4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells

Chronic and acute myeloid leukemia evade immune system surveillance and induce immunosuppression by expanding proleukemic Foxp31 regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, leukemia relapse, and shorter survival. However, mechanisms that promote Tregs in myeloid leukemias remain largely unexplored. Here, we identify leukemic extracellular vesicles (EVs) as drivers of effector proleukemic Tregs. Using mouse model of leukemia-like disease, we found that Rab27adependent secretion of leukemic EVs promoted leukemia engraftment, which was associated with higher abundance of activated, immunosuppressive Tregs. Leukemic EVs attenuated mTOR-S6 and activated STAT5 signaling, as well as evoked significant transcriptomic changes in Tregs. We further identified specific effector signature of Tregs promoted by leukemic EVs. Leukemic EVs-driven Tregs were characterized by elevated expression of effector/tumor Treg markers CD39, CCR8, CD30, TNFR2, CCR4, TIGIT, and IL21R and included 2 distinct effector Treg (eTreg) subsets: CD301CCR8hiTNFR2hi eTreg1 and CD391TIGIThi eTreg2. Finally, we showed that costimulatory ligand 4-1BBL/CD137L, shuttled by leukemic EVs, promoted suppressive activity and effector phenotype of Tregs by regulating expression of receptors such as CD30 and TNFR2. Collectively, our work highlights the role of leukemic extracellular vesicles in stimulation of immunosuppressive Tregs and leukemia growth. We postulate that targeting of Rab27a-dependent secretion of leukemic EVs may be a viable therapeutic approach in myeloid neoplasms

Efeitos do ômega 3 em gestantes obesas: uma revisão da literatura / Effects of omega-3 in obese pregnant women: a review of the literature

Durante a gestação, a obesidade materna está associada ao desenvolvimento do Diabetes Mellitus Gestacional, doenças hipertensivas, intercorrências cardiovasculares, eventos tromboembólicos, cesarianas e complicações cirúrgicas durante o parto. Tendo em vista que a dieta materna, no período pré-natal, é de grande importância para o desenvolvimento fetal, pois determina o tipo de ácido graxo que se acumulará no tecido do feto, e que o transporte do ômega-3 se dá através da placenta, este trabalho tem como objetivo realizar uma revisão bibliográfica acerca dos efeitos do ômega-3 em gestantes obesas. Os resultados sobre os estudos analisados nos mostram que o ômega-3 é capaz de ajudar no controle do perfil lipídico materno e desenvolvimento fetal, conter reações inflamatórias, diminuir o risco de DMG e pré-eclâmpsia e possível redução da predisposição para doenças metabólicas na vida adulta. Portanto, o consumo de ômega-3, durante a gestação, é de grande importância, tanto para a mãe quanto para o concepto

Properties and in vitro digestibility of buckwheat starch compared to wheat starch

Produkty z udziałem mąki gryczanej charakteryzują się dobrą wartością odżywczą i obecnością składników o działaniu prozdrowotnym, w tym niskim indeksem glikemicznym. Cechy te mogą być przydatne w projektowaniu nowych produktów z udziałem ziarniaków gryki. Celem pracy było porównanie wybranych właściwości wyizolowanej skrobi z gryki z właściwościami mąki gryczanej oraz skrobi pszennej. Wykazano, że ze względu na ponad 10-krotnie mniejszą wielkość ziarenek skrobi gryczanej w stosunku do skrobi pszennej ich właściwości znacznie się różnią, pomimo że obie mają ten sam typ struktury polimorficznej i podobną zawartość amylozy. Skrobia gryczana charakteryzowała się większą temperaturą i entalpią przemiany kleikowania niż skrobia pszenna. W przypadku mąki gryczanej obserwowano jeszcze większe wartości temperatury przemiany kleikowania oraz niskie wartości siły pęcznienia i zdolności rozpuszczania amylozy, co wynika prawdopodobnie z obecności białek na powierzchni ziarenek skrobi. Te właściwości wpłynęły na podatność skrobi na trawienie. Skrobia w mące gryczanej (surowej) charakteryzowała się dużym udziałem frakcji opornej (RS), ale po wyizolowaniu skrobi z mąki udział RS był znikomy – mniejszy niż w skrobi pszennej. Po gotowaniu udział skrobi szybko trawionej w mące i w wyizolowanej skrobi był na zbliżonym poziomie. Po skleikowaniu udział RS był większy w skrobi gryczanej niż w pszennej, co wskazuje na większą podatność tej skrobi na retrogradację.Products containing buckwheat flour are characterized by a good nutritional value and pro-health substances contained therein as well as by a low glycemic index. Those features can be useful when designing new products containing buckwheat grains. The objective of the research study was to compare some selected properties of starch isolated from buckwheat with the features of buckwheat flour and wheat starch. It has been proved that, because the size of buckwheat starch granules is more than 10 times smaller than that of wheat starch, their properties vary widely, although the two starches have the same type of polymorphic structure and a similar content of amylose. The buckwheat starch had a higher gelatinization temperature and its enthalpy of gelatinization transition was higher than that of the wheat starch. In the case of the buckwheat flour, even higher values of gelatinization transition temperatures were recorded as were low values of swelling power and amylose leaching ability, which, likely, resulted from the presence of proteins on the surface of starch granules. Those properties affected the digestibility of starch. The starch in the buckwheat (raw) flour was characterized by a high content of resistant starch (RS); however, after it was isolated from the flour, the content of RS was insignificant and lower than that in the wheat starch. After cooking, the percentage contents of rapidly digested starch in the flour and in the isolated starch were at a similar level. After gelatinization, the content of RS was higher in the buckwheat than in the wheat starch; this fact indicated that the susceptibility of buckwheat starch to retrogradation was higher than that of the wheat starch

Effect of processing and thermally treating buckwheat grains on nutrients

Ze względu na cenny skład ziarniaków gryki na rynku pojawiła się szeroka oferta produktów z ich udziałem. Stosowane procesy podczas przetwarzania ziarniaków oraz obróbka kulinarna produktów gryczanych mogą powodować zmiany istotnych składników, mające wpływ na ich właściwości żywieniowe. Celem pracy było określenie zmian w składnikach odżywczych i strawności skrobi spowodowanych wpływem procesów przetwórczych ziarniaków gryki, tj. otrzymywania płatków oraz kaszy prażonej i nieprażonej oraz w przypadku kasz dodatkowo wpływem obróbki kulinarnej przeprowadzonej dwoma sposobami. Wykazano, że płatki w porównaniu z ziarniakami gryki zawierały mniej składników mineralnych i białek, natomiast w kaszach zależność ta była odwrotna. Proces prażenia wpłynął na skład kasz gotowanych, które zawierały mniej związków mineralnych w postaci popiołu, tłuszczu i białek niż gotowane kasze nieprażone. Sposób gotowania w wodzie (z odlewaniem lub bez) nie powodował istotnych różnic zawartości białek w obu rodzajach kasz oraz zawartości tłuszczu w kaszach prażonych. Prażenie wpływało na znaczne obniżenie aktywności inhibitora trypsyny oraz wzrost zawartości azotu niebiałkowego w kaszach gryczanych. W odniesieniu do ziarniaków gryki procesy stosowane w produkcji płatków i kaszy gryczanej spowodowały znaczne zmniejszenie ilości skrobi wolno trawionej i skrobi opornej w wyniku usunięcia składników ograniczających strawność skrobi oraz zabiegów hydrotermicznych powodujących skleikowanie skrobi. Kasze prażone zawierały po gotowaniu ok. czterokrotnie mniej skrobi opornej niż nieprażone. Wysoka zawartość dostępnych grup tiolowych w białkach ziarniaków gryki i produktach gryczanych, także po zastosowanej obróbce kulinarnej kasz, wskazuje na ich potencjalne właściwości funkcjonalne m.in. przeciwutleniające.Because of the valuable composition of buckwheat grains, a wide range of products containing those grains appeared on the market. The processes applied during the processing of those grains and the thermal treatment of buckwheat products can cause changes in significant components, which affect their nutritional properties. The objective of the study was to investigate changes in the nutrients and the digestibility of starch caused by buckwheat grain processing, i.e. by the preparation of flakes and roasted and unroasted groats, and in the case of groats, additionally, the effects of culinary processing carried out in two ways. It was showed that, compared to grains, buckwheat flakes contained less minerals and less proteins, whereas in the groats, this dependence was reversed. The roasting process impacted the composition of boiled groats; they contained less mineral compounds in the form of ash, less fat and less protein than the boiled unroasted groats. The method of boiling in water (with or without pouring out) did not cause significant differences in the protein content in the two types of groats and in the fat content in roasted groats. Roasting caused the trypsin inhibitor activity to considerably decrease and the content of non-protein nitrogen in buckwheat groats to increase. As regards the buckwheat grains, the processes applied in the production of buckwheat flakes and buckwheat groats resulted in a significant reduction in the amount of slow-digested starch and resistant starch because constituents were removed that limited the starch digestion and because of the hydrothermal treatment that caused the starch to gelatinize. After boiling, roasted groats contained about four times less resistant starch than unroasted groats. A high content of available thiol groups in buckwheat grains and buckwheat products, also after culinary treatment of groats, indicates their potential functional properties, e.g. antioxidant properties

Investigation of Phosphorus Release during Annealing of Au Contacts to InP

The analysis of phosphorus release from Au/InP contacts heat treated at temperature from the range 360-480°C showed that P evaporation accompanies any stage of contact reaction. The use of encapsulating layer during contact annealing suppresses the loss of phosphorus and changes the kinetics of thermally activated interfacial reaction

Dual Role of TiN Reaction Barrier in Gold Based Metallization to GaAs

Reactively sputtered TiN films were evaluated as annealing cap improving the formation of Au(Zn) ohmic contact and as antidiffusion barrier protecting contact metallization and underlying GaAs against reaction with Au overlayers

Activity of new N-acylated ciprofloxacin derivatives against faculative intracellular bacteria

Bartonella species are facultative intracellular pathogens responsible for a range of diseases in animals and in humans. A selection of N-acyl ciprofloxacin analogues, chemically synthesized from ciprofloxacin, have been tested in vitro for activity against Bartonella species as models for therapeutic development. Nine Bartonella strains, including five of B. henselae, two of B. quintana, and one each of B. elizabethae and B. vinsonii, have been tested for susceptibility to different N-acyl ciprofloxacin derivatives. Several techniques have been used to test the in vitro antibacterial activity of the derivatives. Seven of them, labeled RC4-125, RC4-143, RC4-147, RC5-28, RC5-29, RC5-32 and RC5-69 showed significant intracellular anti-Bartonella activity. These synthetically derived N-acyl ciprofloxacin derivatives may be useful in the therapeutic treatment of infections caused by Bartonella