Galectin-3 is an immunomodulatory protein with binding capacity for various glycoconjugates including IgE. It has been shown to be produced by epidermal keratinocytes and is present on the surfaces of skin Langerhans cells (LC). Therefore, it may have a role in the pathogenesis of various skin diseases, such as atopic dermatitis. To study the expression of galectin-3 in LC, we used, in addition to specific antibodies, a panel of synthetic, carrier-immobilized, specific oligosaccharides of the A- and B-histo-blood group, which are recognized by this lectin. In the mean time, Birbeck granules were visualized with an anti-Lag antibody. The double labeling experiments showed a remarkable colocalization of signals for Lag antigen (Birbeck granules) and galectin-3, as well as the binding sites for A- and B-histo-blood group trisaccharides. The specificity of the oligosaccharide binding was demonstrated by the lack of binding by Le(c), Le(d) (H blood group antigen), and sLe(x), which are not recognized by galectin-3. These results suggest that galectin-3 is present in Birbeck granules, where it retains reactivity for its glycoligands.

• MeSH
• ABO systém krevních skupin metabolismus   MeSH
• cytoplazmatická granula imunologie   MeSH
• diferenciační antigeny genetika   metabolismus   MeSH
• galektin 3 MeSH
• Langerhansovy buňky imunologie   metabolismus   MeSH
• lidé MeSH
• protilátky imunologie   MeSH
• trisacharidy metabolismus   MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABO systém krevních skupin MeSH
• diferenciační antigeny MeSH
• galektin 3 MeSH
• protilátky MeSH
• trisacharidy MeSH

Sepsis is associated with a dysregulated inflammatory response to infection. Despite the activation of inflammation, an immune suppression is often observed, predisposing patients to secondary infections. Therapies directed at restoration of immunity may be considered but should be guided by the immune status of the patients. In this paper, we described the use of a high-dimensional flow cytometry (HDCyto) panel to assess the immunophenotype of patients with sepsis. We then isolated peripheral blood mononuclear cells (PBMCs) from patients with septic shock and mimicked a secondary infection by stimulating PBMCs for 4 h in vitro with lipopolysaccharide (LPS) with or without prior exposure to either IFN-γ, or LAG-3Ig. We evaluated the response by means of flow cytometry and high-resolution clustering cum differential analysis and compared the results to PBMCs from healthy donors. We observed a heterogeneous immune response in septic patients and identified two major subgroups: one characterized by hypo-responsiveness (Hypo) and another one by hyper-responsiveness (Hyper). Hypo and Hyper groups showed significant differences in the production of cytokines/chemokine and surface human leukocyte antigen-DR (HLA-DR) expression in response to LPS stimulation, which were observed across all cell types. When pre-treated with either interferon gamma (IFN-γ) or lymphocyte-activation gene 3 (LAG)-3 recombinant fusion protein (LAG-3Ig) prior to LPS stimulation, cells from the Hypo group were shown to be more responsive to both immunostimulants than cells from the Hyper group. Our results demonstrate the importance of patient stratification based on their immune status prior to any immune therapies. Once sufficiently scaled, this approach may be useful for prescribing the right immune therapy for the right patient at the right time, the key to the success of any therapy.

• Klíčová slova
• LAG-3Ig, Lipopolysaccharides, high-dimensional flow cytometry, immunophenotype, interferon-γ, sepsis,
• MeSH
• biologické markery krev   MeSH
• CD antigeny farmakologie   MeSH
• cytokiny krev   MeSH
• fenotyp MeSH
• HLA-DR antigeny krev   MeSH
• imunofenotypizace * MeSH
• interferon gama farmakologie   MeSH
• kultivované buňky MeSH
• leukocyty mononukleární účinky léků   imunologie   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• monitorování imunologické * MeSH
• prediktivní hodnota testů MeSH
• protein genu 3 aktivace lymfocytů MeSH
• průběh práce MeSH
• průtoková cytometrie * MeSH
• septický šok krev   diagnóza   imunologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• CD antigeny MeSH
• cytokiny MeSH
• HLA-DR antigeny MeSH
• IFNG protein, human MeSH Prohlížeč
• interferon gama MeSH
• Lag3 protein, human MeSH Prohlížeč
• lipopolysacharidy MeSH
• protein genu 3 aktivace lymfocytů MeSH
• soluble LAG-3 protein, human MeSH Prohlížeč

