotics, (iii) target site modification, (iv) efflux pumps, which prevent drug accumulation by actively expelling antibiotics from the cell and reduce treatment efficacy. For effective management of NTM infections, detailed understanding of resistance mechanisms, development of species-specific treatment protocols, and discovery of new antimicrobial agents are of great importance. In this review, the mechanisms causing drug resistance in NTMs will be reviewed.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Mycobacterium Infections, Nontuberculous * microbiology   drug therapy   MeSH
• Drug Resistance, Bacterial * MeSH
• Bacterial Proteins metabolism   genetics   MeSH
• Biofilms MeSH
• Cell Wall metabolism   MeSH
• Humans MeSH
• Nontuberculous Mycobacteria * drug effects   genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

UNLABELLED: Despite significant advances in knowledge and the development of guidelines, the management of hypoplastic left heart syndrome (HLHS) remains highly variable. A structured questionnaire was circulated across European Association of Paediatric & Congenital Cardiology (AEPC) affiliated centres. The aims were to evaluate standards in pre-operative assessment, types of surgery, follow-up and medical practices in children with HLHS. Thirty-one centres from 20 countries completed the survey. Delivery of babies with HLHS occurred in co-located maternity hospitals in 74% of centres; 29% were planned for spontaneous onset of labour, while 54% decided on a case-by-case basis. The preferred initial palliation was a right ventricle-pulmonary artery conduit in 55% of cases, modified Blalock-Thomas Taussig shunt (mBTTS) in 35%, and hybrid in 15% of cases. Timing for Glenn varied from 3 to 6 months of age and preoperative examination varied greatly: 65% performed cardiac catheterization and only 19% performed cardiac magnetic resonance. Stage III palliation was performed at a highly variable interval (2-6 years of age), nearly always employing an extracardiac conduit. Fenestration was routinely performed in 61% and reserved for borderline cases in 39%. All the centers adopted warfarin for the first 3-12 months after Fontan completion, and continued if a fenestration was present, while in non-fenestrated aspirin was left by most centers (e.g. 68%). However, there was a high disparity in the use of heart failure medications (e.g. in interstage I-II 35% use ACE-inhibitors, and only 26% digoxin). Follow-up practice also varied widely with only 60% employing specific protocols. CONCLUSION: This first multi-centre European survey from 31 centres from 20 different European countries highlighted a high practice variation in HLHS management across all the stages of Single Ventricle (Fontan) palliation. Major variations pertained to pre- and post-surgical investigations, surgical strategy for stage I and III, medical treatment regimens, and follow-up programs. WHAT IS KNOWN: • Hypoplastic left heart syndrome (HLHS) remains one of the most complex and challenging congenital cardiac defects to manage. • Investigating the management of children with HLHS across different European centres can facilitate study of the most effective management strategies. WHAT IS NEW: • Significant variation in HLHS management were reported in relation to pre- and post-surgical examinations, surgical strategy at stage I and III, medical treatment regimens, and follow-up programs. • Greater standardisation of imaging and diagnostic evaluation, medical treatment and follow-up surveillance may improve outcomes for these vulnerable patients and warrants further study.

• MeSH
• Child MeSH
• Infant MeSH
• Practice Patterns, Physicians' * statistics & numerical data   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Palliative Care MeSH
• Child, Preschool MeSH
• Surveys and Questionnaires MeSH
• Hypoplastic Left Heart Syndrome * surgery   diagnosis   therapy   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Europe MeSH

Vysokoškolská učebnice, která se zaměřuje na anatomii člověka.; Anatomii se nestačí jenom jednou naučit, je potřeba si ji tisíckrát zopakovat, aby se informace propojily a uložily v neuronových sítích mozkových hemisfér. Na rozdíl od jiných učebnic je Memorix vytvořen tak, aby čtenářům co nejvíce zjednodušil a urychlil učení tisíců anatomických struktur tím, že je propojuje do přehledného celku. Obecná, speciální i topografická anatomie jsou systematicky popsané na 600 stránkách, přičemž jejich strukturovaný text je obohacen o 1500 obrázků a schémat. Tisíce klinických poznámek vysvětlují důležitost jednotlivých struktur a orgánů, takže čtenář se nejenom rychle a efektivně naučí základní anatomii, ale je schopen nabyté informace využít i v klinické praxi. Kniha je navíc doplněna o mnoho aplikací, které studium anatomie ještě více zefektivňují. Online anatomický slovník vysvětlí význam všech termínů, mobilní aplikace Memorix Anatomy QUIZ výrazně zlepší opakování pomocí 16 000 otázek a 3D anatomický Atlas neuvěřitelně přesně vysvětlí prostorové uložení jednotlivých orgánů. Více informací o projektech www.memorix.cz nebo Google Play a App Store. Kvalitu Memorixu anatomie ocenilo za 8 let už více než 20 000 mediků, lékařů a jiných zdravotníků z více než 50 krajin světa. Kniha totiž vyšla už v 5 jazycích (česky, anglicky, polsky, italsky a maďarsky) a v anglické verzi se z ní učí například i v Japonsku, Kanadě nebo na Novém Zélandu.

• MeSH
• Anatomy MeSH

• Conspectus
• Anatomie člověka a srovnávací anatomie
• Učební osnovy. Vyučovací předměty. Učebnice
• NML Fields
• anatomie
• NML Publication type
• učebnice vysokých škol
• kolektivní monografie

BACKGROUND: Glioblastoma (GBM) is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification. METHODS: We developed a highly reproducible, personalized prognostication, and clinical subgrouping system using machine learning (ML) on routine clinical data, magnetic resonance imaging (MRI), and molecular measures from 2838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, and III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]). RESULTS: The ML model stratified patients into distinct prognostic subgroups with HRs between subgroups I-II and I-III of 1.62 (95% CI: 1.43-1.84, P < .001) and 3.48 (95% CI: 2.94-4.11, P < .001), respectively. Analysis of imaging features revealed several tumor properties contributing unique prognostic value, supporting the feasibility of a generalizable prognostic classification system in a diverse cohort. CONCLUSIONS: Our ML model demonstrates extensive reproducibility and online accessibility, utilizing routine imaging data rather than complex imaging protocols. This platform offers a unique approach to personalized patient management and clinical trial stratification in GBM.

• MeSH
• Adult MeSH
• Glioblastoma * pathology   classification   mortality   diagnostic imaging   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Survival Rate MeSH
• Young Adult MeSH
• Brain Neoplasms * pathology   classification   mortality   diagnostic imaging   MeSH
• Follow-Up Studies MeSH
• Prognosis MeSH
• Aged MeSH
• Machine Learning * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Previous research indicated that the cytotoxic activity of the antitumor platinum(II) complex [Pt(1S,2S-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)]2+ (56MESS) was not primarily attributed to DNA binding, despite the complex being confirmed to localize also in the nucleus. In this study, we have demonstrated that the antiproliferative activity of 56MESS indeed involves DNA binding. Furthermore, in addition to binding duplex DNA, the complex also interacts with non-canonical secondary DNA structures, such as G-quadruplexes (G4s) and i-Motifs (iMs). This interaction leads to the suppression of G-regulated oncogene expression and disrupts key enzymatic processes associated with DNA, potentially contributing to DNA damage and the biological activity of 56MESS. These findings build upon previously published results, revealing that the anticancer activity of 56MESS is significantly more multifaceted than previously understood, involving multiple distinct mechanisms.

• MeSH
• DNA metabolism   chemistry   MeSH
• Down-Regulation * drug effects   MeSH
• G-Quadruplexes * drug effects   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Organoplatinum Compounds * pharmacology   chemistry   MeSH
• DNA Damage * drug effects   MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Proto-Oncogene Proteins c-myc * genetics   metabolism   MeSH
• Proto-Oncogene Proteins p21(ras) * genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH