In higher plants, cell cycle activation in the meristems at germination is essential for the initiation of post-embryonic development. We previously identified the signaling pathways of homeobox transcription factor STIMPY and metabolic sugars as two interacting branches of the regulatory network that is responsible for activating meristematic tissue proliferation in Arabidopsis. In this study, we found that CYCP2;1 is both a direct target of STIMPY transcriptional activation and an early responder to sugar signals. Genetic and molecular studies show that CYCP2;1 physically interacts with three of the five mitotic CDKs in Arabidopsis, and is required for the G2 to M transition during meristem activation. Taken together, our results suggest that CYCP2;1 acts as a permissive control of cell cycle progression during seedling establishment by directly linking genetic control and nutritional cues with the activity of the core cell cycle machinery.

• MeSH
• aktivace transkripce MeSH
• Arabidopsis embryologie   MeSH
• buněčné dělení genetika   MeSH
• cyklin-dependentní kinasy biosyntéza   MeSH
• cykliny biosyntéza   genetika   metabolismus   MeSH
• homeodoménové proteiny genetika   MeSH
• meristém cytologie   embryologie   MeSH
• proliferace buněk MeSH
• proteiny huseníčku biosyntéza   genetika   metabolismus   MeSH
• regulace genové exprese u rostlin MeSH
• rostlinné geny MeSH
• sacharosa farmakologie   MeSH
• semenáček genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

BACKGROUND: Immune checkpoint inhibitors (ICIs), including those targeting PD-1, are currently used in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. The objective of our study was to find predictive peripheral blood-based biomarkers for ICI treatment. METHODS: In 41 patients with advanced malignant melanoma (MM) and NSCLC treated with PD-1 inhibitors, we analyzed peripheral blood-based immune subsets by flow cytometry before treatment initialization and the second therapy dose. Specifically, we assessed basic blood differential count, overall T cells and their subgroups, B cells, and myeloid-derived suppressor cells (MDSC). In detail, CD4 + and CD8 + T cells were assessed according to their subtypes, such as central memory T cells (TCM), effector memory T cells (TEM), and naïve T cells (TN). Furthermore, we also evaluated the predictive value of CD28 and ICOS/CD278 co-expression on T cells. RESULTS: Patients who achieved disease control on ICIs had a significantly lower baseline proportion of CD4 + TEM (p = 0.013) and tended to have a higher baseline proportion of CD4 + TCM (p = 0.059). ICI therapy-induced increase in Treg count (p = 0.012) and the proportion of CD4 + TN (p = 0.008) and CD28 + ICOS- T cells (p = 0.012) was associated with disease control. Patients with a high baseline proportion of CD4 + TCM and a low baseline proportion of CD4 + TEM showed significantly longer PFS (p = 0.011, HR 2.6 and p ˂ 0.001, HR 0.23, respectively) and longer OS (p = 0.002, HR 3.75 and p ˂ 0.001, HR 0.15, respectively). Before the second dose, the high proportion of CD28 + ICOS- T cells after ICI therapy initiation was significantly associated with prolonged PFS (p = 0.017, HR 2.51) and OS (p = 0.030, HR 2.69). Also, a high Treg count after 2 weeks of ICI treatment was associated with significantly prolonged PFS (p = 0.016, HR 2.33). CONCLUSION: In summary, our findings suggest that CD4 + TEM and TCM baselines and an early increase in the Treg count induced by PD-1 inhibitors and the proportion of CD28 + ICOS- T cells may be useful in predicting the response in NSCLC and MM patients.

• MeSH
• antigeny CD278 metabolismus   MeSH
• antigeny CD279 antagonisté a inhibitory   MeSH
• antigeny CD28 MeSH
• CD8-pozitivní T-lymfocyty imunologie   účinky léků   metabolismus   MeSH
• dospělí MeSH
• inhibitory kontrolních bodů * terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom * farmakoterapie   imunologie   krev   patologie   MeSH
• nádory plic * farmakoterapie   imunologie   krev   patologie   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   imunologie   krev   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Climate change is expected to modify plant assemblages in ways that will have major consequences for ecosystem functions. How climate change will affect community composition will depend on how individual species respond, which is likely related to interspecific differences in functional traits. The extraordinary plasticity of some plant traits is typically neglected in assessing how climate change will affect different species. In the Mongolian steppe, we examined whether leaf functional traits under ambient conditions and whether plasticity in these traits under altered climate could explain climate-induced biomass responses in 12 co-occurring plant species. We experimentally created three probable climate change scenarios and used a model selection procedure to determine the set of baseline traits or plasticity values that best explained biomass response. Under all climate change scenarios, plasticity for at least one leaf trait correlated with change in species performance, while functional leaf-trait values in ambient conditions did not. We demonstrate that trait plasticity could play a critical role in vulnerability of species to a rapidly changing environment. Plasticity should be considered when examining how climate change will affect plant performance, species' niche spaces, and ecological processes that depend on plant community composition.