Circadian clock plays an essential role in orchestrating daily physiology, and its disruption can evoke metabolic diseases such as obesity. L-Carnitine can reduce blood lipid levels, and ameliorate fatty liver through regulating lipid metabolism. However, whether L-Carnitine administration may affect the disturbance of lipid metabolism and circadian rhythm of mice induced by prolonged circadian disruption is still unknown. Herein, we investigated the effects of L-Carnitine on conditions of circadian clock and lipid metabolism through a chronic jet-lag mice model which was developed by reversing 12 h light/12 h dark cycle every 4 days for a continuous 12 weeks. Results showed that L-Carnitine administration significantly decreased levels of serum glutamic-oxaloacetic transaminase (GOT) and triglycerides (TG), which were remarkably elevated by chronic jet-lag. More importantly, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that L-Carnitine supplementation would effectively counteract the negative alterations in gene expression which related to lipid metabolism (Srebp1, Acaca, Fasn, and Scd1), metabolic regulator (mTOR) and circadian rhythm (Bmal1, Per1, Cry1 and Dec1) in the liver of mice subjected to the chronic jet-lag. As a conclusion, L-Carnitine was partly effective in preventing the disruption of circadian clock and lipid metabolic disorders induced by the chronic jet-lag.

• MeSH
• chronická nemoc MeSH
• cirkadiánní hodiny účinky léků   fyziologie   MeSH
• cirkadiánní rytmus účinky léků   fyziologie   MeSH
• jet lag syndrom krev   farmakoterapie   genetika   MeSH
• karnitin farmakologie   terapeutické užití   MeSH
• metabolismus lipidů účinky léků   fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• náhodné rozdělení MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• karnitin MeSH

Accumulating evidence indicates that immune checkpoint inhibitors (ICIs) can restore CD8+ cytotoxic T lymphocyte (CTL) functions in preclinical models of acute myeloid leukemia (AML). However, ICIs targeting programmed cell death 1 (PDCD1, best known as PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) have limited clinical efficacy in patients with AML. Natural killer (NK) cells are central players in AML-targeting immune responses. However, little is known on the relationship between co-inhibitory receptors expressed by NK cells and the ability of the latter to control AML. Here, we show that hepatitis A virus cellular receptor 2 (HAVCR2, best known as TIM-3) is highly expressed by NK cells from AML patients, correlating with improved functional licensing and superior effector functions. Altogether, our data indicate that NK cell frequency as well as TIM-3 expression levels constitute prognostically relevant biomarkers of active immunity against AML.

• Klíčová slova
• Co-inhibitory receptor, innate lymphoid cells, lag-3, tigit, vista,
• MeSH
• akutní myeloidní leukemie * farmakoterapie   MeSH
• buněčný receptor 2 viru hepatitidy A * MeSH
• buňky NK * MeSH
• CD8-pozitivní T-lymfocyty MeSH
• cytotoxické T-lymfocyty MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• buněčný receptor 2 viru hepatitidy A * MeSH
• HAVCR2 protein, human MeSH Prohlížeč

STUDY OBJECTIVES: Social jetlag manifests as a difference in sleep timing on workdays and free days. Social jetlag is often associated with shorter, lower-quality sleep, so it is unclear how much the chronic circadian misalignment contributes to observed negative health outcomes. We aimed to (1) investigate associations between social jetlag, chronotype (one of its determinants), and the levels of health markers, (2) describe factors associated with social jetlag, and (3) examine whether working from home can reduce social jetlag. METHODS: Adult respondents participated in a nationally representative longitudinal survey of Czech households (individuals in each wave: n2018/19/20 = 5132/1957/1533), which included Munich ChronoType Questionnaire to evaluate chronotype and social jetlag. A subset provided blood samples (n2019 = 1957) for detection of nine biomarkers and was surveyed in three successive years (social jetlag calculated for n2018/19/20 = 3930/1601/1237). Data were analyzed by nonparametric univariate tests and mixed effects multivariate regression with social jetlag, chronotype, sex, age, body-mass index, and reported diseases as predictors and biomarker levels as outcomes. RESULTS: Higher social jetlag (≥0.65 h) was significantly associated with increased levels of total cholesterol and low-density lipoprotein cholesterol, particularly in participants older than 50 years (Mann-Whitney, men: pCHL = 0.0005, pLDL = 0.0009; women: pCHL = 0.0079, pLDL = 0.0068). Extreme chronotypes were associated with cardiovascular disease risk markers regardless of social jetlag (Kruskal-Wallis, p < 0.0001). Commuting to work and time stress were identified as important contributors to social jetlag. Individual longitudinal data showed that working from home decreased social jetlag and prolonged sleep. CONCLUSIONS: We report significant associations between sleep phase preference, social jetlag, and cardio-metabolic biomarkers.

• Klíčová slova
• Biomarkers, Cholesterol, Chronotype, Circadian Rhythm, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Models, Statistical, Social jetlag,
• MeSH
• biologické markery MeSH
• cholesterol MeSH
• cirkadiánní rytmus * MeSH
• dospělí MeSH
• jet lag syndrom MeSH
• lidé MeSH
• metabolické nemoci * komplikace   MeSH
• průzkumy a dotazníky MeSH
• spánek MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cholesterol MeSH

To investigate the effect of light cue on the resetting of the peripheral clocks, we examined the resetting processes of clock genes (Per1, Per2, Bmal1, Cry1, Dec1, and Rev-erbalpha) in the liver and heart of rats after the feeding and light-dark (LD) reversal via a 24-h light period transition. The liver clock was reset quickly within 3 days, while the heart clock needed a longer time course of 5-7 days to be completely re-entrained. Moreover, the re-entrainment of Per1 and Per2 in the liver clock was more rapid than that of the other four clock genes, suggesting the important role of these two clock genes in initiating the circadian resetting of the hepatic clock. However, the resetting rates of these two clock genes were as similar as the others in the heart clock. Therefore, the resetting mechanisms underlining these two peripheral clocks may be totally distinct. Furthermore, the re-entrainment of the liver and heart clocks were relatively lengthened after the feeding and LD reversal via a light period transition compared to a dark period transition, suggesting a simultaneous shift of feeding schedule and the LD cycle may facilitate the circadian resetting in rats.

• MeSH
• biologické hodiny genetika   MeSH
• cirkadiánní proteiny Period genetika   MeSH
• cirkadiánní rytmus genetika   MeSH
• fotoperioda * MeSH
• homeodoménové proteiny genetika   MeSH
• jaderné receptory - podrodina 1, skupina D, člen 1 genetika   MeSH
• játra metabolismus   MeSH
• jet lag syndrom genetika   patofyziologie   MeSH
• kryptochromy genetika   MeSH
• krysa rodu Rattus MeSH
• messenger RNA metabolismus   MeSH
• myokard metabolismus   MeSH
• podněty MeSH
• potkani Wistar MeSH
• regulace genové exprese MeSH
• stravovací zvyklosti * MeSH
• světelná stimulace MeSH
• transkripční faktory ARNTL genetika   MeSH
• transkripční faktory bHLH genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Bhlhe40 protein, rat MeSH Prohlížeč
• cirkadiánní proteiny Period MeSH
• Cry1 protein, rat MeSH Prohlížeč
• homeodoménové proteiny MeSH
• jaderné receptory - podrodina 1, skupina D, člen 1 MeSH
• kryptochromy MeSH
• messenger RNA MeSH
• Nr1d1 protein, rat MeSH Prohlížeč
• Per1 protein, rat MeSH Prohlížeč
• Per2 protein, rat MeSH Prohlížeč
• transkripční faktory ARNTL MeSH
• transkripční faktory bHLH MeSH

The current study examined the reciprocal association between psychological resilience, physical activity, and self-rated health in older America adults. A 3-wave cross-lagged panel design was employed using data sampled from the Health and Retirement Study 2010, 2014, and 2018. In total, 8380 older adults, age ranged between 56 and 95 years at the baseline (mean age = 68.06, SD = 7.77), were analyzed. Using structural equation modeling, standardized path coefficients were estimated to determine the relationship between physical activity, self-rated health, and psychological resilience across 2 follow-up points. Cross-lagged analysis revealed that higher levels of physical activity at T1 and T2 were significantly associated with higher levels of self-rated health at T2 and T3, respectively. Self-rated health at T1 and T2 were significantly associated with physical activity at T2 and T3, respectively. Self-rated health and psychological resilience were positively related to one another at each time point. However, relationship between physical activity and psychological resilience was complex across time. Study findings support reciprocal prospective relationship between physical activity and self-rated health and the relationship between self-rated health and psychological resilience.

• Klíčová slova
• Health and Retirement Study (HRS), health behavior, health perception, older adults, psychological resource,
• MeSH
• cvičení * MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• psychická odolnost * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

T-cell lymphomas (TCLs) are a rare and heterogeneous subgroup of non-Hodgkin lymphomas (NHLs), forming only 10 % of all NHL cases in Western countries. Resulting from their low incidence and heterogeneity, the current treatment outcome is generally unfavorable, with limited availability of novel therapeutic approaches. Therefore, the recent success of immune checkpoint inhibitors (ICIs) in cancer treatment motivated their clinical investigation in TCLs as well. Multiple studies showed promising results; however, cases of TCL hyperprogression following ICI treatment and secondary T-cell-derived malignancies associated with ICI treatment of other cancer types were also reported. In our review, we first briefly summarize classification of T-cell-derived malignancies, general anti-tumor immune response, immune evasion, and immune checkpoint signaling. Next, we provide an overview of immune checkpoint molecule deregulation in TCLs, summarize available studies of ICIs in TCLs, and review the above-mentioned safety concerns associa-ted with ICI treatment and T-cell-derived malignancies. Despite initial promising results, further studies are necessary to define the most suitable clinical applications and ICI therapeutic combinations with other novel treatment approaches within TCL treatment. ICIs, and their combinations, might hopefully bring the long awaited improvement for the treatment of T-cell-derived malignancies.

• Klíčová slova
• ALCL, CTLA-4, ENKTL, LAG-3, MF, OX40/OX40L, PD-1, PD-L1, PTCL, SS, Sézary syndrome, T-cell lymphoma, T-cell-derived malignancies, TIGIT, TIM-3, anaplastic large cell lymphoma, anti-CTLA-4, anti-PD-1, anti-PD-L1, atezolizumab, avelumab, durvalumab, extranodal NK/T-cell lymphoma, geptanolimab, immune checkpoint inhibitors, immune checkpoints, ipilimumab, mycosis fungoides, nivolumab, pembrolizumab, peripheral T-cell lymphoma, sintilimab, toripalimab,
• MeSH
• inhibitory kontrolních bodů * terapeutické užití   MeSH
• lidé MeSH
• lymfom T-buněčný * farmakoterapie   imunologie   MeSH
• proteiny kontrolních bodů imunitní reakce metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• inhibitory kontrolních bodů * MeSH
• proteiny kontrolních bodů imunitní reakce MeSH

BACKGROUND: Evidence on health effects of ultrafine particles (UFP) is still limited as they are usually not monitored routinely. The few epidemiological studies on UFP and (cause-specific) mortality so far have reported inconsistent results. OBJECTIVES: The main objective of the UFIREG project was to investigate the short-term associations between UFP and fine particulate matter (PM)<2.5μm (PM2.5) and daily (cause-specific) mortality in five European Cities. We also examined the effects of PM<10μm (PM10) and coarse particles (PM2.5-10). METHODS: UFP (20-100nm), PM and meteorological data were measured in Dresden and Augsburg (Germany), Prague (Czech Republic), Ljubljana (Slovenia) and Chernivtsi (Ukraine). Daily counts of natural and cardio-respiratory mortality were collected for all five cities. Depending on data availability, the following study periods were chosen: Augsburg and Dresden 2011-2012, Ljubljana and Prague 2012-2013, Chernivtsi 2013-March 2014. The associations between air pollutants and health outcomes were assessed using confounder-adjusted Poisson regression models examining single (lag 0-lag 5) and cumulative lags (lag 0-1, lag 2-5, and lag 0-5). City-specific estimates were pooled using meta-analyses methods. RESULTS: Results indicated a delayed and prolonged association between UFP and respiratory mortality (9.9% [95%-confidence interval: -6.3%; 28.8%] increase in association with a 6-day average increase of 2750particles/cm(3) (average interquartile range across all cities)). Cardiovascular mortality increased by 3.0% [-2.7%; 9.1%] and 4.1% [0.4%; 8.0%] in association with a 12.4μg/m(3) and 4.7μg/m(3) increase in the PM2.5- and PM2.5-10-averages of lag 2-5. CONCLUSIONS: We observed positive but not statistically significant associations between prolonged exposures to UFP and respiratory mortality, which were independent of particle mass exposures. Further multi-centre studies are needed investigating several years to produce more precise estimates on health effects of UFP.

• Klíčová slova
• Central Europe, Mortality, Particulate matter, Time series, Ultrafine particles,
• MeSH
• dítě MeSH
• dospělí MeSH
• kardiovaskulární nemoci mortalita   MeSH
• kojenec MeSH
• látky znečišťující vzduch škodlivé účinky   analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pevné částice škodlivé účinky   analýza   MeSH
• poruchy dýchání mortalita   MeSH
• předškolní dítě MeSH
• příčina smrti MeSH
• senioři MeSH
• teoretické modely MeSH
• velikost částic * MeSH
• velkoměsta epidemiologie   MeSH
• znečištění ovzduší škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• velkoměsta epidemiologie   MeSH
• Názvy látek
• látky znečišťující vzduch MeSH
• pevné částice MeSH

The present study assesses the short-term association between black smoke (BS) and sulphur dioxide (SO2) levels in urban air and the daily number of emergency room admissions for chronic obstructive pulmonary disease (COPD) in Nis, Serbia. Generalised linear models extending Poisson regression were fitted controlling for time trend, seasonal variations, days of the week, temperature, relative humidity, air pressure, precipitation, rainfall, snowfall, overcast, and wind velocity. The emergency room admissions for all ages for COPD were significantly associated with previous-day level of BS and lag 0-2 (1,60% and 2,26% increase per 10 microg/m3, respectively). After controlling for SO2, single lagged (lag 1 and lag 2) as well as mean lagged values of BS (up to lag 0-3) were significantly associated with COPD emergencies. No effect was found for SO2, even after controlling for black smoke. The present findings support the conclusion that current levels of ambient BS may have an effect on the respiratory health of susceptible persons.

• MeSH
• chronická obstrukční plicní nemoc * MeSH
• hospitalizace statistika a číselné údaje   MeSH
• kouř škodlivé účinky   analýza   MeSH
• látky znečišťující vzduch škodlivé účinky   analýza   MeSH
• lidé MeSH
• oxid siřičitý škodlivé účinky   analýza   MeSH
• počasí MeSH
• Poissonovo rozdělení MeSH
• urgentní služby nemocnice MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Srbsko MeSH
• Názvy látek
• kouř MeSH
• látky znečišťující vzduch MeSH
• oxid siřičitý MeSH