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
• astrocyty * metabolismus   patologie   MeSH
• klusterin * metabolismus   genetika   MeSH
• lidé MeSH
• membránový potenciál mitochondrií * fyziologie   MeSH
• mitochondrie * metabolismus   MeSH
• nádorové buněčné linie MeSH
• oxidační stres fyziologie   MeSH
• oxidativní fosforylace MeSH
• poškození DNA MeSH
• proliferace buněk * MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• stárnutí buněk * fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Modern trends in reconstructive surgery involve the use of free perforator flaps to reduce the donor site morbidity. The course of perforator vessels has a great anatomic variability and demands detailed knowledge of the anatomical relationships and the variability of the course of the perforators. The numerous modifications to perforator nomenclature proposed by various authors resulted in confusion rather than simplification. In our study, we focused on the hypothesis that a septocutaneous perforator traverses from the given source vessel to the deep fascia adherent to but not to within the septum itself. METHODS: Sixty-nine septocutaneous perforators from three different limb donor sites (lateral arm flap, anterolateral thigh flap, and radial forearm free flap) were collected from the gross pathology specimens of 14 fresh cadavers. The gross picture and the cross-sections with the histological cross-sections on different levels were examined to determine the position of the vessel to the septal tissue. RESULTS: Of the observed 69 septal perforators, 61 (88.5%) perforators were adherent to but not within the septum. The remaining eight (12.5%) perforators passed through the septum. All these eight perforators were found in multiple different cross-section levels (2 of 19 in lateral arm flap, 3 of 27 in anterolateral thigh flap, and 3 of 23 in radial forearm free flap). CONCLUSION: Although septocutaneous vessels appear identical macroscopically, microscopically two types of vessels with paraseptal and intraseptal pathways are observed. The majority of these vessels are merely adherent to the septum having a paraseptal pathway, while a minority are within the septum and are "true" septocutaneous perforators. It is advisable to dissect with a piece of the septum in order to avoid damage or injury to the perforator.

• MeSH
• lidé MeSH
• mrtvola MeSH
• perforátorový lalok * krevní zásobení   MeSH
• předloktí krevní zásobení   chirurgie   MeSH
• stehno krevní zásobení   MeSH
• volné tkáňové laloky * krevní zásobení   MeSH
• zákroky plastické chirurgie * metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Úraz elektrickým proudem z vysokého napětí je jedním z nejzávažnějších úrazů, se kterými se můžeme v moderní medicíně setkat. Často bývá spojený s více následky a vysokou náchylností k infekčním komplikacím. Tito pacienti jsou přijímáni do specializovaných popáleninových center a vyžadují rozsáhlou multidisciplinární spolupráci. V této studii se snažíme odhalit prevalenci, typy a charakteristiky mikrobiálních infekcí, které se vyvíjejí po vysokonapěťovém elektrotraumatu, a identifikovat rizikové faktory, které mohou přispívat k náchylnosti pacientů k infekcím. Materiál a metodika: Pro účely této publikace byla zpracována data všech 37 pacientů hospitalizovaných na jednotce intenzivní péče Kliniky popálenin a plastické chirurgie FN Brno s diagnózou úraz elektrickým proudem vysokým napětím v letech 2006–2016. Otisky a stěry z exfoliovaných oblastí byly opakovaně odebírány k mikrobiální analýze spolu s tracheobronchiálním aspirátem, sputem nebo bronchoalveolární laváží, močí a periferní krví. Získaná data byla zpětně analyzována. Výsledky: Mezi 37 pacienty byl medián věku 31,9 s průměrnou dobou hospitalizace 44,3 dne a úmrtností 8,1 %. Na umělé plicní ventilaci bylo závislých celkem 28 osob. Výskyt infekčních komplikací se v průběhu hospitalizace liší podle místa kultivace odběru a doby strávené v nemocnici. U 97,3 % pacientů se vyvinula infekce alespoň v jednom tělesném kompartmentu. V 88,8 % případů byla multipatogenní a ve 41,6 % se rozvinul septický stav. V naší studijní kohortě dominovaly G+ nad G-kmeny. Nejčastějšími zástupci z G+ spektra byli koaguláza negativní stafylokoky (97 %), Staphylococcus aureus (57 %), Enterococcus fecalis et faecium (51 %). V G-spektru bylo pořadí následující: Klebsiella pneumoniae (46 %), Pseudomonas aeruginosa (41 %), Escherichia coli (35 %) a Acinetobacter baumannii (18,9 %). Nejčastější pozorovanou infekcí byla infekce popálenin (BWI), následovaná infekcemi krevního řečiště (BSI), infekcemi dolních cest dýchacích (LRTI) a infekcemi močových cest (UTI), primárně způsobené G+ patogeny. Je pozoruhodné, že delší doba hospitalizace byla spojena s rostoucí prevalencí G-patogenů, zejména K. pneumoniae, P. aeruginosa a A. baumannii, které vykazovaly vysoký stupeň antimikrobiální rezistence. Závěr: Tato studie poskytuje podrobný pohled na výskyt a následky úrazů elektrickým proudem s vysokým napětím na Moravě v průběhu desetiletí. Faktory významně ovlivňující přežití a závažnost výsledků zahrnovaly celkovou plochu popálenin, popáleniny v celé tloušťce, inhalační poranění a potřebu tracheostomie. Studie je však limitována relativně malou velikostí vzorku, dlouhou dobou sběru dat s potenciálními změnami v klinické praxi a jednocentrovým designem, což může ovlivnit zobecnění nálezů. K ověření těchto výsledků a zpřesnění strategií prevence infekcí u této populace pacientů jsou zapotřebí další multicentrické studie.

Background and Aim: High voltage electrotrauma is one of the most serious injuries we can encounter in modern medicine, often associated with multiple disabilities and high susceptibility to infectious complications. These patients are admitted to specialized burn centers and require extensive multidisciplinary collaboration. In this study, we aim to uncover the prevalence, types and characteristics of microbial infections that develop in the aftermath of high voltage electrotrauma and to identify risk factors that may contribute to patients’ susceptibility to infections. Material and Methods: For the purposes of this publication, data of all 37 patients hospitalized in the intensive care unit of the Department of Burns and Plastic Surgery of the University Hospital in Brno with a diagnosis of high-voltage electrical injury between 2006–2016 were processed. Imprints and swaps from exfoliated areas were repeatedly taken for microbial analysis, together with tracheobronchial aspirate fluid, sputum, or bronchoalveolar lavage, urine and peripheral blood. The obtained data were analysed retrospectively. Results: Among the 37 patients, the median age was 31.9, with an average hospital stay of 44.3 days and a mortality rate of 8.1%. A total of 28 individuals were dependent on artificial lung ventilation. The incidence of infectious complications varies during the hospitalization period according to the location of sampling cultivation and time spent at the hospital. 97.3% of patients developed infection in at least one body compartment. In 88.8% of cases, it was multipathogenic and in 41.6% a septic condition developed. In our study cohort, G+ dominated over Gstrains. Most common representatives from G+ spectrum were Coagulase negative Staphylococci (97%), Staphylococcus aureus (57%), Enterococcus fecalis et faecium (51%). In Gspectrum, the order was as followed: Klebsiella pneumoniae (46%), Pseudomonas aeruginosa (41%), Escherichia coli (35%) and Acinetobacter baumannii (18.9%). The most common infection observed was burn wound infection (BWI), followed by bloodstream infections (BSI), lower respiratory tract infections (LRTI), and urinary tract infections (UTI), primarily caused by G+ pathogens. Notably, an increased hospital stay duration was associated with a rising prevalence of Gpathogens, particularly K. pneumoniae P. aeruginosa and A. baumannii which exhibited a high degree of antimicrobial resistance. Conclusion: This study provides a detailed insight into the occurrence and consequences of high-voltage electrical injuries in Moravia over a decade. Factors significantly impacting survival and severity of outcomes included total burn surface area, full-thickness burns, inhalation injury, and the need for tracheostomy. However, the study is limited by its relatively small sample size, long data collection period with potential changes in clinical practice, and single-center design, which may affect the generalizability of the findings. Further multicentric studies are needed to validate these results and refine infection prevention strategies in this patient population.

Pacientka náhle v domácím prostředí dušnost, kolaps a bezvědomí. Provedena laická telefonicky navigovaná kardiopulmonální resuscitace, po příjezdu lékaře rychlé záchranné služby úspěšná rozšířená kardiopulmonální resuscitace a poté pacientka převezena na oddělení urgentního příjmu Nemocnice České Budějovice. Byla provedena základní stabilizace klinického stavu, zajištění pacientky, intubace a odvoz na CT. Zde byla pomocí CT verifikována masivní bilaterální plicní embolie. Ihned v prostorách urgentního příjmu byla provedena trombolýza, stabilizace oběhu a pacientka byla uložena na ARO. Za hodinu na oddělení ARO znovu těžká oběhová nestabilita – vysoká podpora oběhu noradrenalinem. Provedeno UZ a následně CT břicha s nálezem masivního hemoperitonea. Urgentní chirurgické konzilium a doporučena operace z vitální indikace. Provedena urgentní laparotomie u hemodynamicky těžce nestabilní pacientky s TK 60/30 a pulzy 180/min. Za masivní oběhové podpory a převodů erymasy odsáty 4 l zcela nesrážlivé krve v oblasti jater. Játra byla tržena na několika místech od zlomených žeber a nejvíce dorzálně v levém laloku v oblasti jaterních žil. Chirurgicky při těžké oběhové nestabilitě neověřitelné a bylo rozhodnuto o stabilizaci pomocí perihepatického packingu a pacientka byl uložena na ARO RES. ARO pokračuje v konzervativní terapii a dochází k postupnému zmenšení odpadů do drénu. Provedena second-look operace za 48 hod – revize původní ranou, odstranění roušek. Nalezeny mnohočetné trhliny na pravém laloku od zlámaných žeber a dorzálně silně krvácející jaterní žíla. Provedena kombinace selektivních sutur s elektrokoagulací trhlin, pro přetrvávající oběhovou nestabilitu se znovu rozhodujeme dát pouze perihepatický packing. Pacientku znovu necháváme na ARO k oběhové stabilizaci a domlouváme se znovu na operační revizi po stabilizaci oběhu za 48 hod. Přistupujeme k další operační revizi. Provádíme znovu revize perihepatického prostoru a anatomickou resekci jaterního segmentu II a III a selektivní podvaz jaterní žíly. Následně dochází k hemodynamické stabilizaci oběhu. V rámci pooperačního průběhu nejprve dochází k rozvoji fluidothoraxu, který byl vyřešen hrudní drenáží, a akutní akalkulozní cholecystitidě, která byla vyřešena punkční cholecystostomií. Pacientka je nyní primárně zhojena a angiologiem nasazena trvalá antikoagulační terapie. Příčina plicní embolizace nebyla zjištěna.

The patient suddenly experienced shortness of breath, collapse, and loss of consciousness at home. Layperson-performed, telephone-guided cardiopulmonary resuscitation was initiated, and upon the arrival of the emergency medical team, successful extended CPR was performed, after which the patient was transported to the emergency department at Hospital of České Budějovice. Basic stabilization of the clinical condition was carried out, the patient was secured, intubated, and transported to the CT scanner. A massive bilateral pulmonary embolism was verified byCT. Thrombolysis was immediately performed in the emergency room, circulation was stabilized, and the patient was transferred to the ICU. An hour later, the patient experienced severe circulatory instability in the ICU, requiring high-dose norepinephrine support. Ultrasound was performed, followed by a CT scan of the abdomen, which revealed massive hemoperitoneum. An urgent surgical consultation was performed, and surgery was recommended on a vital indication. An urgent laparotomy was performed on a hemodynamically unstable patient with the blood pressure 60/30 and the pulse 180/min. Despite massive circulatory support and erythrocyte transfusion, 4 liters of noncoagulable blood were drained from the hepatic region. The liver was torn in several places due to fractured ribs, most severely in the left lobe at the hepatic veins. Due to severe circulatory instability, the injury was deemed inoperable, and it was decided to stabilize the condition with perihepatic packing, after which the patient was transferred to the ICU. The ICU continued conservative therapy, and there was a gradual reduction in the drainage output. A second-look operation was performed after 48 hours – revision of the original wound and removal of the drapes. Multiple fissures were found in the right lobe, caused by broken ribs, with heavy bleeding from the dorsal hepatic veins. A combination of selective suturing and electrocoagulation of the fissures was performed. Due to ongoing circulatory instability, the decision was made to use perihepatic packing once again. The patient was left in the ICU for further circulatory stabilization, with a plan to do another surgical revision after stabilization in 48 hours. Another surgical revision was performed, revisiting the perihepatic space and performing an anatomical resection of liver segments II and III, followed by selective ligation of the hepatic vein. Hemodynamic stabilization was achieved. Postoperatively, a fluidothorax developed, which was managed by thoracic drainage, and acute acalculous cholecystitis, which was treated with puncture cholecystostomy. The patient is now primarily healed and has been started on long-term anticoagulation therapy by the angiologist. The cause of the pulmonary embolism was not determined.

Detské úrazy predstavujú významný medicínsky a spoločenský problém, pričom závažné úrazy môžu viesť k dlhodobým zdravotným následkom, či úmrtiu. Efektívna prednemocničná zdravotná starostlivosť zohráva kľúčovú úlohu pri stabilizácii pacienta a minimalizácii komplikácií. Tento článok analyzuje najčastejšie príčiny detských úrazov, ako sú dopravné nehody, pády a popáleniny, a poukazuje na zásady poskytovania neodkladnej starostlivosti v prednemocničnej fáze. Cieľom článku je zvýšiť povedomie o správnych postupoch v prednemocničnej fáze s cieľom zlepšiť prognózu detských pacientov so závažnými úrazmi.

Child hood injuries are a significant medical and societal problem, and serious injuries can lead to long-term health consequences or death. Effective prehospital medical careplays a key role in stabilising the patient and mini mising complications. This article reviews the most common causes of child hood injuries, such as car accidents, falls and burns, and high lights the principles of providing emergency care in the prehospital phase. The aim of the articleis to raise awareness of the correct procedures in the prehospital phase in order to improve the prognosis of pediatric patients with serious injuries.

• MeSH
• dítě MeSH
• polytrauma MeSH
• úrazy a nehody MeSH
• urgentní zdravotnické služby MeSH
• zdravotničtí záchranáři MeSH
• Check Tag
• dítě 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 metabolismus   chemie   MeSH
• down regulace * účinky léků   MeSH
• G-kvadruplexy * účinky léků   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• organoplatinové sloučeniny * farmakologie   chemie   MeSH
• poškození DNA * účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• protoonkogenní proteiny c-myc * genetika   metabolismus   MeSH
• protoonkogenní proteiny p21(ras) * genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Severe acute pancreatitis (SAP) is associated with metabolic disorders, hypocalcemia, and multiple organ failure. The objective of this study was to investigate changes in thyroid ultrastructure and function in rats with SAP and to provide a theoretical basis for the clinical treatment of thyroid injury in patients with SAP. 64 male SPF Wistar rats were randomly divided into the SAP group and the control group. Pancreatic enzymatic indicators and thyroid hormones were detected, pathology scores were evaluated, and morphological changes were observed under light microscopy and transmission electron microscopy (TEM) in both groups. The serum levels of triiodothyronine (T3), tetraiodothyronine (T4) and Ca2+ were significantly lower in the SAP group than in the control group (P<0.05), whereas the level of calcitonin (CT) was significantly higher than that in the control group (P<0.05). The thyroid structure (pathology and electron microscopy) of the SAP rats was seriously damaged and worsened over time. SAP can cause thyroid injury through a variety of mechanisms, which can also retroact to pancreatitis to aggravate the inflammatory response. This study may have theoretical significance for basic research on SAP. Key words Severe acute pancreatitis, Thyroid, Structure and functional changes, Transmission electron microscopy.

• MeSH
• akutní nemoc MeSH
• hormony štítné žlázy krev   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• pankreatitida * patologie   MeSH
• potkani Wistar * MeSH
• štítná žláza * patologie   ultrastruktura   metabolismus   MeSH
• stupeň závažnosti nemoci MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

DNA damage is a common event in cells, resulting from both internal and external factors. The maintenance of genomic integrity is vital for cellular function and physiological processes. The inadequate repair of DNA damage results in the genomic instability, which has been associated with the development and progression of various human diseases. Accumulation of DNA damage can lead to multiple diseases, such as neurodegenerative disorders, cancers, immune deficiencies, infertility, and ageing. This comprehensive review delves the impact of alterations in DNA damage response genes (DDR) and tries to elucidate how and to what extent the same traits modulate diverse major human diseases, such as cancer, neurodegenerative diseases, and immunological disorders. DDR is apparently the trait connecting important complex disorders in humans. However, the pathogenesis of the above disorders and diseases are different and lead to divergent consequences. It is important to discover the switch(es) that direct further the pathogenic process either to proliferative, or degenerative diseases. Our understanding of the influence of DNA damage on diverse human disorders may enable the development of the strategies to prevent, diagnose, and treat these diseases. In our article, we analysed publicly available GWAS summary statistics from the NHGRI-EBI GWAS Catalog and identified 12 009 single-nucleotide polymorphisms (SNPs) associated with cancer. Among these, 119 SNPs were found in DDR pathways, exhibiting significant P-values. Additionally, we identified 44 SNPs linked to various cancer types and neurodegenerative diseases (NDDs), including four located in DDR-related genes: ATM, CUX2, and WNT3. Furthermore, 402 SNPs were associated with both cancer and immunological disorders, with two found in the DDR gene RAD51B. This highlights the versatility of the DDR pathway in multifactorial diseases. However, the specific mechanisms that regulate DDR to initiate distinct pathogenic processes remain to be elucidated.

• MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• nádory * genetika   MeSH
• nemoci imunitního systému * genetika   MeSH
• nestabilita genomu genetika   MeSH
• neurodegenerativní nemoci * genetika   MeSH
• oprava DNA * genetika   MeSH
• poškození DNA * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Background: Multiple sclerosis (MS) pathology is characterized by acute and chronic inflammation, demyelination, axonal injury, and neurodegeneration. After decades of research into MS-related degeneration, recent efforts have shifted toward recovery and the prevention of further damage. A key area of focus is the remyelination process, where researchers are studying the effects of pharmacotherapy on myelin repair mechanisms. Multiple compounds are being tested for their potential to foster remyelination in different clinical settings through the application of less or more complex techniques to assess their efficacy. Objective: To review current methods and biomarkers to track myelin regeneration and recovery over time in people with MS (PwMS), with potential implications for promyelinating drug testing. Methods: Narrative review, based on a selection of PubMed articles discussing techniques to measure in vivo myelin repair and functional recovery in PwMS. Results: Non-invasive tools, such as structural Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), are being implemented to track myelin repair, while other techniques like evoked potentials, functional MRI, and digital markers allow the assessment of functional recovery. These methods, alone or in combination, have been employed to obtain precise biomarkers of remyelination and recovery in various clinical trials on MS. Conclusions: Combining different techniques to identify myelin restoration in MS could yield novel biomarkers, enhancing the accuracy of clinical trial outcomes for remyelinating therapies in PwMS.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity. Both HCC cell lines exhibited heightened sensitivity to the combined treatment. The effect of drugs on the expression of proliferation markers in an olaparib-resistant patient-derived xenograft (PDX) model of ovarian cancer was also investigated. Ovarian tumors displayed reduced tissue growth, as reflected by a drop in proliferation marker Ki-67 levels in response to PARPi combined with CHK1i. No changes were observed in corresponding liver tissues using Ki-67 and pCHK staining, which indicates the absence of metastases and a hepatotoxic effect. Thus, our results indicate that the dual inhibition of PARP and CHK1 may prove to be a promising therapeutic approach in the treatment of primary HCC as well as OC tumors without the risk of liver metastases, especially in patients with olaparib-resistant tumor profiles.

• MeSH
• apoptóza účinky léků   MeSH
• buňky Hep G2 MeSH
• checkpoint kinasa 1 metabolismus   antagonisté a inhibitory   MeSH
• ftalaziny * farmakologie   MeSH
• hepatocelulární karcinom * farmakoterapie   patologie   metabolismus   MeSH
• játra účinky léků   patologie   metabolismus   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory jater * farmakoterapie   patologie   metabolismus   MeSH
• nádory vaječníků * farmakoterapie   patologie   metabolismus   MeSH
• PARP inhibitory farmakologie   terapeutické užití   MeSH
• piperaziny * farmakologie   MeSH
• poškození DNA účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   škodlivé účinky   MeSH
• pyrazoly farmakologie   MeSH
• pyrimidiny MeSH
• synergismus léků * MeSH
• viabilita buněk účinky léků   MeSH
• xenogenní modely - testy protinádorové aktivity * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH