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

Renal ischemia-reperfusion injury (IRI) is considered as one of the most prevalent causes of acute kidney injury (AKI), which can happen in various clinical situations including hypovolemic shock, injury, thrombo-embolism, and after a kidney transplant. This paper aims to evaluate the reno-protective effects of Quercetin in induced ischemia/reperfusion injury by regulating apoptosis-related proteins, inflammatory cytokines, MMP-2, MMP-9, and nuclear factor kappa-light-chain-enhancer inactivated B cells (NF-kB) in rats. The male Wistar rats (n=32) were randomly divided into Sham, untreated IR, and Quercetin-treated IR (gavage and intraperitoneal). Quercetin was given orally and intraperitoneally one hour before inducing ischemia-reperfusion injury . After reperfusion, blood samples and kidneys were collected to assess renal function and inflammatory cytokines, apoptotic signaling proteins, and antioxidants. Urea, creatinine, and MDA levels improved in Quercetin-treated groups with different administration methods. In addition, the activities of other antioxidant in Quercetin-treated rats were higher than those in the IR group. Further, Quercetin inhibited NF-kB signaling, apoptosis-associated factors and produced matrix metalloproteinase protein in the kidneys of rats. Based on the findings, the antioxidant, anti-inflammatory, and anti-apoptotic effects of the Quercetin diminished renal ischemia-reperfusion injury in the rats significantly. It is suggested that a single dosage of Quercetin have a reno-protective impact in the case of renal I/R injury.

• MeSH
• akutní poškození ledvin * farmakoterapie   metabolismus   MeSH
• antioxidancia metabolismus   MeSH
• apoptóza MeSH
• cytokiny metabolismus   MeSH
• ischemie komplikace   metabolismus   MeSH
• krysa rodu rattus MeSH
• ledviny MeSH
• NF-kappa B metabolismus   farmakologie   terapeutické užití   MeSH
• oxidační stres MeSH
• potkani Wistar MeSH
• quercetin farmakologie   terapeutické užití   MeSH
• reperfuzní poškození * farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Sirtuin 6 (SIRT6), a member of sirtuin family (SIRT1-7), regulates a variety of cellular processes involved in aging, metabolism, and cancer. Dysregulation of SIRT6 is widely observed in different breast cancer subtypes; however, the role and function of SIRT6 in cancer development remain largely unexplored. The aim of this study was to identify novel compounds targeting SIRT6 which may provide a new approach in development of anti-cancer therapy for breast cancer. Virtual screening was utilized to discover potential compounds targeting SIRT6 for in vitro screening. In addition, novel 1,4-dihydropyridine derivatives were synthetized and further subjected for the screening. The impact of the compounds on the deacetylation activity of SIRT6 was determined with HPLC method. The anti-cancer activities were screened for a panel of breast cancer cells. A set of 1,4-dihydropyridine derivatives was identified as SIRT6 inhibitors. A SIRT6 activating compound, (2,4-dihydroxy-phenyl)-2-oxoethyl 2-(3-methyl-4-oxo-2-phenyl-4H-chromen-8-yl)acetate (later called as 4H-chromen), was discovered and it provided 30-40-fold maximal activation. 4H-chromen was proposed to bind similarly to quercetin and place to previously reported SIRT6 activator sites. 4H-chromen was investigated in various breast cancer cells, and it decreased cell proliferation in all cells as well as arrested cell cycle in triple negative cells. Overall, this study describes a highly potent SIRT6 activator and new inhibitors that represent a novel tool to study the mechanism of SIRT6 function.

• MeSH
• časná detekce nádoru metody   MeSH
• lidé MeSH
• nádory prsu farmakoterapie   metabolismus   MeSH
• protinádorové látky chemie   farmakologie   terapeutické užití   MeSH
• screeningové testy protinádorových léčiv metody   MeSH
• sekundární struktura proteinů MeSH
• simulace molekulového dockingu metody   MeSH
• sirtuiny antagonisté a inhibitory   chemie   metabolismus   MeSH
• terciární struktura proteinů MeSH
• viabilita buněk účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• antibakteriální látky farmakologie   MeSH
• dlouhodobá péče MeSH
• feces mikrobiologie   MeSH
• infekce bakteriemi rodu Klebsiella farmakoterapie   epidemiologie   MeSH
• infekce spojené se zdravotní péčí epidemiologie   MeSH
• Klebsiella pneumoniae účinky léků   izolace a purifikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Portugalsko MeSH

Human yersiniosis caused by pathogenic Yersinia spp. is one of the most common reported zoonoses in the European Union and pigs are considered as the major reservoir of these bacteria. Serological testing represents a suitable method to obtain information about the prevalence of enteropathogenic Yersinia spp. in food animals. The prevalence of antibodies against enteropathogenic Yersinia spp. was studied in 319 slaughtered pigs and 135 wild boars from different production systems in the Moravian region (Czech Republic) using a commercially available ELISA test (an apparent prevalence). The seroprevalence was significantly associated with the type of breeding system, with the lowest seroprevalence being observed in household-raised pigs (13/29, 44.8%). No significant difference between the prevalence of anti-Yersinia antibodies in conventional (146/180, 81.1%) and organic pigs (92/110, 83.6%) was found. Antibodies were found in 65.9% (89/135) of wild boars without a significant difference between adult (23/41, 56.1%) and young (66/94, 70.2%) animals. Seropositivity was significantly higher in domestic (251/319, 78.7% in total) compared to feral pigs. A Bayesian approach taking into account the sensitivity and specificity of the ELISA test was used to estimate the true prevalence of anti-Yersinia antibodies in pigs and wild boars. According to our results, domestic pigs and wild boars proved to be an important reservoir of enteropathogenic Yersinia in the Czech Republic. Attention should be paid to good hygienic practice during slaughtering and handling of meat to prevent meat contamination and subsequently human infection.

• MeSH
• divoká zvířata MeSH
• infekce yersiniemi epidemiologie   veterinární   MeSH
• jatka MeSH
• maso mikrobiologie   MeSH
• nemoci prasat epidemiologie   mikrobiologie   MeSH
• potravinářská mikrobiologie * MeSH
• prasata mikrobiologie   MeSH
• séroepidemiologické studie MeSH
• Yersinia izolace a purifikace   fyziologie   MeSH
• zdroje nemoci MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

• Publikační typ
• abstrakt z konference MeSH

INTRODUCTION: Inappropriate use of antibiotics has resulted in a dramatic increase of antimicrobial resistance in developing countries. We examined knowledge, attitudes, and practices of antibiotic use in three Asian countries. METHODOLOGY: A nationwide cross-sectional study of teachers in large cities of Yemen, Saudi Arabia, and Uzbekistan was conducted. A random sample of 1,200 teachers was selected in each country. Data were collected through a questionnaire-based survey and then analyzed using descriptive and multivariate statistical methods. RESULTS: The prevalence of non-prescription antibiotic use ranged from 48% in Saudi Arabia to 78% in Yemen and Uzbekistan. Pharmacies were the main source of non-prescribed antibiotics. The most common reasons for antibiotic use were cough (40%) and influenza (34%). Forty-nine percent of respondents discontinued antibiotics when they felt better. Although awareness of the dangers of antibiotic use correlated inversely with self-medication, understanding of the appropriate use of antibiotics was limited. CONCLUSIONS: The prevalence of antibiotic self-medication in the educated adult population in the studied countries was found to be alarmingly high. Effective strategies involving regulatory enforcement prohibiting sales of antibiotics without prescription should be implemented along with educational interventions for health professionals and the public.

• MeSH
• akademický sbor statistika a číselné údaje   MeSH
• antibakteriální látky terapeutické užití   MeSH
• bakteriální léková rezistence MeSH
• chřipka lidská farmakoterapie   MeSH
• dospělí MeSH
• kašel farmakoterapie   MeSH
• léky bez předpisu terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• městské obyvatelstvo statistika a číselné údaje   MeSH
• mladý dospělý MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• rozvojové země statistika a číselné údaje   MeSH
• samoléčba * MeSH
• stupeň vzdělání MeSH
• věkové faktory MeSH
• zdraví - znalosti, postoje, praxe * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Jemen MeSH
• Saudská Arábie MeSH
• Uzbekistán MeSH