• MeSH
• biologické modely MeSH
• biomasa * MeSH
• druhová specificita MeSH
• fenotyp MeSH
• klimatické změny * MeSH
• listy rostlin růst a vývoj   fyziologie   MeSH
• pastviny * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Geografické názvy
• Mongolsko MeSH

Background: A brief review is given of Peter W. Barlows' contributions to research on gravity tide-related phenomena in plant biology, or 'selenonastic' effects as he called them, including his early research on root growth. Also, new results are presented here from long-term recordings of spontaneous ultra-weak light emission during germination, reinforcing the relationship between local lunisolar tidal acceleration and seedling growth. Scope: The main ideas and broad relevance of the work by Barlow and his collaborators about the effects of gravity on plants are reviewed, highlighting the necessity of new models to explain the apparent synchronism between root growth and microscale gravity changes 107 times lower than that exerted by the Earth's gravity. The new results, showing for the first time the germination of coffee beans in sequential tests over 2 months, confirm the co-variation between the patterns in ultra-weak light emission and the lunisolar tidal gravity curves for the initial growth phase. For young sprouts (<1 month old), the rhythm of growth as well as variation in light emission exhibit the once a day and twice a day periodic variations, frequency components that are the hallmark of local lunisolar gravimetric tides. Although present, this pattern is less pronounced in coffee beans older than 1 month. Conclusions: The apparent co-variation between ultra-weak light emission and growth pattern in coffee seedlings and the lunisolar gravity cycles corroborate those previously found in seedlings from other species. It is proposed here that such patterns may attenuate with time for older sprouts with slow development. These data suggest that new models considering both intra- and intercellular interactions are needed to explain the putative sensing and reaction of seedlings to the variations in the gravimetric tide. Here, a possible model is presented based on supracellular matrix interconnections.

• MeSH
• Coffea fyziologie   MeSH
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• fyziologie rostlin * MeSH
• gravitace * MeSH
• klíčení fyziologie   MeSH
• světlo * MeSH
• Check Tag
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• Publikační typ
• biografie MeSH
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. 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

Common variable immunodeficiency disorder (CVID) is the most common form of primary antibody immunodeficiency. Due to low antibody levels, CVID patients receive intravenous or subcutaneous immunoglobulin replacement therapy as treatment. CVID is associated with the chronic activation of granulocytes, including an increased percentage of low-density neutrophils (LDNs). In this study, we examined changes in the percentage of LDNs and the expression of their surface markers in 25 patients with CVID and 27 healthy donors (HD) after in vitro stimulation of whole blood using IVIg. An oxidative burst assay was used to assess the functionality of LDNs. CVID patients had increased both relative and absolute LDN counts with a higher proportion of mLDNs compared to iLDNs, distinguished based on the expression of CD10 and CD16. Immature LDNs in the CVID and HD groups had significantly reduced oxidative burst capacity compared to mature LDNs. Interestingly we observed reduced oxidative burst capacity, reduced expression of CD10 after stimulation of WB, and higher expression of PD-L1 in mature LDNs in CVID patients compared to HD cells. Our data indicate that that the functional characteristics of LDNs are closely linked to their developmental stage. The observed reduction in oxidative burst capacity in mLDNs in CVID patients could contribute to an increased susceptibility to recurrent bacterial infections among CVID patients.

• MeSH
• běžná variabilní imunodeficience * MeSH
• fenotyp MeSH
• lidé MeSH
• neutrofily * MeSH
• průtoková cytometrie MeSH
• respirační vzplanutí MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• ateroskleróza prevence a kontrola   MeSH
• dolní končetina MeSH
• ischemie prevence a kontrola   MeSH
• nemoci cév prevence a kontrola   rehabilitace   terapie   MeSH
• rehabilitace metody   MeSH
• životní styl MeSH
• životní změny MeSH
• Publikační typ
• přehledy MeSH

(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM.

