Treatment of Odontogenic Maxillary Sinusitis with the Use of Growth Factors in Advanced Platelet-Rich Fibrin for Immediate Closure of Oro-Antral Communication: A Case Report.

Chronic odontogenic maxillary sinusitis (COMS), a prolonged inflammation of the maxillary sinus lasting over 12 weeks, is often a result of periapical lesions, marginal periodontitis, and complications like oro-antral communication (OAC) and fistula (OAF). OAC, commonly emerging post-teeth extraction in the lateral maxilla, lacks documented treatments using advanced platelet-rich fibrin (A-PRF). This study evaluates A-PRF's efficacy in treating COMS and immediately sealing extensive OAC. A case of a 28-year-old male with COMS linked to a periapical lesion and supernumerary molars is presented. Treatment involved extracting specific teeth while preserving adjacent ones and using A-PRF for immediate OAC closure. A-PRF, enriched with growth factors, was pivotal in healing, showcasing enhanced tissue regeneration, pain reduction, and faster recovery. The findings suggest A-PRF as an effective adjunct in treating extensive OAC and COMS, proposing its inclusion in standard treatment protocols. This study underscores A-PRF's potential in improving outcomes for patients with COMS and related complications.

SARS-CoV-2 and its ORF3a, E and M viroporins activate inflammasome in human macrophages and induce of IL-1α in pulmonary epithelial and endothelial cells.

Inflammasome assembly is a potent mechanism responsible for the host protection against pathogens, including viruses. When compromised, it can allow viral replication, while when disrupted, it can perpetuate pathological responses by IL-1 signaling and pyroptotic cell death. SARS-CoV-2 infection was shown to activate inflammasome in the lungs of COVID-19 patients, however, potential mechanisms responsible for this response are not fully elucidated. In this study, we investigated the effects of ORF3a, E and M SARS-CoV-2 viroporins in the inflammasome activation in major populations of alveolar sentinel cells: macrophages, epithelial and endothelial cells. We demonstrated that each viroporin is capable of activation of the inflammasome in macrophages to trigger pyroptosis-like cell death and IL-1α release from epithelial and endothelial cells. Small molecule NLRP3 inflammasome inhibitors reduced IL-1 release but weakly affected the pyroptosis. Importantly, we discovered that while SARS-CoV-2 could not infect the pulmonary microvascular endothelial cells it induced IL-1α and IL-33 release. Together, these findings highlight the essential role of macrophages as the major inflammasome-activating cell population in the lungs and point to endothelial cell expressed IL-1α as a potential novel component driving the pulmonary immunothromobosis in COVID-19.

Multienzymatic biotransformation of flavokawain B by entomopathogenic filamentous fungi: structural modifications and pharmacological predictions.

BACKGROUND: Flavokawain B is one of the naturally occurring chalcones in the kava plant (Piper methysticum). It exhibits anticancer, anti-inflammatory and antimalarial properties. Due to its therapeutic potential, flavokawain B holds promise for the treatment of many diseases. However, due to its poor bioavailability and low aqueous solubility, its application remains limited. The attachment of a sugar unit impacts the stability and solubility of flavonoids and often determines their bioavailability and bioactivity. Biotransformation is an environmentally friendly way to improve the properties of compounds, for example, to increase their hydrophilicity and thus affect their bioavailability. Recent studies proved that entomopathogenic filamentous fungi from the genera Isaria and Beauveria can perform O-methylglycosylation of hydroxyflavonoids or O-demethylation and hydroxylation of selected chalcones and flavones. RESULTS: In the present study, we examined the ability of entomopathogenic filamentous fungal strains of Beauveria bassiana, Beauveria caledonica, Isaria farinosa, Isaria fumosorosea, and Isaria tenuipes to transform flavokawain B into its glycosylated derivatives. The main process occurring during the reaction is O-demethylation and/or hydroxylation followed by 4-O-methylglycosylation. The substrate used was characterized by low susceptibility to transformations compared to our previously described transformations of flavones and chalcones in the cultures of the tested strains. However, in the culture of the B. bassiana KCh J1.5 and BBT, Metarhizium robertsii MU4, and I. tenuipes MU35, the expected methylglycosides were obtained with high yields. Cheminformatic analyses indicated altered physicochemical and pharmacokinetic properties in the derivatives compared to flavokawain B. Pharmacological predictions suggested potential anticarcinogenic activity, caspase 3 stimulation, and antileishmanial effects. CONCLUSIONS: In summary, the study provided valuable insights into the enzymatic transformations of flavokawain B by entomopathogenic filamentous fungi, elucidating the structural modifications and predicting potential pharmacological activities of the obtained derivatives. The findings contribute to the understanding of the biocatalytic capabilities of these microbial cultures and the potential therapeutic applications of the modified flavokawain B derivatives.

Glycosylation of Quercetin by Selected Entomopathogenic Filamentous Fungi and Prediction of Its Products' Bioactivity.

Quercetin is the most abundant flavonoid in food products, including berries, apples, cauliflower, tea, cabbage, nuts, onions, red wine and fruit juices. It exhibits various biological activities and is used for medical applications, such as treating allergic, inflammatory and metabolic disorders, ophthalmic and cardiovascular diseases, and arthritis. However, its low water solubility may limit quercetin's therapeutic potential. One method of increasing the solubility of active compounds is their coupling to polar molecules, such as sugars. The attachment of a glucose unit impacts the stability and solubility of flavonoids and often determines their bioavailability and bioactivity. Entomopathogenic fungi are biocatalysts well known for their ability to attach glucose and its 4-O-methyl derivative to bioactive compounds, including flavonoids. We investigated the ability of cultures of entomopathogenic fungi belonging to Beauveria, Isaria, Metapochonia, Lecanicillium and Metarhizium genera to biotransform quercetin. Three major glycosylation products were detected: (1), 7-O-ß-D-(4″-O-methylglucopyranosyl)-quercetin, (2) 3-O-ß-D-(4″-O-methylglucopyranosyl)-quercetin and (3) 3-O-ß-D-(glucopyranosyl)-quercetin. The results show evident variability of the biotransformation process, both between strains of the tested biocatalysts from different species and between strains of the same species. Pharmacokinetic and pharmacodynamic properties of the obtained compounds were predicted with the use of cheminformatics tools. The study showed that the obtained compounds may have applications as effective modulators of intestinal flora and may be stronger hepato-, cardio- and vasoprotectants and free radical scavengers than quercetin.

Biological Activity of Extracts from Differently Produced Blueberry Fruits in Inhibiting Proliferation and Inducing Apoptosis of HT-29 Cells.

For several decades, people have been searching for natural substances of plant origin that, when introduced into the diet, could strengthen immunity, have anticancer properties, and support conventional therapy. The development of agriculture with the implementation of various plant cultivation systems, apart from the economic aspect, results in the search for such cultivation conditions that would contribute to obtaining the most beneficial product for health. Therefore, the aim of our research is as follows: (a) to compare the antiproliferative activity and the ability to induce apoptosis of HT-29 cells by extracts from blueberry fruits deriving from different types of cultivation systems (conventional, organic, and biodynamic); (b) to examine whether the interaction of extracts with anticancer drugs used in the treatment of colorectal cancer is influenced by the type of cultivation, and (c) to investigate whether extracts obtained from fruits from subsequent years of cultivation retain the same biological activity. The results of our study are promising but inconclusive. A statistically significant difference occurred in only one of the two years of the study. The greatest inhibition of proliferation is observed for biodynamic cultivation compared to organic cultivation, while the highest levels of apoptosis and necrosis of HT-29 cells are induced by blueberry fruit extracts obtained from organic cultivation. The complementary effect of the extracts on the inhibition of HT-29 cell proliferation by anticancer drugs (5-FU and Erbitux) is not demonstrated. The induction of apoptosis by 5-FU is not enhanced by blueberry extracts, in contrast to necrosis. The level of apoptosis and necrosis induced by Erbitux is potentiated, but no dependence on crop type is shown. Blueberry fruit extracts from two consecutive years of cultivation did not maintain the same activity. A plausible reason for the variability in the composition and biological activity of fruit extracts obtained from two years of cultivation is the varying environmental conditions.

Unbiased proteomic analysis of extracellular vesicles secreted by senescent human vascular smooth muscle cells reveals their ability to modulate immune cell functions.

Atherosclerosis, a common age-related disease, is characterized by intense immunological activity. Atherosclerotic plaque is composed of endothelial cells, vascular smooth muscle cells (VSMCs), lipids and immune cells infiltrating from the blood. During progression of the disease, VSMCs undergo senescence within the plaque and secrete SASP (senescence-associated secretory phenotype) factors that can actively modulate plaque microenvironment. We demonstrated that senescent VSMCs secrete increased number of extracellular vesicles (senEVs). Based on unbiased proteomic analysis of VMSC-derived EVs and of the soluble fraction of SASP (sSASP), more than 900 proteins were identified in each of SASP compartments. Comparison of the composition of VMSC-derived EVs with the SASP atlas revealed several proteins, including Serpin Family F Member 1 (SERPINF1) and Thrombospondin 1 (THBS1), as commonly upregulated components of EVs secreted by senescent VSMCs and fibroblasts. Among soluble SASP factors, only Growth Differentiation Factor 15 (GDF15) was universally increased in the secretome of senescent VSMCs, fibroblasts, and epithelial cells. Bioinformatics analysis of EV proteins distinguished functionally organized protein networks involved in immune cell function regulation. Accordingly, EVs released by senescent VSMCs induced secretion of IL-17, INFγ, and IL-10 by T cells and of TNFα produced by monocytes. Moreover senEVs influenced differentiation of monocytes favoring mix M1/M2 polarization with proinflammatory characteristics. Altogether, our studies provide a complex, unbiased analysis of VSMC SASP and prove that EVs derived from senescent VSMCs influence the cytokine milieu by modulating immune cell activity. Our results strengthen the role of senescent cells as an important inducer of inflammation in atherosclerosis.

Hydroxylation of Progesterone and Its Derivatives by the Entomopathogenic Strain Isaria farinosa KCh KW1.1.

Progesterone biotransformation is worth studying because of the high industrial value of its derivatives. This study investigated the catalytic ability of the entomopathogenic filamentous fungus strain Isaria farinosa KCh KW1.1 to transform progesterone derivatives: 11α-hydroxyprogesterone, 17α-hydroxyprogesterone, 16α,17α-epoxyprogesterone and pregnenolone. In the culture of Isaria farinosa KCh KW1.1, 11α-hydroxyprogesterone was effectively transformed into only one product: 6ß,11α-dihydroxyprogesterone. Transformation of 17α-hydroxyprogesterone gave three hydroxy derivatives: 6ß,17α-dihydroxyprogesterone, 12ß,17α-dihydroxyprogesterone and 6ß,12ß,17α-trihydroxyprogesterone. Two products: 6ß-hydroxy-16α,17α-epoxyprogesterone and 6ß,11α-dihydroxy-16α,17α-epoxyprogesterone, were obtained from the 16α,17α-epoxyprogesterone transformation. We isolated two compounds from the biotransformation medium with pregnenolone: 11α-hydroxy-7-oxopregnenolone and 5α,6α-epoxy-3ß,11α-dihydroxypregnan-7,20-dione. In this study, we observed only mono- and dihydroxy derivatives of the tested substrates, and the number of obtained products for each biotransformation did not exceed three.

Regiospecific Hydrogenation of Bromochalcone by Unconventional Yeast Strains.

This research aimed to select yeast strains capable of the biotransformation of selected 2'-hydroxybromochalcones. Small-scale biotransformations were carried out using four substrates obtained by chemical synthesis (2'-hydroxy-2″-bromochalcone, 2'-hydroxy-3″-bromochalcone, 2'-hydroxy-4″-bromochalcone and 2'-hydroxy-5'-bromochalcone) and eight strains of non-conventional yeasts. Screening allowed for the determination of the substrate specificity of selected microorganisms and the selection of biocatalysts that carried out the hydrogenation of tested compounds in the most effective way. It was found that the position of the bromine atom has a crucial influence on the degree of substrate conversion by the tested yeast strains. As a result of the biotransformation of the 2'-hydroxybromochalcones, the corresponding 2'-hydroxybromodihydrochalcones were obtained. The products obtained belong to the group of compounds with high potential as precursors of sweet substances.

Both Neisseria gonorrhoeae and Neisseria sicca Induce Cytokine Secretion by Infected Human Cells, but Only Neisseria gonorrhoeae Upregulates the Expression of Long Non-Coding RNAs.

Bacteria of the Neisseria genus are Gram-negative diplococci including both pathogenic and commensal species. We focused on pathogenic Neisseria gonorrhoeae and commensal Neisseria sicca. We have demonstrated that not only N. gonorrhoeae, but also N. sicca induce the secretion of pro-inflammatory cytokines IL-6, TNF-α, and chemokines CXCL8 and CCL20 by infected epithelial cells. However, N. sicca triggers a lesser effect than does N. gonorrhoeae. Furthermore, N. gonorrhoeae and N. sicca invoke distinct effects on the expression of genes (JUNB, FOSB, NFKB1, NFKBIA) encoding protein components of AP-1 and NF-κB transcription factors. We have also shown that the infection of epithelial cells by N. gonorrhoeae leads to significant overexpression of the long non-coding RNAs (lncRNAs), including MALAT1, ERICD, and RP11-510N19.5. This effect was not identified for N. sicca. In conclusion, data on the expression of lncRNAs and cytokine secretion in response to Neisseria spp. exposure indicate new directions for research on Neisseria-host interactions and can provide further insights into virulence of not only pathogenic, but also commensal Neisseria spp.

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 Foxp3+ 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 Rab27a-dependent 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: CD30+CCR8hiTNFR2hi eTreg1 and CD39+TIGIThi 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.

Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias.

Both chronic myeloid leukemia and acute myeloid leukemia evade the immune response during their development and disease progression. As myeloid leukemia cells modify their bone marrow microenvironment, they lead to dysfunction of cytotoxic cells, such as CD8+ T cells or NK cells, simultaneously promoting development of immunosuppressive regulatory T cells and suppressive myeloid cells. This facilitates disease progression, spreading of leukemic blasts outside the bone marrow niche and therapy resistance. The following review focuses on main immunosuppressive features of myeloid leukemias. Firstly, factors derived directly from leukemic cells - inhibitory receptors, soluble factors and extracellular vesicles, are described. Further, we outline function, properties and origin of main immunosuppressive cells - regulatory T cells, myeloid derived suppressor cells and macrophages. Finally, we analyze interplay between recovery of effector immunity and therapeutic modalities, such as tyrosine kinase inhibitors and chemotherapy.

Biotransformation of 5,7-Methoxyflavones by Selected Entomopathogenic Filamentous Fungi.

5,7-Dimethoxyflavone, a chrysin derivative, occurs in many plants and shows very low toxicity, even at high doses. On the basis of this phenomenon, we biotransformed a series of methoxy-derivatives of chrysin, apigenin, and tricetin obtained by chemical synthesis. We used entomopathogenic fungal strains with the confirmed ability of simultaneous hydroxylation/demethylation and glycosylation of flavonoid compounds. Both the amount and the place of attachment of the methoxy group influenced the biotransformation rate and the product's amount nascent. Based on product and semi-product structures, it can be concluded that they are the result of cascading transformations. Only in the case of 5,7,3',4',5'-pentamethoxyflavone, the strains were able to attach a sugar molecule in place of the methoxy substituent to give 3'-O-ß-d-(4″-O-methylglucopyranosyl)-5,7,4',5'-tetramethoxyflavone. However, we observed the tested strains' ability to selectively demethylate/hydroxylate the carbon C-3' and C-4' of ring B of the substrates used. The structures of four hydroxyl-derivatives were determined: 4'-hydroxy-5,7-dimethoxyflavone, 3'-hydroxy-5,7-dimethoxyflavone, 3'-hydroxy-5,7,4',5'-tetramethoxyflavone, and 5,7-dimethoxy-3',4'-dihydroxyflavone (5,7-dimethoxy-luteolin).

Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells.

Chalcones are interesting candidates for anti-cancer drugs due to the ease of their synthesis and their extensive biological activity. The study presents antitumor activity of newly synthesized chalcone analogues with a methoxy group on a panel of canine lymphoma and leukemia cell lines. The antiproliferative effect of the 2'-hydroxychalcone and its methoxylated derivatives was evaluated in MTT assay after 48 h of treatment in different concentrations. The proapoptotic activity was studied by cytometric analysis of cells stained with Annexin V/FITC and propidium iodide and by measure caspases 3/7 and 8 activation. The DNA damage was evaluated by Western blot analysis of phosphorylated histone H2AX. The new compounds had selective antiproliferative activity against the studied cell lines, the most effective were the 2'-hydroxy-2″,5″-dimethoxychalcone and 2'-hydroxy-4',6'-dimethoxychalcone. 2'-Hydroxychalcone and the two most active derivatives induced apoptosis and caspases participation, but some percentage of necrotic cells was also observed. Comparing phosphatidylserine externalization after treatment with the different compounds it was noted that the addition of two methoxy groups increased the proapoptotic potential. The most active compounds triggered DNA damage even in the cell lines resistant to chalcone-induced apoptosis. The results confirmed that the analogues could have anticancer potential in the treatment of canine lymphoma or leukemia.

Biotransformation of Methoxyflavones by Selected Entomopathogenic Filamentous Fungi.

The synthesis and biotransformation of five flavones containing methoxy substituents in the B ring: 2'-, 3'-, 4'-methoxyflavones, 2',5'-dimethoxyflavone and 3',4',5'-trimethoxyflavone are described. Strains of entomopathogenic filamentous fungi were used as biocatalysts. Five strains of the species Beauveria bassiana (KCh J1.5, J2.1, J3.2, J1, BBT), two of the species Beauveria caledonica (KCh J3.3, J3.4), one of Isaria fumosorosea (KCh J2) and one of Isaria farinosa (KCh KW 1.1) were investigated. Both the number and the place of attachment of the methoxy groups in the flavonoid structure influenced the biotransformation rate and the amount of nascent products. Based on the structures of products and semi-products, it can be concluded that their formation is the result of a cascading process. As a result of enzymes produced in the cells of the tested strains, the test compounds undergo progressive demethylation and/or hydroxylation and 4-O-methylglucosylation. Thirteen novel flavonoid 4-O-methylglucosides and five hydroxy flavones were isolated and identified.

Comparative Study of Immunomodulatory Agents to Induce Human T Regulatory (Treg) Cells: Preferential Treg-Stimulatory Effect of Prednisolone and Rapamycin.

T regulatory (Treg) cells play a critical role in the maintenance of self-tolerance, as well as in inhibition of inflammation and exaggerated immune response against exogenous antigens. They develop in the thymus (tTreg cells) but also may be generated at the peripheral tissues, including tumor microenvironment (pTreg cells), or induced in vitro in the presence of transforming growth factor (TGF)-ß (iTreg cells). Since tTreg cells constitute a minor fraction of peripheral blood lymphocytes in physiological conditions, an alternative way to obtain high number of functional Treg cells for therapeutic purposes is their generation in vitro from conventional T cells. In our studies, we compared effectiveness of several pharmacological agents with suggested immunomodulatory effects on Treg development (rapamycin, prednisolone, inosine pranobex, glatiramer acetate, sodium butyrate, and atorvastatin) to optimize Treg-inducing protocols. All but one (atorvastatin) immunomodulators augmented induction of polyclonal Treg cells in cultures. They were effective both in increasing the number of CD4+CD25highFoxp3high cells and Foxp3 expression. Rapamycin and prednisolone were found the most effective. Both drugs prolonged also phenotypic stability of Treg cells and induced fully active Treg cells in a functional assay. In the assay, prednisolone appeared superior versus rapamycin. The results, on the one hand, may be helpful in planning optimal protocols for generation of Treg cells for clinical application and, on the other hand, shed some light on mechanisms of the immunomodulatory activity of some tested agents observed in vivo.

Bone marrow is the preferred site of memory CD4+ T cell proliferation during recovery from sepsis.

Sepsis survivors suffer from increased vulnerability to infections, and lymphopenia presumably contributes to this problem. The mechanisms of the recovery of memory CD4+ T cells after sepsis remain elusive. We used the cecal ligation and puncture mouse model of sepsis to study the restoration of the memory CD4+ T cells during recovery from sepsis. Then, adoptive transfer of antigen-specific naive CD4+ T cells followed by immunization and BrdU labeling were performed to trace the proliferation and migration of memory CD4+ T cells. We revealed that the bone marrow (BM) is the primary site of CD4+ memory T cell homing and proliferation after sepsis-induced lymphopenia. Of interest, BM CD4+ T cells had a higher basal proliferation rate in comparison with splenic T cells. These cells also show features of resident memory T cells yet have the capacity to migrate outside the BM niche and engraft secondary lymphoid organs. The BM niche also sustains viability and functionality of CD4+ T cells. We also identified IL-7 as the major inducer of proliferation of the BM memory CD4+ T cells and showed that recombinant IL-7 improves the recovery of these cells. Taken together, we provide data on the mechanism and location of memory CD4+ T cell proliferation during recovery from septic lymphopenia, which are of relevance in studying immunostimulatory therapies in sepsis.

New 6,19-oxidoandrostan derivatives obtained by biotransformation in environmental filamentous fungi cultures.

BACKGROUND: Steroid compounds with a 6,19-oxirane bridge possess interesting biological activities including anticonvulsant and analgesic properties, bacteriostatic activity against Gram-positive bacteria and selective anti-glucocorticoid action, while lacking mineralocorticoid and progestagen activity. RESULTS: The study aimed to obtain new derivatives of 3ß-acetyloxy-5α-chloro-6,19-oxidoandrostan-17-one by microbial transformation. Twelve filamentous fungal strains were used as catalysts, including entomopathogenic strains with specific activity in the transformation of steroid compounds. All selected strains were characterised by high biotransformation capacity for steroid compounds. However, high substrate conversions were obtained in the cultures of 8 strains: Beauveria bassiana KCh BBT, Beauveria caledonica KCh J3.4, Penicillium commune KCh W7, Penicillium chrysogenum KCh S4, Mucor hiemalis KCh W2, Fusarium acuminatum KCh S1, Trichoderma atroviride KCh TRW and Isaria farinosa KCh KW1.1. Based on gas chromatography (GC) and nuclear magnetic resonance (NMR) analyses, it was found that almost all strains hydrolysed the ester bond of the acetyl group. The strain M. hiemalis KCh W2 reduced the carbonyl group additionally. From the P. commune KCh W7 and P. chrysogenum KCh S4 strain cultures a product of D-ring Baeyer-Villiger oxidation was isolated, whereas from the culture of B. bassiana KCh BBT a product of hydroxylation at the 11α position and oxidation of the D ring was obtained. Three 11α-hydroxy derivatives were obtained in the culture of I. farinosa KCh KW1.1: 3ß,11α-dihydroxy-5α-chloro-6,19-oxidoandrostan-17-one, 3ß,11α,19-trihydroxy-5α-chloro-6,19-oxidoandrostan-17-one and 3ß,11α-dihydroxy-5α-chloro-6,19-oxidoandrostan-17,19-dione. They are a result of consecutive reactions of hydrolysis of the acetyl group at C-3, 11α- hydroxylation, then hydroxylation at C-19 and its further oxidation to lactone. CONCLUSIONS: As a result of the biotransformations, seven steroid derivatives, not previously described in the literature, were obtained: 3ß-hydroxy-5α-chloro-6,19-oxidoandrostan-17-one, 3ß,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane, 3ß-hydroxy-5α-chloro-17α-oxa-D-homo-6,19-oxidoandrostan-17-one, 3ß,11α-dihydroxy-5α-chloro-17α-oxa-D-homo-6,19-oxidoandrostan-17-one and the three above-mentioned 11α-hydroxy derivatives. This study will allow a better understanding and characterisation of the catalytic abilities of individual microorganisms, which is crucial for more accurate planning of experiments and achieving more predictable results.

Chronic myeloid leukemia-derived extracellular vesicles increase Foxp3 level and suppressive activity of thymic regulatory T cells.

Mechanisms driving immunosuppression in chronic myeloid leukemia are mostly unknown. We show that leukemic extracellular vesicles (EVs) target lymphocytes and amplify suppressive function of thymic regulatory T cells, by driving expression of Foxp3 transcription factor. This could facilitate expansion of leukemic cells outside the bone marrow, leading to blast crisis.

Effective Hydrogenation of 3-(2"-furyl)- and 3-(2"-thienyl)-1-(2'-hydroxyphenyl)-prop-2-en-1-one in Selected Yeast Cultures.

Biotransformations were performed on eight selected yeast strains, all of which were able to selectively hydrogenate the chalcone derivatives 3-(2"-furyl)- (1) and 3-(2"-thienyl)-1-(2'-hydroxyphenyl)-prop-2-en-1-one (3) into 3-(2"-furyl)- (2) and 3-(2"-thienyl)-1-(2'-hydroxyphenyl)-propan-1-one (4) respectively. The highest efficiency of hydrogenation of the double bond in the substrate 1 was observed in the cultures of Saccharomyces cerevisiae KCh 464 and Yarrowia lipolytica KCh 71 strains. The substrate was converted into the product with > 99% conversion just in six hours after biotransformation started. The compound containing the sulfur atom in its structure was most effectively transformed by the Yarrowia lipolytica KCh 71 culture strain (conversion > 99%, obtained after three hours of substrate incubation). Also, we observed that, different strains of tested yeasts are able to carry out the bioreduction of the used substrate with different yields, depending on the presence of induced and constitutive ene reductases in their cells. The biggest advantage of this process is the efficient production of one product, practically without the formation of side products.