26 research outputs found

    Regulation of immune cell function and differentiation by the NKG2D receptor

    Get PDF
    NKG2D is one of the most intensively studied immune receptors of the past decade. Its unique binding and signaling properties, expression pattern, and functions have been attracting much interest within the field due to its potent antiviral and anti-tumor properties. As an activating receptor, NKG2D is expressed on cells of the innate and adaptive immune system. It recognizes stress-induced MHC class I-like ligands and acts as a molecular sensor for cells jeopardized by viral infections or DNA damage. Although the activating functions of NKG2D have been well documented, recent analysis of NKG2D-deficient mice suggests that this receptor may have a regulatory role during NK cell development. In this review, we will revisit known aspects of NKG2D functions and present new insights in the proposed influence of this molecule on hematopoietic differentiation

    Неоперабельный гепатоцеллюлярный рак — перспективы лекарственной терапии ленватинибом

    Get PDF
    There is a number of unresolved issues regarding the systemic therapy administration for hepatocellular carcinoma (HCC). Their solution is facilitated by accumulating real‑world study results. Lenvatinib therapy is a recognized drug with a good efficacy and safety profile for the treatment of HCC. Subanalyses of the REFLECT study showed that the absence of stratification by baseline AFP and baseline liver function, as well as the lack of options for subsequent drug therapy after lenvatinib, also affects the outcomes. Once these factors are taken into account, the hypothesis of superiority of lenvatinib to sorafenib and other drugs can be tested. Real‑world clinical studies have demonstrated positive results of lenvatinib therapy in patients with Child‑Pugh class B liver function, provided recommendations on the sequence of systemic therapy after lenvatinib and on the use of lenvatinib in patients with BCLC stage B, along with considering the possibility of lenvatinib monotherapy and the prospects for its use in patients with nHCC. Further real‑world studies of lenvatinib for HCC in the Russian population are required.В подходах к назначению лекарственной терапии гепатоцеллюлярного рака (ГЦР) есть ряд еще нерешенных вопросов. Их решению способствует накопление результатов исследований в реальной клинической практике. Методом медикаментозной терапии ГЦР с хорошим профилем эффективности и безопасности признана терапия ленватинибом. В субанализах исследования REFLECT показано, что отсутствие стратификации по исходному уровню альфа-фетопротеина и оценке исходной функции печени, а также дефицит опций последующей после назначения ленватиниба медикаментозной терапии оказывают влияние на результаты. Учет этих факторов даст возможность проверить гипотезу превосходства терапии ленватинибом в сравнении с сорафенибом и другими препаратами. В исследованиях реальной клинической практики продемонстрированы положительные результаты применения ленватиниба у пациентов с нарушением функции печени класса B по шкале Чайлд-Пью, даны рекомендации по последовательности системной терапии после ленватиниба, применению ленватиниба у пациентов стадии BCLC B, а также рассмотрены возможности монотерапии ленватинибом и перспективы его применения у пациентов с нГЦК. Необходимы дальнейшие исследования ленватиниба при ГЦР в реальной клинической практике на российской популяции

    NK cell receptor NKG2D sets activation threshold for the NCR1 receptor early in NK cell development

    Get PDF
    The activation of natural killer (NK) cells depends on a change in the balance of signals from inhibitory and activating receptors. The activation threshold values of NK cells are thought to be set by engagement of inhibitory receptors during development. Here, we found that the activating receptor NKG2D specifically set the activation threshold for the activating receptor NCR1 through a process that required the adaptor DAP12. As a result, NKGD2-deficient (Klrk1-/-) mice controlled tumors and cytomegalovirus infection better than wild-type controls through the NCR1-induced production of the cytokine IFN-γ. Expression of NKG2D before the immature NK cell stage increased expression of the adaptor CD3ζ. Reduced expression of CD3ζ in Klrk1-/- mice was associated with enhanced signal transduction through NCR1, and CD3ζ deficiency resulted in hyper-responsiveness to stimulation via NCR1. Thus, an activating receptor developmentally set the activity of another activating receptor on NK cells and determined NK cell reactivity to cellular threats

    EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

    Get PDF
    More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

    Session 17 Ecophysiology

    Get PDF
    n/

    Bieżąca sytuacja przy zarządzaniu gospodarką odpadów przemysłu odzieżowego Macedonii pochodzących z procesu produkcyjnego

    No full text
    Effective utilisation of textile waste requires an accurate prediction of the quality of waste generated. Textile waste in Macedonia mainly consists of apparel cuttings. The aim of this research was to characterize the apparel cuttings waste, define the current state of apparel waste management and the potential barriers against introducing efficient waste management systems. Data was obtained via a structured questionnaire distributed to top managers in apparel manufacturing companies. The results indicated that almost all apparel manufacturers use landfills to dispose of their waste. The analysis showed that the waste stream consisted principally of woven fabrics, predominately cotton and cotton blends, with the presence of lycra. Bearing in mind the waste composition, the most appropriate end use for the pre-consumer waste produced is insulation materials. Considering that the industry consists of small and medium companies with limited resources, there is a low likelihood of individual investments in recycling equipment.Efektywna utylizacja odpadów tekstylnych wymaga dokładnego przewidywania jakości generowanych odpadów. Odpady odzieżowe Macedonii tworzone są głównie przez ścinki odzieżowe. Celem badań było scharakteryzowanie ścinków, ustalenie odpowiednich metod zarządzania odpadami i identyfikacja barier wpływających na efektywność systemu zarządzania odpadami. Odpowiednio opracowane kwestionariusze zostały rozprowadzone wśród zarządów tekstylnych zakładów produkcyjnych. Wyniki wskazują, że prawie wszyscy wytwórcy tekstyliów stosują wysypiska dla rozdysponowania swoich odpadów. Analiza wykazała, że strumienie odpadów składają się głównie z tkanin, w tym przeważnie bawełnianych, i z mieszanek bawełny z lycrą. Biorąc pod uwagę ten skład materiałów odpadowych, wydaje się, że najbardziej odpowiednim zastosowaniem może być produkcja materiałów izolacyjnych. Ponieważ przemysł przetwórczy skalda się głównie z małych i średnich przedsiębiorstw istnieje małe prawdopodobieństwo zakupu odpowiednio dużych maszyn przetwarzających
    corecore