• MeSH
• diabetes mellitus 2. typu * komplikace   genetika   chirurgie   MeSH
• interleukin-6 metabolismus   MeSH
• kardiochirurgické výkony * MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• nemoci koronárních tepen * komplikace   genetika   chirurgie   MeSH
• perikard metabolismus   MeSH
• TNF-alfa genetika   metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Patofyziologickým podkladom chronickej žilovej insuficiencie s trofickými kožnými zmenami je lézia chlopní V hlbokom a perforátorovom žilovom systéme, ktorá až v 72 % vzniká pri rekanalizácii trombov. Redukcia refluxu valvuloplastikou v popliteálnom úseku s prerušením insuficientných perforátorov (sklerotizáciou) vedie promptne nielen k výraznej subjektívnej úľave, ale dlhodobo zlepšuje kožnú trofiku s hojením sa refraktérnych ulcerácií. Technika valvuloplastiky invagináciou venóznej steny po jej predĺžení axilárnou vénou s funkčnou chlopňou vylučuje venotómiu a použitie cudzorodého šijacieho materiálu poškodzujúceho intimu, čím sa na minimum redukuje možnosť pooperačnej trombózy.

The pathophysiological cause of chronic venous insufficiency with trophic dermal changes is a valvular lesion in the deep and perforating venous system which develops in as many as 72 % during recanalization of thrombi. The reduction of reflux by valvuloplasty in the popliteal section with discontinuation of the insufficient perforating vessels (sclerotization) leads promptly not only to marked subjective relief, but on a long-term basis it improves the trophic state of the skin and healing of refractory ulcerations. The technique of valvuloplasty by invaginatio of the venous wall after its prolongation by the axillary vein with a functional valve rules out venotomy and the use of alien material for suture which would damage the intima, and thus reduces to a minimum the possibility of postoperative thrombosis.

• MeSH
• dospělí MeSH
• lidé MeSH
• nemoci cév chirurgie   terapie   MeSH
• trombóza MeSH
• vena poplitea chirurgie   patologie   MeSH
• žilní insuficience chirurgie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH

Excessive osteoclast differentiation and/or bone resorptive function causes a gradual loss of bone, leading to the pathogenesis of bone diseases such as osteoporosis (OP). In this study, a sulfated glucuronorhamnoxylan polysaccharide (designated SPS-CF) of the green alga Capsosiphon fulvescens was evaluated for anti-osteoporotic activity using osteoclastic cells differentiated from RAW264.7 macrophages by receptor activator of NF-κB ligand (RANKL) treatment and ovariectomized (OVX) female mice as a postmenopausal OP model. With negligible cytotoxicity, SPS-CF (50 μg/mL) significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity, actin ring formation, and expression of matrix metalloproteinase 9 (MMP-9), cathepsin K, TRAF6, p-Pyk2, c-Cbl, c-Src, gelsolin, carbonic anhydrase II (CA II), and integrin β3, indicating that SPS-CF inhibits the differentiation and bone resorptive function of osteoclasts. Removal of sulfate groups from SPS-CF abolished its anti-osteoclastogenic activities, demonstrating that sulfate groups are critical for its activity. Oral administration of SPS-CF (400 mg/kg/day) to OVX mice significantly augmented the bone mineral density (BMD) and serum osteoprotegerin (OPG)/RANKL ratio. These results demonstrated that SPS-CF exerts significant anti-osteoporotic activity by dampening osteoclastogenesis and bone resorption via downregulation of TRAF6-c-Src-Pyk2-c-Cbl-gelsolin signaling and augmentation of serum OPG/RANKL ratios in OVX mice, suggesting that SPS-CF can be a novel anti-osteoporotic compound for treating postmenopausal OP.

• MeSH
• buněčná diferenciace MeSH
• Chlorophyta * metabolismus   MeSH
• faktor 6 asociovaný s receptory TNF metabolismus   MeSH
• fokální adhezní kinasa 2 metabolismus   MeSH
• gelsolin metabolismus   MeSH
• kyselá fosfatasa rezistentní k tartarátu metabolismus   MeSH
• myši MeSH
• NF-kappa B metabolismus   MeSH
• osteoporóza * farmakoterapie   MeSH
• resorpce kosti * farmakoterapie   MeSH
• sírany metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH