Anticarcinogenic effects of ursodeoxycholic acid in pancreatic adenocarcinoma cell models.

Changes to the composition of the microbiome in neoplasia, is termed oncobiosis, may affect tumor behavior through the changes to the secretion of bacterial metabolites. In this study we show, that ursodeoxycholic acid (UDCA), a bacterial metabolite, has cytostatic properties in pancreatic adenocarcinoma cell (PDAC) models. UDCA in concentrations corresponding to the human serum reference range suppressed PDAC cell proliferation.

The PARP inhibitor rucaparib blocks SARS-CoV-2 virus binding to cells and the immune reaction in models of COVID-19.

Background And Purpose: To date, there are limited options for severe Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus. As ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host; we have, here, assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19.

Experimental Approach: The effects of PARP inhibitors on virus uptake were assessed in cell-based experiments using multiple variants of SARS-CoV-2.

EGR2 is an epigenomic regulator of phagocytosis and antifungal immunity in alveolar macrophages.

Alveolar macrophages (AMs) act as gatekeepers of the lung's immune responses, serving essential roles in recognizing and eliminating pathogens. The transcription factor (TF) early growth response 2 (EGR2) has been recently described as required for mature AMs in mice; however, its mechanisms of action have not been explored. Here, we identified EGR2 as an epigenomic regulator and likely direct proximal transcriptional activator in AMs using epigenomic approaches (RNA sequencing, ATAC sequencing, and CUT&RUN).

Cytostatic Bacterial Metabolites Interfere with 5-Fluorouracil, Doxorubicin and Paclitaxel Efficiency in 4T1 Breast Cancer Cells.

The microbiome is capable of modulating the bioavailability of chemotherapy drugs, mainly due to metabolizing these agents. Multiple cytostatic bacterial metabolites were recently identified that have cytostatic effects on cancer cells. In this study, we addressed the question of whether a set of cytostatic bacterial metabolites (cadaverine, indolepropionic acid and indoxylsulfate) can interfere with the cytostatic effects of the chemotherapy agents used in the management of breast cancer (doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib, 5-fluorouracil and paclitaxel).

Guideline for designing microbiome studies in neoplastic diseases.

Oncobiosis has emerged as a key contributor to the development, and modulator of the treatment efficacy of cancer. Hereby, we review the modalities through which the oncobiome can support the progression of tumors, and the emerging therapeutic opportunities they present. The review highlights the inherent challenges and limitations faced in sampling and accurately characterizing oncobiome.

The bacterial metabolite, lithocholic acid, has antineoplastic effects in pancreatic adenocarcinoma.

Lithocholic acid (LCA) is a secondary bile acid. LCA enters the circulation after bacterial synthesis in the gastrointestinal tract, reaches distantly located cancer cells, and influences their behavior. LCA was considered carcinogenic, but recent studies demonstrated that LCA has antitumor effects.

Specific and shared biological functions of PARP2 - is PARP2 really a lil' brother of PARP1?

PARP2, that belongs to the family of ADP-ribosyl transferase enzymes (ART), is a discovery of the millennium, as it was identified in 1999. Although PARP2 was described initially as a DNA repair factor, it is now evident that PARP2 partakes in the regulation or execution of multiple biological processes as inflammation, carcinogenesis and cancer progression, metabolism or oxidative stress-related diseases. Hereby, we review the involvement of PARP2 in these processes with the aim of understanding which processes are specific for PARP2, but not for other members of the ART family.

Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFβ-ERK signaling.

Ascites plays a key role in supporting the metastatic potential of ovarian cancer cells. Shear stress and carry-over of cancer cells by ascites flow support carcinogenesis and metastasis formation. In addition, soluble factors may participate in the procarcinogenic effects of ascites in ovarian cancer.

Distinct subsets of anti-pulmonary autoantibodies correlate with disease severity and survival in severe COVID-19 patients.

Autoantibodies targeting the lung tissue were identified in severe COVID-19 patients in this retrospective study. Fifty-three percent of 104 patients developed anti-pulmonary antibodies, the majority of which were IgM class, suggesting that they developed upon infection with SARS-CoV-2. Anti-pulmonary antibodies correlated with worse pulmonary function and a higher risk of multiorgan failure that was further aggravated if 3 or more autoantibody clones were simultaneously present (multi-producers).

Identification of Bacterial Metabolites Modulating Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition.

Breast cancer patients are characterized by the oncobiotic transformation of multiple microbiome communities, including the gut microbiome. Oncobiotic transformation of the gut microbiome impairs the production of antineoplastic bacterial metabolites. The goal of this study was to identify bacterial metabolites with antineoplastic properties.

PARP2 poly(ADP-ribosyl)ates nuclear factor erythroid 2-related factor 2 (NRF2) affecting NRF2 subcellular localization.

PARP2 is a member of the PARP enzyme family. Although, PARP2 plays role in DNA repair, it has regulatory roles in mitochondrial and lipid metabolism, it has pivotal role in bringing about the adverse effects of pharmacological PARP inhibitors. Previously, we showed that the ablation of PARP2 induces oxidative stress and, consequently, mitochondrial fragmentation.

The pro- and antineoplastic effects of deoxycholic acid in pancreatic adenocarcinoma cell models.

Background: Commensal bacteria secrete metabolites that reach distant cancer cells through the circulation and influence cancer behavior. Deoxycholic acid (DCA), a hormone-like metabolite, is a secondary bile acid specifically synthesized by intestinal microbes. DCA may have both pro- and antineoplastic effects in cancers.

Half-Sandwich Type Platinum-Group Metal Complexes of -Glucosaminyl Azines: Synthesis and Antineoplastic and Antimicrobial Activities.

While platinum-based compounds such as cisplatin form the backbone of chemotherapy, the use of these compounds is limited by resistance and toxicity, driving the development of novel complexes with cytostatic properties. In this study, we synthesized a set of half-sandwich complexes of platinum-group metal ions (Ru(II), Os(II), Ir(III) and Rh(III)) with an N,N-bidentate ligand comprising a -glucosaminyl group and a heterocycle, such as pyridine, pyridazine, pyrimidine, pyrazine or quinoline. The sugar-containing ligands themselves are unknown compounds and were obtained by nucleophilic additions of lithiated heterocycles to -perbenzylated 2-nitro-glucal.

Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria.

The toxicity of and resistance to platinum complexes as cisplatin, oxaliplatin or carboplatin calls for the replacement of these therapeutic agents in clinical settings. We have previously identified a set of half sandwich-type osmium, ruthenium and iridium complexes with bidentate glycosyl heterocyclic ligands exerting specific cytostatic activity on cancer cells but not on non-transformed primary cells. The apolar nature of the complexes, conferred by large, apolar benzoyl protective groups on the hydroxyl groups of the carbohydrate moiety, was the main molecular feature to induce cytostasis.

Methods to Assess the Role of PARPs in Regulating Mitochondrial Oxidative Function.

PARP enzymes are involved in metabolic regulation and impact on a plethora of cellular metabolic pathways, among them, mitochondrial oxidative metabolism. The detrimental effects of PARP1 overactivation upon oxidative stress on mitochondrial oxidative metabolism was discovered in 1998. Since then, there was an enormous blooming in the understanding of the interplay between PARPs and mitochondria.

The majority of severe COVID-19 patients develop anti-cardiac autoantibodies.

Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens.

Nicotinamide-riboside shifts the differentiation of human primary white adipocytes to beige adipocytes impacting substrate preference and uncoupling respiration through SIRT1 activation and mitochondria-derived reactive species production.

Beige adipocytes play key roles in organismal energy and metabolic balance. In this study, we assessed whether the supplementation of human white adipocytes, differentiated from human adipose tissue-derived stem cells, with nicotinamide riboside (NR), a potent NAD + precursor, can shift differentiation to beige adipocytes (beiging). NR induced mitochondrial biogenesis and the expression of beige markers (TBX1 and UCP1) in white adipocytes demonstrating that NR can declutch beiging.

Tissue Transglutaminase Knock-Out Preadipocytes and Beige Cells of Epididymal Fat Origin Possess Decreased Mitochondrial Functions Required for Thermogenesis.

Beige adipocytes with thermogenic function are activated during cold exposure in white adipose tissue through the process of browning. These cells, similar to brown adipocytes, dissipate stored chemical energy in the form of heat with the help of uncoupling protein 1 (UCP1). Recently, we have shown that tissue transglutaminase (TG2) knock-out mice have decreased cold tolerance in parallel with lower utilization of their epididymal adipose tissue and reduced browning.

Targeting Multiresistant Gram-Positive Bacteria by Ruthenium, Osmium, Iridium and Rhodium Half-Sandwich Type Complexes With Bidentate Monosaccharide Ligands.

Bacterial resistance to antibiotics is an ever-growing problem in heathcare. We have previously identified a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich type complexes with bidentate monosaccharide ligands possessing cytostatic properties against carcinoma, lymphoma and sarcoma cells with low micromolar or submicromolar IC values. Importantly, these complexes were not active on primary, non-transformed cells.

The role of bile acids in carcinogenesis.

Bile acids are soluble derivatives of cholesterol produced in the liver that subsequently undergo bacterial transformation yielding a diverse array of metabolites. The bulk of bile acid synthesis takes place in the liver yielding primary bile acids; however, other tissues have also the capacity to generate bile acids (e.g.

Antigen-Presenting Cells in Psoriasis.

Psoriasis is classically considered a chronic inflammatory skin disorder, however the identification of autoantigens in its pathogenesis established it as a T cell mediated autoimmune disease. As such professional antigen-presenting cells (APCs) are key players in the development of lesions. APCs in the skin include dendritic cells, Langerhans cells and monocytes/macrophages.

Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models.

Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich-type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long-term cytostatic activity.

The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer.

Breast cancer, the most frequent cancer in women, is characterized by pathological changes to the microbiome of breast tissue, the tumor, the gut, and the urinary tract. Changes to the microbiome are determined by the stage, grade, origin (NST/lobular), and receptor status of the tumor. This year is the 50th anniversary of when Hill and colleagues first showed that changes to the gut microbiome can support breast cancer growth, namely that the oncobiome can reactivate excreted estrogens.