The occurrence and bioaccumulation of new and legacy persistent organic pollutants (POPs), organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), hexabromocyclododecanes (HBCDs), and Dechlorane Plus (DPs) and their related compounds (Dechloranes) in an ecosystem on King George Island, Antarctica are investigated. The new and legacy POPs were widely detected in the animal samples collected from Antarctica, which included Limpet, Antarctic cod, Amphipods, Antarctic icefish, Gentoo and Chinstrap penguins, Kelp gull, and South polar skua. The trophic magnification factors indicated that the levels of PCNs and HBCDs, as well as the legacy POPs, were magnified through the food web, whereas DPs might be diluted through the trophic levels contradicting the classification of Dechloranes as POPs. This is one of the first extensive surveys on PCNs, HBCDs, and Dechloranes, which provides unique information on the distribution and trophic biomagnification potential of the new and legacy POPs in the Antarctic region.

• MeSH
• bioakumulace MeSH
• chemické látky znečišťující vodu * analýza   MeSH
• ekosystém MeSH
• monitorování životního prostředí MeSH
• perzistentní organické znečišťující látky MeSH
• polychlorované bifenyly * analýza   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Antarktida MeSH

• Publikační typ
• abstrakty MeSH

• Publikační typ
• abstrakt z konference MeSH

Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) toward precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifier genes and activated signaling/myeloid transcription factors (AS/MTFs) with disease progression and treatment failure in patients with CML after tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes, with a limit of detection of 0.2%. Seventy mutations were detected in 57 diagnostic samples (22.4%), whereas 64 mutations were detected in 39 of the follow-up samples (27.9%). Carrying any mutation at initial diagnosis was associated with worse outcomes after TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with imatinib showed higher risks of treatment failure (hazard ratio, 2.53; 95% confidence interval, 1.13-5.66; P = .0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs. The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival, and progression risk. Additionally, there was an observable nonsignificant trend indicating a heightened risk of progression to advanced disease and worse overall survival. In conclusion, mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression and may help upfront TKI selection.

• MeSH
• chronická myeloidní leukemie * genetika   farmakoterapie   mortalita   diagnóza   MeSH
• dospělí MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace * MeSH
• prognóza MeSH
• progrese nemoci MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• signální transdukce MeSH
• transkripční faktory genetika   MeSH
• výsledek terapie MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Low-molecular-weight mannogalactofucans (LMMGFs, <4000g/mol) were prepared by the enzymatic degradation of Undaria pinnatifida sporophyll galactofucan (MF) and evaluated or their antiviral activities and underlying action mechanisms against herpes simplex virus type 1 (HSV-1). The 50% inhibitory concentrations (IC50) of LMMGFs and MF were 2.64 and 2.42μg/mL, respectively. LMMGFs inhibited the viral entry on the host cell surface and also exhibited inhibitory activity directly against viral particles, as observed in a virucidal assay. LMMGFs dose-dependently enhanced the mRNA expression of Toll-like receptor 2 (TLR2) and stimulated the phosphorylation of Akt and JNK in Vero cells. These results clearly demonstrated that LMMGFs use TLR2 as their receptor, preventing HSV-1 infection on the host cell surface and antagonizing viral adsorption via TLR2 pathway activation in Vero cells.

• MeSH
• antivirové látky chemie   farmakologie   MeSH
• Cercopithecus aethiops MeSH
• galaktosa chemie   farmakologie   MeSH
• herpes simplex metabolismus   prevence a kontrola   MeSH
• lidský herpesvirus 1 účinky léků   MeSH
• molekulová hmotnost MeSH
• rozpustnost MeSH
• toll-like receptor 2 metabolismus   MeSH
• Vero buňky MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Low molecular weight mannogalactofucans (LMMGFs) prepared by enzymatic degradation of high molecular weight Undaria galactofucan (MF) were evaluated for their anti-cancer effects against human prostate cancer. Correlation NMR and linkage analyses confirmed that LMMGFs consist mainly of α-fucose and β-galactose units: α-fucose units are 1,3-linked; β-galactose units are terminal, 1,3- and/or 1,6-linked; both sugars are partially sulphated, fucose at positions O-2 and/or O-4 and galactose at O-3. Mannose residue, as a minor sugar, presents as the 1,4-linked terminal units. LMMGFs more significantly induced cell cycle arrest at the G0/G1 phase and cell death via suppression of the Akt/GSK-3β/β-catenin pathway than MF in human PC-3 prostate cancer cells. LMMGFs upregulated mRNA expression of death receptor-5 (DR-5), the ratio of Bax to Bcl-2, the cleavage of caspases and PARP, the depolarisation of mitochondrial membrane potential, and ROS generation. LMMGFs (200-400 mg/kg) effectively reduced both tumour volume and size in a xenografted mouse model. These results demonstrated that LMMGFs attenuate the growth of human prostate cancer cells both in vitro and in vivo, suggesting that LMMGFs can be used as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat androgen-independent human prostate cancer. Graphical Abstract.

• MeSH
• apoptóza účinky léků   MeSH
• beta-katenin metabolismus   MeSH
• GSK3B metabolismus   MeSH
• kontrolní body buněčného cyklu účinky léků   MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• messenger RNA genetika   MeSH
• molekulová hmotnost MeSH
• myši MeSH
• nádory prostaty farmakoterapie   metabolismus   MeSH
• polysacharidy chemie   farmakologie   terapeutické užití   MeSH
• Undaria chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Previously, we reported that the sulphated polysaccharides (SPS)-CF, a water-soluble polysaccharide isolated and purified from Korean green alga Maesaengi (Capsosiphon fulvescens, Chlorophyta), is a glucuronogalactomannan based mainly on the monosaccharide composition determined by high-performance liquid chromatography (HPLC) analysis after 1-phenyl-3-methyl-5-pyrazolone (PMP) labelling of sugars in the acid (trifluoroacetic acid (TFA)) hydrolyzates of SPS-CF, which showed mannose (55.4 mol %), galactose (25.3 mol %) and glucuronic acid (16.3 mol %) as major sugars (Na et al., Int Immunopharmacol 10:364-370, 2010). However, the results of the present study re-performed for monosaccharide composition of this polysaccharide using, in addition to HPLC of PMP-labelled sugars, other separation methods, i.e. high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD), gas chromatography with flame ionising detection (GC-FID) and thin-layer chromatography (TLC), clearly demonstrated that the most prominent neutral monosaccharides of SPS-CF are xylose (38.6-49.4 mol %) and rhamnose (39.6-45 mol %), while mannose and galactose are present at a much lesser extent or in negligible amount. These extensive monosaccharide analyses, correlation nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI-MS) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) measurements confirmed the sulphated glucuronorhamnoxylan (ulvan) type of SPS-CF polysaccharide, whose backbone is composed of alternating sequence of 4-linked L-rhamnose-3-sulphate and D-xylose residues (ulvobiose U3s) carrying monomeric D-glucuronic acid or D-glucuronic acid-3-sulphate on O-2 of some L-rhamnose-3-sulphate units as the side chains. The SPS-CF exhibited significant in vitro anti-coagulant activity by which the activated partial thromboplastin time (aPTT) and thrombin time (TT) were significantly prolonged. The results of this study demonstrated that the ulvan SPS-CF isolated from Korean Maesaengi C. fulvescens can be considered a potential anti-coagulant agent.

• MeSH
• antikoagulancia chemie   izolace a purifikace   farmakologie   MeSH
• Chlorophyta metabolismus   MeSH
• chromatografie na tenké vrstvě MeSH
• chromatografie plynová MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• mannany chemie   izolace a purifikace   farmakologie   MeSH
• monosacharidy analýza   MeSH
• parciální tromboplastinový čas MeSH
• plamínková ionizace MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• trombinový čas MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Compare overall Landing Error Scoring System (LESS) scores, risk categorisation, specific LESS errors, and double-leg jump-landing jump heights between overhead goal and no goal conditions. DESIGN: Randomised cross-over. SETTING: Laboratory. PARTICIPANTS: 76 (51% male). MAIN OUTCOME MEASURES: Participants landed from a 30-cm box to 50% of their body height and immediately jumped vertically for maximum height. Participants completed three trials under two random-ordered conditions: with and without overhead goal. Group-level mean LESS scores, risk categorisation (5-error threshold), specific landing errors, and jump heights were compared between conditions. RESULTS: Mean LESS scores were greater (0.3 errors, p < 0.001) with the overhead goal, but this small difference was not clinically meaningful. Similarly, although the number of high-risk participants was greater with the overhead goal (p = 0.039), the 9.2% difference was trivial. Participants jumped 2.7 cm higher with the overhead goal (p < 0.001) without affecting the occurrence of any specific LESS errors. DISCUSSION: Performing the LESS with an overhead goal enhances sport specificity and elicits greater vertical jump performances with minimal change in landing errors and injury-risk categorisation. Adding an overhead goal to LESS might enhance its suitability for injury risk screening, although the predictive value of LESS with an overhead goal needs confirmation.

• MeSH
• klinické křížové studie MeSH
• kolenní kloub MeSH
• lidé MeSH
• pohyb MeSH
• poranění předního zkříženého vazu * MeSH
• sporty * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

PURPOSE: NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. METHODS: Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). RESULTS: A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. CONCLUSION: N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.

• MeSH
• capecitabinum aplikace a dávkování   MeSH
• chinoliny aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• Kaplanův-Meierův odhad MeSH
• kvalita života MeSH
• lapatinib aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory mozku farmakoterapie   sekundární   MeSH
• nádory prsu u mužů farmakoterapie   metabolismus   patologie   MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   terapie   MeSH
• nauzea chemicky indukované   MeSH
• opakovaná terapie MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• průjem chemicky indukované   MeSH
• receptor erbB-2 metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH