Methods for preventing and treating cancer using N-thiolated β-lactam compounds and analogs thereof

The subject invention concerns N-thiolated β-lactam compounds of formula A, wherein R1 is a hydrocarbon group having 1–8 carbon atoms; R3 is an organothio group; and R4 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, and analogs and pharmaceutically acceptable salts, esters and amides thereof. The subject invention also concerns methods for inducing tumor cell death or inhibiting tumor cell proliferation, and methods for inducing DNA damage, inhibiting DNA replication, activating p38 MAP kinase, or activating caspase cascade activation, or releasing cytochrome C from mitochondria into the cytoplasm in a tumor cell. Methods for treating cancer using N-thiolated β-lactam compounds, as well as pharmaceutical compositions comprising the same are further disclosed

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

Origin and production of silver in early medieval Poland

Modern archaeology makes use of analytical methods in order to answer questions about deposit and technological provenience of artefacts. This paper discusses selected and the most interesting, results obtained during the completion of a research project which focuses on silver from the 10th and 11th centuries in Poland. In total, 200 silver artefacts known from Polish hoards (found in Kalisz-Dobrzec, Nowa Obra, Wolsztyn District, Zalesie, Olsztyn District, Słuszków and Jastrzębniki, Kalisz District, Kalisz-Rajsków and Stojkowo, Kołobrzeg District and Naruszewo, Płońsk District) were studied. A micro-invasion LA-ICP-MS (Laser Inductively Coupled Plasma Mass Spectrometry) was used for determinining lead isotope ratios in silver. The data obtained were evaluated using statistical methods which allowed reliable isotopic ratios in inhomogeneous alloy to be obtained. In order to study the provenance of silver, the obtained lead isotope ratios in the artefacts were compared with those of silver deposits. The use of SEM-EDX allowed the tracing of morphological changes and the measurement of quantitative elemental composition of coins, raw silver and jewellery according to technological traits

Methods for preventing and treating cancer using N-thiolated β-lactam compounds and analogs thereof

The subject invention concerns N-thiolated β-lactam compounds of formula A, wherein R1 is a hydrocarbon group having 1–8 carbon atoms; R3 is an organothio group; and R4 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, and analogs and pharmaceutically acceptable salts, esters and amides thereof. The subject invention also concerns methods for inducing tumor cell death or inhibiting tumor cell proliferation, and methods for inducing DNA damage, inhibiting DNA replication, activating p38 MAP kinase, or activating caspase cascade activation, or releasing cytochrome C from mitochondria into the cytoplasm in a tumor cell. Methods for treating cancer using N-thiolated β-lactam compounds, as well as pharmaceutical compositions comprising the same are further disclosed

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

Methods for preventing and treating cancer using N-thiolated β-lactam compounds and analogs thereof

The subject invention concerns N-thiolated β-lactam compounds of formula A, wherein R1 is a hydrocarbon group having 1-8 carbon atoms; R3 is an organothio group; and R4 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, and analogs and pharmaceutically acceptable salts, esters and amides thereof. The subject invention also concerns methods for inducing tumor cell death or inhibiting tumor cell proliferation, and methods for inducing DNA damage, inhibiting DNA replication, activating p38 MAP kinase, or activating caspase cascade activation, or releasing cytochrome C from mitochondria into the cytoplasm in a tumor cell. Methods for treating cancer using N-thiolated β-lactam compounds, as well as pharmaceutical compositions comprising the same are further disclosed